diff --git "a/val.tsv" "b/val.tsv" new file mode 100644--- /dev/null +++ "b/val.tsv" @@ -0,0 +1,1480 @@ +arg_1 round_1 ann_1 arg_2 round_2 ann_2 annotation_name is_attacks +line 76 and 79: Sentence about two farms with financial support is deleted from the aim. 2 1 In the introduction, (Line 76 79), you present the objectives, but those are not clear, I respectfully suggest focusing on your hypothesis 2. 1 2 agriculture12060868_perova 1 +"Line 78: ""designed to meet behavioural needs...."" is deleted Overall, the objective now is focused on the hypotheses. The reviewer is completely right in adressing this point." 2 1 Line 78: You wrote, “designed to meet the basic behavioral needs of the sow at farrowing”, but this is not tested on the paper. 1 2 agriculture12060868_perova 1 +l 80-83 is now deleted from the objectives 2 1 Lines 80 – 83 moves to discussion section 4. 1 2 agriculture12060868_perova 1 +Figure 1 must was lost from the last document, and we are so sorry for this. The figure is now included in the new document. 2 1 Figure 1 is missing 5. 1 2 agriculture12060868_perova 1 +More explanation is included in the figure text of figure 2 2 1 Figure 2 needs more description, maybe include which wall… Please describe units of the dimensions 6. 1 2 agriculture12060868_perova 1 +Corrections are made in the text of figure 4. 2 1 Figure 4. Please indicate which is “sowconf” and which is “trad”. In the left graph the units are in m2, but in right side it does not have unit, seems ar? 1 2 agriculture12060868_perova 1 +l 206, l225 Info is changed according to the reviewers request. 2 1 Line 206: I don’t understand why you use just 10 o 12 sows, 50% primi and multiparous, but in line 225 mentioned that “there were no secure information about sow parity” please be consistent. 1 2 agriculture12060868_perova 1 +The system we have used is to refer to the table with statistical values when reporting significant differences for the results presented in figures and tables, but for those that are presented in the text only, we also have P- and F-values in brackets. Insted of inserting P-values in the text when reporting significant differences for the ones that are in tables, we have included more references to the stat-tables. I hope the reviewer find that satisfactory. 2 1 Please include P values when report significant differences. 1 2 agriculture12060868_perova 1 +Figure 1 was missed from the last MS. Sorry for this error. This is now included 2 1 Figure 1 does not appear in the pdf that this reviewer could download. Only the Figure Caption appears. 1 2 agriculture12060868_perova 1 +Stillborn piglets vs piglets with no milk: more details are included about this in the description of the M/M 2 1 It is not totally clear to the reviewer how stillborn piglets were evaluated as compared to “piglets with no milk in stomach”. 1 2 agriculture12060868_perova 1 +224-225: confusion about parity is corrected, same comment as reviewer one 2 1 Line 224-225, it states that that no information/security on the productivity data on whether it was primiparous or multiparous sow. Again this creates a bit of confusion. Sows were recorded, 50% primiparous and 50% multiparous to evaluate behaviour, and results are discussed accorging to that (lines 320-321). Why productivity data was not available? 1 2 agriculture12060868_perova 1 +Figure 5 and 7. There is always effects of batches in these types of studies. This is also why we prefer to have several batches, but the main effect should not be biased by the batch effect in the present study, as the main finding are quite clear even in our small data set. However, it would be more elegant to have more batches. This was unfortunately not possible in the present iinnovation project. As mentioned earlier, we did not have resources t continue the data collection within the time period we had. 2 1 Figure 5 and 7 display the overall causes of mortality for the three batches. However, differences in batches were found. Could this overall causes be biased by this batch effect? 1 2 agriculture12060868_perova 1 +mean + se is given in all tables and figures, Replicates are now included and abbreviations explained. 2 1 Please add the important information to the footnote or figure legend of the tables and figures. Such as: abbreviations, replicates n=?, mean±SD/SE, ect. 1 2 agriculture12060868_perova 1 +Italic for P-values in the text. Done! 2 1 Please italic the P value throughout the paper. 1 2 agriculture12060868_perova 1 +Figure 1 was no included by an error in the last MS. It is now inserted again. 2 1 Lines 129-133, where is the figure 1? 1 2 agriculture12060868_perova 1 +Batches and number of litters are added to the figure legends. 2 1 Line 263, please add “(3 batches with TRAD and 2 batches with SOWCOMF)” to the figure legends. 1 2 agriculture12060868_perova 1 +Space before and after sign is added. 2 1 Line 275-276, Space needed before and after “±”. 1 2 agriculture12060868_perova 1 +A new and improved version of figure 6 is now included. 2 1 The quality of the Figrue 6 need to be improved. 1 2 agriculture12060868_perova 1 +We have inserted * to denote differences instead of letters. 2 1 Figure 7, using “*” to substitute the different letters to express the difference. 1 2 agriculture12060868_perova 1 +Table 4 is inserted again in the writing form. 2 1 Table 4, please using the writing way to present the table. 1 2 agriculture12060868_perova 1 +The meaning of ***: this is explained. 2 1 Figure8, do not understand the meaning of “***” here? 1 2 agriculture12060868_perova 1 +Quality of figure 7 is improved. 2 1 Figure 7, please improve the perspective of the figure. 1 2 agriculture12060868_perova 1 +The content of the two papers Reviewer 1 mentions here focussed on the impact of the pandemic on management changes in dogs and on dog owner experiences at a single time point during the most restrictive ‘lockdown’. The current paper is different to either of these, and indeed any other published paper, in that it focusses on changes in separation related behaviour over time, across two different surveys in a longitudinal cohort. 2 1 It seems that the authors of this study have already tackled this topic exhaustively in their previous articles 1 2 ani12040482_makarova 1 +The paper is about separation-related behaviour, not about the pandemic. 2 1 A catchy topic, but its content is unoriginal, bringing nothing new to the pre-pandemic science. 1 2 ani12040482_makarova 1 +Yes, this was purposeful, it provides a summary of the aims & methods to introduce the discussion as not everyone reads papers in a linear fashion. We have not made any changes based on this statement. 2 1 The entire first paragraph of Discussion repeats what has already been written in earlier chapters (line 372-379). 1 2 ani12040482_makarova 1 +There is a difference between something that is considered to be “well-known” or folk-knowledge and demonstrable evidence. The sentence quoted here is not untrue, or exaggerated, however, if the Editor wishes us to explore this further, we would kindly request the Reviewer provide us with examples of publications where this has been empirically demonstrated, as we have not found any in our own searches. 2 1 "Line 382-384 „To our knowledge, this is the first empirical evidence to show a link between changes in dogs’ leaving routines and risk of SRBs.” The authors take priority in the empirical demonstration of changes in dogs when the routine of the day is disturbed. And changing the routine of the day is a well-known factor influencing the dog's welfare and behavior, including the occurrence of separation anxiety, so the above-quoted sentence should be deleted because it is untrue. The authors have hardly studied all the publications on how dogs behave when daily routines were changed, so the term ""first study"" is exaggerated." 1 2 ani12040482_makarova 1 +Given the lack of constructive feedback in these statements, no changes have been made based on these comments. 2 1 Line 444 „This study has provided a unique and valuable insight into…..” the authors also mark their only unique role in the study, which does not bring new content. 1 2 ani12040482_makarova 1 +Thank you, in line 16 and 32 we have added “when restrictions had eased” to explain why we surveyed in October 2020. 2 1 Abstract/simple summary: These are clear and well detailed. My only suggestion is that making it clear why February and October were chosen as survey-points may be beneficial. 1 2 ani12040482_makarova 1 +Thank you, we have now expanded this to read: “In addition to being a welfare concern for the dog, SRBs are often unwanted or problematic for the owner and/or neighbours such as in the case of excessive vocalisation, which may lead to noise complaints, or in terms of house soiling and destruction of property, which may be particularly problematic for people living in rental accommodation. In such cases, these issues may increase risk of relinquishment [7]” (see new lines 56-59) It may be helpful to discuss why there is poor owner adherence to programmes to reduce SRB (Line 66-67). 2 1 Aa little more mention of issues of SRBs from owner perspective (e.g. noise complaints and issues with housing; property damage; decline of human-pet bond) could be beneficial (line 56-57). 1 2 ani12040482_makarova 1 +The following text has now been added beginning at line 69: “Whilst the precise reasons for poor adherence to advice for preventing or reducing SRBs have not been documented, it is at least partly attributed to the relative difficulty of adhering to specific aspects of these programmes, with the easier pieces of advice followed more often than the parts that take more commitment and consideration [13].” I wasn't sure if line 79-80 was needed- about dogs having returned to pre-pandemic pattern, I think it is a little dismissive of your own research which is valuable and applicable beyond the pandemic. 2 1 It may be helpful to discuss why there is poor owner adherence to programmes to reduce SRB (Line 66-67). 1 2 ani12040482_makarova 1 +Thank you for your comment, I think we were pre-judging that people would think it was just another covid paper, and we are glad to see you agree with us that it is valuable beyond the pandemic. This line has now been deleted. 2 1 I wasn't sure if line 79-80 was needed- about dogs having returned to pre-pandemic pattern, I think it is a little dismissive of your own research which is valuable and applicable beyond the pandemic. 1 2 ani12040482_makarova 1 +The findings were all extremely similar, so it felt quite repetitive to discuss them all. We actually had more detail in an early draft then trimmed it out. However, we have now added some more of this detail as requested (see lines 100 to 112), whilst trying to limit repetition. 2 1 Line 96-97- some more detail on the findings of these various surveys would be beneficial similarly to Bowen's study, just so provide a clear background/discussion of literature setting scene for your study. 1 2 ani12040482_makarova 1 +We presumed that at some point owners would pop out of the house, to take out the bin or go to the garage etc.. Such leaving events are likely to be experienced differently by some dogs, as the owners won’t likely give off the same cues as when they leave for an extended period of time, such as picking up house keys, or leaving through a different door. This has been explained now in lines 179-83. 2 1 Methods: This is generally well-detailed. It may be beneficial to make it clear why cut off of 'at least 5 mins' was used, e.g. justification for this/why this time duration used. 1 2 ani12040482_makarova 1 +Thank you, this seemed ok when we submitted it, but must have gone wrong when uploaded but we’ve corrected it now. 2 1 Line 131: There was an error with referencing wanted to flag. 1 2 ani12040482_makarova 1 +We’ve amended description of the study periods in a few places, including between lines 132-142, which we hope addresses this query now. 2 1 Study periods: It may be useful to spell out a little more here why these survey periods were chosen here, this is covered elsewhere but think could be made clearer here and earlier. 1 2 ani12040482_makarova 1 +One of the other reviewers also commented on this and asked for Figure 1 and much of the text to be moved to the supplemental material, so It’s also further explained in the supplementary material how it links to working and in lines 140-142 in the main text which now explains that many businesses were open again in October. 2 1 Figure 1- Perhaps just double-check this is referred to in the text. Think either way this figure would benefit a bit of context on why was included/what was showing in context of this study as currently info is a bit generic and didn't totally tie into people's working from home etc. 1 2 ani12040482_makarova 1 +This was due to the errors you mentioned below. We used the Word automatic referencing and somehow that seemed to get broken when the document was uploaded to the online system. It’s been done manually now. 2 1 Results: These were generally well-detailed with clear layout considering scope of results. However, I don't think the figures were referred to in the text (unless that was the errors highlighted below?) 1 2 ani12040482_makarova 1 +See above. 2 1 There were some errors where reference source not found which would want to look into (line 246; 265; 274; 292; 305; 323 etc). 1 2 ani12040482_makarova 1 +Agreed, this was how we interpreted why the owner was reporting this change. We have rephrased this section now. 2 1 Line 366-369= I'm not sure it's totally fair to interpret this (the dog not always bringing toy when greeting them) as an anthropomorphic interpretation on the part of the owner- the anthropomorphic interpretation seems to be from authors of manuscript not owner? 1 2 ani12040482_makarova 1 +Thank you for your review. We have expanded the discussion to address these points, however due to another reviewer saying the paper was already too long, we have kept this brief. A section detailing relevance to practitioners has been added to lines 545-551. 2 1 Some more detail on the application of the findings to practitioners/owners would be beneficial. 1 2 ani12040482_makarova 1 +Yes, this is correct. This is stated in line 232-233 or the original submission, but it seems we omitted it from the Methods section. Thank you for spotting that. Text has been added to lines 198-200 to explain this. 2 1 P6 L176 I am assuming you excluded dogs that were not left alone in February (or were there none?) 1 2 ani12040482_makarova 1 +Within the results table (Table 2) the direction of the estimate for this result is negative. Whilst we agree that it would be more impactful worded the other way around, we worry that changing the way it is described won’t match up to the data as it was coded and reported. We haven’t changed this wording for these reasons. 2 1 P10 L307-308 Could you make this a positive statement to show highlight the impact of amount of change on SRB: Dogs whose days left alone per week increased the most…If the data support that angle, I think it’s a stronger statement than what is written. 1 2 ani12040482_makarova 1 +Yes, and no, depending on your perspective. Whilst this was a significant predictor in the modelling, in reality 55% of dogs that were being left again changed from SRB+ to SRB-. So whilst 45% of dogs still showed it, a large proportion did not. 2 1 Larger issues: I would like to see the authors address a few different angles in the discussion 1. That dogs showing SRB prior to lockdown were more likely to show it after. Suggests the behavior is fairly robust and dogs having shown it at one point continue to be at risk (without knowing what interventions were taken) 2. 1 2 ani12040482_makarova 1 +Thank you for these thoughtful comments, we agree that we were a bit overly focussed on the results that supported the studies hypothesis and neglected to discuss the findings related to the dogs whose SRB appeared to have resolved. The number and percentage are detailed in the results section (lines 282-283 of the original submission and 298-298 in this one), but we failed to discuss these in the Discussion. We ran two models, one focussing on the dogs who started SRB- to see how many changed to SRB+ or remained SRB- and what factors influenced this, and the other focussing on dogs that started SRB+ to see what factors influence whether they changed to SRB- or remained SRB+. These models therefore, cover the comparisons you suggest (unless we’ve misinterpreted your comments). We have now added some discussion of the dogs who began the pandemic SRB+ however, as this was lacking from the first version (see the paragraph beginning at line 524). 2 1 Can you address the dogs that improved between Feb and Oct? You report the number of new dogs showing SRB but can you report on dogs that went the other way? What was the actual # and %? It seems you have compared within dogs that showed SRB in baseline and other models for dogs that did not. Seems a comparison between SRB- (baseline) → SRB + (post lockdown) and SRB + (baseline) → SRB- (post lockdown) dogs is critical and missing. This comparison seems essential—if some dogs get worse but some get better, than the argument that changes due to COVID might bring about new SRB becomes weaker. 1 2 ani12040482_makarova 1 +Thank you for this comment, we have discussed this further in the Discussion now (see lines 517-523) 2 1 One of the challenges in this is we don’t know background rates of change for dogs with SRB. That is, would the same % of dogs changed (in either direction) regardless of changes in owner schedules? We might see some dogs become sensitized over time and develop SRB (or something else changes in their life to precipitate it), while others might habituate or their behavior undergo extinction. As such, we can’t say for certain that these changes are due to changes in owner schedule. You note that the pseudo-R2 was small but I think you could go into more details and note the possibility that it was unrelated too. However, your results that the greater the change → the greater the new risk of SRB does lend support to the idea that this change in management might be a factor. I would suggest highlighting and discussing this outcome more. 1 2 ani12040482_makarova 1 +Thank you, we have changed the title to: Impact of changes in time left alone on separation-related behaviour in UK pet dogs 2 1 Title: change “Leaving Pattern” to “Time Spent Away”; leaving pattern is less clear (it could be frequency of leaving each day) 1 2 ani12040482_makarova 1 +This is how it was phrased in the survey, so this has not been changed. 2 1 Line 214: if possible (might not be possible if this was how it was phrased in the survey), change “different to before” to “different from before” 1 2 ani12040482_makarova 1 +Thank you, this edit has been applied. 2 1 Lines 383-384: Change “dogs’ leaving routines” to “dogs’ time left alone” Materials and Methods: 1 2 ani12040482_makarova 1 +It seemed unfeasible to expect a dog to never be left for even a minute or two, for example if the owner pops outside to take out the bin or to get something from the garage/shed etc. 2 1 Line 151: how was the criterion of “at least 5 minutes” chosen? My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? 1 2 ani12040482_makarova 1 +The wording given to the owners is all presented here, and in the supplementary material. No further definitions for behaviours or vocalisations were given. Pined, whined and cried were all mentioned, as all are words owner tend to use to describe similar dog vocalisations. As with all owner awareness of SRBs, it is fundamentally challenging unless they use recording equipment to view their dogs when they leave them or are otherwise able to view their dogs when alone such as by looking through a window. As this is a limitation of the method used, the appropriate place to mention this would be in the Discussion, not the Methods, so we have not discussed this limitation there. 2 1 Line 151: how was the criterion of “at least 5 minutes” chosen? My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? 1 2 ani12040482_makarova 1 +The wording of the question asked about the dog being left alone, without human company (see line 173), so it applied to anyone, and specifically meant when no-human was present in the house with the dog. 2 1 Also, I might have missed it, but did all of these owners live alone with their dog(s), meaning no other people in the household? If other people were present, did all of them have to be away or just the dog’s owner? This information might be presented in your other paper, but it would be good to include this basic information here as well, so readers can better understand your methods and findings. 1 2 ani12040482_makarova 1 +This has now been explained, however this section has been moved entirely to the supplementary material on request of other reviewers. 2 1 Line 166: define “devolved nations” for readers unfamiliar with the term. 1 2 ani12040482_makarova 1 +Not strictly speaking, no. Dogs who were not left in February were excluded from the analysis. So, whilst there are 0 of them, that’s because of methodological choice not because there weren’t any dogs left alone. A note explaining this has been added to the figure legend. 2 1 Figure 2: should the blank box for “Feb, Not at all” be 0.0%? 1 2 ani12040482_makarova 1 +There were issues in the figure referencing when we uploaded the manuscript to the submission system. This has now been corrected. 2 1 Figure 4 is not called out in the text of the Results section. 1 2 ani12040482_makarova 1 +For some reason I was convinced I’d read it was optional for longer discussions, but having double checked, you are indeed correct. Thank you. A brief conclusion section has now been added. 2 1 I believe Animals requires a Conclusions section. 1 2 ani12040482_makarova 1 +Thank you, we have corrected the typo. 2 1 Line 100: insert “the” after “in” 1 2 ani12040482_makarova 1 +This has been corrected 2 1 Line 355: delete the first “the” 1 2 ani12040482_makarova 1 +Thank you for your comments. The detail was provided to anchor the study in the background of what was occurring at the time, but we agree it is not necessary to the reader to see in the main text. These details and Figure 1 have been moved to the Supplementary material. 2 1 Therefore, the detailed description of the pandemic is unnecessary and could be moved to the Supplemental material, together with Figure 1. 1 2 ani12040482_makarova 1 +We agree this was completely missed from the Discussion. It wasn’t intentional, we were just overly focussed on the results that related to the research hypothesis. Discussion around this has been added now to lines 524-544. 2 1 What is surprising though is that 55.7% of the dogs who were reported to show SRB in February (before the pandemic) were clear in October which is good news. However, the authors do not focus on this result and do not explain this finding. 1 2 ani12040482_makarova 1 +Agreed, we have altered this part of the simple summary and abstract and included discussion of this in lines 539-544 now as well as into the conclusions, thank you. 2 1 Specific points requiring attention: L18-20 „Whether dogs showed SRBs or not changed considerably over the months of the study, and one in ten dogs were found to have developed new SRBs in October, that they didn’t show before the pandemic” Overall, the percentage of dogs showing SRBs decreased during the study, and this should be clarified in the sentence above. 1 2 ani12040482_makarova 1 +Leaving time has been changed throughout to ‘time left alone’ L33 10th instead of “10th” Thank you, we’ve corrected the typo. 2 1 L22 and elsewhere: dogs’ “leaving time” or “leaving hours” I think this expression is misleading because it is not the dogs that have left home, but the owners. 1 2 ani12040482_makarova 1 +Thank you for pointing this out. We define SRB in the opening lines of the Introduction (45-50), however you are right that in places the terms can get confusing. Section 3.7.3. details behaviours owners reported as associated with separation, that are not what class as SRBs. Those were names ‘other’ separation behaviour but this has now been clarified, hopefully, by remaining the section ‘Other’ separation-linked behaviour, and then in the text it is now stated they are not SRBs. The term ‘separation anxiety’ was used in the introduction where it referenced a study that used that specific term. This has now been put into quote marks to be clear it is their term, not ours. The one mention of separation-distress has also now been changed. 2 1 L45 Separation behaviour, separation-related behaviour, separation distress, separation anxiety terms are used interchangeably throughout the text, although these terms do not necessarily describe the same behaviours. Please provide a clear definition of the behaviour aimed to study and stick to one term. 1 2 ani12040482_makarova 1 +Thank you, we’ve corrected the typo. 2 1 L92 delete the comma after Bowen et al.’s. 1 2 ani12040482_makarova 1 +This has now been discussed further in lines 98-100. 2 1 L92-92 28.5% of dogs reported to have SRPs – this is a much higher number than mentioned in previous studies and needs to be discussed. 1 2 ani12040482_makarova 1 +This has now been moved to the beginning of the methods section. 2 1 L118 Materials and Methods This section (after the Ethics) should begin with the Subjects section. 1 2 ani12040482_makarova 1 +Agreed, this has been amended and condensed, thank you. 2 1 L127-137 The dates of data collections have been already mentioned in L121-126, so there is no need for repeating them. The whole section is not relevant to the main question. 1 2 ani12040482_makarova 1 +Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. 2 1 L131-132 and elsewhere: (Error! Reference source not found.) This error occurs 7 times in the text, please correct. 1 2 ani12040482_makarova 1 +We asked about the dogs’ management and behaviour over the previous 7 days so as to limit recall bias and anchor the data to a specific snapshot of time, rather than being more general. This was first asked for the first survey which was specifically looking at changes in management and behaviour during the strict lockdown period, so needed to be time specific. Questions were then repeated in the follow-up survey. Wording has been added to lines 165-169 now to clarify this. 2 1 L148 Please explain why a periof of 7 days were asked to be reported 1 2 ani12040482_makarova 1 +this has been done now. 2 1 L165-167 Figure 1. This Figure should be moved to the Supplement material as it tells nothing about the dogs’ behaviour. 1 2 ani12040482_makarova 1 +Thank you for spotting this, we have updated both the methods (L243-247) and results section (L370-374) with further detail of inter-rater reliability checks. 2 1 L216-218 “The text was then coded by two researchers” I could not find agreement data reported later. 1 2 ani12040482_makarova 1 +At the end of survey 1 there was the option for people to provide their demographic details, which not everyone did. This was done to conform to GDPR by asking only the most necessary questions. Given that the research question here is related to the dogs’ behaviour change over time versus leaving hours, it wasn’t deemed relevant to include analysis of the owner demographics. 2 1 L238 Do the authors have information about the Owner demographics? What was the proportion of females? Was there a relationship between age and leaving hours? Or explain why this information has not been used. 1 2 ani12040482_makarova 1 +This has now been done. 2 1 L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section 1 2 ani12040482_makarova 1 +For the purpose of this study it was required that we had baseline data on the dogs’ leaving behaviour so that we could classify them as SRB+ or – before the pandemic began. Owners of dogs who were not left alone in a typical week in February, were not asked about their dogs’ separation-related behaviour, so we did not have these data for them which is why they were excluded. New text has been added to the Subjects section of the methodology to explain how many owners answered the follow up questionnaire, the response rate and what percentage and number of dogs were not left home alone before the pandemic. The new section beginning at line 146 now reads: “A total of 2,425 people completed the follow-up survey for the same dog they scored in the original survey (a 51.9% response rate), of which 2,285 had previously provided data to indicate whether their dog was left alone or not in February 2020. Of these, 15.3% dogs (n=305) were not left alone at all in an average week in February, and as such, these dogs did not have baseline data for their behaviour when left so were excluded from further analysis.” Additionally, the number of people we emailed the invitation to (n=4,670) has been added to line 139. 2 1 Among them, what was the proportion of owners who has not responded to the request afterward? 1 2 ani12040482_makarova 1 +For the 1407 dogs who were clear of SRB in February, they changed from being 100% clear to being 90.1% clear, with 1 in 10 of these dogs developing SRB they didn’t have previously. However, because of the dramatic improvement seen in the dogs that had SRB before the pandemic, the overall prevalence of SRB in the population decreased from 22% in February, to 17.2% in October (reported in the paragraph above). The numbers have been clarified in this section to help future readers, and additional discussion has been added around the overall decrease in SRB prevalence in both the abstract and in the discussion (lines 524-544). 2 1 L278-280 “There were 1,407 dogs who were clear of SRB at baseline in February 2020. When looking at SRB status in October, of 1,187 dogs who were left alone in October, 117 (9.9%) were reported to have shown at least one SRB”. In other words, 1407/1807 (78%) of dogs were clear of SRB in February and 90.1% in October. This is good news, and it is unclear for me why is it reported as bad news. 1 2 ani12040482_makarova 1 +Thank you, we’re glad you liked it! Further explanation to help interpret the figure has now been added. 2 1 L285 Figure 4. This is a great figure, thank you for including it. However, an explanation would be useful for those readers who are not familiar with this type of depicting. 1 2 ani12040482_makarova 1 +Thank you for spotting that! 2 1 L291 The odds ratio (OR) is 5.38 and not 4.38 in Table 1. 1 2 ani12040482_makarova 1 +This was explained further down in the section on the multi-variable model, but I have now moved the explanation to here, where it’s first mentioned and added some additional text also. 2 1 L293-295 “The final variable associated with October SRB status was the difference in the number of days dogs were left alone for between the February baseline and lockdown”. OR was 0.81 here. Please explain the relationship between the variables. 1 2 ani12040482_makarova 1 +Thank you, this has been added now. 2 1 L298 Table 1 legend: Add what bold indicates 1 2 ani12040482_makarova 1 +Thank you! Looks like I read the z-value when I was typing. I promise this has been proof read, but it’s so easy to miss things, thank you so much! 2 1 L307 The odds ratio (OR) is 4.97 in Table 1 and not 3.60 1 2 ani12040482_makarova 1 +Since there were no non-significant variables it wasn’t necessary to distinguish the results. 2 1 L314 Table 2: bold is not used here although it was used in Table 1 1 2 ani12040482_makarova 1 +This has been corrected, thank you. 2 1 L333 table 3: same: bold is not used here 1 2 ani12040482_makarova 1 +Thank you for this, we were familiar with the paper but had missed that link. New text has been added here now to discuss this. 2 1 L382 Please refer to Flannigan and Dodman (2001) here (owner’s work schedule affects separation problems). Flannigan, G., & Dodman, N. H. (2001). Risk factors and behaviors associated with separation anxiety in dogs. Journal of the American Veterinary Medical Association, 219(4), 460-466. 1 2 ani12040482_makarova 1 +Agreed, this has been explicitly stated here now. 2 1 L395-397 “This value is likely to be an underestimate” The underestimation has already occurred during the baseline. 1 2 ani12040482_makarova 1 +We agree with the referee that in any open system as we have here , information will leak out and a corresponding backaction on the wavefunction cannot be avoided. However, by operating with ultra-cold quantum particles far of any internal resonance, the coherence time can be pretty long. This was shown with BEC’S trapped in cavities (see e.g. Ref 9). The effect of localization via cavity transmission can be reduced by working at higher cavity photon numbers. Ultimately the interplay between measurement induced localization and coherence spreading by unitary evolution could be one of the most interesting points in setting up such an experiment. One should study a transition from classical to quantum behavior depending on the degree of observation of the system. 2 1 It remains unclear how the quantum regime (with coherent spatial delocalization and interference of probability amplitudes of different paths) could possibly be reached in a real experiment, as spontaneous scattering of photons (of the cavity light or of the side pumper) into free space would localize the atomic wavefuction into one lattice site and thus decohere any spatial delocalization. 1 2 atoms3030433_perova 1 +Axes added. 2 1 For a quick orientation it would be helpful to indicate the x-axis 1 2 atoms3030433_perova 1 +We have reformulated to avoid confusion and unsubstantiated claims: “The mechanism is reminiscent of the one exploited in the creation of artificial potentials in optical lattices~\cite{Struck2012Tunable} applied here to the classical regime” 2 1 "In Section I the authors write: ""The mechanism is similar to the ones exploited in the creation of artificial potentials in optical lattices [17]"". This statement is a bit misleading since [17] uses coherent (quantum-mechanical) tunnelling with complex tunnel amplitudes, whereas the present manuscript deals with classical trajectories and classical jump probabilities." 1 2 atoms3030433_perova 1 +We have added a clarifying statement in the beginning of section 2: “We consider an effective one-dimensional model”. 2 1 In Section II it should be clearly stated that this is a one-dimensional model, transverse forces or motion are not considered. 1 2 atoms3030433_perova 1 +The referee is correct; in the convention that we specify the negative detuning corresponds to the regime where motional instabilities are avoided and cavity cooling is possible. We included this in the figure caption. 2 1 "in Fig. 2: ""such that c < 0 corresponding to the stable regime of cavity QED with moving atoms"": what does this mean? The regime of cavity cooling?" 1 2 atoms3030433_perova 1 +As we specify now in the beginning of section 3: “We treat $\eta_T$ as a free varying parameter. In the following we set $\kappa=1$ for numerical simulations and normalize the time in units of $\kappa^{-1}$”. 2 1 In Section III the numerical value of \kappa is not given (only in the caption of Fig. 3 it is mentioned that \kappa is set to unity). 1 2 atoms3030433_perova 1 +As the referee correctly infers the random walk is merely an effect of the time modulation of the potential. The classical limit without time delayed action (characteristic of the cavity) will reproduce the kind of walk obtained in the LT limit where Fig. 3 and the analysis has been performed. The other regime where the transverse field kicks the particle out of the longitudinal trap is a cavity effect as the effective force (transverse) has a different modulation than the simple cosine of the free space transverse wave. However, for fine tuning of parameters and to insure stability of trajectories we have used the cavity cooling effect. 2 1 The numerical values of the parameters used for the simulation are in the bad cavity regime (g << \kappa, \gamma). Does the special spatio-temporal shape of the potential, which is shown in Fig. 3, and which enables the effective random walk motion, originate in genuine cavity quantum effects, or could a similar potential be generated also in the classical (bad cavity) limit (g -> 0, \eta_L -> infinity and \kappa large), or for a classical standing wave laser beam interfering with a classical transverse running wave? 1 2 atoms3030433_perova 1 +Yes, some momentum diffusion can be expected. In principle using a sufficiently narrow cavity and suitable operation parameters cavity cooling could be tuned to cancel such unwanted heating. However, this is connected to dissipative dynamics and will change the effective operating parameters of the system. In the bad cavity limited on the other hand, one can expect some “cavity heating” instead of cooling, but the rate of this heating should be slow enough to allow for many kicks before it gets relevant. 2 1 In describing the action of the optical potential as quasi-random potential kicks, is there some long-term heating effect (i.e. an increase of the average energy of the atom)? Does cavity cooling play a role to counteract this in the numerical simulations?Response Response We thank the referee for an extremely careful reading of the manuscript, his/her appreciation of it and for the very constructive criticism expressed in this report. 1 2 atoms3030433_perova 1 +We have corrected the sign in the commutation relation. 2 1 In the paragraph following Eq. (2), please check the commutation relations between the raising (sigma^+) and lowering (sigma^-) operators and the Pauli matrix sigma^z. I suspect it should be [sigma^+,sigma^z] = - 2 sigma^+ and [sigma^-,sigma^z] = + 2 sigma^- . 1 2 atoms3030433_perova 1 +We have added a proper reference as Ref. [23]. 2 1 "A couple of lines below Eq. (4), the Authors write ""We proceed in a standard way to derive equations of motion for classical quantities."" I would suggest to provide a reference to guide the less experienced reader." 1 2 atoms3030433_perova 1 +We have added the definition for \gamma in the text. Here we focus on a dispersive regime of weak atomic excitation, where the so called dipole force dominates the mechanical atom field interaction and spontaneous emission plays a negligible role. In this limit the mechanical forces can be derived from a deterministic (time dependent) optical potential (see refs. 7-9 for details). However, as the referee points out, in the nonlinear dynamical regime, the effects stemming from the inclusion of a random spontaneous emission could be amplified. A similar randomness is connected to cavity cooling in a regime of weak coherent intra-cavity fields. This certainly will have to be considered in a quantum treatment. In our simulation we got the “quasi random” dynamics from deterministic motion connected to details of the initial conditions without including random forces. 2 1 In the equations of motion for the atoms [Eqs. (6) and (7)] it is introduced the quantity gamma, which, I guess, is the atomic decay rate. Please, provide a definition of gamma. What is, if any, the role of gamma (spontaneous atomic decay rate) in the physical process under consideration? In the analytical results, derived in the adiabatic limit, gamma is eliminated and does not play any role. I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored. 1 2 atoms3030433_perova 1 +Indeed all the above mentioned expressions were missing a factor of \kappa as the referee correctly observed. 2 1 "At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived. Please, check this value. I'm afraid there is a factor k missing (simple dimensional analysis shows that something is wrong with it)." 1 2 atoms3030433_perova 1 +The analytical considerations fit very well with numerical results. Indeed, in this regime, we have performed the simulations by choosing parameters derived from analytical considerations. The R6 emergence of the jump regime is directly connected with the increase of the LT force to the value of the longitudinally-induced force but the fine tuning of the parameters is a bit tricky in order to insure that only jumps to neighbouring sites occur. Therefore we have restricted our presentation to the other regime where the jumps are strictly occurring owing to the transverse-longitudinal time modulation of the potential. 2 1 "In section VI E. ""Trapping by longitudinal pumping"", one can analytically estimate the threshold value for the transverse pumping. How does this analytical result compare with the numerical simulations?" 1 2 atoms3030433_perova 1 +We have fixed this mistake. 2 1 Please, be consistent with the choice of subscripts and superscripts: in the first column of page 2 the Pauli operator is denoted as sigma^z (superscript), whereas in the second column becomes sigma_z (subscript). 1 2 atoms3030433_perova 1 +We changed the order of the figures and corrected the reference to the wrong figure. 2 1 Figure 4 is mentioned in the main text AFTER Fig. 5. It would be more logical to exchange their presentation order and, consequently, the figures numbering. Indeed, the same Authors already refer to the single trajectory plot as Fig. 4 (c) [see paragraph below Eq. (13)]. 1 2 atoms3030433_perova 1 +Comma has been introduced. 2 1 Page 4, first paragraph, the particle initial conditions are chosen in the interval [ - 0.1, 0.1] (in the text a comma is missing). 1 2 atoms3030433_perova 1 +The b) has been eliminated. 2 1 "Page 5, first column, second paragraph ""... one can inspect Eq. (11) b) where the right-hand side ..."". Please, eliminate ""b)"" since it is simply Eq. (11). The same misprint appears at page 8 in the paragraph between Eqs. (32) and (33)." 1 2 atoms3030433_perova 1 +Subscript has been introduced. 2 1 "Page 6, ""Optical forces"": there is a missing subscript L in the first force term at the end of the first paragraph, just before Eq. (21)." 1 2 atoms3030433_perova 1 +We have restricted the analysis to 2 curves (full and dashed) and a thinner red dashed curve corresponding to the analytical solution in the lower plots. The visibility is clearly increased and the message stays the same. 2 1 Figure 8, Force correlation functions and numerical solutions of the variance: when printed in grey scale some lines are very faint (especially those in green and cyan). Try to use other colors and/or thicker lines. 1 2 atoms3030433_perova 1 +We added references to the Wolf and Tourrencin and A. Peters, K.Y. Chung and S. Chu articles. The latter of these articles does not address the quantum corrections 2. 2 1 The novelty of the paper would not be reduced if the authors had quoted previous works on the same subject or using the same technique: The first example is the result announced in Equation (4), concerning the phase shift due to the gravity gradient gamma. This effect was first calculated by Wolf and Tourrencin Physics Letters A 251 (1999) pp 241–246 and discussed with more details in A. Peters, K.Y. Chung and S. Chu, Metrologia 2001, 38, 25–61. 1 2 atoms4020014_makarova 1 +The referee implies that the leading term is not a quantum correction owing to the cancellation of a numerator proportional to hbar and a denominator in the spatial phase factor that is also proportional to hbar. This is, is some respect, a question of semantics, and has a long history in discussions of quantum effects in atom interferometry. Basically this term is a Doppler shift, which is clearly of classical origin, with no need to impose arguments related to cancellations of hbars in numerators and denominators. In the approach we follow using the Wigner representation, there are no numerators and denominators; the leading term has no hbar. 2 1 Moreover, the authors call this effect a quantum correction probably because it is proportional to hbar but it would be more clear to explain that, the leading term of the gravitation phase being independent of hbar because of a cancellation (hbar appears in the numerator and denominator of the quantity giving the phase), the term linear in gamma is also proportional to the recoil velocity which itself is proportional to hbar. 1 2 atoms4020014_makarova 1 +The density matrix in the Wigner representation has been widely used in problems related to the recoil effect and laser cooling. For some mysterious reason it hasn’t used in much in problems involving atom interferometry. Of course there are hundreds of articles (maybe more) and books on the Wigner representation; however here we are concerned mainly with its application to calculations involving atom interferometry. The only examples we know of are the ones referred to in the paper. 2 1 The treatment involves quantum corrections which are treated by calculating the Wigner representation of the density matrix and I am not aware of the use of such an extensive use of Wigner representation to describe atom interferometry experiments. 1 2 atoms4020014_makarova 1 +The article by Fam is devoted to the use of Wigner representation for the two-particle density matrix, which is outside the scope of our article. Moreover, in contrast to that article, we do not use an expansion of the equation for the Wigner distribution in powers of hbar. For both these reasons, we do not include a reference on this article 5. 2 1 The treatment involves quantum corrections which are treated by calculating the Wigner representation of the density matrix and I am not aware of the use of such an extensive use of Wigner representation to describe atom interferometry experiments. 1 2 atoms4020014_makarova 1 +As far as we can tell, the phi_Q term is not related directly to the spreading of the wave-packet. 2 1 In my opinion, phi_Q is the real quantum correction due to the spreading of the wavepacket during propagation. If I am correct, this should be explained. 1 2 atoms4020014_makarova 1 +We added a paragraph re-emphasizing the choice of x_C, x_qC and x_QC just after Equation (99); these terms do not have to the same leading terms in T^2. 2 1 The meaning of the three x_C, x_qC and x_QC (Equation (99)) is far from obvious but it is very surprising that the leading term in T^2 is different? 1 2 atoms4020014_makarova 1 +Several additional paragraphs have been added near the figures to help explain the plots appearing in these figures. For the stationary atom case, the limits on y_{m0} are determined from inequality (106) and it is indeed possible for y_{m0} to be less than y_{min}. The manner in which we arrived at the regions of validity of the approximations is now described in more detail. 2 1 The paper is quite difficult to read, because of very many bulky equations. I do not see how to reduce the number of equations but I think that some more comments would help the reader. For instance, the equations 12 to 14 were not clear for me but I found an explanation at Equation (37). 1 2 atoms4020014_makarova 1 +In the article we obtained results that are specific for the parameters of the atom interferometer and test mass’ shape and trajectory. We think for the each case one should generate one figure 3 to answer all questions regarding the validity and role of different parts of the phase and approximate expressions for them. Instead of using a lot of dashed curves, we decided to use a panel of figures. 2 1 The paper contains only one figure with 28 panels presenting the results of the calculations. I think that this figure is very difficult to read! I do not understand clearly why results are plotted with y < y_min if this not physical: please explain! 1 2 atoms4020014_makarova 1 +We added a schematic figure of the geometry of our problem. 2 1 A figure explaining the geometry of the experiment would also help. 1 2 atoms4020014_makarova 1 +In the paragraph after Equation (30) we added a list of requirements that will insure that the signal does not depend critically on the initial atomic state phase space distribution. These requirements minimize the corrections arising from diffraction to which the referee refers 11. 2 1 The diffraction probability is assumed to be exactly ½ for the pi/2 pulses, with no dependence with x or p. Is this justified? 1 2 atoms4020014_makarova 1 +Difficulties related to stray interferometers exist and are important, but are not addressed in our paper, as the referee points out. We are assuming that the effects can be minimized in a fountain geometry using a variety of experimental techniques. In any event, a discussion of these effects is beyond what we are able to discuss in this article. 2 1 The fountain is assumed to be exactly symmetric (see line after Equation (100)). It is well known that with symmetric fountains diffraction with retro-reflected laser beams produces stray interferometers... Minor Remarks 1 2 atoms4020014_makarova 1 +The word “potential” has been changed to “acceleration” in the sentence after Equation (1). 2 1 I noted an error after Equation (1): ... the gravitational potential is constant... I assume that the authors meant acceleration g, not the potential. 1 2 atoms4020014_makarova 1 +A figure has been added to clarify the geometry of the problem. Moreover, additional discussion of the trajectories involved are now given in paragraphs that were added to help explain the plots given in Figures 2 and 3. 4 1 The relative location of the test mass to the cold atom cloud should be clearly stated during the calculation, as the gravitational force is a vector. If the test mass is not located in the direction of the evolution trajectory of the atom cloud, the applicability of some formulas (e.g. Equation (3)) need to be verified. 3 2 atoms4020014_makarova 1 +The wave function cannot be used when we know only some statistical properties of the initial phase space distribution. 4 1 The cloud is assumed to be characterized by a Wigner distribution function. What are the advantages to use Wigner distribution function instead of wave function? 3 2 atoms4020014_makarova 1 +We thank the referee for pointing out this additional reference and have added it to the references. 4 1 Just for the note of the authors, there are some new applications of atom interferometer, e.g., in the accurate measurement of the quadratic Zeeman coefficient [J. Phys. B: At. Mol. Opt. Phys., 47(1): 015001, 2014]. 3 2 atoms4020014_makarova 1 +We have introduced new several sentences in this paragraph of Materials and Methods, which define these ad-hoc rules. Lines 154-155: “mgR51C read-outs have been introduced into the classification system as PVS1_O or BP7_O codes of variable evidence strength depending on the splicing outcome [P, Sup-porting (±1 point); M, Moderate (±2); Strong (±4); Very Strong (±8)].” Lines 163-179: “we have developed some ad-hoc rules that take into consideration the coding potential of each individual transcript and its relative contribution to the overall expression to reach the appropriate PVS1_O or BP/_O evidence strength. In brief, for each complex read-out we have applied the following algorithm: (i) De-convolute mgR51C read-outs in-to individual transcripts; (ii) apply ACMG/AMP evidences to each individual transcript; (iii) produce an overall PVS1_O (or BP7_O) code strength based on the relative contribu-tion of individual transcripts/evidences to the overall expression. Thus, if pathogenic supporting transcripts contribute ≥90% to the overall expression, PVS1_O_ code is applied (if different transcripts support different pathogenic evidence strengths, the lowest strength contributing >10% to the overall expression is selected for overall evidence strength). Similarly, BP7_O_ code is applied if benign supporting transcripts contribute ≥90% to the overall expression (if different transcripts support different pathogenic evi-dence strengths, the lowest strength contributing >10% to the overall expression is selected for overall evidence strength). If neither pathogenic nor benign supporting transcripts contribute ≥90% to the overall expression, the splicing assay is considered not providing any evidence in favor, or against, pathogenicity. Recently, we have used a similar ap-proach to deal with complex PALB2/ATM minigene read-outs [20,30].” 2 - 2 1 Line 156 – the authors refer to “ad-hoc rules” that they have developed for consideration of the different coding transcripts associated with the same spliceogenic variant in variant interpretation and classification. Although a reference is provided so that the reader can look up what these ad-hoc rules are, it would also be helpful to briefly describe these in the current manuscript. 1 2 cancers14122960_perova 1 +The five RAD51 paralogs are known to be required for homologous recombination and maintenance of genomic stability. Indeed, RAD51C interacts with RAD51B, RAD51D, XRCC2 and XRCC3 in two different complexes that play a role in homologous recombination. Miller et al studied the interaction between RAD51B and D (and also XRCC3) with deletion mutants. These authors found that Rad51C1-285 (includes β-strands 1-5) or Rad51C285-376 (includes β-strands 6-9) did not bind RAD51B. So, a complete beta-sheet is important in maintaining the overall fold of the protein. Moreover, the missense variant p.Arg312Trp (ß-strand 6) has been shown to impair RAD51C function (Gayarre et al 2017). Both studies indicate that this protein region is essential for RAD51C function so that transcripts lacking any of the β-strands, such as ▼(E6q4)-a, ▼(E6q4)-b, Δ(E7), Δ(E8) or the in-frame isoform Δ(E5), is probably deleterious. - We have modified this part, adding several sentences to clarify it. 2 1 Lines 250-251 and 263-265– In these lines the authors discuss transcripts in which the encoded proteins lack some beta strands. The lack of these protein structures are used as evidence to support pathogenicity. It is not clear from the text how lack of these beta strands is predicted to impact protein function. Is there evidence from another source that these beta strands are critical to protein function and that their loss is deleterious (rather than resulting in normal or slightly reduced protein activity)? 1 2 cancers14122960_perova 1 +We have added all the transcript names and their contribution in Table 2 (Column PVS1_O/BP7_O mgR51C_ex2-8). - We have included cross-references to Table 1 to facilitate understanding of the manuscript. 2 1 Lines 259-274 – This paragraph refers to evidence used in the variant interpretation of three aberrant transcripts that kept the open reading-frame (Δ(E2p3), Δ(E5) and ▼(E8p3)). However, the corresponding tables that summarizes variant classification according to the ACMG/AMP-based criteria (Table 2), does not include these transcript isoform names. As such, in order to correlate the discussion in this paragraph with the information in table 2, the reader also needs to cross reference Table 1 or 3. Incorporation of the transcript isoform names in table 2 would assist the reader in correlating this discussion of transcript isoforms with the corresponding evidence used to classify each of the variants. 1 2 cancers14122960_perova 1 +Very important comment. As the reviewer indicates, it would be essential to define the threshold of RAD51C expression from which it keeps its tumor suppressor activity. Unfortunately, it is not known by now but this finding would provide critical information to determine the pathogenicity of leaky spliceogenic variants. - So, we have modified this paragraph to introduce this information: “Only two variants (c.404+3A>G and c.705+3A>G) displayed 26% and 21% of the mgFL-transcript, respectively. Unfortunately, it is not known the minimal amount of RAD51C expression to confer tumor suppressor haplosufficiency so, these splicing assays were not considered informative (PVS1_O_N/A).” Note that leaky variants generate complex minigene read-outs (two or more transcripts), and are therefore classified accordingly (see methods). 2 1 Lines 342-359 – This paragraph discusses two RAD51C variants, c.404+3A>G and c.705+3A>G, for which mg-FL transcripts were detected in 26.3% and 21.3% or transcripts, respectively. The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. Leaky splice variants have been reported in various genes and sometimes can be associated with milder phenotypes (or no phenotypes), presumably because the canonical isoforms contribute to a “phenotypic rescue”. Is it known whether there is a threshold of RAD51C deficiency that is tolerated before associated cancer risks become increased? 1 2 cancers14122960_perova 1 +Acknowledge this suggestion. We have added two references of BRCA1 and BRCA2 studies. 2 1 in the Introduction in the sentence 61-69 the authors do not mention anything about BRCA1 (they mention MLH1 though); 1 2 cancers14122960_perova 1 +Acknowledge this comment. In this section we have tried to describe the classification approach and the rules we have followed to classify the variants. Certainly, we agree with the referee as sometimes the method is mixed with some results. So, we have moved some sentences of the last paragraph of Materials and Methods to Results. “The PM3 evidence (in trans with a pathogenic variant in a recessive disorder) did not con-tribute to the final classification. Not surprisingly (FANCO is an extremely rare FA complementation group) [37], none of the tested variants has been identified in Fanconi Anemia patients (ClinVar and Global Variome shared LOVD databases and literature search-es). Similarly, the BS2 evidence (in trans with a pathogenic variant in a healthy individual) does not contribute to the final classification of our tested variants. Finally, we have considered that some pathogenic (PS2, PM1, PM6, PP2, PP4) and benign (BP1, BP3, BP5) codes are not applicable to the classification of RAD51C variants.” 3- 2 1 I would expect that as BRCA1 splice variants are deeply studied. In the Materials and Methods, the section 2.6 is not actually a section that described some methodology. It appears to be more appropriate as results and maybe some information could be in the introduction. 1 2 cancers14122960_perova 1 +We have included explanations of these acronyms in text and Table 1 and have modified the following sentence: “Of the 19 characterized transcripts, 14 introduced premature termination codons (PTC; PTC transcripts), and of these, 10 are predicted to be degraded by the Nonsense-Mediated Decay pathway (NMD; PTC-NMD transcripts) that is considered convincing evidence of deleteriousness (Supplementary Table S3). “ - We have modified the sentence of the Fl-transcript: “All variants altered splicing, 18 of which produced no traces of the mgFL-transcript or almost undetectable levels (<2.4%, c.904G>A)…” 2 1 The acronyms need to be explained. Not all readers are familiar with PTC (premature termination codon) and NMD (nonsense mediated decay); as some variants are found PTC-NMD, this needs to be explained better. I would also stress a little more that FL is almost undetectable. 1 2 cancers14122960_perova 1 +Acknowledge this comment. 2 1 Splicing variants are called solely based on the size difference. It is good to look into Sanger sequence of splice variants after gel elution of the band and sequencing. 1 2 cancers14122960_perova 1 +Acknowledge this comment. We have sequenced the RT-PCR products of all variant assays (indicated in Materials and Methods, section 2.5. Minigene Splicing Assays). In fact, all the *.ab1 sequence and*.fsa fragment analysis files of RT-PCR products will be freely available at http://hdl.handle.net/10261/270934; https://doi.org/10.20350/digitalCSIC/14662 upon manuscript acceptance (links indicated in the manuscript section “Data Availability Statement”). Unfortunately, Sanger sequencing only allowed us to characterize the main transcripts, while the minor ones (<10% of the overall expression) are really difficult to characterize since gel band extraction does not work properly with these small amounts, or other methods (e.g. subcloning of RT-PCR products into a PCR-vector, or RNAseq of minigene outcomes) are laborious and not cost-effective. Anyway, we have also been using Fluorescent fragment analysis for transcript characterization in our previous studies (since Acedo et al, 2012). We have shown that this technique is highly sensitive, accurate and shows high resolution. For example, in Figure 1c, transcripts with minimal size differences (1-3 nt) are well-discriminated. So, for minor-rare transcripts is a good option (not perfect, we agree with the reviewer) to annotate them. - To clarify it, we have modified this part: Lines 132-134: “RT-PCR products were sequenced by Macrogen (Madrid, Spain), which allowed the characterization of the main variant-induced transcripts. Minor transcripts were annotated according to fluorescent fragment electrophoresis size data (see below).” 2 1 Splicing variants are called solely based on the size difference. It is good to look into Sanger sequence of splice variants after gel elution of the band and sequencing. 1 2 cancers14122960_perova 1 +According to the reviewer suggestion, FT-IR peaks shift related to chromium ion adsorption are discussed in the mechanism section and is incorporated in the revised manuscript. 2 1 Some FT-IR peaks shift with adsorption of Cr, and some not. Please add the discussion which peak shift is related to Cr, the authors can combine these with the discussion of the mechanism. 1 2 catal12030290_perova 1 +EDX analysis (In Figure 3) – is a conditional type of analysis of the chemical composition of the surface. In EDX, often, spectra with different atomic abundances of elements can be obtained even from the same sample. 2 1 In Figure 3, what is the origin of the increase concentration of Al and S? 1 2 catal12030290_perova 1 +The sulphuric acid disintegrated the leaves. Most of the substances in the leaves are reduced to carbon after two hours. Charring takes place by adding sulphuric acid and by the action of heat, charring removes hydrogen and oxygen from the solid, so that the remaining char is composed primarily of carbon. It also helps to remove the moist content in the leaves. The pollution problem may not be takes place. 2 1 In the experiment, H2SO4 is added in the first step, what is the purpose? Will this bring pollution problem? 1 2 catal12030290_perova 1 +Chromium is a potentially toxic metal occurring in water and groundwater as a result of natural and anthropogenic sources. The prepared adsorbent is well suitable in the real condition. Since the prepared adsorbent (Al-GNSC) is successfully reduces the chromium (VI) ion form the real groundwater samples. 2 1 How about the Cr concentration in the polluted ground water? Is the products suitable for this real condition? 1 2 catal12030290_perova 1 +Based on the reviewer suggestion, regeneration studies were performed briefly. Four different desorption agents such as tap water, 0.1M HCl, 0.1M H2SO4 and 0.1M NaOH were utilized to remove the adsorbed chromium ions from the Al-GNSC adsorbent. From this various desorption agents it was identified that 0.1M NaOH was more effective. Hence, the reuse of Al-GNSC from Cr(VI)-loaded material was studied for sorption and desorption cycles using sodium hydroxide as a regenerated agent. Relevant references are quoted in the revised manuscript. Reference: Sujitha Ravulapalli and Ravindhranath Kunta reported that sodium hydroxide was used as a regenerating agent for the sorption and desorption of Cr(VI) by activated carbon derived from Lantana camara plant. [Enhanced removal of chromium (VI) from wastewater using active carbon derived from Lantana camara plant as adsorbent. Water Sci Technol (2018) 78 (6): 1377–1389. https://doi.org/10.2166/wst.2018.413] Reference: M.A. Tandal and B.N.OZA. reported that Sodium hydroxide as a regenerating agent for the sorption and desorption of Cr(VI) by Granular activated carbon. [Adsorption and regeneration studies for the removal of Chromium (VI) from the waste water of electroplating industry using Granular activated carbon. Asian Journal of chemistry. Vol. 17, No.4 (2005), 2524-2530] Page 2 of 2 Comment 2: 2 1 The issue of regeneration has not been sufficiently worked out, but the authors themselves write about this, and it is not clear why NaOH was used for this. 1 2 catal12030290_perova 1 +For the preparation of 1kg of Al-GNSC adsorbent, approximately 150 to 200 mL of hydrochloric acid was added in order to blend the aluminum in to the ground nut shell carbon. Thank you for your valuable comment. 2 1 It was also not clear to me how much hydrochloric acid was eventually added during the preparation of the adsorbent. 1 2 catal12030290_perova 1 +According to the reviewer suggestion, the expression of separation factor is mentioned in the revised manuscript. 𝑅𝐿= 1 1+𝑏𝐶𝑖, where “Ci” is the initial concentration of Cr(VI) and “b” is the Langmuir constant. 2 1 The authors did not indicate how the “separation factor ‘RL’ is calculated and did not give a link to the equation for its calculation, and if the readers are not quite in the subject, then what kind of factor they do not understand. 1 2 catal12030290_perova 1 +However, we regret that we were not able to investigate the BET analysis due to pandemic situation, which could definitely give us additional information. 2 1 One could also estimate the specific surface area and porosity. So, the paper can be published after revision. 1 2 catal12030290_perova 1 +According to the reviewer suggestion, the complete terms of all abbreviations are mentioned before the first use in the revised manuscript. 2 1 The authors should write the complete terms of all abbreviations (including the instruments) before the first use in the abstract and main manuscript i.e. FT-IR and SEM in abstract section et al. 1 2 catal12030290_perova 1 +As suggested, the novelty of the research work is explained in the introduction part of the revised manuscript, and the Page 2 of 4 obtained results are compared with the recent literature. 2 1 The authors should clearly explain the innovation and importance of their work on the introduction of the manuscript. They should justify the value of the work and compare their work with previously similar published papers. 1 2 catal12030290_perova 1 +According to the reviewer suggestion, the SEM images with same scale are provided in the revised manuscript. 2 1 Fig. 1 - for a more effective visual comparison, authors recommended to provide SEM images of the same scale. In such form is rather difficult to make adequate comparison. 1 2 catal12030290_perova 1 +We hope the reviewer understand the experimental deficiencies at the stage of the present experiments. We deeply appreciate the comment raised by the reviewer. Thank you very much. However, we regret that we were not able to investigate the XPS analysis due to pandemic situation, which could definitely give us additional information about the elemental confirmation. 2 1 EDX analysis (Fig 3) - a very conditional (not specific) type of analysis of the chemical composition of the surface. Often, spectra with different atomic abundances of elements can be obtained even from the same sample. First of all, authors have to attach a EDX mapping images before/after sorption of chromium ions. And the authors are strongly recommended to add XPS spectra to this section of revised manuscript. The XPS method is much more sensitive and more accurately determines changes in the chemical composition of samples. 1 2 catal12030290_perova 1 +According to the reviewer suggestion, XRD study has been performed and incorporated in the revised manuscript. 2 1 Why authors did not use XRD technique for sample characterization? 1 2 catal12030290_perova 1 +According to the reviewer suggestion, kinetic study has been performed and incorporated in the revised manuscript. 2 1 The adsorption capacities of Al-GNSC adsorbents at different contact times have been provided. Which kinetics are right? Please add missing information about appropriate kinetic model in revised manuscript. 1 2 catal12030290_perova 1 +According to the reviewer suggestion, the conditions for testing adsorbents of Cr(VI) is incorporated in the Table and is mentioned in the revised manuscript. 2 1 It is rather difficult to make an adequate comparison of certain properties (catalysts or sorbents) with the already available results, since the concentration of the pollutant and the mass of the loaded sorbent vary in each experiment. Therefore, the authors are recommended to add the missing information (i.e. conditions for testing sorbents of Cr(VI) ions) to Table 3. 1 2 catal12030290_perova 1 +According to the reviewer suggestion the adsorption capacity of groundnut shell activated carbon (Qe= 7.4 mg/g) is mentioned in the revised manuscript. 2 1 In order to confirm proposed mechanism of Cr(VI) adsorption (illustrated on the fig 6) Authors should provide data on adsorption capacity of pristine groundnut shell activated carbon (not modified with Al). 1 2 catal12030290_perova 1 +Thank you for your valuable suggestion. According to the reviewer suggestion the conclusion section is elaborated with specific conclusions in the revised manuscript. 2 1 The conclusion section should be elaborated and improved. The author should bring specific conclusions in accordance with obtained results. 1 2 catal12030290_perova 1 +We acknowledge the reviewer’s opinion. As suggested by the reviewer, we checked the manuscript carefully and enlisted a professional English language service to eliminate the spelling mistakes and grammatical errors. Thank you for your valuable suggestion for strengthening the quality of the manuscript. 2 1 Moderate English changes required 1 2 catal12030290_perova 1 +Indeed, the liposomes are prepared by a conventional method. However, here and in our previous work [1] we use the term liposomal nanotraps to reflect the functional aspect of the liposomal action. In this context, the liposomes act as traps for bacterial toxins. 2 1 The authors used the term liposome nanotraps. The authors have used conventional liposome preparations. It is not clear why they are calling the preparations as the nanotraps. 1 2 cells11010166_makarova 1 +We verified the total protein content of the supernatants by Coomassie blue staining, which was similar for all strains (Figure. 1, for referee inspection only). The experiments were performed using different bacterial supernatant batches and results were remarkably consistent. All the supernatants were collected at the exact same bacterial culture’s optical density to harvest the bacteria in a comparable state between batches and strains. In our previous work we have shown that cholesterol-dependent cytolysins (SLO, PLY) displayed different kinetics and dynamics of their hemolytic activity compared to SLS. As a result, the total hemolytic activities of individual streptococcal supernatants were not represented by a simple sum of activities (concentrations) of their individual toxins but displayed more complex time- and amount-dependent behavior: e.g. – the activity of PLY/SLO was prevalent at the initial times of incubation and at relatively high amounts (volume) of supernatants, whereas SLS activity fully developed only after initial lag period but was prevalent when relatively low amounts of supernatants were used in the assays. The relative quantifications of toxins between streptococcal species and strains were performed in a previous publication [1] and are referred to throughout the manuscript. We added a paragraph in the result section (line 215-222) that summarizes those points. Moreover, in our current experiments we aim not only at the neutralization of the whole hemolytic secretome of streptococcus (as described in [1]) but also include (putative) cytotoxic/cytostatic activities that might be carried out either by hemolysins (SLO/SLS) or other not yet identified toxins that display cytotoxic/cytostatic but no hemolytic activities. For these reasons, in our current experiments, we use specific cytotoxic/cytostatic activities of total supernatants derived from a toxicity assay displayed in (Figure. 1), instead of concentrations of individual (partly unknown) toxins. However, we agree with the reviewers that using volume units is confusing. We therefore, edited our manuscript to display the lethal dose (LD%) interpolated from results shown in Figure 1 instead. Using LD% units accounts for the batch variability. 2 1 The authors have used bacterial culture supernatants to examine the cytotoxic effect on the THP-1, Jurkat, and Raji cell lines. Quantitation fo the the culture medium is required (by measuring the total protein content, or by providing some quantitative indicator). Volume of the culture supernatant is mentioned in the results. It is not quantitative, and will vary from batch to bath of the bacterial culture. 1 2 cells11010166_makarova 1 +While LDH-release or MTT assay are frequently used techniques and might be preferred by some investigators, other approaches assessing cell viability might be more popular by others, dependent on particular experimental settings of a particular study. Figure 2 (for referee inspection only) demonstrates that Alamar blue cell viability assay and Trypan blue live/dead quantification provide results that are identical to those obtained in the cell proliferation protocol used in our study. We believe that the latter protocol is the most suitable experimental approach for our study since it allows distinguishing between cell lysis, cytotoxisity and cytostatic effects (i.e. between cytolysins, cytotoxins and cytostatic agents) in a single experiment. The techniques and algorithms used by the CellDrop relies on accurate and unbiased measurements, akin to previously published techniques[2,3]. The following text was added to the material and method section: Alamar blue cell viability assay and Trypan blue live/dead quantification provide results that are identical to those obtained in the cell proliferation protocol used in our study (not shown). 2 1 LDH-release assay of cytotoxicity or MTT assay of cell viability should have been used for measuring the cell death. 1 2 cells11010166_makarova 1 +The focus of our study is to highlight that successful protection against the whole palette of streptococcal toxins can be achieved by using liposomal nanotraps and to show that the liposome requirements differs between bacterial species and between different types of immune cells. We agree that the SLO neutralization is not novel and simply confirm results from previous publications by us and others. In the current work we do not intend to reveal new neutralization mechanisms either for SLO or for SLS. 2 1 It is well-known that SLO binds to the cholesterol-containing lipid bilayer. Therefore, it is obvious that the cholesterol-containing liposomes would neutralise SLO present in the bacterial culture. Therefore, no new information is provided with these experiments. 1 2 cells11010166_makarova 1 +Streptolysin S (SLS) is a small, non-immunogenic, peptide. This means that no commercial antibody against it is available and the peptide is too small for reliable mass spectrometry detection. It is heavily post-translationally modified and is the product of a complex operon. Its exact mode-of-action is still not yet fully clarified. In a previous publication, we were able to show that SLS is neutralized by phosphatidylcholine as well as sphingomyelin liposomes [1]. However, given the poor characterization of SLS, its unavailability from commercial providers and its extremely tedious purification, the mechanistic details of the SLS neutralization will require an extensive a project of its own and are beyond the scope of the current study. We added a paragraph in the discussion section (line 378-382) to summarize those points. 2 1 In my opinion, differential inhibition of the SLS activity in GGS supernatant by the liposome preparations is interesting, and may provide new insights, if explored in more detail. 1 2 cells11010166_makarova 1 +We used two controls in the protection experiments. In one control we challenged the cells with bacterial supernatant without adding liposomes, to determine that the baseline cytotoxicity is in line with the results displayed in the Figure 1. The second control consists of the immune cells without toxin or liposomes. This control represents 100% survival and allows us to normalize our survival data. We also tested the intrinsic toxicity of liposomes on their own to see if they did impede cell growth or were cytotoxic. At the concentrations used in current study the liposomes were not cytotoxic (data not shown). The following text was added to the material and method section: The data were normalized to a control incubated with PBS instead of bacterial supernatant (considered as 0% cell death). A control challenged by bacterial supernatant without liposomes was added for each assay to verify the expected cytotoxic activity 2. 2 1 Although the sensitivity of immune cells to GAS or GGS supernatants is shown in the first section of the results, were any controls used in the neutralization assays with liposomes? 1 2 cells11010166_makarova 1 +We selected the specific supernatant volumes used to reach a similar lethal dose to compare the protection capability and efficiency of the liposomal nanotraps. However, as the immune cell lines have different sensitivities depending on the toxin profile of the tested strain, a similar lethal dose corresponds to different supernatant volumes. We used the results displayed in Figure 1 of the manuscript to determine which volume to use. We agree that the way we presented it can lead to confusion and we replaced the supernatant volume values by LD% values. The following text was added to the material and method section: The added supernatant volume was determined based on the toxicity assay results and was used either at saturating dose (lethal dose >90, LD>90) or at non-saturating dose (LD60-90) to study minor toxin activities. We agree that the distinction between saturating (LD>90) and non-saturating (LD60-90) was confusing. To clarify our process we did add clarifications throughout the results part and we added a panel in figure 2 to include results obtained after challenge of LD>90 of GGS 5804 supernatant. 2 1 Furthermore, it should be justified why this difference does not influence the comparison of the results with the different cell lines (THP1, Jurkat, Raji). 1 2 cells11010166_makarova 1 +Following the reviewer’s comments, we have now focused on one detailed analysis based on adequate tests and a discussion of the results. The revised version drops Descriptive statistics in old Table 2, rates of increase given in the old Table 3, correlations reported in old Table 4, the regressions in old Table 5, and pooled regressions of old Table 6. The discussion based on these Tables has consequently been omitted from the revision. The unit-root-test Tables have been moved from the Appendix to the text as Table 2, and in view of the evidence in favor of unit roots, rates of growth of GDP and government variables have been shown in Table 3 somewhat like the old Table 3. These are the most major changes. 2 1 I don’t really doubt the empirical findings of the paper (which I see as support for the hypothesis in Japan and possibly in Korea), but I dislike the approach of spending a lot of space on various, often pointless, tests. There should be one detailed analysis based on adequate tests, and a discussion about the results. After all, government expenditure is a political decision. 1 2 economies3040150_makarova 1 +The authors are aware of the Johnson et al. paper (JME 2013) and other critiques of the PWT data. However, while the LCU numbers are appropriate for single-country analysis, these are not suitable for panel-data format which is a significant part of this study. Therefore, we use the PWT numbers throughout and hope that single-country analysis with these numbers is a reasonable approximation to the scenario indicated by LCU data. 2 1 An import question is why are the series for real GDP per capita are taken from PWT 7.0? These series are constructed to be used in cross-country studies, and they are not suitable for the analyses in the paper. See the paper by Johnson et al. (2009). 1 2 economies3040150_makarova 1 +The dependency variable has been removed from the analysis. 2 1 The dependency ratio has not been included mechanically in most papers, as it is this one. It is supposed to pick up changes in demand for government expenditure, such as schooling and pensions. The general idea is that these have increased government expenditure, both because per-capita schooling and pensions have expanded and because the dependency ratio has increased. In most of the countries studied, as is well-known, the dependency ratio declined during the period studied, while expenditure per person probably increased. Japan is most likely an exception; it should have entered the demographic transition much earlier than the other countries. There is thus no a priory no reason to expect the dependency ratio to play an important role in the Wagner hypothesis in general. It can thus be removed from the analysis, or moved to a footnote. If the author(s) wish to pursue the approach of testing other potentially relevant variables, see Shelton 2007. 1 2 economies3040150_makarova 1 +Figure 1 has been redone with separate scales for logarithms of real GDP per capita and government share. 2 1 Figure 1 tends to hide co-movements between the variables by mixing of scales. I suggest the graphs are re-done using two y-axes and preferably logs. 1 2 economies3040150_makarova 1 +The correlations of old Table 4, the static regressions of Table 5, and the discussion of endogeneity have been omitted. 2 1 In Table 5 we can get information about cointegration from the R2 and the t-values. Only Japan shows any promise, in all other cases R2 are very low. I would say they are suspiciously low for time series data. Are thy correct? 1 2 economies3040150_makarova 1 +Since our data cover a long period of nearly 50 years, we are inclined to rely on Johansen tests although the number of data points is smaller than 100. The Gregory-Hansen test is done for Japan and Korea also just for completeness, and might be of some methodological interest since it does not show cointegration even for Japan and Korea. The reviewer’s observation has been acknowledged in note 2. 2 1 Gregory–Hansen is used when one fails to find cointegration with standard tests. There is no point in testing countries such as Japan and Korea, when a superior test shows that they are cointegrated. 1 2 economies3040150_makarova 1 +We agree with the reviewer about the limited usefulness of MTAR in small samples and for Japan and Korea. However, it is included in the hope it would indicate whether lack of cointegration for Malaysia, Philippines, Singapore and Thailand might be due to asymmetric adjustment. The reviewer’s observation has been acknowledged in note 3. 2 1 The use of the MTAR model is dubious because of the small sample, and it should not be used when cointegration has been established. It is unlikely that there is enough information in the data to capture asymmetric effects and the standard procedure is to use MTAR when Engle-Granger fails to show cointegration. 1 2 economies3040150_makarova 1 +We have highlighted the alternative hypothesis in Pedroni’s tests on Page 8. As Pedroni (1999) clearly points out, the alternative hypothesis rejects the null of no-cointegration across all cross-sections in both within- and between-dimension tests. 2 1 What is the alternative hypothesis of the Pedroni test, that there is cointegration in any country or or in all countries? This should be made clear. 1 2 economies3040150_makarova 1 +The “provocative conclusion” reflected one author’s subjective perception and was stated as such. He shares the perspective noted by Bennett McCallum’s in his “Is the spurious regression problem spurious?” (Economics Letters, 2010). However, the segment cited by the reviewer has been deleted since it is a more general proposition and is not necessary for the limited analysis reported in our paper. 2 1 “Methodologically, while the pattern is reflected fairly well in plots and simple correlations, and even in regressions, the widely-used cointegration methodology yields a diverse scenario in four different procedures, and, through a choice of the procedure and the model, it seems as easy to conclude that there is no cointegration, and thus no support for the hypothesis as to conclude that the evidence supports the hypothesis in a majority of the cases. At any rate, it is not obvious that such sophisticated and complex tests of cointegration provide any useful additional insight regarding the empirical status of the hypothesis. More generally, we venture the highly subjective view that despite the immense mathematical sophistication of cointegration tests and their application in perhaps thousands of studies, it is not obvious how much additional substantive insight has been gained in the wide variety of contexts in which these tests have been used.” These statements should be explained. Is the second one a rejection of the last 40 years of advances in times series analysis? 1 2 economies3040150_makarova 1 +We completely share the reviewer’s view that despite Biehl’s PF/FP essay, almost everyone follows the standard approach, and we do the same. Our observation is just a restatement of the proposition that our approach is traditional. 2 1 Despite Biehl’s (1998) insightful essay, almost all empirical research on the topic has interpreted the Wagnerian proposition 1 2 economies3040150_makarova 1 +Please note the following changes in revised version: (a) the plots in Figure 1 have been rescaled and now there are cross-overs in the plot for Japan, (b) years have been shown on the horizontal axis in Figure 1, (c) a sizable addition has been made toward the end of Section 3 to address the reviewer’s observations about possible reasons for lack of cointegration in most countries, and (d) a few minor editorial alterations have been made. 4 1 The x-axes in Figure 1 should have years. 3 2 economies3040150_makarova 1 +Several new references, including those kindly mentioned by the reviewer, have been added, and there is a concise description of these in note 1. 2 1 List of references is scant and limited. It is necessary to add more recent works on the subject with alternative ways of testing for Wagner’s Law. Suggestions include “Testing the Validity of Wagner’s Law in Bolivia: A Cointegration and Causality Analysis with Disaggregated Data” by A. Bojanic (2013); “Wagner’s Law and Italian Disaggregated Public Spending: Some Empirical Evidences” by C. Magazzino (2010); and “Panel Data, Cointegration, Causality and Wagner’s Law: Empirical Evidence from Chinese Provinces” by Narayan, P.K., et al. (2008). 1 2 economies3040150_makarova 1 +Several formats in which Wagner’s hypothesis has been formulated and tested have been listed on page 5 of the revision. That paragraph includes six different approaches. 2 1 The paper only lists one way of testing for Wagner’s hypothesis (i.e., analyzing the relation between the share on GDP of government spending and real GDP per capita) when in fact there are many ways of looking at the hypothesis. The authors should include at least a couple of recent ways of testing this law, in addition to the traditional way of testing for it. 1 2 economies3040150_makarova 1 +Real GDP per capita is a fairly standard proxy for the “level of development” in the context of Wagner’s hypothesis. It might not be appropriate to use nominal GDP per capita. For the government share, it seems better to take the current-price ratio which indicates what fraction of the current output is used for government activities. The deflators for GDP and government spending are different and “real” government-share may not be a good indicator of the resource-use by the government during the current year. 2 1 The variables used do not have the same units, which may clog the analysis of the paper. Specifically, real GDP per capita is measured in 2005 dollars while the share of government consumption on GDP is measured in current prices. Either both should be in real terms or both in current prices, but not as is currently the case. 1 2 economies3040150_makarova 1 +The old Table 2 has been deleted. Those descriptive statistics were for the entire period. The growth rates in the new Table 3 are also for the entire period, and that has been indicated. 2 1 The descriptive stats in Table 2 reflect stats for the whole period? If so, the table should explicitly state this fact. 1 2 economies3040150_makarova 1 +The redundant graphs for Philippines have been deleted. 2 1 Why are there 3 graphs for the Philippines in Figure 1? By the way, if the variables were measured in either current prices or utilizing the same base year, these graphs would likely be quite different (same goes for all statistical analysis, it is likely to vary when the two variables are measured the same way) 6. 1 2 economies3040150_makarova 1 +The dependency-rate variable has been dropped. 2 1 What is the point of the dependency rate? The authors should expand on the need to add this variable and what exactly is it trying to capture. In the same vein, what do the authors mean by “however, it seems that the fall in young-dependency ratio was greater than the rise in the old-dependency rate” on p. 4? 1 2 economies3040150_makarova 1 +The old Table 4 has been deleted along with the remark about p-values being taken from SAS. 2 1 In Table 4, delete the “generated by SAS” note. 1 2 economies3040150_makarova 1 +Thank you. 4 1 My recommendation is to accept the paper for publication. 3 2 economies3040150_makarova 1 +The colour refer to the SEEBASE depth to basement, the legend has been added • Figure 2: The left spine (or border) does not appear on the pdf reviewed. 2 1 Figure 1: Are colors in Figure 1 A related to the hydrostratigraphy or depicting topography? If the latter applies, make sure to provide a scale. 1 2 geosciences12010037_perova 1 +Thanks, the figure have been entirely revisited and divided into four subfigures. 2 1 Figure 2: The left spine (or border) does not appear on the pdf reviewed. This figure could be improved by adding shaded satellite image to help the reader compare the mapped drainage systems (which were automatically mapped) and fault traces/lineaments with the real features observed. 1 2 geosciences12010037_perova 1 +The figure has been redrawn and the magnetic lineaments indicated • Figure 4: This figure could go in the appendix. 2 1 Figure 3: The text (lines 258-259) mentions magnetic lineaments as prominent features, which can be caused by faulting. Such features are hard to visualize. It would certainly help if they were highlighted directly on the figure. 1 2 geosciences12010037_perova 1 +Thank you. We hesitated on this point but decided to keep the figure in as the quality of the seismic in the shallow level is really crucial to the discussion. We need to know if the interpretation is reliable, especially in this shallow zone that is not well imaged by this type of data. A misinterpretation can led to the targeting of circulation pathways that are in fact only artefacts. 2 1 Figure 4: This figure could go in the appendix. It is good to let the reader know that not all seismic surveys provided the same quality, but this is more a technical point. 1 2 geosciences12010037_perova 1 +We 2 1 Figure 7: What is special about the locations highlighted by the markers (crosses on Figure 7B and square markers on Figure 7C). At this scale, the reader can’t see much detail. 1 2 geosciences12010037_perova 1 +done, 2 1 Figure 9: Remove ‘s’ from <10 yearss. Also, increase the thickness of the fault lines to make them more obvious. 1 2 geosciences12010037_perova 1 +‘this is due to the different seismic acquisition technics and processing applied in each survey as well as the fact that our interval of interest is shallow and not fitting with the interval of interest the companies tried to best image with those datasets” 2 1 Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? 1 2 geosciences12010037_perova 1 +as the presence of fluid or gas can locally alter the seismic signal” 2 1 Lines 323-324: The authors should explain why low magnitude local seismic signals can be believed to represent permeable pathways promoting water or gas migration. 1 2 geosciences12010037_perova 1 +We added: “We define as recent tectonic activity the events that are recorded at the surface and can alter the surface with active tectonic features, such as modifications of the drainage system” • Discussion: One general comment, could the use of other tracers (radon, of stable isotopes of water) yield also insight on the origin of the fluids sampled in this study? 2 1 Line 360: Here and throughout the text, the word ‘recent’ is used to describe some tectonic activity. It would be good define what recent means in the context of this study. An indication is provided in the Discussion (Line 414), but it would go to state this value upfront in the text. 1 2 geosciences12010037_perova 1 +Radon cannot give this information since with the short half-live of 3.8days it's signal comes only from the direct vicinity of the sampled location. Stable isotopes of water could in principle do this if there is a geothermal signature on them (such as plotting far left to the meteoric water line - see inset in Figure 1 of McIntosh and Ferguson, 2020 – Geophysical research Letter) - but we have not seen such a signature. We may mention that in the text - but for such a signature to be discernible the bulk of the water needs to be geothermal, and what we see is only a small admixture. 2 1 Discussion: One general comment, could the use of other tracers (radon, of stable isotopes of water) yield also insight on the origin of the fluids sampled in this study? 1 2 geosciences12010037_perova 1 +The revisited figure 43 is now providing this information Seismic reflection 2D lines (1989-2015). 2 1 Aeromagnetic survey data acquired over the last 50+ years were employed for mapping structural and lithological features. Although the aeromagnetic data is said to be employed for structural interpretation, details somewhat sketchy. Reference is made to “…prominent […] magnetic lineaments which can be caused by faulting”, and “…several circular low magnetization anomalies, approximately two kilometers in diameter, aligned with northwest trending lineaments”. It would be nice to include a map with these features and lineaments interpreted from the aeromagnetic datasets. This would also tie the observations based on this dataset closer to the seismic interpretation (see below). 1 2 geosciences12010037_perova 1 +Thank you, the details comments on those figures have been followed and new figures are provided Helium measurements from groundwater samples. 2 1 Seismic reflection 2D lines (1989-2015). 8500 km. Interpretation of shallow horizons and faults using all publicly available geological and geophysical data of the Beetaloo region. Fault polygons defined for five horizons. Depth conversion using check-shot velocities from 26 wells. See comments to Figure 4. The depth maps provided in Figure 5 should be supplemented by isochore maps for the rock volumes between pairs of mapped reflectors. See also comments to Figure 7. 1 2 geosciences12010037_perova 1 +"There is no other reference to date to the ""primary documentation"" but the link to the data (they should now be online) which are in the fact sheets." 2 1 Helium measurements from groundwater samples. With respect to the helium measurements, no detailed documentation of where these samples were collected is provided beyond referring to Geological and Bioregional Assessment Program (2021a) Fact sheet 12, and Geological and Bioregional Assessment Program (2021b) Regional tracer results from the Cambrian Limestone Aquifer. These are both summary documents. Please provide a reference to the primary documentation. 1 2 geosciences12010037_perova 1 +We have redone the figure 2 and added explanations on the process (see reply to comments on figure 2). Figure 8 should now be easier to read The surface drainage network line dataset was indeed based on the simplified (n=130) network following the following approach: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. 2 1 Fault and surface drainage network mapping (tectonic geomorphology). The drainage network was extracted automatically. It is not clear if the “simplified” drainage network shown in Figure 2 was also extracted automatically. The data is summarized in Figure 8 (see also comments to Figure 8 below). It is not clear if the surface drainage network line dataset is based on the “unfiltered” or “simplified” data shown in Figure 2. Since n=130, one can assume the latter. It is however not made clear how this “simplified” network was generated, but there appear to be a substantial number of instances where the “simplification” provides apparent mismatches with the original data (see examples included in comments to Figure 2 below). The accuracy of the resulting plot can therefore be questioned. If the “simplified” network was generated automatically, I encourage the authors to do a manual QC of the results. 1 2 geosciences12010037_perova 1 +There is indeed an error on the figure referencing, we modified to Figure 3B where the lineaments are now clearly indicated. 2 1 Line 303: “We reviewed the seismic data in detail at the intersections with north-northwest trending lineaments observed on the magnetic dataset (Figure 4).” No such lineaments are shown in Figure 4. 1 2 geosciences12010037_perova 1 +We indeed need to add this link- we will put a link in place upon acceptance of the paper Figures Figure 1A. 2 1 Line 582. Link for supplementary materials does not work. 1 2 geosciences12010037_perova 1 +done, we also modified the fault legend to add clarity - Replace white labels with black lettering with no labels and white lettering. 2 1 Poor visual discretization of main surface fault traces and Post Wilton geophysical faults (maybe use different colour for the two?) 1 2 geosciences12010037_perova 1 +We separated the legends from figures 1A and 1B as to add clarity. This article is focused on the Beetaloo subbasin and we use the direct input for Geoscience Australia in this stratigraphic column. We are not willing to add complexity by presenting in detail the Basins that are covering the Beetaloo Sub-Basin. We removed from the legend the details on the different basins as we understand that it is leading the reviewer in directions we are not exploring on the CLA stratigraphy- we do not refer this complexity in the results and discussion. 2 1 Consider adding a small inset table or schematic to showing the Cambrian Limestone Aquifer stratigraphy in the Georgina, Daly and Wiso basin. Although this is described in the caption, it is not easy to grasp for someone not familiar with the stratigraphy in the area without spending time some time with paper and pencil. 1 2 geosciences12010037_perova 1 +Thanks, the figure have been entirely revisited and divided into four subfigures as advised below -Consider splitting into several maps, e.g. 2 1 Very, very overloaded figure, screen-dump from a mapping programme? 1 2 geosciences12010037_perova 1 +This output was then overlayed upon satellite and magnetic images where lineaments are evident for checking and quality control. In this process, minor mismatches of the automated simplified lines were removed and small drainage segments were connected along major lineaments for further simplification and reduction of the dataset. The adopted approach was: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. We added this description of the adopted approach in the legend Figure 3 -Very small/illegible typeface on map coordinates – consider simplifying scales and use larger typeface. 2 1 How the authors arrive at the simplified drainage network is not very clear 1 2 geosciences12010037_perova 1 +figure redrawn - Replace white labels with black typeface with white typeface. 2 1 Poor quality figure (low resolution) in the version available to the reviewer. 1 2 geosciences12010037_perova 1 +Well label typos modified -Thin grey seismic lines are not explained in the legend or caption. 2 1 Many well-name labels are hard difficult to read/illegible. Consider replacing well names on the map with numbers at the well position (white circles, black typeface) and add a table in the legend listing number and corresponding name of the well. 1 2 geosciences12010037_perova 1 +Legend added for those lines -The outline of the Eastern and Western Beetaloo Basin in Figure 3 and 4 should be kept identical in order to position Figure 6 A, B and C in relation to the seismic lines shown in Figure 4. 2 1 Thin grey seismic lines are not explained in the legend or caption. Why are these not classified in terms of signal quality? 1 2 geosciences12010037_perova 1 +isochores added as supplementary material Figure 6 Add scale(s).done Figure 7. 2 1 Consider adding isochore maps for intervals between interpreted reflectors. These often highlight tectonic accommodation space creation better than maps. 1 2 geosciences12010037_perova 1 +done, legend cleared from information not represented 2 1 Explain/improve labels (what do you mean by “ntspr_2M_gw”? “Coast_10million”? “frameworkboundaries”? “State_Borders_10million”. Amend labels or explain in caption. 1 2 geosciences12010037_perova 1 +checked and clarified Clean up map: 1. 2 1 Several items in the legend appear to have the same or very similar signatures. 1 2 geosciences12010037_perova 1 +identified in the legend and representation 2 1 Not possible to differentiate post-Wilton fault types properly in the figure. 1 2 geosciences12010037_perova 1 +removed 2 1 Could not find “Coast_10million”, “frameworkboundaries” or “State_Borders_10million” on the map. If these items are present, please use a more contrasting signatures to make it more visible. If they are not present on the map, remove these items from the legend. 1 2 geosciences12010037_perova 1 +Outline size modified and homogenised with other figures 4. 2 1 Consider replacing the purple outline of the eastern and western sub-basin with light grey shading. 1 2 geosciences12010037_perova 1 +Red selected 5. 2 1 Consider using the most prominent colour (red) for the possible fluid escape features as this is the key element of the map. Bright green might also bee an option. 1 2 geosciences12010037_perova 1 +modified 2 1 Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). 1 2 geosciences12010037_perova 1 +modified accordingly Consider adding a simple conceptual sketch highlighting the stratigraphic position of the different faults (and possible fluid escape structures– this would also help visualizing which stratigraphic intervals the potential fluid escapes originate from and which stratigraphic intervals are potentially connected along potential fault-related fluid flow pathways. 2 1 The link between interpreted faults and fluid or gas escape features is a key feature of this figure. The map differentiates between “BaseCambrian seismic faults”, Post-Wilton “Strike-slip” and “Reverse” faults, and “FAULTS”. The categorization is not adequately explained (e.g. what differentiates “FAULT” from a “BaseCambrianSeismic fault”?). 1 2 geosciences12010037_perova 1 +With the new classification the reader should be able to better read the paper and can now directly refer to the stratigraphic table Figure 8. 2 1 Consider adding a simple conceptual sketch highlighting the stratigraphic position of the different faults (and possible fluid escape structures– this would also help visualizing which stratigraphic intervals the potential fluid escapes originate from and which stratigraphic intervals are potentially connected along potential fault-related fluid flow pathways. 1 2 geosciences12010037_perova 1 +Done, figure clarified as well Figure 9. 2 1 Please provide a more informative caption to what these plots show. What is included in the “Drainage and structural lineament analysis” plot? 1 2 geosciences12010037_perova 1 +we also totally revisited this figure as to have a cleared output 2 1 Figure 9. Poor resolution in the copy provided for the review. Consider using higher contrast colours or thicker lines to highlight different faults on the map. 1 2 geosciences12010037_perova 1 +Thank you, we truly appreciated the time took by the reviewer to provide detail guidance to improve the manuscript and the figures 2 1 I hope you will find these comments useful when revising the manuscript and look forward to seeing the paper published in Geoscience. 1 2 geosciences12010037_perova 1 +The helium measurements have been added as supplementary data and the author made a clear difference between this study Helium measurements and other tracer studies we are citing. 4 1 With respect to the helium measurements, the references to the primary documentation requested by the reviewer in comments to v.1 of the manuscript are not provided, nor do the authors provide any comment as to why they deem this unnecessary. Section 4.3 Helium concentrations and isotopic composition measured in groundwater, is framed around results from previous studies. Providing references to these original studies (including access to the actual data that allow objective verification) rather than referencing to summary papers would be more in line with scientific publishing practice. If the primary documentation is not accessible, the authors should state this clearly. 3 2 geosciences12010037_perova 1 +Done, thank you 4 1 Figure 4. Seismic reflection data quality is ranked and colour-coded as “Excellent”, “Average” and “Poor”. Where does the fourth category, “Fair”, which also is a qualitative category, fit in, and why not include this category in the legend? 3 2 geosciences12010037_perova 1 +The isochores have been added in the seismic supplementary dataset 4 1 Figure 5. Isochron maps have been included in the supplementary material, the initial review suggested isoCHORE maps. Including these is maybe not critical, but as mentioned in the initial review, thickness maps sometimes highlight structural lineaments quite well. I don't know if this is the case here, but if they do, including isochore maps would enhance the readers' understanding of basin geometry and -infill. 3 2 geosciences12010037_perova 1 +Post Wilton “Strike-slip” and “Reverse” faults have been redrawn in all figures (Figure 1, 7, 9) with a new colour code, the fluid escape features are now shown as red dots in the legend as well. 4 1 If I understand the map correctly, fluid escape features on the map are shown as red dots. Why does the legend show these as thick red lines? 3 2 geosciences12010037_perova 1 +Number of measurements added in each plot. Figure 2a correspond to the SEEBASE structural lineaments (n=681). 4 1 Figure 8. Please keep the number of measurements included in each plot. The plot “Surface drainage network from this study” is identical to the original figure and should have n=130 measurements. According to the new caption shows the unfiltered surface drainage network. To my understanding this should correspond to Figure 2 a, which shows substantially more than 130 lineaments. How did you pick the ones you measured? Please clarify. 3 2 geosciences12010037_perova 1 +The second part of this analysis, titled: “Body composition assessment in Mexican children and adolescents. Part 2: Cross-validation of three bio-electrical impedance methods against dual X-ray absorptiometry for whole-body and regional body composition”, has already been accepted by Nutrients #1604578. The two analyses were conducted on the same children’s database and closely complement each other. As the accepted manuscript already includes the phrase ‘Part 2’ we prefer to keep ‘Part 1’ here ABSTRACT 2. 2 1 The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. This does not seem to be addressed in the article, thus there seems to be no reason to include this phrase in the title. 1 2 nu14051073_perova 1 +Corrected, we adjusted this paragraph together with the next one to give a clearer explanation of the motivation of this study. 2 1 P2 L61: FFM is obtained via the 4C model – it is not a surrogate. Also, the difference(s) between FFM and LM definitions are nuanced and complex and should either be defined, or alternate text should be used here. It seems that the authors are simply trying to point out that use of the 4C model is not common and that other methods are normally used. Best to clarify this statement. 1 2 nu14051073_perova 1 +We have adjusted accordingly. We hope now we can give a clearer explanation about the motivation of this study. 2 1 P2 L69: The aim stated here does not follow the logic of the preceding statements in the paragraph, i.e., what does comparing BC methods have to do with lack of healthcare or technology? Is the focus then on finding low cost, easy to apply methods? The aim (and intent) of the study seems too simplistic as stated here – merely comparing methods. How would the results be applied to the healthcare situation in Mexico? These topics should be tied together, or an alternative motivation needs to be presented. 1 2 nu14051073_perova 1 +Clarified in lines 164. 2 1 P3 L94: This is awkwardly worded. Who was asked to assent? 1 2 nu14051073_perova 1 +The data used was total body with head, as recommended for the ISCD when using DXA for body composition instead of for bone densitometry. We clarified and referenced this in the text, lines 204-208. 2 1 P3 L125: DXA: Was the head ROI excluded from the analyses (as per recommendation by the ISCD)? If so, it should be stated. If not, DXA analysis should be redone and all relationships recalculated. 1 2 nu14051073_perova 1 +This was a typo, we corrected it. Line 260. 2 1 P5 L176: “(n=52?? )” Is there uncertainty of the number of participants or is this merely a typo? 1 2 nu14051073_perova 1 +We corrected (lines 287-288). 2 1 P5 L207: The means of FM would be compared using t-test, not calculated. 1 2 nu14051073_perova 1 +Indeed, it was like that. We have changed it to show only the data of the 288 subjects (without the 5 outliers). 2 1 Table 1: The n values in the column headers add up to 293 rather than 288. Are the n values incorrect or is the entire cohort presented here? 1 2 nu14051073_perova 1 +This was because of the inclusion of the 5 outliers in table 1, which has been corrected. 2 1 Table 1; Body Composition Variables: The mean values do not all agree with those in supplementary Table 1. 1 2 nu14051073_perova 1 +We have 2 1 Table 1; MRI subsample: There is no indication of age, BMI, etc. in this group. That information may be helpful, perhaps also as supplementary data. 1 2 nu14051073_perova 1 +Added, the analysis was for the total sample and by subgroups by age and sex, line 287 14. 2 1 P7 L226: It would be helpful if it was made clear that this refers to comparisons of means of all subjects (not broken down by age, sex). 1 2 nu14051073_perova 1 +We have corrected as recommended. Table 4 sent to supplementary material as supplementary table 3. 2 1 P12 L283: Is Table 4 necessary? The title (and aim?) of the paper is all about comparing techniques against the 4C model. One also begins to wonder about affecting type 1 errors due to multiplicity of comparisons (debatable but worth considering). It may be worth considering moving Table 4 to the supplementary file and bringing supplementary Table 1 into the main document. If the focus (see the title) of the article is comparisons with the 4C model, then supplementary Table 1 seems to merit more direct attention. 1 2 nu14051073_perova 1 +Changed as supplementary figure 3. 2 1 As stated above, it may be worth considering moving these Bland-Altman figures to the supplementary file. 1 2 nu14051073_perova 1 +Changed, line 19 INTRODUCTION 3. 2 1 P15 L393: This paragraph reads more like a conclusion and seem out of place. It should perhaps be the last paragraph in the Discussion. 1 2 nu14051073_perova 1 +We have stated in the conclusion that while individual methods show bias relative to the 4-component reference, the high correlations indicate that all the methods perform well in ranking individual children as having high or low FFM and fat mass. This ranking is itself very valuable in routine clinical care, particularly for longitudinal assessment. We have provided new evidence for the Mexican population that all the methods have utility for this purpose. Furthermore, some of the biases for individual methods can be resolved by the publication of method-specific reference data, whereby all data can be converted to method-specific z-scores. Publishing such reference data is a further aim of our project. 2 1 Much of the Discussion addresses strengths and weaknesses of the different BC methods, as if to provide guidance for clinicians in selecting the best techniques according to their needs and capabilities. None of the methods are ideal – all are flawed (in comparison with a gold standard). Yet a firm conclusion seems to be lacking. Concluding that methods differ is not surprising. One may be better served by discussing how the differences in methods (i.e. over or under estimating FM) may affect health assessments. That is, what impact may underestimating FM, by relying on one particular method, have on child care? How critical is the method selection? Somehow this needs to be tied more firmly to the population and environment being studied. 1 2 nu14051073_perova 1 +added 2 1 "I am not familiar with the Bland-Altman method, so was unclear when I read the methods section whether the text in lines 204-207 was explaining the Bland-Altman method or describing a separate procedure. I take from the results that those sentences were describing the Bland-Altman procedure, and if so, adding some text along the lines of ""In this procedure..."" would be helpful. As it was, I couldn't understand the description provided, and it didn't seem to match the figures, which were simply labeled as FM, so seemed to be a simple plots of FM using 2 methods on first read." 1 2 nu14051073_perova 1 +Added to supplementary figure 1 and main figures 1 and 2 3. 2 1 "Relatedly, it would have been helpful to have more explanatory titles for the plots--eg ""Differential correlation between methods across levels of FM"". And, the meaning of the trend line was very counter-intuitive, so an interpretive note under the plots would have been helpful. (E.g., ""A positive trend indicates increasing underestimation of FM at high FM levels; a negative trend indicates increasing overestimation of FM at high FM levels." 1 2 nu14051073_perova 1 +Specified in limitations lines 993-997. Important to say is that ~89% of Mexican population is Hispanic. Only 6.6% belong to indigenous population and 5.9% to Afro-Mexican ethnic groups. 2 1 There is no description of the race and ethnic composition of the sample. I am not well-versed in the ethnic composition of Mexico, however, would it be helpful to know the degree of representation of, for example, youth who are Black, of Indigenous ancestry, and of European ancestry? Or are there other ethnic or cultural groups that should be represented? 1 2 nu14051073_perova 1 +Corrected. In the previous version we put data of the whole sample of 293 subjects (including 5 outliers that should not been there). We have corrected the data, and now we only present data on the 288 subjects for both tables. 2 1 I didn't understand why the data differed between Table 1 and Supplementary Table 1. Why did Ns (and means/SDs) differ? 1 2 nu14051073_perova 1 +Added to table 1. 2 1 Not all abbreviations are listed for the table footnotes (FFM, D2O, DXA, LM, BV, ADP) 1 2 nu14051073_perova 1 +The definition of glaucomatous visual field loss was elaborated in the corresponding reference. However, we agree that we were very brief in explaining glaucomatous visual field loss in the manuscript. Therefore we made the following changes to elaborate: In lines 89-98, we changed: “iOAG was defined as glaucomatous visual field loss in at least one eye with reproducibility of the defect, independent of IOP” To: “All participants underwent visual field testing using the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Jena, Germany). A second supra-threshold test was performed when a visual field defect appeared to be present. Details have been described elsewhere. [1] If the second supra-threshold test showed at least one overlapping abnormality in the same hemifield, Goldmann kinetic perimetry (RS-I-1 and RS-I-3; Haag-Streit) or full-threshold HFA (all other cohort visits) was performed on both eyes. If abnormalities were consecutive and reproducible, thus present on the Goldmann or full-threshold test and on both supra-threshold tests, visual field loss was considered to be present. Defects had to be in a consistent hemifield and a least one depressed test point had to have exactly the same location on all fields.” In lines 98-100, we changed: “All other possible causes of visual field loss were excluded.” To: “Glaucoma specialists examined fundus photographs, ophthalmic examination reports, medical histories, and MRI scans of the brain to exclude all other possible causes of visual field loss. Discrepancies were resolved by consensus.” In lines 103-104, we added: “For IOP, three measurements were taken from each eye, of which the median value was recorded. [2] For iOAG cases, we used IOP measurements of the affected eye. If both eyes were affected or unaffected, a random eye was selected. IOP was not included in the definition of iOAG.” Was glaucoma also defined by an objective finding, such as the optic disc finding or imaging of the optic disc? 2 1 What was the definition of visual field loss that defined glaucoma? 1 2 nu14122490_makarova 1 +OCT images were taken with SD-OCT (Topcon Corp., Tokyo, Japan) since 2007. This means that OCT images are not available for the first four visits of RS-I, and the first two visits of RS-II. Additionally, only part of the images are focused on the disc and even less are reliably segmented. Fundus images were available and were used rather to exclude other cases of visual field loss in participants that showed visual field defects than to observe optic disc abnormalities. 2 1 Was glaucoma also defined by an objective finding, such as the optic disc finding or imaging of the optic disc? 1 2 nu14122490_makarova 1 +Thank you for this comment. We understand that it might be useful to present the number of treated glaucoma cases in our baseline characteristics table. Unfortunately, detailed information on prior treatment/surgery for glaucoma is limited (only present for RS-I), and therefore we did not include this variable as covariate in our models. It is thus possible that incident glaucoma cases have received treatment for glaucoma in between two research visits. However, since all participants were (confirmed by examination) free of OAG at baseline, treatment for glaucoma could not have been longer than maximum of one follow-up visit. Although not having this data is a limitation of this study, we do not think it is an important confounding factor, since we do not expect that glaucoma treatment would influence one’s diet. More importantly, dietary information was collected at baseline, with all participants free of OAG. Therefore, if glaucoma presence or glaucoma treatment would have an effect on dietary intake, this would not be applicable in our study. We have added a short sentence explaining this in lines 312-316 of the manuscript. 2 1 Were the incident cases of glaucoma or controls being treated in any case prior to their diagnoses? 1 2 nu14122490_makarova 1 +We agree that, although our findings confirm earlier reported associations between dietary nitrate intake and OAG, intervention studies are necessary to investigate and confirm the association between dietary nitrate intake and iOAG. Therefore, we will change all references to “protective (effect)” to “association/associated with”. 2 1 """ As we did not observe an association between dietary nitrate intake and IOP, nitrate may protect against glaucoma via other, IOP-independent, mechanisms. "" The authors should avoid making statements such as ""nitrate is protective"" since what they have found is a statistical association." 1 2 nu14122490_makarova 1 +Thank you for this suggestion. Although the evidence for the association between ischemia--reperfusion and glaucoma pathogenesis might be scarce, this is only one possible pathway that is addressed in explaining the inverse association between dietary nitrate intake and glaucoma incidence. Nevertheless, we will adjust the manuscript (lines: 271-288) so that this statement is less strong and the focus is more on (a combination with) other pathways, rather than this pathway alone. 2 1 There is very little association between ischemia--reperfusion and glaucoma pathogenesis hence the statements on page nine are irrelevant. 1 2 nu14122490_makarova 1 +We agree that the baseline dates of all three cohorts (RS-I, 1991-1993; RS-II, 2000-2001; RS-III, 2006-2008) are already quite some years ago and that dietary patterns in general have changed over time. However, since dietary recommendations are not standard of care for glaucoma patients, we believe that this would likely lead to non-differential misclassification (that causes a bias towards the null hypothesis), since we would expect that glaucoma cases would change their diet similarly to our control population and vice versa. We thus feel that this study and its findings are still highly relevant today since nutrition has become ever more important in medical sciences. Ophthalmology is one of the disciplines which has gained enormous insights from these recent developments. However, to date, no nutritional recommendations have been made for glaucoma patients and research into the association between nutrition (on each level, e.g. diets, food groups, nutrients) and glaucoma is scarce. If associated, this may support diet recommendations in patients that show first signs of developing glaucoma and/or people at-risk for glaucoma as well, impacting millions of people worldwide. Especially since diet changes into a vegetarian of vegan diet are becoming more popular, we think that understanding the potential beneficial effects of these changes, thus the effects of vegetables and their nutrients, is more important than ever. We do agree that these findings should be replicated or validated in another (preferably, an intervention study) study before dietary nitrate intake should be considered as an important public health implication. To address your question about the change of dietary patterns over time more thoroughly: Dinnisen et al. [6] recently published an article in Nutrients where they described changes in dietary intakes of Dutch adults between 2007-2010 and 2012-2016, and evaluated these changes by age, gender, and education. They demonstrated that there was no significant increase in vegetable intake for Dutch adults aged 19–69 years between 2007–2010 (n = 2106; DNFCS 2007–2010) and 2012–2016 (n = 1540; DNFCS 2007–2010) for the total population. There was also no difference when they compared the change in vegetable intake over time per sex or per age category (51-69 years being closest to the baseline age used in our study). Only in the group with the highest educational level, the mean consumption of vegetables increased over time. However, since there was no significant difference in education level in our study between cases and controls (Table 1), we assume that changes in vegetable intake would be similar between both groups, leading to non-differential misclassification. Moreover, we adjusted for education level in our additional model. Regarding dietary nitrate intake from non-vegetable sources, this article states that the intake of red or processed meat decreased over time. This was applicable to both males and females and seen for all age groups. Again, we would expect that this decrease is similar for glaucoma cases and controls. Another Dutch study [7], starting in 1986 (which is more close to the first visit of RS-I) stated that “Another potential limitation that should be considered is whether the food frequency questionnaire at baseline was a reliable estimate of past and future diet. The stability of dietary habits over time was evaluated from five annually repeated questionnaire administrations in independent random samples of the cohort. The mean intakes barely changed and the correlation between two measurements decreased only slightly over an increasing time interval. It was concluded that the single food frequency questionnaire measurement characterizes dietary habits for a period of at least 5 to 10 years.” [8] Nevertheless, since both studies are not directly translatable to the Rotterdam Study, we have assessed the association between the dietary nitrate intake and iOAG over cumulative follow-up periods to provide insight into the stability of the found estimates over time. Please see our comment regarding your next suggestion for more details. 2 1 If I am calculating correctly it has been over 20 years since the incident cases average followup occurred, that is 10-20 years after the start of a study in 1991. How much might the diet of persons in this population have changed since then? Thus, is this study still relevant to today? 30 years ago eating more vegetables was not the vogue it is today. 1 2 nu14122490_makarova 1 +We agree that the lack of follow-up food questionnaires is a major limitation of this study. Please find an additional supplementary figure (Figure S1; original Figure S1 has now become Figure S2) below and in the supplements of the manuscript, to show that we assessed the association between the dietary nitrate intake and iOAG over cumulative follow-up periods (x-axis) to provide insight into possible reversed causality. The persistence of the association over time implies that reverse causality is unlikely. The effect of (baseline) dietary nitrate intake on glaucoma appears to be relatively stable over time. We therefore consider our results reliable, although we agree limitations are present and these findings should be interpreted with caution. In addition to the new supplementary figure, we have added information about this analysis to the methods (lines 152-153), results (209-211), and discussion (296-298). 2 1 This study would have been that much stronger if a follow-up food questionnaire had been administered. The long space between the questionnaire and the incidence of glaucoma (only mentioned at the last part of the limitations) is quite a major limitation. 1 2 nu14122490_makarova 1 +Thank you very much for assessing the covariates included in these analyses so thoroughly. Unfortunately, family history of glaucoma was only available for a subset of the first cohort, and not for the second and third cohort. Therefore, we were unable to include this variable as a covariate, as this would severely limit our power (528 participants of 1038 participants; 133 glaucoma cases and 389 controls). As cup-to-disc ratio is highly correlated with glaucoma diagnosis, we feel that cup-to-disc ratio should not be included in the model. Moreover, cup-to-disc ratio is not associated with dietary nitrate intake, and therefore cannot be considered as confounding factor. By including cup-to-disc ratio into the model, we would adjust the association between dietary nitrate intake and glaucoma by “glaucoma presence” and thus diminish any existing association. To meet your comment/suggestion, we have added baseline spherical equivalent (proxy for myopia, excluding aphakic or pseudophakic participants) to model 3. As you can see in the results below (original results visualized in Figure 2 in the manuscript), adjusting additionally for SE did not change the results of the continuous nitrate intake analyses and did only marginally change the results of the quintile analyses, leading to a more significant finding for Q5 as compared to Q1. Because both analyses are similar, and since myopia is associated with education level, we chose to keep the original model 3 in the manuscript, adjusting for education level, but without adjustment for SE. To address your question, in lines 318-323, we will change: “Finally, although the analyses were adjusted for several confounders, residual confounding cannot completely be excluded.” To: “Although the analyses were adjusted for multiple confounders, we were unable to adjust for other possible confounders such as family history of glaucoma due to a lack of data. We did consider the risk factor myopia, for which we adjusted by including education level into model 3. We also included spherical equivalent into the model (data not shown), but this did not change the results. Lastly, residual confounding cannot completely be excluded.” Original model 3: model 1 additionally adjusted for education level and smoking status. 2 1 Past studies of the Rotterdam population mention several other risk factors which were not taken into account in this study including myopia, cup-to-disc ratio, and family history of glaucoma, as well as other features such as exfoliation. How big is the nitrate association compared to these? 1 2 nu14122490_makarova 1 +In the introduction section we have suggested that dietary nitrate might have both IOP-dependent, or blood pressure dependent, and IOP-independent effects that could affect glaucoma risk. Unfortunately, we were only able to assess the effect of dietary nitrate intake on IOP and blood pressure. In the most ideal situation, we would have assessed the effect of dietary nitrate intake on retinal nerve fiber layer (RNFL) thickness. Unfortunately, due to limitations as described above, we were not able to do so. Since we found no significant effects of dietary nitrate intake on IOP and blood pressure, we suggest that IOP-independent effects of dietary nitrate intake might influence glaucoma risk. This should be further investigated in future studies. 2 1 Overall the finding seems to be an association without a rationale since in effect of nitric oxide presumably related to past nitrate intake would, by their own discussion, change eye pressure or blood pressure yet neither variable was associated with the incident glaucoma. 1 2 nu14122490_makarova 1 +We would like to thank the reviewer for the positive feedback on our study design and our final manuscript. 2 1 The authors have conducted a case-control analysis based on a large epidemiological prospective study and investigated an association between dietary nitrate intake and incidence of OAG. The study has been well planned and performed. Chapter Material and Methods contain all necessary information. The writing is of perfect quality and the results are clearly presented. The results and conclusions of this study are important. 1 2 nu14122490_makarova 1 +We would like to thank the reviewer for this interesting comment. In the Rotterdam Study we indeed find an inverse association between BMI and OAG incidence (Table 1). When we divide the participants in three categories based on their BMI (BMI < 18.5, BMI 18.5-24.9, or BMI >= 24.9), the difference between cases and controls is still (borderline) significant (p=0.054), with more people being overweight (68.7%) in the control group than in the glaucoma group (59.3%). The finding that BMI is inversely associated with OAG is in line with previous studies. Lin et al. [1] found that lower BMI was associated with increased odds of OAG, especially in younger females. Ramdas et al. found similar results, with an association between obesity and a lower risk of developing OAG, although only present in women. [2] In line with these findings, underweight was associated with increased risk of primary OAG in diabetes patients. [3] Moreover, in a group of patients in which visual field loss progressed despite treatment with eye drops, lower BMI was associated with progression of visual field loss in normal-tension glaucoma patients. [4] One possible explanation for this is that cerebrospinal fluid pressure (CSFP) has a positive, linear relationship with BMI. [5] As reduced CSFP may be a risk factor for primary OAG, individuals with lower BMI may have an increased risk for developing primary OAG. [6] Again, a higher BMI may be protective. We acknowledge that BMI is an important confounder in our study, as BMI is associated with both our outcome (OAG) and exposure (diet). We have therefore included BMI as covariate in our main model. Adding or removing BMI from the multivariate model (model 1) did not change the results, as can be seen in the table below. That the association did not change after adjustment for BMI suggests that the association between dietary nitrate intake and OAG cannot be explained by BMI, although residual confounding may persist. To account for a possible effect of BMI on the association between dietary nitrate intake and OAG, we performed additional matching. We returned to the original dataset and matched cases and controls based on age (3-years range) and sex, as done previously, and additionally for BMI (2 kg/m2 range). Please see below for the “new” baseline characteristics table. Once the participants have been matched on age, sex and BMI, you can see that none of the covariates included in the models are significant between iOAG cases and controls. Cases only have a significantly higher IOP, which is expected, and somewhat shorter follow-up (not surprising, since they are excluded one they are diagnosed with iOAG). Diastolic blood pressure, BMI, and the dietary nitrate intakes are no longer different in the univariate analyses between cases and controls. We have created two supplementary tables (Table S4 and Table S5), to show that the associations found between dietary nitrate intake and iOAG or IOP, were largely similar in the analyses where we matched on BMI additionally, as compared to including BMI as covariate into model 1. Only the association between dietary nitrate intake from non-vegetable food sources and iOAG is no longer significant, but the change in effect estimates was minimal and they remained far below 1 (Table S4). For the analyses of IOP, the association between dietary nitrate intake from non-vegetable food sources goes from borderline significant to significant (Table S5). By displaying these results, we hope to have shown that the associations described in the original manuscript are most likely true associations and explained by dietary nitrate intake rather than age, sex, or BMI. Although an association between glaucoma and cardiovascular disease has been described in the literature [7-9], we believe this is more linked to their shared pathology, impaired auto regulatory capacity of glaucomatous eyes and arterial stiffness of CVD [7], or even genetics [10], than mediated by BMI. Apart from the two additional supplementary figures, we have added some information regarding this comment in lines 301-304 of the manuscript. 2 1 I would only like to ask about one fact that I find intriguing. The authors have found that participants without OAG had a significantly higher BMI than those with OAG. Their mean BMI was found to be 27.1 kg/m2 which is considered overweight. Lower risk of OAG would be related to a higher total dietary nitrate intake. “Previous research has shown that a higher dietary nitrate intake was associated with significantly wider retinal arterioles. [46] Widening of retinal arteriolar caliber is not only associated with lower risk of cardiovascular and cerebrovascular diseases [47,48], but also with lower risk of glaucoma”. On the other hand, “compared with individuals with a normal BMI (defined as a BMI of 18.5 to 24.9), lifetime risks for incident CVD [cardiovascular disease] were higher in middle-aged adults in the overweight and obese groups” Khan SS, Ning H, Wilkins JT, et al. Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. JAMA Cardiol. 2018;3(4):280–287. doi:10.1001/jamacardio.2018.0022 I wonder if the authors could comment on this in the Discussion. 1 2 nu14122490_makarova 1 +Authors immensely thank reviewer for the constructive suggestions and valuable comments which greatly helped in the improvement of the manuscript. The corrections have been incorporated as per the suggestions made by the reviewer. 2 1 The ms is the result of an intensive and years-long work of breeding, that eventually pyramidized several resistance genes and QTLs for abiotic traits into an indian elite rice variety. The work is not unprecedented in the concept, but provides interesting breeding material for specific indian farmers, which is an important achievement and is correctly taken up by authorities and international research centers. 1 2 plants11050622_perova 1 +Figures have been revised with addition of arrows and text to represent the data. Since a large number of ILs were screened, susceptible check (SC) was used with a set of ILs and hence SC couldn’t be shown in all figures. However, SC ‘HR12’ for blast disease was shown in all blast screening figures 3 to 5. Similarly, in Fig 5, ‘TN1’ and ‘Improved Samba Mahsuri’ as susceptible and resistant checks respectively for BB in comparison with IL-19031 were shown. Authors once again thank the reviewer for pointing out the mistake in legends. Now, we have rephrased the legends clearly describing all the terms. 2 1 The main issue with the ms is the quality of the figures: they are not clearly representing the data, arrows and text may help the reader, the controls are missing in most cases, and a general lack of precision is affecting them. Also, the legends are not clearly describing all the terms and should be revised. Legends should describe what is to be observed in the figure, possibly pointing to parts of special interest. 1 2 plants11050622_perova 1 +Figure 1 legend has been revised with inclusion of the details of kharif and rabi seasons. kharif is the wet season with crop growing period from June to November and rabi is the dry season with crop growing period from December to May. We described kharif as wet season and rabi as dry season in the materials and methods section also. 2 1 Explaining briefly which and what are the indian sesasons during which experiments have been conducted would help clarity. 1 2 plants11050622_perova 1 +Since the number of ILs is large, presenting phenotypic data for each IL will result in increasing the size of the main tables, hence data was earlier presented in supplementary tables. As suggested by the reviewers, we have revised the tables and presented the mean phenotypic data of BB, blast and drought screening in the main tables for each IL in parenthesis. Column on ‘no. of genes/QTL’ has been removed as suggested. Entry nos have been replaced with IL No as suggested. 2 1 "The phenotypic data are important, but currently they are presented only as additional material. The authors should consider reshaping the tables, eliminating unnecessary columns (e.g. no. of genes / QTLs, which is already represented in column 1) and add the most striking phenotypic data, when possible and relevant for discussion. Also ""entry nos."" is probably not clear and ILs no should maybe considered instead." 1 2 plants11050622_perova 1 +The present work is not essentially a backcross breeding program aimed at development of near isogenic lines. However, Krishna Hamsa was the common background into which several genes/QTL were targeted from multiple donors and considering the morphological similarity between 27 ILs and Krishna Hamsa, background selection was done retrospectively. BGS validated our observations on morphological similarity. The same has been discussed in the 5th para under ‘discussion’. Also results on BGS have been presented under subsection 2.3 of results with data on polymorphic markers for BGS in supplementary table S8. 2 1 The data on bgs are not sufficiently presented in the text nor discussed. 1 2 plants11050622_perova 1 +“()” have been removed while mentioned the numbers of the ILs and sentences have been revised appropriately in the manuscript. 2 1 "revise the use of ""-"" instead of ""( )"" when mentioning the numbers of the ILs, or any other system which would ensure a better homogeneity in comparison to the one present in the ms." 1 2 plants11050622_perova 1 +The above mentioned lines have been checked and found either spelling mistakes or revision of sentences. Accordingly, corrections were made. 2 1 check lines 21, 37, 93, 153, 183-184, 312, 351-353, 360, 377, 466 1 2 plants11050622_perova 1 +BLB has been replaced with BB throughout the manuscript. 2 1 stick to BB instead of BLB 1 2 plants11050622_perova 1 +Legends of figures and tables and text in the results section have been revised with explanation of acronyms as suggested. 2 1 consider anticipating the explanation of the acronyms which are eventually presented only in the M&M, to facilitate the reading; consider this aspect also in the legends 1 2 plants11050622_perova 1 +The sentence here is required to maintain flow of the subsequent content. 2 1 Lines 403 et seq. are redundant Response: 1 2 plants11050622_perova 1 +Both lines explain our observations in different sets of ILs. Sentence at 351 explains susceptibility in ILs despite possessing the targeted gene/QTLs while sentence at 414 explains resistance in ILs despite the absence of targeted gene/QTLs. 2 1 lines 414 et seq. seem to be contradicting lines 351 et seq. 1 2 plants11050622_perova 1 +The 85 ILs is a sum total of nine ILs marker positive to blast- R genes, nine ILs harbouring QTLs for drought tolerance and 67 ILs marker positive to BB-R genes mentioned at the beginning of 4th paragraph of discussion. As suggested, we have added in brief about the same at line 414. 2 1 the 85 ILs presented at 414 seem to be a bit out of the blue: a short intro to where they are coming from would help the reader. 1 2 plants11050622_perova 1 +Yes, we agree that there were some typo and spelling mistakes in the manuscript. The manuscript has been thoroughly revised for the same. 2 1 With minor grammatical revisions, the manuscript can be accepted as is. 1 2 plants11050622_perova 1 +Authors once again thank the reviewer for correct assessment of the basic purpose of the manuscript. Yes, this is truly an overview paper presenting the interesting observations from our study. The introgression scheme and phenotyping of various biotic traits and drought phenotyping have been described in detail under ‘Materials and Methods’ section. The metric data on yield traits was statistically analyzed and results of ANOVA, heritability and critical differences have been presented in the manuscript. Authors agree that it would be more inferential with chi square values. However, the crossing scheme was viewed holistically and data on each cross was not maintained separately as the present study aimed at selecting introgression lines from multiples crosses with multiple stress resistance/tolerance by pooling several genes and QTLs into a common background. Despite maintaining large base populations, plants per se were selected based on marker positivity for inter-crossing and selfing and further stringent phenotypic selection for the targeted traits. Hence, chi-square which is perfectly apt for population derived from biparental crosses is not used in our study. 2 1 It is also acknowledged that this paper is probably the first of many papers to emerge from the study. As such, it is an overview paper that raises many questions. It would be interesting for the authors to provide more information about the research design and estimation methodologies, such as chi-square analysis of introgression lines, if possible for each crossed IL population. I only recommend some minor revisions before acceptance. 1 2 plants11050622_perova 1 +Authors feel greatly encouraged and motivated with the reviewer’s comments. 2 1 This work is of outstanding quality, and I normally present more critical points in my reviews. However, this time it is just very beautiful work. 1 2 plants11050622_perova 1 +‘=261%’ has been corrected to ‘+261%’ and typo error of ‘linkes’ corrected to ‘linked’ 2 1 Line 262: “=261 %” , and Line 312 “linkes” a typo? Correct it Response: 1 2 plants11050622_perova 1 +Added references appropriately at two places as suggested by the reviewer. 2 1 L48-63: should add some citations on the first part of introduction. 1 2 plants11050622_perova 1 +Explanation for boro season has been added. 2 1 L127: Please add the explanation of “boro season”. 1 2 plants11050622_perova 1 +Legends of the supplementary tables have been revised and inference of the table is given in foot note. 2 1 The legend of supplementary table should be improved. Table and main text are independent, so the authors have to describe the table more carefully. 1 2 plants11050622_perova 1 +Authors once again thank the reviewer for the valuable suggestion. More details on the statistical analysis have been added as suggested. 2 1 L562: the section of statistical analysis should add more details. Also please indicate the R version. For example, how does H2 calculate? 1 2 plants11050622_perova 1 +Yes, significant means p-value. In the supplementary tables, expanded form of DFF is given as suggested. Treatments refers to introgression lines and check to control. For uniformity, we have changed the terminology to treatment instead of using IL or variety and check to control in all the revised supplementary tables and rephrased the legends accordingly. 2 1 On Supplementary table S2, does significant mean p-value? Indicate DFF = days to fifty percent flowering. What is the “treatment”? What do the results on “check” mean? How did you analyze “control vs IL”? 1 2 plants11050622_perova 1 +Similar to Supplementary Table S2, S3 has been revised 2 1 On Supplementary table S3, similar questions as S2, please also explain. 1 2 plants11050622_perova 1 +CD is the critical difference at 1% and 5% level of significance (p-value) for testing of significant differences among the ILs. The details of CD calculation have been added in the materials and methods section as suggested. 2 1 On Supplementary table S5, what is “C.D”? How did you calculate those values on those comparison types? 1 2 plants11050622_perova 1 +Supplementary table S5 is on CD and corrections have been addressed as suggested as at S. No 7. Supplementary table S6 have been modified by shifting data of BB and blast scores to main table. Each PC group is mentioned on top as sub heading at the start of each group. Each IL is presented only once in the entire table under separate PC groups. 2 1 Please re-organize the Supplementary table S5, I suggest use each ILs only appear one time and add one more column to show their PC groups. Then the table can be more informative and ease to read. 1 2 plants11050622_perova 1 +Full names of the abbreviations have been added as suggested. 2 1 Please add the full name of abbreviations. For example on L203 “CD”, L211 “SES“, L228 “UBN“ and L332 “ICAR-IRRR”. 1 2 plants11050622_perova 1 +Subtitle has been added as suggested. 2 1 The last paragraph of results is about background selection. Suggest to add subtitle “2.2.8”. 1 2 plants11050622_perova 1 +A representative gel picture has been added as suggested. 2 1 Please add some gel pictures of the foreground selection markers you used in order to visualize the genotyping results and showed the polymorphism of these markers on gel. 1 2 plants11050622_perova 1 +Table S8 represents polymorphic markers between pairs of parents including some common polymorphic markers. Hence the total number represented in the table S8 is not additive and not matching with the numbers given in the text. 124 is the total polymorphic markers excluding repetition. 27 ILs were selected based on their agro-morphological similarity with recurrent parent ‘Krishna Hamsa’ and evaluated for background recovery. The list of 27 ILs has been included in the revised manuscript as suggested. 2 1 L296-L302: the marker descriptions on main text cannot match the supplementary table S8. Also, what are those 27 ILs on L298? 1 2 plants11050622_perova 1 +Mention of appendix at L602 is a typo error and has been removed 2 1 L602: there is no appendix. 1 2 plants11050622_perova 1 +We very much appreciate the contributions. 2 1 Thank you for giving the opportunity to read such an interesting paper. 1 2 su14095590_makarova 1 +An analysis of extreme values was carried out, using univariate and multivariate detection methods. The analysis resulted in the elimination of 34 univariate extreme values and 2 multivariate extreme values. All statistical analysis was repeated considering a database of 520 companies. 2 1 For a better and accurate model I recommend the authors to eliminate from the model the extreme value. For example in Fig 2. - workers values greater then 40, community greater than 58, environment 45, customers 46 (the bullets), in Fig 3 - values with global score greater than 130, in Fig. 5 also all the bullets. Then repeat all the statistical analysis. 1 2 su14095590_makarova 1 +Thank you for your suggestion. We researched more literature on the subject and adopted a more moderate perspective for assessing normality (|Sk|>2-3, |Ku|>7-10 and |KuMult|>10). As you mention, with the elimination of the extreme values, the skewness and kurtosis values improved significantly, approaching the range -1 to 1. 2 1 In lines 391-395 I would prefer an Sk and Ku between -1 and 1. You have some values that are not included in this interval - maybe because of the outliers from the figures above that I recommend to exclude. 1 2 su14095590_makarova 1 +The discussion section has been improved and future research recommendations have been added in the conclusions. 2 1 The paper is interesting; however, it is not clear what the authors are trying to achieve with this study. The authors test a popular assessment tool using confirmatory factor analysis and finds that the model is weak. However, there is no in-depth discussion or recommendations that follow. In fact, the discussion needs to be grounded in previous research findings in regard to CSR/sustainability indices/assessment tools/initiatives. Unfortunately, I am really not sure what the point is here. 1 2 su14095590_makarova 1 +The hypothesis was removed since, as mentioned, it doesn't state what we are trying to test in this study. Factor analysis involves the examination of interdependence relationship, so it shouldn’t be expressed as a hypothesis that establishes dependence relationships. 2 1 Further, the hypothesis does not seem to be written correctly. First, it should be stated prior to the methods section. Second, currently it is descriptive. In other words, it doesn't state what the authors are trying to test in this study. 1 2 su14095590_makarova 1 +Major changes have been made to the paper. We hope that this new version may deserve your recommendation for publication. 2 1 Unfortunately, I cannot recommend publication unless major changes are made to the discussion section and possibly recommendations are added for future research and practice. 1 2 su14095590_makarova 1 +The manuscript has been revised to improve grammar and english language. 4 1 English language and style are fine/minor spell check required . 3 2 su14095590_makarova 1 +The discussion and conclusions sections have been improved (text in blue). 4 1 Are the arguments and discussion of findings coherent, balanced and compelling? 3 2 su14095590_makarova 1 +Thanks for the comment. The conclusions section has been improved (text in blue). 4 1 Are the conclusions thoroughly supported by the results presented in the article or referenced in secondary literature? Must be improved Response 4: Thanks for the comment. 3 2 su14095590_makarova 1 +Thank you! 4 1 Thank you for your revisions. 3 2 su14095590_makarova 1 +We very much appreciate the comment. 2 1 The paper is well structured and presented in a very meaningful manner. It definitely adds a value to the existed literature. 1 2 su14095590_makarova 1 +The argument associated with studies [28] & [29] was added. 2 1 There are minor corrections to be considered. This includes: Line 169 page 4, studies [28] & [29] do not reference to any presented argument(s) unless the preceding para. 1 2 su14095590_makarova 1 +The words Table and Figure have all been revised to start with a capital letter. 2 1 The word of Table in all text should start with capital letter (e.g. Line 199, L. 223) 1 2 su14095590_makarova 1 +Paragraph presented after Table 2 (page 7) has been moved to footnote. 2 1 Paragraph presented after Table 2 (page 7) is a repetitive content to what has been presented in the Table. It could be removed or move to footnote. 1 2 su14095590_makarova 1 +• The (***) have been replaced by the p-values (<0.001) in Table - B Impact Assessment - Regression Weights (original model) (current Table 6). 2 1 Paragraph presented after Table 2 (page 7) is a repetitive content to what has been presented in the Table. It could be removed or move to footnote. 1 2 su14095590_makarova 1 +Future research recommendations have been added to the conclusions. 2 1 Very good practical recommendations and criticism to the B Corp certification have been presented in the last para. of section (6). No any future research recommendations have been suggested by the respected authors. 1 2 su14095590_makarova 1 +Thank you. 2 1 References list is well prepared. 1 2 su14095590_makarova 1 +Thank you for the suggestion. The title has been clarified in line with the main objective. 2 1 Title: The title demands a review because there isn’t a connection between the first part and the second one. We understand what the authors intend to inform us after reading the paper. Even though this was clear to me, the title doesn’t show the real idea developed in the paper. The objective is a good guide for the title. 1 2 su14095590_makarova 1 +The results were improved and the paper's contribution was added. 2 1 Abstract: The content is well organized, but the results need some to attract the reader. What is the main result of the B assessment with the confirmatory analysis? Besides, the contribution isn’t clear here. 1 2 su14095590_makarova 1 +The introduction has been improved, including a better explaination of B Impact Assessment. The use of confirmatory factor analysis has been explained. The aim of the paper was revised in the abstract to be aligned with the one presented in the introduction. 2 1 Introduction: This section demands more attention because there are some empty spaces to fill. The authors should explain better what is B Impact Assessment. What is its contribution to the structure of a model using Confirmatory Analysis? For me, lines 39 and 40 show the aim of the paper, but the idea is different from the ones presented in the abstract (“The main objective is to understand the B Impact Assessment, verifying its added value in the sustainability process and socio-economic development of the business sector”). The sentence in the Introduction is more complete than the main objective in the Abstract. The ‘areas’ represent a broader goal than the main dimensions of sustainability (Triple Bottom Line). 1 2 su14095590_makarova 1 +Lines 70 to 82 have been revised and included in the introduction. Lines 90 to 103 have been revised and decided to be kept in the literature review as they express arguments from important scientific research ( S. Poponi, A. Colantoni, S. R. S. Cividino, and E. M. Mosconi, “The Stakeholders’ perspective within the B corp certification for a circular approach,” Sustain., vol. 11, no. 6, pp. 1–15, 2019, doi: 10.3390/su11061584. / T. De Mendonca and Y. Zhou, “What does targeting ecological sustainability mean for company financial performance?,” Bus. Strateg. Environ., vol. 28, no. 8, pp. 1583–1593, 2019, doi: 10.1002/bse.2334. / C. Putnam Rankin and T. L. Matthews, “Patterns of B Corps Certification: The Role of Institutional, Economic, and Political Resources,” Societies, vol. 10, no. 3, p. 72, 2020, doi: 10.3390/soc10030072.). The literature review was enhanced with scientific information in the fields of sustainability and certification, and, B Lab certification and sustainability. 2 1 Literature review: The lines from 70 to 82 could be summarized, and cut and paste in the Introduction section. I suggest cutting the text from lines 90 to 103 because it’s quite an advertisement for the B Certificate. The content in this section is exclusively dedicated to the Certification and the Corporation which offers it, there isn’t any scientific information there. The section demands a literature review about the theme, as the relationship between the certificate with adding value, sustainability, and the ‘areas’ governance, workers, community, environment, and customers. What is the idea of the assessment of sustainability, in these areas? This discussion is the basis of the paper, related to the objective, and connected with Figure 1 presented in the next section, Method. Even though the areas are from B Lab, the authors should study and related them to sustainability and value creation. There isn’t a literature review in this work. 1 2 su14095590_makarova 1 +The economic dimension has been added in the former lines 180 and 181. We clarify that figure 1 is original and was created by the authors. Regarding the data, we confirm that it was taken from the official website, during the period between March and May 2021. The link provided (https://bcorporation.eu/directory) was the one used. In the meantime, the site has been changed and the directory of certified companies can be found in another link. Table 2 has been eliminated. To avoid the repetition of information in Table 2 and the paragraph after, we followed the recommendations of another reviewer by placing the paragraph as a footnote. The reduction in the number of companies was based on the analysis of the database and information collected from B Lab that allowed us to see that there was a change in the measurement model used in B Corp certification during the period January 2017 and March 2021. Thus, to ensure the 3 consistency of the database and the statistical analysis subsequently performed, we reduced the database to a recent period in which the same measurement model was used. Finally, the hypothesis was removed since, as suggested by another reviewer, it doesn't state what we are trying to test in this study. Factor analysis involves the examination of interdependence relationship, so it shouldn’t be expressed as a hypothesis that establishes dependence relationships. 2 1 Method: In the Abstract, the objective added an economic dimension to the development, but in lines 180 and 181 the impact to be measured includes just environmental and social. It was not clear to me who is the author of Figure 1, the B Lab, or the authors of this paper? There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. The source of data from all companies in the sample isn’t clear, is B Corporation (site) or authors contact all these companies and did the survey? I understood that the data is from the B Corporation website. I accessed the link available in line 191 and there was a message ‘404 page not found, but when I clicked on ‘What is B Corporation’, I found the ‘areas’ and the steps for a company that intends to assess its practices and be certified. The authors should develop more theory than describe a model which has already existed. Table 2 and the paragraph after it is a repetition of Figure 1 and Table 1, could be cut. It’s clever to reduce the number of companies, though it isn’t clear who contacts the companies, the authors or Company B? The hypothesis is interesting when they come from a discussion in the literature review to the field research to test a theory (models, methods, frameworks, etc). Suddenly, appears one in the Method section, in a paper with a limited presentation of a technical model/certificate from an existed company. 1 2 su14095590_makarova 1 +"We have replaced the word ""indicator"" with ""aspect"" to eliminate possible confusion with the 5 indicators in the B Impact Assessment Model (Figure 6). The text has been completely revised and the word 'indices' has been used as the standard. The word ‘chapter’ has been replaced by ‘section’. Finally, we are thankful for the good appreciation to the many models studied in our research." 2 1 Results: The sentence from line 137 to line 138 isn’t clear when I saw Figure 6. The authors could use a standard for a plural of index word, ‘indices’ (345) or ‘indexes’ (362). In line 384 the authors should substitute ‘chapter’ for ‘section’. The authors presented and analyzed the variables/areas of certification with many models, it is interesting and is a basis for analysis in the next section. 1 2 su14095590_makarova 1 +The topic is “B Corp certification”. The text has been revised and the source has been added (E. Diez-Busto, L. Sanchez-Ruiz, and A. Fernandez-Laviada, “The b corp movement: A systematic literature review,” Sustain., vol. 13, no. 5, pp. 1–17, 2021, doi: 10.3390/su13052508.). Hypothesis 1 has been removed with the justification provided in response 5. Information was added on Cronbach’s Alpha and its impact on the need for B Impact Assessment improvement. 2 1 Discussion: In the first sentence, what is the topic that the authors mentioned? What source provided that information? The analysis is interesting, but demands more comparisons and explanations for cuts and adds. For me, the answer to Hypothesis 1 isn’t clear. The authors should reflect the presence of that in the text. The Cronbach’s Alpha ‘selected’ just ‘environment’ area of the B Lab model. This is an interesting result, which could be more analyzed with other assessment models presented in the text, to say what the authors wrote at the end of the section. 1 2 su14095590_makarova 1 +Thank you for the suggestions. The word was changed to “objective”. The discussion section has been improved in line with the suggestions made in the conclusion. 2 1 Conclusion: I just see one objective, but in the first sentence the authors wrote ‘objectives’. Where are they? The suggestions are interesting, but demand more analysis in the previous section. 1 2 su14095590_makarova 1 +The manuscript has been revised. The literature review has been improved, and new references have been added (text in blue). 4 1 Is the content succinctly described and contextualized with respect to previous and present theoretical background and empirical research (if applicable) on the topic? Must be improved. 3 2 su14095590_makarova 1 +The method section has been improved (text in blue). 4 1 Can be improved. Are the research design, questions, hypotheses and methods clearly stated? 3 2 su14095590_makarova 1 +We believe that the reviewers' suggestions have been very helpful in improving the manuscript. Thank you for the comment. The manuscript has been entirely revised. 4 1 The text has some improvements, but there are some points that still demand more attention. 3 2 su14095590_makarova 1 +We added more coherent theoretical arguments to the discussion based on the most recently published relevant academic papers on the topic (lines 125-133, 153-158, 442-452). The incorporated studies include Yarram and Adapa (2021), Boukattaya and Omri (2021), Shakil (2021), Wang, Wilson & Li, (2021), Cordeiro et al 2020, Birindelli, et al. (2019), and Nuber & Velte (2021). In total, the list of references increased from 21 to 36. The details of these studies and the logic behind their inclusion are explained in the text (pages 3 and 4). For the quantitative papers, our guiding line is the inclusion of papers proposing a reliable strategy to address the problem of endogeneity characterizing virtually all studies dealing with gender diversity. In a nutshell, gender diversity and firms’ performances (be they financial, ESG or environmental) have reverse causality. More gender-diverse boards are found to improve firms’ performances, and at the same time, better performing firms are more attractive to females. Any study incorporating these two variables would suffer from endogeneity. Therefore, inference and results are biased. Finding an instrument for gender diversity becomes a concern of first importance. The task is challenging as all potential candidates for being a suitable instrument should be already part of the regression equation. So far, the literature has not found an instrument unanimously agreed upon. This is the reason for which our selection of papers is rather limited. We focused on those papers with a choice of instrumental variables that are well explained and papers that ‘’go around’’ the problem by making use of a method that does not rely on external instruments. This includes papers using difference-GMM or system-GMM estimators. Their principal advantage is the use of internal instruments instead of external ones. Indeed, the instruments chosen are difference and the level of the covariates themselves. There are only a few of these studies available, including ours. This again explains the relatively restricted number of references we are considering. 2 1 Need to update the literature review with recent studies 1 2 su14127346_perova 1 +Initially, we opted for integrating the theoretical background disseminated throughout the text to connect to the findings of related papers and to avoid redundancy and repetition. Changes that we incorporated in response to this comment improve the overall theoretical framework of the paper, including concepts, definitions and links to relevant literature. We also articulated theoretical assumptions and added a comprehensive discussion of the observed phenomena. Specifically, we added critical mass theory discussion in the literature review section (lines 125-132). We added interpretation of corresponding results in the findings and discussions section (lines 445-452) and the conclusion section (lines 482-503). These changes in addition to the existing discussions of theories and concepts significantly improve the theoretical background of the paper. 2 1 Please add a theoretical background section 1 2 su14127346_perova 1 +We also emphasize the policy implications of these findings (lines 453-462, 497-503). To better reflect the policy implications of the study, we incorporate changes that are diffuse through the text. In particular, we argue that promoting gender diversity cannot deliver its full potential, and may even lead to adverse results unless it is accompanied by measures that mitigate political and economic uncertainty. These measures would create an enabling environment both for households and entrepreneurs. Such measures should increase agents’ confidence, dump their willingness to invest and expand the activity by reducing their aversion to risk. The accompanying measures should primarily target building and strengthening institutions to unlock this potential. Institutions are a defence against uncertainty. They contribute to anchoring economic agents’ expectations and stabilize the economy. We also elaborate on the finding of the critical mass theory. This result suggests that a very effective way to improve environmental quality and mitigate the adverse effects of economic activities is to encourage gender diversity in corporate boards in countries with low uncertainty where we find a higher impact on firms’ environmental performances. In these countries, the margin for progress is large and the effect of improving gender diversity in corporate boards materializes more easily and at lower costs, as these countries are far from their efficiency frontiers (lines 445-461 and 482-503). 2 1 What are the policy implications of your study 1 2 su14127346_perova 1 +We addressed your suggestion to improve arguments and discussion of findings by revising existing and adding new paragraphs better explaining regression coefficients that demonstrate how political and economic uncertainty shapes the relationship between corporate board gender diversity and firms’ environmental performance. (Lines 379-389). Furthermore, we added supporting arguments disseminated across the text (particularly in lines 348-361, lines 379-389, etc). These relate our finding to theory. We focus here on the attitude towards risk and uncertainties. Women on corporate boards tend to be more risk-averse and lean more toward conservatism in uncertain environments. Therefore, the more females there are on corporate boards, the higher their weight in the board decisions would be, and by the same token, the higher the effect of uncertainty on firms’ decisions. Moreover, we also relate our findings to the critical mass theory, suggesting that the impact of gender diversity on the environmental performances of firms materializes only when a critical mass weight of females is realized in corporate boards (Konrad et al. 2008, Torchia et al. 2011, Schwartz-Ziv, 2017- page 12, lines 445-451). 2 1 Add discussion of results section and relate your results with theories. 1 2 su14127346_perova 1 +Absolutely. Changed accordingly (line 160). 2 1 "--> I believe the authors intended ""moderating role.""" 1 2 su14127346_perova 1 +We answered this comment along different dimensions. We revise and elaborate on the explanation and interpretation of the results. We provide further explanations on the ways political and economic uncertainty shapes the relationship between corporate board gender diversity and firms’ environmental performance. We also emphasize the policy implications of these findings (lines 453-461, 487-496). In addition, we add more theoretical arguments to the discussion based on the most recently published academic papers on the topic. (Lines 421-452) “ 2 1 The authors could go into greater detail to explain the logic behind this relationship. As it stands, the paper offers little insight into the reasoning behind their hypothesis.” We answered this comment along different dimensions. 1 2 su14127346_perova 1 +The related theory posits that females’ attitude when facing uncertainty is different from males. They tend to exhibit a strong inclination to wait until the uncertainty is resolved before making major business decisions. To address this comment, we added supporting arguments disseminated across the text (particularly in lines 348-361, lines 421-428, etc). These explain the finding you are referring to by attitude towards risk and uncertainties. Women on corporate boards tend to be more risk-averse and lean more toward conservatism in an uncertain environment. Therefore, the more females there are on corporate boards, the higher would be their weight in the board decisions, and by the same token, the higher would be the effect of uncertainty on firms’ decisions. 2 1 It would be useful if the authors provided some speculative thoughts on the finding that the slope of the GenDiv variable is negative in highly uncertain countries on the firm's environmental performance (Figure 3 (c) red line). 1 2 su14127346_perova 1 +The literature on the relationship between gender diversity and environmental performances of firms that addresses dynamic endogeneity is rather limited. We mention Gaio and Gonçalves (2022), Lu and Herremans (2019), Kassini et al (2016), Silla, et al (2016) that opt for a dynamic modelling using a System-GMM estimator. This estimator is particularly suitable to panels with large number of individual and few time periods, which the case for our paper. Moreover, it accommodates situations where the independent variable changes slowly (Antoniou et al., 2008). To keep a good flow in the text, we only mention these papers in the introduction section. We elaborate further on them in the literature review section. We describe their main purpose and explain how our analysis departs from them. 2 1 In lines 28 and onwards, you argue a lack of literature looking at dynamic (GMM) analysis of the role of female on CSR and ESG issues, but fail to mention some examples. Please provide some, and position your work in that (brief) strand of literature. One example you should consider is Gaio, C., & Gonçalves, T. C. (2022). Gender diversity on the board and firms’ corporate social responsibility. International Journal of Financial Studies, 10(1), 15. 1 2 su14127346_perova 1 +Thanks for the Suggestion. We highlighted the research hypothesis by moving it the introduction. We also added another hypothesis. The first relates to the very existence of a relationship between gender diversity on corporate boards and firms’ performances. The second, deals with the intensity and shape of this relationship. We believe, this adds a deal of clarity to the text and purpose of the paper. 2 1 Please revise if it makes sense to present your research hypothesis in the introduction. 1 2 su14127346_perova 1 +We reviewed all the text and changed wording in different parts of the text. 2 1 "Please reconsider the use of adjectives such as ""complicated"" (line 79), interestingly (line 88) and so on." 1 2 su14127346_perova 1 +We initially meant, among all these papers, there is one that… We rephrased this sentence and reviewed all the text. We edited sentences when needed. 2 1 "What do you mean by ""in the crowd"" (line 141). Please revise carefully english for clarity." 1 2 su14127346_perova 1 +In our initial submission, we used winsorized data for all our econometric analysis. However, we, inadvertently, displayed summary statistics (Table 2) for raw data, i.e., before winsorizing. We should have reported only winsorized summary statistics. This is precisely what we do in this revised version of the paper. The reason for winsorizing data (beyond its advantage of having regular statistical distribution) was that we initially have detected outliers. Further investigation revealed that one company (RIC: OBE.TO; CompName: Obsidian Energy Ltd) is responsible for these outliers. The company had presumably reported wrong values in FY-12, where PP&E was higher than Total Assets (see table below from Refinitiv Eikon). We have reported this case to Refinitiv (Case number: 11297339) and our doubts were confirmed (See their response below). Refinitiv Eikon replaced old value of PP&E (27834189009) with a correct value (10788172656). In order to avoid similar mistakes, we opted for winsorizing data and avoid outliers. Similarly, only one company had negative Tobins’ Q in 2017 (RIC: ELR.TO ; company name: Eastern Platinum Ltd), which was a reporting typo as well. However, our analysis is not affected by these outliers which are removed after winsorizing all the variables. In this revised version of the paper, we replace the table of summary statistics with the one based on winsorized variables. 2 1 Please revise your data: your max tangibility is over 2 (which means that Net PP&E, a subset of Assets, is 2 times those same Assets - this should be a typo. Similar problems might exist for a negative tobin's Q. 1 2 su14127346_perova 1 +The sentence “The global average of corporate boards’ gender diversity for all the sectors during 2008-2018 was about 13.5%” is correct as it is calculated based on all industries (5120 firms in total). However, since we are focusing on “Mining, Quarrying, and Oil and Gas Extraction Industry”, it makes more sense indeed to report the value for that particular sector. Therefore, we update the text as follows: “The average of corporate boards’ gender diversity for Mining, Quarrying, and Oil and Gas Extraction Industry during 2008-2018 was about 9.6%”. 2 1 "In line 192 you mention ""all the sectors"". But you are working one sector only, aren't you?" 1 2 su14127346_perova 1 +This is an explanation of the following sentence in our article: “To avoid bias and inconsistency that might be caused by instruments proliferation, we collapse the instruments matrix.” We are using longer lags of the dependent variable as additional instruments. Intuitively, there is a trade-off, on one hand, using longer lags gives more information and improves efficiency, but on the other hand sample gets smaller (as it is the case in standard 2SLS models). GMM is a way around this trade-off between lag length and sample length. However, implementation of System-GMM is not exempt from weaknesses. With the instruments count being quadratic in the time dimension, the variance matrix of the moments can be very large. Estimating its elements may be problematic in particular in a finite sample lacking the adequate amount of information. This finite sample bias can weaken Hansen J-test and overstate its p-value and therefore generate suspicious high pass rate of instruments validity. The problem is known as instruments proliferation (Roodman 2009). To avoid bias and inconsistency due to instruments proliferation, we limit the number of instruments used and collapse the instrument matrix which prevents the model from being over-fitted. 2 1 Explain your sentences in lines 242-244. What did you do specifically? 1 2 su14127346_perova 1 +We revised the concerned section and rewrote the text in order to improve on clarity. The revised text reads as follows: Greater gender diversity for a firm located in a country with high political and economic uncertainty would lower the firm’s environmental performance (0.616-0.853=-0.237). More precisely, a 1 percentage point increase in GenDiv in a country with high political and economic uncertainty 5 leads to an average decline of 0.24% in the firm’s environmental performance in the following year. This suggests that the previous finding on the positive relationship between more gender-diverse boards and a firms’ environmental performances tends to be conditional on reduced policy and economic uncertainty. More gender-diverse corporate boards would not lead to better environmental performances of firms in countries with higher uncertainty (higher WUI score). The rational for this result stems from the idea that uncertainty adversely affects the enabling environment of an economy. This may induce financial outcomes for firms that are so negative and diffuse that they could hardly be balanced by the benefits brought with more gender- diverse boards (Bloom 2014, Atsu and Adams 2021). Indeed, uncertainty hampers household confidence and makes it difficult for businesses to plan for the future. The lack of visibility for future economic and political prospects undermines agents’ confidence and further raises their aversion to risk. In terms of policy, our finding suggests that promoting gender diversity on corporate boards should be accompanied by measures that reduce political and economic uncertainty. This is particularly relevant for countries vulnerable to shocks whether internal or external (Covid-19, war, conflicts, trade tensions, etc.). These can further exacerbate agents’ risk-aversion and deteriorate the market ability to create a sound economic and political environment in which agents interact effectively. In order to assess which level of the country’s uncertainty induces the negative effect of gender diversity, we introduce interaction terms with WUI quartile dummies (again, with two specifications, allowing slope and then the both slope and intercept to change). The findings are summarized in Table 4 (columns 3 and 4). They suggest that the interaction term with only the last quartile is statistically significant (at the 10% level), indicating that the impact of GenDiv on environmental performance is mostly driven by highly uncertain countries (those in the last quartile of the distribution). Countries below the 75th percentile of the WUI do not exhibit statistically significant differences among each other. We investigate this finding further by examining, for different gender diversity levels, (a) the intensity of the relationship across high and low uncertainty levels and (b) the marginal impact of a country’s uncertainty status on the firm’s environmental performance (Figure 3). We find that in countries with a high (above median) uncertainty level, the environmental performances of firms are significantly lower than in countries with low uncertainty, and this impact is magnified as gender diversity in corporate boards increases. The finding is robust for both specifications, with fixed and without fixed intercepts. Higher gender diversity in countries with lower uncertainty increases a firm’s environmental performance, whereas, in countries with high uncertainty, an increase in female board members has a negligible positive impact (Figure 3a) or even a negative impact (Figure 3c). The gap in environmental performance between countries with high versus low uncertainty increases as gender diversity in corporate boards increases. A potential explanation of this finding refers to the exacerbating effects of political and economic uncertainties on entrepreneurs’ risk-aversion. This, in turn, discourages in-vestments in costly abatements technologies and environmental-friendly processes. More generally, increased risk aversion reduces investments and activities whose returns accrue more in a long-run. These include research and development efforts, and particularly 6 environmental-led activities, which are seen as secondary in firms’ scale of priorities. Ultimately, this would put pressure on firms’ behavior and worsen their environmental performances (Bloom, 20149; Atsu and Adams, 202137). The arguments above provides a rationale for the worsened environmental performances of firms in response to higher uncertainties, and explains the gap in effects for firms across countries of different uncertainty levels. However, this does not address the potential reasons behind the widening of this gap for higher gender diversity levels. One potential explanation of this result relates to the particular attitude of women toward risk. Females on boards tend to exhibit more risk aversion compared to their male peers. They tend to show more patience and are typically more willing to look for professional guidance when facing uncertainty (Liu, 201838). Females on boards tend to be more inclined to wait until uncertainty is resolved before making major business decisions. Therefore, the more females on corporate boards, the greater the weight of their decisions (i.e., the higher would be the effect of uncertainty in firms’ decisions). This finding begs the question of whether the differential between countries with high versus low uncertainly levels is statistically significant for increasing gender diversity levels. Figure 3 (b and d) trace the magnitude of the gap between the low and high uncertainty scores. It states that this gap is increasing, in absolute value, and is statistically significant at the 95% level for all values of gender diversity (for gender diversity levels larger than 10%, for both specification Figures 3b and 3d). This threshold value points to a standard and very important result in the literature. This refers to the critical mass theory, by which the impact of gender diversity on the environmental performance of firms materializes only when a critical mass weight of females is realized in corporate boards (Konrad et al., 200839; Torchia et al., 201140; Schwartz-Ziv, 201741; among others). This suggests that an effective way to improve environmental quality and mitigate the adverse effects of economic activities is to encourage gender diversity in corporate boards in countries with low uncertainty where we find a higher impact on the firms’ environmental performances. In terms of policy, our findings suggest that promoting gender diversity cannot reach full potential, and may even lead to adverse results unless accompanied by measures that mitigate political and economic uncertainty. These measures would create an enabling environment both for households and entrepreneurs. These reduce their aversion to risk, which increases their confidence and willingness to invest. To unlock this potential, a country should implement accompanying measures that promote and strengthen stable institutions – as a defense against uncertainty. They contribute to anchoring economic agents’ expectations, and stabilize the economy. 2 1 "Lines 330 and onwards are presenting conclusions that are not warranted by the results and the english is a bit strange (what do you measnby ""households' anxiety""?). Similar problems stem from the following paragraphs discussing the results." 1 2 su14127346_perova 1 +the inoculation points were labeled with the red arrows in Figure 1 as suggested. 2 1 I would like to suggest authors label inoculation points in Figure 1, which could give readers a clear view of three different inoculation methods. 1 2 toxins14060409_perova 1 +Sorry for carelessness. We corrected it as suggested. (Pag.4 Line 157) Point 3: Line 143: “PPSD-premature spike death” should be “PPSD-proportion of premature spike death”. 2 1 Line 142: “proportion of PPSD” should be “proportion of PSD or PPSD”. 1 2 toxins14060409_perova 1 +We revised the expression in the footnote of Table 1. (Pag.4 Line 158) Point 4: Lines 168 - 169: Should it be that DON content of most lines without Fhb1 exceeded 1000 µg/kg under UBFI? 2 1 Line 143: “PPSD-premature spike death” should be “PPSD-proportion of premature spike death”. 1 2 toxins14060409_perova 1 +we revised the sentence as “DON content of most lines without Fhb1 exceeded 1000 μg∙kg-1 under UBFI method (Figure 2), with the highest reaching 4224.38 μg∙kg-1 (Table S1)”. (Pag.5 Line 184-186) Point 5: Lines 411 & 413: “PPSB” should be “PPSD”. 2 1 Lines 168 - 169: Should it be that DON content of most lines without Fhb1 exceeded 1000 µg/kg under UBFI? Where is 4224.38 µg/kg in Table 1? Do you mean in Table S1? 1 2 toxins14060409_perova 1 +We corrected it. (Pag.11 Line 441 & 443) Point 6: Table S1: “PPSD - premature spike death” in the footnote should be “PPSD - proportion of premature spike death”. 2 1 Lines 411 & 413: “PPSB” should be “PPSD”. 1 2 toxins14060409_perova 1 +We revised the expression in the footnote of Table S1. 2 1 Table S1: “PPSD - premature spike death” in the footnote should be “PPSD - proportion of premature spike death”. 1 2 toxins14060409_perova 1 +Thanks. We revised the annotations in Table S1. 2 1 Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. 1 2 toxins14060409_perova 1 +We agree with the reviewer’s comments and make Figure S4 as Figure 4 in this revised version. 2 1 I would suggest to avoid citing supplementary figures at the beginning of the chapter. See for example chapter 2.4. Given that 2.4 chapter discusses data of supplementary figure 4 would suggest to make figure S4 as Figure 4 of the manuscript. 1 2 toxins14060409_perova 1 +We marked the inoculation sites with red arrows in Figure 1. 2 1 To further clarify the infection methods a supplementary figure detailing graphically the modes of inoculation with figures would make the paper extremely useful for the community. 1 2 toxins14060409_perova 1 +We added more details about the strain and cited the following paper. (Pag.10 Line 402-403) Zhang, Y.; Li, A.; Zhu, S.; Li, L.; He, X.; Sun, Z.; Li, T. Basal Rachis Internode Injection (BRII): A novel inoculation method to evaluate wheat resistance to Fusarium head blight. Phytopathology, 2021, 111, 1670-1674, doi:10.1094/PHYTO-11-20-0488-R. Point 4: Mycotoxin data analysis should be provided (I guess is policy of mdpi to make raw data available together with the publication) Response 4: Thanks! 2 1 Identity of the strain used for infection should be confirmed: a multilocus species characterisation is needed to confirm the species of the strain or a reference to a publication where the strain was described and appropriately characterised. 1 2 toxins14060409_perova 1 +Thanks! We uploaded the raw mycotoxin data as suggested. 2 1 Mycotoxin data analysis should be provided (I guess is policy of mdpi to make raw data available together with the publication) 1 2 toxins14060409_perova 1 +The innovation of this research has been clarified in the abstract, the introduction, and the conclusion. 2 1 The innovation of this research needs to be better explored. 1 2 w14030367_makarova 1 +Three references have been cited. Please see lines 40-41 in the revised manuscript. 2 1 Lines 33-38: You should mention that discharge of PPCPs degrades water quality and thus it cannot be directly used for potable water (via desalination) and industrial applications. Cite the following references: Panagopoulos, A. (2021). Energetic, economic and environmental assessment of zero liquid discharge (ZLD) brackish water and seawater desalination systems. Energy Conversion and Management, 235. Panagopoulos, A. (2021). Techno-economic assessment of Minimal Liquid Discharge (MLD) treatment systems for saline wastewater (brine) management and treatment. Process Safety and Environmental Protection, 146, pp. 656-669. Study and evaluation of the characteristics of saline wastewater (brine) produced by desalination and industrial plants. Environmental Science and Pollution Research, 1-14. 1 2 w14030367_makarova 1 +Thanks very much for the reviewer. The conclusion has been revised according to the reviewer’s suggestion. The added paragraph in the revised manuscript is as follow: To sum up, the results show that the proposed BAC-UF system can be effective in the treatment of river water polluted by PPCPs, conventional organic pollutants and ammonia nitrogen. 2 1 Conclusion: Discuss the applicability of your findings/results and future study in this field. 1 2 w14030367_makarova 1 +Thanks for the reviewer’s suggestion. The conclusion has been revised and integrated into two paragraphs. The first paragraph mainly includes important findings, and the second paragraph mainly includes the outlook for the future in this field. 2 1 Conclusion: Make it as one or two paragraphs. 1 2 w14030367_makarova 1 +The salinity concentrations in the samples have been added to Table 1 in the revised manuscript. 2 1 Table 1: What is the salinity (in mg/L) of the samples ? 1 2 w14030367_makarova 1 +We agree with the suggestion and comments of the reviewer. All comments have been revised one by one, and the modifications are highlighted in yellow in the marked revised manuscript. Thanks again for your patient review. 2 1 Overall, the manuscript can be accepted after the minor correction/revision to be published in the journal of Water. 1 2 w14030367_makarova 1 +Thanks for the reviewer’s helpful suggestion. The objective statement has been added to the abstract to support the seriousness of the problem, and the revised sentences are as follows: Biological activated carbon (BAC) biofilter coupling ultrafiltration (UF) is a promising process for the treatment of river water contaminated by pharmaceutical and personal care products (PPCPs). However, the pilot-scale study should be conducted to reveal the long-term removal performance and the respective contributions of BAC and UF. 2 1 The title seems good, but the abstract seems to be fine. Please add one problem statement line in abstract to justify this sentence ``the long-term pilot-scale study is urged to be investigated.``. 1 2 w14030367_makarova 1 +We agree with the suggestion of this reviewer. The two-stage biofilms located in the activated carbon column and on the UF membrane synergistically, can be conducive to the removal performances. However, the mechanisms of the two-stage biofilm, such as bacterial and metazoan communities, membrane fouling and dissolved oxygen transfer, should be further investigated to enhance the removal efficiency and stability of this system. The research gap has been added in the Conclusion and is as follow: To sum up, the results show that the proposed BAC-UF system can be effective in the treatment of river water polluted by PPCPs, conventional organic pollutants and ammonia nitrogen. Besides, the results of this analysis can have significant implications for the conven-tional UF operation procedure and the ozone-activated carbon process, providing a simple decentralized approach to drinking water treatment for the areas where source water is contaminated with PPCPs. 2 1 Research gap should be delivered on more clear way with directed necessity for the future research work. 1 2 w14030367_makarova 1 +Thanks for the reviewer’s comment. The introduction has been revised carefully, including using up-to-date references. For example, the outdated references have been removed. Meanwhile, the articles published within the last two years were added, such as (the Reference2 Yu et al., 2020) and (the Reference21 Tang et al., 2018). 2 1 Introduction section must be written on more quality way, i.e., more up-to-date references addressed. Please target the specific gap such as 2015-2021 etc. 1 2 w14030367_makarova 1 +The reference has been cited. Please see line 38 in the revised manuscript. 2 1 Page 1 Line 38. Please cite this reference with existing reference 3….Role of nanotechnology for design and development of cosmeceutical: application in makeup and skin care. 1 2 w14030367_makarova 1 +The BAC biofilter can remove the PPCPs, and then the following UF can reject micro-organisms and particles flowing out from the biofilter to ensure the quality of drinking water. The above coupling process makes up for the defects concerning respective operations of the BAC biofilter and UF. Although many pilot-scale setups were used to treat secondary wastewater effluent for water reclamation, this type of raw water quality was different from the river water, causing the different potential of biofilm growing. As far as we investigated, the lack of enough attention to long-term pilot study exists. Therefore, in this study, a BAC-UF system was carried out for several months with pilot scale to access the long-term removal performances and the respective contributions of BAC and UF. The relevant content has been supplemented and revised in the abstract to highlight the innovative points. 2 1 The novelty of the work must be clearly addressed and discussed, compare previous research with existing research findings and highlight novelty. 1 2 w14030367_makarova 1 +Biological activated carbon (BAC) combined the adsorption and biologic degradation consuming low power energy and chemicals without concern of DBPs production as well as no frequent updates for activated carbon media. The BAC biofilter can remove the PPCPs pollutants, and then the followed UF can reject microorganisms and particles flowing out from the biofilter to ensure the quality of drinking water. Thus, the BAC-UF process makes up for the defects of the respective operations of BAC biofilter and UF. Although many pilot-scale setups were used to treat secondary wastewater effluent for water reclamation, this type of raw water quality was different from the river water, causing the potential of biofilm growing differently. As far as we investigated, the lack of enough attention to long-term pilot study is present. Therefore, in this study, a BAC-UF system was carried out for several months with a pilot scale. 2 1 What is the main challenge? Why author choose this material? Please highlight in the introduction part. 1 2 w14030367_makarova 1 +The two references have been cited. Please see the lines 58. 2 1 Page 2 Line 55 need a reference. Please consider these at end of this sentence……The oxidation method exhibited a fast reaction speed and high removal efficiency…(i) Role of nanomaterials in the treatment of wastewater: A review (ii) Advances and challenges in developing efficient graphene oxide-based ZnO photocatalysts for dye photo-oxidation. 1 2 w14030367_makarova 1 +T Thanks very much for this comment. The introduction has been improved for better reading. 2 1 The main objective of the work must be written on the more clear and more concise way at the end of introduction section. 1 2 w14030367_makarova 1 +Two PPCP mistakes have been revised. The abbreviation of chemical oxygen demand in previous version has been corrected to CODMn. The unnecessary abbreviations have been also corrected in the abstract. 2 1 Please check the abbreviations of words throughout the article. All should be consistent. 1 2 w14030367_makarova 1 +The added paragraph is as follows: Potassium permanganate, H2SO4, potassium sodium tartrate tetrahydrate, Nessler’s reagent and NaOH were purchased from a commercial company and certified as AR purity (Guangzhou Chemical Reagent Factory, Guangzhou, China), while PPCP standards were provided by three companies. Sulfamethoxazole (SMX), Sulfadoxine (SD), Sulfachloropyridazine (SCP), Sulfamethoxypyridazine (SMP), Sulfaquinoxaline (SQX), Sulfathiazole (STZ), Doxycycline (DOX), Erythromycin (EM), Anhydroerythromycin (EA), Roxithromycin (ROX), Penicillin-G (PEN G), Clarithromycin (CAM), Norfloxacin (NOR), Oxociprofloxacin (OFL), Enrofloxacin (EFL), Flumequine (FQ), Acetaminophen (APAP), Diclofenac sodium (DCF), Naproxen (NAP), Indomethacine (IND), Metoprolol (METO), Propranolol (), Atenolol (ATL), Primidone (PRM), Carbamazepine (CMZ), and Sulpiride (SP) were obtained from the Dr. Ehrenstorfer Company in Germany. Furthermore, Sulfadimidine (SM2), Sulfadiazine (SDZ), Sulfapyridine (SP), Sulfamonomethoxine (SMM), Tetracycline (TC), Ofloxacin (OFL), Amoxicillin (AM), Dimetridazole (DMZ), Trimethoprim (TMP) were bought from the National Institute of Metrology in China, whereas Oxytetracycline (OTC), Caffeine (CF), and Diethyltoluamide (DEET) were acquired from the Toronto Research Chemicals Company in Canada. 2 1 Please add chemical reagents section and stated all chemical with brand specifications. 1 2 w14030367_makarova 1 +These three GAC-UF systems were operated in parallel. Samples of the feedwater and effluent from three systems were taken simultaneously and measured once. The standard deviation was obtained by the detection over the full period of the experiment. 2 1 Regarding the replications, authors confirmed that replications of experiment were carried out. However, these results are not shown in the manuscript, how many replicated were carried out by experiment? Results seem to be related to a unique experiment. Please, clarify whether the results of this document are from a single experiment or from an average resulting from replications. If replicated were carried out, the use of average data is required as well as the standard deviation in the results and figures shown throughout the manuscript. In case of showing only one replicate explain why only one is shown and include the standard deviations. 1 2 w14030367_makarova 1 +The figure is used as the only pattern in the revised manuscript. 2 1 Please revise your paper accordingly since some issue occurs on several spots in the paper. Please use Fig. or figure? It very confusing. Article should be in one pattern. 1 2 w14030367_makarova 1 +The front sizes in the figure 1 have been increased. The quality of the figure 1 has been also improved. 2 1 Please provide high quality image of figure 1. 1 2 w14030367_makarova 1 +The style for units has been revised and unified. 2 1 Please use one style for units such as m3/h or m3h-1 Please revise your paper accordingly since some issue occurs on several spots in the paper. 1 2 w14030367_makarova 1 +The comparison of previous research with existing research findings was added in the final part of the results and discussion. The added paragraph is as follows: PPCPs risks have been posing severe challenges to the safety of drinking water supply in rural areas due to the absence of the process with simple operation and maintenance as well as reliable performance. In this study, BAC coupling gravi-ty-driven UF was performed continuously, and the rejection performance of mem-brane filtration and BAC filtration both showed barriers for the conventional pollu-tants and PPCPs. Furthermore, this study indicated the respective contributions of BAC and UF, showing the role of the two-stage biofilm. Previous works involving BAC generally combined the ozonation with the BAC filter for treating the contaminants of emerging concern, eliminating a majority of PPCPs by more than 90% [34]. However, the regulation and maintenance of machines for ozone products are complicated, and the disinfection by-products will be newly generated in the effluent, which is incon-venient to use in rural areas [35]. In general, coagulation, filtration and single BAC units worked inefficiently and removed the detected PPCPs by less than 50%, as they were not hydrophobic [34, 36]. Hybrid membrane processes such as inline dosing of powdered activated carbon (PAC) prior to UF have already shown promising potential for the abatement of PPCPs; however, the inline dosing PAC is infeasible in rural areas [37]. In this study, the BAC prior to UF enhanced the biological activity by forming a two-stage biofilm system. Therefore, the integrated BAC-UF process can be considered as an economically and technically feasible approach to the decentralized and emer-gency drinking water treatment. 2 1 Please add a comparative profile section to compare your results and prove how it better than previous. 1 2 w14030367_makarova 1 +The conclusion has been modified as suggested by reviewers. Please see lines 325-350 in the revised manuscript. 2 1 Section 4 should be renamed by Conclusion and Future perspectives. Conclusion section is missing some perspective related to the future research work, quantify main research findings, highlight relevance of the work with respect to the field aspect. In the present form conclusion is very weird. 1 2 w14030367_makarova 1 +Two native English-speaking colleagues help us verify the manuscript. Hope the revised manuscript would be more satisfactory. We are so sorry to make reviewer’s reading uncomfortable. We have used an English Language Editing service to correct the grammatical and spelling errors and to make the expressions conform to correct scientific English (the Language Editing Certification is attached below). 2 1 To avoid grammar and linguistic mistakes, Major level English language should be thoroughly checked. Please revise your paper accordingly since several language issue occurs on several spots in the paper. 1 2 w14030367_makarova 1 +We agree with the reviewer. The reference formatting has been corrected. Thanks very much for the patient review again. 2 1 Please follow the journal guidelines. Reference formatting need carefully revision. All must be consistent in one formate. 1 2 w14030367_makarova 1 +Thank you very much for your support and help. 4 1 Dear Authors, i reviewed again the revised version. I would like to recommend the publication in present form. Authors shows sincere efforts during revision. 3 2 w14030367_makarova 1 +Full names of BAC, UF, and PPCPs are used in the title and the abstract to show the results briefly. As for NH4+-N, NO2−-N, and NO3—N, the full names have been used instead of abbreviations in the abstract. 2 1 Authors should avoid abbreviations in the title and the abstract. 1 2 w14030367_makarova 1 +The title has been revised to river water. 2 1 Authors may revise the title to include river water instead of surface water. 1 2 w14030367_makarova 1 +The references format has been corrected. 2 1 References should be according to the journal format. 1 2 w14030367_makarova 1 +We are very sorry for the confusion caused to the reviewers, the sentences have been revised from the words and Grammarly. The revised sentences are shown below: Ultrafiltration (UF) as an emerging alternative technology to conventional water treatment processes, has been widely used to remove pollutants such as particles, col-loids, bacteria, and viruses, thus reducing the risk of water-borne diseases [10]. However, in the case of the PPCPs with a small molecular weight (typically < 600 Da), UF membranes also cannot effectively reject these PPCPs, but nanofiltration and reverse osmosis are able to remove these PPCPs based on the thin-film composite [11, 12]. 2 1 Line 44-45: Ultrafiltration (UF) as emerging technology, has been widely used to remove pollutants such as particles, colloids, bacteria and viruses, reducing the risk of water-borne diseases and …UF membranes cannot effectively rejected these soluble substances”. Please clarify, why ultrafiltration cannot remove the PPCPs since it can remove bacteria and viruses. 1 2 w14030367_makarova 1 +The t-test results have been added in the revised Table1. 2 1 Please add t-test results in Table 1 for each parameter to understand the significant differences. Authors may provide data in the supporting information file. 1 2 w14030367_makarova 1 +"The statistical t-test was evaluated for Figure 4, which was added in the text of ""3.2. Removal of nitrogen"" Section." 2 1 The reviewer suggests evaluating the statistical t-test for Figures 4. 1 2 w14030367_makarova 1 +The t-test results have been added to the revised Table2. The concentration of Erythromycin was generally varied between 1047.14 ng L−1 and 2037.72 ng L−1. 2 1 t-test results should be included in Table 2. Why is the standard deviation of Erythromycin showing a high value? 1 2 w14030367_makarova 1 +Some symbols were overlapped in Figure 5h. The symbols near 85 days have been entirely shown by correcting Y-axis settings, such as Figures 5a and 5f. 2 1 Please look at the curve of BAC/UF; there was a symbol missing in near 85 days. Please show each symbol. 1 2 w14030367_makarova 1 +The conclusion has been revised, including the style and sentences. 2 1 The conclusion may be revised. 1 2 w14030367_makarova 1 +We agree with this suggestion. The abbreviations in the title have been deleted. Besides, a list of abbreviations has been added before the references. 4 1 Authors should avoid abbreviations in the title. Authors should add a list of abbreviations before the references. 3 2 w14030367_makarova 1 +Thanks to the reviewer for the patient comment. The above mistakes have been revised. 4 1 Please avoid repeating the full name and abbreviation throughout the manuscript if you used the first-time abbreviation. 3 2 w14030367_makarova 1 +Thanks to this reviewer for the comment. Common waterborne viruses include Shigella, Vibrio cholerae, Poliovirus, adenovirus, and coxsackie virus, with sizes of 26 nm, 27 nm, 30 nm, 90 nm, and 30 nm, respectively [1-5]. The molecular weights of PPCPs are generally less than 1000 Da (about 1-2 nm), obviously smaller than the virus. The molecular weight cut off of UF membranes was an average 100 000 Da in this work, which was similar to the virus but larger than the PPCPs molecules. Karthik K, Dhanuskodi S, Gobinath C, et al. Multifunctional properties of microwave assisted CdO–NiO–ZnO mixed metal oxide nanocomposite: enhanced photocatalytic and antibacterial activities [J]. Journal of Materials Science: Materials in Electronics, 2018, 29(7): 5459-71. Song S, Liu Z, Zhou J, et al. An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin-inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model [J]. Journal of Medical Virology, 2019, 91(1): 14-21. Kim K, Choi J-W, Ma K, et al. Nanoisland-Based Random Activation of Fluorescence for Visualizing Endocytotic Internalization of Adenovirus [J]. Small, 2010, 6(12): 1293-9. Dourmashkin R R, Mccall S A, Dourmashkin N, et al. Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson's disease [J]. F1000Res, 2018, 7: 302-. Tamano K, Aizawa S-I, Katayama E, et al. Supramolecular structure of the Shigella type III secretion machinery: the needle part is changeable in length and essential for delivery of effectors [J]. The EMBO Journal, 2000, 19(15): 3876-87. 4 1 Line 46-52: & line 84-85 “Ultrafiltration (UF) as an emerging alternative technology to conventional water treatment processes, has been widely used to remove pollutants such as particles, colloids, bacteria, and viruses, thus reducing the risk of water-borne diseases [10]. Size exclusion is considered the primary removal mechanism for the UF. However, in the case of the PPCPs with a small molecular weight (typically < 600 Da), UF membranes also cannot effectively reject these PPCPs, but nanofiltration and reverse osmosis are able to remove these PPCPs based on the thin-film composite”. Sorry, but I don't see why UF can reject viruses and bacteria but not PPCPs. Is it true that the molecular weight of viruses and bacteria is more than that of PPCPs? Please elaborate. 3 2 w14030367_makarova 1 +The information regarding the biological degradation of PPCPs has been added in the introduction. The revised sentences are shown below: In the BAC biofilters, the biotransformation and adsorption both contributed to the PPCPs removal. The activated carbon adsorbed PPCPs to the surface and interior, where microorganisms were suitable for growth. Under the long-term effect of high-concentration PPCPs, the dominant microorganisms in the biofilter were selected to survive. These microorganisms mostly transformed PPCPs into many segments and even directly mineralized them to CO2 [3, 14]. 4 1 The authors should include some information regarding the biological degradation of PPCPs by microorganisms in the introduction section. 3 2 w14030367_makarova 1 +“The combined process with ultrafiltration may be another promising choice, featuring a comparable removing performance as the nanofiltration and low operational cost”. This claim is not supported by our research. To avoid misunderstandings for readers, we changed the claim and revised the sentence. The revised version is as follows: The combined process with UF may be another promising choice as an alternative to nanofiltration for removing PPCPs in rural areas. It can be seen in lines 54-55. 4 1 Line 53-55: Have the authors compared the BAC-UF performance to that of nanofiltration? 3 2 w14030367_makarova 1 +The method of the t-tests has been explained in section 2.4 (lines 157-158) in the revised manuscript. The sample size (n) has also been added in Table 1 and Table 2. 4 1 I strongly suggest that the authors explain how they performed the t-tests. Please include the sample size (n) or degree of freedom (df). 3 2 w14030367_makarova 1 +Thank you very much for your kind reminder. The values have been modified in the revised manuscript in yellow highlight. 4 1 Please show the t-value and p-value in a scientific view (e.g., 2.79E-4 would be P <.001). 3 2 w14030367_makarova 1 +Thanks for the kind reminder. All the names of medicinal compounds not used have been deleted, including Sulfaquinoxaline (SQX), Sulfathiazole (STZ), Doxycycline (DOX), Roxithromycin (ROX), Penicillin-G (PEN-G), Clarithromycin (CAM), Norfloxacin (NOR), Oxociprofloxacin (OFL), Enrofloxacin (EFL), Flumequine (FQ), Acetaminophen (APAP), Diclofenac sodium (DCF), Naproxen (NAP), Indomethacin (IND), Metoprolol (METO), Propranolol (PRO), Atenolol (ATL), Primidone (PRM), Carbamazepine (CMZ), Sulpiride (SP), Sulfapyridine (SPN), Sulfamonomethoxine (SMM), Tetracycline (TC), Amoxicillin (AM), Dimetridazole (DMZ), Oxytetracycline (OTC) and DEET. 4 1 Line 161-176: Please delete the name of medicinal compounds not used for this study. 3 2 w14030367_makarova 1 +The results and discussion has been supplemented in section 3.1. Please see lines 180-185 in the revised manuscript. 4 1 Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. Please explain it in the manuscript. The reviewer suggests statistical analysis using a t-test (Raw water- BAC-Effluent and Raw water – BAC/UF-effluent). Point 6: Why the same trend of increase or decrease in graphs (Fig. The same trend (Figure 2) was mainly due to the stable removal ability of BAC and UF for organics, causing the removal restriction. The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. After the gas scrubbing and the hydraulic backwashing, the dissolved oxygen detection of the effluent was carried out, resulting in the above results for dissolved oxygen. Besides, the t-test was used and proved the significant difference between BAC-Effluent and BAC/UF-effluent. Thanks for the response. Please include it in the manuscript. Response 6: Thanks very much for this comment. 3 2 w14030367_makarova 1 +Thanks very much for this comment. With a turbulent current and dozens of kilometers in length, this river is located in the mountains of Foshan city. The PPCPs sludge at the bottom of the river never executes removal. Thanks for the suggestion from the reviewer. We will further precipitate the PPCPs sludge before the water treatment plant or excavate the PPCPs sludge from the river and study the effects on drinking water quality. The relevant results will be published in another paper in the future. 4 1 What is the utility or deterioration of PPCPs sludge after removing it from river water? If possible, please add at least one paragraph. 3 2 w14030367_makarova 1 +There are only minor comments with very specific issues: In the introduction, (Line 76 79), you present the objectives, but those are not clear, I respectfully suggest focusing on your hypothesis 2. 1 2 agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. Line 78: You wrote, “designed to meet the basic behavioral needs of the sow at farrowing”, but this is not tested on the paper. 1 2 agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. Lines 80 – 83 moves to discussion section 4. 1 2 agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. Figure 1 is missing 5. 1 2 agriculture12060868_perova 0 +The writing and data presenting need to be improved. Figure 2 needs more description, maybe include which wall… Please describe units of the dimensions 6. 1 2 agriculture12060868_perova 0 +There are only minor comments with very specific issues: Figure 4. Please indicate which is “sowconf” and which is “trad”. In the left graph the units are in m2, but in right side it does not have unit, seems ar? 1 2 agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Line 206: I don’t understand why you use just 10 o 12 sows, 50% primi and multiparous, but in line 225 mentioned that “there were no secure information about sow parity” please be consistent. 1 2 agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Please include P values when report significant differences. 1 2 agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Figure 1 does not appear in the pdf that this reviewer could download. Only the Figure Caption appears. 1 2 agriculture12060868_perova 0 +The writing and data presenting need to be improved. It is not totally clear to the reviewer how stillborn piglets were evaluated as compared to “piglets with no milk in stomach”. 1 2 agriculture12060868_perova 0 +The writing and data presenting need to be improved. Line 224-225, it states that that no information/security on the productivity data on whether it was primiparous or multiparous sow. Again this creates a bit of confusion. Sows were recorded, 50% primiparous and 50% multiparous to evaluate behaviour, and results are discussed accorging to that (lines 320-321). Why productivity data was not available? 1 2 agriculture12060868_perova 0 +The writing and data presenting need to be improved. Figure 5 and 7 display the overall causes of mortality for the three batches. However, differences in batches were found. Could this overall causes be biased by this batch effect? 1 2 agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Please add the important information to the footnote or figure legend of the tables and figures. Such as: abbreviations, replicates n=?, mean±SD/SE, ect. 1 2 agriculture12060868_perova 0 +The following changes could improve the quality of the paper. Please italic the P value throughout the paper. 1 2 agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Lines 129-133, where is the figure 1? 1 2 agriculture12060868_perova 0 +The following changes could improve the quality of the paper. Line 263, please add “(3 batches with TRAD and 2 batches with SOWCOMF)” to the figure legends. 1 2 agriculture12060868_perova 0 +There are only minor comments with very specific issues: Line 275-276, Space needed before and after “±”. 1 2 agriculture12060868_perova 0 +Finally, thank you for being so patient with our manuscript The quality of the Figrue 6 need to be improved. 1 2 agriculture12060868_perova 0 +The paper is clearly written, with nice figures and with a discussion supported by the results obtained. Figure 7, using “*” to substitute the different letters to express the difference. 1 2 agriculture12060868_perova 0 +The following changes could improve the quality of the paper. Table 4, please using the writing way to present the table. 1 2 agriculture12060868_perova 0 +The following changes could improve the quality of the paper. Figure8, do not understand the meaning of “***” here? 1 2 agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. Figure 7, please improve the perspective of the figure. 1 2 agriculture12060868_perova 0 +Discussion: The results are appropriately discussed though perhaps more discussion about further study would be beneficial. It seems that the authors of this study have already tackled this topic exhaustively in their previous articles 1 2 ani12040482_makarova 0 +"The authors have hardly studied all the publications on how dogs behave when daily routines were changed, so the term ""first study"" is exaggerated." A catchy topic, but its content is unoriginal, bringing nothing new to the pre-pandemic science. 1 2 ani12040482_makarova 0 +But the questionnaire only asked how long the dogs had been alone and what they were doing during this time. The entire first paragraph of Discussion repeats what has already been written in earlier chapters (line 372-379). 1 2 ani12040482_makarova 0 +Results: These were generally well-detailed with clear layout considering scope of results. "Line 382-384 „To our knowledge, this is the first empirical evidence to show a link between changes in dogs’ leaving routines and risk of SRBs.” The authors take priority in the empirical demonstration of changes in dogs when the routine of the day is disturbed. And changing the routine of the day is a well-known factor influencing the dog's welfare and behavior, including the occurrence of separation anxiety, so the above-quoted sentence should be deleted because it is untrue. The authors have hardly studied all the publications on how dogs behave when daily routines were changed, so the term ""first study"" is exaggerated." 1 2 ani12040482_makarova 0 +half of the dogs from the SRB group moved to the Clear group in October. Line 444 „This study has provided a unique and valuable insight into…..” the authors also mark their only unique role in the study, which does not bring new content. 1 2 ani12040482_makarova 0 +An error message occurred in several places (e.g., line 131, line 246, line 265) Abstract/simple summary: These are clear and well detailed. My only suggestion is that making it clear why February and October were chosen as survey-points may be beneficial. 1 2 ani12040482_makarova 0 +Manuscript has been slightly improved, but my comments were not included. Aa little more mention of issues of SRBs from owner perspective (e.g. noise complaints and issues with housing; property damage; decline of human-pet bond) could be beneficial (line 56-57). 1 2 ani12040482_makarova 0 +Discussion: The results are appropriately discussed though perhaps more discussion about further study would be beneficial. It may be helpful to discuss why there is poor owner adherence to programmes to reduce SRB (Line 66-67). 1 2 ani12040482_makarova 0 +Author Response Thank you for your time in reviewing this manuscript and for your constructive, helpful feedback. I wasn't sure if line 79-80 was needed- about dogs having returned to pre-pandemic pattern, I think it is a little dismissive of your own research which is valuable and applicable beyond the pandemic. 1 2 ani12040482_makarova 0 +There would be evidence for some behaviors, such as destructive behavior or defecation, but how would owners know about pacing or tail-chasing? Line 96-97- some more detail on the findings of these various surveys would be beneficial similarly to Bowen's study, just so provide a clear background/discussion of literature setting scene for your study. 1 2 ani12040482_makarova 0 +This is a well written and clear manuscript which would be of interest to academics, practitioners and dog owners. Methods: This is generally well-detailed. It may be beneficial to make it clear why cut off of 'at least 5 mins' was used, e.g. justification for this/why this time duration used. 1 2 ani12040482_makarova 0 +There would be evidence for some behaviors, such as destructive behavior or defecation, but how would owners know about pacing or tail-chasing? Line 131: There was an error with referencing wanted to flag. 1 2 ani12040482_makarova 0 +Line 214: if possible (might not be possible if this was how it was phrased in the survey), change “different to before” to “different from before” Study periods: It may be useful to spell out a little more here why these survey periods were chosen here, this is covered elsewhere but think could be made clearer here and earlier. 1 2 ani12040482_makarova 0 +(*Christley, R.M.; Murray, J.K.; Anderson, K.L.; Buckland, E.L.; Casey, R.A.; Harvey, N.D.; Harris, L.; Holland, K.E.; McMillan, 523 K.M.; Mead, R.; et al. Figure 1- Perhaps just double-check this is referred to in the text. Think either way this figure would benefit a bit of context on why was included/what was showing in context of this study as currently info is a bit generic and didn't totally tie into people's working from home etc. 1 2 ani12040482_makarova 0 +One of the challenges in this is we don’t know background rates of change for dogs with SRB. Results: These were generally well-detailed with clear layout considering scope of results. However, I don't think the figures were referred to in the text (unless that was the errors highlighted below?) 1 2 ani12040482_makarova 0 +Conclusions: I believe Animals requires a Conclusions section. There were some errors where reference source not found which would want to look into (line 246; 265; 274; 292; 305; 323 etc). 1 2 ani12040482_makarova 0 +L307 The odds ratio (OR) is 4.97 in Table 1 and not 3.60 Thank you! Line 366-369= I'm not sure it's totally fair to interpret this (the dog not always bringing toy when greeting them) as an anthropomorphic interpretation on the part of the owner- the anthropomorphic interpretation seems to be from authors of manuscript not owner? 1 2 ani12040482_makarova 0 +Impact of the first COVID-19 lockdown on management of pet dogs in the UK. Some more detail on the application of the findings to practitioners/owners would be beneficial. 1 2 ani12040482_makarova 0 +The authors still take priority in the empirical demonstration of changes in dogs when the routine of the day is disturbed. P6 L176 I am assuming you excluded dogs that were not left alone in February (or were there none?) 1 2 ani12040482_makarova 0 +P6 L176 I am assuming you excluded dogs that were not left alone in February (or were there none?) P10 L307-308 Could you make this a positive statement to show highlight the impact of amount of change on SRB: Dogs whose days left alone per week increased the most…If the data support that angle, I think it’s a stronger statement than what is written. 1 2 ani12040482_makarova 0 +We have addressed your comments and responded in the attached file. Larger issues: I would like to see the authors address a few different angles in the discussion 1. That dogs showing SRB prior to lockdown were more likely to show it after. Suggests the behavior is fairly robust and dogs having shown it at one point continue to be at risk (without knowing what interventions were taken) 2. 1 2 ani12040482_makarova 0 +Thank you so much for your time and these comments, they have really helped to strengthen the paper and we really appreciate it. Can you address the dogs that improved between Feb and Oct? You report the number of new dogs showing SRB but can you report on dogs that went the other way? What was the actual # and %? It seems you have compared within dogs that showed SRB in baseline and other models for dogs that did not. Seems a comparison between SRB- (baseline) → SRB + (post lockdown) and SRB + (baseline) → SRB- (post lockdown) dogs is critical and missing. This comparison seems essential—if some dogs get worse but some get better, than the argument that changes due to COVID might bring about new SRB becomes weaker. 1 2 ani12040482_makarova 0 +Some more detail on the application of the findings to practitioners/owners would be beneficial. One of the challenges in this is we don’t know background rates of change for dogs with SRB. That is, would the same % of dogs changed (in either direction) regardless of changes in owner schedules? We might see some dogs become sensitized over time and develop SRB (or something else changes in their life to precipitate it), while others might habituate or their behavior undergo extinction. As such, we can’t say for certain that these changes are due to changes in owner schedule. You note that the pseudo-R2 was small but I think you could go into more details and note the possibility that it was unrelated too. However, your results that the greater the change → the greater the new risk of SRB does lend support to the idea that this change in management might be a factor. I would suggest highlighting and discussing this outcome more. 1 2 ani12040482_makarova 0 +I think that after the revision, the paper would make an interesting contribution to the journal. Title: change “Leaving Pattern” to “Time Spent Away”; leaving pattern is less clear (it could be frequency of leaving each day) 1 2 ani12040482_makarova 0 +But this is the opinion of a person using English as a second language. Line 214: if possible (might not be possible if this was how it was phrased in the survey), change “different to before” to “different from before” 1 2 ani12040482_makarova 0 +According to the authors, the main finding is that dogs whose leaving time reduced the most during the lockdown were most at risk of developing new SRBs. Lines 383-384: Change “dogs’ leaving routines” to “dogs’ time left alone” Materials and Methods: 1 2 ani12040482_makarova 0 +That dogs showing SRB prior to lockdown were more likely to show it after. Line 151: how was the criterion of “at least 5 minutes” chosen? My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? 1 2 ani12040482_makarova 0 +Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. Line 151: how was the criterion of “at least 5 minutes” chosen? My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? 1 2 ani12040482_makarova 0 +The sample size is good, and the results are interesting. Also, I might have missed it, but did all of these owners live alone with their dog(s), meaning no other people in the household? If other people were present, did all of them have to be away or just the dog’s owner? This information might be presented in your other paper, but it would be good to include this basic information here as well, so readers can better understand your methods and findings. 1 2 ani12040482_makarova 0 +(*Christley, R.M.; Murray, J.K.; Anderson, K.L.; Buckland, E.L.; Casey, R.A.; Harvey, N.D.; Harris, L.; Holland, K.E.; McMillan, 523 K.M.; Mead, R.; et al. Line 166: define “devolved nations” for readers unfamiliar with the term. 1 2 ani12040482_makarova 0 +Specific points requiring attention: L18-20 „Whether dogs showed SRBs or not changed considerably over the months of the study, and one in ten dogs were found to have developed new SRBs in October, that they didn’t show before the pandemic” Overall, the percentage of dogs showing SRBs decreased during the study, and this should be clarified in the sentence above. Figure 2: should the blank box for “Feb, Not at all” be 0.0%? 1 2 ani12040482_makarova 0 +P10 L307-308 Could you make this a positive statement to show highlight the impact of amount of change on SRB: Dogs whose days left alone per week increased the most…If the data support that angle, I think it’s a stronger statement than what is written. Figure 4 is not called out in the text of the Results section. 1 2 ani12040482_makarova 0 +It is perfectly feasible that some owners did not leave their homes because they were for example, ill, but they did so during the pandemic. I believe Animals requires a Conclusions section. 1 2 ani12040482_makarova 0 +noise complaints and issues with housing; property damage; decline of human-pet bond) could be beneficial (line 56-57). Line 100: insert “the” after “in” 1 2 ani12040482_makarova 0 +The changes in leaving routine that occurred during the pandemic afforded the opportunity to study what impact this had on a large population of pet dogs over time, that would otherwise have been impossible to capture at such scale. Line 355: delete the first “the” 1 2 ani12040482_makarova 0 +This is a well written and clear manuscript which would be of interest to academics, practitioners and dog owners. Therefore, the detailed description of the pandemic is unnecessary and could be moved to the Supplemental material, together with Figure 1. 1 2 ani12040482_makarova 0 +I do think this is of interest to a range of stakeholders. What is surprising though is that 55.7% of the dogs who were reported to show SRB in February (before the pandemic) were clear in October which is good news. However, the authors do not focus on this result and do not explain this finding. 1 2 ani12040482_makarova 0 +What I see in Figure 4 and in the text is that approx. Specific points requiring attention: L18-20 „Whether dogs showed SRBs or not changed considerably over the months of the study, and one in ten dogs were found to have developed new SRBs in October, that they didn’t show before the pandemic” Overall, the percentage of dogs showing SRBs decreased during the study, and this should be clarified in the sentence above. 1 2 ani12040482_makarova 0 +What I see in Figure 4 and in the text is that approx. L22 and elsewhere: dogs’ “leaving time” or “leaving hours” I think this expression is misleading because it is not the dogs that have left home, but the owners. 1 2 ani12040482_makarova 0 +L382 Please refer to Flannigan and Dodman (2001) here (owner’s work schedule affects separation problems). L45 Separation behaviour, separation-related behaviour, separation distress, separation anxiety terms are used interchangeably throughout the text, although these terms do not necessarily describe the same behaviours. Please provide a clear definition of the behaviour aimed to study and stick to one term. 1 2 ani12040482_makarova 0 +This is discussed later on but highlighting here would be useful. L92 delete the comma after Bowen et al.’s. 1 2 ani12040482_makarova 0 +It may be beneficial to make it clear why cut off of 'at least 5 mins' was used, e.g justification for this/why this time duration used. L92-92 28.5% of dogs reported to have SRPs – this is a much higher number than mentioned in previous studies and needs to be discussed. 1 2 ani12040482_makarova 0 +This information would have been interesting if data on the mood, stress level, general mental health of the owners had also been collected in connection with the pandemic and the links with dog behaviour have been investigated. L118 Materials and Methods This section (after the Ethics) should begin with the Subjects section. 1 2 ani12040482_makarova 0 +Author Response Thank you for your time in reviewing this manuscript and for your constructive, helpful feedback. L127-137 The dates of data collections have been already mentioned in L121-126, so there is no need for repeating them. The whole section is not relevant to the main question. 1 2 ani12040482_makarova 0 +Animals 2021, 11, 5, 524 doi:10.3390/ani11010005; *Holland, K.E. ; Owczarczak-Garstecka, S.C.; Anderson, K.L.; Casey, R.A.; Christley, R.M.; Harris, L.; McMillan, K.M.; Mead, 529 R.; Murray, J.K.; Samet, L.; et al. L131-132 and elsewhere: (Error! Reference source not found.) This error occurs 7 times in the text, please correct. 1 2 ani12040482_makarova 0 +It seems you have compared within dogs that showed SRB in baseline and other models for dogs that did not. L148 Please explain why a periof of 7 days were asked to be reported 1 2 ani12040482_makarova 0 +This is discussed later on but highlighting here would be useful. L165-167 Figure 1. This Figure should be moved to the Supplement material as it tells nothing about the dogs’ behaviour. 1 2 ani12040482_makarova 0 +I think that according to the statistics, the strongest finding is that dogs who showed SRB in February or May had increased odds of having SRB during the subsequent measures which is not surprising. L216-218 “The text was then coded by two researchers” I could not find agreement data reported later. 1 2 ani12040482_makarova 0 +You note that the pseudo-R2 was small but I think you could go into more details and note the possibility that it was unrelated too. L238 Do the authors have information about the Owner demographics? What was the proportion of females? Was there a relationship between age and leaving hours? Or explain why this information has not been used. 1 2 ani12040482_makarova 0 +But this is the opinion of a person using English as a second language. L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section 1 2 ani12040482_makarova 0 +Aa little more mention of issues of SRBs from owner perspective (e.g. Among them, what was the proportion of owners who has not responded to the request afterward? 1 2 ani12040482_makarova 0 +Was there a relationship between age and leaving hours? L278-280 “There were 1,407 dogs who were clear of SRB at baseline in February 2020. When looking at SRB status in October, of 1,187 dogs who were left alone in October, 117 (9.9%) were reported to have shown at least one SRB”. In other words, 1407/1807 (78%) of dogs were clear of SRB in February and 90.1% in October. This is good news, and it is unclear for me why is it reported as bad news. 1 2 ani12040482_makarova 0 +This is good news, and it is unclear for me why is it reported as bad news. L285 Figure 4. This is a great figure, thank you for including it. However, an explanation would be useful for those readers who are not familiar with this type of depicting. 1 2 ani12040482_makarova 0 +Minor issues: Line 35: insert “of” after 9.9% L291 The odds ratio (OR) is 5.38 and not 4.38 in Table 1. 1 2 ani12040482_makarova 0 +L314 Table 2: bold is not used here although it was used in Table 1 L293-295 “The final variable associated with October SRB status was the difference in the number of days dogs were left alone for between the February baseline and lockdown”. OR was 0.81 here. Please explain the relationship between the variables. 1 2 ani12040482_makarova 0 +This topic is not addressed until the Discussion section (line 395) but should be addressed here in the Methods and Materials section. L298 Table 1 legend: Add what bold indicates 1 2 ani12040482_makarova 0 +L45 Separation behaviour, separation-related behaviour, separation distress, separation anxiety terms are used interchangeably throughout the text, although these terms do not necessarily describe the same behaviours. L307 The odds ratio (OR) is 4.97 in Table 1 and not 3.60 1 2 ani12040482_makarova 0 +As I wrote in the previous manuscript review: “Impact of changes in time left alone on separation-related behaviour in UK pet dogs” is one more paper on the behavior of dogs in the COVID-19 pandemic developed in the last two years. L314 Table 2: bold is not used here although it was used in Table 1 1 2 ani12040482_makarova 0 +We might see some dogs become sensitized over time and develop SRB (or something else changes in their life to precipitate it), while others might habituate or their behavior undergo extinction. L333 table 3: same: bold is not used here 1 2 ani12040482_makarova 0 +This information might be presented in your other paper, but it would be good to include this basic information here as well, so readers can better understand your methods and findings. L382 Please refer to Flannigan and Dodman (2001) here (owner’s work schedule affects separation problems). Flannigan, G., & Dodman, N. H. (2001). Risk factors and behaviors associated with separation anxiety in dogs. Journal of the American Veterinary Medical Association, 219(4), 460-466. 1 2 ani12040482_makarova 0 +Lines 383-384: Change “dogs’ leaving routines” to “dogs’ time left alone” Thank you, this edit has been applied. L395-397 “This value is likely to be an underestimate” The underestimation has already occurred during the baseline. 1 2 ani12040482_makarova 0 +"“In section VI E. ""Trapping by longitudinal pumping"", one can analytically estimate the threshold value for the transverse pumping." It remains unclear how the quantum regime (with coherent spatial delocalization and interference of probability amplitudes of different paths) could possibly be reached in a real experiment, as spontaneous scattering of photons (of the cavity light or of the side pumper) into free space would localize the atomic wavefuction into one lattice site and thus decohere any spatial delocalization. 1 2 atoms3030433_perova 0 +I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored.” For a quick orientation it would be helpful to indicate the x-axis 1 2 atoms3030433_perova 0 +“Page 4, first paragraph, the particle initial conditions are chosen in the interval [ - 0.1, 0.1] (in the text a comma is missing).” "In Section I the authors write: ""The mechanism is similar to the ones exploited in the creation of artificial potentials in optical lattices [17]"". This statement is a bit misleading since [17] uses coherent (quantum-mechanical) tunnelling with complex tunnel amplitudes, whereas the present manuscript deals with classical trajectories and classical jump probabilities." 1 2 atoms3030433_perova 0 +However, the Authors outline possible generalizations to the quantum regime in the concluding section. In Section II it should be clearly stated that this is a one-dimensional model, transverse forces or motion are not considered. 1 2 atoms3030433_perova 0 +I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored.” "in Fig. 2: ""such that c < 0 corresponding to the stable regime of cavity QED with moving atoms"": what does this mean? The regime of cavity cooling?" 1 2 atoms3030433_perova 0 +The approach is scientifically sound and convincing. In Section III the numerical value of \kappa is not given (only in the caption of Fig. 3 it is mentioned that \kappa is set to unity). 1 2 atoms3030433_perova 0 +It would be more logical to exchange their presentation order and, consequently, the figures numbering. The numerical values of the parameters used for the simulation are in the bad cavity regime (g << \kappa, \gamma). Does the special spatio-temporal shape of the potential, which is shown in Fig. 3, and which enables the effective random walk motion, originate in genuine cavity quantum effects, or could a similar potential be generated also in the classical (bad cavity) limit (g -> 0, \eta_L -> infinity and \kappa large), or for a classical standing wave laser beam interfering with a classical transverse running wave? 1 2 atoms3030433_perova 0 +I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored.” In describing the action of the optical potential as quasi-random potential kicks, is there some long-term heating effect (i.e. an increase of the average energy of the atom)? Does cavity cooling play a role to counteract this in the numerical simulations?Response Response We thank the referee for an extremely careful reading of the manuscript, his/her appreciation of it and for the very constructive criticism expressed in this report. 1 2 atoms3030433_perova 0 +The authors could help readers by better putting their work into context and improving some of their explanations. In the paragraph following Eq. (2), please check the commutation relations between the raising (sigma^+) and lowering (sigma^-) operators and the Pauli matrix sigma^z. I suspect it should be [sigma^+,sigma^z] = - 2 sigma^+ and [sigma^-,sigma^z] = + 2 sigma^- . 1 2 atoms3030433_perova 0 +The approach is scientifically sound and convincing. "A couple of lines below Eq. (4), the Authors write ""We proceed in a standard way to derive equations of motion for classical quantities."" I would suggest to provide a reference to guide the less experienced reader." 1 2 atoms3030433_perova 0 +The same misprint appears at page 8 in the paragraph between Eqs. In the equations of motion for the atoms [Eqs. (6) and (7)] it is introduced the quantity gamma, which, I guess, is the atomic decay rate. Please, provide a definition of gamma. What is, if any, the role of gamma (spontaneous atomic decay rate) in the physical process under consideration? In the analytical results, derived in the adiabatic limit, gamma is eliminated and does not play any role. I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored. 1 2 atoms3030433_perova 0 +"(4), the Authors write ""We proceed in a standard way to derive equations of motion for classical quantities.""" "At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived. Please, check this value. I'm afraid there is a factor k missing (simple dimensional analysis shows that something is wrong with it)." 1 2 atoms3030433_perova 0 +“However, I have a few comments and suggestions to improve the overall quality and readability of the paper. "In section VI E. ""Trapping by longitudinal pumping"", one can analytically estimate the threshold value for the transverse pumping. How does this analytical result compare with the numerical simulations?" 1 2 atoms3030433_perova 0 +However, the Authors outline possible generalizations to the quantum regime in the concluding section. Please, be consistent with the choice of subscripts and superscripts: in the first column of page 2 the Pauli operator is denoted as sigma^z (superscript), whereas in the second column becomes sigma_z (subscript). 1 2 atoms3030433_perova 0 +"Please, eliminate ""b)"" since it is simply Eq." Figure 4 is mentioned in the main text AFTER Fig. 5. It would be more logical to exchange their presentation order and, consequently, the figures numbering. Indeed, the same Authors already refer to the single trajectory plot as Fig. 4 (c) [see paragraph below Eq. (13)]. 1 2 atoms3030433_perova 0 +"Please, eliminate ""b)"" since it is simply Eq." Page 4, first paragraph, the particle initial conditions are chosen in the interval [ - 0.1, 0.1] (in the text a comma is missing). 1 2 atoms3030433_perova 0 +“Finally, some stylistic considerations: Please, be consistent with the choice of subscripts and superscripts: in the first column of page 2 the Pauli operator is denoted as sigma^z (superscript), whereas in the second column becomes sigma_z (subscript).” "Page 5, first column, second paragraph ""... one can inspect Eq. (11) b) where the right-hand side ..."". Please, eliminate ""b)"" since it is simply Eq. (11). The same misprint appears at page 8 in the paragraph between Eqs. (32) and (33)." 1 2 atoms3030433_perova 0 +The simultaneous driving at two different frequencies gives rise to interference terms in the optical force acting on the particle. "Page 6, ""Optical forces"": there is a missing subscript L in the first force term at the end of the first paragraph, just before Eq. (21)." 1 2 atoms3030433_perova 0 +The same misprint appears at page 8 in the paragraph between Eqs. Figure 8, Force correlation functions and numerical solutions of the variance: when printed in grey scale some lines are very faint (especially those in green and cyan). Try to use other colors and/or thicker lines. 1 2 atoms3030433_perova 0 +I am not sufficiently aware of the use f Wigner function but I am sure that there are better and more useful references to quote in addition to ref 17! The novelty of the paper would not be reduced if the authors had quoted previous works on the same subject or using the same technique: The first example is the result announced in Equation (4), concerning the phase shift due to the gravity gradient gamma. This effect was first calculated by Wolf and Tourrencin Physics Letters A 251 (1999) pp 241–246 and discussed with more details in A. Peters, K.Y. Chung and S. Chu, Metrologia 2001, 38, 25–61. 1 2 atoms4020014_makarova 0 +The results obtained seem reasonable, although I have no time to verify all the derivations. Moreover, the authors call this effect a quantum correction probably because it is proportional to hbar but it would be more clear to explain that, the leading term of the gravitation phase being independent of hbar because of a cancellation (hbar appears in the numerator and denominator of the quantity giving the phase), the term linear in gamma is also proportional to the recoil velocity which itself is proportional to hbar. 1 2 atoms4020014_makarova 0 +The response to these comments and changes to the manuscript in response to these comments is given below: 1. The treatment involves quantum corrections which are treated by calculating the Wigner representation of the density matrix and I am not aware of the use of such an extensive use of Wigner representation to describe atom interferometry experiments. 1 2 atoms4020014_makarova 0 +It will be helpful to the readers if a figure is provided to show the locations. The treatment involves quantum corrections which are treated by calculating the Wigner representation of the density matrix and I am not aware of the use of such an extensive use of Wigner representation to describe atom interferometry experiments. 1 2 atoms4020014_makarova 0 +Authors’ response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. In my opinion, phi_Q is the real quantum correction due to the spreading of the wavepacket during propagation. If I am correct, this should be explained. 1 2 atoms4020014_makarova 0 +Two processes are considered, one occurs during the interaction between the cold atom cloud and the Raman beams, the other occurs during the free evolution of the cold atom cloud in vacuum. The meaning of the three x_C, x_qC and x_QC (Equation (99)) is far from obvious but it is very surprising that the leading term in T^2 is different? 1 2 atoms4020014_makarova 0 +I recommend accepting this manuscript, provided the following points are clarified: The paper is quite difficult to read, because of very many bulky equations. I do not see how to reduce the number of equations but I think that some more comments would help the reader. For instance, the equations 12 to 14 were not clear for me but I found an explanation at Equation (37). 1 2 atoms4020014_makarova 0 +Author response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. The paper contains only one figure with 28 panels presenting the results of the calculations. I think that this figure is very difficult to read! I do not understand clearly why results are plotted with y < y_min if this not physical: please explain! 1 2 atoms4020014_makarova 0 +Two processes are considered, one occurs during the interaction between the cold atom cloud and the Raman beams, the other occurs during the free evolution of the cold atom cloud in vacuum. A figure explaining the geometry of the experiment would also help. 1 2 atoms4020014_makarova 0 +The response to these comments and changes to the manuscript in response to these comments is given below: 1. The diffraction probability is assumed to be exactly ½ for the pi/2 pulses, with no dependence with x or p. Is this justified? 1 2 atoms4020014_makarova 0 +Although each plot is difficult to read at “normal” magnification, the online reader can easily magnify any plot when accessing the article in PDF format. The fountain is assumed to be exactly symmetric (see line after Equation (100)). It is well known that with symmetric fountains diffraction with retro-reflected laser beams produces stray interferometers... Minor Remarks 1 2 atoms4020014_makarova 0 +It arises as a quantum correction to phase factors during periods of free evolution. I noted an error after Equation (1): ... the gravitational potential is constant... I assume that the authors meant acceleration g, not the potential. 1 2 atoms4020014_makarova 0 +The response to these comments and changes to the manuscript in response to these comments is given below: 1. The relative location of the test mass to the cold atom cloud should be clearly stated during the calculation, as the gravitational force is a vector. If the test mass is not located in the direction of the evolution trajectory of the atom cloud, the applicability of some formulas (e.g. Equation (3)) need to be verified. 3 2 atoms4020014_makarova 0 +The response to these comments and changes to the manuscript in response to these comments is given below: 1. The cloud is assumed to be characterized by a Wigner distribution function. What are the advantages to use Wigner distribution function instead of wave function? 3 2 atoms4020014_makarova 0 +Authors’ response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. Just for the note of the authors, there are some new applications of atom interferometer, e.g., in the accurate measurement of the quadratic Zeeman coefficient [J. Phys. B: At. Mol. Opt. Phys., 47(1): 015001, 2014]. 3 2 atoms4020014_makarova 0 +Many nucleotide variants, whether they affect protein changes or not can affect potential splicing of exons. Line 156 – the authors refer to “ad-hoc rules” that they have developed for consideration of the different coding transcripts associated with the same spliceogenic variant in variant interpretation and classification. Although a reference is provided so that the reader can look up what these ad-hoc rules are, it would also be helpful to briefly describe these in the current manuscript. 1 2 cancers14122960_perova 0 +describes about the analysis of RAD51C variants using mini-gene assays for splicing defect. Lines 250-251 and 263-265– In these lines the authors discuss transcripts in which the encoded proteins lack some beta strands. The lack of these protein structures are used as evidence to support pathogenicity. It is not clear from the text how lack of these beta strands is predicted to impact protein function. Is there evidence from another source that these beta strands are critical to protein function and that their loss is deleterious (rather than resulting in normal or slightly reduced protein activity)? 1 2 cancers14122960_perova 0 +These variant interpretations were generally evidence based and well thought out. Lines 259-274 – This paragraph refers to evidence used in the variant interpretation of three aberrant transcripts that kept the open reading-frame (Δ(E2p3), Δ(E5) and ▼(E8p3)). However, the corresponding tables that summarizes variant classification according to the ACMG/AMP-based criteria (Table 2), does not include these transcript isoform names. As such, in order to correlate the discussion in this paragraph with the information in table 2, the reader also needs to cross reference Table 1 or 3. Incorporation of the transcript isoform names in table 2 would assist the reader in correlating this discussion of transcript isoforms with the corresponding evidence used to classify each of the variants. 1 2 cancers14122960_perova 0 +Lines 250-251 and 263-265– In these lines the authors discuss transcripts in which the encoded proteins lack some beta strands. Lines 342-359 – This paragraph discusses two RAD51C variants, c.404+3A>G and c.705+3A>G, for which mg-FL transcripts were detected in 26.3% and 21.3% or transcripts, respectively. The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. Leaky splice variants have been reported in various genes and sometimes can be associated with milder phenotypes (or no phenotypes), presumably because the canonical isoforms contribute to a “phenotypic rescue”. Is it known whether there is a threshold of RAD51C deficiency that is tolerated before associated cancer risks become increased? 1 2 cancers14122960_perova 0 +As such, in order to correlate the discussion in this paragraph with the information in table 2, the reader also needs to cross reference Table 1 or 3. in the Introduction in the sentence 61-69 the authors do not mention anything about BRCA1 (they mention MLH1 though); 1 2 cancers14122960_perova 0 +I would also stress a little more that FL is almost undetectable. I would expect that as BRCA1 splice variants are deeply studied. In the Materials and Methods, the section 2.6 is not actually a section that described some methodology. It appears to be more appropriate as results and maybe some information could be in the introduction. 1 2 cancers14122960_perova 0 +The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. The acronyms need to be explained. Not all readers are familiar with PTC (premature termination codon) and NMD (nonsense mediated decay); as some variants are found PTC-NMD, this needs to be explained better. I would also stress a little more that FL is almost undetectable. 1 2 cancers14122960_perova 0 +The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. Splicing variants are called solely based on the size difference. It is good to look into Sanger sequence of splice variants after gel elution of the band and sequencing. 1 2 cancers14122960_perova 0 +In general, I thought that this manuscript was interesting to read and added important information to the literature to facilitate accurate variant interpretation of RAD51C spliceogenic variants, which in turn can better facilitate risk assessment and genetic counselling in families carrying these variants. Splicing variants are called solely based on the size difference. It is good to look into Sanger sequence of splice variants after gel elution of the band and sequencing. 1 2 cancers14122960_perova 0 +Our decision on this manuscript – Major revision. Some FT-IR peaks shift with adsorption of Cr, and some not. Please add the discussion which peak shift is related to Cr, the authors can combine these with the discussion of the mechanism. 1 2 catal12030290_perova 0 +We hope the reviewer understand the experimental deficiencies at the stage of the present experiments. In Figure 3, what is the origin of the increase concentration of Al and S? 1 2 catal12030290_perova 0 +And the authors are strongly recommended to add XPS spectra to this section of revised manuscript. In the experiment, H2SO4 is added in the first step, what is the purpose? Will this bring pollution problem? 1 2 catal12030290_perova 0 +The paper mainly presents two key contributions: Synthesis of bioadsorbent and evaluation of its structure using SEM and FT-IR spectroscopy. How about the Cr concentration in the polluted ground water? Is the products suitable for this real condition? 1 2 catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. The issue of regeneration has not been sufficiently worked out, but the authors themselves write about this, and it is not clear why NaOH was used for this. 1 2 catal12030290_perova 0 +A point-by-point response to the reviewer-2 comments is appended below for your convenience. It was also not clear to me how much hydrochloric acid was eventually added during the preparation of the adsorbent. 1 2 catal12030290_perova 0 +The authors are very thankful to the Reviewer for their valuable suggestions for the improvement of the manuscript. The authors did not indicate how the “separation factor ‘RL’ is calculated and did not give a link to the equation for its calculation, and if the readers are not quite in the subject, then what kind of factor they do not understand. 1 2 catal12030290_perova 0 +A point-by-point response to the reviewer-3 comments is appended below for your convenience. One could also estimate the specific surface area and porosity. So, the paper can be published after revision. 1 2 catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. The authors should write the complete terms of all abbreviations (including the instruments) before the first use in the abstract and main manuscript i.e. FT-IR and SEM in abstract section et al. 1 2 catal12030290_perova 0 +Author Response We appreciate the efforts of the reviewers for their detailed and insightful comments, which have helped us to improve the quality of our manuscript. The authors should clearly explain the innovation and importance of their work on the introduction of the manuscript. They should justify the value of the work and compare their work with previously similar published papers. 1 2 catal12030290_perova 0 +The manuscript is well- organized, all the conclusions are supported by the presented data. Fig. 1 - for a more effective visual comparison, authors recommended to provide SEM images of the same scale. In such form is rather difficult to make adequate comparison. 1 2 catal12030290_perova 0 +Comment 3: It is better to show the SEM images using the same scale. EDX analysis (Fig 3) - a very conditional (not specific) type of analysis of the chemical composition of the surface. Often, spectra with different atomic abundances of elements can be obtained even from the same sample. First of all, authors have to attach a EDX mapping images before/after sorption of chromium ions. And the authors are strongly recommended to add XPS spectra to this section of revised manuscript. The XPS method is much more sensitive and more accurately determines changes in the chemical composition of samples. 1 2 catal12030290_perova 0 +A point-by-point response to the reviewer-3 comments is appended below for your convenience. Why authors did not use XRD technique for sample characterization? 1 2 catal12030290_perova 0 +A point-by-point response to the reviewer-2 comments is appended below for your convenience. The adsorption capacities of Al-GNSC adsorbents at different contact times have been provided. Which kinetics are right? Please add missing information about appropriate kinetic model in revised manuscript. 1 2 catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. It is rather difficult to make an adequate comparison of certain properties (catalysts or sorbents) with the already available results, since the concentration of the pollutant and the mass of the loaded sorbent vary in each experiment. Therefore, the authors are recommended to add the missing information (i.e. conditions for testing sorbents of Cr(VI) ions) to Table 3. 1 2 catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. In order to confirm proposed mechanism of Cr(VI) adsorption (illustrated on the fig 6) Authors should provide data on adsorption capacity of pristine groundnut shell activated carbon (not modified with Al). 1 2 catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. The conclusion section should be elaborated and improved. The author should bring specific conclusions in accordance with obtained results. 1 2 catal12030290_perova 0 +A point-by-point response to the reviewer-3 comments is appended below for your convenience. Moderate English changes required 1 2 catal12030290_perova 0 +Streptolysin S (SLS) is a small, non-immunogenic, peptide. The authors used the term liposome nanotraps. The authors have used conventional liposome preparations. It is not clear why they are calling the preparations as the nanotraps. 1 2 cells11010166_makarova 0 +Counting unstained, confluent cells by modified bright- field microscopy. The authors have used bacterial culture supernatants to examine the cytotoxic effect on the THP-1, Jurkat, and Raji cell lines. Quantitation fo the the culture medium is required (by measuring the total protein content, or by providing some quantitative indicator). Volume of the culture supernatant is mentioned in the results. It is not quantitative, and will vary from batch to bath of the bacterial culture. 1 2 cells11010166_makarova 0 +Besançon H, Babiychuk V, Larpin Y, Köffel R, Schittny D, Brockhus L, et al. LDH-release assay of cytotoxicity or MTT assay of cell viability should have been used for measuring the cell death. 1 2 cells11010166_makarova 0 +However, authors did not make any attempt to explore this aspect in mechanistic detail. It is well-known that SLO binds to the cholesterol-containing lipid bilayer. Therefore, it is obvious that the cholesterol-containing liposomes would neutralise SLO present in the bacterial culture. Therefore, no new information is provided with these experiments. 1 2 cells11010166_makarova 0 +The following text was added to the material and method section: The data were normalized to a control incubated with PBS instead of bacterial supernatant (considered as 0% cell death). In my opinion, differential inhibition of the SLS activity in GGS supernatant by the liposome preparations is interesting, and may provide new insights, if explored in more detail. 1 2 cells11010166_makarova 0 +In this manuscript, the Authors examined the efficacy of the liposome preparations to neutralise the exotoxins like SLO and SLS present in the bacterial culture medium. Although the sensitivity of immune cells to GAS or GGS supernatants is shown in the first section of the results, were any controls used in the neutralization assays with liposomes? 1 2 cells11010166_makarova 0 +At the concentrations used in current study the liposomes were not cytotoxic (data not shown). Furthermore, it should be justified why this difference does not influence the comparison of the results with the different cell lines (THP1, Jurkat, Raji). 1 2 cells11010166_makarova 0 +Moreover, most studies that add variables to the models, such as the dependency ratio, argue that Wagner’s law holds conditional on it. I don’t really doubt the empirical findings of the paper (which I see as support for the hypothesis in Japan and possibly in Korea), but I dislike the approach of spending a lot of space on various, often pointless, tests. There should be one detailed analysis based on adequate tests, and a discussion about the results. After all, government expenditure is a political decision. 1 2 economies3040150_makarova 0 +Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. An import question is why are the series for real GDP per capita are taken from PWT 7.0? These series are constructed to be used in cross-country studies, and they are not suitable for the analyses in the paper. See the paper by Johnson et al. (2009). 1 2 economies3040150_makarova 0 +Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. The dependency ratio has not been included mechanically in most papers, as it is this one. It is supposed to pick up changes in demand for government expenditure, such as schooling and pensions. The general idea is that these have increased government expenditure, both because per-capita schooling and pensions have expanded and because the dependency ratio has increased. In most of the countries studied, as is well-known, the dependency ratio declined during the period studied, while expenditure per person probably increased. Japan is most likely an exception; it should have entered the demographic transition much earlier than the other countries. There is thus no a priory no reason to expect the dependency ratio to play an important role in the Wagner hypothesis in general. It can thus be removed from the analysis, or moved to a footnote. If the author(s) wish to pursue the approach of testing other potentially relevant variables, see Shelton 2007. 1 2 economies3040150_makarova 0 +While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. Figure 1 tends to hide co-movements between the variables by mixing of scales. I suggest the graphs are re-done using two y-axes and preferably logs. 1 2 economies3040150_makarova 0 +Now the paper is mainly an econometric exercise. In Table 5 we can get information about cointegration from the R2 and the t-values. Only Japan shows any promise, in all other cases R2 are very low. I would say they are suspiciously low for time series data. Are thy correct? 1 2 economies3040150_makarova 0 +While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. Gregory–Hansen is used when one fails to find cointegration with standard tests. There is no point in testing countries such as Japan and Korea, when a superior test shows that they are cointegrated. 1 2 economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. The use of the MTAR model is dubious because of the small sample, and it should not be used when cointegration has been established. It is unlikely that there is enough information in the data to capture asymmetric effects and the standard procedure is to use MTAR when Engle-Granger fails to show cointegration. 1 2 economies3040150_makarova 0 +Round 1: The paper analyzes the validity of Wagner’s law in six East Asian countries during the period 1960- 2008. What is the alternative hypothesis of the Pedroni test, that there is cointegration in any country or or in all countries? This should be made clear. 1 2 economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. “Methodologically, while the pattern is reflected fairly well in plots and simple correlations, and even in regressions, the widely-used cointegration methodology yields a diverse scenario in four different procedures, and, through a choice of the procedure and the model, it seems as easy to conclude that there is no cointegration, and thus no support for the hypothesis as to conclude that the evidence supports the hypothesis in a majority of the cases. At any rate, it is not obvious that such sophisticated and complex tests of cointegration provide any useful additional insight regarding the empirical status of the hypothesis. More generally, we venture the highly subjective view that despite the immense mathematical sophistication of cointegration tests and their application in perhaps thousands of studies, it is not obvious how much additional substantive insight has been gained in the wide variety of contexts in which these tests have been used.” These statements should be explained. Is the second one a rejection of the last 40 years of advances in times series analysis? 1 2 economies3040150_makarova 0 +Moreover, most studies that add variables to the models, such as the dependency ratio, argue that Wagner’s law holds conditional on it. Despite Biehl’s (1998) insightful essay, almost all empirical research on the topic has interpreted the Wagnerian proposition 1 2 economies3040150_makarova 0 +While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. The x-axes in Figure 1 should have years. 3 2 economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. List of references is scant and limited. It is necessary to add more recent works on the subject with alternative ways of testing for Wagner’s Law. Suggestions include “Testing the Validity of Wagner’s Law in Bolivia: A Cointegration and Causality Analysis with Disaggregated Data” by A. Bojanic (2013); “Wagner’s Law and Italian Disaggregated Public Spending: Some Empirical Evidences” by C. Magazzino (2010); and “Panel Data, Cointegration, Causality and Wagner’s Law: Empirical Evidence from Chinese Provinces” by Narayan, P.K., et al. (2008). 1 2 economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. The paper only lists one way of testing for Wagner’s hypothesis (i.e., analyzing the relation between the share on GDP of government spending and real GDP per capita) when in fact there are many ways of looking at the hypothesis. The authors should include at least a couple of recent ways of testing this law, in addition to the traditional way of testing for it. 1 2 economies3040150_makarova 0 +Even if many studies have failed to that Wagner’s law holds, there is a common perception that it holds over periods when countries become developed. The variables used do not have the same units, which may clog the analysis of the paper. Specifically, real GDP per capita is measured in 2005 dollars while the share of government consumption on GDP is measured in current prices. Either both should be in real terms or both in current prices, but not as is currently the case. 1 2 economies3040150_makarova 0 +This makes the unconditional correlations uninteresting. The descriptive stats in Table 2 reflect stats for the whole period? If so, the table should explicitly state this fact. 1 2 economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. Why are there 3 graphs for the Philippines in Figure 1? By the way, if the variables were measured in either current prices or utilizing the same base year, these graphs would likely be quite different (same goes for all statistical analysis, it is likely to vary when the two variables are measured the same way) 6. 1 2 economies3040150_makarova 0 +This is a major flaw of the paper and the choice should be defended by showing that using the ‘standard’ real GDP series’ would give the same results. What is the point of the dependency rate? The authors should expand on the need to add this variable and what exactly is it trying to capture. In the same vein, what do the authors mean by “however, it seems that the fall in young-dependency ratio was greater than the rise in the old-dependency rate” on p. 4? 1 2 economies3040150_makarova 0 +The suggestions are listed below in no particular order of importance: 1. In Table 4, delete the “generated by SAS” note. 1 2 economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. My recommendation is to accept the paper for publication. 3 2 economies3040150_makarova 0 +done Figure 1B -Consider adding a small inset table or schematic to showing the Cambrian Limestone Aquifer stratigraphy in the Georgina, Daly and Wiso basin. Figure 1: Are colors in Figure 1 A related to the hydrostratigraphy or depicting topography? If the latter applies, make sure to provide a scale. 1 2 geosciences12010037_perova 0 +The present paper is thus part of an ongoing debate and the findings presented here are likely to influence discussions and decisions by stakeholders. Figure 2: The left spine (or border) does not appear on the pdf reviewed. This figure could be improved by adding shaded satellite image to help the reader compare the mapped drainage systems (which were automatically mapped) and fault traces/lineaments with the real features observed. 1 2 geosciences12010037_perova 0 +Results appear to be sound and supported by the illustrations. Figure 3: The text (lines 258-259) mentions magnetic lineaments as prominent features, which can be caused by faulting. Such features are hard to visualize. It would certainly help if they were highlighted directly on the figure. 1 2 geosciences12010037_perova 0 +An indication is provided in the Discussion (Line 414), but it would go to state this value upfront in the text. Figure 4: This figure could go in the appendix. It is good to let the reader know that not all seismic surveys provided the same quality, but this is more a technical point. 1 2 geosciences12010037_perova 0 +done • Line 360: Here and throughout the text, the word ‘recent’ is used to describe some tectonic activity. Figure 7: What is special about the locations highlighted by the markers (crosses on Figure 7B and square markers on Figure 7C). At this scale, the reader can’t see much detail. 1 2 geosciences12010037_perova 0 +In this process, minor mismatches of the automated simplified lines were removed and small drainage segments were connected along major lineaments for further simplification and reduction of the dataset. Figure 9: Remove ‘s’ from <10 yearss. Also, increase the thickness of the fault lines to make them more obvious. 1 2 geosciences12010037_perova 0 +Alternatively the position of Figure 6 A, B and C should be indicated in Figure 4 as well as Figure 3. done Figure 5. Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? 1 2 geosciences12010037_perova 0 +Radon cannot give this information since with the short half-live of 3.8days it's signal comes only from the direct vicinity of the sampled location. Lines 323-324: The authors should explain why low magnitude local seismic signals can be believed to represent permeable pathways promoting water or gas migration. 1 2 geosciences12010037_perova 0 +Although the aeromagnetic data is said to be employed for structural interpretation, details somewhat sketchy. Line 360: Here and throughout the text, the word ‘recent’ is used to describe some tectonic activity. It would be good define what recent means in the context of this study. An indication is provided in the Discussion (Line 414), but it would go to state this value upfront in the text. 1 2 geosciences12010037_perova 0 +• Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? Discussion: One general comment, could the use of other tracers (radon, of stable isotopes of water) yield also insight on the origin of the fluids sampled in this study? 1 2 geosciences12010037_perova 0 +Why are these not classified in terms of signal quality? Aeromagnetic survey data acquired over the last 50+ years were employed for mapping structural and lithological features. Although the aeromagnetic data is said to be employed for structural interpretation, details somewhat sketchy. Reference is made to “…prominent […] magnetic lineaments which can be caused by faulting”, and “…several circular low magnetization anomalies, approximately two kilometers in diameter, aligned with northwest trending lineaments”. It would be nice to include a map with these features and lineaments interpreted from the aeromagnetic datasets. This would also tie the observations based on this dataset closer to the seismic interpretation (see below). 1 2 geosciences12010037_perova 0 +done -Many well-name labels are hard difficult to read/illegible. Seismic reflection 2D lines (1989-2015). 8500 km. Interpretation of shallow horizons and faults using all publicly available geological and geophysical data of the Beetaloo region. Fault polygons defined for five horizons. Depth conversion using check-shot velocities from 26 wells. See comments to Figure 4. The depth maps provided in Figure 5 should be supplemented by isochore maps for the rock volumes between pairs of mapped reflectors. See also comments to Figure 7. 1 2 geosciences12010037_perova 0 +Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). Helium measurements from groundwater samples. With respect to the helium measurements, no detailed documentation of where these samples were collected is provided beyond referring to Geological and Bioregional Assessment Program (2021a) Fact sheet 12, and Geological and Bioregional Assessment Program (2021b) Regional tracer results from the Cambrian Limestone Aquifer. These are both summary documents. Please provide a reference to the primary documentation. 1 2 geosciences12010037_perova 0 +Please provide a reference to the primary documentation. Fault and surface drainage network mapping (tectonic geomorphology). The drainage network was extracted automatically. It is not clear if the “simplified” drainage network shown in Figure 2 was also extracted automatically. The data is summarized in Figure 8 (see also comments to Figure 8 below). It is not clear if the surface drainage network line dataset is based on the “unfiltered” or “simplified” data shown in Figure 2. Since n=130, one can assume the latter. It is however not made clear how this “simplified” network was generated, but there appear to be a substantial number of instances where the “simplification” provides apparent mismatches with the original data (see examples included in comments to Figure 2 below). The accuracy of the resulting plot can therefore be questioned. If the “simplified” network was generated automatically, I encourage the authors to do a manual QC of the results. 1 2 geosciences12010037_perova 0 +It would certainly help if they were highlighted directly on the figure. Line 303: “We reviewed the seismic data in detail at the intersections with north-northwest trending lineaments observed on the magnetic dataset (Figure 4).” No such lineaments are shown in Figure 4. 1 2 geosciences12010037_perova 0 +We added : ‘this is due to the different seismic acquisition technics and processing applied in each survey as well as the fact that our interval of interest is shallow and not fitting with the interval of interest the companies tried to best image with those datasets” • Lines 323-324: The authors should explain why low magnitude local seismic signals can be believed to represent permeable pathways promoting water or gas migration. Line 582. Link for supplementary materials does not work. 1 2 geosciences12010037_perova 0 +Although the design of the figure is very much improved compared to the one submitted initially, it is still difficult differentiate between the Post Wilton “Strike-slip” and “Reverse” faults. Poor visual discretization of main surface fault traces and Post Wilton geophysical faults (maybe use different colour for the two?) 1 2 geosciences12010037_perova 0 +If the “simplified” network was generated automatically, I encourage the authors to do a manual QC of the results. Consider adding a small inset table or schematic to showing the Cambrian Limestone Aquifer stratigraphy in the Georgina, Daly and Wiso basin. Although this is described in the caption, it is not easy to grasp for someone not familiar with the stratigraphy in the area without spending time some time with paper and pencil. 1 2 geosciences12010037_perova 0 +Link for supplementary materials does not work. Very, very overloaded figure, screen-dump from a mapping programme? 1 2 geosciences12010037_perova 0 +Please find attached the revised manuscript with track changes as well as the reply to the detailed comments, directly in purple. How the authors arrive at the simplified drainage network is not very clear 1 2 geosciences12010037_perova 0 +Figure 4 -Poor quality figure (low resolution) in the version available to the reviewer. Poor quality figure (low resolution) in the version available to the reviewer. 1 2 geosciences12010037_perova 0 +Consider using the most prominent colour (red) for the possible fluid escape features as this is the key element of the map. Many well-name labels are hard difficult to read/illegible. Consider replacing well names on the map with numbers at the well position (white circles, black typeface) and add a table in the legend listing number and corresponding name of the well. 1 2 geosciences12010037_perova 0 +The figure has been redrawn and the magnetic lineaments indicated • Figure 4: This figure could go in the appendix. Thin grey seismic lines are not explained in the legend or caption. Why are these not classified in terms of signal quality? 1 2 geosciences12010037_perova 0 +Poor resolution in the copy provided for the review. Consider adding isochore maps for intervals between interpreted reflectors. These often highlight tectonic accommodation space creation better than maps. 1 2 geosciences12010037_perova 0 +Recent fault activity was identified using a combination of sub-surface imaging and comparison of fault orientations and surface drainage networks. Explain/improve labels (what do you mean by “ntspr_2M_gw”? “Coast_10million”? “frameworkboundaries”? “State_Borders_10million”. Amend labels or explain in caption. 1 2 geosciences12010037_perova 0 +Reply to review Thank you for this complete review. Several items in the legend appear to have the same or very similar signatures. 1 2 geosciences12010037_perova 0 +What is included in the “Drainage and structural lineament analysis” plot? Not possible to differentiate post-Wilton fault types properly in the figure. 1 2 geosciences12010037_perova 0 +I don't know if this is the case here, but if they do, including isochore maps would enhance the readers' understanding of basin geometry and -infill. Could not find “Coast_10million”, “frameworkboundaries” or “State_Borders_10million” on the map. If these items are present, please use a more contrasting signatures to make it more visible. If they are not present on the map, remove these items from the legend. 1 2 geosciences12010037_perova 0 +Overall, the implications of this study are important not only for industrial purposes (reservoir exploration and operation) but also for our basic understanding of subsurface flow processes over geological timescales. Consider replacing the purple outline of the eastern and western sub-basin with light grey shading. 1 2 geosciences12010037_perova 0 +• Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? Consider using the most prominent colour (red) for the possible fluid escape features as this is the key element of the map. Bright green might also bee an option. 1 2 geosciences12010037_perova 0 +It is not clear if the “simplified” drainage network shown in Figure 2 was also extracted automatically. Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). 1 2 geosciences12010037_perova 0 +The colour refer to the SEEBASE depth to basement, the legend has been added • Figure 2: The left spine (or border) does not appear on the pdf reviewed. The link between interpreted faults and fluid or gas escape features is a key feature of this figure. The map differentiates between “BaseCambrian seismic faults”, Post-Wilton “Strike-slip” and “Reverse” faults, and “FAULTS”. The categorization is not adequately explained (e.g. what differentiates “FAULT” from a “BaseCambrianSeismic fault”?). 1 2 geosciences12010037_perova 0 +Although the authors point out that more data is needed to identify the source of the gas, the observations made in this study confirm the presence of fault-controlled fluid flow pathways connecting the stratigraphic levels where the unconventional plays are located with shallower aquifers the Beetaloo basin. Consider adding a simple conceptual sketch highlighting the stratigraphic position of the different faults (and possible fluid escape structures– this would also help visualizing which stratigraphic intervals the potential fluid escapes originate from and which stratigraphic intervals are potentially connected along potential fault-related fluid flow pathways. 1 2 geosciences12010037_perova 0 +• Figure 1: Are colors in Figure 1 A related to the hydrostratigraphy or depicting topography? Please provide a more informative caption to what these plots show. What is included in the “Drainage and structural lineament analysis” plot? 1 2 geosciences12010037_perova 0 +Isochron maps have been included in the supplementary material, the initial review suggested isoCHORE maps. Figure 9. Poor resolution in the copy provided for the review. Consider using higher contrast colours or thicker lines to highlight different faults on the map. 1 2 geosciences12010037_perova 0 +frameworkboundaries to framework boundaries; populated places to Populated places/(Settlements?); PossibleFluidEscapeFeatures to Possible fluid-escape features etc. ). done, legend cleared from information not represented 4. d) Explain/improve labels (what do you mean by “ntspr_2M_gw”? I hope you will find these comments useful when revising the manuscript and look forward to seeing the paper published in Geoscience. 1 2 geosciences12010037_perova 0 +Interpretation of shallow horizons and faults using all publicly available geological and geophysical data of the Beetaloo region. With respect to the helium measurements, the references to the primary documentation requested by the reviewer in comments to v.1 of the manuscript are not provided, nor do the authors provide any comment as to why they deem this unnecessary. Section 4.3 Helium concentrations and isotopic composition measured in groundwater, is framed around results from previous studies. Providing references to these original studies (including access to the actual data that allow objective verification) rather than referencing to summary papers would be more in line with scientific publishing practice. If the primary documentation is not accessible, the authors should state this clearly. 3 2 geosciences12010037_perova 0 +According to the new caption shows the unfiltered surface drainage network. Figure 4. Seismic reflection data quality is ranked and colour-coded as “Excellent”, “Average” and “Poor”. Where does the fourth category, “Fair”, which also is a qualitative category, fit in, and why not include this category in the legend? 3 2 geosciences12010037_perova 0 +Although the authors point out that more data is needed to identify the source of the gas, the observations made in this study confirm the presence of fault-controlled fluid flow pathways connecting the stratigraphic levels where the unconventional plays are located with shallower aquifers the Beetaloo basin. Figure 5. Isochron maps have been included in the supplementary material, the initial review suggested isoCHORE maps. Including these is maybe not critical, but as mentioned in the initial review, thickness maps sometimes highlight structural lineaments quite well. I don't know if this is the case here, but if they do, including isochore maps would enhance the readers' understanding of basin geometry and -infill. 3 2 geosciences12010037_perova 0 +We need to know if the interpretation is reliable, especially in this shallow zone that is not well imaged by this type of data. If I understand the map correctly, fluid escape features on the map are shown as red dots. Why does the legend show these as thick red lines? 3 2 geosciences12010037_perova 0 +We tried to improve the figures at best- attached is a detailed reply to reviews. Figure 8. Please keep the number of measurements included in each plot. The plot “Surface drainage network from this study” is identical to the original figure and should have n=130 measurements. According to the new caption shows the unfiltered surface drainage network. To my understanding this should correspond to Figure 2 a, which shows substantially more than 130 lineaments. How did you pick the ones you measured? Please clarify. 3 2 geosciences12010037_perova 0 +As stated above, it may be worth considering moving these Bland-Altman figures to the supplementary file. The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. This does not seem to be addressed in the article, thus there seems to be no reason to include this phrase in the title. 1 2 nu14051073_perova 0 +P2 L69: The aim stated here does not follow the logic of the preceding statements in the paragraph, i.e., what does comparing BC methods have to do with lack of healthcare or technology? P2 L61: FFM is obtained via the 4C model – it is not a surrogate. Also, the difference(s) between FFM and LM definitions are nuanced and complex and should either be defined, or alternate text should be used here. It seems that the authors are simply trying to point out that use of the 4C model is not common and that other methods are normally used. Best to clarify this statement. 1 2 nu14051073_perova 0 +Reviewer two comments: I am not familiar with the Bland-Altman method, so was unclear when I read the methods section whether the text in lines 204-207 was explaining the Bland-Altman method or describing a separate procedure. P2 L69: The aim stated here does not follow the logic of the preceding statements in the paragraph, i.e., what does comparing BC methods have to do with lack of healthcare or technology? Is the focus then on finding low cost, easy to apply methods? The aim (and intent) of the study seems too simplistic as stated here – merely comparing methods. How would the results be applied to the healthcare situation in Mexico? These topics should be tied together, or an alternative motivation needs to be presented. 1 2 nu14051073_perova 0 +The two analyses were conducted on the same children’s database and closely complement each other. P3 L94: This is awkwardly worded. Who was asked to assent? 1 2 nu14051073_perova 0 +Hospital Infantil de México Federico Gómez Instituto Nacional de Salud UNIDAD DE EPIDEMIOLOGÍA CLÍNICA Hospital Infantil de México Federico Gómez Instituto Nacional de Salud UNIDAD DE EPIDEMIOLOGÍA CLÍNICA Mexico City, February 23, 2022 To the Editorial Board and Expert Reviewers: We, the authors, want to express our gratitude to the Editorial Board and the experts that reviewed our manuscript for their contributions. P3 L125: DXA: Was the head ROI excluded from the analyses (as per recommendation by the ISCD)? If so, it should be stated. If not, DXA analysis should be redone and all relationships recalculated. 1 2 nu14051073_perova 0 +None of the methods are ideal – all are flawed (in comparison with a gold standard). P5 L176: “(n=52?? )” Is there uncertainty of the number of participants or is this merely a typo? 1 2 nu14051073_perova 0 +RESULTS Table 1: The n values in the column headers add up to 293 rather than 288. P5 L207: The means of FM would be compared using t-test, not calculated. 1 2 nu14051073_perova 0 +Please find our answers in the following lines. Table 1: The n values in the column headers add up to 293 rather than 288. Are the n values incorrect or is the entire cohort presented here? 1 2 nu14051073_perova 0 +"(E.g., ""A positive trend indicates increasing underestimation of FM at high FM levels; a negative trend indicates increasing overestimation of FM at high FM levels." Table 1; Body Composition Variables: The mean values do not all agree with those in supplementary Table 1. 1 2 nu14051073_perova 0 +I am not well-versed in the ethnic composition of Mexico, however, would it be helpful to know the degree of representation of, for example, youth who are Black, of Indigenous ancestry, and of European ancestry? Table 1; MRI subsample: There is no indication of age, BMI, etc. in this group. That information may be helpful, perhaps also as supplementary data. 1 2 nu14051073_perova 0 +P13 L294: The legend for Figure 3 seems incorrect. P7 L226: It would be helpful if it was made clear that this refers to comparisons of means of all subjects (not broken down by age, sex). 1 2 nu14051073_perova 0 +It seems that the authors are simply trying to point out that use of the 4C model is not common and that other methods are normally used. P12 L283: Is Table 4 necessary? The title (and aim?) of the paper is all about comparing techniques against the 4C model. One also begins to wonder about affecting type 1 errors due to multiplicity of comparisons (debatable but worth considering). It may be worth considering moving Table 4 to the supplementary file and bringing supplementary Table 1 into the main document. If the focus (see the title) of the article is comparisons with the 4C model, then supplementary Table 1 seems to merit more direct attention. 1 2 nu14051073_perova 0 +Only 6.6% belong to indigenous population and 5.9% to Afro-Mexican ethnic groups. As stated above, it may be worth considering moving these Bland-Altman figures to the supplementary file. 1 2 nu14051073_perova 0 +)” Is there uncertainty of the number of participants or is this merely a typo? P15 L393: This paragraph reads more like a conclusion and seem out of place. It should perhaps be the last paragraph in the Discussion. 1 2 nu14051073_perova 0 +As stated above, it may be worth considering moving these Bland-Altman figures to the supplementary file. Much of the Discussion addresses strengths and weaknesses of the different BC methods, as if to provide guidance for clinicians in selecting the best techniques according to their needs and capabilities. None of the methods are ideal – all are flawed (in comparison with a gold standard). Yet a firm conclusion seems to be lacking. Concluding that methods differ is not surprising. One may be better served by discussing how the differences in methods (i.e. over or under estimating FM) may affect health assessments. That is, what impact may underestimating FM, by relying on one particular method, have on child care? How critical is the method selection? Somehow this needs to be tied more firmly to the population and environment being studied. 1 2 nu14051073_perova 0 +As it was, I couldn't understand the description provided, and it didn't seem to match the figures, which were simply labeled as FM, so seemed to be a simple plots of FM using 2 methods on first read. "I am not familiar with the Bland-Altman method, so was unclear when I read the methods section whether the text in lines 204-207 was explaining the Bland-Altman method or describing a separate procedure. I take from the results that those sentences were describing the Bland-Altman procedure, and if so, adding some text along the lines of ""In this procedure..."" would be helpful. As it was, I couldn't understand the description provided, and it didn't seem to match the figures, which were simply labeled as FM, so seemed to be a simple plots of FM using 2 methods on first read." 1 2 nu14051073_perova 0 +We have found your recommendations and commentaries of great value and have made appropriate changes. "Relatedly, it would have been helpful to have more explanatory titles for the plots--eg ""Differential correlation between methods across levels of FM"". And, the meaning of the trend line was very counter-intuitive, so an interpretive note under the plots would have been helpful. (E.g., ""A positive trend indicates increasing underestimation of FM at high FM levels; a negative trend indicates increasing overestimation of FM at high FM levels." 1 2 nu14051073_perova 0 +06720, Mexico City, Mexico E-mail: desiree_15@hotmail.com, dradesireelopez@gmail.com Dr. Márquez 162, Col. Doctores, C.P. There is no description of the race and ethnic composition of the sample. I am not well-versed in the ethnic composition of Mexico, however, would it be helpful to know the degree of representation of, for example, youth who are Black, of Indigenous ancestry, and of European ancestry? Or are there other ethnic or cultural groups that should be represented? 1 2 nu14051073_perova 0 +Somehow this needs to be tied more firmly to the population and environment being studied. I didn't understand why the data differed between Table 1 and Supplementary Table 1. Why did Ns (and means/SDs) differ? 1 2 nu14051073_perova 0 +P7 L226: It would be helpful if it was made clear that this refers to comparisons of means of all subjects (not broken down by age, sex). Not all abbreviations are listed for the table footnotes (FFM, D2O, DXA, LM, BV, ADP) 1 2 nu14051073_perova 0 +; Chou, P. Patients with Primary Open-Angle Glaucoma May Develop Ischemic Heart Disease More Often than Those without Glaucoma: An 11-Year Population-Based Cohort Study. What was the definition of visual field loss that defined glaucoma? 1 2 nu14122490_makarova 0 +"""As we did not observe an association between dietary nitrate intake and IOP, nitrate may protect against glaucoma via other, IOP-independent, mechanisms.""" Was glaucoma also defined by an objective finding, such as the optic disc finding or imaging of the optic disc? 1 2 nu14122490_makarova 0 +We appreciate the critical review and suggestions to improve our manuscript. Were the incident cases of glaucoma or controls being treated in any case prior to their diagnoses? 1 2 nu14122490_makarova 0 +Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. """ As we did not observe an association between dietary nitrate intake and IOP, nitrate may protect against glaucoma via other, IOP-independent, mechanisms. "" The authors should avoid making statements such as ""nitrate is protective"" since what they have found is a statistical association." 1 2 nu14122490_makarova 0 +doi:10.1001/jamacardio.2018.0022 I wonder if the authors could comment on this in the Discussion. There is very little association between ischemia--reperfusion and glaucoma pathogenesis hence the statements on page nine are irrelevant. 1 2 nu14122490_makarova 0 +OR (95%CI) P-value Total dietary nitrate intake (per 10 mg/day) Model 1 (including BMI) 0.95 (0.91-0.98) .002 Model 1 (excluding BMI) 0.94 (0.91-0.97) <.001 Vegetable dietary nitrate intake (per 10 mg/day) Model 1 (including BMI) 0.95 (0.91-0.98) .004 Model 1 (excluding BMI) 0.94 (0.91-0.98) .001 Nitrate intake from non-vegetable food sources (per 10 mg/day) Model 1 (including BMI) 0.63 (0.41-0.96) .03 Model 1 (excluding BMI) 0.61 (0.40-0.93) .02 If I am calculating correctly it has been over 20 years since the incident cases average followup occurred, that is 10-20 years after the start of a study in 1991. How much might the diet of persons in this population have changed since then? Thus, is this study still relevant to today? 30 years ago eating more vegetables was not the vogue it is today. 1 2 nu14122490_makarova 0 +The long space between the questionnaire and the incidence of glaucoma (only mentioned at the last part of the limitations) is quite a major limitation. This study would have been that much stronger if a follow-up food questionnaire had been administered. The long space between the questionnaire and the incidence of glaucoma (only mentioned at the last part of the limitations) is quite a major limitation. 1 2 nu14122490_makarova 0 +I would only like to ask about one fact that I find intriguing. Past studies of the Rotterdam population mention several other risk factors which were not taken into account in this study including myopia, cup-to-disc ratio, and family history of glaucoma, as well as other features such as exfoliation. How big is the nitrate association compared to these? 1 2 nu14122490_makarova 0 +Were the incident cases of glaucoma or controls being treated in any case prior to their diagnoses? Overall the finding seems to be an association without a rationale since in effect of nitric oxide presumably related to past nitrate intake would, by their own discussion, change eye pressure or blood pressure yet neither variable was associated with the incident glaucoma. 1 2 nu14122490_makarova 0 +; Sturmans, F.; Hermus, R.J. Reproducibility of a food frequency questionnaire and stability of dietary habits determined from five annually repeated measurements. The authors have conducted a case-control analysis based on a large epidemiological prospective study and investigated an association between dietary nitrate intake and incidence of OAG. The study has been well planned and performed. Chapter Material and Methods contain all necessary information. The writing is of perfect quality and the results are clearly presented. The results and conclusions of this study are important. 1 2 nu14122490_makarova 0 +Were the incident cases of glaucoma or controls being treated in any case prior to their diagnoses? I would only like to ask about one fact that I find intriguing. The authors have found that participants without OAG had a significantly higher BMI than those with OAG. Their mean BMI was found to be 27.1 kg/m2 which is considered overweight. Lower risk of OAG would be related to a higher total dietary nitrate intake. “Previous research has shown that a higher dietary nitrate intake was associated with significantly wider retinal arterioles. [46] Widening of retinal arteriolar caliber is not only associated with lower risk of cardiovascular and cerebrovascular diseases [47,48], but also with lower risk of glaucoma”. On the other hand, “compared with individuals with a normal BMI (defined as a BMI of 18.5 to 24.9), lifetime risks for incident CVD [cardiovascular disease] were higher in middle-aged adults in the overweight and obese groups” Khan SS, Ning H, Wilkins JT, et al. Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. JAMA Cardiol. 2018;3(4):280–287. doi:10.1001/jamacardio.2018.0022 I wonder if the authors could comment on this in the Discussion. 1 2 nu14122490_makarova 0 +Author Response Point-by-point response to reviewer's comments Thank you for inviting me to review this manuscript. The ms is the result of an intensive and years-long work of breeding, that eventually pyramidized several resistance genes and QTLs for abiotic traits into an indian elite rice variety. The work is not unprecedented in the concept, but provides interesting breeding material for specific indian farmers, which is an important achievement and is correctly taken up by authorities and international research centers. 1 2 plants11050622_perova 0 +However, the authors have conducted a thorough literature review, undertaken a rigorous piece of data collection, and have generalized information accurately. The main issue with the ms is the quality of the figures: they are not clearly representing the data, arrows and text may help the reader, the controls are missing in most cases, and a general lack of precision is affecting them. Also, the legends are not clearly describing all the terms and should be revised. Legends should describe what is to be observed in the figure, possibly pointing to parts of special interest. 1 2 plants11050622_perova 0 +Dear Editor, Thank you for inviting me to review this manuscript. Explaining briefly which and what are the indian sesasons during which experiments have been conducted would help clarity. 1 2 plants11050622_perova 0 +This work is of outstanding quality, and I normally present more critical points in my reviews. "The phenotypic data are important, but currently they are presented only as additional material. The authors should consider reshaping the tables, eliminating unnecessary columns (e.g. no. of genes / QTLs, which is already represented in column 1) and add the most striking phenotypic data, when possible and relevant for discussion. Also ""entry nos."" is probably not clear and ILs no should maybe considered instead." 1 2 plants11050622_perova 0 +The work is not unprecedented in the concept, but provides interesting breeding material for specific indian farmers, which is an important achievement and is correctly taken up by authorities and international research centers. The data on bgs are not sufficiently presented in the text nor discussed. 1 2 plants11050622_perova 0 +This paper described the multi-parents introgression assisted by molecular markers. "revise the use of ""-"" instead of ""( )"" when mentioning the numbers of the ILs, or any other system which would ensure a better homogeneity in comparison to the one present in the ms." 1 2 plants11050622_perova 0 +Legends should describe what is to be observed in the figure, possibly pointing to parts of special interest. check lines 21, 37, 93, 153, 183-184, 312, 351-353, 360, 377, 466 1 2 plants11050622_perova 0 +Explaining briefly which and what are the Indian seasons during which experiments have been conducted would help clarity. stick to BB instead of BLB 1 2 plants11050622_perova 0 +L48-63: should add some citations on the first part of introduction. consider anticipating the explanation of the acronyms which are eventually presented only in the M&M, to facilitate the reading; consider this aspect also in the legends 1 2 plants11050622_perova 0 +Correct it It was a pleasure to read this manuscript. Lines 403 et seq. are redundant Response: 1 2 plants11050622_perova 0 +Please see the suggestion and comments below. lines 414 et seq. seem to be contradicting lines 351 et seq. 1 2 plants11050622_perova 0 +The main issue with the ms is the quality of the figures: they are not clearly representing the data, arrows and text may help the reader, the controls are missing in most cases, and a general lack of precision is affecting them. the 85 ILs presented at 414 seem to be a bit out of the blue: a short intro to where they are coming from would help the reader. 1 2 plants11050622_perova 0 +However, this time it is just very beautiful work. With minor grammatical revisions, the manuscript can be accepted as is. 1 2 plants11050622_perova 0 +L562: the section of statistical analysis should add more details. It is also acknowledged that this paper is probably the first of many papers to emerge from the study. As such, it is an overview paper that raises many questions. It would be interesting for the authors to provide more information about the research design and estimation methodologies, such as chi-square analysis of introgression lines, if possible for each crossed IL population. I only recommend some minor revisions before acceptance. 1 2 plants11050622_perova 0 +How did you calculate those values on those comparison types? This work is of outstanding quality, and I normally present more critical points in my reviews. However, this time it is just very beautiful work. 1 2 plants11050622_perova 0 +With minor grammatical revisions, the manuscript can be accepted as is. Line 262: “=261 %” , and Line 312 “linkes” a typo? Correct it Response: 1 2 plants11050622_perova 0 +Author Response Point-by-point response to the reviewer's comments are given below L48-63: should add some citations on the first part of introduction. 1 2 plants11050622_perova 0 +Please see the suggestion and comments below. L127: Please add the explanation of “boro season”. 1 2 plants11050622_perova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. The legend of supplementary table should be improved. Table and main text are independent, so the authors have to describe the table more carefully. 1 2 plants11050622_perova 0 +The data on bgs are not sufficiently presented in the text nor discussed. L562: the section of statistical analysis should add more details. Also please indicate the R version. For example, how does H2 calculate? 1 2 plants11050622_perova 0 +L48-63: should add some citations on the first part of introduction. On Supplementary table S2, does significant mean p-value? Indicate DFF = days to fifty percent flowering. What is the “treatment”? What do the results on “check” mean? How did you analyze “control vs IL”? 1 2 plants11050622_perova 0 +Author Response Point-by-point response to reviewer's comments This paper described the multi-parents introgression assisted by molecular markers. On Supplementary table S3, similar questions as S2, please also explain. 1 2 plants11050622_perova 0 +The main issue with the ms is the quality of the figures: they are not clearly representing the data, arrows and text may help the reader, the controls are missing in most cases, and a general lack of precision is affecting them. On Supplementary table S5, what is “C.D”? How did you calculate those values on those comparison types? 1 2 plants11050622_perova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. Please re-organize the Supplementary table S5, I suggest use each ILs only appear one time and add one more column to show their PC groups. Then the table can be more informative and ease to read. 1 2 plants11050622_perova 0 +The authors should consider reshaping the tables, eliminating unnecessary columns (e.g. Please add the full name of abbreviations. For example on L203 “CD”, L211 “SES“, L228 “UBN“ and L332 “ICAR-IRRR”. 1 2 plants11050622_perova 0 +L127: Please add the explanation of “boro season”. The last paragraph of results is about background selection. Suggest to add subtitle “2.2.8”. 1 2 plants11050622_perova 0 +How did you calculate those values on those comparison types? Please add some gel pictures of the foreground selection markers you used in order to visualize the genotyping results and showed the polymorphism of these markers on gel. 1 2 plants11050622_perova 0 +However, the authors have conducted a thorough literature review, undertaken a rigorous piece of data collection, and have generalized information accurately. L296-L302: the marker descriptions on main text cannot match the supplementary table S8. Also, what are those 27 ILs on L298? 1 2 plants11050622_perova 0 +For example on L203 “CD”, L211 “SES“, L228 “UBN“ and L332 “ICAR-IRRR”. L602: there is no appendix. 1 2 plants11050622_perova 0 +Point 7: Discussion: In the first sentence, what is the topic that the authors mentioned? Thank you for giving the opportunity to read such an interesting paper. 1 2 su14095590_makarova 0 +Unfortunately, I am really not sure what the point is here. For a better and accurate model I recommend the authors to eliminate from the model the extreme value. For example in Fig 2. - workers values greater then 40, community greater than 58, environment 45, customers 46 (the bullets), in Fig 3 - values with global score greater than 130, in Fig. 5 also all the bullets. Then repeat all the statistical analysis. 1 2 su14095590_makarova 0 +For me, lines 39 and 40 show the aim of the paper, but the idea is different from the ones presented in the abstract (“The main objective is to understand the B Impact Assessment, verifying its added value in the sustainability process and socio-economic development of the business sector”). In lines 391-395 I would prefer an Sk and Ku between -1 and 1. You have some values that are not included in this interval - maybe because of the outliers from the figures above that I recommend to exclude. 1 2 su14095590_makarova 0 +- workers values greater then 40, community greater than 58, environment 45, customers 46 (the bullets), in Fig 3 - values with global score greater than 130, in Fig. The paper is interesting; however, it is not clear what the authors are trying to achieve with this study. The authors test a popular assessment tool using confirmatory factor analysis and finds that the model is weak. However, there is no in-depth discussion or recommendations that follow. In fact, the discussion needs to be grounded in previous research findings in regard to CSR/sustainability indices/assessment tools/initiatives. Unfortunately, I am really not sure what the point is here. 1 2 su14095590_makarova 0 +The ‘areas’ represent a broader goal than the main dimensions of sustainability (Triple Bottom Line). Further, the hypothesis does not seem to be written correctly. First, it should be stated prior to the methods section. Second, currently it is descriptive. In other words, it doesn't state what the authors are trying to test in this study. 1 2 su14095590_makarova 0 +In line 384 the authors should substitute ‘chapter’ for ‘section’. Unfortunately, I cannot recommend publication unless major changes are made to the discussion section and possibly recommendations are added for future research and practice. 1 2 su14095590_makarova 0 +Abstract: The main objective is to analyze the B Impact Assessment, verifying the robustness and consistency of the model to measure and improve the economic, social, and environmental impact of companies. English language and style are fine/minor spell check required . 3 2 su14095590_makarova 0 +However, there is no in-depth discussion or recommendations that follow. Are the arguments and discussion of findings coherent, balanced and compelling? 3 2 su14095590_makarova 0 +Point 2: Are the research design, questions, hypotheses and methods clearly stated? Are the conclusions thoroughly supported by the results presented in the article or referenced in secondary literature? Must be improved Response 4: Thanks for the comment. 3 2 su14095590_makarova 0 +Point 2: For a better and accurate model I recommend the authors to eliminate from the model the extreme value. Thank you for your revisions. 3 2 su14095590_makarova 0 +It’s clever to reduce the number of companies, though it isn’t clear who contacts the companies, the authors or Company B? The paper is well structured and presented in a very meaningful manner. It definitely adds a value to the existed literature. 1 2 su14095590_makarova 0 +Point 7: Discussion: In the first sentence, what is the topic that the authors mentioned? There are minor corrections to be considered. This includes: Line 169 page 4, studies [28] & [29] do not reference to any presented argument(s) unless the preceding para. 1 2 su14095590_makarova 0 +Response 5: We believe that the reviewers' suggestions have been very helpful in improving the manuscript. The word of Table in all text should start with capital letter (e.g. Line 199, L. 223) 1 2 su14095590_makarova 0 +1 Response to Reviewer 2 Comments Point 1: Excellent work. Paragraph presented after Table 2 (page 7) is a repetitive content to what has been presented in the Table. It could be removed or move to footnote. 1 2 su14095590_makarova 0 +However, there is no in-depth discussion or recommendations that follow. Paragraph presented after Table 2 (page 7) is a repetitive content to what has been presented in the Table. It could be removed or move to footnote. 1 2 su14095590_makarova 0 +Point 2: Further, the hypothesis does not seem to be written correctly. Very good practical recommendations and criticism to the B Corp certification have been presented in the last para. of section (6). No any future research recommendations have been suggested by the respected authors. 1 2 su14095590_makarova 0 +For me, lines 39 and 40 show the aim of the paper, but the idea is different from the ones presented in the abstract (“The main objective is to understand the B Impact Assessment, verifying its added value in the sustainability process and socio-economic development of the business sector”). References list is well prepared. 1 2 su14095590_makarova 0 +The source of data from all companies in the sample isn’t clear, is B Corporation (site) or authors contact all these companies and did the survey? Title: The title demands a review because there isn’t a connection between the first part and the second one. We understand what the authors intend to inform us after reading the paper. Even though this was clear to me, the title doesn’t show the real idea developed in the paper. The objective is a good guide for the title. 1 2 su14095590_makarova 0 +It was not clear to me who is the author of Figure 1, the B Lab, or the authors of this paper? Abstract: The content is well organized, but the results need some to attract the reader. What is the main result of the B assessment with the confirmatory analysis? Besides, the contribution isn’t clear here. 1 2 su14095590_makarova 0 +Point 2: Further, the hypothesis does not seem to be written correctly. Introduction: This section demands more attention because there are some empty spaces to fill. The authors should explain better what is B Impact Assessment. What is its contribution to the structure of a model using Confirmatory Analysis? For me, lines 39 and 40 show the aim of the paper, but the idea is different from the ones presented in the abstract (“The main objective is to understand the B Impact Assessment, verifying its added value in the sustainability process and socio-economic development of the business sector”). The sentence in the Introduction is more complete than the main objective in the Abstract. The ‘areas’ represent a broader goal than the main dimensions of sustainability (Triple Bottom Line). 1 2 su14095590_makarova 0 +This discussion is the basis of the paper, related to the objective, and connected with Figure 1 presented in the next section, Method. Literature review: The lines from 70 to 82 could be summarized, and cut and paste in the Introduction section. I suggest cutting the text from lines 90 to 103 because it’s quite an advertisement for the B Certificate. The content in this section is exclusively dedicated to the Certification and the Corporation which offers it, there isn’t any scientific information there. The section demands a literature review about the theme, as the relationship between the certificate with adding value, sustainability, and the ‘areas’ governance, workers, community, environment, and customers. What is the idea of the assessment of sustainability, in these areas? This discussion is the basis of the paper, related to the objective, and connected with Figure 1 presented in the next section, Method. Even though the areas are from B Lab, the authors should study and related them to sustainability and value creation. There isn’t a literature review in this work. 1 2 su14095590_makarova 0 +Point 2: Abstract: The content is well organized, but the results need some to attract the reader. Method: In the Abstract, the objective added an economic dimension to the development, but in lines 180 and 181 the impact to be measured includes just environmental and social. It was not clear to me who is the author of Figure 1, the B Lab, or the authors of this paper? There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. The source of data from all companies in the sample isn’t clear, is B Corporation (site) or authors contact all these companies and did the survey? I understood that the data is from the B Corporation website. I accessed the link available in line 191 and there was a message ‘404 page not found, but when I clicked on ‘What is B Corporation’, I found the ‘areas’ and the steps for a company that intends to assess its practices and be certified. The authors should develop more theory than describe a model which has already existed. Table 2 and the paragraph after it is a repetition of Figure 1 and Table 1, could be cut. It’s clever to reduce the number of companies, though it isn’t clear who contacts the companies, the authors or Company B? The hypothesis is interesting when they come from a discussion in the literature review to the field research to test a theory (models, methods, frameworks, etc). Suddenly, appears one in the Method section, in a paper with a limited presentation of a technical model/certificate from an existed company. 1 2 su14095590_makarova 0 +The source of data from all companies in the sample isn’t clear, is B Corporation (site) or authors contact all these companies and did the survey? Results: The sentence from line 137 to line 138 isn’t clear when I saw Figure 6. The authors could use a standard for a plural of index word, ‘indices’ (345) or ‘indexes’ (362). In line 384 the authors should substitute ‘chapter’ for ‘section’. The authors presented and analyzed the variables/areas of certification with many models, it is interesting and is a basis for analysis in the next section. 1 2 su14095590_makarova 0 +I suggest cutting the text from lines 90 to 103 because it’s quite an advertisement for the B Certificate. Discussion: In the first sentence, what is the topic that the authors mentioned? What source provided that information? The analysis is interesting, but demands more comparisons and explanations for cuts and adds. For me, the answer to Hypothesis 1 isn’t clear. The authors should reflect the presence of that in the text. The Cronbach’s Alpha ‘selected’ just ‘environment’ area of the B Lab model. This is an interesting result, which could be more analyzed with other assessment models presented in the text, to say what the authors wrote at the end of the section. 1 2 su14095590_makarova 0 +The sentence in the Introduction is more complete than the main objective in the Abstract. Conclusion: I just see one objective, but in the first sentence the authors wrote ‘objectives’. Where are they? The suggestions are interesting, but demand more analysis in the previous section. 1 2 su14095590_makarova 0 +The literature review has been improved, and new references have been added (text in blue). Is the content succinctly described and contextualized with respect to previous and present theoretical background and empirical research (if applicable) on the topic? Must be improved. 3 2 su14095590_makarova 0 +There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. Can be improved. Are the research design, questions, hypotheses and methods clearly stated? 3 2 su14095590_makarova 0 +The authors test a popular assessment tool using confirmatory factor analysis and finds that the model is weak. The text has some improvements, but there are some points that still demand more attention. 3 2 su14095590_makarova 0 +Please let me know if you have any questions. Need to update the literature review with recent studies 1 2 su14127346_perova 0 +The only remark on the content refers to “Are the arguments and discussion of finding coherent, balanced and compelling? Please add a theoretical background section 1 2 su14127346_perova 0 +Please let me know if you have any questions. What are the policy implications of your study 1 2 su14127346_perova 0 +Please let me know if you have any questions. Add discussion of results section and relate your results with theories. 1 2 su14127346_perova 0 +We take this review as a valuable opportunity to foster the quality of the paper. "--> I believe the authors intended ""moderating role.""" 1 2 su14127346_perova 0 +2- Please revise if it makes sense to present your research hypothesis in the introduction. The authors could go into greater detail to explain the logic behind this relationship. As it stands, the paper offers little insight into the reasoning behind their hypothesis.” We answered this comment along different dimensions. 1 2 su14127346_perova 0 +"8- Lines 330 and onwards are presenting conclusions that are not warranted by the results and the english is a bit strange (what do you mean by ""households' anxiety""?)." It would be useful if the authors provided some speculative thoughts on the finding that the slope of the GenDiv variable is negative in highly uncertain countries on the firm's environmental performance (Figure 3 (c) red line). 1 2 su14127346_perova 0 +"8- Lines 330 and onwards are presenting conclusions that are not warranted by the results and the english is a bit strange (what do you mean by ""households' anxiety""?)." In lines 28 and onwards, you argue a lack of literature looking at dynamic (GMM) analysis of the role of female on CSR and ESG issues, but fail to mention some examples. Please provide some, and position your work in that (brief) strand of literature. One example you should consider is Gaio, C., & Gonçalves, T. C. (2022). Gender diversity on the board and firms’ corporate social responsibility. International Journal of Financial Studies, 10(1), 15. 1 2 su14127346_perova 0 +The reviewer kindly gives details of the elements that can be improved in the field ‘’Comments and Suggestion for Authors’’. Please revise if it makes sense to present your research hypothesis in the introduction. 1 2 su14127346_perova 0 +"2 4- What do you mean by ""in the crowd"" (line 141)." "Please reconsider the use of adjectives such as ""complicated"" (line 79), interestingly (line 88) and so on." 1 2 su14127346_perova 0 +I believe that, despite being a topic that is widely discussed in the literature, it is interesting to be able to provide new orientations, in this case the gender diversity firms’ environmental performances . "What do you mean by ""in the crowd"" (line 141). Please revise carefully english for clarity." 1 2 su14127346_perova 0 +I only have a few minor concerns that I'd like the authors to clarify and address when revising. Please revise your data: your max tangibility is over 2 (which means that Net PP&E, a subset of Assets, is 2 times those same Assets - this should be a typo. Similar problems might exist for a negative tobin's Q. 1 2 su14127346_perova 0 +The related theory posits that females’ attitude when facing uncertainty is different from males. "In line 192 you mention ""all the sectors"". But you are working one sector only, aren't you?" 1 2 su14127346_perova 0 +We deeply regret the inconvenience caused due to this. Explain your sentences in lines 242-244. What did you do specifically? 1 2 su14127346_perova 0 +Dear Authors The paper has been significantly improved since the previous version. "Lines 330 and onwards are presenting conclusions that are not warranted by the results and the english is a bit strange (what do you measnby ""households' anxiety""?). Similar problems stem from the following paragraphs discussing the results." 1 2 su14127346_perova 0 +While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. I would like to suggest authors label inoculation points in Figure 1, which could give readers a clear view of three different inoculation methods. 1 2 toxins14060409_perova 0 +The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. Line 142: “proportion of PPSD” should be “proportion of PSD or PPSD”. 1 2 toxins14060409_perova 0 +Point 7: Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. Line 143: “PPSD-premature spike death” should be “PPSD-proportion of premature spike death”. 1 2 toxins14060409_perova 0 +Studies show that infection timing has effect on disease severity and DON distribution in wheat spikes, and a late infection is an important factor for high DON levels found in healthy-looking kernels. Lines 168 - 169: Should it be that DON content of most lines without Fhb1 exceeded 1000 µg/kg under UBFI? Where is 4224.38 µg/kg in Table 1? Do you mean in Table S1? 1 2 toxins14060409_perova 0 +It is clearly written so it is suitable for publication given some minor changes/modifications: 1) Lines 411 & 413: “PPSB” should be “PPSD”. 1 2 toxins14060409_perova 0 +Studies show that infection timing has effect on disease severity and DON distribution in wheat spikes, and a late infection is an important factor for high DON levels found in healthy-looking kernels. Table S1: “PPSD - premature spike death” in the footnote should be “PPSD - proportion of premature spike death”. 1 2 toxins14060409_perova 0 +Minimizing DON contamination in grains is a major goal of Fusarium Head Blight (FHB) research community. Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. 1 2 toxins14060409_perova 0 +2) To futher clarify the infection methods a supplementary figure detailing graphically the modes of inoculation with figures would make the paper extremely useful for the community 3) I would suggest to avoid citing supplementary figures at the beginning of the chapter. See for example chapter 2.4. Given that 2.4 chapter discusses data of supplementary figure 4 would suggest to make figure S4 as Figure 4 of the manuscript. 1 2 toxins14060409_perova 0 +Given that 2.4 chapter discusses data of supplementary figure 4 I would suggest to make figure S4 as Figure 4 of the manuscript. To further clarify the infection methods a supplementary figure detailing graphically the modes of inoculation with figures would make the paper extremely useful for the community. 1 2 toxins14060409_perova 0 +The paper describes a set of experiments carried out in 2020 2021 on isogenic lines of wheat using different methods of Fusarium inoculation in order to assess the effect of Fusarium inoculation on FHB disease index and DON accumulation. Identity of the strain used for infection should be confirmed: a multilocus species characterisation is needed to confirm the species of the strain or a reference to a publication where the strain was described and appropriately characterised. 1 2 toxins14060409_perova 0 +The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. Mycotoxin data analysis should be provided (I guess is policy of mdpi to make raw data available together with the publication) 1 2 toxins14060409_perova 0 +Point 17: To avoid grammar and linguistic mistakes, Major level English language should be thoroughly checked. The innovation of this research needs to be better explored. 1 2 w14030367_makarova 0 +Please clarify, why ultrafiltration cannot remove the PPCPs since it can remove bacteria and viruses. Lines 33-38: You should mention that discharge of PPCPs degrades water quality and thus it cannot be directly used for potable water (via desalination) and industrial applications. Cite the following references: Panagopoulos, A. (2021). Energetic, economic and environmental assessment of zero liquid discharge (ZLD) brackish water and seawater desalination systems. Energy Conversion and Management, 235. Panagopoulos, A. (2021). Techno-economic assessment of Minimal Liquid Discharge (MLD) treatment systems for saline wastewater (brine) management and treatment. Process Safety and Environmental Protection, 146, pp. 656-669. Study and evaluation of the characteristics of saline wastewater (brine) produced by desalination and industrial plants. Environmental Science and Pollution Research, 1-14. 1 2 w14030367_makarova 0 +These 38 PPCPs generally present in waters at trace concentrations, ranging from several ng/L to 39 thousands μg/L [4]. Conclusion: Discuss the applicability of your findings/results and future study in this field. 1 2 w14030367_makarova 0 +In this study, a 17 BAC-UF system with treatment capacity of 0.16 m3/h was operated. Conclusion: Make it as one or two paragraphs. 1 2 w14030367_makarova 0 +The same trend (Figure 2) was mainly due to the stable removal ability of BAC and UF for organics, causing the removal restriction. Table 1: What is the salinity (in mg/L) of the samples ? 1 2 w14030367_makarova 0 +Point 17: To avoid grammar and linguistic mistakes, Major level English language should be thoroughly checked. Overall, the manuscript can be accepted after the minor correction/revision to be published in the journal of Water. 1 2 w14030367_makarova 0 +Point 2: Authors may revise the title to include river water instead of surface water. The title seems good, but the abstract seems to be fine. Please add one problem statement line in abstract to justify this sentence ``the long-term pilot-scale study is urged to be investigated.``. 1 2 w14030367_makarova 0 +The paper is interesting.I recommend publication only if the following issues can be addressed. Research gap should be delivered on more clear way with directed necessity for the future research work. 1 2 w14030367_makarova 0 +Please revise your paper accordingly since some issue occurs on several spots in the paper. Introduction section must be written on more quality way, i.e., more up-to-date references addressed. Please target the specific gap such as 2015-2021 etc. 1 2 w14030367_makarova 0 +Point 5: Please add t-test results in Table 1 for each parameter to understand the significant differences. Page 1 Line 38. Please cite this reference with existing reference 3….Role of nanotechnology for design and development of cosmeceutical: application in makeup and skin care. 1 2 w14030367_makarova 0 +The BAC biofilter can remove the PPCPs, and then the following UF can reject micro-organisms and particles flowing out from the biofilter to ensure the quality of drinking water. The novelty of the work must be clearly addressed and discussed, compare previous research with existing research findings and highlight novelty. 1 2 w14030367_makarova 0 +Moreover, the authors present the results properly. What is the main challenge? Why author choose this material? Please highlight in the introduction part. 1 2 w14030367_makarova 0 +##Comments on the title, Abstract, and References Page 2 Line 55 need a reference. Please consider these at end of this sentence……The oxidation method exhibited a fast reaction speed and high removal efficiency…(i) Role of nanomaterials in the treatment of wastewater: A review (ii) Advances and challenges in developing efficient graphene oxide-based ZnO photocatalysts for dye photo-oxidation. 1 2 w14030367_makarova 0 +Point 16: Section 4 should be renamed by Conclusion and Future perspectives. The main objective of the work must be written on the more clear and more concise way at the end of introduction section. 1 2 w14030367_makarova 0 +Besides, the t-test was used and proved the significant difference between BAC-Effluent and BAC/UF-effluent. Please check the abbreviations of words throughout the article. All should be consistent. 1 2 w14030367_makarova 0 +##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). Please add chemical reagents section and stated all chemical with brand specifications. 1 2 w14030367_makarova 0 +Title: Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface water. Regarding the replications, authors confirmed that replications of experiment were carried out. However, these results are not shown in the manuscript, how many replicated were carried out by experiment? Results seem to be related to a unique experiment. Please, clarify whether the results of this document are from a single experiment or from an average resulting from replications. If replicated were carried out, the use of average data is required as well as the standard deviation in the results and figures shown throughout the manuscript. In case of showing only one replicate explain why only one is shown and include the standard deviations. 1 2 w14030367_makarova 0 +The reviewer suggests statistical analysis using a t-test (Raw water- BAC-Effluent and Raw water – BAC/UF-effluent). Please revise your paper accordingly since some issue occurs on several spots in the paper. Please use Fig. or figure? It very confusing. Article should be in one pattern. 1 2 w14030367_makarova 0 +Energetic, economic and environmental assessment of zero liquid discharge (ZLD) brackish water and seawater desalination systems. Please provide high quality image of figure 1. 1 2 w14030367_makarova 0 +The results showed that the BAC unit reduced CODMn 19 with 35.45%, while the BAC-UF further decreased to 56.00%. Please use one style for units such as m3/h or m3h-1 Please revise your paper accordingly since some issue occurs on several spots in the paper. 1 2 w14030367_makarova 0 +##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). Please add a comparative profile section to compare your results and prove how it better than previous. 1 2 w14030367_makarova 0 +43 Citation: Wanga, Q.; Tanga, X.; Zenga, W.; Wangb, F.; Gongb, W.; Chena, J.; Wanga, J.; Lia, G.; Lianga, H. Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface wa- ter. Section 4 should be renamed by Conclusion and Future perspectives. Conclusion section is missing some perspective related to the future research work, quantify main research findings, highlight relevance of the work with respect to the field aspect. In the present form conclusion is very weird. 1 2 w14030367_makarova 0 +Response 6: Thanks very much for this comment. To avoid grammar and linguistic mistakes, Major level English language should be thoroughly checked. Please revise your paper accordingly since several language issue occurs on several spots in the paper. 1 2 w14030367_makarova 0 +Title: Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface water. Please follow the journal guidelines. Reference formatting need carefully revision. All must be consistent in one formate. 1 2 w14030367_makarova 0 +Point 3: References should be according to the journal format. Dear Authors, i reviewed again the revised version. I would like to recommend the publication in present form. Authors shows sincere efforts during revision. 3 2 w14030367_makarova 0 +Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. Authors should avoid abbreviations in the title and the abstract. 1 2 w14030367_makarova 0 +Samples of the feedwater and effluent from three systems were taken simultaneously and measured once. Authors may revise the title to include river water instead of surface water. 1 2 w14030367_makarova 0 +Two native English-speaking colleagues help us verify the manuscript. References should be according to the journal format. 1 2 w14030367_makarova 0 +Response 9: Thank you very much for your kind reminder. Line 44-45: Ultrafiltration (UF) as emerging technology, has been widely used to remove pollutants such as particles, colloids, bacteria and viruses, reducing the risk of water-borne diseases and …UF membranes cannot effectively rejected these soluble substances”. Please clarify, why ultrafiltration cannot remove the PPCPs since it can remove bacteria and viruses. 1 2 w14030367_makarova 0 +Response 10: Thanks very much for this comment. Please add t-test results in Table 1 for each parameter to understand the significant differences. Authors may provide data in the supporting information file. 1 2 w14030367_makarova 0 +Point 5: Please add t-test results in Table 1 for each parameter to understand the significant differences. The reviewer suggests evaluating the statistical t-test for Figures 4. 1 2 w14030367_makarova 0 +The comparison of previous research with existing research findings was added in the final part of the results and discussion. t-test results should be included in Table 2. Why is the standard deviation of Erythromycin showing a high value? 1 2 w14030367_makarova 0 +I can see very well-defined experiments and produced good results. Please look at the curve of BAC/UF; there was a symbol missing in near 85 days. Please show each symbol. 1 2 w14030367_makarova 0 +Response 6: Thanks very much for this comment. The conclusion may be revised. 1 2 w14030367_makarova 0 +It was found that the BAC unit 25 played a key role in PPCPs removal and the UF unit also degraded them by the biomass on UF 26 membranes. Authors should avoid abbreviations in the title. Authors should add a list of abbreviations before the references. 3 2 w14030367_makarova 0 +Please revise your paper accordingly since several language issue occurs on several spots in the paper. Please avoid repeating the full name and abbreviation throughout the manuscript if you used the first-time abbreviation. 3 2 w14030367_makarova 0 +The BAC biofilter can remove the PPCPs, and then the following UF can reject micro-organisms and particles flowing out from the biofilter to ensure the quality of drinking water. Line 46-52: & line 84-85 “Ultrafiltration (UF) as an emerging alternative technology to conventional water treatment processes, has been widely used to remove pollutants such as particles, colloids, bacteria, and viruses, thus reducing the risk of water-borne diseases [10]. Size exclusion is considered the primary removal mechanism for the UF. However, in the case of the PPCPs with a small molecular weight (typically < 600 Da), UF membranes also cannot effectively reject these PPCPs, but nanofiltration and reverse osmosis are able to remove these PPCPs based on the thin-film composite”. Sorry, but I don't see why UF can reject viruses and bacteria but not PPCPs. Is it true that the molecular weight of viruses and bacteria is more than that of PPCPs? Please elaborate. 3 2 w14030367_makarova 0 +The authors have used pump water from the river to the storage tank and used supernatant water from the storage tank (Fig. The authors should include some information regarding the biological degradation of PPCPs by microorganisms in the introduction section. 3 2 w14030367_makarova 0 +I am pleased to send you major level comments, there are some serious flaws which need to be corrected before publication. Line 53-55: Have the authors compared the BAC-UF performance to that of nanofiltration? 3 2 w14030367_makarova 0 +Point 17: To avoid grammar and linguistic mistakes, Major level English language should be thoroughly checked. I strongly suggest that the authors explain how they performed the t-tests. Please include the sample size (n) or degree of freedom (df). 3 2 w14030367_makarova 0 +Point 15: Please add a comparative profile section to compare your results and prove how it better than previous. Please show the t-value and p-value in a scientific view (e.g., 2.79E-4 would be P <.001). 3 2 w14030367_makarova 0 +Please revise your paper accordingly since several language issue occurs on several spots in the paper. Line 161-176: Please delete the name of medicinal compounds not used for this study. 3 2 w14030367_makarova 0 +Point 5: The novelty of the work must be clearly addressed and discussed, compare previous research with existing research findings and highlight novelty. Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. Please explain it in the manuscript. The reviewer suggests statistical analysis using a t-test (Raw water- BAC-Effluent and Raw water – BAC/UF-effluent). Point 6: Why the same trend of increase or decrease in graphs (Fig. The same trend (Figure 2) was mainly due to the stable removal ability of BAC and UF for organics, causing the removal restriction. The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. After the gas scrubbing and the hydraulic backwashing, the dissolved oxygen detection of the effluent was carried out, resulting in the above results for dissolved oxygen. Besides, the t-test was used and proved the significant difference between BAC-Effluent and BAC/UF-effluent. Thanks for the response. Please include it in the manuscript. Response 6: Thanks very much for this comment. 3 2 w14030367_makarova 0 +In case of showing only one replicate explain why only one is shown and include the standard deviations. What is the utility or deterioration of PPCPs sludge after removing it from river water? If possible, please add at least one paragraph. 3 2 w14030367_makarova 0 +line 76 and 79: Sentence about two farms with financial support is deleted from the aim. 2 1 The paper is clearly written, with nice figures and with a discussion supported by the results obtained. agriculture12060868_perova 0 +"Line 78: ""designed to meet behavioural needs...."" is deleted Overall, the objective now is focused on the hypotheses. The reviewer is completely right in adressing this point." 2 1 The following changes could improve the quality of the paper. agriculture12060868_perova 0 +l 80-83 is now deleted from the objectives 2 1 The following changes could improve the quality of the paper. agriculture12060868_perova 0 +Figure 1 must was lost from the last document, and we are so sorry for this. The figure is now included in the new document. 2 1 The writing and data presenting need to be improved. agriculture12060868_perova 0 +More explanation is included in the figure text of figure 2 2 1 The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). agriculture12060868_perova 0 +Corrections are made in the text of figure 4. 2 1 The writing and data presenting need to be improved. agriculture12060868_perova 0 +l 206, l225 Info is changed according to the reviewers request. 2 1 The following changes could improve the quality of the paper. agriculture12060868_perova 0 +The system we have used is to refer to the table with statistical values when reporting significant differences for the results presented in figures and tables, but for those that are presented in the text only, we also have P- and F-values in brackets. Insted of inserting P-values in the text when reporting significant differences for the ones that are in tables, we have included more references to the stat-tables. I hope the reviewer find that satisfactory. 2 1 Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +Figure 1 was missed from the last MS. Sorry for this error. This is now included 2 1 The following changes could improve the quality of the paper. agriculture12060868_perova 0 +Stillborn piglets vs piglets with no milk: more details are included about this in the description of the M/M 2 1 Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +224-225: confusion about parity is corrected, same comment as reviewer one 2 1 The writing and data presenting need to be improved. agriculture12060868_perova 0 +Figure 5 and 7. There is always effects of batches in these types of studies. This is also why we prefer to have several batches, but the main effect should not be biased by the batch effect in the present study, as the main finding are quite clear even in our small data set. However, it would be more elegant to have more batches. This was unfortunately not possible in the present iinnovation project. As mentioned earlier, we did not have resources t continue the data collection within the time period we had. 2 1 The writing and data presenting need to be improved. agriculture12060868_perova 0 +mean + se is given in all tables and figures, Replicates are now included and abbreviations explained. 2 1 Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +Italic for P-values in the text. Done! 2 1 The paper is clearly written, with nice figures and with a discussion supported by the results obtained. agriculture12060868_perova 0 +Figure 1 was no included by an error in the last MS. It is now inserted again. 2 1 Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +Batches and number of litters are added to the figure legends. 2 1 There are only minor comments with very specific issues: agriculture12060868_perova 0 +Space before and after sign is added. 2 1 Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +A new and improved version of figure 6 is now included. 2 1 The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). agriculture12060868_perova 0 +We have inserted * to denote differences instead of letters. 2 1 Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +Table 4 is inserted again in the writing form. 2 1 There are only minor comments with very specific issues: agriculture12060868_perova 0 +The meaning of ***: this is explained. 2 1 Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +Quality of figure 7 is improved. 2 1 Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +The content of the two papers Reviewer 1 mentions here focussed on the impact of the pandemic on management changes in dogs and on dog owner experiences at a single time point during the most restrictive ‘lockdown’. The current paper is different to either of these, and indeed any other published paper, in that it focusses on changes in separation related behaviour over time, across two different surveys in a longitudinal cohort. 2 1 They do not seem to state dog is favouring them less unless text was omitted here. ani12040482_makarova 0 +The paper is about separation-related behaviour, not about the pandemic. 2 1 According to the authors, the main finding is that dogs whose leaving time reduced the most during the lockdown were most at risk of developing new SRBs. ani12040482_makarova 0 +Yes, this was purposeful, it provides a summary of the aims & methods to introduce the discussion as not everyone reads papers in a linear fashion. We have not made any changes based on this statement. 2 1 L238 Do the authors have information about the Owner demographics? ani12040482_makarova 0 +There is a difference between something that is considered to be “well-known” or folk-knowledge and demonstrable evidence. The sentence quoted here is not untrue, or exaggerated, however, if the Editor wishes us to explore this further, we would kindly request the Reviewer provide us with examples of publications where this has been empirically demonstrated, as we have not found any in our own searches. 2 1 Think either way this figure would benefit a bit of context on why was included/what was showing in context of this study as currently info is a bit generic and didn't totally tie into people's working from home etc. ani12040482_makarova 0 +Given the lack of constructive feedback in these statements, no changes have been made based on these comments. 2 1 There would be evidence for some behaviors, such as destructive behavior or defecation, but how would owners know about pacing or tail-chasing? ani12040482_makarova 0 +Thank you, in line 16 and 32 we have added “when restrictions had eased” to explain why we surveyed in October 2020. 2 1 The study reports that pet dogs whose leaving routines changed most during the COVID-19 pandemic (i.e., their owners left them alone less frequently) would be at greater risk of developing separation-related behaviours following the lifting of pandemic restrictions. ani12040482_makarova 0 +Thank you, we have now expanded this to read: “In addition to being a welfare concern for the dog, SRBs are often unwanted or problematic for the owner and/or neighbours such as in the case of excessive vocalisation, which may lead to noise complaints, or in terms of house soiling and destruction of property, which may be particularly problematic for people living in rental accommodation. In such cases, these issues may increase risk of relinquishment [7]” (see new lines 56-59) It may be helpful to discuss why there is poor owner adherence to programmes to reduce SRB (Line 66-67). 2 1 When looking at SRB status in October, of 1,187 dogs who were left alone in October, 117 (9.9%) were reported to have shown at least one SRB”. ani12040482_makarova 0 +The following text has now been added beginning at line 69: “Whilst the precise reasons for poor adherence to advice for preventing or reducing SRBs have not been documented, it is at least partly attributed to the relative difficulty of adhering to specific aspects of these programmes, with the easier pieces of advice followed more often than the parts that take more commitment and consideration [13].” I wasn't sure if line 79-80 was needed- about dogs having returned to pre-pandemic pattern, I think it is a little dismissive of your own research which is valuable and applicable beyond the pandemic. 2 1 Were behaviors, including different vocalizations, defined for owners? ani12040482_makarova 0 +Thank you for your comment, I think we were pre-judging that people would think it was just another covid paper, and we are glad to see you agree with us that it is valuable beyond the pandemic. This line has now been deleted. 2 1 Minor issues: Line 35: insert “of” after 9.9% ani12040482_makarova 0 +The findings were all extremely similar, so it felt quite repetitive to discuss them all. We actually had more detail in an early draft then trimmed it out. However, we have now added some more of this detail as requested (see lines 100 to 112), whilst trying to limit repetition. 2 1 The authors gathered data (via owner surveys) about the same dogs before the pandemic, at the beginning of the pandemic and approx. ani12040482_makarova 0 +We presumed that at some point owners would pop out of the house, to take out the bin or go to the garage etc.. Such leaving events are likely to be experienced differently by some dogs, as the owners won’t likely give off the same cues as when they leave for an extended period of time, such as picking up house keys, or leaving through a different door. This has been explained now in lines 179-83. 2 1 Line 96-97- some more detail on the findings of these various surveys would be beneficial similarly to Bowen's study, just so provide a clear background/discussion of literature setting scene for your study. ani12040482_makarova 0 +Thank you, this seemed ok when we submitted it, but must have gone wrong when uploaded but we’ve corrected it now. 2 1 The entire first paragraph of Discussion repeats what has already been written in earlier chapters (line 372-379). ani12040482_makarova 0 +We’ve amended description of the study periods in a few places, including between lines 132-142, which we hope addresses this query now. 2 1 Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. ani12040482_makarova 0 +One of the other reviewers also commented on this and asked for Figure 1 and much of the text to be moved to the supplemental material, so It’s also further explained in the supplementary material how it links to working and in lines 140-142 in the main text which now explains that many businesses were open again in October. 2 1 L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section ani12040482_makarova 0 +This was due to the errors you mentioned below. We used the Word automatic referencing and somehow that seemed to get broken when the document was uploaded to the online system. It’s been done manually now. 2 1 The next section (l281-283) emphasizes that 55.7% of the dogs who were reported to show SRB in February were clear in October. ani12040482_makarova 0 +See above. 2 1 My only suggestion is that making it clear why February and October were chosen as survey-points may be beneficial. ani12040482_makarova 0 +Agreed, this was how we interpreted why the owner was reporting this change. We have rephrased this section now. 2 1 L118 Materials and Methods This section (after the Ethics) should begin with the Subjects section. ani12040482_makarova 0 +Thank you for your review. We have expanded the discussion to address these points, however due to another reviewer saying the paper was already too long, we have kept this brief. A section detailing relevance to practitioners has been added to lines 545-551. 2 1 Were behaviors, including different vocalizations, defined for owners? ani12040482_makarova 0 +Yes, this is correct. This is stated in line 232-233 or the original submission, but it seems we omitted it from the Methods section. Thank you for spotting that. Text has been added to lines 198-200 to explain this. 2 1 There were some errors where reference source not found, which would want to look into (line 246; 265; 274; 292; 305; 323 etc). ani12040482_makarova 0 +Within the results table (Table 2) the direction of the estimate for this result is negative. Whilst we agree that it would be more impactful worded the other way around, we worry that changing the way it is described won’t match up to the data as it was coded and reported. We haven’t changed this wording for these reasons. 2 1 L127-137 The dates of data collections have been already mentioned in L121-126, so there is no need for repeating them. ani12040482_makarova 0 +Yes, and no, depending on your perspective. Whilst this was a significant predictor in the modelling, in reality 55% of dogs that were being left again changed from SRB+ to SRB-. So whilst 45% of dogs still showed it, a large proportion did not. 2 1 This is discussed later on but highlighting here would be useful. ani12040482_makarova 0 +Thank you for these thoughtful comments, we agree that we were a bit overly focussed on the results that supported the studies hypothesis and neglected to discuss the findings related to the dogs whose SRB appeared to have resolved. The number and percentage are detailed in the results section (lines 282-283 of the original submission and 298-298 in this one), but we failed to discuss these in the Discussion. We ran two models, one focussing on the dogs who started SRB- to see how many changed to SRB+ or remained SRB- and what factors influenced this, and the other focussing on dogs that started SRB+ to see what factors influence whether they changed to SRB- or remained SRB+. These models therefore, cover the comparisons you suggest (unless we’ve misinterpreted your comments). We have now added some discussion of the dogs who began the pandemic SRB+ however, as this was lacking from the first version (see the paragraph beginning at line 524). 2 1 The authors gathered data (via owner surveys) about the same dogs before the pandemic, at the beginning of the pandemic and approx. ani12040482_makarova 0 +Thank you for this comment, we have discussed this further in the Discussion now (see lines 517-523) 2 1 I hope this review helps – thank you for the opportunity. ani12040482_makarova 0 +Thank you, we have changed the title to: Impact of changes in time left alone on separation-related behaviour in UK pet dogs 2 1 Among them, what was the proportion of owners who has not responded to the request afterward? ani12040482_makarova 0 +This is how it was phrased in the survey, so this has not been changed. 2 1 However, currently, the paper seems too long, and it goes into too much detail about how the pandemic took place in the UK. ani12040482_makarova 0 +Thank you, this edit has been applied. 2 1 But this is the opinion of a person using English as a second language. ani12040482_makarova 0 +It seemed unfeasible to expect a dog to never be left for even a minute or two, for example if the owner pops outside to take out the bin or to get something from the garage/shed etc. 2 1 They do not seem to state dog is favouring them less unless text was omitted here. ani12040482_makarova 0 +The wording given to the owners is all presented here, and in the supplementary material. No further definitions for behaviours or vocalisations were given. Pined, whined and cried were all mentioned, as all are words owner tend to use to describe similar dog vocalisations. As with all owner awareness of SRBs, it is fundamentally challenging unless they use recording equipment to view their dogs when they leave them or are otherwise able to view their dogs when alone such as by looking through a window. As this is a limitation of the method used, the appropriate place to mention this would be in the Discussion, not the Methods, so we have not discussed this limitation there. 2 1 L291 The odds ratio (OR) is 5.38 and not 4.38 in Table 1. ani12040482_makarova 0 +The wording of the question asked about the dog being left alone, without human company (see line 173), so it applied to anyone, and specifically meant when no-human was present in the house with the dog. 2 1 Among them, what was the proportion of owners who has not responded to the request afterward? ani12040482_makarova 0 +This has now been explained, however this section has been moved entirely to the supplementary material on request of other reviewers. 2 1 However, the authors do not focus on this result and do not explain this finding. ani12040482_makarova 0 +Not strictly speaking, no. Dogs who were not left in February were excluded from the analysis. So, whilst there are 0 of them, that’s because of methodological choice not because there weren’t any dogs left alone. A note explaining this has been added to the figure legend. 2 1 This topic is not addressed until the Discussion section (line 395) but should be addressed here in the Methods and Materials section. ani12040482_makarova 0 +There were issues in the figure referencing when we uploaded the manuscript to the submission system. This has now been corrected. 2 1 The manuscript: Impact of Changes in Owner Leaving Pattern on Separation- Related Behavior in Pet Dogs in the UK is one more paper on the behavior of dogs in the COVID-19 pandemic developed in the last two years. ani12040482_makarova 0 +For some reason I was convinced I’d read it was optional for longer discussions, but having double checked, you are indeed correct. Thank you. A brief conclusion section has now been added. 2 1 What is surprising though is that 55.7% of the dogs who were reported to show SRB in February (before the pandemic) were clear in October which is good news. ani12040482_makarova 0 +Thank you, we have corrected the typo. 2 1 L148 Please explain why a period of 7 days were asked to be reported ani12040482_makarova 0 +This has been corrected 2 1 However, the authors do not focus on this result and do not explain this finding. ani12040482_makarova 0 +Thank you for your comments. The detail was provided to anchor the study in the background of what was occurring at the time, but we agree it is not necessary to the reader to see in the main text. These details and Figure 1 have been moved to the Supplementary material. 2 1 It is confusing to read about the surveys without knowing the sample sizes per survey and the demographics. ani12040482_makarova 0 +We agree this was completely missed from the Discussion. It wasn’t intentional, we were just overly focussed on the results that related to the research hypothesis. Discussion around this has been added now to lines 524-544. 2 1 Suggests the behavior is fairly robust and dogs having shown it at one point continue to be at risk (without knowing what interventions were taken) ani12040482_makarova 0 +Agreed, we have altered this part of the simple summary and abstract and included discussion of this in lines 539-544 now as well as into the conclusions, thank you. 2 1 Author Response Thank you for your time in reviewing this manuscript and for your constructive, helpful feedback. ani12040482_makarova 0 +Leaving time has been changed throughout to ‘time left alone’ L33 10th instead of “10th” Thank you, we’ve corrected the typo. 2 1 Author Response Thank you for your time in reviewing this manuscript and for your constructive, helpful feedback. ani12040482_makarova 0 +Thank you for pointing this out. We define SRB in the opening lines of the Introduction (45-50), however you are right that in places the terms can get confusing. Section 3.7.3. details behaviours owners reported as associated with separation, that are not what class as SRBs. Those were names ‘other’ separation behaviour but this has now been clarified, hopefully, by remaining the section ‘Other’ separation-linked behaviour, and then in the text it is now stated they are not SRBs. The term ‘separation anxiety’ was used in the introduction where it referenced a study that used that specific term. This has now been put into quote marks to be clear it is their term, not ours. The one mention of separation-distress has also now been changed. 2 1 Here are some suggestions that can be made throughout the paper: ani12040482_makarova 0 +Thank you, we’ve corrected the typo. 2 1 Thank you for your comments and for the constructive feedback. ani12040482_makarova 0 +This has now been discussed further in lines 98-100. 2 1 But the questionnaire only asked how long the dogs had been alone and what they were doing during this time. ani12040482_makarova 0 +This has now been moved to the beginning of the methods section. 2 1 In other words, 1407/1807 (78%) of dogs were clear of SRB in February and 90.1% in October. ani12040482_makarova 0 +Agreed, this has been amended and condensed, thank you. 2 1 My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? ani12040482_makarova 0 +Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. 2 1 It is perfectly feasible that some owners did not leave their homes because they were for example, ill, but they did so during the pandemic. ani12040482_makarova 0 +We asked about the dogs’ management and behaviour over the previous 7 days so as to limit recall bias and anchor the data to a specific snapshot of time, rather than being more general. This was first asked for the first survey which was specifically looking at changes in management and behaviour during the strict lockdown period, so needed to be time specific. Questions were then repeated in the follow-up survey. Wording has been added to lines 165-169 now to clarify this. 2 1 But this is the opinion of a person using English as a second language. ani12040482_makarova 0 +this has been done now. 2 1 Or explain why this information has not been used. ani12040482_makarova 0 +Thank you for spotting this, we have updated both the methods (L243-247) and results section (L370-374) with further detail of inter-rater reliability checks. 2 1 Line 27: change “reduced” to “decreased” Thank you, this edit has been applied. ani12040482_makarova 0 +At the end of survey 1 there was the option for people to provide their demographic details, which not everyone did. This was done to conform to GDPR by asking only the most necessary questions. Given that the research question here is related to the dogs’ behaviour change over time versus leaving hours, it wasn’t deemed relevant to include analysis of the owner demographics. 2 1 That is, would the same % of dogs changed (in either direction) regardless of changes in owner schedules? ani12040482_makarova 0 +This has now been done. 2 1 I have minor comments below and a few larger comments: ani12040482_makarova 0 +For the purpose of this study it was required that we had baseline data on the dogs’ leaving behaviour so that we could classify them as SRB+ or – before the pandemic began. Owners of dogs who were not left alone in a typical week in February, were not asked about their dogs’ separation-related behaviour, so we did not have these data for them which is why they were excluded. New text has been added to the Subjects section of the methodology to explain how many owners answered the follow up questionnaire, the response rate and what percentage and number of dogs were not left home alone before the pandemic. The new section beginning at line 146 now reads: “A total of 2,425 people completed the follow-up survey for the same dog they scored in the original survey (a 51.9% response rate), of which 2,285 had previously provided data to indicate whether their dog was left alone or not in February 2020. Of these, 15.3% dogs (n=305) were not left alone at all in an average week in February, and as such, these dogs did not have baseline data for their behaviour when left so were excluded from further analysis.” Additionally, the number of people we emailed the invitation to (n=4,670) has been added to line 139. 2 1 L293-295 “The final variable associated with October SRB status was the difference in the number of days dogs were left alone for between the February baseline and lockdown”. ani12040482_makarova 0 +For the 1407 dogs who were clear of SRB in February, they changed from being 100% clear to being 90.1% clear, with 1 in 10 of these dogs developing SRB they didn’t have previously. However, because of the dramatic improvement seen in the dogs that had SRB before the pandemic, the overall prevalence of SRB in the population decreased from 22% in February, to 17.2% in October (reported in the paragraph above). The numbers have been clarified in this section to help future readers, and additional discussion has been added around the overall decrease in SRB prevalence in both the abstract and in the discussion (lines 524-544). 2 1 Line 131: There was an error with referencing wanted to flag. ani12040482_makarova 0 +Thank you, we’re glad you liked it! Further explanation to help interpret the figure has now been added. 2 1 The study reports that pet dogs whose leaving routines changed most during the COVID-19 pandemic (i.e., their owners left them alone less frequently) would be at greater risk of developing separation-related behaviours following the lifting of pandemic restrictions. ani12040482_makarova 0 +Thank you for spotting that! 2 1 I think that according to the statistics, the strongest finding is that dogs who showed SRB in February or May had increased odds of having SRB during the subsequent measures which is not surprising. ani12040482_makarova 0 +This was explained further down in the section on the multi-variable model, but I have now moved the explanation to here, where it’s first mentioned and added some additional text also. 2 1 My main question when reading this section concerned how owners would know that certain separation-related behaviors occurred when they were away? ani12040482_makarova 0 +Thank you, this has been added now. 2 1 Specific points requiring attention: L18-20 „Whether dogs showed SRBs or not changed considerably over the months of the study, and one in ten dogs were found to have developed new SRBs in October, that they didn’t show before the pandemic” Overall, the percentage of dogs showing SRBs decreased during the study, and this should be clarified in the sentence above. ani12040482_makarova 0 +Thank you! Looks like I read the z-value when I was typing. I promise this has been proof read, but it’s so easy to miss things, thank you so much! 2 1 L127-137 The dates of data collections have been already mentioned in L121-126, so there is no need for repeating them. ani12040482_makarova 0 +Since there were no non-significant variables it wasn’t necessary to distinguish the results. 2 1 Line 214: if possible (might not be possible if this was how it was phrased in the survey), change “different to before” to “different from before” ani12040482_makarova 0 +This has been corrected, thank you. 2 1 I do think this is of interest to a range of stakeholders. ani12040482_makarova 0 +Thank you for this, we were familiar with the paper but had missed that link. New text has been added here now to discuss this. 2 1 However, currently, the paper seems too long, and it goes into too much detail about how the pandemic took place in the UK. ani12040482_makarova 0 +Agreed, this has been explicitly stated here now. 2 1 Line 166: define “devolved nations” for readers unfamiliar with the term. ani12040482_makarova 0 +We agree with the referee that in any open system as we have here , information will leak out and a corresponding backaction on the wavefunction cannot be avoided. However, by operating with ultra-cold quantum particles far of any internal resonance, the coherence time can be pretty long. This was shown with BEC’S trapped in cavities (see e.g. Ref 9). The effect of localization via cavity transmission can be reduced by working at higher cavity photon numbers. Ultimately the interplay between measurement induced localization and coherence spreading by unitary evolution could be one of the most interesting points in setting up such an experiment. One should study a transition from classical to quantum behavior depending on the degree of observation of the system. 2 1 In this respect the Authors meet their goal to provide a possible quantum optical setting for the observation of a classical random walk. atoms3030433_perova 0 +Axes added. 2 1 The idea is clever and original and lends itself to further extensions: for instance, to simulate a kicked rotor, by means of a frequency comb drive, or towards hybrid optomechanics, when the two-level atom is replaced by a doped nano-sphere. atoms3030433_perova 0 +We have reformulated to avoid confusion and unsubstantiated claims: “The mechanism is reminiscent of the one exploited in the creation of artificial potentials in optical lattices~\cite{Struck2012Tunable} applied here to the classical regime” 2 1 In the analytical results, derived in the adiabatic limit, gamma is eliminated and does not play any role. atoms3030433_perova 0 +We have added a clarifying statement in the beginning of section 2: “We consider an effective one-dimensional model”. 2 1 "“Page 6, ""Optical forces"": there is a missing subscript L in the first force term at the end of the first paragraph, just before Eq." atoms3030433_perova 0 +The referee is correct; in the convention that we specify the negative detuning corresponds to the regime where motional instabilities are avoided and cavity cooling is possible. We included this in the figure caption. 2 1 I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored.” atoms3030433_perova 0 +As we specify now in the beginning of section 3: “We treat $\eta_T$ as a free varying parameter. In the following we set $\kappa=1$ for numerical simulations and normalize the time in units of $\kappa^{-1}$”. 2 1 "“At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived." atoms3030433_perova 0 +As the referee correctly infers the random walk is merely an effect of the time modulation of the potential. The classical limit without time delayed action (characteristic of the cavity) will reproduce the kind of walk obtained in the LT limit where Fig. 3 and the analysis has been performed. The other regime where the transverse field kicks the particle out of the longitudinal trap is a cavity effect as the effective force (transverse) has a different modulation than the simple cosine of the free space transverse wave. However, for fine tuning of parameters and to insure stability of trajectories we have used the cavity cooling effect. 2 1 The manuscript is generally well organized and clearly written. atoms3030433_perova 0 +Yes, some momentum diffusion can be expected. In principle using a sufficiently narrow cavity and suitable operation parameters cavity cooling could be tuned to cancel such unwanted heating. However, this is connected to dissipative dynamics and will change the effective operating parameters of the system. In the bad cavity limited on the other hand, one can expect some “cavity heating” instead of cooling, but the rate of this heating should be slow enough to allow for many kicks before it gets relevant. 2 1 The manuscript is generally well organized and clearly written. atoms3030433_perova 0 +We have corrected the sign in the commutation relation. 2 1 Analytic approximations of the effective trapping forces give some insight into the origin of the special form of the optical potential and delineate the regimes in which random walks are expected to occur.The proposal of this somewhat unconventional random-walk regime in cavity-QED is interesting and deserves publication. atoms3030433_perova 0 +We have added a proper reference as Ref. [23]. 2 1 I suspect it should be [sigma^+,sigma^z] = - 2 sigma^+ and [sigma^-,sigma^z] = + 2 sigma^- .” atoms3030433_perova 0 +We have added the definition for \gamma in the text. Here we focus on a dispersive regime of weak atomic excitation, where the so called dipole force dominates the mechanical atom field interaction and spontaneous emission plays a negligible role. In this limit the mechanical forces can be derived from a deterministic (time dependent) optical potential (see refs. 7-9 for details). However, as the referee points out, in the nonlinear dynamical regime, the effects stemming from the inclusion of a random spontaneous emission could be amplified. A similar randomness is connected to cavity cooling in a regime of weak coherent intra-cavity fields. This certainly will have to be considered in a quantum treatment. In our simulation we got the “quasi random” dynamics from deterministic motion connected to details of the initial conditions without including random forces. 2 1 The resulting trajectory closely resembles a random walk. atoms3030433_perova 0 +Indeed all the above mentioned expressions were missing a factor of \kappa as the referee correctly observed. 2 1 The approach is scientifically sound and convincing. atoms3030433_perova 0 +The analytical considerations fit very well with numerical results. Indeed, in this regime, we have performed the simulations by choosing parameters derived from analytical considerations. The R6 emergence of the jump regime is directly connected with the increase of the LT force to the value of the longitudinally-induced force but the fine tuning of the parameters is a bit tricky in order to insure that only jumps to neighbouring sites occur. Therefore we have restricted our presentation to the other regime where the jumps are strictly occurring owing to the transverse-longitudinal time modulation of the potential. 2 1 "(4), the Authors write ""We proceed in a standard way to derive equations of motion for classical quantities.""" atoms3030433_perova 0 +We have fixed this mistake. 2 1 “Figure 4 is mentioned in the main text AFTER Fig. atoms3030433_perova 0 +We changed the order of the figures and corrected the reference to the wrong figure. 2 1 "“Page 6, ""Optical forces"": there is a missing subscript L in the first force term at the end of the first paragraph, just before Eq." atoms3030433_perova 0 +Comma has been introduced. 2 1 Reviewer 2: Report and Author Response The manuscript reports a theoretical study of the dynamics of an atom inside a time-dependent optical potential, generated in a two-color pumped cavity. atoms3030433_perova 0 +The b) has been eliminated. 2 1 In particular, a force term contains a time modulation at the beat note between the two frequencies of the pump fields. atoms3030433_perova 0 +Subscript has been introduced. 2 1 "“At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived." atoms3030433_perova 0 +We have restricted the analysis to 2 curves (full and dashed) and a thinner red dashed curve corresponding to the analytical solution in the lower plots. The visibility is clearly increased and the message stays the same. 2 1 Reviewer 2: Report and Author Response The manuscript reports a theoretical study of the dynamics of an atom inside a time-dependent optical potential, generated in a two-color pumped cavity. atoms3030433_perova 0 +We added references to the Wolf and Tourrencin and A. Peters, K.Y. Chung and S. Chu articles. The latter of these articles does not address the quantum corrections 2. 2 1 I recommend accepting this manuscript, provided the following points are clarified: atoms4020014_makarova 0 +The referee implies that the leading term is not a quantum correction owing to the cancellation of a numerator proportional to hbar and a denominator in the spatial phase factor that is also proportional to hbar. This is, is some respect, a question of semantics, and has a long history in discussions of quantum effects in atom interferometry. Basically this term is a Doppler shift, which is clearly of classical origin, with no need to impose arguments related to cancellations of hbars in numerators and denominators. In the approach we follow using the Wigner representation, there are no numerators and denominators; the leading term has no hbar. 2 1 I am not sufficiently aware of the use f Wigner function but I am sure that there are better and more useful references to quote in addition to ref 17! atoms4020014_makarova 0 +The density matrix in the Wigner representation has been widely used in problems related to the recoil effect and laser cooling. For some mysterious reason it hasn’t used in much in problems involving atom interferometry. Of course there are hundreds of articles (maybe more) and books on the Wigner representation; however here we are concerned mainly with its application to calculations involving atom interferometry. The only examples we know of are the ones referred to in the paper. 2 1 Author response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. atoms4020014_makarova 0 +The article by Fam is devoted to the use of Wigner representation for the two-particle density matrix, which is outside the scope of our article. Moreover, in contrast to that article, we do not use an expansion of the equation for the Wigner distribution in powers of hbar. For both these reasons, we do not include a reference on this article 5. 2 1 It will be helpful to the readers if a figure is provided to show the locations. atoms4020014_makarova 0 +As far as we can tell, the phi_Q term is not related directly to the spreading of the wave-packet. 2 1 These results are interesting to the people working in the field of atom interferometer, because the test mass are often used in the practical experiment. atoms4020014_makarova 0 +We added a paragraph re-emphasizing the choice of x_C, x_qC and x_QC just after Equation (99); these terms do not have to the same leading terms in T^2. 2 1 It arises as a quantum correction to phase factors during periods of free evolution. atoms4020014_makarova 0 +Several additional paragraphs have been added near the figures to help explain the plots appearing in these figures. For the stationary atom case, the limits on y_{m0} are determined from inequality (106) and it is indeed possible for y_{m0} to be less than y_{min}. The manner in which we arrived at the regions of validity of the approximations is now described in more detail. 2 1 Authors’ response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. atoms4020014_makarova 0 +In the article we obtained results that are specific for the parameters of the atom interferometer and test mass’ shape and trajectory. We think for the each case one should generate one figure 3 to answer all questions regarding the validity and role of different parts of the phase and approximate expressions for them. Instead of using a lot of dashed curves, we decided to use a panel of figures. 2 1 Two processes are considered, one occurs during the interaction between the cold atom cloud and the Raman beams, the other occurs during the free evolution of the cold atom cloud in vacuum. atoms4020014_makarova 0 +We added a schematic figure of the geometry of our problem. 2 1 This remains an interesting topic for future work, but is outside the scope of our article. atoms4020014_makarova 0 +In the paragraph after Equation (30) we added a list of requirements that will insure that the signal does not depend critically on the initial atomic state phase space distribution. These requirements minimize the corrections arising from diffraction to which the referee refers 11. 2 1 Two processes are considered, one occurs during the interaction between the cold atom cloud and the Raman beams, the other occurs during the free evolution of the cold atom cloud in vacuum. atoms4020014_makarova 0 +Difficulties related to stray interferometers exist and are important, but are not addressed in our paper, as the referee points out. We are assuming that the effects can be minimized in a fountain geometry using a variety of experimental techniques. In any event, a discussion of these effects is beyond what we are able to discuss in this article. 2 1 The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +The word “potential” has been changed to “acceleration” in the sentence after Equation (1). 2 1 I am not sufficiently aware of the use f Wigner function but I am sure that there are better and more useful references to quote in addition to ref 17! atoms4020014_makarova 0 +A figure has been added to clarify the geometry of the problem. Moreover, additional discussion of the trajectories involved are now given in paragraphs that were added to help explain the plots given in Figures 2 and 3. 4 1 The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +The wave function cannot be used when we know only some statistical properties of the initial phase space distribution. 4 1 Review Report 2 In this manuscript, the influences of an external test mass on the phase of the signal of an atom interferometer are studied theoretically. atoms4020014_makarova 0 +We thank the referee for pointing out this additional reference and have added it to the references. 4 1 Author response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. atoms4020014_makarova 0 +We have introduced new several sentences in this paragraph of Materials and Methods, which define these ad-hoc rules. Lines 154-155: “mgR51C read-outs have been introduced into the classification system as PVS1_O or BP7_O codes of variable evidence strength depending on the splicing outcome [P, Sup-porting (±1 point); M, Moderate (±2); Strong (±4); Very Strong (±8)].” Lines 163-179: “we have developed some ad-hoc rules that take into consideration the coding potential of each individual transcript and its relative contribution to the overall expression to reach the appropriate PVS1_O or BP/_O evidence strength. In brief, for each complex read-out we have applied the following algorithm: (i) De-convolute mgR51C read-outs in-to individual transcripts; (ii) apply ACMG/AMP evidences to each individual transcript; (iii) produce an overall PVS1_O (or BP7_O) code strength based on the relative contribu-tion of individual transcripts/evidences to the overall expression. Thus, if pathogenic supporting transcripts contribute ≥90% to the overall expression, PVS1_O_ code is applied (if different transcripts support different pathogenic evidence strengths, the lowest strength contributing >10% to the overall expression is selected for overall evidence strength). Similarly, BP7_O_ code is applied if benign supporting transcripts contribute ≥90% to the overall expression (if different transcripts support different pathogenic evi-dence strengths, the lowest strength contributing >10% to the overall expression is selected for overall evidence strength). If neither pathogenic nor benign supporting transcripts contribute ≥90% to the overall expression, the splicing assay is considered not providing any evidence in favor, or against, pathogenicity. Recently, we have used a similar ap-proach to deal with complex PALB2/ATM minigene read-outs [20,30].” 2 - 2 1 Author Response Thank you very much for the positive comments 1) cancers14122960_perova 0 +The five RAD51 paralogs are known to be required for homologous recombination and maintenance of genomic stability. Indeed, RAD51C interacts with RAD51B, RAD51D, XRCC2 and XRCC3 in two different complexes that play a role in homologous recombination. Miller et al studied the interaction between RAD51B and D (and also XRCC3) with deletion mutants. These authors found that Rad51C1-285 (includes β-strands 1-5) or Rad51C285-376 (includes β-strands 6-9) did not bind RAD51B. So, a complete beta-sheet is important in maintaining the overall fold of the protein. Moreover, the missense variant p.Arg312Trp (ß-strand 6) has been shown to impair RAD51C function (Gayarre et al 2017). Both studies indicate that this protein region is essential for RAD51C function so that transcripts lacking any of the β-strands, such as ▼(E6q4)-a, ▼(E6q4)-b, Δ(E7), Δ(E8) or the in-frame isoform Δ(E5), is probably deleterious. - We have modified this part, adding several sentences to clarify it. 2 1 describes about the analysis of RAD51C variants using mini-gene assays for splicing defect. cancers14122960_perova 0 +We have added all the transcript names and their contribution in Table 2 (Column PVS1_O/BP7_O mgR51C_ex2-8). - We have included cross-references to Table 1 to facilitate understanding of the manuscript. 2 1 The minigene splicing assay is simplistic in its design, yet provides important functional evidence for the evaluation of spliceogenic variants. cancers14122960_perova 0 +Very important comment. As the reviewer indicates, it would be essential to define the threshold of RAD51C expression from which it keeps its tumor suppressor activity. Unfortunately, it is not known by now but this finding would provide critical information to determine the pathogenicity of leaky spliceogenic variants. - So, we have modified this paragraph to introduce this information: “Only two variants (c.404+3A>G and c.705+3A>G) displayed 26% and 21% of the mgFL-transcript, respectively. Unfortunately, it is not known the minimal amount of RAD51C expression to confer tumor suppressor haplosufficiency so, these splicing assays were not considered informative (PVS1_O_N/A).” Note that leaky variants generate complex minigene read-outs (two or more transcripts), and are therefore classified accordingly (see methods). 2 1 The assay results enabled direct measurement of the percentage of the isoforms generated thus facilitating a better understanding of the dominant isoform generated by each variant and their effect on protein coding. cancers14122960_perova 0 +Acknowledge this suggestion. We have added two references of BRCA1 and BRCA2 studies. 2 1 Lines 259-274 – This paragraph refers to evidence used in the variant interpretation of three aberrant transcripts that kept the open reading-frame (Δ(E2p3), Δ(E5) and ▼(E8p3)). cancers14122960_perova 0 +Acknowledge this comment. In this section we have tried to describe the classification approach and the rules we have followed to classify the variants. Certainly, we agree with the referee as sometimes the method is mixed with some results. So, we have moved some sentences of the last paragraph of Materials and Methods to Results. “The PM3 evidence (in trans with a pathogenic variant in a recessive disorder) did not con-tribute to the final classification. Not surprisingly (FANCO is an extremely rare FA complementation group) [37], none of the tested variants has been identified in Fanconi Anemia patients (ClinVar and Global Variome shared LOVD databases and literature search-es). Similarly, the BS2 evidence (in trans with a pathogenic variant in a healthy individual) does not contribute to the final classification of our tested variants. Finally, we have considered that some pathogenic (PS2, PM1, PM6, PP2, PP4) and benign (BP1, BP3, BP5) codes are not applicable to the classification of RAD51C variants.” 3- 2 1 This was a very interesting manuscript that was well written. cancers14122960_perova 0 +We have included explanations of these acronyms in text and Table 1 and have modified the following sentence: “Of the 19 characterized transcripts, 14 introduced premature termination codons (PTC; PTC transcripts), and of these, 10 are predicted to be degraded by the Nonsense-Mediated Decay pathway (NMD; PTC-NMD transcripts) that is considered convincing evidence of deleteriousness (Supplementary Table S3). “ - We have modified the sentence of the Fl-transcript: “All variants altered splicing, 18 of which produced no traces of the mgFL-transcript or almost undetectable levels (<2.4%, c.904G>A)…” 2 1 The lack of these protein structures are used as evidence to support pathogenicity. cancers14122960_perova 0 +Acknowledge this comment. 2 1 describes about the analysis of RAD51C variants using mini-gene assays for splicing defect. cancers14122960_perova 0 +Acknowledge this comment. We have sequenced the RT-PCR products of all variant assays (indicated in Materials and Methods, section 2.5. Minigene Splicing Assays). In fact, all the *.ab1 sequence and*.fsa fragment analysis files of RT-PCR products will be freely available at http://hdl.handle.net/10261/270934; https://doi.org/10.20350/digitalCSIC/14662 upon manuscript acceptance (links indicated in the manuscript section “Data Availability Statement”). Unfortunately, Sanger sequencing only allowed us to characterize the main transcripts, while the minor ones (<10% of the overall expression) are really difficult to characterize since gel band extraction does not work properly with these small amounts, or other methods (e.g. subcloning of RT-PCR products into a PCR-vector, or RNAseq of minigene outcomes) are laborious and not cost-effective. Anyway, we have also been using Fluorescent fragment analysis for transcript characterization in our previous studies (since Acedo et al, 2012). We have shown that this technique is highly sensitive, accurate and shows high resolution. For example, in Figure 1c, transcripts with minimal size differences (1-3 nt) are well-discriminated. So, for minor-rare transcripts is a good option (not perfect, we agree with the reviewer) to annotate them. - To clarify it, we have modified this part: Lines 132-134: “RT-PCR products were sequenced by Macrogen (Madrid, Spain), which allowed the characterization of the main variant-induced transcripts. Minor transcripts were annotated according to fluorescent fragment electrophoresis size data (see below).” 2 1 Using the minigene assay the authors were able to demonstrate that all 20 variants altered splicing of the minigene compared to wildtype constructs. cancers14122960_perova 0 +According to the reviewer suggestion, FT-IR peaks shift related to chromium ion adsorption are discussed in the mechanism section and is incorporated in the revised manuscript. 2 1 The XPS method is much more sensitive and more accurately determines changes in the chemical composition of samples. catal12030290_perova 0 +EDX analysis (In Figure 3) – is a conditional type of analysis of the chemical composition of the surface. In EDX, often, spectra with different atomic abundances of elements can be obtained even from the same sample. 2 1 In such form is rather difficult to make adequate comparison. catal12030290_perova 0 +The sulphuric acid disintegrated the leaves. Most of the substances in the leaves are reduced to carbon after two hours. Charring takes place by adding sulphuric acid and by the action of heat, charring removes hydrogen and oxygen from the solid, so that the remaining char is composed primarily of carbon. It also helps to remove the moist content in the leaves. The pollution problem may not be takes place. 2 1 However, we regret that we were not able to investigate the BET analysis due to pandemic situation, which could definitely give us additional information. catal12030290_perova 0 +Chromium is a potentially toxic metal occurring in water and groundwater as a result of natural and anthropogenic sources. The prepared adsorbent is well suitable in the real condition. Since the prepared adsorbent (Al-GNSC) is successfully reduces the chromium (VI) ion form the real groundwater samples. 2 1 Comment 4: EDX analysis (Fig 3) - a very conditional (not specific) type of analysis of the chemical composition of the surface. catal12030290_perova 0 +Based on the reviewer suggestion, regeneration studies were performed briefly. Four different desorption agents such as tap water, 0.1M HCl, 0.1M H2SO4 and 0.1M NaOH were utilized to remove the adsorbed chromium ions from the Al-GNSC adsorbent. From this various desorption agents it was identified that 0.1M NaOH was more effective. Hence, the reuse of Al-GNSC from Cr(VI)-loaded material was studied for sorption and desorption cycles using sodium hydroxide as a regenerated agent. Relevant references are quoted in the revised manuscript. Reference: Sujitha Ravulapalli and Ravindhranath Kunta reported that sodium hydroxide was used as a regenerating agent for the sorption and desorption of Cr(VI) by activated carbon derived from Lantana camara plant. [Enhanced removal of chromium (VI) from wastewater using active carbon derived from Lantana camara plant as adsorbent. Water Sci Technol (2018) 78 (6): 1377–1389. https://doi.org/10.2166/wst.2018.413] Reference: M.A. Tandal and B.N.OZA. reported that Sodium hydroxide as a regenerating agent for the sorption and desorption of Cr(VI) by Granular activated carbon. [Adsorption and regeneration studies for the removal of Chromium (VI) from the waste water of electroplating industry using Granular activated carbon. Asian Journal of chemistry. Vol. 17, No.4 (2005), 2524-2530] Page 2 of 2 Comment 2: 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +For the preparation of 1kg of Al-GNSC adsorbent, approximately 150 to 200 mL of hydrochloric acid was added in order to blend the aluminum in to the ground nut shell carbon. Thank you for your valuable comment. 2 1 Page 3 of 4 Comment 7: It is rather difficult to make an adequate comparison of certain properties (catalysts or sorbents) with the already available results, since the concentration of the pollutant and the mass of the loaded sorbent vary in each experiment. catal12030290_perova 0 +According to the reviewer suggestion, the expression of separation factor is mentioned in the revised manuscript. 𝑅𝐿= 1 1+𝑏𝐶𝑖, where “Ci” is the initial concentration of Cr(VI) and “b” is the Langmuir constant. 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +However, we regret that we were not able to investigate the BET analysis due to pandemic situation, which could definitely give us additional information. 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +According to the reviewer suggestion, the complete terms of all abbreviations are mentioned before the first use in the revised manuscript. 2 1 A point-by-point response to the reviewer-1 comments is appended below for your convenience. catal12030290_perova 0 +As suggested, the novelty of the research work is explained in the introduction part of the revised manuscript, and the Page 2 of 4 obtained results are compared with the recent literature. 2 1 Our decision on this manuscript – Major revision. catal12030290_perova 0 +According to the reviewer suggestion, the SEM images with same scale are provided in the revised manuscript. 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +We hope the reviewer understand the experimental deficiencies at the stage of the present experiments. We deeply appreciate the comment raised by the reviewer. Thank you very much. However, we regret that we were not able to investigate the XPS analysis due to pandemic situation, which could definitely give us additional information about the elemental confirmation. 2 1 Please add the discussion which peak shift is related to Cr, the authors can combine these with the discussion of the mechanism. catal12030290_perova 0 +According to the reviewer suggestion, XRD study has been performed and incorporated in the revised manuscript. 2 1 However, we regret that we were not able to investigate the BET analysis due to pandemic situation, which could definitely give us additional information. catal12030290_perova 0 +According to the reviewer suggestion, kinetic study has been performed and incorporated in the revised manuscript. 2 1 (ppm) pH Contact Time (min) Adsorbent dosage (g l-1) Maximum adsorption capability (mg g-1) References Activated carbon (AC) prepared from coconut tree sawdust 10 3.0 180 0.2 3.46 [29] Raw coconut fiber 250 1.0 270 10 18.60 [30] Sugarcane bagasse 100 2.0 90 10 1.76 [31] Canadian peat Coconut fiber 50 2.0 4320 25 4.61 4.71 [32] peanut shell (P. Shell), sawdust (S. Dust) and Cassia fistula leaves (C.F. catal12030290_perova 0 +According to the reviewer suggestion, the conditions for testing adsorbents of Cr(VI) is incorporated in the Table and is mentioned in the revised manuscript. 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +According to the reviewer suggestion the adsorption capacity of groundnut shell activated carbon (Qe= 7.4 mg/g) is mentioned in the revised manuscript. 2 1 conditions for testing sorbents of Cr(VI) ions) to Table 3. catal12030290_perova 0 +Thank you for your valuable suggestion. According to the reviewer suggestion the conclusion section is elaborated with specific conclusions in the revised manuscript. 2 1 Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +We acknowledge the reviewer’s opinion. As suggested by the reviewer, we checked the manuscript carefully and enlisted a professional English language service to eliminate the spelling mistakes and grammatical errors. Thank you for your valuable suggestion for strengthening the quality of the manuscript. 2 1 The paper now can be accpeted for publication. catal12030290_perova 0 +Indeed, the liposomes are prepared by a conventional method. However, here and in our previous work [1] we use the term liposomal nanotraps to reflect the functional aspect of the liposomal action. In this context, the liposomes act as traps for bacterial toxins. 2 1 While LDH-release or MTT assay are frequently used techniques and might be preferred by some investigators, other approaches assessing cell viability might be more popular by others, dependent on particular experimental settings of a particular study. cells11010166_makarova 0 +We verified the total protein content of the supernatants by Coomassie blue staining, which was similar for all strains (Figure. 1, for referee inspection only). The experiments were performed using different bacterial supernatant batches and results were remarkably consistent. All the supernatants were collected at the exact same bacterial culture’s optical density to harvest the bacteria in a comparable state between batches and strains. In our previous work we have shown that cholesterol-dependent cytolysins (SLO, PLY) displayed different kinetics and dynamics of their hemolytic activity compared to SLS. As a result, the total hemolytic activities of individual streptococcal supernatants were not represented by a simple sum of activities (concentrations) of their individual toxins but displayed more complex time- and amount-dependent behavior: e.g. – the activity of PLY/SLO was prevalent at the initial times of incubation and at relatively high amounts (volume) of supernatants, whereas SLS activity fully developed only after initial lag period but was prevalent when relatively low amounts of supernatants were used in the assays. The relative quantifications of toxins between streptococcal species and strains were performed in a previous publication [1] and are referred to throughout the manuscript. We added a paragraph in the result section (line 215-222) that summarizes those points. Moreover, in our current experiments we aim not only at the neutralization of the whole hemolytic secretome of streptococcus (as described in [1]) but also include (putative) cytotoxic/cytostatic activities that might be carried out either by hemolysins (SLO/SLS) or other not yet identified toxins that display cytotoxic/cytostatic but no hemolytic activities. For these reasons, in our current experiments, we use specific cytotoxic/cytostatic activities of total supernatants derived from a toxicity assay displayed in (Figure. 1), instead of concentrations of individual (partly unknown) toxins. However, we agree with the reviewers that using volume units is confusing. We therefore, edited our manuscript to display the lethal dose (LD%) interpolated from results shown in Figure 1 instead. Using LD% units accounts for the batch variability. 2 1 Streptolysin S (SLS) is a small, non-immunogenic, peptide. cells11010166_makarova 0 +While LDH-release or MTT assay are frequently used techniques and might be preferred by some investigators, other approaches assessing cell viability might be more popular by others, dependent on particular experimental settings of a particular study. Figure 2 (for referee inspection only) demonstrates that Alamar blue cell viability assay and Trypan blue live/dead quantification provide results that are identical to those obtained in the cell proliferation protocol used in our study. We believe that the latter protocol is the most suitable experimental approach for our study since it allows distinguishing between cell lysis, cytotoxisity and cytostatic effects (i.e. between cytolysins, cytotoxins and cytostatic agents) in a single experiment. The techniques and algorithms used by the CellDrop relies on accurate and unbiased measurements, akin to previously published techniques[2,3]. The following text was added to the material and method section: Alamar blue cell viability assay and Trypan blue live/dead quantification provide results that are identical to those obtained in the cell proliferation protocol used in our study (not shown). 2 1 THP-1 cells were challenged with bacterial supernatant of the GGS ATCC 12394 strain and the survival rate was measured via CellDrop counting, Trypan Blue live/dead staining or Alamar Blue metabolic activity assay. cells11010166_makarova 0 +The focus of our study is to highlight that successful protection against the whole palette of streptococcal toxins can be achieved by using liposomal nanotraps and to show that the liposome requirements differs between bacterial species and between different types of immune cells. We agree that the SLO neutralization is not novel and simply confirm results from previous publications by us and others. In the current work we do not intend to reveal new neutralization mechanisms either for SLO or for SLS. 2 1 The results were normalized to a control incubated with PBS instead of bacterial supernatant. cells11010166_makarova 0 +Streptolysin S (SLS) is a small, non-immunogenic, peptide. This means that no commercial antibody against it is available and the peptide is too small for reliable mass spectrometry detection. It is heavily post-translationally modified and is the product of a complex operon. Its exact mode-of-action is still not yet fully clarified. In a previous publication, we were able to show that SLS is neutralized by phosphatidylcholine as well as sphingomyelin liposomes [1]. However, given the poor characterization of SLS, its unavailability from commercial providers and its extremely tedious purification, the mechanistic details of the SLS neutralization will require an extensive a project of its own and are beyond the scope of the current study. We added a paragraph in the discussion section (line 378-382) to summarize those points. 2 1 Besançon H, Babiychuk V, Larpin Y, Köffel R, Schittny D, Brockhus L, et al. cells11010166_makarova 0 +We used two controls in the protection experiments. In one control we challenged the cells with bacterial supernatant without adding liposomes, to determine that the baseline cytotoxicity is in line with the results displayed in the Figure 1. The second control consists of the immune cells without toxin or liposomes. This control represents 100% survival and allows us to normalize our survival data. We also tested the intrinsic toxicity of liposomes on their own to see if they did impede cell growth or were cytotoxic. At the concentrations used in current study the liposomes were not cytotoxic (data not shown). The following text was added to the material and method section: The data were normalized to a control incubated with PBS instead of bacterial supernatant (considered as 0% cell death). A control challenged by bacterial supernatant without liposomes was added for each assay to verify the expected cytotoxic activity 2. 2 1 The results were normalized to a control incubated with PBS instead of bacterial supernatant. cells11010166_makarova 0 +We selected the specific supernatant volumes used to reach a similar lethal dose to compare the protection capability and efficiency of the liposomal nanotraps. However, as the immune cell lines have different sensitivities depending on the toxin profile of the tested strain, a similar lethal dose corresponds to different supernatant volumes. We used the results displayed in Figure 1 of the manuscript to determine which volume to use. We agree that the way we presented it can lead to confusion and we replaced the supernatant volume values by LD% values. The following text was added to the material and method section: The added supernatant volume was determined based on the toxicity assay results and was used either at saturating dose (lethal dose >90, LD>90) or at non-saturating dose (LD60-90) to study minor toxin activities. We agree that the distinction between saturating (LD>90) and non-saturating (LD60-90) was confusing. To clarify our process we did add clarifications throughout the results part and we added a panel in figure 2 to include results obtained after challenge of LD>90 of GGS 5804 supernatant. 2 1 The following text was added to the material and method section: The added supernatant volume was determined based on the toxicity assay results and was used either at saturating dose (lethal dose >90, LD>90) or at non-saturating dose (LD60-90) to study minor toxin activities. cells11010166_makarova 0 +Following the reviewer’s comments, we have now focused on one detailed analysis based on adequate tests and a discussion of the results. The revised version drops Descriptive statistics in old Table 2, rates of increase given in the old Table 3, correlations reported in old Table 4, the regressions in old Table 5, and pooled regressions of old Table 6. The discussion based on these Tables has consequently been omitted from the revision. The unit-root-test Tables have been moved from the Appendix to the text as Table 2, and in view of the evidence in favor of unit roots, rates of growth of GDP and government variables have been shown in Table 3 somewhat like the old Table 3. These are the most major changes. 2 1 But later tests show that the variables are non-stationary. economies3040150_makarova 0 +The authors are aware of the Johnson et al. paper (JME 2013) and other critiques of the PWT data. However, while the LCU numbers are appropriate for single-country analysis, these are not suitable for panel-data format which is a significant part of this study. Therefore, we use the PWT numbers throughout and hope that single-country analysis with these numbers is a reasonable approximation to the scenario indicated by LCU data. 2 1 The suggestions are listed below in no particular order of importance: 1. economies3040150_makarova 0 +The dependency variable has been removed from the analysis. 2 1 This makes the unconditional correlations uninteresting. economies3040150_makarova 0 +Figure 1 has been redone with separate scales for logarithms of real GDP per capita and government share. 2 1 This is a major flaw of the paper and the choice should be defended by showing that using the ‘standard’ real GDP series’ would give the same results. economies3040150_makarova 0 +The correlations of old Table 4, the static regressions of Table 5, and the discussion of endogeneity have been omitted. 2 1 This makes the unconditional correlations uninteresting. economies3040150_makarova 0 +Since our data cover a long period of nearly 50 years, we are inclined to rely on Johansen tests although the number of data points is smaller than 100. The Gregory-Hansen test is done for Japan and Korea also just for completeness, and might be of some methodological interest since it does not show cointegration even for Japan and Korea. The reviewer’s observation has been acknowledged in note 2. 2 1 Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. economies3040150_makarova 0 +We agree with the reviewer about the limited usefulness of MTAR in small samples and for Japan and Korea. However, it is included in the hope it would indicate whether lack of cointegration for Malaysia, Philippines, Singapore and Thailand might be due to asymmetric adjustment. The reviewer’s observation has been acknowledged in note 3. 2 1 References: Cameron A. Shelton (2007) “The size and composition of government expenditure” Journal of Public Economics, 91 (11–12) Simon Johnson, William Larson, Chris Papageorgiou, Arvind Subramanian. economies3040150_makarova 0 +We have highlighted the alternative hypothesis in Pedroni’s tests on Page 8. As Pedroni (1999) clearly points out, the alternative hypothesis rejects the null of no-cointegration across all cross-sections in both within- and between-dimension tests. 2 1 Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. economies3040150_makarova 0 +The “provocative conclusion” reflected one author’s subjective perception and was stated as such. He shares the perspective noted by Bennett McCallum’s in his “Is the spurious regression problem spurious?” (Economics Letters, 2010). However, the segment cited by the reviewer has been deleted since it is a more general proposition and is not necessary for the limited analysis reported in our paper. 2 1 Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +We completely share the reviewer’s view that despite Biehl’s PF/FP essay, almost everyone follows the standard approach, and we do the same. Our observation is just a restatement of the proposition that our approach is traditional. 2 1 Or the GDP series, downloaded from World Development Indicators (local currency, constant prices), should be used. economies3040150_makarova 0 +Please note the following changes in revised version: (a) the plots in Figure 1 have been rescaled and now there are cross-overs in the plot for Japan, (b) years have been shown on the horizontal axis in Figure 1, (c) a sizable addition has been made toward the end of Section 3 to address the reviewer’s observations about possible reasons for lack of cointegration in most countries, and (d) a few minor editorial alterations have been made. 4 1 Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. economies3040150_makarova 0 +Several new references, including those kindly mentioned by the reviewer, have been added, and there is a concise description of these in note 1. 2 1 This makes the unconditional correlations uninteresting. economies3040150_makarova 0 +Several formats in which Wagner’s hypothesis has been formulated and tested have been listed on page 5 of the revision. That paragraph includes six different approaches. 2 1 Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. economies3040150_makarova 0 +Real GDP per capita is a fairly standard proxy for the “level of development” in the context of Wagner’s hypothesis. It might not be appropriate to use nominal GDP per capita. For the government share, it seems better to take the current-price ratio which indicates what fraction of the current output is used for government activities. The deflators for GDP and government spending are different and “real” government-share may not be a good indicator of the resource-use by the government during the current year. 2 1 Now the paper is mainly an econometric exercise. economies3040150_makarova 0 +The old Table 2 has been deleted. Those descriptive statistics were for the entire period. The growth rates in the new Table 3 are also for the entire period, and that has been indicated. 2 1 Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +The redundant graphs for Philippines have been deleted. 2 1 But later tests show that the variables are non-stationary. economies3040150_makarova 0 +The dependency-rate variable has been dropped. 2 1 Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +The old Table 4 has been deleted along with the remark about p-values being taken from SAS. 2 1 References: Cameron A. Shelton (2007) “The size and composition of government expenditure” Journal of Public Economics, 91 (11–12) Simon Johnson, William Larson, Chris Papageorgiou, Arvind Subramanian. economies3040150_makarova 0 +Thank you. 4 1 Now the paper is mainly an econometric exercise. economies3040150_makarova 0 +The colour refer to the SEEBASE depth to basement, the legend has been added • Figure 2: The left spine (or border) does not appear on the pdf reviewed. 2 1 Not possible to differentiate post-Wilton fault types properly in the figure. geosciences12010037_perova 0 +Thanks, the figure have been entirely revisited and divided into four subfigures. 2 1 Could not find “Coast_10million”, “frameworkboundaries” or “State_Borders_10million” on the map. geosciences12010037_perova 0 +The figure has been redrawn and the magnetic lineaments indicated • Figure 4: This figure could go in the appendix. 2 1 Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). geosciences12010037_perova 0 +Thank you. We hesitated on this point but decided to keep the figure in as the quality of the seismic in the shallow level is really crucial to the discussion. We need to know if the interpretation is reliable, especially in this shallow zone that is not well imaged by this type of data. A misinterpretation can led to the targeting of circulation pathways that are in fact only artefacts. 2 1 Review summary Scientific aims clearly stated. geosciences12010037_perova 0 +We 2 1 frameworkboundaries to framework boundaries; populated places to Populated places/(Settlements?); PossibleFluidEscapeFeatures to Possible fluid-escape features etc. ). done, legend cleared from information not represented 4. d) Explain/improve labels (what do you mean by “ntspr_2M_gw”? geosciences12010037_perova 0 +done, 2 1 done, legend cleared from information not represented 5. e) Several items in the legend appear to have the same or very similar signatures. geosciences12010037_perova 0 +‘this is due to the different seismic acquisition technics and processing applied in each survey as well as the fact that our interval of interest is shallow and not fitting with the interval of interest the companies tried to best image with those datasets” 2 1 Consider adding isochore maps for intervals between interpreted reflectors. geosciences12010037_perova 0 +as the presence of fluid or gas can locally alter the seismic signal” 2 1 done, we also totally revisited this figure as to have a cleared output I hope you will find these comments useful when revising the manuscript and look forward to seeing the paper published in Geoscience. geosciences12010037_perova 0 +We added: “We define as recent tectonic activity the events that are recorded at the surface and can alter the surface with active tectonic features, such as modifications of the drainage system” • Discussion: One general comment, could the use of other tracers (radon, of stable isotopes of water) yield also insight on the origin of the fluids sampled in this study? 2 1 done -Many well-name labels are hard difficult to read/illegible. geosciences12010037_perova 0 +Radon cannot give this information since with the short half-live of 3.8days it's signal comes only from the direct vicinity of the sampled location. Stable isotopes of water could in principle do this if there is a geothermal signature on them (such as plotting far left to the meteoric water line - see inset in Figure 1 of McIntosh and Ferguson, 2020 – Geophysical research Letter) - but we have not seen such a signature. We may mention that in the text - but for such a signature to be discernible the bulk of the water needs to be geothermal, and what we see is only a small admixture. 2 1 The drainage network was extracted automatically. geosciences12010037_perova 0 +The revisited figure 43 is now providing this information Seismic reflection 2D lines (1989-2015). 2 1 frameworkboundaries to framework boundaries; populated places to Populated places/(Settlements?); PossibleFluidEscapeFeatures to Possible fluid-escape features etc. ). done, legend cleared from information not represented 4. d) Explain/improve labels (what do you mean by “ntspr_2M_gw”? geosciences12010037_perova 0 +Thank you, the details comments on those figures have been followed and new figures are provided Helium measurements from groundwater samples. 2 1 Please provide a more informative caption to what these plots show. geosciences12010037_perova 0 +"There is no other reference to date to the ""primary documentation"" but the link to the data (they should now be online) which are in the fact sheets." 2 1 done -Replace the white label with black typeface with plain white typeface. geosciences12010037_perova 0 +We have redone the figure 2 and added explanations on the process (see reply to comments on figure 2). Figure 8 should now be easier to read The surface drainage network line dataset was indeed based on the simplified (n=130) network following the following approach: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. 2 1 The replies to detailed comments are in purples, directly below each comment Frery et al. geosciences12010037_perova 0 +There is indeed an error on the figure referencing, we modified to Figure 3B where the lineaments are now clearly indicated. 2 1 Not possible to differentiate post-Wilton fault types properly in the figure. geosciences12010037_perova 0 +We indeed need to add this link- we will put a link in place upon acceptance of the paper Figures Figure 1A. 2 1 the seismic interpretation of figure 7G (cross) that were misleading the reader and add the interpretation of the fluid leakage features on the images • Figure 9: Remove ‘s’ from <10 yearss. geosciences12010037_perova 0 +done, we also modified the fault legend to add clarity - Replace white labels with black lettering with no labels and white lettering. 2 1 Helium isotope data do not provide an unequivocal answer to whether the gas originates from the unconventional plays or a deeper source. geosciences12010037_perova 0 +We separated the legends from figures 1A and 1B as to add clarity. This article is focused on the Beetaloo subbasin and we use the direct input for Geoscience Australia in this stratigraphic column. We are not willing to add complexity by presenting in detail the Basins that are covering the Beetaloo Sub-Basin. We removed from the legend the details on the different basins as we understand that it is leading the reviewer in directions we are not exploring on the CLA stratigraphy- we do not refer this complexity in the results and discussion. 2 1 Author Response The authors would like to thank you the reviewer 2 for this second round of reviews. geosciences12010037_perova 0 +Thanks, the figure have been entirely revisited and divided into four subfigures as advised below -Consider splitting into several maps, e.g. 2 1 Magnetic data and 2D seismic reflection profiles were used to image structural features, and fluid/gas leakage pathways. geosciences12010037_perova 0 +This output was then overlayed upon satellite and magnetic images where lineaments are evident for checking and quality control. In this process, minor mismatches of the automated simplified lines were removed and small drainage segments were connected along major lineaments for further simplification and reduction of the dataset. The adopted approach was: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. We added this description of the adopted approach in the legend Figure 3 -Very small/illegible typeface on map coordinates – consider simplifying scales and use larger typeface. 2 1 To my understanding this should correspond to Figure 2 a, which shows substantially more than 130 lineaments. geosciences12010037_perova 0 +figure redrawn - Replace white labels with black typeface with white typeface. 2 1 This would also tie the observations based on this dataset closer to the seismic interpretation (see below). geosciences12010037_perova 0 +Well label typos modified -Thin grey seismic lines are not explained in the legend or caption. 2 1 Poor resolution in the copy provided for the review. geosciences12010037_perova 0 +Legend added for those lines -The outline of the Eastern and Western Beetaloo Basin in Figure 3 and 4 should be kept identical in order to position Figure 6 A, B and C in relation to the seismic lines shown in Figure 4. 2 1 done -Many well-name labels are hard difficult to read/illegible. geosciences12010037_perova 0 +isochores added as supplementary material Figure 6 Add scale(s).done Figure 7. 2 1 If they are not present on the map, remove these items from the legend. geosciences12010037_perova 0 +done, legend cleared from information not represented 2 1 Recent fault activity was identified using a combination of sub-surface imaging and comparison of fault orientations and surface drainage networks. geosciences12010037_perova 0 +checked and clarified Clean up map: 1. 2 1 Why are these not classified in terms of signal quality? geosciences12010037_perova 0 +identified in the legend and representation 2 1 • Lines 323-324: The authors should explain why low magnitude local seismic signals can be believed to represent permeable pathways promoting water or gas migration. geosciences12010037_perova 0 +removed 2 1 The drainage network was extracted automatically. geosciences12010037_perova 0 +Outline size modified and homogenised with other figures 4. 2 1 done Figure 4 -Poor quality figure (low resolution) in the version available to the reviewer. geosciences12010037_perova 0 +Red selected 5. 2 1 If these items are present, please use a more contrasting signatures to make it more visible. geosciences12010037_perova 0 +modified 2 1 Magnetic data and 2D seismic reflection profiles were used to image structural features, and fluid/gas leakage pathways. geosciences12010037_perova 0 +modified accordingly Consider adding a simple conceptual sketch highlighting the stratigraphic position of the different faults (and possible fluid escape structures– this would also help visualizing which stratigraphic intervals the potential fluid escapes originate from and which stratigraphic intervals are potentially connected along potential fault-related fluid flow pathways. 2 1 It is good to let the reader know that not all seismic surveys provided the same quality, but this is more a technical point. geosciences12010037_perova 0 +With the new classification the reader should be able to better read the paper and can now directly refer to the stratigraphic table Figure 8. 2 1 done • Line 360: Here and throughout the text, the word ‘recent’ is used to describe some tectonic activity. geosciences12010037_perova 0 +Done, figure clarified as well Figure 9. 2 1 The plot “Surface drainage network from this study” is identical to the original figure and should have n=130 measurements. geosciences12010037_perova 0 +we also totally revisited this figure as to have a cleared output 2 1 Helium content of the aquifer systems was sampled and measured. geosciences12010037_perova 0 +Thank you, we truly appreciated the time took by the reviewer to provide detail guidance to improve the manuscript and the figures 2 1 It doesn’t read well otherwise.done • Figure 7: What is special about the locations highlighted by the markers (crosses on Figure 7B and square markers on Figure 7C). geosciences12010037_perova 0 +The helium measurements have been added as supplementary data and the author made a clear difference between this study Helium measurements and other tracer studies we are citing. 4 1 Helium isotope data do not provide an unequivocal answer to whether the gas originates from the unconventional plays or a deeper source. geosciences12010037_perova 0 +Done, thank you 4 1 Outline size modified and homogenised with other figures 4. geosciences12010037_perova 0 +The isochores have been added in the seismic supplementary dataset 4 1 The map differentiates between “BaseCambrian seismic faults”, Post-Wilton “Strike-slip” and “Reverse” faults, and “FAULTS”. geosciences12010037_perova 0 +Post Wilton “Strike-slip” and “Reverse” faults have been redrawn in all figures (Figure 1, 7, 9) with a new colour code, the fluid escape features are now shown as red dots in the legend as well. 4 1 • Figure 6: Put the title of each subfigure above the plot. geosciences12010037_perova 0 +Number of measurements added in each plot. Figure 2a correspond to the SEEBASE structural lineaments (n=681). 4 1 Please use contrasting colours to differentiate them. geosciences12010037_perova 0 +The second part of this analysis, titled: “Body composition assessment in Mexican children and adolescents. Part 2: Cross-validation of three bio-electrical impedance methods against dual X-ray absorptiometry for whole-body and regional body composition”, has already been accepted by Nutrients #1604578. The two analyses were conducted on the same children’s database and closely complement each other. As the accepted manuscript already includes the phrase ‘Part 2’ we prefer to keep ‘Part 1’ here ABSTRACT 2. 2 1 We have corrected the data, and now we only present data on the 288 subjects for both tables. nu14051073_perova 0 +Corrected, we adjusted this paragraph together with the next one to give a clearer explanation of the motivation of this study. 2 1 "Added Relatedly, it would have been helpful to have more explanatory titles for the plots--eg ""Differential correlation between methods across levels of FM""." nu14051073_perova 0 +We have adjusted accordingly. We hope now we can give a clearer explanation about the motivation of this study. 2 1 P2 L69: The aim stated here does not follow the logic of the preceding statements in the paragraph, i.e., what does comparing BC methods have to do with lack of healthcare or technology? nu14051073_perova 0 +Clarified in lines 164. 2 1 Only 6.6% belong to indigenous population and 5.9% to Afro-Mexican ethnic groups. nu14051073_perova 0 +The data used was total body with head, as recommended for the ISCD when using DXA for body composition instead of for bone densitometry. We clarified and referenced this in the text, lines 204-208. 2 1 I am not familiar with the Bland-Altman method, so was unclear when I read the methods section whether the text in lines 204-207 was explaining the Bland-Altman method or describing a separate procedure. nu14051073_perova 0 +This was a typo, we corrected it. Line 260. 2 1 P7 L226: It would be helpful if it was made clear that this refers to comparisons of means of all subjects (not broken down by age, sex). nu14051073_perova 0 +We corrected (lines 287-288). 2 1 P2 L69: The aim stated here does not follow the logic of the preceding statements in the paragraph, i.e., what does comparing BC methods have to do with lack of healthcare or technology? nu14051073_perova 0 +Indeed, it was like that. We have changed it to show only the data of the 288 subjects (without the 5 outliers). 2 1 We have corrected the data, and now we only present data on the 288 subjects for both tables. nu14051073_perova 0 +This was because of the inclusion of the 5 outliers in table 1, which has been corrected. 2 1 Cost, manpower, location, all play a role in driving the selection of BC techniques. nu14051073_perova 0 +We have 2 1 MATERIALS AND METHODS P3 L94: This is awkwardly worded. nu14051073_perova 0 +Added, the analysis was for the total sample and by subgroups by age and sex, line 287 14. 2 1 P3 L125: DXA: Was the head ROI excluded from the analyses (as per recommendation by the ISCD)? nu14051073_perova 0 +We have corrected as recommended. Table 4 sent to supplementary material as supplementary table 3. 2 1 We have added this in supplementary table as S table 1. nu14051073_perova 0 +Changed as supplementary figure 3. 2 1 Also, the difference(s) between FFM and LM definitions are nuanced and complex and should either be defined, or alternate text should be used here. nu14051073_perova 0 +Changed, line 19 INTRODUCTION 3. 2 1 Response to reviewers' comments: Reviewer one: TITLE The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. nu14051073_perova 0 +We have stated in the conclusion that while individual methods show bias relative to the 4-component reference, the high correlations indicate that all the methods perform well in ranking individual children as having high or low FFM and fat mass. This ranking is itself very valuable in routine clinical care, particularly for longitudinal assessment. We have provided new evidence for the Mexican population that all the methods have utility for this purpose. Furthermore, some of the biases for individual methods can be resolved by the publication of method-specific reference data, whereby all data can be converted to method-specific z-scores. Publishing such reference data is a further aim of our project. 2 1 Concluding that methods differ is not surprising. nu14051073_perova 0 +added 2 1 We clarified and referenced this in the text, lines 204-208. nu14051073_perova 0 +Added to supplementary figure 1 and main figures 1 and 2 3. 2 1 As it was, I couldn't understand the description provided, and it didn't seem to match the figures, which were simply labeled as FM, so seemed to be a simple plots of FM using 2 methods on first read. nu14051073_perova 0 +Specified in limitations lines 993-997. Important to say is that ~89% of Mexican population is Hispanic. Only 6.6% belong to indigenous population and 5.9% to Afro-Mexican ethnic groups. 2 1 P7 L226: It would be helpful if it was made clear that this refers to comparisons of means of all subjects (not broken down by age, sex). nu14051073_perova 0 +Corrected. In the previous version we put data of the whole sample of 293 subjects (including 5 outliers that should not been there). We have corrected the data, and now we only present data on the 288 subjects for both tables. 2 1 over or under estimating FM) may affect health assessments. nu14051073_perova 0 +Added to table 1. 2 1 As the accepted manuscript already includes the phrase ‘Part 2’ we prefer to keep ‘Part 1’ here ABSTRACT Regarding “The clinical context in which BC is evaluated usually defines the ideal model to be used”: This is somewhat confusing. nu14051073_perova 0 +The definition of glaucomatous visual field loss was elaborated in the corresponding reference. However, we agree that we were very brief in explaining glaucomatous visual field loss in the manuscript. Therefore we made the following changes to elaborate: In lines 89-98, we changed: “iOAG was defined as glaucomatous visual field loss in at least one eye with reproducibility of the defect, independent of IOP” To: “All participants underwent visual field testing using the Humphrey Field Analyzer (HFA; Carl Zeiss Meditec, Jena, Germany). A second supra-threshold test was performed when a visual field defect appeared to be present. Details have been described elsewhere. [1] If the second supra-threshold test showed at least one overlapping abnormality in the same hemifield, Goldmann kinetic perimetry (RS-I-1 and RS-I-3; Haag-Streit) or full-threshold HFA (all other cohort visits) was performed on both eyes. If abnormalities were consecutive and reproducible, thus present on the Goldmann or full-threshold test and on both supra-threshold tests, visual field loss was considered to be present. Defects had to be in a consistent hemifield and a least one depressed test point had to have exactly the same location on all fields.” In lines 98-100, we changed: “All other possible causes of visual field loss were excluded.” To: “Glaucoma specialists examined fundus photographs, ophthalmic examination reports, medical histories, and MRI scans of the brain to exclude all other possible causes of visual field loss. Discrepancies were resolved by consensus.” In lines 103-104, we added: “For IOP, three measurements were taken from each eye, of which the median value was recorded. [2] For iOAG cases, we used IOP measurements of the affected eye. If both eyes were affected or unaffected, a random eye was selected. IOP was not included in the definition of iOAG.” Was glaucoma also defined by an objective finding, such as the optic disc finding or imaging of the optic disc? 2 1 We appreciate the positive review and acknowledgement of these important findings. nu14122490_makarova 0 +OCT images were taken with SD-OCT (Topcon Corp., Tokyo, Japan) since 2007. This means that OCT images are not available for the first four visits of RS-I, and the first two visits of RS-II. Additionally, only part of the images are focused on the disc and even less are reliably segmented. Fundus images were available and were used rather to exclude other cases of visual field loss in participants that showed visual field defects than to observe optic disc abnormalities. 2 1 Cancer Epidemiol Biomarkers Prev 2005, 14, 483-490. nu14122490_makarova 0 +Thank you for this comment. We understand that it might be useful to present the number of treated glaucoma cases in our baseline characteristics table. Unfortunately, detailed information on prior treatment/surgery for glaucoma is limited (only present for RS-I), and therefore we did not include this variable as covariate in our models. It is thus possible that incident glaucoma cases have received treatment for glaucoma in between two research visits. However, since all participants were (confirmed by examination) free of OAG at baseline, treatment for glaucoma could not have been longer than maximum of one follow-up visit. Although not having this data is a limitation of this study, we do not think it is an important confounding factor, since we do not expect that glaucoma treatment would influence one’s diet. More importantly, dietary information was collected at baseline, with all participants free of OAG. Therefore, if glaucoma presence or glaucoma treatment would have an effect on dietary intake, this would not be applicable in our study. We have added a short sentence explaining this in lines 312-316 of the manuscript. 2 1 The writing is of perfect quality and the results are clearly presented. nu14122490_makarova 0 +We agree that, although our findings confirm earlier reported associations between dietary nitrate intake and OAG, intervention studies are necessary to investigate and confirm the association between dietary nitrate intake and iOAG. Therefore, we will change all references to “protective (effect)” to “association/associated with”. 2 1 In this letter we will address the comments of reviewer #2 point by point. nu14122490_makarova 0 +Thank you for this suggestion. Although the evidence for the association between ischemia--reperfusion and glaucoma pathogenesis might be scarce, this is only one possible pathway that is addressed in explaining the inverse association between dietary nitrate intake and glaucoma incidence. Nevertheless, we will adjust the manuscript (lines: 271-288) so that this statement is less strong and the focus is more on (a combination with) other pathways, rather than this pathway alone. 2 1 Cardiovascular Disease Predicts Structural and Functional Progression in Early Glaucoma. nu14122490_makarova 0 +We agree that the baseline dates of all three cohorts (RS-I, 1991-1993; RS-II, 2000-2001; RS-III, 2006-2008) are already quite some years ago and that dietary patterns in general have changed over time. However, since dietary recommendations are not standard of care for glaucoma patients, we believe that this would likely lead to non-differential misclassification (that causes a bias towards the null hypothesis), since we would expect that glaucoma cases would change their diet similarly to our control population and vice versa. We thus feel that this study and its findings are still highly relevant today since nutrition has become ever more important in medical sciences. Ophthalmology is one of the disciplines which has gained enormous insights from these recent developments. However, to date, no nutritional recommendations have been made for glaucoma patients and research into the association between nutrition (on each level, e.g. diets, food groups, nutrients) and glaucoma is scarce. If associated, this may support diet recommendations in patients that show first signs of developing glaucoma and/or people at-risk for glaucoma as well, impacting millions of people worldwide. Especially since diet changes into a vegetarian of vegan diet are becoming more popular, we think that understanding the potential beneficial effects of these changes, thus the effects of vegetables and their nutrients, is more important than ever. We do agree that these findings should be replicated or validated in another (preferably, an intervention study) study before dietary nitrate intake should be considered as an important public health implication. To address your question about the change of dietary patterns over time more thoroughly: Dinnisen et al. [6] recently published an article in Nutrients where they described changes in dietary intakes of Dutch adults between 2007-2010 and 2012-2016, and evaluated these changes by age, gender, and education. They demonstrated that there was no significant increase in vegetable intake for Dutch adults aged 19–69 years between 2007–2010 (n = 2106; DNFCS 2007–2010) and 2012–2016 (n = 1540; DNFCS 2007–2010) for the total population. There was also no difference when they compared the change in vegetable intake over time per sex or per age category (51-69 years being closest to the baseline age used in our study). Only in the group with the highest educational level, the mean consumption of vegetables increased over time. However, since there was no significant difference in education level in our study between cases and controls (Table 1), we assume that changes in vegetable intake would be similar between both groups, leading to non-differential misclassification. Moreover, we adjusted for education level in our additional model. Regarding dietary nitrate intake from non-vegetable sources, this article states that the intake of red or processed meat decreased over time. This was applicable to both males and females and seen for all age groups. Again, we would expect that this decrease is similar for glaucoma cases and controls. Another Dutch study [7], starting in 1986 (which is more close to the first visit of RS-I) stated that “Another potential limitation that should be considered is whether the food frequency questionnaire at baseline was a reliable estimate of past and future diet. The stability of dietary habits over time was evaluated from five annually repeated questionnaire administrations in independent random samples of the cohort. The mean intakes barely changed and the correlation between two measurements decreased only slightly over an increasing time interval. It was concluded that the single food frequency questionnaire measurement characterizes dietary habits for a period of at least 5 to 10 years.” [8] Nevertheless, since both studies are not directly translatable to the Rotterdam Study, we have assessed the association between the dietary nitrate intake and iOAG over cumulative follow-up periods to provide insight into the stability of the found estimates over time. Please see our comment regarding your next suggestion for more details. 2 1 Cha, S.; Gu, B.; Sagong, M.; Son, J.; Kim, M. Association between glaucoma and cardiovascular disease risk in Korean population based study. nu14122490_makarova 0 +We agree that the lack of follow-up food questionnaires is a major limitation of this study. Please find an additional supplementary figure (Figure S1; original Figure S1 has now become Figure S2) below and in the supplements of the manuscript, to show that we assessed the association between the dietary nitrate intake and iOAG over cumulative follow-up periods (x-axis) to provide insight into possible reversed causality. The persistence of the association over time implies that reverse causality is unlikely. The effect of (baseline) dietary nitrate intake on glaucoma appears to be relatively stable over time. We therefore consider our results reliable, although we agree limitations are present and these findings should be interpreted with caution. In addition to the new supplementary figure, we have added information about this analysis to the methods (lines 152-153), results (209-211), and discussion (296-298). 2 1 Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. nu14122490_makarova 0 +Thank you very much for assessing the covariates included in these analyses so thoroughly. Unfortunately, family history of glaucoma was only available for a subset of the first cohort, and not for the second and third cohort. Therefore, we were unable to include this variable as a covariate, as this would severely limit our power (528 participants of 1038 participants; 133 glaucoma cases and 389 controls). As cup-to-disc ratio is highly correlated with glaucoma diagnosis, we feel that cup-to-disc ratio should not be included in the model. Moreover, cup-to-disc ratio is not associated with dietary nitrate intake, and therefore cannot be considered as confounding factor. By including cup-to-disc ratio into the model, we would adjust the association between dietary nitrate intake and glaucoma by “glaucoma presence” and thus diminish any existing association. To meet your comment/suggestion, we have added baseline spherical equivalent (proxy for myopia, excluding aphakic or pseudophakic participants) to model 3. As you can see in the results below (original results visualized in Figure 2 in the manuscript), adjusting additionally for SE did not change the results of the continuous nitrate intake analyses and did only marginally change the results of the quintile analyses, leading to a more significant finding for Q5 as compared to Q1. Because both analyses are similar, and since myopia is associated with education level, we chose to keep the original model 3 in the manuscript, adjusting for education level, but without adjustment for SE. To address your question, in lines 318-323, we will change: “Finally, although the analyses were adjusted for several confounders, residual confounding cannot completely be excluded.” To: “Although the analyses were adjusted for multiple confounders, we were unable to adjust for other possible confounders such as family history of glaucoma due to a lack of data. We did consider the risk factor myopia, for which we adjusted by including education level into model 3. We also included spherical equivalent into the model (data not shown), but this did not change the results. Lastly, residual confounding cannot completely be excluded.” Original model 3: model 1 additionally adjusted for education level and smoking status. 2 1 The writing is of perfect quality and the results are clearly presented. nu14122490_makarova 0 +In the introduction section we have suggested that dietary nitrate might have both IOP-dependent, or blood pressure dependent, and IOP-independent effects that could affect glaucoma risk. Unfortunately, we were only able to assess the effect of dietary nitrate intake on IOP and blood pressure. In the most ideal situation, we would have assessed the effect of dietary nitrate intake on retinal nerve fiber layer (RNFL) thickness. Unfortunately, due to limitations as described above, we were not able to do so. Since we found no significant effects of dietary nitrate intake on IOP and blood pressure, we suggest that IOP-independent effects of dietary nitrate intake might influence glaucoma risk. This should be further investigated in future studies. 2 1 Enclosed please find our revised manuscript, which incorporates the comments and suggestions of both reviewers. nu14122490_makarova 0 +We would like to thank the reviewer for the positive feedback on our study design and our final manuscript. 2 1 Model 1: adjusted for body mass index, total energy intake, diet quality, physical activity, and follow-up time. nu14122490_makarova 0 +We would like to thank the reviewer for this interesting comment. In the Rotterdam Study we indeed find an inverse association between BMI and OAG incidence (Table 1). When we divide the participants in three categories based on their BMI (BMI < 18.5, BMI 18.5-24.9, or BMI >= 24.9), the difference between cases and controls is still (borderline) significant (p=0.054), with more people being overweight (68.7%) in the control group than in the glaucoma group (59.3%). The finding that BMI is inversely associated with OAG is in line with previous studies. Lin et al. [1] found that lower BMI was associated with increased odds of OAG, especially in younger females. Ramdas et al. found similar results, with an association between obesity and a lower risk of developing OAG, although only present in women. [2] In line with these findings, underweight was associated with increased risk of primary OAG in diabetes patients. [3] Moreover, in a group of patients in which visual field loss progressed despite treatment with eye drops, lower BMI was associated with progression of visual field loss in normal-tension glaucoma patients. [4] One possible explanation for this is that cerebrospinal fluid pressure (CSFP) has a positive, linear relationship with BMI. [5] As reduced CSFP may be a risk factor for primary OAG, individuals with lower BMI may have an increased risk for developing primary OAG. [6] Again, a higher BMI may be protective. We acknowledge that BMI is an important confounder in our study, as BMI is associated with both our outcome (OAG) and exposure (diet). We have therefore included BMI as covariate in our main model. Adding or removing BMI from the multivariate model (model 1) did not change the results, as can be seen in the table below. That the association did not change after adjustment for BMI suggests that the association between dietary nitrate intake and OAG cannot be explained by BMI, although residual confounding may persist. To account for a possible effect of BMI on the association between dietary nitrate intake and OAG, we performed additional matching. We returned to the original dataset and matched cases and controls based on age (3-years range) and sex, as done previously, and additionally for BMI (2 kg/m2 range). Please see below for the “new” baseline characteristics table. Once the participants have been matched on age, sex and BMI, you can see that none of the covariates included in the models are significant between iOAG cases and controls. Cases only have a significantly higher IOP, which is expected, and somewhat shorter follow-up (not surprising, since they are excluded one they are diagnosed with iOAG). Diastolic blood pressure, BMI, and the dietary nitrate intakes are no longer different in the univariate analyses between cases and controls. We have created two supplementary tables (Table S4 and Table S5), to show that the associations found between dietary nitrate intake and iOAG or IOP, were largely similar in the analyses where we matched on BMI additionally, as compared to including BMI as covariate into model 1. Only the association between dietary nitrate intake from non-vegetable food sources and iOAG is no longer significant, but the change in effect estimates was minimal and they remained far below 1 (Table S4). For the analyses of IOP, the association between dietary nitrate intake from non-vegetable food sources goes from borderline significant to significant (Table S5). By displaying these results, we hope to have shown that the associations described in the original manuscript are most likely true associations and explained by dietary nitrate intake rather than age, sex, or BMI. Although an association between glaucoma and cardiovascular disease has been described in the literature [7-9], we believe this is more linked to their shared pathology, impaired auto regulatory capacity of glaucomatous eyes and arterial stiffness of CVD [7], or even genetics [10], than mediated by BMI. Apart from the two additional supplementary figures, we have added some information regarding this comment in lines 301-304 of the manuscript. 2 1 Association of Body Mass Index With Lifetime Risk of Cardiovascular Disease and Compression of Morbidity. nu14122490_makarova 0 +Authors immensely thank reviewer for the constructive suggestions and valuable comments which greatly helped in the improvement of the manuscript. The corrections have been incorporated as per the suggestions made by the reviewer. 2 1 of genes / QTLs, which is already represented in column 1) and add the most striking phenotypic data, when possible and relevant for discussion. plants11050622_perova 0 +Figures have been revised with addition of arrows and text to represent the data. Since a large number of ILs were screened, susceptible check (SC) was used with a set of ILs and hence SC couldn’t be shown in all figures. However, SC ‘HR12’ for blast disease was shown in all blast screening figures 3 to 5. Similarly, in Fig 5, ‘TN1’ and ‘Improved Samba Mahsuri’ as susceptible and resistant checks respectively for BB in comparison with IL-19031 were shown. Authors once again thank the reviewer for pointing out the mistake in legends. Now, we have rephrased the legends clearly describing all the terms. 2 1 Explaining briefly which and what are the Indian seasons during which experiments have been conducted would help clarity. plants11050622_perova 0 +Figure 1 legend has been revised with inclusion of the details of kharif and rabi seasons. kharif is the wet season with crop growing period from June to November and rabi is the dry season with crop growing period from December to May. We described kharif as wet season and rabi as dry season in the materials and methods section also. 2 1 L127: Please add the explanation of “boro season”. plants11050622_perova 0 +Since the number of ILs is large, presenting phenotypic data for each IL will result in increasing the size of the main tables, hence data was earlier presented in supplementary tables. As suggested by the reviewers, we have revised the tables and presented the mean phenotypic data of BB, blast and drought screening in the main tables for each IL in parenthesis. Column on ‘no. of genes/QTL’ has been removed as suggested. Entry nos have been replaced with IL No as suggested. 2 1 L296-L302: the marker descriptions on main text cannot match the supplementary table S8. plants11050622_perova 0 +The present work is not essentially a backcross breeding program aimed at development of near isogenic lines. However, Krishna Hamsa was the common background into which several genes/QTL were targeted from multiple donors and considering the morphological similarity between 27 ILs and Krishna Hamsa, background selection was done retrospectively. BGS validated our observations on morphological similarity. The same has been discussed in the 5th para under ‘discussion’. Also results on BGS have been presented under subsection 2.3 of results with data on polymorphic markers for BGS in supplementary table S8. 2 1 The last paragraph of results is about background selection. plants11050622_perova 0 +“()” have been removed while mentioned the numbers of the ILs and sentences have been revised appropriately in the manuscript. 2 1 The ms is the result of an intensive and years-long work of breeding, that eventually pyramidized several resistance genes and QTLs for abiotic traits into an indian elite rice variety. plants11050622_perova 0 +The above mentioned lines have been checked and found either spelling mistakes or revision of sentences. Accordingly, corrections were made. 2 1 The data on bgs are not sufficiently presented in the text nor discussed. plants11050622_perova 0 +BLB has been replaced with BB throughout the manuscript. 2 1 The work is not unprecedented in the concept, but provides interesting breeding material for specific indian farmers, which is an important achievement and is correctly taken up by authorities and international research centers. plants11050622_perova 0 +Legends of figures and tables and text in the results section have been revised with explanation of acronyms as suggested. 2 1 For example on L203 “CD”, L211 “SES“, L228 “UBN“ and L332 “ICAR-IRRR”. plants11050622_perova 0 +The sentence here is required to maintain flow of the subsequent content. 2 1 The data on bgs are not sufficiently presented in the text nor discussed. plants11050622_perova 0 +Both lines explain our observations in different sets of ILs. Sentence at 351 explains susceptibility in ILs despite possessing the targeted gene/QTLs while sentence at 414 explains resistance in ILs despite the absence of targeted gene/QTLs. 2 1 However, this time it is just very beautiful work. plants11050622_perova 0 +The 85 ILs is a sum total of nine ILs marker positive to blast- R genes, nine ILs harbouring QTLs for drought tolerance and 67 ILs marker positive to BB-R genes mentioned at the beginning of 4th paragraph of discussion. As suggested, we have added in brief about the same at line 414. 2 1 L562: the section of statistical analysis should add more details. plants11050622_perova 0 +Yes, we agree that there were some typo and spelling mistakes in the manuscript. The manuscript has been thoroughly revised for the same. 2 1 However, this time it is just very beautiful work. plants11050622_perova 0 +Authors once again thank the reviewer for correct assessment of the basic purpose of the manuscript. Yes, this is truly an overview paper presenting the interesting observations from our study. The introgression scheme and phenotyping of various biotic traits and drought phenotyping have been described in detail under ‘Materials and Methods’ section. The metric data on yield traits was statistically analyzed and results of ANOVA, heritability and critical differences have been presented in the manuscript. Authors agree that it would be more inferential with chi square values. However, the crossing scheme was viewed holistically and data on each cross was not maintained separately as the present study aimed at selecting introgression lines from multiples crosses with multiple stress resistance/tolerance by pooling several genes and QTLs into a common background. Despite maintaining large base populations, plants per se were selected based on marker positivity for inter-crossing and selfing and further stringent phenotypic selection for the targeted traits. Hence, chi-square which is perfectly apt for population derived from biparental crosses is not used in our study. 2 1 It is also acknowledged that this paper is probably the first of many papers to emerge from the study. plants11050622_perova 0 +Authors feel greatly encouraged and motivated with the reviewer’s comments. 2 1 However, the authors have conducted a thorough literature review, undertaken a rigorous piece of data collection, and have generalized information accurately. plants11050622_perova 0 +‘=261%’ has been corrected to ‘+261%’ and typo error of ‘linkes’ corrected to ‘linked’ 2 1 I only recommend some minor revisions before acceptance. plants11050622_perova 0 +Added references appropriately at two places as suggested by the reviewer. 2 1 It would be interesting for the authors to provide more information about the research design and estimation methodologies, such as chi-square analysis of introgression lines, if possible for each crossed IL population. plants11050622_perova 0 +Explanation for boro season has been added. 2 1 of genes / QTLs, which is already represented in column 1) and add the most striking phenotypic data, when possible and relevant for discussion. plants11050622_perova 0 +Legends of the supplementary tables have been revised and inference of the table is given in foot note. 2 1 Please add some gel pictures of the foreground selection markers you used in order to visualize the genotyping results and showed the polymorphism of these markers on gel. plants11050622_perova 0 +Authors once again thank the reviewer for the valuable suggestion. More details on the statistical analysis have been added as suggested. 2 1 Indicate DFF = days to fifty percent flowering. plants11050622_perova 0 +Yes, significant means p-value. In the supplementary tables, expanded form of DFF is given as suggested. Treatments refers to introgression lines and check to control. For uniformity, we have changed the terminology to treatment instead of using IL or variety and check to control in all the revised supplementary tables and rephrased the legends accordingly. 2 1 On Supplementary table S3, similar questions as S2, please also explain. plants11050622_perova 0 +Similar to Supplementary Table S2, S3 has been revised 2 1 I only recommend some minor revisions before acceptance. plants11050622_perova 0 +CD is the critical difference at 1% and 5% level of significance (p-value) for testing of significant differences among the ILs. The details of CD calculation have been added in the materials and methods section as suggested. 2 1 The ms is the result of an intensive and years-long work of breeding, that eventually pyramidized several resistance genes and QTLs for abiotic traits into an indian elite rice variety. plants11050622_perova 0 +Supplementary table S5 is on CD and corrections have been addressed as suggested as at S. No 7. Supplementary table S6 have been modified by shifting data of BB and blast scores to main table. Each PC group is mentioned on top as sub heading at the start of each group. Each IL is presented only once in the entire table under separate PC groups. 2 1 Response: Thank you for the positive comments. plants11050622_perova 0 +Full names of the abbreviations have been added as suggested. 2 1 Dear Editor, Thank you for inviting me to review this manuscript. plants11050622_perova 0 +Subtitle has been added as suggested. 2 1 This paper described the multi-parents introgression assisted by molecular markers. plants11050622_perova 0 +A representative gel picture has been added as suggested. 2 1 L127: Please add the explanation of “boro season”. plants11050622_perova 0 +Table S8 represents polymorphic markers between pairs of parents including some common polymorphic markers. Hence the total number represented in the table S8 is not additive and not matching with the numbers given in the text. 124 is the total polymorphic markers excluding repetition. 27 ILs were selected based on their agro-morphological similarity with recurrent parent ‘Krishna Hamsa’ and evaluated for background recovery. The list of 27 ILs has been included in the revised manuscript as suggested. 2 1 The content is informative, however, the tables should be reorganized and the statistical methods description have to be improved. plants11050622_perova 0 +Mention of appendix at L602 is a typo error and has been removed 2 1 The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. plants11050622_perova 0 +We very much appreciate the contributions. 2 1 You have some values that are not included in this interval - maybe because of the outliers from the figures above that I recommend to exclude. su14095590_makarova 0 +An analysis of extreme values was carried out, using univariate and multivariate detection methods. The analysis resulted in the elimination of 34 univariate extreme values and 2 multivariate extreme values. All statistical analysis was repeated considering a database of 520 companies. 2 1 Point 4: Literature review: The lines from 70 to 82 could be summarized, and cut and paste in the Introduction section. su14095590_makarova 0 +Thank you for your suggestion. We researched more literature on the subject and adopted a more moderate perspective for assessing normality (|Sk|>2-3, |Ku|>7-10 and |KuMult|>10). As you mention, with the elimination of the extreme values, the skewness and kurtosis values improved significantly, approaching the range -1 to 1. 2 1 Some authors were added, but for me, this section demands an improvement to enhance the quality of the text, and to turn it into a scientific paper. su14095590_makarova 0 +The discussion section has been improved and future research recommendations have been added in the conclusions. 2 1 Point 8: Conclusion: I just see one objective, but in the first sentence the authors wrote ‘objectives’. su14095590_makarova 0 +The hypothesis was removed since, as mentioned, it doesn't state what we are trying to test in this study. Factor analysis involves the examination of interdependence relationship, so it shouldn’t be expressed as a hypothesis that establishes dependence relationships. 2 1 There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. su14095590_makarova 0 +Major changes have been made to the paper. We hope that this new version may deserve your recommendation for publication. 2 1 It definitely adds a value to the existed literature. su14095590_makarova 0 +The manuscript has been revised to improve grammar and english language. 4 1 We believe that the reviewers' suggestions have been very helpful in improving the manuscript. su14095590_makarova 0 +The discussion and conclusions sections have been improved (text in blue). 4 1 1 Response to Reviewer 4 Comments Point 1: The paper is well structured and presented in a very meaningful manner. su14095590_makarova 0 +Thanks for the comment. The conclusions section has been improved (text in blue). 4 1 There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. su14095590_makarova 0 +Thank you! 4 1 Point 4: Literature review: The lines from 70 to 82 could be summarized, and cut and paste in the Introduction section. su14095590_makarova 0 +We very much appreciate the comment. 2 1 I understood that the data is from the B Corporation website. su14095590_makarova 0 +The argument associated with studies [28] & [29] was added. 2 1 - workers values greater then 40, community greater than 58, environment 45, customers 46 (the bullets), in Fig 3 - values with global score greater than 130, in Fig. su14095590_makarova 0 +The words Table and Figure have all been revised to start with a capital letter. 2 1 The authors presented and analyzed the variables/areas of certification with many models, it is interesting and is a basis for analysis in the next section. su14095590_makarova 0 +Paragraph presented after Table 2 (page 7) has been moved to footnote. 2 1 I suggest the explanation given in the reviewers’ response about the decrease of companies in the sample be available in the text (“The reduction in the number of companies was based on the analysis of the database and information collected from B Lab that allowed us to see that there was a change in the measurement model used in B Corp certification during the period January 2017 and March 2021. su14095590_makarova 0 +• The (***) have been replaced by the p-values (<0.001) in Table - B Impact Assessment - Regression Weights (original model) (current Table 6). 2 1 Thus, to ensure the 3 consistency of the database and the statistical analysis subsequently performed, we reduced the database to a recent period in which the same measurement model was used.” Results: I didn’t see ads in Cronbach’s alpha analysis (the text is the same as the first version, see lines 457-486 – new version and compare with an old version from line 405- 433), though there are some adjustments in their numeric results. su14095590_makarova 0 +Future research recommendations have been added to the conclusions. 2 1 I suggest the explanation given in the reviewers’ response about the decrease of companies in the sample be available in the text (“The reduction in the number of companies was based on the analysis of the database and information collected from B Lab that allowed us to see that there was a change in the measurement model used in B Corp certification during the period January 2017 and March 2021. su14095590_makarova 0 +Thank you. 2 1 Point 3: The text has some improvements, but there are some points that still demand more attention. su14095590_makarova 0 +Thank you for the suggestion. The title has been clarified in line with the main objective. 2 1 Point 3: In lines 391-395 I would prefer an Sk and Ku between -1 and 1. su14095590_makarova 0 +The results were improved and the paper's contribution was added. 2 1 Point 2: There are minor corrections to be considered. su14095590_makarova 0 +The introduction has been improved, including a better explaination of B Impact Assessment. The use of confirmatory factor analysis has been explained. The aim of the paper was revised in the abstract to be aligned with the one presented in the introduction. 2 1 What is its contribution to the structure of a model using Confirmatory Analysis? su14095590_makarova 0 +Lines 70 to 82 have been revised and included in the introduction. Lines 90 to 103 have been revised and decided to be kept in the literature review as they express arguments from important scientific research ( S. Poponi, A. Colantoni, S. R. S. Cividino, and E. M. Mosconi, “The Stakeholders’ perspective within the B corp certification for a circular approach,” Sustain., vol. 11, no. 6, pp. 1–15, 2019, doi: 10.3390/su11061584. / T. De Mendonca and Y. Zhou, “What does targeting ecological sustainability mean for company financial performance?,” Bus. Strateg. Environ., vol. 28, no. 8, pp. 1583–1593, 2019, doi: 10.1002/bse.2334. / C. Putnam Rankin and T. L. Matthews, “Patterns of B Corps Certification: The Role of Institutional, Economic, and Political Resources,” Societies, vol. 10, no. 3, p. 72, 2020, doi: 10.3390/soc10030072.). The literature review was enhanced with scientific information in the fields of sustainability and certification, and, B Lab certification and sustainability. 2 1 The manuscript has been revised to improve grammar and english language. su14095590_makarova 0 +The economic dimension has been added in the former lines 180 and 181. We clarify that figure 1 is original and was created by the authors. Regarding the data, we confirm that it was taken from the official website, during the period between March and May 2021. The link provided (https://bcorporation.eu/directory) was the one used. In the meantime, the site has been changed and the directory of certified companies can be found in another link. Table 2 has been eliminated. To avoid the repetition of information in Table 2 and the paragraph after, we followed the recommendations of another reviewer by placing the paragraph as a footnote. The reduction in the number of companies was based on the analysis of the database and information collected from B Lab that allowed us to see that there was a change in the measurement model used in B Corp certification during the period January 2017 and March 2021. Thus, to ensure the 3 consistency of the database and the statistical analysis subsequently performed, we reduced the database to a recent period in which the same measurement model was used. Finally, the hypothesis was removed since, as suggested by another reviewer, it doesn't state what we are trying to test in this study. Factor analysis involves the examination of interdependence relationship, so it shouldn’t be expressed as a hypothesis that establishes dependence relationships. 2 1 1 Response to Reviewer 1 Comments Point 1: Thank you for giving the opportunity to read such an interesting paper. su14095590_makarova 0 +"We have replaced the word ""indicator"" with ""aspect"" to eliminate possible confusion with the 5 indicators in the B Impact Assessment Model (Figure 6). The text has been completely revised and the word 'indices' has been used as the standard. The word ‘chapter’ has been replaced by ‘section’. Finally, we are thankful for the good appreciation to the many models studied in our research." 2 1 First, it should be stated prior to the methods section. su14095590_makarova 0 +The topic is “B Corp certification”. The text has been revised and the source has been added (E. Diez-Busto, L. Sanchez-Ruiz, and A. Fernandez-Laviada, “The b corp movement: A systematic literature review,” Sustain., vol. 13, no. 5, pp. 1–17, 2021, doi: 10.3390/su13052508.). Hypothesis 1 has been removed with the justification provided in response 5. Information was added on Cronbach’s Alpha and its impact on the need for B Impact Assessment improvement. 2 1 1 Response to Reviewer 3 Comments Point 1: The paper is interesting; however, it is not clear what the authors are trying to achieve with this study. su14095590_makarova 0 +Thank you for the suggestions. The word was changed to “objective”. The discussion section has been improved in line with the suggestions made in the conclusion. 2 1 No any future research recommendations have been suggested by the respected authors. su14095590_makarova 0 +The manuscript has been revised. The literature review has been improved, and new references have been added (text in blue). 4 1 In the first round, I observed and commented that the link in line 191 wasn’t working. su14095590_makarova 0 +The method section has been improved (text in blue). 4 1 The authors could use a standard for a plural of index word, ‘indices’ (345) or ‘indexes’ (362). su14095590_makarova 0 +We believe that the reviewers' suggestions have been very helpful in improving the manuscript. Thank you for the comment. The manuscript has been entirely revised. 4 1 In line 384 the authors should substitute ‘chapter’ for ‘section’. su14095590_makarova 0 +We added more coherent theoretical arguments to the discussion based on the most recently published relevant academic papers on the topic (lines 125-133, 153-158, 442-452). The incorporated studies include Yarram and Adapa (2021), Boukattaya and Omri (2021), Shakil (2021), Wang, Wilson & Li, (2021), Cordeiro et al 2020, Birindelli, et al. (2019), and Nuber & Velte (2021). In total, the list of references increased from 21 to 36. The details of these studies and the logic behind their inclusion are explained in the text (pages 3 and 4). For the quantitative papers, our guiding line is the inclusion of papers proposing a reliable strategy to address the problem of endogeneity characterizing virtually all studies dealing with gender diversity. In a nutshell, gender diversity and firms’ performances (be they financial, ESG or environmental) have reverse causality. More gender-diverse boards are found to improve firms’ performances, and at the same time, better performing firms are more attractive to females. Any study incorporating these two variables would suffer from endogeneity. Therefore, inference and results are biased. Finding an instrument for gender diversity becomes a concern of first importance. The task is challenging as all potential candidates for being a suitable instrument should be already part of the regression equation. So far, the literature has not found an instrument unanimously agreed upon. This is the reason for which our selection of papers is rather limited. We focused on those papers with a choice of instrumental variables that are well explained and papers that ‘’go around’’ the problem by making use of a method that does not rely on external instruments. This includes papers using difference-GMM or system-GMM estimators. Their principal advantage is the use of internal instruments instead of external ones. Indeed, the instruments chosen are difference and the level of the covariates themselves. There are only a few of these studies available, including ours. This again explains the relatively restricted number of references we are considering. 2 1 The related theory posits that females’ attitude when facing uncertainty is different from males. su14127346_perova 0 +Initially, we opted for integrating the theoretical background disseminated throughout the text to connect to the findings of related papers and to avoid redundancy and repetition. Changes that we incorporated in response to this comment improve the overall theoretical framework of the paper, including concepts, definitions and links to relevant literature. We also articulated theoretical assumptions and added a comprehensive discussion of the observed phenomena. Specifically, we added critical mass theory discussion in the literature review section (lines 125-132). We added interpretation of corresponding results in the findings and discussions section (lines 445-452) and the conclusion section (lines 482-503). These changes in addition to the existing discussions of theories and concepts significantly improve the theoretical background of the paper. 2 1 We revise and elaborate on the explanation and interpretation of the results. su14127346_perova 0 +We also emphasize the policy implications of these findings (lines 453-462, 497-503). To better reflect the policy implications of the study, we incorporate changes that are diffuse through the text. In particular, we argue that promoting gender diversity cannot deliver its full potential, and may even lead to adverse results unless it is accompanied by measures that mitigate political and economic uncertainty. These measures would create an enabling environment both for households and entrepreneurs. Such measures should increase agents’ confidence, dump their willingness to invest and expand the activity by reducing their aversion to risk. The accompanying measures should primarily target building and strengthening institutions to unlock this potential. Institutions are a defence against uncertainty. They contribute to anchoring economic agents’ expectations and stabilize the economy. We also elaborate on the finding of the critical mass theory. This result suggests that a very effective way to improve environmental quality and mitigate the adverse effects of economic activities is to encourage gender diversity in corporate boards in countries with low uncertainty where we find a higher impact on firms’ environmental performances. In these countries, the margin for progress is large and the effect of improving gender diversity in corporate boards materializes more easily and at lower costs, as these countries are far from their efficiency frontiers (lines 445-461 and 482-503). 2 1 "8- Lines 330 and onwards are presenting conclusions that are not warranted by the results and the english is a bit strange (what do you mean by ""households' anxiety""?)." su14127346_perova 0 +We addressed your suggestion to improve arguments and discussion of findings by revising existing and adding new paragraphs better explaining regression coefficients that demonstrate how political and economic uncertainty shapes the relationship between corporate board gender diversity and firms’ environmental performance. (Lines 379-389). Furthermore, we added supporting arguments disseminated across the text (particularly in lines 348-361, lines 379-389, etc). These relate our finding to theory. We focus here on the attitude towards risk and uncertainties. Women on corporate boards tend to be more risk-averse and lean more toward conservatism in uncertain environments. Therefore, the more females there are on corporate boards, the higher their weight in the board decisions would be, and by the same token, the higher the effect of uncertainty on firms’ decisions. Moreover, we also relate our findings to the critical mass theory, suggesting that the impact of gender diversity on the environmental performances of firms materializes only when a critical mass weight of females is realized in corporate boards (Konrad et al. 2008, Torchia et al. 2011, Schwartz-Ziv, 2017- page 12, lines 445-451). 2 1 Similar problems might exist for a negative tobin's Q. su14127346_perova 0 +Absolutely. Changed accordingly (line 160). 2 1 The reviewer kindly gives details of the elements that can be improved in the field ‘’Comments and Suggestion for Authors’’. su14127346_perova 0 +We answered this comment along different dimensions. We revise and elaborate on the explanation and interpretation of the results. We provide further explanations on the ways political and economic uncertainty shapes the relationship between corporate board gender diversity and firms’ environmental performance. We also emphasize the policy implications of these findings (lines 453-461, 487-496). In addition, we add more theoretical arguments to the discussion based on the most recently published academic papers on the topic. (Lines 421-452) “ 2 1 We take this review as a valuable opportunity to foster the quality of the paper. su14127346_perova 0 +The related theory posits that females’ attitude when facing uncertainty is different from males. They tend to exhibit a strong inclination to wait until the uncertainty is resolved before making major business decisions. To address this comment, we added supporting arguments disseminated across the text (particularly in lines 348-361, lines 421-428, etc). These explain the finding you are referring to by attitude towards risk and uncertainties. Women on corporate boards tend to be more risk-averse and lean more toward conservatism in an uncertain environment. Therefore, the more females there are on corporate boards, the higher would be their weight in the board decisions, and by the same token, the higher would be the effect of uncertainty on firms’ decisions. 2 1 Author Response Dear Reviewer, Many thanks for your comments and suggestions. su14127346_perova 0 +The literature on the relationship between gender diversity and environmental performances of firms that addresses dynamic endogeneity is rather limited. We mention Gaio and Gonçalves (2022), Lu and Herremans (2019), Kassini et al (2016), Silla, et al (2016) that opt for a dynamic modelling using a System-GMM estimator. This estimator is particularly suitable to panels with large number of individual and few time periods, which the case for our paper. Moreover, it accommodates situations where the independent variable changes slowly (Antoniou et al., 2008). To keep a good flow in the text, we only mention these papers in the introduction section. We elaborate further on them in the literature review section. We describe their main purpose and explain how our analysis departs from them. 2 1 Similar problems stem from the following paragraphs discussing the results. su14127346_perova 0 +Thanks for the Suggestion. We highlighted the research hypothesis by moving it the introduction. We also added another hypothesis. The first relates to the very existence of a relationship between gender diversity on corporate boards and firms’ performances. The second, deals with the intensity and shape of this relationship. We believe, this adds a deal of clarity to the text and purpose of the paper. 2 1 As it stands, the paper offers little insight into the reasoning behind their hypothesis. su14127346_perova 0 +We reviewed all the text and changed wording in different parts of the text. 2 1 It would be useful if the authors provided some speculative thoughts on the finding that the slope of the GenDiv variable is negative in highly uncertain countries on the firm's environmental performance (Figure 3 (c) red line). su14127346_perova 0 +We initially meant, among all these papers, there is one that… We rephrased this sentence and reviewed all the text. We edited sentences when needed. 2 1 Your review truly helped improve further the paper. su14127346_perova 0 +In our initial submission, we used winsorized data for all our econometric analysis. However, we, inadvertently, displayed summary statistics (Table 2) for raw data, i.e., before winsorizing. We should have reported only winsorized summary statistics. This is precisely what we do in this revised version of the paper. The reason for winsorizing data (beyond its advantage of having regular statistical distribution) was that we initially have detected outliers. Further investigation revealed that one company (RIC: OBE.TO; CompName: Obsidian Energy Ltd) is responsible for these outliers. The company had presumably reported wrong values in FY-12, where PP&E was higher than Total Assets (see table below from Refinitiv Eikon). We have reported this case to Refinitiv (Case number: 11297339) and our doubts were confirmed (See their response below). Refinitiv Eikon replaced old value of PP&E (27834189009) with a correct value (10788172656). In order to avoid similar mistakes, we opted for winsorizing data and avoid outliers. Similarly, only one company had negative Tobins’ Q in 2017 (RIC: ELR.TO ; company name: Eastern Platinum Ltd), which was a reporting typo as well. However, our analysis is not affected by these outliers which are removed after winsorizing all the variables. In this revised version of the paper, we replace the table of summary statistics with the one based on winsorized variables. 2 1 5- Please revise your data: your max tangibility is over 2 (which means that Net PP&E, a subset of Assets, is 2 times those same Assets - this should be a typo. su14127346_perova 0 +The sentence “The global average of corporate boards’ gender diversity for all the sectors during 2008-2018 was about 13.5%” is correct as it is calculated based on all industries (5120 firms in total). However, since we are focusing on “Mining, Quarrying, and Oil and Gas Extraction Industry”, it makes more sense indeed to report the value for that particular sector. Therefore, we update the text as follows: “The average of corporate boards’ gender diversity for Mining, Quarrying, and Oil and Gas Extraction Industry during 2008-2018 was about 9.6%”. 2 1 The reviewer kindly gives details of the elements that can be improved in the field ‘’Comments and Suggestion for Authors’’. su14127346_perova 0 +This is an explanation of the following sentence in our article: “To avoid bias and inconsistency that might be caused by instruments proliferation, we collapse the instruments matrix.” We are using longer lags of the dependent variable as additional instruments. Intuitively, there is a trade-off, on one hand, using longer lags gives more information and improves efficiency, but on the other hand sample gets smaller (as it is the case in standard 2SLS models). GMM is a way around this trade-off between lag length and sample length. However, implementation of System-GMM is not exempt from weaknesses. With the instruments count being quadratic in the time dimension, the variance matrix of the moments can be very large. Estimating its elements may be problematic in particular in a finite sample lacking the adequate amount of information. This finite sample bias can weaken Hansen J-test and overstate its p-value and therefore generate suspicious high pass rate of instruments validity. The problem is known as instruments proliferation (Roodman 2009). To avoid bias and inconsistency due to instruments proliferation, we limit the number of instruments used and collapse the instrument matrix which prevents the model from being over-fitted. 2 1 They tend to exhibit a strong inclination to wait until the uncertainty is resolved before making major business decisions. su14127346_perova 0 +We revised the concerned section and rewrote the text in order to improve on clarity. The revised text reads as follows: Greater gender diversity for a firm located in a country with high political and economic uncertainty would lower the firm’s environmental performance (0.616-0.853=-0.237). More precisely, a 1 percentage point increase in GenDiv in a country with high political and economic uncertainty 5 leads to an average decline of 0.24% in the firm’s environmental performance in the following year. This suggests that the previous finding on the positive relationship between more gender-diverse boards and a firms’ environmental performances tends to be conditional on reduced policy and economic uncertainty. More gender-diverse corporate boards would not lead to better environmental performances of firms in countries with higher uncertainty (higher WUI score). The rational for this result stems from the idea that uncertainty adversely affects the enabling environment of an economy. This may induce financial outcomes for firms that are so negative and diffuse that they could hardly be balanced by the benefits brought with more gender- diverse boards (Bloom 2014, Atsu and Adams 2021). Indeed, uncertainty hampers household confidence and makes it difficult for businesses to plan for the future. The lack of visibility for future economic and political prospects undermines agents’ confidence and further raises their aversion to risk. In terms of policy, our finding suggests that promoting gender diversity on corporate boards should be accompanied by measures that reduce political and economic uncertainty. This is particularly relevant for countries vulnerable to shocks whether internal or external (Covid-19, war, conflicts, trade tensions, etc.). These can further exacerbate agents’ risk-aversion and deteriorate the market ability to create a sound economic and political environment in which agents interact effectively. In order to assess which level of the country’s uncertainty induces the negative effect of gender diversity, we introduce interaction terms with WUI quartile dummies (again, with two specifications, allowing slope and then the both slope and intercept to change). The findings are summarized in Table 4 (columns 3 and 4). They suggest that the interaction term with only the last quartile is statistically significant (at the 10% level), indicating that the impact of GenDiv on environmental performance is mostly driven by highly uncertain countries (those in the last quartile of the distribution). Countries below the 75th percentile of the WUI do not exhibit statistically significant differences among each other. We investigate this finding further by examining, for different gender diversity levels, (a) the intensity of the relationship across high and low uncertainty levels and (b) the marginal impact of a country’s uncertainty status on the firm’s environmental performance (Figure 3). We find that in countries with a high (above median) uncertainty level, the environmental performances of firms are significantly lower than in countries with low uncertainty, and this impact is magnified as gender diversity in corporate boards increases. The finding is robust for both specifications, with fixed and without fixed intercepts. Higher gender diversity in countries with lower uncertainty increases a firm’s environmental performance, whereas, in countries with high uncertainty, an increase in female board members has a negligible positive impact (Figure 3a) or even a negative impact (Figure 3c). The gap in environmental performance between countries with high versus low uncertainty increases as gender diversity in corporate boards increases. A potential explanation of this finding refers to the exacerbating effects of political and economic uncertainties on entrepreneurs’ risk-aversion. This, in turn, discourages in-vestments in costly abatements technologies and environmental-friendly processes. More generally, increased risk aversion reduces investments and activities whose returns accrue more in a long-run. These include research and development efforts, and particularly 6 environmental-led activities, which are seen as secondary in firms’ scale of priorities. Ultimately, this would put pressure on firms’ behavior and worsen their environmental performances (Bloom, 20149; Atsu and Adams, 202137). The arguments above provides a rationale for the worsened environmental performances of firms in response to higher uncertainties, and explains the gap in effects for firms across countries of different uncertainty levels. However, this does not address the potential reasons behind the widening of this gap for higher gender diversity levels. One potential explanation of this result relates to the particular attitude of women toward risk. Females on boards tend to exhibit more risk aversion compared to their male peers. They tend to show more patience and are typically more willing to look for professional guidance when facing uncertainty (Liu, 201838). Females on boards tend to be more inclined to wait until uncertainty is resolved before making major business decisions. Therefore, the more females on corporate boards, the greater the weight of their decisions (i.e., the higher would be the effect of uncertainty in firms’ decisions). This finding begs the question of whether the differential between countries with high versus low uncertainly levels is statistically significant for increasing gender diversity levels. Figure 3 (b and d) trace the magnitude of the gap between the low and high uncertainty scores. It states that this gap is increasing, in absolute value, and is statistically significant at the 95% level for all values of gender diversity (for gender diversity levels larger than 10%, for both specification Figures 3b and 3d). This threshold value points to a standard and very important result in the literature. This refers to the critical mass theory, by which the impact of gender diversity on the environmental performance of firms materializes only when a critical mass weight of females is realized in corporate boards (Konrad et al., 200839; Torchia et al., 201140; Schwartz-Ziv, 201741; among others). This suggests that an effective way to improve environmental quality and mitigate the adverse effects of economic activities is to encourage gender diversity in corporate boards in countries with low uncertainty where we find a higher impact on the firms’ environmental performances. In terms of policy, our findings suggest that promoting gender diversity cannot reach full potential, and may even lead to adverse results unless accompanied by measures that mitigate political and economic uncertainty. These measures would create an enabling environment both for households and entrepreneurs. These reduce their aversion to risk, which increases their confidence and willingness to invest. To unlock this potential, a country should implement accompanying measures that promote and strengthen stable institutions – as a defense against uncertainty. They contribute to anchoring economic agents’ expectations, and stabilize the economy. 2 1 We take this review as a valuable opportunity to foster the quality of the paper. su14127346_perova 0 +the inoculation points were labeled with the red arrows in Figure 1 as suggested. 2 1 The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. toxins14060409_perova 0 +Sorry for carelessness. We corrected it as suggested. (Pag.4 Line 157) Point 3: Line 143: “PPSD-premature spike death” should be “PPSD-proportion of premature spike death”. 2 1 Studies show that infection timing has effect on disease severity and DON distribution in wheat spikes, and a late infection is an important factor for high DON levels found in healthy-looking kernels. toxins14060409_perova 0 +We revised the expression in the footnote of Table 1. (Pag.4 Line 158) Point 4: Lines 168 - 169: Should it be that DON content of most lines without Fhb1 exceeded 1000 µg/kg under UBFI? 2 1 The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. toxins14060409_perova 0 +we revised the sentence as “DON content of most lines without Fhb1 exceeded 1000 μg∙kg-1 under UBFI method (Figure 2), with the highest reaching 4224.38 μg∙kg-1 (Table S1)”. (Pag.5 Line 184-186) Point 5: Lines 411 & 413: “PPSB” should be “PPSD”. 2 1 While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. toxins14060409_perova 0 +We corrected it. (Pag.11 Line 441 & 443) Point 6: Table S1: “PPSD - premature spike death” in the footnote should be “PPSD - proportion of premature spike death”. 2 1 Studies show that infection timing has effect on disease severity and DON distribution in wheat spikes, and a late infection is an important factor for high DON levels found in healthy-looking kernels. toxins14060409_perova 0 +We revised the expression in the footnote of Table S1. 2 1 I would like to recommend its acceptance for publication. toxins14060409_perova 0 +Thanks. We revised the annotations in Table S1. 2 1 Point 3: Identity of the strain used for infection should be confirmed: a multilocus species characterisation is needed to confirm the species of the strain or a reference to a publication where the strain was described and appropriately characterised. toxins14060409_perova 0 +We agree with the reviewer’s comments and make Figure S4 as Figure 4 in this revised version. 2 1 I would like to recommend its acceptance for publication. toxins14060409_perova 0 +We marked the inoculation sites with red arrows in Figure 1. 2 1 While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. toxins14060409_perova 0 +We added more details about the strain and cited the following paper. (Pag.10 Line 402-403) Zhang, Y.; Li, A.; Zhu, S.; Li, L.; He, X.; Sun, Z.; Li, T. Basal Rachis Internode Injection (BRII): A novel inoculation method to evaluate wheat resistance to Fusarium head blight. Phytopathology, 2021, 111, 1670-1674, doi:10.1094/PHYTO-11-20-0488-R. Point 4: Mycotoxin data analysis should be provided (I guess is policy of mdpi to make raw data available together with the publication) Response 4: Thanks! 2 1 Studies show that infection timing has effect on disease severity and DON distribution in wheat spikes, and a late infection is an important factor for high DON levels found in healthy-looking kernels. toxins14060409_perova 0 +Thanks! We uploaded the raw mycotoxin data as suggested. 2 1 1 Response to Reviewer 2 Comments Point 1: I would suggest to avoid citing supplementary figures at the beginning of the chapter. toxins14060409_perova 0 +The innovation of this research has been clarified in the abstract, the introduction, and the conclusion. 2 1 In case of showing only one replicate explain why only one is shown and include the standard deviations. w14030367_makarova 0 +Three references have been cited. Please see lines 40-41 in the revised manuscript. 2 1 Please consider these suggestions as listed below. w14030367_makarova 0 +Thanks very much for the reviewer. The conclusion has been revised according to the reviewer’s suggestion. The added paragraph in the revised manuscript is as follow: To sum up, the results show that the proposed BAC-UF system can be effective in the treatment of river water polluted by PPCPs, conventional organic pollutants and ammonia nitrogen. 2 1 Author Response Thank you very much for your support and help. w14030367_makarova 0 +Thanks for the reviewer’s suggestion. The conclusion has been revised and integrated into two paragraphs. The first paragraph mainly includes important findings, and the second paragraph mainly includes the outlook for the future in this field. 2 1 Although many pilot-scale setups were used to treat secondary wastewater effluent for water reclamation, this type of raw water quality was different from the river water, causing the different potential of biofilm growing. w14030367_makarova 0 +The salinity concentrations in the samples have been added to Table 1 in the revised manuscript. 2 1 Point 5: Please add t-test results in Table 1 for each parameter to understand the significant differences. w14030367_makarova 0 +We agree with the suggestion and comments of the reviewer. All comments have been revised one by one, and the modifications are highlighted in yellow in the marked revised manuscript. Thanks again for your patient review. 2 1 Title: Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface water. w14030367_makarova 0 +Thanks for the reviewer’s helpful suggestion. The objective statement has been added to the abstract to support the seriousness of the problem, and the revised sentences are as follows: Biological activated carbon (BAC) biofilter coupling ultrafiltration (UF) is a promising process for the treatment of river water contaminated by pharmaceutical and personal care products (PPCPs). However, the pilot-scale study should be conducted to reveal the long-term removal performance and the respective contributions of BAC and UF. 2 1 Response to Reviewer 1 Comments Point 1: The innovation of this research needs to be better explored. w14030367_makarova 0 +We agree with the suggestion of this reviewer. The two-stage biofilms located in the activated carbon column and on the UF membrane synergistically, can be conducive to the removal performances. However, the mechanisms of the two-stage biofilm, such as bacterial and metazoan communities, membrane fouling and dissolved oxygen transfer, should be further investigated to enhance the removal efficiency and stability of this system. The research gap has been added in the Conclusion and is as follow: To sum up, the results show that the proposed BAC-UF system can be effective in the treatment of river water polluted by PPCPs, conventional organic pollutants and ammonia nitrogen. Besides, the results of this analysis can have significant implications for the conven-tional UF operation procedure and the ozone-activated carbon process, providing a simple decentralized approach to drinking water treatment for the areas where source water is contaminated with PPCPs. 2 1 Response to Reviewer 4 Comments Point 1: Authors should avoid abbreviations in the title and the abstract. w14030367_makarova 0 +Thanks for the reviewer’s comment. The introduction has been revised carefully, including using up-to-date references. For example, the outdated references have been removed. Meanwhile, the articles published within the last two years were added, such as (the Reference2 Yu et al., 2020) and (the Reference21 Tang et al., 2018). 2 1 Point 8: Line 161-176: Please delete the name of medicinal compounds not used for this study. w14030367_makarova 0 +The reference has been cited. Please see line 38 in the revised manuscript. 2 1 These 38 PPCPs generally present in waters at trace concentrations, ranging from several ng/L to 39 thousands μg/L [4]. w14030367_makarova 0 +The BAC biofilter can remove the PPCPs, and then the following UF can reject micro-organisms and particles flowing out from the biofilter to ensure the quality of drinking water. The above coupling process makes up for the defects concerning respective operations of the BAC biofilter and UF. Although many pilot-scale setups were used to treat secondary wastewater effluent for water reclamation, this type of raw water quality was different from the river water, causing the different potential of biofilm growing. As far as we investigated, the lack of enough attention to long-term pilot study exists. Therefore, in this study, a BAC-UF system was carried out for several months with pilot scale to access the long-term removal performances and the respective contributions of BAC and UF. The relevant content has been supplemented and revised in the abstract to highlight the innovative points. 2 1 Response 7: Thank you very much for your kind reminder. w14030367_makarova 0 +Biological activated carbon (BAC) combined the adsorption and biologic degradation consuming low power energy and chemicals without concern of DBPs production as well as no frequent updates for activated carbon media. The BAC biofilter can remove the PPCPs pollutants, and then the followed UF can reject microorganisms and particles flowing out from the biofilter to ensure the quality of drinking water. Thus, the BAC-UF process makes up for the defects of the respective operations of BAC biofilter and UF. Although many pilot-scale setups were used to treat secondary wastewater effluent for water reclamation, this type of raw water quality was different from the river water, causing the potential of biofilm growing differently. As far as we investigated, the lack of enough attention to long-term pilot study is present. Therefore, in this study, a BAC-UF system was carried out for several months with a pilot scale. 2 1 The results showed that the BAC unit reduced CODMn 19 with 35.45%, while the BAC-UF further decreased to 56.00%. w14030367_makarova 0 +The two references have been cited. Please see the lines 58. 2 1 Cite the following references: Panagopoulos, A. w14030367_makarova 0 +T Thanks very much for this comment. The introduction has been improved for better reading. 2 1 Two native English-speaking colleagues help us verify the manuscript. w14030367_makarova 0 +Two PPCP mistakes have been revised. The abbreviation of chemical oxygen demand in previous version has been corrected to CODMn. The unnecessary abbreviations have been also corrected in the abstract. 2 1 Response 17: We are so sorry to make reviewer’s reading uncomfortable. w14030367_makarova 0 +The added paragraph is as follows: Potassium permanganate, H2SO4, potassium sodium tartrate tetrahydrate, Nessler’s reagent and NaOH were purchased from a commercial company and certified as AR purity (Guangzhou Chemical Reagent Factory, Guangzhou, China), while PPCP standards were provided by three companies. Sulfamethoxazole (SMX), Sulfadoxine (SD), Sulfachloropyridazine (SCP), Sulfamethoxypyridazine (SMP), Sulfaquinoxaline (SQX), Sulfathiazole (STZ), Doxycycline (DOX), Erythromycin (EM), Anhydroerythromycin (EA), Roxithromycin (ROX), Penicillin-G (PEN G), Clarithromycin (CAM), Norfloxacin (NOR), Oxociprofloxacin (OFL), Enrofloxacin (EFL), Flumequine (FQ), Acetaminophen (APAP), Diclofenac sodium (DCF), Naproxen (NAP), Indomethacine (IND), Metoprolol (METO), Propranolol (), Atenolol (ATL), Primidone (PRM), Carbamazepine (CMZ), and Sulpiride (SP) were obtained from the Dr. Ehrenstorfer Company in Germany. Furthermore, Sulfadimidine (SM2), Sulfadiazine (SDZ), Sulfapyridine (SP), Sulfamonomethoxine (SMM), Tetracycline (TC), Ofloxacin (OFL), Amoxicillin (AM), Dimetridazole (DMZ), Trimethoprim (TMP) were bought from the National Institute of Metrology in China, whereas Oxytetracycline (OTC), Caffeine (CF), and Diethyltoluamide (DEET) were acquired from the Toronto Research Chemicals Company in Canada. 2 1 Point 8: Line 161-176: Please delete the name of medicinal compounds not used for this study. w14030367_makarova 0 +These three GAC-UF systems were operated in parallel. Samples of the feedwater and effluent from three systems were taken simultaneously and measured once. The standard deviation was obtained by the detection over the full period of the experiment. 2 1 Point 18: Reference formatting need carefully revision. w14030367_makarova 0 +The figure is used as the only pattern in the revised manuscript. 2 1 Point 5: The novelty of the work must be clearly addressed and discussed, compare previous research with existing research findings and highlight novelty. w14030367_makarova 0 +The front sizes in the figure 1 have been increased. The quality of the figure 1 has been also improved. 2 1 Response 8: Thanks very much for this comment. w14030367_makarova 0 +The style for units has been revised and unified. 2 1 Response 6: Thanks very much for this comment. w14030367_makarova 0 +The comparison of previous research with existing research findings was added in the final part of the results and discussion. The added paragraph is as follows: PPCPs risks have been posing severe challenges to the safety of drinking water supply in rural areas due to the absence of the process with simple operation and maintenance as well as reliable performance. In this study, BAC coupling gravi-ty-driven UF was performed continuously, and the rejection performance of mem-brane filtration and BAC filtration both showed barriers for the conventional pollu-tants and PPCPs. Furthermore, this study indicated the respective contributions of BAC and UF, showing the role of the two-stage biofilm. Previous works involving BAC generally combined the ozonation with the BAC filter for treating the contaminants of emerging concern, eliminating a majority of PPCPs by more than 90% [34]. However, the regulation and maintenance of machines for ozone products are complicated, and the disinfection by-products will be newly generated in the effluent, which is incon-venient to use in rural areas [35]. In general, coagulation, filtration and single BAC units worked inefficiently and removed the detected PPCPs by less than 50%, as they were not hydrophobic [34, 36]. Hybrid membrane processes such as inline dosing of powdered activated carbon (PAC) prior to UF have already shown promising potential for the abatement of PPCPs; however, the inline dosing PAC is infeasible in rural areas [37]. In this study, the BAC prior to UF enhanced the biological activity by forming a two-stage biofilm system. Therefore, the integrated BAC-UF process can be considered as an economically and technically feasible approach to the decentralized and emer-gency drinking water treatment. 2 1 Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. w14030367_makarova 0 +The conclusion has been modified as suggested by reviewers. Please see lines 325-350 in the revised manuscript. 2 1 In case of showing only one replicate explain why only one is shown and include the standard deviations. w14030367_makarova 0 +Two native English-speaking colleagues help us verify the manuscript. Hope the revised manuscript would be more satisfactory. We are so sorry to make reviewer’s reading uncomfortable. We have used an English Language Editing service to correct the grammatical and spelling errors and to make the expressions conform to correct scientific English (the Language Editing Certification is attached below). 2 1 Nev- 21 ertheless, BAC and UF were both related to the removal effects of NH4+-N, NO2−-N and NO3−-N. 22 Importantly, the BAC-UF process showed high efficiency in the removal PPCPs micropollutants 23 and the average removal of total PPCPs reached 47.84%, especially Anhydroerythromycin, Sul- 24 fachloropyridazine, Sulfadiazine, Trimethoprim, and Caffeine. w14030367_makarova 0 +We agree with the reviewer. The reference formatting has been corrected. Thanks very much for the patient review again. 2 1 Besides, the t-test was used and proved the significant difference between BAC-Effluent and BAC/UF-effluent. w14030367_makarova 0 +Thank you very much for your support and help. 4 1 “The combined process with ultrafiltration may be another promising choice, featuring a comparable removing performance as the nanofiltration and low operational cost”. w14030367_makarova 0 +Full names of BAC, UF, and PPCPs are used in the title and the abstract to show the results briefly. As for NH4+-N, NO2−-N, and NO3—N, the full names have been used instead of abbreviations in the abstract. 2 1 The reviewer suggests statistical analysis using a t-test (Raw water- BAC-Effluent and Raw water – BAC/UF-effluent). w14030367_makarova 0 +The title has been revised to river water. 2 1 The results showed that the BAC unit reduced CODMn 19 with 35.45%, while the BAC-UF further decreased to 56.00%. w14030367_makarova 0 +The references format has been corrected. 2 1 I am pleased to send you major level comments, there are some serious flaws which need to be corrected before publication. w14030367_makarova 0 +We are very sorry for the confusion caused to the reviewers, the sentences have been revised from the words and Grammarly. The revised sentences are shown below: Ultrafiltration (UF) as an emerging alternative technology to conventional water treatment processes, has been widely used to remove pollutants such as particles, col-loids, bacteria, and viruses, thus reducing the risk of water-borne diseases [10]. However, in the case of the PPCPs with a small molecular weight (typically < 600 Da), UF membranes also cannot effectively reject these PPCPs, but nanofiltration and reverse osmosis are able to remove these PPCPs based on the thin-film composite [11, 12]. 2 1 Authors may provide data in the supporting information file. w14030367_makarova 0 +The t-test results have been added in the revised Table1. 2 1 Overall, the article structure and content are suitable for the WATER journal. w14030367_makarova 0 +"The statistical t-test was evaluated for Figure 4, which was added in the text of ""3.2. Removal of nitrogen"" Section." 2 1 After the process, the water quality was analyzed including CODMn, UV254, NH4+-N, and PPCPs. w14030367_makarova 0 +The t-test results have been added to the revised Table2. The concentration of Erythromycin was generally varied between 1047.14 ng L−1 and 2037.72 ng L−1. 2 1 ##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). w14030367_makarova 0 +Some symbols were overlapped in Figure 5h. The symbols near 85 days have been entirely shown by correcting Y-axis settings, such as Figures 5a and 5f. 2 1 The article topic is intriguing and promising in the area. w14030367_makarova 0 +The conclusion has been revised, including the style and sentences. 2 1 : +86 15765532017; E-mail: chnwangjinlong@163.com (J. Wang) 14 Abstract: Biological activated carbon (BAC) biofilter coupling ultrafiltration (UF) is a promising 15 process for the treatment of surface water contaminated by pharmaceutical and personal care prod- 16 ucts (PPCPs). w14030367_makarova 0 +We agree with this suggestion. The abbreviations in the title have been deleted. Besides, a list of abbreviations has been added before the references. 4 1 However, in the case of the PPCPs with a small molecular weight (typically < 600 Da), UF membranes also cannot effectively reject these PPCPs, but nanofiltration and reverse osmosis are able to remove these PPCPs based on the thin-film composite”. w14030367_makarova 0 +Thanks to the reviewer for the patient comment. The above mistakes have been revised. 4 1 Author Response Please see the attachment Author Response File: Author Response.docx w14030367_makarova 0 +Thanks to this reviewer for the comment. Common waterborne viruses include Shigella, Vibrio cholerae, Poliovirus, adenovirus, and coxsackie virus, with sizes of 26 nm, 27 nm, 30 nm, 90 nm, and 30 nm, respectively [1-5]. The molecular weights of PPCPs are generally less than 1000 Da (about 1-2 nm), obviously smaller than the virus. The molecular weight cut off of UF membranes was an average 100 000 Da in this work, which was similar to the virus but larger than the PPCPs molecules. Karthik K, Dhanuskodi S, Gobinath C, et al. Multifunctional properties of microwave assisted CdO–NiO–ZnO mixed metal oxide nanocomposite: enhanced photocatalytic and antibacterial activities [J]. Journal of Materials Science: Materials in Electronics, 2018, 29(7): 5459-71. Song S, Liu Z, Zhou J, et al. An adjuvant compound that enhances immunogenicity at fractional doses of the Sabin-inactivated poliovirus vaccine (sIPV) with a long duration of protection in a rat model [J]. Journal of Medical Virology, 2019, 91(1): 14-21. Kim K, Choi J-W, Ma K, et al. Nanoisland-Based Random Activation of Fluorescence for Visualizing Endocytotic Internalization of Adenovirus [J]. Small, 2010, 6(12): 1293-9. Dourmashkin R R, Mccall S A, Dourmashkin N, et al. Virus-like particles and enterovirus antigen found in the brainstem neurons of Parkinson's disease [J]. F1000Res, 2018, 7: 302-. Tamano K, Aizawa S-I, Katayama E, et al. Supramolecular structure of the Shigella type III secretion machinery: the needle part is changeable in length and essential for delivery of effectors [J]. The EMBO Journal, 2000, 19(15): 3876-87. 4 1 Response 6: Thanks very much for this comment. w14030367_makarova 0 +The information regarding the biological degradation of PPCPs has been added in the introduction. The revised sentences are shown below: In the BAC biofilters, the biotransformation and adsorption both contributed to the PPCPs removal. The activated carbon adsorbed PPCPs to the surface and interior, where microorganisms were suitable for growth. Under the long-term effect of high-concentration PPCPs, the dominant microorganisms in the biofilter were selected to survive. These microorganisms mostly transformed PPCPs into many segments and even directly mineralized them to CO2 [3, 14]. 4 1 The article topic is intriguing and promising in the area. w14030367_makarova 0 +“The combined process with ultrafiltration may be another promising choice, featuring a comparable removing performance as the nanofiltration and low operational cost”. This claim is not supported by our research. To avoid misunderstandings for readers, we changed the claim and revised the sentence. The revised version is as follows: The combined process with UF may be another promising choice as an alternative to nanofiltration for removing PPCPs in rural areas. It can be seen in lines 54-55. 4 1 Response 14: Thank you very much for your kind reminder. w14030367_makarova 0 +The method of the t-tests has been explained in section 2.4 (lines 157-158) in the revised manuscript. The sample size (n) has also been added in Table 1 and Table 2. 4 1 Response 10: Thank you very much for your kind reminder. w14030367_makarova 0 +Thank you very much for your kind reminder. The values have been modified in the revised manuscript in yellow highlight. 4 1 However, the long-term pilot-scale study is urge to be investigated. w14030367_makarova 0 +Thanks for the kind reminder. All the names of medicinal compounds not used have been deleted, including Sulfaquinoxaline (SQX), Sulfathiazole (STZ), Doxycycline (DOX), Roxithromycin (ROX), Penicillin-G (PEN-G), Clarithromycin (CAM), Norfloxacin (NOR), Oxociprofloxacin (OFL), Enrofloxacin (EFL), Flumequine (FQ), Acetaminophen (APAP), Diclofenac sodium (DCF), Naproxen (NAP), Indomethacin (IND), Metoprolol (METO), Propranolol (PRO), Atenolol (ATL), Primidone (PRM), Carbamazepine (CMZ), Sulpiride (SP), Sulfapyridine (SPN), Sulfamonomethoxine (SMM), Tetracycline (TC), Amoxicillin (AM), Dimetridazole (DMZ), Oxytetracycline (OTC) and DEET. 4 1 Response 8: Thanks very much for this comment. w14030367_makarova 0 +The results and discussion has been supplemented in section 3.1. Please see lines 180-185 in the revised manuscript. 4 1 ##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). w14030367_makarova 0 +Thanks very much for this comment. With a turbulent current and dozens of kilometers in length, this river is located in the mountains of Foshan city. The PPCPs sludge at the bottom of the river never executes removal. Thanks for the suggestion from the reviewer. We will further precipitate the PPCPs sludge before the water treatment plant or excavate the PPCPs sludge from the river and study the effects on drinking water quality. The relevant results will be published in another paper in the future. 4 1 Results seem to be related to a unique experiment. w14030367_makarova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. The writing and data presenting need to be improved. agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). agriculture12060868_perova 0 +There are only minor comments with very specific issues: The paper is clearly written, with nice figures and with a discussion supported by the results obtained. agriculture12060868_perova 0 +The writing and data presenting need to be improved. There are only minor comments with very specific issues: agriculture12060868_perova 0 +There are only minor comments with very specific issues: The paper is clearly written, with nice figures and with a discussion supported by the results obtained. agriculture12060868_perova 0 +The writing and data presenting need to be improved. The writing and data presenting need to be improved. agriculture12060868_perova 0 +Finally, thank you for being so patient with our manuscript The writing and data presenting need to be improved. agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. There are only minor comments with very specific issues: agriculture12060868_perova 0 +The following changes could improve the quality of the paper. The following changes could improve the quality of the paper. agriculture12060868_perova 0 +Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. There are only minor comments with very specific issues: agriculture12060868_perova 0 +There are only minor comments with very specific issues: Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +The paper is clearly written, with nice figures and with a discussion supported by the results obtained. Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). The writing and data presenting need to be improved. agriculture12060868_perova 0 +Finally, thank you for being so patient with our manuscript The paper is clearly written, with nice figures and with a discussion supported by the results obtained. agriculture12060868_perova 0 +There are only minor comments with very specific issues: The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). agriculture12060868_perova 0 +Finally, thank you for being so patient with our manuscript Andersen and Marko have analyzed the design of farrowing pens and present the first production results of the “SowComfort farrowing pen”. agriculture12060868_perova 0 +There are only minor comments with very specific issues: Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +The following changes could improve the quality of the paper. Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +Finally, thank you for being so patient with our manuscript The writing and data presenting need to be improved. agriculture12060868_perova 0 +The paper deals with an interesting topic and totally up to date to provide farmers with solutions for free farrowing (which in Europe may become mandatory under The End of the Cage Age initiative). Finally, thank you for being so patient with our manuscript agriculture12060868_perova 0 +The following changes could improve the quality of the paper. The following changes could improve the quality of the paper. agriculture12060868_perova 0 +Figure 1- Perhaps just double-check this is referred to in the text. We might see some dogs become sensitized over time and develop SRB (or something else changes in their life to precipitate it), while others might habituate or their behavior undergo extinction. ani12040482_makarova 0 +For example, what is the difference between pined, whined, and cried? But this is the opinion of a person using English as a second language. ani12040482_makarova 0 +I think that after the revision, the paper would make an interesting contribution to the journal. They do not seem to state dog is favouring them less unless text was omitted here. ani12040482_makarova 0 +“More Attention than Usual”: A Thematic Analysis of Dog Ownership Experiences in the 530 UK during the First COVID-19 Lockdown. Anim. 2021, Vol. 11, Page 240 2021, 11, 240, doi:10.3390/ANI11010240). But this is the opinion of a person using English as a second language. ani12040482_makarova 0 +Impact of the first COVID-19 lockdown on management of pet dogs in the UK. Materials and Methods: Line 151: how was the criterion of “at least 5 minutes” chosen? ani12040482_makarova 0 +Abstract/simple summary: These are clear and well detailed. Among them, what was the proportion of owners who has not responded to the request afterward? ani12040482_makarova 0 +This error occurs 7 times in the text, please correct. I think that according to the statistics, the strongest finding is that dogs who showed SRB in February or May had increased odds of having SRB during the subsequent measures which is not surprising. ani12040482_makarova 0 +Here are some suggestions that can be made throughout the paper: Title: change “Leaving Pattern” to “Time Spent Away”; leaving pattern is less clear (it could be frequency of leaving each day) If other people were present, did all of them have to be away or just the dog’s owner? ani12040482_makarova 0 +L45 Separation behaviour, separation-related behaviour, separation distress, separation anxiety terms are used interchangeably throughout the text, although these terms do not necessarily describe the same behaviours. There were some errors where reference source not found, which would want to look into (line 246; 265; 274; 292; 305; 323 etc). ani12040482_makarova 0 +Was there a relationship between age and leaving hours? Here are some suggestions that can be made throughout the paper: Title: change “Leaving Pattern” to “Time Spent Away”; leaving pattern is less clear (it could be frequency of leaving each day) ani12040482_makarova 0 +Also, I might have missed it, but did all of these owners live alone with their dog(s), meaning no other people in the household? L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section ani12040482_makarova 0 +Discussion: The results are appropriately discussed though perhaps more discussion about further study would be beneficial. L291 The odds ratio (OR) is 5.38 and not 4.38 in Table 1. ani12040482_makarova 0 +Line 131: There was an error with referencing wanted to flag. This is a great figure, thank you for including it. ani12040482_makarova 0 +I felt the discussion about changes in greeting behaviour as an early indicator was interesting and could be expanded. Can you address the dogs that improved between Feb and Oct? ani12040482_makarova 0 +I think that after the revision, the paper would make an interesting contribution to the journal. But this is the opinion of a person using English as a second language. ani12040482_makarova 0 +Risk factors and behaviors associated with separation anxiety in dogs. Suggests the behavior is fairly robust and dogs having shown it at one point continue to be at risk (without knowing what interventions were taken) ani12040482_makarova 0 +I think that after the revision, the paper would make an interesting contribution to the journal. A catchy topic, but its content is unoriginal, bringing nothing new to the pre-pandemic science. ani12040482_makarova 0 +Line 382-384 „To our knowledge, this is the first empirical evidence to show a link between changes in dogs’ leaving routines and risk of SRBs.” The authors take priority in the empirical demonstration of changes in dogs when the routine of the day is disturbed. Animals 2021, 11, 5, 524 doi:10.3390/ani11010005; *Holland, K.E. ; Owczarczak-Garstecka, S.C.; Anderson, K.L.; Casey, R.A.; Christley, R.M.; Harris, L.; McMillan, K.M.; Mead, 529 R.; Murray, J.K.; Samet, L.; et al. ani12040482_makarova 0 +Seems a comparison between SRB- (baseline) → SRB + (post lockdown) and SRB + (baseline) → SRB- (post lockdown) dogs is critical and missing. There would be evidence for some behaviors, such as destructive behavior or defecation, but how would owners know about pacing or tail-chasing? ani12040482_makarova 0 +half of the dogs from the SRB group moved to the Clear group in October. Journal of the American Veterinary Medical Association, 219(4), 460-466. ani12040482_makarova 0 +The authors found that owners reported that nearly 10% of dogs that did not show SRB behaviors prior to lockdown were reported to show SRB after lockdown, and the greater the change in the dog’s routine, the greater chance they had of showing new SRB. That is, would the same % of dogs changed (in either direction) regardless of changes in owner schedules? ani12040482_makarova 0 +Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. We have addressed your comments and responded in the attached file. ani12040482_makarova 0 +The changes in leaving routine that occurred during the pandemic afforded the opportunity to study what impact this had on a large population of pet dogs over time, that would otherwise have been impossible to capture at such scale. The authors examined how separation-related behaviors in pet dogs changed in relation to time spent away from home by UK owners in February 2020 (pre-pandemic), May-July 2020 (first lockdown during the pandemic), and October-November 2020 (local tier-system for restrictions; follow-up). ani12040482_makarova 0 +L22 and elsewhere: dogs’ “leaving time” or “leaving hours” I think this expression is misleading because it is not the dogs that have left home, but the owners. When looking at SRB status in October, of 1,187 dogs who were left alone in October, 117 (9.9%) were reported to have shown at least one SRB”. ani12040482_makarova 0 +Some more detail on the application of the findings to practitioners/owners would be beneficial. They do not seem to state dog is favouring them less unless text was omitted here. ani12040482_makarova 0 +This information would have been interesting if data on the mood, stress level, general mental health of the owners had also been collected in connection with the pandemic and the links with dog behaviour have been investigated. Line 29: change “dogs whose leaving hours reduce most” to “dogs whose time left alone decreased most” Thank you, this edit has been applied. ani12040482_makarova 0 +Please explain the relationship between the variables. Line 461: change “onto” to “on to” Thank you, we’ve corrected the typo. ani12040482_makarova 0 +I think that according to the statistics, the strongest finding is that dogs who showed SRB in February or May had increased odds of having SRB during the subsequent measures which is not surprising. The authors found that owners reported that nearly 10% of dogs that did not show SRB behaviors prior to lockdown were reported to show SRB after lockdown, and the greater the change in the dog’s routine, the greater chance they had of showing new SRB. ani12040482_makarova 0 +Line 30: change “leaving hours increase again” to “time left alone increased again” Thank you, this edit has been applied. It is confusing to read about the surveys without knowing the sample sizes per survey and the demographics. ani12040482_makarova 0 +L118 Materials and Methods This section (after the Ethics) should begin with the Subjects section. That is, would the same % of dogs changed (in either direction) regardless of changes in owner schedules? ani12040482_makarova 0 +You report the number of new dogs showing SRB but can you report on dogs that went the other way? P6 L176 I am assuming you excluded dogs that were not left alone in February (or were there none?) ani12040482_makarova 0 +Were behaviors, including different vocalizations, defined for owners? The study reports that pet dogs whose leaving routines changed most during the COVID-19 pandemic (i.e., their owners left them alone less frequently) would be at greater risk of developing separation-related behaviours following the lifting of pandemic restrictions. ani12040482_makarova 0 +Line 29: change “dogs whose leaving hours reduce most” to “dogs whose time left alone decreased most” Thank you, this edit has been applied. Here are some suggestions that can be made throughout the paper: ani12040482_makarova 0 +L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. ani12040482_makarova 0 +Minor issues: Line 35: insert “of” after 9.9% I felt the discussion about changes in greeting behaviour as an early indicator was interesting and could be expanded. ani12040482_makarova 0 +What was the proportion of owners who did not leave their dog at home before the pandemic? Larger issues: I would like to see the authors address a few different angles in the discussion 1. ani12040482_makarova 0 +I hope this review helps – thank you for the opportunity. If other people were present, did all of them have to be away or just the dog’s owner? ani12040482_makarova 0 +An error message occurred in several places (e.g., line 131, line 246, line 265) Line 29: change “dogs whose leaving hours reduce most” to “dogs whose time left alone decreased most” Thank you, this edit has been applied. ani12040482_makarova 0 +Results: These were generally well-detailed with clear layout considering scope of results. L232-242 These sections should be moved to the Materials and Methods as a “Subjects” section ani12040482_makarova 0 +Line 100: insert “the” after “in” Thank you, we have corrected the typo. Line 444 „This study has provided a unique and valuable insight into…..” the authors also mark their only unique role in the study, which does not bring new content. ani12040482_makarova 0 +L395-397 “This value is likely to be an underestimate” The underestimation has already occurred during the baseline. The sample size is good, and the results are interesting. ani12040482_makarova 0 +I felt the discussion about changes in greeting behaviour as an early indicator was interesting and could be expanded. Aa little more mention of issues of SRBs from owner perspective (e.g. ani12040482_makarova 0 +L278-280 “There were 1,407 dogs who were clear of SRB at baseline in February 2020. However, I don't think the figures were referred to in the text (unless that was the errors highlighted below?) ani12040482_makarova 0 +It is confusing to read about the surveys without knowing the sample sizes per survey and the demographics. “More Attention than Usual”: A Thematic Analysis of Dog Ownership Experiences in the 530 UK during the First COVID-19 Lockdown. Anim. 2021, Vol. 11, Page 240 2021, 11, 240, doi:10.3390/ANI11010240). ani12040482_makarova 0 +Seems a comparison between SRB- (baseline) → SRB + (post lockdown) and SRB + (baseline) → SRB- (post lockdown) dogs is critical and missing. I think that after the revision, the paper would make an interesting contribution to the journal. ani12040482_makarova 0 +Please explain the relationship between the variables. Study periods: It may be useful to spell out a little more here why these survey periods were chosen here, this is covered elsewhere but think could be made clearer here and earlier. ani12040482_makarova 0 +One of the challenges in this is we don’t know background rates of change for dogs with SRB. I felt the discussion about changes in greeting behaviour as an early indicator was interesting and could be expanded. ani12040482_makarova 0 +In other words, 1407/1807 (78%) of dogs were clear of SRB in February and 90.1% in October. L293-295 “The final variable associated with October SRB status was the difference in the number of days dogs were left alone for between the February baseline and lockdown”. ani12040482_makarova 0 +There would be evidence for some behaviors, such as destructive behavior or defecation, but how would owners know about pacing or tail-chasing? This is a well written and clear manuscript which would be of interest to academics, practitioners and dog owners. ani12040482_makarova 0 + Line 461: change “onto” to “on to” Thank you, we’ve corrected the typo. L118 Materials and Methods This section (after the Ethics) should begin with the Subjects section. ani12040482_makarova 0 +Please explain the relationship between the variables. Please explain the relationship between the variables. ani12040482_makarova 0 +However, currently, the paper seems too long, and it goes into too much detail about how the pandemic took place in the UK. The authors gathered data (via owner surveys) about the same dogs before the pandemic, at the beginning of the pandemic and approx. ani12040482_makarova 0 +I think that after the revision, the paper would make an interesting contribution to the journal. Thank you, this seemed ok until the manuscript was uploaded but we’ve corrected it now. ani12040482_makarova 0 +Animals 2021, 11, 5, 524 doi:10.3390/ani11010005; *Holland, K.E. ; Owczarczak-Garstecka, S.C.; Anderson, K.L.; Casey, R.A.; Christley, R.M.; Harris, L.; McMillan, K.M.; Mead, 529 R.; Murray, J.K.; Samet, L.; et al. Discussion: The results are appropriately discussed though perhaps more discussion about further study would be beneficial. ani12040482_makarova 0 +Line 30: change “leaving hours increase again” to “time left alone increased again” Thank you, this edit has been applied. Also, I might have missed it, but did all of these owners live alone with their dog(s), meaning no other people in the household? ani12040482_makarova 0 +As I wrote in the previous manuscript review: “Impact of changes in time left alone on separation-related behaviour in UK pet dogs” is one more paper on the behavior of dogs in the COVID-19 pandemic developed in the last two years. I have minor comments below and a few larger comments: ani12040482_makarova 0 +"The authors have hardly studied all the publications on how dogs behave when daily routines were changed, so the term ""first study"" is exaggerated." Specific points requiring attention: L18-20 „Whether dogs showed SRBs or not changed considerably over the months of the study, and one in ten dogs were found to have developed new SRBs in October, that they didn’t show before the pandemic” Overall, the percentage of dogs showing SRBs decreased during the study, and this should be clarified in the sentence above. ani12040482_makarova 0 +The authors still take priority in the empirical demonstration of changes in dogs when the routine of the day is disturbed. L278-280 “There were 1,407 dogs who were clear of SRB at baseline in February 2020. ani12040482_makarova 0 +L22 and elsewhere: dogs’ “leaving time” or “leaving hours” I think this expression is misleading because it is not the dogs that have left home, but the owners. I felt the discussion about changes in greeting behaviour as an early indicator was interesting and could be expanded. ani12040482_makarova 0 +According to the authors, the main finding is that dogs whose leaving time reduced the most during the lockdown were most at risk of developing new SRBs. Author Response Thank you for your time in reviewing this manuscript and for your constructive, helpful feedback. ani12040482_makarova 0 +Abstract/simple summary: These are clear and well detailed. Can you address the dogs that improved between Feb and Oct? ani12040482_makarova 0 +The same misprint appears at page 8 in the paragraph between Eqs. How does this analytical result compare with the numerical simulations?” atoms3030433_perova 0 +(2), please check the commutation relations between the raising (sigma^+) and lowering (sigma^-) operators and the Pauli matrix sigma^z. Try to use other colors and/or thicker lines.” atoms3030433_perova 0 +The manuscript is generally well organized and clearly written. R4 However, I have a few comments and suggestions to improve the overall quality and readability of the paper. atoms3030433_perova 0 +(2), please check the commutation relations between the raising (sigma^+) and lowering (sigma^-) operators and the Pauli matrix sigma^z. The simultaneous driving at two different frequencies gives rise to interference terms in the optical force acting on the particle. atoms3030433_perova 0 +I would suggest to provide a reference to guide the less experienced reader.” The authors could help readers by better putting their work into context and improving some of their explanations. atoms3030433_perova 0 +"“At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived." “Page 4, first paragraph, the particle initial conditions are chosen in the interval [ - 0.1, 0.1] (in the text a comma is missing).” atoms3030433_perova 0 +The authors could help readers by better putting their work into context and improving some of their explanations. “Figure 4 is mentioned in the main text AFTER Fig. atoms3030433_perova 0 +R4 However, I have a few comments and suggestions to improve the overall quality and readability of the paper. How does this analytical result compare with the numerical simulations?” atoms3030433_perova 0 +"“At the end of Section IV C. ""Optical forces"" the time independent value of the force is derived." Therefore, the manuscript is worthy of publication. atoms3030433_perova 0 +R4 However, I have a few comments and suggestions to improve the overall quality and readability of the paper. “Figure 4 is mentioned in the main text AFTER Fig. atoms3030433_perova 0 +The authors could help readers by better putting their work into context and improving some of their explanations. In the analytical results, derived in the adiabatic limit, gamma is eliminated and does not play any role. atoms3030433_perova 0 +I would suggest to provide a reference to guide the less experienced reader.” The manuscript is generally well organized and clearly written. atoms3030433_perova 0 +The same argument (dimensional analysis) applies to Eqs. Indeed, the analysis here is restricted to the classical regime for both the field and atomic variables. atoms3030433_perova 0 +“Finally, some stylistic considerations: Please, be consistent with the choice of subscripts and superscripts: in the first column of page 2 the Pauli operator is denoted as sigma^z (superscript), whereas in the second column becomes sigma_z (subscript).” R4 However, I have a few comments and suggestions to improve the overall quality and readability of the paper. atoms3030433_perova 0 +“Figure 8, Force correlation functions and numerical solutions of the variance: when printed in grey scale some lines are very faint (especially those in green and cyan). "(4), the Authors write ""We proceed in a standard way to derive equations of motion for classical quantities.""" atoms3030433_perova 0 +The approach is scientifically sound and convincing. Analytic approximations of the effective trapping forces give some insight into the origin of the special form of the optical potential and delineate the regimes in which random walks are expected to occur.The proposal of this somewhat unconventional random-walk regime in cavity-QED is interesting and deserves publication. atoms3030433_perova 0 +"“In section VI E. ""Trapping by longitudinal pumping"", one can analytically estimate the threshold value for the transverse pumping." “In the equations of motion for the atoms [Eqs. atoms3030433_perova 0 +The same argument (dimensional analysis) applies to Eqs. I wonder if one can draw any conclusion from the numerical simulations, where other regimes could have been explored.” atoms3030433_perova 0 +Numerical simulations predict quasi-random jumps to neighbouring lattice sites at regular time intervals leading to diffusive motion over long times. The consequence is a sign change in the effective potential that induces the atom to perform an erratic motion, hopping between neighbouring lattice sites. atoms3030433_perova 0 +This remains an interesting topic for future work, but is outside the scope of our article. In the Introduction, quite a lot of papers are cited concerning the applications of atom interferometer in varies fields. atoms4020014_makarova 0 +1 Review Report 1 Originality/Novelty This paper treats an important question concerning the measurement of the gravitational constant G by atom interferometry. We know that this paper is “equation-rich”, but we have tried to provide some physical guidance for the reader. atoms4020014_makarova 0 +We do not know yet how this term would manifest itself in the other approaches (path-integrals, ABCD theorem and etc.). The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +The results obtained seem reasonable, although I have no time to verify all the derivations. We know that this paper is “equation-rich”, but we have tried to provide some physical guidance for the reader. atoms4020014_makarova 0 +Although each plot is difficult to read at “normal” magnification, the online reader can easily magnify any plot when accessing the article in PDF format. It arises as a quantum correction to phase factors during periods of free evolution. atoms4020014_makarova 0 +Review Report 2 In this manuscript, the influences of an external test mass on the phase of the signal of an atom interferometer are studied theoretically. We do not know yet how this term would manifest itself in the other approaches (path-integrals, ABCD theorem and etc.). atoms4020014_makarova 0 +The correction phi_Q was not discussed in the previous papers I know on the subject and I think that the paper must be published but, as explained below, important improvements are needed. Although each plot is difficult to read at “normal” magnification, the online reader can easily magnify any plot when accessing the article in PDF format. atoms4020014_makarova 0 +At this point, we do not have any other physical interpretation. The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +The correction phi_Q was not discussed in the previous papers I know on the subject and I think that the paper must be published but, as explained below, important improvements are needed. Author response We would like to thank the referee for his/her careful reading of the manuscript and the helpful comments. atoms4020014_makarova 0 +It will be helpful to the readers if a figure is provided to show the locations. It arises as a quantum correction to phase factors during periods of free evolution. atoms4020014_makarova 0 +We do not know yet how this term would manifest itself in the other approaches (path-integrals, ABCD theorem and etc.). At this point, we do not have any other physical interpretation. atoms4020014_makarova 0 +It will be helpful to the readers if a figure is provided to show the locations. This remains an interesting topic for future work, but is outside the scope of our article. atoms4020014_makarova 0 +I am not sufficiently aware of the use f Wigner function but I am sure that there are better and more useful references to quote in addition to ref 17! The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +The correction phi_Q was not discussed in the previous papers I know on the subject and I think that the paper must be published but, as explained below, important improvements are needed. We do not know yet how this term would manifest itself in the other approaches (path-integrals, ABCD theorem and etc.). atoms4020014_makarova 0 +This remains an interesting topic for future work, but is outside the scope of our article. The response to these comments and changes to the manuscript in response to these comments is given below: 1. atoms4020014_makarova 0 +Author Response Thank you very much for the positive comments 1- It appears to be more appropriate as results and maybe some information could be in the introduction. cancers14122960_perova 0 +Further, structural features (the order of the ß--strands in space is not the same as their order in sequence) predict that proteins lacking any single b-strand would fail to form the ß--sheet resulting in a collapse of the protein core and misfolding of the protein [33]. Lines 259-274 – This paragraph refers to evidence used in the variant interpretation of three aberrant transcripts that kept the open reading-frame (Δ(E2p3), Δ(E5) and ▼(E8p3)). cancers14122960_perova 0 +The discussion of these variants in this section (and in other sections) does not address the significance of canonical transcripts in these cases. Many nucleotide variants, whether they affect protein changes or not can affect potential splicing of exons. cancers14122960_perova 0 +Thank you for the opportunity to review this interesting manuscript. Is it known whether there is a threshold of RAD51C deficiency that is tolerated before associated cancer risks become increased? cancers14122960_perova 0 +It is good to look into Sanger sequence of splice variants after gel elution of the band and sequencing. It appears to be more appropriate as results and maybe some information could be in the introduction. cancers14122960_perova 0 +The minigene splicing assay is simplistic in its design, yet provides important functional evidence for the evaluation of spliceogenic variants. The assay used is well established and has been used previously to evaluate spliceogenic variants in RAD51C and other hereditary breast/ovarian cancer-associated genes. cancers14122960_perova 0 +Author Response - Thank you very much for the positive comments and the revision of our manuscript. Lines 342-359 – This paragraph discusses two RAD51C variants, c.404+3A>G and c.705+3A>G, for which mg-FL transcripts were detected in 26.3% and 21.3% or transcripts, respectively. cancers14122960_perova 0 +I would also stress a little more that FL is almost undetectable. present an interesting manuscript that utilizes a minigene splicing assay to examine twenty RAD51C variants catalogued through ClinVar. cancers14122960_perova 0 +Is there evidence from another source that these beta strands are critical to protein function and that their loss is deleterious (rather than resulting in normal or slightly reduced protein activity)? describes about the analysis of RAD51C variants using mini-gene assays for splicing defect. cancers14122960_perova 0 +The author should bring specific conclusions in accordance with obtained results. We hope the reviewer understand the experimental deficiencies at the stage of the present experiments. catal12030290_perova 0 +A point-by-point response to the reviewer-2 comments is appended below for your convenience. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +We deeply appreciate the comment raised by the reviewer. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +In such form is rather difficult to make adequate comparison. Page 2 of 2 Comment 5: In the experiment, H2SO4 is added in the first step, what is the purpose? catal12030290_perova 0 +Comment 6: How about the Cr concentration in the polluted ground water? The magnified images can be shown separately or as inset. catal12030290_perova 0 +A point-by-point response to the reviewer-3 comments is appended below for your convenience. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. Comment 1: Some FT-IR peaks shift with adsorption of Cr, and some not. catal12030290_perova 0 +conditions for testing sorbents of Cr(VI) ions) to Table 3. Examination of prepared adsorbents for Cr(VI) ions removal. catal12030290_perova 0 +Comment 3: It is better to show the SEM images using the same scale. The authors are very thankful to the Reviewer for their valuable suggestions for the improvement of the manuscript. catal12030290_perova 0 +: catalysts-1584262 Title: Bio-stimulated adsorption of Cr(VI) from aqueous solution by Groundnut Shell Activated Carbon@Al embedded material Response to Reviewer-1 Comments We appreciate the efforts of the reviewers for their detailed and insightful comments, which have helped us to improve the quality of our manuscript. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +The magnified images can be shown separately or as inset. The paper mainly presents two key contributions: Synthesis of bioadsorbent and evaluation of its structure using SEM and FT-IR spectroscopy. catal12030290_perova 0 + Response: We acknowledge the reviewer’s opinion. A point-by-point response to the reviewer-3 comments is appended below for your convenience. catal12030290_perova 0 +The manuscript is well- organized, all the conclusions are supported by the presented data. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +Comment 3: It is better to show the SEM images using the same scale. : catalysts-1584262 Title: Bio-stimulated adsorption of Cr(VI) from aqueous solution by Groundnut Shell Activated Carbon@Al embedded material Response to Reviewer-3 Comments We appreciate the efforts of the reviewers for their detailed and insightful comments, which have helped us to improve the quality of our manuscript. catal12030290_perova 0 +(ppm) pH Contact Time (min) Adsorbent dosage (g l-1) Maximum adsorption capability (mg g-1) References Activated carbon (AC) prepared from coconut tree sawdust 10 3.0 180 0.2 3.46 [29] Raw coconut fiber 250 1.0 270 10 18.60 [30] Sugarcane bagasse 100 2.0 90 10 1.76 [31] Canadian peat Coconut fiber 50 2.0 4320 25 4.61 4.71 [32] peanut shell (P. Shell), sawdust (S. Dust) and Cassia fistula leaves (C.F. 1 - for a more effective visual comparison, authors recommended to provide SEM images of the same scale. catal12030290_perova 0 +1 - for a more effective visual comparison, authors recommended to provide SEM images of the same scale. Comment 8: In order to confirm proposed mechanism of Cr(VI) adsorption (illustrated on the fig 6) Authors should provide data on adsorption capacity of pristine groundnut shell activated carbon (not modified with Al). catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. The manuscript is well-organized, all the conclusions are supported by the presented data. catal12030290_perova 0 +Response: We acknowledge the reviewer’s opinion. Response: We acknowledge the reviewer’s opinion. catal12030290_perova 0 +Point-by-point response to reviewers: Reviewer 1 comments 1. In this manuscript, the Authors examined the efficacy of the liposome preparations to neutralise the exotoxins like SLO and SLS present in the bacterial culture medium. cells11010166_makarova 0 +While LDH-release or MTT assay are frequently used techniques and might be preferred by some investigators, other approaches assessing cell viability might be more popular by others, dependent on particular experimental settings of a particular study. LDH-release assay of cytotoxicity or MTT assay of cell viability should have been used for measuring the cell death. cells11010166_makarova 0 +The authors used the term liposome nanotraps. In the material and methods section it is stated that the cells survival assays start with the addition of a fixed volume of supernatant but it is not clear to me the criteria for reflecting different amounts of supernatant in Figures 2 and 3. cells11010166_makarova 0 +This means that no commercial antibody against it is available and the peptide is too small for reliable mass spectrometry detection. Indeed, the liposomes are prepared by a conventional method. cells11010166_makarova 0 +However, as the immune cell lines have different sensitivities depending on the toxin profile of the tested strain, a similar lethal dose corresponds to different supernatant volumes. Streptolysin S (SLS) is a small, non-immunogenic, peptide. cells11010166_makarova 0 +Dear Ms. Tongtong Yan, dear reviewers, We would like to thank the reviewers for their contributions and feel that our study has clearly benefitted from their suggestions. In my opinion, differential inhibition of the SLS activity in GGS supernatant by the liposome preparations is interesting, and may provide new insights, if explored in more detail. cells11010166_makarova 0 +We used two controls in the protection experiments. LDH-release assay of cytotoxicity or MTT assay of cell viability should have been used for measuring the cell death. cells11010166_makarova 0 +Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. Even if many studies have failed to that Wagner’s law holds, there is a common perception that it holds over periods when countries become developed. economies3040150_makarova 0 +The autoregressive distributed lags model is a much better choice in general. While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. economies3040150_makarova 0 +Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. This is a major flaw of the paper and the choice should be defended by showing that using the ‘standard’ real GDP series’ would give the same results. economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. The suggestions are listed below in no particular order of importance: 1. economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +While interesting, generally well written and scientifically sound, several suggestions should be considered before further consideration. Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. economies3040150_makarova 0 +Round 1: The paper analyzes the validity of Wagner’s law in six East Asian countries during the period 1960- 2008. Even if many studies have failed to that Wagner’s law holds, there is a common perception that it holds over periods when countries become developed. economies3040150_makarova 0 +Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. The autoregressive distributed lags model is a much better choice in general. economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. Round 1: The paper analyzes the validity of Wagner’s law in six East Asian countries during the period 1960- 2008. economies3040150_makarova 0 +But later tests show that the variables are non-stationary. The suggestions are listed below in no particular order of importance: 1. economies3040150_makarova 0 +The suggestions are listed below in no particular order of importance: 1. References: Cameron A. Shelton (2007) “The size and composition of government expenditure” Journal of Public Economics, 91 (11–12) Simon Johnson, William Larson, Chris Papageorgiou, Arvind Subramanian. economies3040150_makarova 0 +Even if many studies have failed to that Wagner’s law holds, there is a common perception that it holds over periods when countries become developed. Penn World Table Revisions and Their Impact on Growth Estimates” NBER Working Paper No. economies3040150_makarova 0 +This makes the unconditional correlations uninteresting. This is a major flaw of the paper and the choice should be defended by showing that using the ‘standard’ real GDP series’ would give the same results. economies3040150_makarova 0 +Moreover, most studies that add variables to the models, such as the dependency ratio, argue that Wagner’s law holds conditional on it. Round 1: The paper analyzes the validity of Wagner’s law in six East Asian countries during the period 1960- 2008. economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. economies3040150_makarova 0 +Second Round of Evaluation Round 2: The paper is much better and I only have some minor comments. Unit roots and the demand for cigarettes in Turkey: pitfalls and possibilities. economies3040150_makarova 0 +But later tests show that the variables are non-stationary. But later tests show that the variables are non-stationary. economies3040150_makarova 0 +Round 1: The paper analyzes the validity of Wagner’s law in six East Asian countries during the period 1960- 2008. But later tests show that the variables are non-stationary. economies3040150_makarova 0 +The depth maps provided in Figure 5 should be supplemented by isochore maps for the rock volumes between pairs of mapped reflectors. Figure 2 -Poor quality figure (low resolution) in the version available to the reviewer. geosciences12010037_perova 0 +This would also tie the observations based on this dataset closer to the seismic interpretation (see below). Figures, however, need to be significantly improved for the final manuscript (see detailed comments below). geosciences12010037_perova 0 +Improving the design of the figures and adding links/references to primary data sources would go a long way towards addressing this. These often highlight tectonic accommodation space creation better than maps. geosciences12010037_perova 0 +what differentiates “FAULT” from a “BaseCambrianSeismic fault”?). Figure 2 -Poor quality figure (low resolution) in the version available to the reviewer. geosciences12010037_perova 0 +Why are these not classified in terms of signal quality? In this process, minor mismatches of the automated simplified lines were removed and small drainage segments were connected along major lineaments for further simplification and reduction of the dataset. geosciences12010037_perova 0 +It is however not made clear how this “simplified” network was generated, but there appear to be a substantial number of instances where the “simplification” provides apparent mismatches with the original data (see examples included in comments to Figure 2 below). Depth conversion using check-shot velocities from 26 wells. geosciences12010037_perova 0 +We have redone the figure 2 and added explanations on the process (see reply to comments on figure 2). Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). geosciences12010037_perova 0 +With respect to the helium measurements, no detailed documentation of where these samples were collected is provided beyond referring to Geological and Bioregional Assessment Program (2021a) Fact sheet 12, and Geological and Bioregional Assessment Program (2021b) Regional tracer results from the Cambrian Limestone Aquifer. Interpretation of shallow horizons and faults using all publicly available geological and geophysical data of the Beetaloo region. geosciences12010037_perova 0 +Not possible to differentiate “ntspr_2M_gw” (whatever that is) and “PossibleFluidEscapeStructures” (same colour). It would be good define what recent means in the context of this study. geosciences12010037_perova 0 +It would be nice to include a map with these features and lineaments interpreted from the aeromagnetic datasets. Isochron maps have been included in the supplementary material, the initial review suggested isoCHORE maps. geosciences12010037_perova 0 +done Figure 4 -Poor quality figure (low resolution) in the version available to the reviewer. Although this is described in the caption, it is not easy to grasp for someone not familiar with the stratigraphy in the area without spending time some time with paper and pencil. geosciences12010037_perova 0 +We are not willing to add complexity by presenting in detail the Basins that are covering the Beetaloo Sub-Basin. The drainage network was extracted automatically. geosciences12010037_perova 0 +Review summary Scientific aims clearly stated. modified The link between interpreted faults and fluid or gas escape features is a key feature of this figure. geosciences12010037_perova 0 +Consider replacing the purple outline of the eastern and western sub-basin with light grey shading. Although the aeromagnetic data is said to be employed for structural interpretation, details somewhat sketchy. geosciences12010037_perova 0 +• Figure 3: The text (lines 258-259) mentions magnetic lineaments as prominent features, which can be caused by faulting. Figure 8 should now be easier to read The surface drainage network line dataset was indeed based on the simplified (n=130) network following the following approach: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. geosciences12010037_perova 0 +Consider replacing well names on the map with numbers at the well position (white circles, black typeface) and add a table in the legend listing number and corresponding name of the well. The depth maps provided in Figure 5 should be supplemented by isochore maps for the rock volumes between pairs of mapped reflectors. geosciences12010037_perova 0 +: Fault related fluid flow implications for unconventional hydrocarbon development, Beetaloo Sub-basin (Northern Territory, Australia) The reviewer's comments have largely been addressed by the authors. Figures, however, need to be significantly improved for the final manuscript (see detailed comments below). geosciences12010037_perova 0 +Providing references to these original studies (including access to the actual data that allow objective verification) rather than referencing to summary papers would be more in line with scientific publishing practice. The study concludes that there the shallow aquifers are connected to deep-seated gas source along faults, some of which show evidence of recent movement. geosciences12010037_perova 0 +modified The link between interpreted faults and fluid or gas escape features is a key feature of this figure. Review summary Scientific aims clearly stated. geosciences12010037_perova 0 +However, there are still a couple of minor issues. It is not clear if the surface drainage network line dataset is based on the “unfiltered” or “simplified” data shown in Figure 2. geosciences12010037_perova 0 +Poor resolution in the copy provided for the review. If they are not present on the map, remove these items from the legend. geosciences12010037_perova 0 +done -Replace the white label with black typeface with plain white typeface. Please provide a more informative caption to what these plots show. geosciences12010037_perova 0 +Consider adding isochore maps for intervals between interpreted reflectors. • Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? geosciences12010037_perova 0 +• Figure 1: Are colors in Figure 1 A related to the hydrostratigraphy or depicting topography? one showing unfiltered + simplified drainage network, and one showing faults).done -How the authors arrive at the simplified drainage network is not very clear The adopted approach was: Small segments with less than 10 nodes were automatically removed in SKUA (Paradigm/Emerson Trademark) and one iteration of smoothing was applied that further removed small irregularities without changing the overall orientation of major drainage lines. geosciences12010037_perova 0 +Please provide a reference to the primary documentation. Results appear to be sound and supported by the illustrations. geosciences12010037_perova 0 +• Lines 271-272: Why is the signal quality so variable, and how were the categories (excellent, average and poor) defined? Development of the petroleum resources in this region is controversial and faces opposition from Traditional Owners as well as climate scientists, and environmentalists. geosciences12010037_perova 0 +Improving the design of the figures and adding links/references to primary data sources would go a long way towards addressing this. Helium content of the aquifer systems was sampled and measured. geosciences12010037_perova 0 +We tried to improve the figures at best- attached is a detailed reply to reviews. Methods are sound and clearly described, There are some shortcomings in documentation and presentation of results, which weaken the link between observations and conclusion. geosciences12010037_perova 0 +Including these is maybe not critical, but as mentioned in the initial review, thickness maps sometimes highlight structural lineaments quite well. Improving the design of the figures and adding links/references to primary data sources would go a long way towards addressing this. geosciences12010037_perova 0 +We added this description of the adopted approach in the legend Figure 3 -Very small/illegible typeface on map coordinates – consider simplifying scales and use larger typeface. The revisited figure 43 is now providing this information Seismic reflection 2D lines (1989-2015). geosciences12010037_perova 0 +This would also tie the observations based on this dataset closer to the seismic interpretation (see below). I don't know if this is the case here, but if they do, including isochore maps would enhance the readers' understanding of basin geometry and -infill. geosciences12010037_perova 0 +Helium isotope data do not provide an unequivocal answer to whether the gas originates from the unconventional plays or a deeper source. It is not clear if the “simplified” drainage network shown in Figure 2 was also extracted automatically. geosciences12010037_perova 0 +Development of the petroleum resources in this region is controversial and faces opposition from Traditional Owners as well as climate scientists, and environmentalists. Please find attached the revised manuscript with track changes as well as the reply to the detailed comments, directly in purple. geosciences12010037_perova 0 +Helium content of the aquifer systems was sampled and measured. Review summary Scientific aims clearly stated. geosciences12010037_perova 0 +Isochron maps have been included in the supplementary material, the initial review suggested isoCHORE maps. • Figure 6: Put the title of each subfigure above the plot. geosciences12010037_perova 0 +Please provide a more informative caption to what these plots show. Although the aeromagnetic data is said to be employed for structural interpretation, details somewhat sketchy. geosciences12010037_perova 0 +However, there are still a couple of minor issues. Clearly identified in the legend and representation 2. geosciences12010037_perova 0 +The replies to detailed comments are in purples, directly below each comment Frery et al. done Figure 4 -Poor quality figure (low resolution) in the version available to the reviewer. geosciences12010037_perova 0 +figure redrawn - Replace white labels with black typeface with white typeface. Consider using higher contrast colours or thicker lines to highlight different faults on the map. geosciences12010037_perova 0 +one showing unfiltered + simplified drainage network, and one showing faults).done -How the authors arrive at the simplified drainage network is not very clear I don't know if this is the case here, but if they do, including isochore maps would enhance the readers' understanding of basin geometry and -infill. geosciences12010037_perova 0 +Consider adding isochore maps for intervals between interpreted reflectors. Depth conversion using check-shot velocities from 26 wells. geosciences12010037_perova 0 +There is no description of the race and ethnic composition of the sample. This was because of the inclusion of the 5 outliers in table 1, which has been corrected. nu14051073_perova 0 +I didn't understand why the data differed between Table 1 and Supplementary Table 1. Perhaps a simpler definition or specification could be used here, as clinical ‘context’ more often dictates the availability of methods, not necessarily models. nu14051073_perova 0 +None of the methods are ideal – all are flawed (in comparison with a gold standard). I hope that you find this work suitable for your Journal and I look forward to hearing from you. nu14051073_perova 0 +Table 4 sent to supplementary material as supplementary table 3. 06720, Alcaldía Cuauhtémoc, Ciudad de México Teléfono: (52) 55 5228 9917 Ext. nu14051073_perova 0 +It should perhaps be the last paragraph in the Discussion. My expertise on BC measurement methods and some of the included statistical methods is limited. nu14051073_perova 0 +Response to reviewers' comments: Reviewer one: TITLE The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. Is the focus then on finding low cost, easy to apply methods? nu14051073_perova 0 +Is the focus then on finding low cost, easy to apply methods? Only 6.6% belong to indigenous population and 5.9% to Afro-Mexican ethnic groups. nu14051073_perova 0 +OVERALL Much of the Discussion addresses strengths and weaknesses of the different BC methods, as if to provide guidance for clinicians in selecting the best techniques according to their needs and capabilities. MATERIALS AND METHODS P3 L94: This is awkwardly worded. nu14051073_perova 0 +Added to supplementary figure 1 and main figures 1 and 2 There is no description of the race and ethnic composition of the sample. One also begins to wonder about affecting type 1 errors due to multiplicity of comparisons (debatable but worth considering). nu14051073_perova 0 +These topics should be tied together or an alternative motivation needs to be presented. Important to say is that ~89% of Mexican population is Hispanic. nu14051073_perova 0 +ABSTRACT Regarding “The clinical context in which BC is evaluated usually defines the ideal model to be used”: This is somewhat confusing. Cost, manpower, location, all play a role in driving the selection of BC techniques. nu14051073_perova 0 +I didn't understand why the data differed between Table 1 and Supplementary Table 1. P13 L294: The legend for Figure 3 seems incorrect. nu14051073_perova 0 +Added to supplementary figure 1 and main figures 1 and 2 There is no description of the race and ethnic composition of the sample. Some specific comments and questions: TITLE The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. nu14051073_perova 0 +It should perhaps be the last paragraph in the Discussion. I didn't understand why the data differed between Table 1 and Supplementary Table 1. nu14051073_perova 0 +Somehow this needs to be tied more firmly to the population and environment being studied. If not, DXA analysis should be redone and all relationships recalculated. nu14051073_perova 0 +MATERIALS AND METHODS P3 L94: This is awkwardly worded. Added to supplementary figure 1 and main figures 1 and 2 There is no description of the race and ethnic composition of the sample. nu14051073_perova 0 +We feel confident that the manuscript has been strengthened by this. Cost, manpower, location, all play a role in driving the selection of BC techniques. nu14051073_perova 0 +I hope that you find this work suitable for your Journal and I look forward to hearing from you. Added, the analysis was for the total sample and by subgroups by age and sex, line 287 P12 L283: Is Table 4 necessary? nu14051073_perova 0 +As the accepted manuscript already includes the phrase ‘Part 2’ we prefer to keep ‘Part 1’ here ABSTRACT Regarding “The clinical context in which BC is evaluated usually defines the ideal model to be used”: This is somewhat confusing. Some specific comments and questions: TITLE The “Part 1” in the title, while perhaps intriguing, calls for some explanation of future directions. nu14051073_perova 0 +Publishing such reference data is a further aim of our project. "I take from the results that those sentences were describing the Bland-Altman procedure, and if so, adding some text along the lines of ""In this procedure..."" would be helpful." nu14051073_perova 0 +Cancer Epidemiol Biomarkers Prev 2005, 14, 483-490. ; Chou, P. Patients with Primary Open-Angle Glaucoma May Develop Ischemic Heart Disease More Often than Those without Glaucoma: An 11-Year Population-Based Cohort Study. nu14122490_makarova 0 +c Odds Ratios (95%CI) for open-angle glaucoma by total dietary nitrate intake, nitrate intake from vegetables, and nitrate intake from non-vegetable food sources (as continuous variables) analyzed using conditional logistic regression. c Betas (95%CI) for intraocular pressure by total dietary nitrate intake, nitrate intake from vegetables, and nitrate intake from non-vegetable food sources (as continuous variables) analyzed using linear regression. nu14122490_makarova 0 +In this letter we will address the comments of reviewer #2 point by point. doi:10.1001/jamacardio.2018.0022 I wonder if the authors could comment on this in the Discussion. nu14122490_makarova 0 +Fleischman, D.; Berdahl, J.P.; Zaydlarova, J.; Stinnett, S.; Fautsch, M.P. ; Chou, P. Patients with Primary Open-Angle Glaucoma May Develop Ischemic Heart Disease More Often than Those without Glaucoma: An 11-Year Population-Based Cohort Study. nu14122490_makarova 0 +Analysis performed in participants matched on age, sex and BMI. c Odds Ratios (95%CI) for open-angle glaucoma by total dietary nitrate intake, nitrate intake from vegetables, and nitrate intake from non-vegetable food sources (as continuous variables) analyzed using conditional logistic regression. nu14122490_makarova 0 +Analysis performed in participants matched on age and sex. jkos 2017, 58, 1404-1409, doi:10.3341/jkos.2017.58.12.1404. nu14122490_makarova 0 +jkos 2017, 58, 1404-1409, doi:10.3341/jkos.2017.58.12.1404. ; Sturmans, F.; Hermus, R.J. Reproducibility of a food frequency questionnaire and stability of dietary habits determined from five annually repeated measurements. nu14122490_makarova 0 +Enclosed please find our revised manuscript, which incorporates the comments and suggestions of both reviewers. In this letter we will address the comments of reviewer #2 point by point. nu14122490_makarova 0 +doi:10.1001/jamacardio.2018.0022 I wonder if the authors could comment on this in the Discussion. Dielemans, I.; Vingerling, J.R.; Hofman, A.; Grobbee, D.E. nu14122490_makarova 0 +The results and conclusions of this study are important. Marshall, H.; Mullany, S.; Han, X.; Berry, E.C. nu14122490_makarova 0 +Marshall, H.; Mullany, S.; Qassim, A.; Siggs, O.; Hassall, M.; Ridge, B.; Nguyen, T.; Awadalla, M.; Andrew, N.H.; Healey, P.R., et al. Progression of Visual Field Loss and Body Mass Index in Normal Tension Glaucoma. nu14122490_makarova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. plants11050622_perova 0 +The legend of supplementary table should be improved. Correct it It was a pleasure to read this manuscript. plants11050622_perova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. This work is of outstanding quality, and I normally present more critical points in my reviews. plants11050622_perova 0 +I only recommend some minor revisions before acceptance. With minor grammatical revisions, the manuscript can be accepted as is. plants11050622_perova 0 +The content is informative, however, the tables should be reorganized and the statistical methods description have to be improved. Author Response Point-by-point response to reviewer's comments Thank you for inviting me to review this manuscript. plants11050622_perova 0 +The phenotypic data are important, but currently they are presented only as additional material. How did you calculate those values on those comparison types? plants11050622_perova 0 +Legends should describe what is to be observed in the figure, possibly pointing to parts of special interest. Author Response Point-by-point response to reviewer's comments Thank you for inviting me to review this manuscript. plants11050622_perova 0 +However, this time it is just very beautiful work. Author Response Point-by-point response to reviewer's comments Thank you for inviting me to review this manuscript. plants11050622_perova 0 +With minor grammatical revisions, the manuscript can be accepted as is. The last paragraph of results is about background selection. plants11050622_perova 0 +L562: the section of statistical analysis should add more details. How did you calculate those values on those comparison types? plants11050622_perova 0 +Then the table can be more informative and ease to read. However, this time it is just very beautiful work. plants11050622_perova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. Then the table can be more informative and ease to read. plants11050622_perova 0 +This work is of outstanding quality, and I normally present more critical points in my reviews. However, the authors have conducted a thorough literature review, undertaken a rigorous piece of data collection, and have generalized information accurately. plants11050622_perova 0 +The ms is the result of an intensive and years-long work of breeding, that eventually pyramidized several resistance genes and QTLs for abiotic traits into an indian elite rice variety. However, the authors have conducted a thorough literature review, undertaken a rigorous piece of data collection, and have generalized information accurately. plants11050622_perova 0 +L562: the section of statistical analysis should add more details. Also, the legends are not clearly describing all the terms and should be revised. plants11050622_perova 0 +Author Response Point-by-point response to the reviewer's comments are given below The legend of supplementary table should be improved. plants11050622_perova 0 +Also, the legends are not clearly describing all the terms and should be revised. The main issue with the ms is the quality of the figures: they are not clearly representing the data, arrows and text may help the reader, the controls are missing in most cases, and a general lack of precision is affecting them. plants11050622_perova 0 +Line 262: “=261 %” , and Line 312 “linkes” a typo? Table and main text are independent, so the authors have to describe the table more carefully. plants11050622_perova 0 +This work is of outstanding quality, and I normally present more critical points in my reviews. The work is not unprecedented in the concept, but provides interesting breeding material for specific indian farmers, which is an important achievement and is correctly taken up by authorities and international research centers. plants11050622_perova 0 +Line 262: “=261 %” , and Line 312 “linkes” a typo? With minor grammatical revisions, the manuscript can be accepted as is. plants11050622_perova 0 +L127: Please add the explanation of “boro season”. the 85 ILs presented at 414 seem to be a bit out of the blue: a short intro to where they are coming from would help the reader. plants11050622_perova 0 +The paper itself is well written, although 1) somewhat results are partially descriptive and partially inferential. Author Response Point-by-point response to reviewer's comments This paper described the multi-parents introgression assisted by molecular markers. plants11050622_perova 0 +Author Response Point-by-point response to the reviewer's comments are given below On Supplementary table S2, does significant mean p-value? plants11050622_perova 0 +Author Response Point-by-point response to the reviewer's comments are given below Then the table can be more informative and ease to read. plants11050622_perova 0 +The data on bgs are not sufficiently presented in the text nor discussed. The phenotypic data are important, but currently they are presented only as additional material. plants11050622_perova 0 +However, this time it is just very beautiful work. Legends should describe what is to be observed in the figure, possibly pointing to parts of special interest. plants11050622_perova 0 +Please see the suggestion and comments below. The data on bgs are not sufficiently presented in the text nor discussed. plants11050622_perova 0 +L562: the section of statistical analysis should add more details. With minor grammatical revisions, the manuscript can be accepted as is. plants11050622_perova 0 +Response: We appreciate the suggestions from the reviewer, which has resulted in improving the message of the manuscript. L127: Please add the explanation of “boro season”. plants11050622_perova 0 +In fact, the discussion needs to be grounded in previous research findings in regard to CSR/sustainability indices/assessment tools/initiatives. This link remains in the new version, in line 231. su14095590_makarova 0 +1 Response to Reviewer 5 Comments (round 2) Point 1: Is the content succinctly described and contextualized with respect to previous and present theoretical background and empirical research (if applicable) on the topic? Point 7: Discussion: In the first sentence, what is the topic that the authors mentioned? su14095590_makarova 0 +• It is better to show the P-values in Table 3 rather than (***) although a note is indicated in this regard. It’s their signature in the text, so I understand that they deserve this recognition. su14095590_makarova 0 +The hypothesis is interesting when they come from a discussion in the literature review to the field research to test a theory (models, methods, frameworks, etc). We believe that the reviewers' suggestions have been very helpful in improving the manuscript. su14095590_makarova 0 +The authors should explain better what is B Impact Assessment. We have made all the minor corrections indicated. su14095590_makarova 0 +Point 2: Are the research design, questions, hypotheses and methods clearly stated? In other words, it doesn't state what the authors are trying to test in this study. su14095590_makarova 0 +Point 3: In lines 391-395 I would prefer an Sk and Ku between -1 and 1. 1 Response to Reviewer 4 Comments Point 1: The paper is well structured and presented in a very meaningful manner. su14095590_makarova 0 +In the new version, although the authors – in the review response file - recognize that the link changed (“The link provided (https://bcorporation.eu/directory) was the one used. Table 2 and the paragraph after it is a repetition of Figure 1 and Table 1, could be cut. su14095590_makarova 0 +We understand what the authors intend to inform us after reading the paper. We believe that the reviewers' suggestions have been very helpful in improving the manuscript. su14095590_makarova 0 +This includes: • Line 169 page 4, studies [28] & [29] do not reference to any presented argument(s) unless the preceding para. Suddenly, appears one in the Method section, in a paper with a limited presentation of a technical model/certificate from an existed company. su14095590_makarova 0 +The literature review has been improved, and new references have been added (text in blue). Point 3: Unfortunately, I cannot recommend publication unless major changes are made to the discussion section and possibly recommendations are added for future research and practice. su14095590_makarova 0 +I suggest cutting the text from lines 90 to 103 because it’s quite an advertisement for the B Certificate. Point 4: Overall the information presented it makes sense to me. su14095590_makarova 0 +Point 4: Overall the information presented it makes sense to me. This includes: • Line 169 page 4, studies [28] & [29] do not reference to any presented argument(s) unless the preceding para. su14095590_makarova 0 +• Very good practical recommendations and criticism to the B Corp certification have been presented in the last para. The content in this section is exclusively dedicated to the Certification and the Corporation which offers it, there isn’t any scientific information there. su14095590_makarova 0 +If the rules of the Journal don’t allow to write down the Figures who is the author, I suggest to authors write it in a paragraph before the Fig 1, or in a footnote, according to Editor’s allowance. • It is better to show the P-values in Table 3 rather than (***) although a note is indicated in this regard. su14095590_makarova 0 +Literature review: There is still work to do discussing the five areas, not just relating them to each dimension of the Triple Bottom Line of the sustainability concept. Very well structured, with a critical and current problem. su14095590_makarova 0 +Point 2: Further, the hypothesis does not seem to be written correctly. I strongly recommend the authors find the new one. su14095590_makarova 0 +In other words, it doesn't state what the authors are trying to test in this study. There isn’t a source below the Title of Figure 1, though after that seems that B Corporation is the owner of it. su14095590_makarova 0 +The authors presented and analyzed the variables/areas of certification with many models, it is interesting and is a basis for analysis in the next section. Response 5: We believe that the reviewers' suggestions have been very helpful in improving the manuscript. su14095590_makarova 0 +Point 2: Are the research design, questions, hypotheses and methods clearly stated? - workers values greater then 40, community greater than 58, environment 45, customers 46 (the bullets), in Fig 3 - values with global score greater than 130, in Fig. su14095590_makarova 0 +Discussion: The authors made an effort to add more discussion, though no one was about Cronbach’s alpha. Response 5: We believe that the reviewers' suggestions have been very helpful in improving the manuscript. su14095590_makarova 0 +Point 3: Unfortunately, I cannot recommend publication unless major changes are made to the discussion section and possibly recommendations are added for future research and practice. 2nd round Title: OK Abstract: OK Introduction: There is an improvement to do in the objective because it is still different from the one presented in the Abstract, and needs a correction to be aligned with the content of the text. su14095590_makarova 0 +Point 6: Results: The sentence from line 137 to line 138 isn’t clear when I saw Figure 6. Point 2: Are the research design, questions, hypotheses and methods clearly stated? su14095590_makarova 0 +Point 3: Unfortunately, I cannot recommend publication unless major changes are made to the discussion section and possibly recommendations are added for future research and practice. The method section has been improved (text in blue). su14095590_makarova 0 +• Very good practical recommendations and criticism to the B Corp certification have been presented in the last para. I suggest cutting the text from lines 90 to 103 because it’s quite an advertisement for the B Certificate. su14095590_makarova 0 +Even though this was clear to me, the title doesn’t show the real idea developed in the paper. 1 Response to Reviewer 1 Comments (round 2) Point 1: su14095590_makarova 0 +If the rules of the Journal don’t allow to write down the Figures who is the author, I suggest to authors write it in a paragraph before the Fig 1, or in a footnote, according to Editor’s allowance. It’s clever to reduce the number of companies, though it isn’t clear who contacts the companies, the authors or Company B? su14095590_makarova 0 +The manuscript has been revised to improve grammar and english language. The authors should reflect the presence of that in the text. su14095590_makarova 0 +1- need to update the literature review with recent studies 2- Please add a theoretical background section 3- What are the policy implications of your study 4- Author Response Dear Reviewer, Many thanks for your comments and suggestions. su14127346_perova 0 +I see the work interesting, although it needs a good reorientation, in order to make it more attractive to reading. 5- Please revise your data: your max tangibility is over 2 (which means that Net PP&E, a subset of Assets, is 2 times those same Assets - this should be a typo. su14127346_perova 0 +Please find the details in the attachment for Total Assets, Property, plant and equipment pulled in eikon excel and find the Eikon excel formula. "We address each of them as follows: +Reviewer_2 Author 1 1 0 2 ""To the best of our knowledge, this is the only study that addresses the role of economic and political uncertainty as a moderator in a model that accounts for the dynamic patterns of firm environmental performance"" (line 128)." su14127346_perova 0 +The only remark on the content refers to “Are the arguments and discussion of finding coherent, balanced and compelling? Regards, Pavagal Latha Fundamentals Content Support su14127346_perova 0 +Your review truly helped improve further the paper. Author Response Dear Reviewer, Many thanks for your comments and suggestions. su14127346_perova 0 +The authors could go into greater detail to explain the logic behind this relationship. "We address each of them as follows: +Reviewer_2 Author 1 1 0 2 ""To the best of our knowledge, this is the only study that addresses the role of economic and political uncertainty as a moderator in a model that accounts for the dynamic patterns of firm environmental performance"" (line 128)." su14127346_perova 0 +Dear Authors The paper has been significantly improved since the previous version. Dear Authors The paper has been significantly improved since the previous version. su14127346_perova 0 +The authors could go into greater detail to explain the logic behind this relationship. 1- need to update the literature review with recent studies 2- Please add a theoretical background section 3- What are the policy implications of your study 4- su14127346_perova 0 +It would be useful if the authors provided some speculative thoughts on the finding that the slope of the GenDiv variable is negative in highly uncertain countries on the firm's environmental performance (Figure 3 (c) red line). We take this review as a valuable opportunity to foster the quality of the paper. su14127346_perova 0 +"=@TR(""OBE.TO"",""TR.TotalAssetsReported;TR.PropertyPlantEquipmentTotalNet"",""Period=FY0 Frq=FY SDate=0 EDate=-12 Curn=USD CH=Fd RH=IN;periodenddate;currency;rfperiod"",C3) We have worked with content team to avoid this type of issue henceforth." Yet, some issues still need to be addressed: 1- su14127346_perova 0 +However, I will make some suggestions, so that it can be improved. "We address each of them as follows: +Reviewer_2 Author 1 1 0 2 ""To the best of our knowledge, this is the only study that addresses the role of economic and political uncertainty as a moderator in a model that accounts for the dynamic patterns of firm environmental performance"" (line 128)." su14127346_perova 0 +Author Response Please see the attachment Author Response File: Author Response.pdf 5- Please revise your data: your max tangibility is over 2 (which means that Net PP&E, a subset of Assets, is 2 times those same Assets - this should be a typo. su14127346_perova 0 +"4 6 - In line 192 you mention ""all the sectors""." Author Response Please see the attachment Author Response File: Author Response.pdf su14127346_perova 0 +Below we provide the details on how your comments and suggestions have been addressed. Please find the details in the attachment for Total Assets, Property, plant and equipment pulled in eikon excel and find the Eikon excel formula. su14127346_perova 0 +This is a well-executed study with a solid research base. 2- Please revise if it makes sense to present your research hypothesis in the introduction. su14127346_perova 0 +The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. Point 7: Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. toxins14060409_perova 0 +Minimizing DON contamination in grains is a major goal of Fusarium Head Blight (FHB) research community. Among the three methods used, the upper bilateral floret injection (UBFI) maximizes DON accumulation in grain and significantly distinguishes DON content in different wheat genotypes, indicating that the method could be useful for breeding program to develop wheat cultivars with resistance to DON accumulation. toxins14060409_perova 0 +Point 7: Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. Authors in this manuscript report that DON accumulation in wheat grain is affected by inoculation methods (infection points). toxins14060409_perova 0 +While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. toxins14060409_perova 0 +1 Response to Reviewer 1 Comments Point 1: I would like to suggest authors label inoculation points in Figure 1, which could give readers a clear view of three different inoculation methods. Point 2: Line 142: “proportion of PPSD” should be “proportion of PSD or PPSD”. toxins14060409_perova 0 +The following are some comments and suggestions. 1 Response to Reviewer 2 Comments Point 1: I would suggest to avoid citing supplementary figures at the beginning of the chapter. toxins14060409_perova 0 +The paper describes a set of experiments carried out in 2020 2021 on isogenic lines of wheat using different methods of Fusarium inoculation in order to assess the effect of Fusarium inoculation on FHB disease index and DON accumulation. Among the three methods used, the upper bilateral floret injection (UBFI) maximizes DON accumulation in grain and significantly distinguishes DON content in different wheat genotypes, indicating that the method could be useful for breeding program to develop wheat cultivars with resistance to DON accumulation. toxins14060409_perova 0 +The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. toxins14060409_perova 0 +Point 7: Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. The following are some comments and suggestions. toxins14060409_perova 0 +Point 7: Fhb1- and Fhb1+ don’t appear in Table S1, so they can be removed from the footnote. While DON concentrations in grains are usually correlated with disease severity, high DON levels have been observed in asymptomatic kernels. toxins14060409_perova 0 +The paper is of high interest for the community working on FHB and shows the importance of inoculation method on the results of disease and mycotoxin accumulation. It is clearly written so it is suitable for publication given some minor changes/modifications: 1) toxins14060409_perova 0 +##Comments on the title, Abstract, and References Response 16: Thank you very much for your kind reminder. w14030367_makarova 0 +The BAC-UF process in this work was considered feasible to produce 28 clean drinking water. The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. w14030367_makarova 0 +Please, clarify whether the results of this document are from a single experiment or from an average resulting from replications. Point 8: T-test results should be included in Table 2. w14030367_makarova 0 +The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. Please consider these at end of this sentence……The oxidation method exhibited a fast reaction speed and high removal efficiency…(i) Role of nanomaterials in the treatment of wastewater: A review (ii) Advances and challenges in developing efficient graphene oxide-based ZnO photocatalysts for dye photo-oxidation. w14030367_makarova 0 +##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). Response 7: Thank you very much for your kind reminder. w14030367_makarova 0 +Please consider these suggestions as listed below. Point 6: I strongly suggest that the authors explain how they performed the t-tests. w14030367_makarova 0 +The same trend (Figure 2) was mainly due to the stable removal ability of BAC and UF for organics, causing the removal restriction. Please, clarify whether the results of this document are from a single experiment or from an average resulting from replications. w14030367_makarova 0 +Response 9: Thank you very much for your kind reminder. The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. w14030367_makarova 0 +Point 7: The reviewer suggests evaluating the statistical t-test for Figures 4. ##Comments on the title, Abstract, and References w14030367_makarova 0 +Cite the following references: Panagopoulos, A. Study and evaluation of the characteristics of saline wastewater (brine) produced by desalination and industrial plants. w14030367_makarova 0 +Response to Reviewer 3 Comments Point 1: The title seems good, but the abstract seems to be fine. In this study, the authors investigated the removal efficiency of Biological activated carbon (BAC) and biofilter coupling ultrafiltration (UF) system process for the treatment of surface water contaminated by pharmaceutical and personal care products (PPCPs). w14030367_makarova 0 +After the process, the water quality was analyzed including CODMn, UV254, NH4+-N, and PPCPs. The study was carried out in the pilot-scale BAC-UF process with a treatment capacity of 0.16 m3/h. w14030367_makarova 0 +Process Safety and Environmental Protection, 146, pp. Response 14: Thank you very much for your kind reminder. w14030367_makarova 0 +Nev- 21 ertheless, BAC and UF were both related to the removal effects of NH4+-N, NO2−-N and NO3−-N. 22 Importantly, the BAC-UF process showed high efficiency in the removal PPCPs micropollutants 23 and the average removal of total PPCPs reached 47.84%, especially Anhydroerythromycin, Sul- 24 fachloropyridazine, Sulfadiazine, Trimethoprim, and Caffeine. Why is the standard deviation of Erythromycin showing a high value? w14030367_makarova 0 +The paper is interesting.I recommend publication only if the following issues can be addressed. Response 3: Thank you very much for your kind reminder. w14030367_makarova 0 +Point 8: The main objective of the work must be written on the more clear and more concise way at the end of introduction section. Therefore, in this study, a BAC-UF system was carried out for several months with pilot scale to access the long-term removal performances and the respective contributions of BAC and UF. w14030367_makarova 0 +Generally, many PPCPs 41 flow through conventional water treatment processes with little degradation due to their 42 persistency or/and the continuous introduction [5]. Please revise your paper accordingly since some issue occurs on several spots in the paper. w14030367_makarova 0 +The reviewer suggests at least a t-test analysis. Please cite this reference with existing reference 3….Role of nanotechnology for design and development of cosmeceutical: application in makeup and skin care. w14030367_makarova 0 +Response 9: Thanks very much for this comment. Point 9: Point 6: Why the same trend of increase or decrease in graphs (Fig. w14030367_makarova 0 +Response 6: Thanks very much for this comment. Point 7: Table 1: What is the salinity (in mg/L) of the samples ? w14030367_makarova 0 +Have the authors compared the BAC-UF performance to that of nanofiltration? Besides, the t-test was used and proved the significant difference between BAC-Effluent and BAC/UF-effluent. w14030367_makarova 0 +The reviewer suggests statistical analysis using a t-test (Raw water- BAC-Effluent and Raw water – BAC/UF-effluent). Point 10: Please add chemical reagents section and stated all chemical with brand specifications. w14030367_makarova 0 +The above coupling process makes up for the defects concerning respective operations of the BAC biofilter and UF. Response to Reviewer 3 Comments Point 1: The title seems good, but the abstract seems to be fine. w14030367_makarova 0 +The concentration of ammonia nitro- 20 gen in the raw water was closely related to the removal rate of BAC-UF on ammonia nitrogen. I reviewed the article with title Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface water``. w14030367_makarova 0 +We have used an English Language Editing service to correct the grammatical and spelling errors and to make the expressions conform to correct scientific English (the Language Editing Certification is attached below). Authors should add a list of abbreviations before the references. w14030367_makarova 0 +Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. Author Response Please see the attachment Author Response File: Author Response.docx w14030367_makarova 0 +Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. Why is the DO concentration of BAC-effluent sometimes higher than the Raw water. w14030367_makarova 0 +Concentrations of typical antibiotics in the raw water (significant value, 0.05). Point 7: Please show the t-value and p-value in a scientific view (e.g., 2.79E-4 would be P <.001). w14030367_makarova 0 +Response 7: Thank you very much for your kind reminder. Response 9: Thanks very much for this comment. w14030367_makarova 0 +Response 10: Thanks very much for this comment. Point 7: Please show the t-value and p-value in a scientific view (e.g., 2.79E-4 would be P <.001). w14030367_makarova 0 +The article topic is intriguing and promising in the area. The periodic backwash (7days) of BAC caused sometimes the dissolved oxygen concentration of BAC-effluent higher than that of raw water. w14030367_makarova 0 +Response 17: We are so sorry to make reviewer’s reading uncomfortable. Point 5: Please add t-test results in Table 1 for each parameter to understand the significant differences. w14030367_makarova 0 +Point 9: Please check the abbreviations of words throughout the article. Point 14: Please use one style for units such as m3/h or m3h-1 Please revise your paper accordingly since some issue occurs on several spots in the paper. w14030367_makarova 0 +Response 7: Thank you very much for your kind reminder. Please, clarify whether the results of this document are from a single experiment or from an average resulting from replications. w14030367_makarova 0 +Results seem to be related to a unique experiment. Point 5: The novelty of the work must be clearly addressed and discussed, compare previous research with existing research findings and highlight novelty. w14030367_makarova 0 +43 Citation: Wanga, Q.; Tanga, X.; Zenga, W.; Wangb, F.; Gongb, W.; Chena, J.; Wanga, J.; Lia, G.; Lianga, H. Pilot-scale biological activated carbon filtration-ultrafiltration (BAC-UF) system for removing pharmaceutical and personal care products (PPCPs) from surface wa- ter. After the gas scrubbing and the hydraulic backwashing, the dissolved oxygen detection of the effluent was carried out, resulting in the above results for dissolved oxygen. w14030367_makarova 0 +Point 7: The reviewer suggests evaluating the statistical t-test for Figures 4. However, these results are not shown in the manuscript, how many replicated were carried out by experiment? w14030367_makarova 0 +Response 10: Thanks very much for this comment. Point 5: Conclusion: Make it as one or two paragraphs. w14030367_makarova 0 +Authors should add a list of abbreviations before the references. Two native English-speaking colleagues help us verify the manuscript. w14030367_makarova 0 +Point 4: Conclusion: Discuss the applicability of your findings/results and future study in this field. They also discussed their results in detail and put the difference in their results compared to the data with the literature. w14030367_makarova 0 +However, the mechanisms of the two-stage biofilm, such as bacterial and metazoan communities, membrane fouling and dissolved oxygen transfer, should be further investigated to enhance the removal efficiency and stability of this system. Response to Reviewer 4 Comments Point 1: Authors should avoid abbreviations in the title. w14030367_makarova 0 +##Overall comments The authors described a pilot-scale BAC and BAC-MF technology to remove PPCPs from the river water (Foshan, Guangdong, China). Point 16: Section 4 should be renamed by Conclusion and Future perspectives. w14030367_makarova 0 +Response 9: Thank you very much for your kind reminder. Results seem to be related to a unique experiment. w14030367_makarova 0 +Response 6: Thanks very much for this comment. Point 7: The reviewer suggests evaluating the statistical t-test for Figures 4. w14030367_makarova 0