We highlight empirical examples and present a conceptual model for the generation of resource polymorphism – emphasizing eco evo devo, and identify current gaps in knowledge.A major goal of evolutionary science is to understand how biological diversity is generated and altered. Despite considerable advances, we still have limited insight into how phenotypic variation arises and is sorted by natural selection. Here we argue that an integrated view, which merges ecology, evolution and developmental biology (eco evo devo) on an equal footing, is needed to understand the multifaceted role of the environment in simultaneously determining the development of the phenotype and the nature of the selective environment, and how organisms in turn affect the environment through eco evo and eco devo feedbacks. To illustrate the usefulness of an integrated eco evo devo perspective, we connect it with the theory of resource polymorphism (i.e. the phenotypic and genetic diversification that occurs in response to variation in available resources). In so doing, we highlight fishes from recently glaciated freshwater systems as exceptionally well‐suited model systems for testing predictions of an eco evo devo framework in studies of diversification. Studies on these fishes show that intraspecific diversity can evolve rapidly, and that this process is jointly facilitated by ( I.et al., et al., Many key advances in evolutionary biology over the last century, such as the modern synthesis, have resulted from synergies among fields. Yet, our understanding of what drives the evolution of biological diversity is still limited – not least because we often adopt a discipline‐specific focus. For instance, the fields of evolutionary ecology and population genetics have both yielded strong empirical evidence for the role of natural selection in the evolution of biological diversity Endler, , but theet al., et al., The origins of phenotypic variation have been a focus of the field of evolutionary developmental biology  and how this affects evolution  requires the integration of more than two approaches Givnish, . SubsequIII.(1)et al., Resource polymorphism is defined by the occurrence of intraspecific morphs that show differential resource use, usually through differences in feeding biology and habitat use  exploitation by a monomorphic population of a new or unexploited environment – often with high levels of intraspecific competition; (ii) rapid phenotypic shifts, especially in behaviour, morphology and life history, primarily mediated through phenotypic plasticity; (iii) divergent selection and the evolution of specialized and more distinct morphological groups, accompanied by reduced phenotypic plasticity and, finally; (iv) reduced gene flow and the evolution of prezygotic and potentially postzygotic reproductive isolation Salvelinus), whitefish (genera: Coregonus and Prosopium), three‐spined stickleback (Gasterosteus aculeatus) and Eurasian perch (Perca fluviatilis)  makes them ecologically tractable. Their recent evolutionary divergence, and associated incomplete reproductive isolation (i.e. ongoing gene flow), opens a window to evolution where processes facilitating or impeding divergence can be studied along a so‐called ‘speciation continuum’  and Eurasian perch show greater survival in vegetated littoral habitats, whereas streamlined individuals survive better in open water when exposed to predation et al., et al., et al., et al., et al., et al., via niche construction, see Section I).The development of the field of eco‐evo dynamics has been motivated by the recognition that ecological and evolutionary processes can occur at similar time scales, and by our limited understanding of what defines a selection regime   and whitefish (Coregonus lavaretus)  et al., et al., et al., et al., et al., et al., et al., et al., et al., Many natural populations show substantial fluctuations in density over time  morphs in the sub‐Arctic Norwegian lake Fjellfrosvatn was characterized by temporally stable resource use, most likely reflecting predictable ecological conditions  to lakes has led to alterations in the visual conditions and changes in the resource base and, subsequently, to increased phenotypic divergence between littoral and pelagic Eurasian perch et al., et al., et al., et al., et al., et al., et al., PPARAa gene involved in mitochondrial regulation) appears to facilitate colonization of freshwater environments by marine fish et al., et al., et al., et al., et al., et al., et al., et al., et al., Understanding the molecular genetic basis of phenotypic change has long been a prevalent theme in research on polymorphic postglacial fishes. Recently, molecular genetic technologies have started to provide more direct insight into the genetic mechanisms underlying resource polymorphism in postglacial fishes than was possible with quantitative genetic approaches alone. For example, quantitative trait locus (QTL) mapping continues to yield valuable information on the genomic architecture  of traits involved in phenotypic divergence [e.g. Arctic charr  is variation in number of lateral armour plates in three‐spined stickleback. The ancestral marine type has bony armour plates along its body, while the derived freshwater types have variably reduced plate numbers , which are likely to have a complex genetic basis with gene × environment interactions Edwards, . For exa(3)As we understand better the genetic basis of complex phenotypic variation, we will also need to broaden our thinking to include dynamic gene–environment interactions, such as phenotypic plasticity and transgenerational  effects. Cues from the offspring's own environment as well as the parental phenotype  jaw morphologies by benthic and limnetic food is associated with the effects of a regulatory locus, the patched 1 (ptch1) gene, which affects jaw structure through variable mediation of bone deposition around the cartilaginous precursor  showed that variation in eye and orbit size in surface fish was plastically increased by exposure of embryos to the low water conductivity typical of cave environments , exposure of larger embryos to stressful environments resulted in greater plasticity and a wider developmental trajectory than in smaller embryos  can respond to signals effected by yolk quantity    under relevant ecological conditions provides an important empirical focus to help integrate eco evo devo Fig. . Such stIV.In certain resource‐polymorphic fishes, aspects of the eco evo devo framework have been examined, illustrating the strength of an integrated approach.(1)et al., et al., et al., et al., et al., et al., Littoral and pelagic individuals of Eurasian perch exhibit greater phenotypic divergence in lakes with invasive zebra mussels than in those without zebra mussels (Hirsch (2)et al., 1989a; Ahi et al., et al., et al., et al., et al., Salvelinus malma), differences in adult morphology are related to variable embryonic skull ossification . Research on craniofacial transcriptional dynamics in the progeny of benthic and pelagic Arctic charr morphs has identified a gene network, related to glucocorticoid (GC) signalling, that influences bone development and is expressed at higher levels in the benthic than the pelagic progeny et al., et al., et al., et al., Coregonus sp. “Bodenbalchen” and a limnetic C. zugensis) species  during early divergence in novel environments  the role of spatial and temporal variability and discreteness of resources; (ii) the significance of transgenerational effects; (iii) the role of eco‐evo feedbacks across generations and eco‐devo feedbacks during ontogeny; and (iv) structuring of ecosystems and developmental architecture. We strongly advocate that future research should consider explicitly the integration of these processes rather than focusing on the alternatives (such as genes versus environment). Thus, we need studies that explore how evolutionary and developmental processes feed back on ecosystems, both in controlled mesocosms and field experiments (e.g. Lundsgaard‐Hansen et al., et al., et al., et al., In practical terms, rigorous tests of the different pathways of such an eco evo devo framework Figs  and 4 arVIII.et al., et al.,et al.,We believe that the integration of multiple interacting processes into the eco evo devo framework proposed here Fig.  will allWe emphasize that an eco evo devo approach is a powerful conceptual framework for understanding the complex integrated processes that ultimately determine the patterns of biological diversity in nature. Thus, we have discussed how natural selection is not an autonomous process that is only driven by factors external to the respective organisms, but also by intrinsic factors whereby organisms can shape their own external environment. The external factors that determine selection can often be the same as those that influence individual development through phenotypic plasticity. Thus, the snapshot of phenotype–fitness relationships we often use to measure natural selection empirically may be a subset of much broader and highly dynamic eco evo devo processes. It follows that these relationships could be viewed as evidence for coordinated variation between dynamic intrinsic developmental factors, which affect the outward phenotype, and current ecological factors. We hope that future advances in evolutionary biology will accommodate more forcefully the role of development and apply a scientific thinking that fully integrates the sub‐fields of eco, evo and devo.Table S1. Examples of empirical evidence for different patterns of resource polymorphism in postglacial freshwater fishes including phenotypic distribution, trait type, ecological axis of divergence, and evidence of reproductive isolation.Appendix S1. Overview of resource polymorphism in fish in postglacial freshwater systems.Click here for additional data file.


In focusing on how organisms' generalizable functional properties (traits) interact mechanistically with environments across spatial scales and levels of biological organization, trait‐based approaches provide a powerful framework for attaining synthesis, generality and prediction. Trait‐based research has considerably improved understanding of the assembly, structure and functioning of plant communities. Further advances in ecology may be achieved by exploring the trait–environment relationships of non‐sessile, heterotrophic organisms such as terrestrial arthropods, which are geographically ubiquitous, ecologically diverse, and often important functional components of ecosystems. Trait‐based studies and trait databases have recently been compiled for groups such as ants, bees, beetles, butterflies, spiders and many others; however, the explicit justification, conceptual framework, and primary‐evidence base for the burgeoning field of ‘terrestrial arthropod trait‐based ecology’ have not been well established. Consequently, there is some confusion over the scope and relevance of this field, as well as a tendency for studies to overlook important assumptions of the trait‐based approach. Here we aim to provide a broad and accessible overview of the trait‐based ecology of terrestrial arthropods. We first define and illustrate foundational concepts in trait‐based ecology with respect to terrestrial arthropods, and justify the application of trait‐based approaches to the study of their ecology. Next, we review studies in community ecology where trait‐based approaches have been used to elucidate how assembly processes for terrestrial arthropod communities are influenced by niche filtering along environmental gradients  and by abiotic and biotic disturbances . We also review studies in ecosystem ecology where trait‐based approaches have been used to investigate biodiversity–ecosystem function relationships: how the functional diversity of arthropod communities relates to a host of ecosystem functions and services that they mediate, such as decomposition, pollination and predation. We then suggest how future work can address fundamental assumptions and limitations by investigating trait functionality and the effects of intraspecific variation, assessing the potential for sampling methods to bias the traits and trait values observed, and enhancing the quality and consolidation of trait information in databases. A roadmap to guide observational trait‐based studies is also presented. Lastly, we highlight new areas where trait‐based studies on terrestrial arthropods are well positioned to advance ecological understanding and application. These include examining the roles of competitive, non‐competitive and (multi‐)trophic interactions in shaping coexistence, and macro‐scaling trait–environment relationships to explain and predict patterns in biodiversity and ecosystem functions across space and time. We hope this review will spur and guide future applications of the trait‐based framework to advance ecological insights from the most diverse eukaryotic organisms on Earth. I.et al., et al., et al., et al., Biodiversity is often described exclusively in terms of the distinct taxonomic entities (species) which it contains, and measured in terms of its taxonomic component, taxonomic diversity (e.g. species richness). Taxonomic approaches, however, offer limited insight into the evolutionary and mechanistic underpinnings of ecological phenomena; these have recently been studied using alternative approaches for describing biodiversity. For instance, phylogenetic approaches emphasize organisms' evolutionary affiliations, and measure the phylogenetic component of biodiversity, phylogenetic diversity i) traits are phenotypic entities that are strictly measured on individual organisms; and (ii) traits are functional, in the sense that their interactions with biotic and abiotic environments affect performance, and consequently organism fitness . These are twofold: et al., via their responses and effects. This makes it possible to aggregate and integrate different traits to explain structure and functioning mechanistically across different scales of organization   constrained to examining one particular ecological theory or question; the predictive value of trait‐based approaches essentially stems from their versatile potential to test different ecological theories empirically, and reveal mechanisms across different organizational scales. Much of the existing research on terrestrial arthropods has applied trait‐based approaches to investigate community assembly within the context of ecological filters , functional divergence (FDiv), and functional evenness (FEve); see Mouchet et al. et al., et al., In addition to the notable contributions of trait‐based studies on plants, trait‐based research on other taxa has considerable potential to improve ecological theory and practice. We suggest that terrestrial arthropods represent an ideal group for such work because their taxonomic and ecological diversity is unmatched. Most eukaryotic species on Earth are terrestrial arthropods Zhang, ; they aret al., et al., et al., et al., et al., et al., To facilitate trait‐based research on terrestrial arthropods, there is an abundance of information in the literature and extensive physical and digital collections via a functional group approach akin to that used in plants ; the number of groups within a particular scale of biological organization determined its functional diversity. Examples of widely used functional groupings include those for ants and termites, based on taxonomic relationships and diet specialization et al., et al., et al., et al., ‘Community’ refers to a set of species with shared ecological characteristics that coexist in the same area Chesson, . CommuniIn addition to establishing the overall deterministic nature of the assembly process, trait‐based approaches can be used to reveal how specific niche‐based mechanisms operate in community assembly. Thus far, trait‐based studies on terrestrial arthropods have predominantly investigated how the mechanism of niche filtering influences community assembly along various environmental gradients (see Section (a)et al., et al., et al., Niche filtering  occurs when the abiotic or biotic environment imposes barriers to establishment and/or survival, thus favouring the co‐occurrence of individuals with similar traits. It then follows that the typical signature of niche filtering is a non‐random pattern of clustering among trait values  in the emergent community et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al. et al., et al., et al. . Studies on European Lepidoptera report equivocal results. Some found evidence for functional clustering in homogenous habitats with shorter vegetation, where species with higher mobility, growth and fecundity were selected for et al. Disturbances are abiotic or biotic forces or processes that result in perturbations, where ecosystems deviate – that is, are changed – from their reference states Rykiel, . Below w(i)et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., In line with theoretical expectations Swengel, , trait‐b(ii)et al., et al., et al., et al., et al., et al., et al., et al., et al., Like fire, flood events generally act as strong niche‐filtering mechanisms across multiple taxonomic groups (Dziock (iii)et al., et al. et al., et al., et al., et al., et al., et al., et al., Knowledge of the effects of biodiversity on ecosystem functions (BEF relationships) is integral to safeguarding Earth systems and human wellbeing , as well as the specific techniques used (e.g. different ways of measuring the same ecosystem function). Spatial scale is another vital factor to consider and may explain interaction effects between functional identity and functional complementarity. For instance, research on plant communities suggests that functional identity better predicts BEF relationships at larger spatial scales, where niche filtering along environmental gradients leads to the clustering of trait values that in turn dominate communities and ecosystem functions et al., et al., et al., et al., et al., et al., et al., A fundamental assumption of the trait‐based approach is trait functionality; all studies should use traits that possess fitness‐functionality, and where BEF studies are concerned, those traits should also possess ecosystem‐functionality. However, these assumptions of trait functionality have not been explicitly tested for the overwhelming majority of terrestrial arthropods, and the problem is further compounded by the diversity of traits recorded for each species. For instance, some studies used multiple morphological measurements with limited evidence for the functionality of these separate ‘traits’ (Wiescher (a)et al. et al., et al., et al., Naturally, experiments involving performance measures along environmental gradients can only be undertaken for a fraction of terrestrial arthropods. However, standards for observational trait‐based studies can still be raised so as to enhance their potential for synthesis, generality and prediction. First, investigators should strive to justify explicitly the functionality of the traits used. In the absence of evidence, traits should at the very least be selected on the theoretical bases of their functionality – that is, how their abiotic or biotic interactions may impact specific fitness components  and relevant ecosystem processes. Selecting traits in this manner will better facilitate a mechanistic understanding of observed empirical patterns (i.e. trait–environment relationships) to generate good predictions. Essentially, only traits with demonstrable indirect or direct links to performance should be selected, while also balancing this with the important objective of maximizing the functional niche represented   environmental gradient (e.g. Gerisch (2)et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Intraspecific variation in phenotypic traits within a species may be generated through mechanisms such as local adaptation, parental conditions, ontogeny and phenotypic plasticity et al., et al., et al., Most if not all sampling methods bias detection towards particular species and away from others. When sampling methods consistently fail to detect certain species because of their particular traits or trait values (detection filtering), the effects on observed trait–environment relationships may be substantial in situ will be most representative of the ecological relationships investigated, since these are the traits directly undergoing selection by, or affecting, the studied environment. Continuous data will better reflect changes in the intensities of a trait's interactions than discrete categorical data  one plant species; (ii) two plant species; and (iii) three plant species, etc.’  one plant species; (ii) more than one species from the same genus; (iii) more than one genus from the same family; and (iv) more than one family from the same order, etc.’  or categorical form . The particular source and structure of trait information used will affect the quality of results obtained. Where possible, investigators should prioritize the collection of primary data on traits, and in continuous form. Primary data on traits measured et al., et al., et al., http://carabids.org; Homburg et al., et al., et al., et al., et al., Of course, it will not always be feasible to collect primary data on traits. There is a general lack of knowledge on species' traits, ecological functions and interactions et al., et al., et al., et al., et al., The sheer biological diversity of terrestrial arthropods affords new and exciting opportunities for exploring the ecological effects of distinct phenotypes that are absent from other organisms. Many of these idiosyncratic traits have not been investigated in trait‐based studies thus far. Especially relevant to intraspecific variation are traits that reflect ‘personality’: temporally consistent individual differences in behaviour along one or more behavioural axes (Modlmeier (2)et al., et al., The biotic force of competition has traditionally been thought to shape community assembly by preventing individuals with very similar niches from coexisting  (e.g. storage effects and relative non‐linearities) mediated by species' niche differences, and the effects of differences in competitive abilities  that favour particular species over others in the absence of stabilization  as well as performance traits which may conceivably directly impact growth rates (e.g. fecundity) are not distinguished from traits that are assumed to reflect niche differences, which potentially contribute to A.Integrating modern coexistence theory with trait‐based ecology may provide a powerful paradigm for tackling the fundamental question of coexistence , dynamic , unstable  and quasi‐neutral  sensu Vellend, et al., et al., et al., et al., et al., et al., et al., via trait‐matching also has facilitated assessments of the impact of environmental changes on multiple trophic levels  with the functional components of BEF research (e.g. species' responses to and effects on their environments) have been proposed to improve prediction of the many ecosystem functions encompassing multi‐trophic interactions et al., i) describe the distribution of traits along environmental gradients and across spatial scales; then, using this information; (ii) explain the geographic distribution of organisms, biodiversity patterns, and ecosystem processes; and (iii) predict responses to environmental changes using trait‐based predictive functions and models , by providing insights into the spatial scaling of assembly processes (e.g. species interactions) across broad gradients (Violle et al., et al., et al., et al., The emerging field of functional biogeography investigates the patterns, causes, and consequences of the geographic distribution of trait diversity (Violle , et al.  showed tV.By focussing on the functional properties of individual organisms, trait‐based ecology provides a broad, mechanistic framework for synthesizing, explaining and predicting structure and function across different levels of biological organization.The time is ripe for a trait‐based ecology of terrestrial arthropods. Such work will improve understanding of the processes underlying patterns of diversity for complex ecological communities encompassing multiple trophic levels, and provide mechanistic insights to the functioning of essential ecosystem services such as pollination, biological control and nutrient cycling. For many terrestrial arthropods, taxonomic impediments have limited ecological research, and a focus on traits will be particularly useful for expediting understanding some of the interactions and functions of these taxa. The growing volume of data on the traits of terrestrial arthropods in databases and the wider literature, as well as physical and digital collections, will facilitate work on the generality of functional relationships across geographic regions and spatial scales.Findings from pioneering studies on the trait‐based ecology of terrestrial arthropods attest to the value of this burgeoning field. Here, trait‐based approaches have been especially useful for elucidating the specific mechanisms driving the deterministic assembly of diverse communities across different environmental gradients, as well as their responses to disturbances – often revealing distinct patterns in functional diversity not detected by taxonomic and phylogenetic approaches. Preliminary work investigating terrestrial arthropod‐mediated ecosystem functions did not observe a consistent relationship between functional diversity and ecosystem function, although comparisons are strictly limited by differences among studies in terms of the focal scale, community characteristics and methods used.New studies expanding the scope of terrestrial arthropod trait‐based research will advance knowledge in longstanding as well as emerging areas in ecology. As previous studies mainly focused on the interactions between traits and abiotic environments, one immediate avenue for future work will be to explore how biotic interactions – including various competitive, non‐competitive, and multi‐trophic interactions among species – shape structure and function across different environmental gradients and spatial scales. At the same time, novel research on the functional biogeography of terrestrial arthropods may succeed in mapping global distributions of their functional diversity, thereby enhancing ecological forecasting and the management of ecosystem services in the face of climate change and the spread of invasive species. Importantly, such efforts will be undermined if trait functionality is not rigorously tested, if the effects of intraspecific variation are not accounted for, and if the collection of trait information is biased or inconsistent. The predictive value of future work also rests upon the willingness of researchers to go beyond describing patterns to identify mechanisms – that is, by undertaking hypotheses‐driven investigations grounded in ecological theory. Future studies in terrestrial arthropod trait‐based ecology should thus explicitly address these aspects in the critical stages of study design, trait selection, sampling and measurement, as well as in the treatment and consolidation of trait data.Realizing trait‐based ecology's higher goal of synthesis, generality and prediction also demands taxonomic excellence – to safeguard the accuracy and coherence of trait data. Thus it is important to recognize that functional approaches to describing biodiversity are ultimately complements, and not substitutes to taxonomic ones. While a focus on traits can help to overcome significant taxonomic impediments to the understanding of ecology, trait‐based research faces an even greater impediment – the lack of information on the form and functionality of organisms. Especially in the hyper‐diverse terrestrial arthropods, basic data are lacking on diet, physiology, phenology and behaviour – let alone information on how these vary intraspecifically along environmental gradients. In conclusion, we propose that reconciling contemporary trait‐based research with the long‐established study of taxonomy and natural history will pave the way for a more robust understanding of the mechanisms structuring arthropod diversity across space and time.


We appreciate the interest and comments from Joshi et al.  regardinFirst, the authors cite a paper by Anderson et al.  that demSecond, Joshi et al.  point toThe third comment involved concerns the differing levels of support in the Saslow et al.  and HallFourth, the concerns raised about the findings from Hallberg et al.  are riddUtility of Unrefined Carbohydrates in Type 2 Diabetes. Comment on Reversing Type 2 Diabetes: A Narrative Review of the Evidence, Nutrients 2019, 11, 766 [Furthermore, this review was not intended to be a systematic review, and therefore does not reflect the entirety of the current evidence. However, we feel that this review gives an accurate depiction of the evidence that exists for diabetes reversal. Joshi et al. present no evidence to support the title of their paper (presumably their point) We hope the above gives clarity to the issues raised by Joshi et al. . We appr


Although violence is a vital public health problem, no prospective studies have tested for subsequent vulnerability to violence, as a victim or witness, in members of the general population with a range of psychiatric symptoms, or evaluated the importance of higher symptom burden on this vulnerability.We used successive waves of a household survey of Southeast London, taken 2 years apart, to test if association exists between psychiatric symptoms  and later victimisation, in the form of either witnessing violence or being physically victimised, in weighted logistic regression models. Statistical adjustment was made for prior violence exposure, sociodemographic confounders, substance/alcohol use and violence perpetration. Sensitivity analyses were stratified by violence perpetration, sex and history of mental health service use.After adjustments, psychiatric symptoms were prospectively associated with reporting any subsequent victimisation (odds ratio (OR) 1.88, 95% confidence interval (CI) 1.25–2.83), a two times greater odds of reporting witnessed violence  and reporting physical victimisation . One more symptom endorsed was accompanied by 47% greater odds of subsequent victimisation . In stratified analyses, statistical associations remained evident in non-perpetrators, and among those without a history of using mental health services, and were similar in magnitude in both men and women.Psychiatric symptoms increase liability to victimisation compared with those without psychiatric symptoms, independently of a prior history of violence exposure and irrespective of whether they themselves are perpetrators of violence. Clinicians should be mindful of the impact of psychiatric symptoms on vulnerability to victimisation, including among those with common psychiatric symptoms and among those who are not considered at risk of perpetrating violence. We hypothesise that the presence of psychiatric symptoms, and increasing number of symptom domains present, will be associated with later victimisation.et al., et al., et al., The South East London Community Health study   . Employment status was categorised into employed, student, unemployed and other  in the last 12 months. Finally, a binary ‘overall victimisation’ variable was created, reflecting endorsement of either being physically victimised or witnessing violence.et al., All statistical analyses were performed in STATA 14  participated in SELCoH-2  was found for a linear trend between the number of symptom domains endorsed and overall victimisation. Compared with those not endorsing any symptom domain, those reporting 3–4 symptom domains had more than three times the odds of reporting recently witnessed violence, and twice the odds of reporting physical victimisation, in adjusted models. For each further symptom domain endorsed, there was a 1.55-fold increase in the odds of later witnessed violence, a 1.3-fold increase in the odds of later physical victimisation, and a 1.47-fold increase in the odds of overall victimisation.After adjustment, endorsing any psychiatric symptom domain was associated with a greater than twofold increase in the odds of later witnessed violence, a 1.75-fold increase in the odds of being physically victimised and a close to twofold increase in the odds of overall victimisation see . StatistIn order to examine the influence of important potential confounders in more depth, we repeated the analyses shown in In a sample of Southeast London household residents, psychiatric symptoms, ascertained based on endorsement of epidemiological screening tools for different domains of psychopathology, were prospectively associated with later victimisation over a 3-year period, both overall, by being physically victimised, and as a witness, compared with those without symptoms at baseline. An increasing number of symptom domains predicted greater odds of victimisation over time. The association was not limited to perpetrators of violence, or to those without a history of mental health service use. Although associations between endorsing any psychiatric symptom domain and later victimisation were observed in both men and women, estimates for women were of greater magnitude.et al., et al., et al., et al., We suggest that our study significantly strengthens a limited literature (Silver et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al. found prospective association between a single scale reflecting psychiatric morbidity and violent experiences, but examined only individuals remaining in the study at age 46 (Hart et al., et al. (The psychiatric consequences of victimisation are well known, and include psychosis (Varese , et al.  reportedet al., et al., et al., et al., et al., et al., This study was longitudinal and based on a randomly selected baseline sample. Detailed measurements of psychopathology were gathered, and we used conservative cut-offs to identify individuals in whom we could be reasonably confident there were clinically relevant symptoms in the various domains. On the other hand, there was attrition, which reduced the precision of estimates and limited study power to estimate associations with specific symptom domains in detail, as planned. People with psychiatric symptoms might have been more or less liable to report victimisation compared with people without psychiatric symptoms, leading to misclassification and resulting over or underestimation of the main association. However, studies indicate that the recall of victimisation events is generally reliable (Schneider, et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Although our results suggest that psychiatric symptoms may increase liability to subsequent victimisation, the exact explanations remain unclear. Our findings may, for example, be consistent with a ‘routine activities’ model of victimisation where violent experiences arise from the convergence of motive, opportunity and lack of adequate safeguards against violence (Miethe et al., We present the first prospective evidence that people with common psychiatric symptoms, and higher number of symptoms, have greater vulnerability to victimisation than those without symptoms, not limited to those with a history of perpetrating violence, those using services or those with prior exposure to violence. Lifestyle factors such as hazardous alcohol use and drug use, as well as perpetration history, appear to account for some of this association. There is already evidence that people with psychiatric disorders are systematically excluded from the benefits of public health interventions addressing, for example, smoking (Szatkowski and McNeill,


After decades of debate about the existence of non‐genetic inheritance, the focus is now slowly shifting towards dissecting its underlying mechanisms. Here, we propose a new mechanism that, by integrating non‐genetic and genetic inheritance, may help build the long‐sought inclusive vision of evolution. After briefly reviewing the wealth of evidence documenting the existence and ubiquity of non‐genetic inheritance in a table, we review the categories of mechanisms of parent–offspring resemblance that underlie inheritance. We then review several lines of argument for the existence of interactions between non‐genetic and genetic components of inheritance, leading to a discussion of the contrasting timescales of action of non‐genetic and genetic inheritance. This raises the question of how the fidelity of the inheritance system can match the rate of environmental variation. This question is central to understanding the role of different inheritance systems in evolution. We then review and interpret evidence indicating the existence of shifts from inheritance systems with low to higher transmission fidelity. Based on results from different research fields we propose a conceptual hypothesis linking genetic and non‐genetic inheritance systems. According to this hypothesis, over the course of generations, shifts among information systems allow gradual matching between the rate of environmental change and the inheritance fidelity of the corresponding response. A striking conclusion from our review is that documented shifts between types of inherited non‐genetic information converge towards epigenetics (i.e. inclusively heritable molecular variation in gene expression without change in DNA sequence). We then interpret the well‐documented mutagenicity of epigenetic marks as potentially generating a final shift from epigenetic to genetic encoding. This sequence of shifts suggests the existence of a relay in inheritance systems from relatively labile ones to gradually more persistent modes of inheritance, a relay that could constitute a new mechanistic basis for the long‐proposed, but still poorly documented, hypothesis of genetic assimilation. A profound difference between the genocentric and the inclusive vision of heredity revealed by the genetic assimilation relay proposed here lies in the fact that a given form of inheritance can affect the rate of change of other inheritance systems. To explore the consequences of such inter‐connection among inheritance systems, we briefly review published theoretical models to build a model of genetic assimilation focusing on the shift in the engraving of environmentally induced phenotypic variation into the DNA sequence. According to this hypothesis, when environmental change remains stable over a sufficient number of generations, the relay among inheritance systems has the potential to generate a form of genetic assimilation. In this hypothesis, epigenetics appears as a hub by which non‐genetically inherited environmentally induced variation in traits can become genetically encoded over generations, in a form of epigenetically facilitated mutational assimilation. Finally, we illustrate some of the major implications of our hypothetical framework, concerning mutation randomness, the central dogma of molecular biology, concepts of inheritance and the curing of inherited disorders, as well as for the emergence of the inclusive evolutionary synthesis. I.et al., et al., et al., et al., There is currently a heated debate about the necessity to modernize the modern synthesis of evolution (a)et al., The existence of non‐genetic inheritance has long been debated et al., et al., et al., et al.,Today, the focus is slowly shifting towards the understanding of the mechanisms and evolutionary consequences of non‐genetic inheritance, which remains one of the major challenges of modern biology This review focuses on the molecular mechanisms of non‐genetic inheritance in order to unify them with genetic inheritance into a single inclusive evolutionary synthesis. During this process, a new framework emerges that we propose here as a working hypothesis. The main idea is that of the existence of a relay among inheritance systems from more labile to more stable forms of inherited information following a persistent environmental change. The idea of a relay among inheritance systems was suggested previously  in inheritance systems seem to converge towards epigenetics. When this is the case, this epigenetic stage may generate a final handover towards genetic encoding. In this hypothesis, epigenetic marking constitutes a major hub linking non‐genetic germline inheritance with genetic inheritance. A profound difference between the genocentric and the inclusive vision of heredity revealed by the genetic assimilation relay proposed here lies in the fact that a given form of inheritance can affect the rate of change of other inheritance systems. We then use a simple theoretical model to investigate consequences of this relay in inheritance systems. We find that this form of epigenetically facilitated mutational assimilation i) be genetic, (ii) involve the germline, or (iii) generate germline‐dependent transmission  overlapping, classification focuses on mechanisms of resemblance rather than patterns. It includes three categories of processes: simultaneous exposure effects, germline‐independent transmission and non‐genetic germline transmission (Anway (a)simultaneous exposure effects germline‐independent transmission non‐genetic germline transmission et al., et al., et al., et al., et al., The existence of various categories of inheritance mechanisms raises the question of their roles in evolution  that exists in two highly heritable morphs, the most common having flowers with a marked dorsoventral asymmetry, and a peloric form  where flowers have radial symmetry  affecting flower asymmetry, which appears to be silenced in the peloric morph. This shows the extent to which epigenetic and genetic variation produce patterns of phenotypic change that are very difficult to distinguish. Many other examples are provided in Table There are many instances in which a heritable phenotypic change first attributed to a genetic change (i.e. a change in the DNA sequence) was later proved to be due to a functionally efficient heritable change in epigenetic marks. The most famous example is that of the toadflax The relay starts when previously non‐transmitted variation becomes transmitted. For example, behavioural innovations are reinvented regularly until social learning eventually triggers transgenerational stability et al., et al., et al., et al., et al., germline‐independent transmission in which epigenetically induced maternal behaviour becomes the environmental cause of the reconstruction of similar epigenetic marks in their developing daughters, and continues over many generations, leading to persistent mother–daughter resemblance in maternal care.The second step is when parental effects lead to heritable epigenetic marks arrow 2, Fig. , Fig. 2.More generally, parental capacity to modulate their offspring's epigenetic marks constitutes an ideal candidate inheritance mechanism for germline‐independent inheritance Stellaria longipes, this non‐genetic change has been linked to a lower level of DNA methylation  often can be transferred across generations (Cubas (4)et al., et al., germline‐independent transmission and non‐genetic germline transmission of behaviour.Epigenetics is also involved in long‐term memory systems, which can link cultural transmission to its potential epigenetic bases epigenetic germline transmission well after the disappearance of the environmental stress , this methylation pattern was transmitted to unexposed F1 and F2 offspring that then feared the same odour (but not a different odour) when first exposed to it.Mice provide another fascinating example of environmentally acquired traits that are directly epigenetically inherited over several generations (a)et al., et al., et al., et al., Perhaps the most direct pathway in the genetic assimilation relay from non‐genetic to genetic inheritance et al., et al., et al., et al., et al., At the larger scale of genomic regions , various studies suggest that the statistical link between epigenetic marks or chromatin state and mutation is very general  and local DNA‐sequence variation. This association was documented in a large epigenome‐wide association study in Chlamydomonas reinhardtii found that ‘differences in methylation patterns were not associated with nearby genetic mutations’  fraction of the population may take between 30 and 140 generations et al., et al., et al., et al., et al., et al., et al., et al., Drosophila and zebrafish, diverse classes of retrotransposons were recently shown to act ‘as molecular stowaways to gain passage from their site of production … to the oocyte germ plasm’  by epigenetic marks mutational assimilation’ , and eventually become genetically encoded, provided that the new environment remains stable for sufficient time for this multi‐generation mechanism to induce mutations that can then be selected. It thus corresponds to a ‘Intuitively, the proposed mechanism linking epigenetic and genetic changes has the potential to accelerate genetic evolution. Below, we present a model studying the extent to which this form of genetic assimilation can accelerate the genetic encoding of acquired heritable adaptations.III.et al., We now outline a model to explore the possible evolutionary consequences of epigenetically facilitated transfer of information between the environment and the epigenetic and genetic materials. The model simulates the evolution of populations experiencing a sudden environmental change that shifts an adaptive peak. We compare populations with specific strategies of hereditary transmission to assess how rapidly they can reach the new fitness peak. For that goal, as in previous studies (Herman (1)et al. , except when epigenes are costly to maintain (wcostly epigene peak < wgene peak). The population is limited to a fixed carrying capacity.The model is based on Klironomos et al. , with thet al.  and expls et al. , the ada(2)We explore a series of strategies of inheritance mechanisms Fig. . Importagenes‐only: individuals consist of only one genetic sequence, mutating with rate μgene. A similar strategy is ‘epigenes‐only’ . This amounts to the gene‐only strategy, with a higher mutation rate. All other strategies use both genes and epigenes. With the strategy genes‐and‐epigenes, genes and epigenes mutate independently (according to their respective mutation rates). These strategies correspond to the Klironomos et al. . This strategy is similar to that of Jablonka & Lamb . This simulates a situation where regulatory patterns, or maternal effects, are adaptively induced by the environment. In this strategy and the following ones, epigenetic marks generate new variation that is then open to selection in the model.The simplest strategy is s et al.  model. Wa & Lamb . This sicostly‐inducible‐mutagenic‐epigenes is identical to the inducible‐mutagenic‐epigenes one, except that the fitness peak for epigenes is inferior to the fitness peak for genes.We also explore the case where maintaining an epigenetic system is costly . The strategy flexible‐inducible‐mutagenic‐epigenes). This strategy can be thought of as simulating a situation of mutational assimilation i) individuals reproduce (according to their fitness), individuals in excess, if any, are randomly removed; (ii) for each remaining individual, the genetic and epigenetic sequences undergo possible mutations (according to their respective rates). Each simulation is run for 106 generations.Only one strategy of hereditary transmission is tested at a time. The starting population is monomorphic, offpeak . The dynamics consists of a succession of generations where:  is recorded, and the geometric average of the fitness since the beginning of the simulation is computed. The geometric average at a given time indicates which strategy would win (i.e. be more numerous) at this time , thus indicating the timescales at which the strategy is adaptive in comparison to the others.(4)As qualitative results depend only upon the relative orders of magnitude of the parameters, results are illustrated with a single set of parameters Fig. . HoweverWe found that the relative timescale of adaptation depends strongly on the mechanistic links between genetic and epigenetic mechanisms Fig. . In all genes‐only strategy , but genes then take longer to find their peak. This is because the presence of fit epigenes slightly decreases the relative fitness of fit genes, increasing the probability that fit genes are lost by drift. Thus, having both genes and epigenes accelerates phenotypic adaptation  at which point epigenes drift, leading to a higher proportion being in the non‐mutagenic stage, thus removing the mutation load on genes. This strategy represents our primary model of mutational assimilation, and replicates that of Jablonka & Lamb i) environmental change induces epigenetic change that interacts with TEs to produce germline genetic variation in specific loci, (ii) germline altered epigenetic patterns can be transmitted for many generations, and (iii) epigenetic marks are mutagenic, imply that the localization of genetic change is partly environmentally driven et al., C. elegans where neuron‐produced double‐stranded RNAs generate both intragenerational epigenetic silencing in somatic cells, and intergenerational epigenetic silencing in germ cells . At the across‐generations timescale, they affect the mutability of the very same DNA sequences, hence affecting evolutionary changes in the relevant functional DNA sequence over generations (Rey (3)Weismann's view was that acquired characters cannot be inherited Fig. . After tet al., et al., 4 for methylcytosine Another interesting twist in this vision concerns the central dogma of molecular biology, which was formulated in terms of sequence (i.e. primary structure) of macromolecules  of Fig. (5)Our review also underlines the lack of data causally linking epigenetic marks to mutation rates. In particular, such links may vary according to mutation type. In both germline and somatic cells, regions of closed chromatin show higher levels of base substitutions  as in Kronholm et al.  represenet al. , its det(6)Our goal is to help to integrate scientific approaches at the infra‐ and supra‐individual levels into a unified view accounting for the fact that the various inheritance systems interact as runners in a relay race, handing over heritable information between stages, hence potentially matching the timescales of inheritance with those of environmental variation. What we need now are models of informational dynamics integrating such a relay at the ecological and evolutionary timescales. Comparing Figs et al., et al., Although several theoretical studies have tackled questions such as the interaction between epigenetic and genetic evolution et al., et al., et al., et al., et al., et al., Inclusive inheritance has paramount medical implications by allowing the study of the various components of the inheritance of so‐called ‘genetic disorders’, which in fact may be substantially inherited non‐genetically et al., et al., Although the discovery of genetics dramatically improved our understanding of inheritance and evolutionary biology, it had the downside of considerably narrowing our vision of inheritance and evolutionary biology, hence pushing the role of other inheritance mechanisms out of view. One consequence of this is that established textbook examples of genetic determinism have later been revealed to be caused by epigenetic variation (Cubas V.(1) We revisited the diverse mechanisms of inheritance according to relevant timescales. We suggest the existence of shifts between inheritance mechanisms that produce a relay in information encoding that enables a lineage to match the pace of environmental change.(2) We reviewed the evidence for such potential shifts of information. Epigenetics appears as a major hub in this relay towards genetics, linking non‐genetic germline inheritance with genetic inheritance in a form of epigenetically facilitated mutational assimilation.(3) A theoretical model suggests that such mutational assimilation may considerably accelerate (or slow down) the genetic encoding of initially non‐genetically inherited adaptations, by a factor commensurate with that of the mutagenicity of epigenetic marks.(4) This view of inheritance has major practical implications, and opens the way for new studies at scales ranging from the molecular to the population levels.VI.2 ANR project (ANR‐13‐BSV7‐0007‐01) to E.D. B.P. was also supported by the CAPA ANR project (ANR‐13‐JSV7‐0002), and is part of a project that received funding from the European Research Council (ERC) under the European Union's Horizon 2020 research and innovation program (ERC consolidator grant agreement No ERC‐CoG681484‐ANGI). A.P. was supported by the Templeton World Charity Foundation, Inc. (grant TWCF0242). The opinions in this publication are those of the authors and do not necessarily reflect the views of the Templeton World Charity Foundation, Inc.Aurélien Pocheville greatly helped in programming the model. At the time of writing, A.P. had a postdoctoral fellowship at the Centre for Philosophy of Science, University of Pittsburgh. Philippe Huneman helped in discussing several points in this review. We are thankful to the CNRS InEE pluridisciplinary research network (RTP) in Epigenetics in Ecology and Evolution (3E) for insightful discussions. This work was supported by the ‘Laboratoires d'Excellences (LABEX)' TULIP (ANR‐10‐LABX‐41), as well as ANR funded Toulouse Initiative of Excellence ‘IDEX UNITI’ (ANR11‐IDEX‐0002‐02). E.D., S.B. and B.P. were supported by the Soc‐HTable S1. A description of published models of non‐genetic inheritance and genetic assimilation.Table S2. Description of the model parameters.Click here for additional data file.


IUCrJ features a significant step forward in X-ray PDF methodology for thin films, with substantial improvements in both sensitivity and time resolution.Atomic pair distribution (PDF) analysis has proven to be an exceptionally robust tool for probing the structure of amorphous, crystalline and crystallographically challenged materials. This issue of  While G(r) and I(Q) contain identical information, the PDF provides a unique ‘real-space’ view, giving the likelihood of finding pairs of atoms at a certain distance r. As assumptions regarding periodicity are not necessary, PDF analysis has proven particularly useful for nanomaterials  materials in the beam path. For bulk powders measured in the standard transmission geometry at modern synchrotrons, this is usually straightforward, as the signal-to-background ratio is large.In the case of thin films on thick substrates, background subtraction in a transmission geometry is critically important and at times a limitation. As film thicknesses decreases relative to the substrate, the contribution of the film to the scattered signal similarly decreases. The result is often that the measured signal is dominated by the substrate, while the signal from the film of interest is buried in noise. While this issue can be remedied by increasing measurement times compared with those for standard bulk powders, the necessary times are often unfeasible. This has limited the applicability of PDF analysis to thin films, imposing hard restrictions on both film thickness and temporal resolution.et al. (2019The recent work of Dippel  al. 2019 represenet al. successfully measured PDFs from crystalline and amorphous thin films down to 3 nm, with count times on the order of one second. This represents a factor of ten decrease in the minimum detectable film thickness, and a decrease of several orders of magnitude in the measurement time. Beyond this, their subsequent analysis results agree with previous studies on the same materials, demonstrating robustness and reproducibility.Their work makes several key improvements on past GIPDF geometries. By using hard X-rays combined with a fast two-dimensional detector they achieve PDF resolutions and count times comparable with what is seen in more standard transmission geometries for bulk powders. Additionally, careful control over the beam footprint yields manageable instrumental resolution broadening. Using beamline P07 at PETRA III, Dippel et al., 2017et al., 2017et al., 2017et al., 2016et al., 2016et al., 2016et al., 2017et al., 2017et al. have successfully demonstrated the feasibility of the GIPDF technique, bringing within reach a whole new class of in situ and operando structure studies on thin film devices and functional materials.Thin films are particularly relevant in technological applications including energy storage and conversion (Gao


In an interesting paper by Zhang et al. , flavor Zhang et al.  reportedIn rats, duodenal and jejunal glucose infusions conditioned similar flavor preference whereas ileal infusions were ineffective; yet infusions at all three sites increased blood glucose levels (Ackroff et al., Zhang et al.  assumed How reinforcing signals, generated by peripheral glucose and MDG, reach the brain is uncertain. Zhang et al.  dismisseIn summary, the Zhang et al.  study prAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Parental depression is a risk factor for the development of child internalizing  and externalizing problems  –4. EckshEckshtain et al.  found thOther factors that may have influenced the relationship observed between parental depression and child internalizing and externalizing problems are discussed below. We comment on a few factors that, if taken into consideration by Eckshtain et al. , may havSibling relationships have been implicated as potential influencing factors in children’s internalizing and externalizing problems. Buist and Vermande  found thParental psychopathology has also been found to influence child behavior problems. Eckshtain et al.  measuredEckshtain et al.  did not All authors listed have made a substantial, direct, and intellectual contribution to the work, and approved it for publication.The authors declare that this manuscript was written in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Journal of Clinical Medicine was specifically dedicated to research evaluating the effects of exercise on cognitive function. This Special Issue published 23 articles dedicated to this topic (Cognitive function is associated with longevity and is of critical importance for optimal daily functioning . As suchis topic . These sSeveral interesting findings were observed from this collective body of work. As an example, Chen et al.  evaluate


An important element of the initiation of meiotic recombination is histone H3 lysine 4 trimethylation (H3K4me3) that marks meiotic DSB sites (Borde et al., A paper recently published by Karanyi et al (Karanyi et al., Saccharomyces cerevisiae with an increased resolution for Hi-C experiments and tracked the behavior of this re-designed region during the first stages of meiotic prophase (Muller et al., in situ Hi-C (Rao et al., Ample cytological evidence supports the dynamic reorganization of meiotic chromosomes during the prophase of meiosis (Zickler and Kleckner, All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Hidradenitis Suppurativa: A Systematic Review Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model” by Vossen et al.  as defined by American College of Genetic Medicine (ACGM) criteria (uncertain significance.” Genome Wide Association Studies (GWAS) as well as functional and proteomic data linking identified sequence variants to the inflammatory mechanisms driving HS are currently not available. Both areas of research are vital in further evaluating the role of genetic variants in HS pathogenesis. It remains plausible that a complex polygenic model better describes observations in some cases of familial HS  underlying the development of sinus tracts. Vossen et al.  discuss known unknowns” in our understanding of this disease and the impact that bias in existing data may have in our current understanding of HS pathogenesis.Vossen et al.  are to bJF is responsible for the conception, design, writing, and review of this manuscript.The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Dear editor Ferula and its bioactive constituents” published by Avicenna Journal of Phytomedicine Umbelliprenin has different pharmacological effects such as cytotoxic and apoptosis inducing activities  mechanism (Iranshahi et al., 2018As it is mentioned in the article, we showed that umbelliprenin induced apoptosis in leukemic cell lines. dose- and time- dependently (Ziai et al., 2012The hormetic dose-response relationship becomes the object of considerable investigations on a broad range of chemicals over the past 2 decades (Calabrese, 2013Ferula and its bioactive constituents in future.In the end, we congratulate Iranshahi et al. for their article and we appreciate Avicenna Journal of Phytomedicine editorial board for their judicious concern on this topic. We are looking to read well-original and review articles regarding the beneficiary effects of the genus The authors declare no conflicts of interest.


Malignant diseases, as all chronic diseases, follow a distinct and specific trajectory that can lead to development of cachexia. When cachexia develops, patients will often have a stage of the disease with limited life expectancy. There are no proven and clinically effective interventions to improve quality of life and/or life expectancy in patients with cachexia.et al. in this issue of the journalIn this context, contribution by Anker et al.FigureOne of key messages from the paper by Anker et al.Although the work by Anker FigureIn line with cancer but also other disease awareness campaigns,The authors acknowledge the project  was financially supported by the Slovenian Research Agency.ML reports owning shares of Actimed Therapeutics.


Speech communication under adverse conditions (Mattys et al., Hardy et al.'s recent approach to degrading such information is to use sinewave speech: Sinusoids, which follow the center frequencies of the original utterance's formants, trace only modes of the supralaryngeal vocal tract resonant frequency (Remez et al., Vesicles of the neurotransmitter acetylcholine convey information from neuron-to-neuron Figure . ReductiHardy et al. presented persons with Alzheimer's disease and healthy elderly control adults with either clear speech or sinewave replicas. These stimuli were 3-digit lists such as “eight hundred and eighty-seven” Figure . To-be-aHaving Alzheimer's disease hampers perception of the degraded sinewave speech Figure  yet not An extant cognitive hearing science account of the influence of selective auditory attention on speech perception under adverse conditions adopts a cholinergic top-down control assumption (Marsh and Campbell, An unexplored corollary of this cholinergic top-down control assumption is that the cholinergic cortical attentional system, including the prefrontal cortices, controls an early filter (Sarter et al., Hardy et al.'s findings thus unleash the potential of a new cognitive hearing science. This science could establish how acetylcholine affects speech-in-noise performance in persons with hearing or cognitive impairments: Empirically undetermined is whether Hardy et al.'s cholinergic influence confines to a top-down focusing of the listening to attended speech information; be that signal degraded or obscured. During speech-in-noise perception and understanding, another cholinergic influence may also be upon the top-down selective inhibition of ascending to-be-ignored noise (Petersen et al., Some sobering words of caution are necessary: Without the design administering Donepezil to healthy controls, a question germane to the cholinergic top-down control assumption goes unaddressed. Could there be a cholinergic influence on speech perception in persons without Alzheimer's Disease? Hardy et al. do provide normative data that tend toward ceiling Figure , in whicTurning from theoretical caution to conservative assays of clinical potential, a subtle breakdown of the brain's network for language comprehension predicts the conversion of individuals with mild cognitive impairment into persons with Alzheimer's disease (Mazaheri et al., Both JM and TC made substantial contributions to the concept and interpretation in drafting the manuscript, approved the submitted materials, and have agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Brain states like sleep and vigilance, as well as fluctuating levels of arousal and attention, are characterized by diverse patterns of brain activity. These global dynamics are strongly driven by the activity of catecholaminergic neuromodulatory systems (Sara and Bouret, Using fMRI and pharmacological intervention, van den Brink et al.  sought tTo compare the spatial modes with well-known brain characteristics, the authors correlate these spatial modes with canonical resting-state FC networks (Smith et al., If the above were true, a strong coupling between the spatial modes and the localization of NE receptors would be expected. Indeed, using the receptor's transcriptional maps from the Allen Brain Institute (Hawrylycz et al., Humans interact with the dynamic nature of the world with a high temporal resolution. Placing van den Brink et al.  findingsThe results presented by van den Brink et al.  extend ovan den Brink et al.  contribuAll authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Late Jurassic to Early Cretaceous interval represents a time of environmental upheaval and cataclysmic events, combined with disruptions to terrestrial and marine ecosystems. Historically, the Jurassic/Cretaceous (J/K) boundary was classified as one of eight mass extinctions. However, more recent research has largely overturned this view, revealing a much more complex pattern of biotic and abiotic dynamics than has previously been appreciated. Here, we present a synthesis of our current knowledge of Late Jurassic–Early Cretaceous events, focusing particularly on events closest to the J/K boundary. We find evidence for a combination of short‐term catastrophic events, large‐scale tectonic processes and environmental perturbations, and major clade interactions that led to a seemingly dramatic faunal and ecological turnover in both the marine and terrestrial realms. This is coupled with a great reduction in global biodiversity which might in part be explained by poor sampling. Very few groups appear to have been entirely resilient to this J/K boundary ‘event’, which hints at a ‘cascade model’ of ecosystem changes driving faunal dynamics. Within terrestrial ecosystems, larger, more‐specialised organisms, such as saurischian dinosaurs, appear to have suffered the most. Medium‐sized tetanuran theropods declined, and were replaced by larger‐bodied groups, and basal eusauropods were replaced by neosauropod faunas. The ascent of paravian theropods is emphasised by escalated competition with contemporary pterosaur groups, culminating in the explosive radiation of birds, although the timing of this is obfuscated by biases in sampling. Smaller, more ecologically diverse terrestrial non‐archosaurs, such as lissamphibians and mammaliaforms, were comparatively resilient to extinctions, instead documenting the origination of many extant groups around the J/K boundary. In the marine realm, extinctions were focused on low‐latitude, shallow marine shelf‐dwelling faunas, corresponding to a significant eustatic sea‐level fall in the latest Jurassic. More mobile and ecologically plastic marine groups, such as ichthyosaurs, survived the boundary relatively unscathed. High rates of extinction and turnover in other macropredaceous marine groups, including plesiosaurs, are accompanied by the origin of most major lineages of extant sharks. Groups which occupied both marine and terrestrial ecosystems, including crocodylomorphs, document a selective extinction in shallow marine forms, whereas turtles appear to have diversified. These patterns suggest that different extinction selectivity and ecological processes were operating between marine and terrestrial ecosystems, which were ultimately important in determining the fates of many key groups, as well as the origins of many major extant lineages. We identify a series of potential abiotic candidates for driving these patterns, including multiple bolide impacts, several episodes of flood basalt eruptions, dramatic climate change, and major disruptions to oceanic systems. The J/K transition therefore, although not a mass extinction, represents an important transitional period in the co‐evolutionary history of life on Earth.The  I.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., The Late Jurassic–Early Cretaceous interval (164–100 Ma) represents a transitional period in the history of life on Earth, coeval with significant environmental fluctuations and changes in Earth systems processes et al., et al.  the base of the Calpionella Zone and the sudden decline in species of Crassicollaria; (ii) the explosive radiation of small, globular forms of Calpionella alpine  the first appearances of two subspecies of Nannoconus (a)et al., Early research into Phanerozoic macroevolutionary patterns led to the inclusion of the end‐Jurassic as one of eight mass extinction events based upon a 20% level of extinction et al., et al., et al., et al., et al., et al.  have noted a sharp decline in diversity around the J/K boundary et al., et al., et al., et al., i) the Indian Ocean  the Pacific Ocean, which is thought to have had a stable circulatory regime  the Atlantic Ocean with a distinct North–South salinity gradient  carbonate platforms experienced severe growth crises et al., et al., et al., et al., et al., et al.  sea‐level curves show a peak in the Kimmeridgian–early Tithonian, prior to a double‐dip decline and lowstand through the J/K boundary. This was followed by a slight rise to levels seen at the end of the Jurassic, before plummeting again in the Valanginian–Hauterivian  is an indicator of the rate of erosion of continental crust relative to enrichment from hydrothermal sources, and therefore acts as a proxy for marine sedimentation rate: peaks in the strontium curve correspond to minimum levels of associated sedimentation, and vice versa , which might have created toxic oceanic conditions et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., During the Late Jurassic, periods of enhanced continental erosion and oceanic productivity, combined with increased sedimentation rates, were driven by a dominantly tropical or arid climate with frequent monsoons at low latitudes i) lowering air temperatures through direct insolation from ash and sulphate aerosols; (ii) increasing atmospheric toxicity and poisoning; (iii) acid rain and biocalcification crises; (iv) increasing atmospheric temperatures through release of greenhouse gases; and (v) ocean anoxia  10–20 km thick sequences in the Jurassic to Early Cretaceous of Chile  evidence for a plume event  plume‐associated activity from the J/K boundary of the Liberian margin  Berriasian–Hauterivian mantle plume activity in northern Israel  a 1500 km wide magmatic province initiated in the Hauterivian–Barremian of Australia (5)et al., et al., i) the 70–80 km diameter Morokweng impact crater in the Kalahari Desert, South Africa, dated at 145 ± 2 Ma  the 40 km wide Mjølnir crater in Norway, dated as 142 Ma  the 22 km wide crater at Gosses Bluff, Northern Territory in Australia, dated at 142.5 Ma , in South America, Europe, Africa, Australia, and Asia. Presently, geochemical data are limited in extent, but there are multiple regional anomalies whereby trace metals  are enriched around the J/K boundary, suggesting extra‐terrestrial input on a global scale et al., Early investigations into the trajectory of diversity on a geological time scale typically used raw counts of fossil taxa, i.e. numbers of species, genera, and/or families through time  sampling bias; (ii) an external ‘common cause’, such as sea level; and/or (iii) redundancy, resulting from the non‐independence of sampling metrics and diversity . These methods seek to explain whether diversity is driven by:  and Fossilworks (http://www.fossilworks.org), synchronous with the progress in analytical techniques outlined above. Macroevolutionary studies that include the J/K interval have explored the effects of uneven sampling on vertebrate diversity at regional and global levels et al., et al., et al., et al., et al., Numerous studies have documented changes in sampling quality over the J/K boundary. Notable examples include the sharp decline in fossiliferous marine‐ , the total numbers of taxonomic occurrences, fossil‐bearing collections, and raw species diversity all show substantial declines over the J/K boundary (a)et al., et al., et al., et al., et al., et al., et al., et al., et al., Of all Mesozoic vertebrate groups, dinosaurs have the best‐sampled and most‐studied fossil record. Non‐avian dinosaur diversity halved from the Tithonian to Berriasian  of China , followed by an apparent dramatic decline over the J/K boundary, based on both raw et al., et al., et al., et al., Most Laurasian pterosaur taxa are known from Konservat‐Lagerstätten, including the Late Jurassic Solnhofen Limestones of southeastern Germany  becoming extinct Unwin, , a patte(c)et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., Thalattosuchian crocodylomorphs, comprising two major pelagic groups, Teleosauridae and Metriorhynchoidea, achieved the height of their diversity during the Late Jurassic . During this period, thalattosuchians achieved a broad ecological range, with a variety of feeding modes, craniofacial forms, dental morphologies, functional biomechanical behaviours, and a wide spectrum of body sizes et al., et al., et al., et al., Malawania, from the Early Cretaceous of Iraq, demonstrates that at least one basal non‐ophthalmosaurid lineage passed through the J/K boundary et al., Taxonomic diversity of Plesiosauria declined greatly across the J/K boundary, with the extinction of microcleidid and rhomaleosaurid taxa, known almost exclusively from Euamerica Bakker, . Recover(f)et al., et al. et al., et al., et al., et al., et al., Choristoderes were small‐ to medium‐sized semi‐aquatic middle‐tier predators of Laurasian ecosystems, whose placement within Diapsida remains enigmatic et al., Lepidosauria comprises the diverse and extant groups Rhynchocephalia and Squamata , Scincoidea (skinks), and the clade comprising Acrodonta and Pleurodonta (iguanians), are either close to the J/K boundary et al., et al., et al., Lissamphibia comprises anurans (frogs), caudatans , albanerpetontids  and gymnophionans (caecilians). Within Lissamphibia, there was a small increase in total diversity over the J/K boundary Fara, . Moleculet al., et al., et al., et al., In the Late Jurassic of North America, the lissamphibian fossil record documents a mixture of stem caudates and anurans, as well as the first North American crown caudate et al., et al., et al., et al., The Late Jurassic was an important time in the rise of modern‐day mammal clades, with the diversification of Theria (comprising Eutheria and Metatheria) occurring around 160 Ma, during the Oxfordian Early studies found either a small increase Benton,  or smallet al., Neoselachia, the clade including all modern forms of shark, and Batoidea (skates and rays) both underwent a phase of high diversification rates during the latest Jurassic Kriwet, . This wa(4)et al., et al.  taxic invertebrate diversity have been superseded by global data sets and advanced analytical subsampling approaches et al., et al., et al., et al., Both raw and subsampled bivalve generic diversity declined at the J/K boundary Early studies found little evidence for a significant drop in brachiopod diversity at the J/K boundary Ager, . However(c)et al., et al., Coral diversity appears to have increased linearly through the J/K boundary based on subsampled estimates Alroy, ; however(d)et al., et al., The impact of sampling on global patterns of pre‐Cretaceous echinoderm diversity has yet to be explored in a manner similar to that of other marine invertebrate groups Alroy, , hinderi(e)All major hexapod groups passed through the J/K boundary  appear to have increased dramatically in diversity in the Late Jurassic (Kimmeridgian), followed by a burst of intra‐family diversification during the Early Cretaceous Late Jurassic and Early Cretaceous bryozoan faunas were almost entirely comprised of cyclostome stenolaemates et al., et al., et al., et al., In the Early Cretaceous, microfossil groups became the most volumetrically significant biogenic constituent of deep‐sea sediments for the first time et al., et al., Global studies indicate that foraminiferan standing diversity was not affected at the J/K boundary, but that extinction rates in the Middle–Late Jurassic were of equal magnitude to the ‘Big Five’ mass extinctions, and accompanied by high origination rates et al., et al., Radiolarians experienced declining diversification rates throughout most of the Late Jurassic, in concert with a dramatic fall in their diversity et al., et al., et al., et al., et al., 13C values decreased through the J/K boundary; rather than being indicative of increased oceanic productivity, such isotopic trends are typically associated with decelerating hydrological cycling and increasingly oligotrophic conditions et al., et al., et al., et al., Cascales‐Miñana & Cleal  recentlyet al., et al., ,et al., During the Jurassic, floral diversity and productivity were highest at mid‐latitudes, due to the migration of productivity concentrations during greenhouse episodes et al., Whether or not there was a mass extinction at the J/K boundary is a multi‐faceted issue, and occluded by the relatively poor sampling and dating of earliest Cretaceous fossil‐bearing deposits Fig. , as wellVertebrate groups such as theropod and sauropod dinosaurs, rhamphorhynchid pterosaurs, marine crocodylomorphs and testudines, sauropterygians, and groups of fishes, all show evidence of a decline in diversity across the J/K boundary. However, in almost all of these cases, total net diversity of their more inclusive higher clade remained high, with heightened rates of speciation accompanying elevated rates of extinction. Within invertebrates, reef‐dwelling taxa, including corals and some arthropod groups, were the primary victims across the J/K boundary. Furthermore, ammonites, gastropods, brachiopods, foraminiferans, and calcareous phytoplankton all have documented drops in diversity or increased extinction rates at the J/K boundary. Currently, however, the evidence from the fossil record indicates that the J/K boundary cannot be regarded as a mass extinction of the same magnitude as the ‘Big Five’.(2)(a)et al., et al., et al., et al., There is some evidence for geographic selectivity of extinction in theropods through the J/K boundary, with the differentiation between coelurosaurian and non‐coelurosaurian‐dominated theropod faunas within Gondwana and Laurasia, respectively et al., et al., et al., et al., et al., et al., A faunal turnover is documented in sauropterygian taxa, along with the extinction of shallow marine and semi‐aquatic crocodylomorphs and testudines at the J/K boundary et al., et al., i) enhanced extinction through contraction of shallow marine ecosystems and increasingly anoxic bottom waters; and (ii) decreased preservation of sedimentary rocks, impacting upon on our ability to sample marine assemblages. This regression, combined with increased continental input, and a possible minor ocean anoxic event (a)et al., et al., et al., et al., et al., et al., et al., Recent developments in assessing the macroevolutionary and macroecological history of dinosaurs have provided insight into potential selectivity patterns in different subgroups. For example, there is a seemingly selective extinction of larger‐sized dinosaurs (sauropods and theropods) across the J/K boundary et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., The low ecological diversity of plesiosaurians and testudines might have been a distinct contributing factor to their decline and turnover at the J/K boundary There is strong evidence for a coupled ecological–taxonomic mode of extinction and faunal turnover across the J/K boundary for both small‐ and large‐bodied terrestrial tetrapods. In a range of groups spanning the marine and terrestrial realms, including mammaliaforms, lissamphibians, and ichthyosaurs, ecological specialisation and plasticity plays a clear role, with surviving groups possessing broader morphologies, or key morphological adaptations that appear to be associated with higher survivability rates. For marine tetrapod groups in particular, it appears that the J/K interval represents a staggered cascade model of extinction, with different groups responding in a variety of ways to a range of ecological perturbations, and with fluctuations in sea level possibly acting as the principal driver of change .There is widespread evidence for a major faunal turnover in both the marine and terrestrial realms during the J/K interval. Whereas the effect of this is clearer in larger‐bodied organisms such as dinosaurs, we also see evidence for either competitive displacement or opportunistic replacement in smaller‐bodied groups such as lepidosaurs, lissamphibians and mammaliaforms. There is some evidence that pterosaurs and paravian theropods rapidly diversified and adopted new ecomorphotypes in the Early Cretaceous, including the explosive radiation of the most successful extant tetrapod group, birds, although the precise timing of these events is obscured by varying spatiotemporal sampling of these clades. Low‐latitude and shallow marine to semi‐aquatic faunas, including testudines, crocodylomorphs, and reef‐dwelling and sessile invertebrates, suffered the greatest diversity loss in the marine realm, whereas more mobile taxa with greater dispersal ability, such as ichthyosaurs, appear to have been relatively unaffected.i) at least three large bolide impacts in the latest Jurassic, one of which might have been bigger than the end‐Cretaceous Chicxulub impact  a Late Jurassic–Cretaceous ‘greenhouse’ world, interrupted by a latest Jurassic ‘cold snap’ and corresponding aridity episode; (iii) a global drop in sea level to a eustatic lowstand through the J/K boundary  potentially heightened levels of anoxia, oceanic stagnation, and sulphur toxicity over the J/K boundary; (v) a series of repeated ‘biocalcification crises’ in the Early Cretaceous, along with two purported oceanic anoxic events in the Valanginian and Hauterivian; (vi) the emplacement of the Paraná and Etendeka  and Ontong Java Plateau (Barremian–early Aptian) flood basalts, the latter of which might have been three times as voluminous as the end‐Cretaceous Deccan volcanism; and (vii) some of the largest volcanic episodes in the history of the Earth, following the emplacement of the Shatsky Rise supervolcano at the J/K boundary. This series of environmental perturbations warrants further investigation in the context of potential biotic effects throughout this time.The Late Jurassic–Early Cretaceous was a period of major environmental perturbations that have largely been ignored or overlooked in historical analyses of Mesozoic diversity dynamics, in favour of more ‘exotic’ extinction intervals. A range of evidence indicates the following major changes:  a ary Fig. ; (iv) poet al., The J/K boundary represents an opportunity to investigate the environmental and ecological factors governing recovery , and the biotic and abiotic drivers of these patterns. Substantial progress has recently been made in modelling the possible drivers of diversification and extinction, especially in terrestrial tetrapods , 2014b aAppendix S1. List of studies that analyse the magnitude of the J/K boundary extinction for different taxonomic groups. For further details on analytical statistics, see references cited within.Click here for additional data file.


Global inequity in access to and availability of essential mental health services is well recognized. The mental health treatment gap is approximately 50% in all countries, with up to 90% of people in the lowest-income countries lacking access to required mental health services. Increased investment in global mental health (GMH) has increased innovation in mental health service delivery in LMICs. Situational analyses in areas where mental health services and systems are poorly developed and resourced are essential when planning for research and implementation, however, little guidance is available to inform methodological approaches to conducting these types of studies. This scoping review provides an analysis of methodological approaches to situational analysis in GMH, including an assessment of the extent to which situational analyses include equity in study designs. It is intended as a resource that identifies current gaps and areas for future development in GMH. Formative research, including situational analysis, is an essential first step in conducting robust implementation research, an essential area of study in GMH that will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in low- and middle-income countries (LMICs). While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions. We also complemented our database search with a review of the reference lists of included articles to ensure we did not overlook relevant studies  took place in an LMIC context as defined by World Bank criteria , purpose, country of origin, objectives, methods, situational analysis tool characteristics and use, inclusion of equity in study design, and limitations as described by the study authors. The inclusion and exclusion criteria and the data extraction categories were decided through discussion amongst authors JM, EEM and RWL, with further consultation with the full study team. We analysed the results using a combination of numerical descriptive summary and qualitative thematic analysis  of the 24 studies took place in Sub-Saharan Africa, 37.5% (n  =  9) took place is South Asia and 8.3% (n  =  2) two took place in East Asia. None were performed in Latin America, the Caribbean or Middle East and North Africa regions.et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., For this analysis, studies are counted as ‘single country’ if they reported results from only one country in a paper, regardless of their broader affiliation with multi-country research programs. Of the studies, 14 (58.3%) took place in multiple countries, with high representation in this review of papers published by consortia such as the Programme to Improve Mental Health Care (PRIME)  conducted situational analyses and formative research to inform the development or design of mental health programmes or services. Objectives included the development of a package of community-based mental health and mobile health services  papers used situational analyses and formative research before developing specific clinical mental health interventions. These sought to: inform the design of acceptable and feasible interventions for the study context  of studies included qualitative research, using key informant and in-depth interviews and/or focus group discussions  of the studies reviewed secondary data; 14 used a specifically designed situational analysis tool and two studies did not use a tool. Tools used for situational analysis varied, with the majority (7) using the PRIME situational analysis tool, which was specifically designed for the PRIME study  of the studies used priority setting exercises as part of their situational analyses and formative research. Three of these studies (Jordans , et al.  also useet al., et al., et al., et al., The priority-setting workshops were used to inform the development of an intervention (Asher et al., et al., et al., et al. (et al., Three studies explicitly included equity considerations in their study designs (Abdulmalik , et al.  used a f et al.,  to guideet al.,'s (The overall goal of Hailemariam t al.,'s  study waet al.,'s (Mugisha t al.,'s  situatioet al., et al., et al., et al., et al., Five other studies implicitly addressed issues related to equity but did not incorporate it in their study design; that was addressed by discussing the impact of poverty on help-seeking (Angdembe et al., et al., et al., et al., et al., et al., Seven studies did not describe limitations related to situational analysis methodology (Ofori-Atta et al., et al., et al., et al., et al., et al., The most common limitation identified by those that did describe limitations of situational analyses related to use of secondary data (Hanlon et al., et al., et al., et al., Several studies without a qualitative component identified an inability to include findings on knowledge, attitudes and beliefs of stakeholders as a study limitation. Some authors indicated that complementary qualitative studies were being or would be untaken to capture this information (Hanlon et al., et al., et al., et al., et al., The most commonly cited limitation of qualitative studies was the limited scope of the study area and of study participants, which could limit generalizability of findings (Jordans et al., et al. (et al. (For studies using priority-setting exercises, limitations included the risk of social desirability bias due to the study's affiliation with the national government (Asher , et al.  describe (et al.  cite theThis review identified a number of themes that are important to implementation research in GMH, pointing both to gaps and strengths in the field. Improving GMH depends not only on implementing evidence-based interventions, but also on modifying and implementing interventions that anticipate local implementation barriers across behavioural, managerial, economic, and social domains. Understanding these complex barriers, and ensuring that equity in health can be championed, requires sophistication in the situational analysis. Our review explored various methodological approaches to situational analysis as a guide to enhancing implementation strategies. We discovered that relatively few studies address situational analyses in GMH, with additional key findings noting the paucity of local mental health system data and an absence of consideration of equity. Fortunately, our review also identified the development of several situational analysis tools that can serve as key resources, and a methodological strategy—mixed methods—that can address challenges.et al., et al., et al., et al., We found that the scope of published situational analyses and formative research in GMH is limited. Twelve of the studies included in the review were representative of the PRIME or EMERALD studies, which both include sites in Ethiopia, India, Nepal, South Africa and Uganda, while EMERALD also includes Nigeria (Lund Though outside the scope of this review, an informal search of situational analysis literature and tools from HICs also revealed a gap. There appears to be limited peer-reviewed literature detailing situational analysis tools and methods in mental health or the broader health sector in HICs, though some examples are found in the grey literature. For example, Alberta Health Services in the Canadian province of Alberta conducted a situational analysis of the use of impact assessments in the health sector (Alberta Health Services, et al., et al. (et al., Many of the studies included in this review used or developed situational analysis tools that provide a comprehensive and systematic template for the analysis of complex factors at multiple levels of a mental health system. The PRIME investigators developed their own tool, adapted from WHO-AIMS, to assess district-level mental health needs (Hanlon , et al.  develope et al., .et al., et al., et al., While the tools represent a considerable asset to GMH researchers, their potential to contribute to robust situational analysis research relies on the quality of their implementation and on the availability of secondary data. A major limitation identified by study authors was the often limited availability of mental health system data. Mental health information systems in LMICs are at varying stages of development and may be disjointed and under-resourced. Their strengthening has been identified as a priority in GMH (Ryan et al., et al., et al., Using mixed methods to conduct situational analyses could help to mitigate some of these challenges, along with the limitations of both qualitative research and priority setting exercises described above. Mixed methods approaches combine both quantitative and qualitative data collection, analysis and interpretation in order to provide a deeper understanding of phenomena (Johnson et al., Finally, only three of the 24 studies explicitly considered equity in their study design. While the PRIME situational analysis tool does include indicators related to equity, these were not explicitly discussed in the papers included in this review. Equity on a global scale is a fundamental concern of GMH, which aims to close the gap in treatment within and between countries, improving access to and availability of treatment and improving the lives of people suffering from mental disorders (Patel We only included English language studies in this review which may have led to the omission of relevant research in this area published in other languages. It is also likely that situational analyses and formative studies have been conducted in GMH using different terminology and were thus not identified with the search terms used in this scoping review. The use of MeSH terms in the search may also have yielded additional results. We are confident, however, that the review has captured a representative sample of the GMH literature on situational analysis methodology in GMH, and that it offers a useful overview of current practice and guidance on next steps in this important field of research.Implementation research is an essential area of study in GMH and will help to promote improved availability of, access to and reach of mental health services for people living with mental illness in LMICs. Formative research, including situational analysis, is an essential first step in conducting robust implementation research. While strong leadership in this field exists, there remain significant opportunities for enhanced research representing different LMICs and regions.This review of existing methodological approaches in situational analysis for GMH reveals limitations and opportunities that can inform the design of future studies. The field will benefit from prioritizing mixed methods approaches to implementation research and including equity considerations in the study design of formative research, including situational analyses.


In the final publication of “iMicrobe: Tools and data-driven discovery platform for the microbiome sciences” by Ken Youens-Clark et al., there was an erroneous typo in the title of the article. The typo has been corrected and the title appears correctly online.The Publisher regrets this error.