Among the constituents of food, volatile compounds are a particularly intriguing group of molecules, because they give rise to odour and aroma. Indeed, olfaction is one of the main aspects influencing the appreciation or dislike of particular food items. Volatile compounds are perceived through the smelling sensory organs of the nasal cavity, and evoke numerous associations and emotions, even before the food is tasted. Such a reaction occurs because the information from these receptors is directed to the hippocampus and amygdala, the key regions of the brain involved in learning and memory.In addition to identifying the odour-active compounds, the analysis of the volatile compounds in food is also applied for detecting the ripening, senescence, and decay in fruit and vegetables, as well as monitoring and controlling the changes during food processing and storage . Nineteen research papers and two review papers cover the topics of this Special Issue. The majority of the papers investigated volatile compounds from vegetable origin products (16) and four papers reported volatile compounds from animal origin products (dairy products).Six of the research papers were mainly focused on the sensory aspects related to volatile compounds ,3,4,5,6,Muñoz-González et al.  studied Endrizzi et al.  studied Deuscher et al.  used gasLiberto et al.  exploredIn the work of Genovese et al.,  it was sYan et al.  used fasFatty acids and their derived volatile compounds were studied in “Thompson Seedless” Raisins during air-drying and sun-drying processes by Wang et al. . The stuThe work of Ma et al.  evaluateVidal et al.  in theirChitarrini et al.  combinedIn a further work, Chitarrini and co-workers  used theSmith and Peterson  combinedIanni et al.  studied A further study on the effect of animal feeding on volatile compounds in dairy products was undertaken by Bennato and co-workers . These aSlaghenaufi et al.  studied Yang et al.  studied Lobo-Prieto et al.  tracked In the paper of Coelho and co-workers , a liquiIn the work of Capozzi et al.  two compTanaka and co-workers , in theiIanni et al.,  in theirIn conclusion, volatile compounds are responsible for the aroma of food and may be influenced by processing, storage, harvesting or animal feeding, and they require a dedicated analytical approach for the identification and the monitoring All these aspects were covered by the manuscripts submitted and published in the Special Issue “Volatile Compounds and Smell Chemicals (Odor and Aroma) of Food”. These manuscripts contributed—with their topics and their quality—to the success of this Special Issue.


As cancer continues to pose a major health risk and the global incidence rate is expected to almost double in the next two decades, the importance of radiation therapy will continue to grow. Radiation oncology will be shaped by oncoming advances in medicine, including early and lower‐cost detection methods, integrated multidisciplinary approaches, personalized medical strategies, and cancer prevention. In addition, radiation oncology will be influenced by future societal changes, including the establishment of more efficient, value‐based healthcare systems, and, importantly, extended European and global cooperation in research and care for the fight against disease.et al., The establishment of a radiotherapy department needs considerable upfront investment in state‐of‐the‐art diagnostic and therapeutic technologies and devices. Nevertheless, as these devices can be used for many years, radiotherapy enables cost‐efficient treatment of thousands of patients.Radiotherapy needs to be administered by well‐trained personnel and by multiprofessional teams. But, Europe does not have enough well‐trained staff and will need national overarching efforts to train a sufficient number of experts in the coming years. These expert teams should consist at least of radiation oncologists, medical physicists, and radiation therapy technologists. In addition, radiation biologists, data scientists, engineers, and experts from many other fields are of fundamental importance for the further development of radiation oncology.Radiotherapy requires a certain degree of centralization to ensure that a critical mass of equipment and personell are available for delivering all of radiotherapy required by current and future cancer treatment regiments. Consequently, radiotherapy departments cannot be established in all medical centers and sites within a country. This can cause problems for decision‐makers as to selecting locations for radiotherapy centers.Radiotherapy is only one component of cancer treatment, as it is always combined with other diagnostic and therapeutic disciplines in a multidisciplinary framework. Radiotherapy departments are therefore best located within multidisciplinary cancer treatment units, such as comprehensive cancer centers.If decentralized radiotherapy units are needed to provide access for all citizens nationwide, these units can, for example, be connected to larger network centers. In general, decentralized services closer to the patients’ homes are more beneficial and practical for palliative care, or if tumors require well‐defined and frequently applied standard treatments. More specialized treatment should ideally be provided by larger departments. Last but not least, modern telemedicine connectivity and reliable and ubiquitous patient referral systems are needed to ensure that even patients living in more remote areas have access to all treatments offered.The importance of a common European mission is evident in view of the current enormous disparity regarding patient access to state‐of‐the‐art radiotherapy from one European country to the other (Lievens Finally, going beyond patient care, Europe also needs innovation. Europe has a strong track record not only in biological research and drug development, but particularly also in medical engineering and medical technologies that form the backbone of modern radiotherapy. As the driving ideas behind new generations of technology often stem from close interactions among the clinical care sector, academic research, and industry, investment into radiation oncology will also boost European research and economies.Molecular Oncology discusses central questions of the future direction and development of radiotherapy in Europe. The cancer mission must take into account the needs of tomorrow’s aging population, as well as the nationwide diversity of systems in Europe. This is only possible if all research areas are brought together in a symbiotic approach to cure and slow down tumor growth and combat comorbidities.This thematic issue in 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., We would like to thank the authors of this special issue for providing the data and for laying the foundation for further developments in radiation oncology, covering a broad range of topics from innovative, technology‐, and data‐driven approaches to translational medicine and personalized strategies to cancer prevention and patient care in radiation oncology (Lievens


Ever since it was first discussed in evolutionary terms by Haldane , MedawarStead et al., with special emphasis on ways that modulation of autophagy can be beneficial for healthy aging. A specific focus on lessons learned from Drosophila on the functional connection between autophagy and aging is provided by Marusz et al. However, what is less clear from the data available so far is whether enhanced autophagy on its own is necessary and sufficient to extend life span. Some studies strongly support the idea that this is the case  material in cells as a function of age. Such material can be dysfunctional mitochondria, accumulated lipids and, in the case of neurons, aggregated proteins potentially causing neurodegeneration (Gatica et al., Kounakis et al. Finally, it is important to remember that aging is a very complex process that affects with different severity and timing the various bodily tissues. Along those lines, the relation between autophagy and aging of specific cells and tissues is also addressed in this collection. Macian reviews the role of autophagy in T cell function and immunosenescence, a very interesting phenomenon in immune cells, whereas Eckhart et al. discuss how the various cells of the skin activate autophagy and the connection of this process to skin aging.How does autophagy engage with the aging process? At one level this is related to caloric restriction, one of the most reliable ways to extend life span in model organisms (López-Otín et al., Schmeisser and Parker. Of note, several genes whose downregulation enhances lifespan are also shown to be important for early development (Kenyon, The developmental theory of aging proposes that the optimization of developmental programs necessary for reproductive fitness has the unwanted consequence of also causing aging when these programs continue to operate past reproductive age (de Magalhães and Church,  Kenyon, . AutophaWe hope that the articles collected in this volume will stimulate further hypothesis-driven experimental work detailing the role of autophagy in the aging process.TP-C and NK wrote and edited the manuscript.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.


We read with great interest the article by Posma et al. who reported that early lactate levels were strongly associated with mortality and, irrespective of the degree of hyperlactatemia, similar lactate levels were associated with a lower mortality rate in metformin (MET) users compared with MET non-users . We woul


The lung epithelium is a cellular barrier that protects the lung from environmental exposure to pathogens and chemical insults that could otherwise compromise its physiological role in gas exchange during respiration. In the distal lung, the exchange of oxygen and carbon dioxide occurs within the alveoli, facilitated by type I alveolar epithelial cells (AECs). In addition to their important role in gas exchange, mucus and surfactant secreted by AECs contain a range of host‐defence proteins which aid epithelial barrier function and protection from invading pathogens. The lung epithelium is supported by a network of mesenchymal cells including fibroblasts that form the basement membrane that acts as a further layer of protection to prevent access of microbes to the underlying tissue.Clinical & Translational Immunology, the reviews include a broad range of topics examining the clinical challenges associated with the diagnosis of ILDs and the nature of the innate and adaptive immune responses elicited following tissue damage in ILDs and in lung regeneration. This series of articles explores how the immune response is modulated during lung cancer and how novel immunotherapeutic approaches are being explored to treat this disease. The use of animal models to study the pathobiology of ILDs is discussed and highlights how these models may inform novel therapeutic strategies to treat ILDs or lung cancer in humans.Many interstitial lung diseases (ILDs) share similar clinical symptoms and findings on radiographic or pathologic assessment often making diagnosis difficult. The accurate diagnosis of an ILD is critical for the long‐term management of the disease and can inform the choice of treatment a patient receives and their prognosis. We are beginning to appreciate the importance that immune status has on disease progression and clinical outcome. In this Special Feature of MUC5B, SPC , TOLLIP (innate immune cells) or PARN, TERT (telomere genes),The review by McLean‐Tooke and colleagues examines the challenges associated with the accurate diagnosis of ILDs in patients.et al.et al.et al.et al.The reviews by Warheit‐Niemi et al.et al. describe a range of preclinical mouse studies using various anti‐cytokine therapy approaches and cytokine gene knockout models. Although some of these approaches have shown promise, this success has not yet been translated to human patients. Collectively, the three reviews by Warheit‐Niemi et al., Denneney et al. and Lucas et al. highlight the important role of innate and adaptive immune responses in tissue damage and repair mechanisms.Lucas et al.Miles et al.+ cytotoxic T cells is critical for eliminating cancer cells and reducing tumor burden. However, it is now known that tumor cells can subvert the immune system by expressing checkpoint ligands which bind to inhibitory receptors on T cells, rendering them ineffective for tumor surveillance and eradication. A range of checkpoint inhibitory receptors and ligands have been defined and are being evaluated in a range of clinical trials in cancer. Checkpoint therapy has revolutionised cancer therapy for melanoma, and it is being evaluated for the treatment of lung cancer and other cancer types. Early indications are that monotherapies of checkpoint inhibitors in lung cancer may not be effective in all tumors, thus prompting the use of combination therapies.The final review by Neeve Chronic diseases of the lung, such as pulmonary fibrosis or lung cancer, can disrupt the delicate tissue architecture and compromise gas exchange across alveoli. If disease pathology is not arrested, it can severely impact the quality of life and long‐term survival of the patient. We need to better understand the complex relationship between host genetics, the environment, and the host immune response, and how this shapes disease pathogenesis within the lung. Improved diagnostics will be developed with integration of new emerging technologies such as immune cell phenotyping, transcriptomics and metabolomics that may help to better stratify patients into appropriate clinical subgroups. This may have the benefit of improving the outcome of clinical trials of novel interventions that may be targeted to a specific response pathway.The authors declare no conflict of interest.Cecilia Prêle: Conceptualization; Writing‐original draft; Writing‐review & editing. Gerard Hoyne: Conceptualization; Writing‐original draft; Writing‐review & editing.


The number of oncology, surgery and anaesthesia procedures in older patients has greatly increased in recent years due to ageing populations. Older patients are typically characterised by physical changes such as comorbidities, decline in physiological activities and cognitive impairment. All these factors, together with polypharmacological therapies, may substantially impact perioperative outcome, quality of recovery and, more in general, quality of life. A comprehensive multidisciplinary approach to perioperative care is thus needed. The assessment of frailty has a central role in the pre-operative evaluation of older patients and, with a multidisciplinary approach. The best surgical procedures and oncologic therapies can be accurately discussed in the pre- and post-operative periods. All clinicians involved in this scenario should be proactive in multidisciplinary care to achieve better outcomes. It is well known that cancer is typically an age-related disease with approximately 60% of all newly diagnosed malignant tumours and 70% of all cancer deaths occurring in persons aged 65 years or older . This olet al [et al [et al [et al [et al [et al [The constant and progressive ageing of the population in recent years has led to an increase in the number of surgeries in older cancer patients and consequently also the risk of mortality and morbidity after such operations . In the et al  recruiteet al , but recl [et al  developel [et al  evaluatel [et al  assessedl [et al  evaluatel [et al  proposedl [et al . The tril [et al .Older patients are at an increased risk of surgical complications, and this makes pre-operative evaluation by an anaesthesiologist more difficult . As mentet al [et al [et al [et al [The definition of frailty in geriatric oncology is very difficult, and still, there is no universal consensus about the right definition. Frailty in oncology could be defined as an impairment of at least one of the four geriatric domains evaluated with CGA , 39. Theet al  validateet al . Furtheret al  and a poet al . VES-13 et al . VES-13 l [et al  in a stul [et al . VES-13 l [et al . Even mol [et al  and consl [et al . CARG scl [et al  developel [et al ), cognitl [et al ) and ECOl [et al  were thel [et al  is recoml [et al . Falls al [et al . AssessiThis review was intended to highlight the current oncological, surgical and anaesthesiological knowledge concerning the elderly population. With the review of the literature, it is clear that the multidimensional geriatric evaluation represents an extremely useful and important tool in everyday clinical practice for all older patients undergoing surgery or oncologic treatments. Their careful pre-surgical evaluation and precautions even during surgery could avoid many complications during surgery and during post-operative stay in hospital, but, unfortunately, we have seen that, in real-life, there are few surgeons and surgical centres that apply this evaluation model. We hope that, in the future, older patients will gain attention from the medical class because, given the constant increase in the average age, the number of these patients will increase more and more, and willingly or not, all health professionals will have to interface with this population.The authors declare that they have no conflicts of interest.No funding was received.


In an interesting study, Wu et al.  exploredper se, or whether the effect of EFT on DD is temporally invariant. Recently, reduced DD could be observed not only in participants who had imagined future events, but also in those who had remembered past events or imagined, vividly, present events alternative to the current experience, as compared to merely describing the current situation, before making intertemporal choices (Ciaramelli et al., Wu et al.  also remIt is well-established that EFT and DD rely on a common neural network that encompasses fronto-medial regions, and lesional studies have clearly shown that disruption of such areas results in both increased DD (Frost and Mcnaughton, Wu et al.  showed tFinally, it is worth noting that Wu et al.  tested EThe author confirms being the sole contributor of this work and has approved it for publication.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.


Trends in Digital Medicine provided a series of contributed papers covering a variety of aspects currently defining the digital paradigm  and the effect of advancing translational medicine toward the identification of new principles useful to define healthy vs. diseased individuals and predict their profiles and health/disease trajectories.We asked to refer to a few basic questions, following widely debated topics –5 such aAssale et al. who examined the relevance of the notes produced in clinical practice whose unstructured nature prevents a profitable secondary use but whose potential is increasingly relevant in digitized facilities for improving data quality and thus enabling predictive inference models to be designed and implemented. Other examples were provided by Cazzaniga et al., who discussed cancer registries as main resources for real world data research, and by Geldof et al. who discussed sector-specific challenges in exploratory and hypothesis-driven studies aimed at assessing treatment effectiveness.The first question about digitalization was addressed by a few contributed papers, such as Riba et al., who reviewed current issues related to data integration and governance in the medical field, by Silverio et al., who discussed of CVD and the importance of harmonizing large data sets to build algorithms for targeting and personalizing treatments, and then by Pala et al., who examined in urban contexts the role of both environmental and socioeconomic factors influencing common pathological outcomes such as asthma. The study has introduced spatial methodologies cross-linking data from hospitalized patients and pollution plus other factors and then enabling stratifications based on conditions such as poverty and health insurance together with well-studied race and obesity.The second question on EHR was addressed by Gialluisi et al. have discussed of healthy aging and in particular of biological age, a sort of latent feature of every organism that can be derived from the combination of various biomarkers . Of relevance to screening and risk profiling practices, the concept has been applied to the Moli-sani, a prospective population-based cohort study of 24,325 subjects (35–99 years). In such context, the analysis of brain age via neuroimaging combined with epidemiological, environmental and genetic variables may be very useful to advancing knowledge on common age-related diseases such as Alzheimer.The third question on the relationships between Big Data and Big Killers has been elaborated by three studies. Franchini et al. introduced a model called Individual Profile of Pathology (IPP) designed to stratify populations affected by chronic diseases. When such conditions are considered dynamically driven by evolving multifactorial processes, then IPP offers advantages in assessing surveillance programs and guiding public health policy makers.Finally, EC wrote the article. All authors shared and approved the contents.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.


Histopathology.As the wave of COVID‐19 disease has spread across the globe, so medical publications have followed as part of scientific efforts to characterise, manage and hopefully prevent this disease. Papers pertaining to pathology have, by their very nature, lagged slightly behind those describing clinical and imaging cohorts, but we are now seeing increasing numbers of publications that give us insight into how human tissues are infected and damaged by the virus, three in this particular issue of et al. report a cohort of 21 patients dying of COVID‐19 infection. Acute lung injury was the main pathology at autopsy, primarily showing the exudative phase of diffuse alveolar damage (DAD), with a minority displaying the organising (or proliferative) phase.Menter The identification of vascular lung pathology in some, but not all, patients is also consistent with clinical and imaging data in relation to pro‐thrombotic states,et al. describe a patient operated on for a benign lung lesion before developing symptoms of COVID 19 infection.In the second paper, Zeng et al. is also interesting for its description of a moderately intense lymphoid infiltrate within the interstitium, focally cuffing the pulmonary vasculature. This is also seen in other reports,et al., whereas a relative dearth of lymphoid infiltrate is reported in other cases.et al. report a relative lack of CD8+ lymphocytes in the alveolar interstitium, also reported in the haematological literature.+ lymphocytes outnumbering CD4+ lymphocytes.+ lymphocytes were, however, present in the paper by Zeng et al., the latter again reported by others in bronchoalveolar lavageThe paper by Zeng et al. in 2002,As data amass on COVID‐19‐related lung pathology, it is worth taking a step back and reviewing the variety of patterns of interstitial lung disease that have been reported since the beginning of the pandemic, ranging from interstitial lymphoid infiltrates, oedematous exudates, acute fibrinous and organising pneumonia (AFOP)Therefore, it is important that a balance is maintained between splitting COVID‐19 into a multitude of histological patterns for research into pathogenesis and merging them all together as ‘COVID‐lung’ for the purposes of management, as is the case with other interstitial lung diseases.et al., reporting an individual suffered erosive gastrointestinal injury following intentional repetitive sublethal ingestion of ethanol‐based hand cleaner.et al.et al. has wonderful direct links to whole slide images. Our approach to all forms of education will surely change.The COVID‐19 pandemic also has seen many indirect consequences, as shown in the third paper by Binder However, the basics still apply. The autopsy remains a valuable source of information which, whether it be a full autopsy or minimally invasive, if coupled with thorough sampling and retention of tissue for research and taken with appropriate consent, is key to understanding diseases and helping in their prevention.None.All authors contributed to the writing and editing of the manuscript.


The employment of directed acyclic graphs to advance the tracking, control and appraisal of crystallographic phasing strategies is discussed. Phasertng, which uses directed acyclic graphs natively for input/output, has been initiated. In Phasertng, the codebase of Phaser has been rebuilt, with an emphasis on modularity, on scripting, on speed and on continuing algorithm development. As a first application of phasertng, its advantages are demonstrated in the context of phasertng.xtricorder, a tool to analyse and triage merged data in preparation for molecular replacement or experimental phasing. The description of the phasing strategy with directed acyclic graphs is a generalization that extends beyond the functionality of Phasertng, as it can incorporate results from bioinformatics and other crystallographic tools, and will facilitate multifaceted search strategies, dynamic ranking of alternative search pathways and the exploitation of machine learning to further improve phasing strategies.Crystallographic phasing strategies increasingly require the exploration and ranking of many hypotheses about the number, types and positions of atoms, molecules and/or molecular fragments in the unit cell, each with only a small chance of being correct. Accelerating this move has been improvements in phasing methods, which are now able to extract phase information from the placement of very small fragments of structure, from weak experimental phasing signal or from combinations of molecular replacement and experimental phasing information. Describing phasing in terms of a directed acyclic graph allows graph-management software to track and manage the path to structure solution. The crystallographic software supporting the graph data structure must be strictly modular so that nodes in the graph are efficiently generated by the encapsulated functionality. To this end, the development of new software,  All entries are found in the PDB-REDO database  with optimization level 3. Differences between runtimes for 4.3.Phasertng over Phaser . Average speed improvements are shown in Table 2Phasertng code without threading runs between threefold and eightfold faster than the broadly equivalent Phaser code. With threading, the total runtime  runs between fivefold and 30-fold faster when using five threads. The dependence of runtime on the number of threads is shown for one case each of no TNCS, TNCS of order 2 and TNCS of order greater than 2 ; in the ARCIMBOLDO suite there are ARCIMBOLDO, ARCIMBOLDO_LITE, ARCIMBOLDO_BORGES and ARCIMBOLDO_SHREDDER (Rodríguez et al., 2009et al., 2013et al., 2018Auto-Rickshaw (Panjikar et al., 2005Phaser. Phaser is also used as the engine behind the UCLA Diffraction Anisotropy Server (Strong et al., 2006SBGrid wide-search MR server (Stokes-Rees & Sliz, 2010Phaser-dependent difference-map pipeline DIMPLE for ligand screening (Wojdyr, 2018Phaser for specific purposes in laboratory and synchrotron settings of which we are not aware.We hope that shifting to the phenix.MRage pipeline processes many MR models in parallel and if a solution is found with one model then all models are superimposed on the solution and rescored, so that the best model can be used to phase the map put forward for model building (Bunkóczi et al., 2013ARCIMBOLBO software makes high-level use of persistence of solutions while the model is systematically varied (Rodríguez et al., 2009et al., 2013et al., 2018et al., 2016ab initio phasing using molecular averaging (Tsao et al., 1992et al., 2004et al., 2000et al., 2005et al., 2010et al., 1999Phasertng.A simplistic approach to phasing is best described as a disjoint union of DAGs: every MR or SAD phasing trial is treated independently. More sophisticated search strategies simultaneously consider results from searches with different MR models or SAD substructures or both, as in MR-SAD. The Phasertng is central to the development of phaser.voyager, which will leverage the solution-tracking capabilities of the DAG in sophisticated and exhaustive phasing pathways. The DAG, paired with a formal database architecture for efficient model storage and retrieval, will streamline the termination and restarting of phasing pathways in order to simplify user intervention in search strategies. Wrapping Phasertng and the DAG data structure in phaser.voyager enables us to make optimal use of the maximum-likelihood and multivariate statistics for the preparation and selection of the data, the choice of SAD or MR as the primary phasing strategy, the generation of ensemble models customized to both the data and the hypothesis of the contents of the unit cell, tracking the persistence of solutions, managing coordinate editing and refinement. By applying graph analysis and data-mining methods to databases of phaser.voyager-generated DAGs, we aim to improve the efficiency of phasing and discover unexpected dependencies between DAG node data elements. Details of the phaser.voyager pipeline will be published elsewhere.Phasertng, phasertng.xtricorder and phaser.voyager will be made available through the Phenix (Liebschner et al., 2019CCP4 (Winn et al., 2011


Many of us work from home, at least partially. Traveling, especially in an international context, is restricted. Performing research and providing education is challenging. Although we aim for On the other hand, a crisis like the COVID-19 pandemic, also opens new chances. For example, the digital transformation of our societies gets a real push and might help us to develop a more sustainable behaviour. Videoconferences are now fully accepted, beneficial effects of remote teaching become visible, and thus in the future we will be better able to evaluate if travels are really needed.The digital transformation also affects our glass research – and this will definitely continue: Digital image processing is used in the paper of Dix et al. for the evaluation of anisotropy effects in pre-stressed glass; Drass et al. use semantic segmentation with deep learning for the detection of cracks at cut edges of flat glass, Hayez et al. give design rules for silicone joints in cold bent glass based on numerical simulations.The other papers in the current issue focus on the glass itself and material combinations with glass. Pauli et al. perform experimental and numerical investigations on glass fragments to derive a material model which in the future might be used to enhance post-fracture models for laminated glass, Brokmann et al. revisit the well-known problem of subcritical crack growth as a function of the environmental conditions, Joachim et al. perform testing of a novel combination of materials in composite panels made of glass and fibre-reinforced plastics and finally Götzinger et al. show first results of a new type of glass laminates adding paper as an interlayer.Stay healthy and keep reading our journal - especially if you are trapped at home!


Frontiers in Phytolith Research Topic includes high quality work across this whole range of phytolith research.Interest in phytoliths has grown significantly in recent years. The Research Topic is unusual in its highly interdisciplinary nature, and in the huge range of scales covered: from cellular and molecular studies of phytolith formation to investigations focussing on the role of phytoliths in biogeochemical cycling. This Bokor et al. paper in our issue reports a Si transporter in date palm for the first time. Two papers in our collection  investigate the effects of Si fertilization on phytolith accumulation in rice, and in both cases showed significant increases in deposition. Whether Si transporters are directly involved in the formation of phytoliths remains to be studied.For phytoliths to form, plants need to absorb silicon (Si) from their environment. Since Ma et al.  first deVolkov et al.) in our collection. The authors investigate silica and its carbohydrate matrix in the elaters of Equisetum arvense, using Raman and scanning electron microscopy, assisted by density functional theory. Phytolith chemistry has usually been analyzed in bulk samples, but Zancajo et al. investigate individual phytoliths in the leaves of Sorghum bicolor using Raman and synchrotron FTIR microspectroscopies. They show that bilobate silica cells have a different silica molecular structure and type of occluded organic matter compared with prickles and long cells.Plant internal processes and structure also impact on phytoliths. Phytoliths not only vary in shape and size, but also in their chemistry, and this is influenced by the environment in which they form Hodson, . Carole Ge et al. and Bhat et al. worked on members of the Panicoideae. Ge et al. consider morphological variation in the phytoliths from the inflorescence bracts of 38 weed and crop species in China, while Bhat et al. work on the leaf and synflorescence phytoliths of three Setaria species. In both cases the authors report that it is possible to distinguish fairly closely related taxa using phytolith morphological and morphometric traits. Two papers take very different approaches to the study of palm phytoliths . Bokor et al. work on the phytoliths found in stegmata cells present in roots, stems and leaves. The stegmata are located on the outer surface of sclerenchyma bundles or associated with the vascular bundles. Huisman et al. study the phytoliths of 12 palm species from mid-elevation Andean forests and identify a number of distinctive morphotypes that are characteristic of a particular species. But phytoliths do not always distinguish between related taxa. Wang et al. show that bulliform phytolith size could not be reliably used to distinguish between cultivated rice and three wild rice species, and moreover hydrothermal factors  led to increased size.One of the areas of phytolith research where we have seen major advances in the last 20 years is morphometrics. This work was further advanced by the publication of the International Code for Phytolith Nomenclature (ICPN) 2.0, while we were in the midst of compiling our collection [International Committee for Phytolith Taxonomy (ICPT), Mir et al. added to this body of literature, showing that Si fertilization of rescuegrass decreases herbivory by a grasshopper. They went on to show that the increased silica content of the plants caused greater mandibular wear of the grasshoppers.Plants deposit phytoliths for many reasons. It has been known for many years that plant silica acts as a physical defense against grazing and pathogens. Liu et al. study the translocation of phytoliths in soil profiles in Northeast China. They find that 22% of phytoliths are translocated beneath the surface, and that translocation depends on phytolith size and aspect ratio. The authors suggest that phytolith translocation should be considered in investigations concerning palaeoclimate and palaeovegetation reconstructions. Strömberg et al.  investigate the effects of fertilization on carbon sequestration in phytoliths from rice. In both cases fertilization has no effect on the carbon content of phytoliths, but it did increase the mass of phytoliths in the plants, and hence the total amounts of carbon sequestered. A further two papers  emphasize the importance of bamboo in carbon sequestration. Chen et al. work on the belowground biomass of monopodial bamboo species in China, and find that this represents an important and overlooked PhytOC stock. Zhang et al. carry out a wider scale investigation of carbon sequestration in phytoliths in the forests of China. They find that sequestration is particularly high in bamboo, and that the litter layer beneath bamboo plants is very high in PhytOC. This could make a very significant contribution to the long term global biogeochemical carbon sink.Parr and Sullivan  first suHodson assesses this whole controversy, and attempts to find a way forward. He suggests that cell wall phytoliths are much richer in PhytOC than lumen phytoliths, as demonstrated by Zancajo et al., and that they may be highly significant in global carbon sequestration. Two hypotheses are advanced, one to explain what happens to phytoliths when they are prepared in the laboratory for analysis, and the other what happens in the soil. Hodson concludes that phytoliths probably are an important global carbon store.In recent years the whole topic of carbon sequestration in phytoliths has become mired in controversy. Some (e.g., Song et al., Zuo and Lu provide a comprehensive review of this topic. They are critical of the “old carbon hypothesis” and suggest that dating of phytoliths often gives consistent results.The carbon dating of phytoliths has become another controversial area in phytolith research. Discrepancies in dating have been suggested to indicate that it is not a reliable technique, and some workers have suggested the “old carbon hypothesis” to explain these problems (Reyerson et al., Zancajo et al. which suggests that bilobate silica cells in sorghum leaves have a different type of occluded organic matter compared with prickles and long cells may yet prove important when we consider carbon sequestration and dating. Therefore, phytolith researchers need to be aware of work that is some way from their immediate field of research. If this does not happen then we will all miss out. In his opinion article, Katz suggests that we need to break down the disciplinary barriers within phytolith research to produce a superdiscipline. He ends by stating, “Hence, embedding superdisciplinary thinking in plant silicon and phytolith research can not only advance our field, but increase its impact in the merger of Earth and life sciences into a single superdiscipline. Working toward this goal is a true new frontier for plant silicon and phytolith research, for Earth-life sciences and for science in general.” There is much to be said in favor of this idea. We hope that Frontiers in Phytolith Research has, in some way, contributed to advancing the superdiscipline.Phytolith research is multidisciplinary and undertaken at many different scales. Often work in one area of research throws light on a topic at a different scale. So it is quite possible that the work of MH wrote the first draft of the editorial. ZS, TB, RE, and ES all commented on the draft. All authors agreed with the final draft.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.


Dear Editor,I read with interest the meta‐analysis of patient clinical characteristics and fatality rates in COVID‐19 from Chinese samples by Li et al.Li et al do not include Guan et al in their meta‐analysis of fatality rates and no reason is given for its omission. This is a concern, as the study by Guan et al is twice as large as all the other studies reporting fatality rates combined, and would significantly reduce the overall pooled fatality rate.


People residing in care homes may not be able to see visitors due to social distancing and other measures to restrict movement and contact outside the “household.” In addition, people who are at very high risk from COVID-19 because of severe preexisting health conditions may be required to “shield”  orders, and ceiling of care and treatments such as avoiding hospitalization and declining antibiotic use at the end of life. End-of-life care discussions are encouraged with the aim to maximize comfort and avoid potentially futile and burdensome interventions at the end of life, increasing the quality of the dying experience for all.et al., et al., Having discussions about end-of-life care can have multiple benefits. Significantly, it provides an opportunity for older persons to express their preferences for end-of-life care or to indicate who they would like to be involved in the decision-making process. This is important as they may be unable or lack capacity to contribute to these discussions when closer to end of life. There are also benefits for healthcare professionals, given that their confidence to discuss end-of-life care improves when they are equipped with knowledge of patient and family wishes (Poppe et al., et al., Guidelines generally recommend that these discussions take place during the early stages of a disease trajectory, in particular, in conditions where mental capacity may become compromised such as dementia (van der Steen et al., et al., et al., During the pandemic, however, as death and dying become the focus of our day-to-day lives, the impetus for having these discussions and considering our end-of-life care preferences may be brought to the fore. Previous barriers, such as not perceiving death as imminent or difficulties anticipating the future (Dening et al., et al., et al., Families may be struggling to recall what they previously discussed with the individual, considering their previous wishes, and balancing that with would their wishes be the same in the current situation. However, for many where conversations have not occurred, they will be faced with uncertainty and trying to anticipate what they think the individual would want (Lamahewa et al., The substituted interests model is an approach that may help reduce the stress on family in end-of-life decision-making (Sulmasy and Snyder, et al., During the pandemic, there has been a public rhetoric around DNACPR plans and hospitalization which may not be helpful. It is important to understand that this is not a binary decision but a conversation that opens up alternative and just as important types of care. Adopting a palliative approach is not denying care but means a person receives a more holistic and person-centered approach that is in keeping with their previous wishes and may maintain comfort, quality of life, and ensure a good death. Society as a whole has their part to play with this; supportive social networks and communities can help to desensitize these conversations and ensure conversations are discussed before acute events, better preparing everyone involved (Sawyer et al., et al., et al., Carers may benefit from support with making decisions (Mathew et al., et al., et al., COVID-19 will bring forward death for many older people. While grief is a normal part of life and death, circumstances around death can impact the grief process. Having discussions and being involved in decision-making are important elements for helping families and carers prepare for end of life. Feeling unprepared for death is associated with higher levels of complicated grief after death (Hebert et al., et al., et al., The three-tiered public health approach to bereavement suggests that most people will manage grief with support through their social network (Aoun “All societies have a death system with the basic functions of warning and prediction, prevention, caring for the dying, disposing of the dead, social consolidation after death, making sense of death, and killing” (Kastenbaum, The COVID-19 pandemic may help stimulate discussions regarding people’s end-of-life care preferences and break down some of the stigma associated with these discussions. However, within this context, there are also new challenges and obstacles to overcome. Greater pressures on healthcare systems will mean access to scarce intensive care resources may not be available to all, particularly those who may be considered less likely to recover from a severe case of COVID-19. Discussions about end of life usually benefit from relationship building between healthcare professionals, patients, and families, but current circumstances may limit communication between all parties. Technology may offer alternative forms for communicating where social distancing is in place, but these options may be challenging or not possible for many frail older people and people with moderate to advanced dementia. Decision aids may offer a practical tool to help carers make difficult decisions as proxies for the family members.As the death toll from COVID-19 rises, particularly among older people, the opportunities for social support and rituals around death have become limited. This will impact on how people process their grief and may have lasting consequences after the worst of the pandemic has passed. Community acknowledgement and support for grief will require new approaches within the context of the COVID-19 era.


Increasing numbers of young adults need continued support for their attention deficit hyperactivity disorder (ADHD) beyond the age-boundary for children's services. The sparse literature on transition in general suggests patchy provision and huge gaps in transitional care, but also that young people with ADHD and other neurodevelopmental disorders fair particularly badly. Transition in health care coincides with many other important life-transitions while the difficulties associated with ADHD may make these challenges particularly hard to cope with. Parents or other advocates therefore often need to be involved, which can present problems in adult mental health services given that they tend to be less family oriented than children's services. Importantly, young people need help negotiating the transition from passive recipient of care to active self-management, and in building relationships with the adult team.In addition to patchy provision of adult ADHD services, transition is currently hampered by poor understanding of ADHD as a long term condition and uncertain knowledge of what services are available among young people and parents as well as the clinicians working with them. Guidelines recommend, and more importantly young people want, access to psycho-social interventions as well as medication. However, available evidence suggests poor quality transitional care and adult services that are highly focused on medication.v. generic adult mental health services, for young adults with ADHD the training, experience and availability of professionals are more important than their qualifications or setting.Adult ADHD services need to undergo similar development to that experienced by Child and Adolescent Mental Health Services and community paediatrics over the last few decades. While we debate the relative merits of dedicated or specialist  Prospective reports by consultant paediatricians and child psychiatrists across the United Kingdom and Southern Ireland suggest that between 270 and 599 per 100 000 17–19 year olds per year needed transition (Eke et al., et al., et al., et al., The focus on medication to the exclusion of other types of intervention is problematic (Janssens et al., et al., et al., et al., et al., et al., et al., et al., The difference in culture between child centred services, where parental involvement is assumed, to adult oriented services where parents were not necessarily included, causes problems for young people in transition and their carers (Singh et al., et al., et al., et al., Provision is strongly influenced by the historical development and funding processes (Crowley and Wolfe, et al., et al., et al., There have been a flurry of concerns about the provision of mental health care for young people, as well as for adolescents with long term conditions across high income countries (Crowley and Wolfe, et al., A systematic review identified three distinct but not mutually exclusive models of transitional care, all originating from the United States of America, as well as a lack of evidence to support their application (Nguyen generic adult mental health services or whether dedicated specialist services are preferable. There is also debate about what constitutes a specialist service? A Delphi study conducted about this issue in relation to eating disorders that concluded specialist services provide evidence-based interventions, must be multi-disciplinary, and staff working within the service must have a clear focus on, and expertise in, the focus condition (Petkova et al., v. generic eating disorder services for young people suggested that specialist services did not produce better outcomes but as they worked with young people who had more severe difficulties, they were cost-effective depending on willingness to pay (Byford et al., Despite the lack of evidence to support particular models of care in ADHD (Cortese and Barbui, transitional care, assessment and diagnostic services, drug titration, monitoring and review, and psychoeducation (Nutt et al., et al., et al., et al., et al., Adult ADHD services need to undergo similar development to that experienced by CAMHS and community paediatrics over the last three decades Coghill, . Clinicaet al., et al., et al., increase in the number of young adults who should transition. Service providers and commissioners should plan accordingly. As Professor Coghill argues, the training, experience and availability of professionals are more important than their qualifications or setting, but given how complex and variable the manifestations of ADHD can be, management by primary care without the support of specialist services may miss important comorbidities, even in ‘uncomplicated cases’ (Coghill, et al., We should be reassured that the epidemiological evidence points to continued under-recognition and under-treatment of children and young people in many countries (Ford Coghill, . What is


Perioperative neurocognitive disorder (PND) is a common phenomenon associated with anesthesia and surgery and has been frequently described in the elderly and susceptible individuals. Microglia, which are the brain’s major resident immune cells, play critical roles in maintaining neuronal homeostasis and synaptic plasticity. Accumulating evidence suggests microglial dysfunction occurring after anesthesia and surgery might perturb neuronal function and induce PND. This review aims to provide an overview of the involvement of microglia in PND to date. Possible cellular and molecular mechanisms regarding the connection between microglial activation and PND are discussed. Microglia are a type of neuroglia occurring in the central nervous system (CNS) and can be defined as tissue-resident macrophages  and cognitive decline diagnosed up to 30 days after the procedure (delayed neurocognitive recovery) and up to 12 months , fractalkine receptor CX3CR1, Csf-1R and CD68  and other inflammatory mediators (Buvanendran et al., Systemic inflammation can induce neuroinflammation and cognitive dysfunction in aged animals (Yamanaka et al., in vivo two-photon microscopy (Sun et al., in vitro studies show propofol has neuroprotective effects by attenuating inflammatory response in microglia (Gui et al., in vivo imaging in awake and anesthetized animals could help study microglia-neuron interactions (Liu Y. U. et al., The target organ of general anesthesia is the brain, but whether it is the main culprit causing cognitive decline by microglia remains controversial. The isoflurane or ketamine anesthesia causes morphological changes of microglia in rodents by using A recent study showed that peripheral surgery-induced CNS mast cell degranulation, which could trigger microglial activation and neuronal damage, contributing to PND (Zhang et al., via neuronal TNF receptors (Stellwagen and Malenka, Microglia mediate the inflammatory response in the hippocampus, resulting in the alteration of glutamatergic synaptic transmission and plasticity, which may underlie the behavioral comorbidities seen in patients (Riazi et al., As mentioned above, microglia play an important role in PND associated with neuroinflammation. PND is mainly seen in the elderly, and experimental studies also showed that it occurs frequently in old animals. Anesthesia and/or surgery did not cause a change in cognitive function in young adult mice (Zhao et al., PND is a widespread phenomenon following the surgery and anesthesia and can have detrimental effects on an individual’s quality of life and well-being. The pathogenesis of PND is not fully understood. Activation of microglia and neuro-glial interactions seem to be key mechanisms in PND . The preWF designed and drafted the manuscript and figure. LM and XZ analyzed the data. FH and HH revised the manuscript. All authors contributed to the article and approved the submitted version.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.


The giant panda is one of the most endangered mammals in the world, and many studies have revealed their evolutionary adaptation to the local environment  on the evidences from population genetics and their gut microbiome. Here, based on the results of our analysis of the giant panda gut microbiome, we concluded that instability and resilience are the two primary characteristics of the giant panda gut microbiome. This basic information may have an impact on giant panda conservation, as well the management of other animal species. Additionally, increasing the connectivity among fragmented and isolated populations can increase gene flow and genetic diversity, which can mitigate negative effects due to inbreeding (Epps et al., 2.3Based on our previous research, we found some differences in the gut microbiome between wild Xiaoxiangling population and Minshan populations (Yao, Xu, Hu, et al., 2.4Antibiotic‐resistant pathogens can have a profound effect on animal and human health (Allen et al., None declared.All authors contributed to the manuscript writing. ZZ and TH contributed equally to this work.


Dogs and cats have gained a special position in human society by becoming our principal companion animals. In this context, efforts to ensure their health and well‐fare have increased exponentially, with in recent times a growing interest in assessing the impact of the gut microbiota on canine and feline health. Recent technological advances have generated new tools to not only examine the intestinal microbial composition of dogs and cats, but also to scrutinize the genetic repertoire and associated metabolic functions of this microbial community, revealing that the taxonomic composition and the metabolic repertoire of the intestinal microbial population of dogs and cats may be influenced by several factors, including diet, age and anthropogenic aspects, as well as intestinal dysbiosis. Dogs and cats have gained a special position in human society by becoming our principal companion animals. In this context, efforts to ensure their health and welfare have increased exponentially, with in recent times a growing interest in assessing the impact of the gut microbiota on canine and feline health. Recent technological advances have generated new tools to not only examine the intestinal microbial composition of dogs and cats, but also to scrutinize the genetic repertoire and associated metabolic functions of this microbial community. The application of high‐throughput sequencing techniques to canine and feline faecal samples revealed similarities in their bacterial composition, with Fusobacteria, Firmicutes and Bacteroidetes as the most prevalent and abundant phyla, followed by Proteobacteria and Actinobacteria. Although key bacterial members were consistently present in their gut microbiota, the taxonomic composition and the metabolic repertoire of the intestinal microbial population may be influenced by several factors, including diet, age and anthropogenic aspects, as well as intestinal dysbiosis. The current review aims to provide a comprehensive overview of the multitude of factors which play a role in the modulation of the canine and feline gut microbiota and that of their human owners with whom they share the same environment. Indeed, in addition to taxonomic composition, WMS offers in‐depth insights into the genomic content and compositional arrangement of bacterial consortia, also allowing predictions of their functional features  per gram of luminal content , XI (Peptostreptococcaceae family) and XIVa (Lachnospiraceae family and Blautia), while the Erysipelotrichi is mainly represented by Turicibacter, Catenibacterium and Coprobacillus genera . Furthermore, the total concentration of SCFAs was higher in faecal samples of treated cats when compared to the cellulose control , instead of the more conventional commercial dry food , while a negative correlation was observed with faecal output, indicating that the increased abundance of Clostridiaceae taxa in the faecal microbiota of dogs fed on a BARF diet is not detrimental for canine health, but, rather, is associated with protein degradation  is, indeed, generally accompanied by an increase in the biodiversity of the pups' gut microbiota  responsible for enhancing glucose‐dependent insulin secretion by pancreatic β‐cells , osteoarthritis or cardiovascular diseases that undermine canine and feline health  typical of an inflammatory status   and acute haemorrhagic diarrhoea syndrome  refers to a heterogeneous group of intestinal disorders that are generally classified in accordance to their response to treatment, encompassing diet‐responsive enteropathy (FRE), antibiotic‐responsive enteropathy (ARE) and immunosuppressant‐responsive enteropathy (IRE) better known as idiopathic inflammatory bowel diseases , highlighted that cats with CE generally show a decrease in the relative abundance of the Bifidobacterium genus, a trend that had not been documented for dogs suffering from CE  have been employed as therapeutic treatments  that promote proliferation of beneficial bacteria residing in the GIT of the host  and the method of faecal supplementation .et al., et al., et al., et al., et al., et al., et al., et al., et al., Alistipes, Pseudomonas, Slackia, Subdoligranulum, Eubacterium coprostanoligenes and Barnesiella, have apparently been lost by the domesticated canine core gut microbiota, the latter have acquired five other microbial taxa, including Dorea, Parabacteroides, Streptococcus, U. m. of Bacteroidales order and U. m. of Clostridiales order, which are typical components of the human core intestinal microbiota (Alessandri et al., Streptococcus genus was absent in the intestinal community of wolves, it was detected in the canine one (Wu et al., et al., et al., Ruminococcaceae, Desulfuromusa, Lactobacillus, Carnobacillus and Faecalibacterium, showed a significantly higher relative abundance in dogs, thus indicating that the composition of the canine gut microbiota has been influenced by dietary changes imposed by humans (Lyu et al., et al., Humans have been identified as major players in driving several evolutionary events, encompassing extinction or speciation through domestication, relocation and creation of novel ecosystems (Bull and Maron, et al., et al., et al., et al., Ruminococcus and Oscillospira genera, in the infant intestinal microbial community (Tun et al., Oscillospira is associated with leanness and lower body mass index in both adults and infants, Ruminococcus is linked to the maintenance of the intestinal barrier integrity (Tun et al., Ruminococcus and Oscillospira have been negatively related to the development of infant atopy and obesity, respectively, suggesting that pet‐associated microbiota may have a role in modulating the infant gut microbiota (Tun et al., et al., Escherichia coli, Salmonella and Campylobacter that may be transmitted horizontally, and may thus cause zoonotic enteric diseases to humans (Morato et al., et al., et al., et al., However, cohabitation and the resulting close relationship between humans and their pets have not only significantly influenced the animal microbiota, but also the human‐associated microbial community (Song During the course of evolution, dogs and cats have become the main companion animals for humans. Being an integral part of human life, interest for pet health and well‐being has rapidly increased during recent decades and has consequently promoted many studies concerning the canine and feline gut microbiota, which are known to influence the health status of the host. In this perspective, it has been demonstrated that diet, age, anthropogenic influences and several other environmental factors play a role in modulating both the taxonomical composition and the functional activities of the intestinal microbial community of dogs and cats. Furthermore, alterations of the intestinal homeostasis are generally associated with a dysbiotic gut microbiota and the onset of inflammatory bowel diseases that may be treated with different therapies, including prebiotics, probiotics, synbiotics, antibiotics or FMT as for humans IBD. Nevertheless, further research is necessary to deepen our understanding of the role of this microbial community and to better appreciate how it interacts with dogs and cats.The authors declare that they have no competing interests.


As the first case–control study of malignant mesothelioma of the pericardium and the tunica vaginalis testis (mTVT), the paper by Marinaccio et al  is potencontrols by year of birth are distinctly different (P<0.002), whereas the birth-year distributions of cases of mesothelioma by site and gender are not (P≈0.8).Any case–control study can be viewed as being nested within a conceptual cohort, with controls being sampled from the at-risk cohort as cases arise over time. This view of case–control studies leads to the concept of incidence-density sampling of controls . For Marinaccio et al  this wouIn the Marinaccio et al  sensitivThe second major issue of concern has to do with ascertainment of asbestos exposure. Information on exposure for the cases was presumably obtained at the time of registration. The two sets of controls, obtained from previously unpublished case-control studies, were interviewed during 2014–2015 and 2014–2016; that is, many years after the exposure for most cases was ascertained 1993–2015). Few other details of the control groups are provided, except that participation by one set of controls was <50%, raising additional concerns about selection bias. For details on the second set of controls, Marinaccio et al  would be helpful. Marinaccio et al  remarkedThe fact that few, if any, cases of mTVT and pericardial mesothelioma occurred in industries traditionally associated with high asbestos exposure raises the possibility that the results of Marinaccio et al  are attrThis research has received no outside funding. All authors are employees of Exponent, Inc., an international scientific and engineering consulting company. All authors have worked as both consulting and testifying experts in litigation matters related to asbestos exposure and asbestos-related disease.


Despite the progress made in HIV treatment and prevention, HIV remains a major cause of adolescent morbidity and mortality in sub-Saharan Africa. As perinatally infected children increasingly survive into adulthood, the quality of life and mental health of this population has increased in importance. This review provides a synthesis of the prevalence of mental health problems in this population and explores associated factors. A systematic database search  with an additional hand search was conducted. Peer-reviewed studies on adolescents (aged 10–19), published between 2008 and 2019, assessing mental health symptoms or psychiatric disorders, either by standardized questionnaires or by diagnostic interviews, were included. The search identified 1461 articles, of which 301 were eligible for full-text analysis. Fourteen of these, concerning HIV-positive adolescents, met the inclusion criteria and were critically appraised. Mental health problems were highly prevalent among this group, with around 25% scoring positive for any psychiatric disorder and 30–50% showing emotional or behavioral difficulties or significant psychological distress. Associated factors found by regression analysis were older age, not being in school, impaired family functioning, HIV-related stigma and bullying, and poverty. Social support and parental competence were protective factors. Mental health problems among HIV-positive adolescents are highly prevalent and should be addressed as part of regular HIV care. Of the 1.6 million adolescents living with HIV globally, around 1.1 million reside in Eastern and Southern Africa and another 430 000 in West and Central Africa UNICEF, . Approxiet al., et al., et al., et al., et al., et al., et al. . The systematic review aims at updating the findings from the review of Cortina et al.  on childet al., The systematic review was undertaken by the MEGA project team. MEGA is an international collaborative project for mental health promotion among adolescents in South Africa and Zambia ;− lack of prevalence data;− non-standardized or incomplete instruments, not regularly used in mental health research;− reviews, validation studies, or qualitative studies.Exclusion criteria were:The following search terms were used: child*, youth, adolesc*; sub-Saharan, Africa, South Africa, Zambia; prevalence, incidence, epidemiol*; psychiat*, mental, depress*, ADHD, anxiety . The database search revealed 1374 articles. In total, 65 additional articles were found through Google Scholar, further 22 through reference lists, citations, and contact with other researchers. After the removal of duplicates, 1070 records were left for the screening of title and abstract. After exclusion of articles on clinical psychiatric populations or youth beyond the age range of 10–19 and articles with a wrong publication type or date, 301 articles were eligible for full-text assessment.The exclusion of articles was done according to the PICO-based taxonomy  Critical Appraisal Checklist for Studies Reporting Prevalence Data . In eight of the studies, screening scales were used to assess mental health symptoms or behavior . Four stet al., et al., et al., et al., et al., and Menon et al., who focused on younger adolescents and Okawa et al., who focused on older adolescents   enrolled in a disclosure intervention trial in Kenya  and Namibia , reported a prevalence of 28.5% and 29.1% for emotional and behavioral problems   reported on the percentage that scored in the clinical range (29.2%)  to a sample of school children (n = 420) . Three studies also reported results for the different subscales of the SDQ  from Uganda and reported a prevalence of 51%.Musisi and Kinyanda  made useSymptoms of depression were assessed in five of the studies , 25.3% of adolescents had high scores of depressive symptoms, according to the short form of the Center for Epidemiologic Studies Depression Scale (CES-D)  that used the Center for Epidemiologic Studies Depression Scale for Children (CES-DC) , 19% of adolescents scored positive for depression, according to the Patient Health Questionnaire (PHQ-9). However, 15% showed minimal, 3% minor, and 2% moderate or severe symptoms  showed symptoms of depression, according to the Child Depression Inventory (CDI)  were only reported from the South African sample , 21% of HIV-positive adolescents reported suicidal behavior (including self-harm) during the previous 6 months, compared to 13% of unaffected adolescents. Kemigisha et al. . In total, 69.2% of adolescents reporting suicidal ideation were female and 30.8% were male. Furthermore, 81% of adolescents reporting suicidality also scored positive for depression.Three studies assessed g et al.  reporteda et al.  reportedet al., et al., et al., et al., The prevalence of mental disorders was assessed by structured or semi-structured diagnostic interviews  in three studies   and anxiety disorders were the most prevalent type of emotional disorders (14.7%). The prevalence of major depressive disorder was 5.2%. Prevalence according to self-report alone were much lower .An overall prevalence of depressive disorder was 18.9% in a large sample  from Malawi  , 41.9% were diagnosed with depression, with the highest prevalence (83.3%) found in the 14–16 years age group  found a depression prevalence of 40.8% . Furthermore, 19.5% reported ever having made a suicide attempt and 17.1% had attempted suicide within the past 12 months.In a sample from Nigeria  and the experience of violence or abuse were associated with poor mental health. Social support through community, family, or friends, and good parenting were associated with better mental health outcomes in several studies. Individual-level factors such as feeling able to control the future and having dreams for the future were likewise associated with better mental health.Factors identified by logistic regression are shown in et al., et al., et al., found a significant association between conduct problems and non-adherence and also, though weaker, between self-reported depression and non-adherence. Okawa et al., did not find a significant association between depressive symptoms and non-adherence.Two other studies explored the factors associated with non-adherence, using mental health as an independent variable in logistic regression  who had to figure out their HIV status on their own were more likely to show mental health symptoms and internal stigma, compared to youth who were disclosed to (Ramos et al., The disclosure of HIV was not identified as a predictive factor for mental health in regression models. The bivariate analysis suggested no adverse effects of disclosure, but associations between mental health problems and disclosure of HIV status to others. WHO strongly recommends timely disclosure WHO, . Studieset al., et al., et al., et al., et al., et al., et al., suggests that the mode of infection might be an important factor for both mental health outcomes and retention in care and that it also has an influence on how adolescents are treated by health care workers.Findings on mental health as an independent factor for ART adherence were contradictory (Smith Fawzi et al., et al., et al., et al., et al., Given the high prevalence of mental health problems among HIV-positive adolescents, identifying and addressing these problems is crucial. Screening for mental health problems and integrating mental health care into regular HIV services is highly recommended (Musisi and Kinyanda, et al., et al., et al., Lyambai and Mwape  conducteet al., et al., et al., et al., et al., et al., et al., There are multiple approaches for improving the mental health of HIV-positive adolescents, e.g. enhancement of self-regulation skills and coping strategies (Bhana et al., et al., et al., et al., As different samples are exposed to a different set of risk and protective factors, differences in prevalence are comprehensible (Fisher et al., et al., et al., Two studies on younger adolescents reported a low prevalence of emotional and behavioral problems, almost comparable to the general adolescent population (Menon et al., et al. (et al., and only found a modest correlation between the two. A low inter-informant agreement was also reported by Doku and Minnis (Differences between self- and caregiver-report were described in two of the studies (Lyambai and Mwape, , et al.  exploredd Minnis  from a set al., et al., et al., Reviews on child and adolescent mental health found that studies that used screening instruments reported higher rates of mental health problems, compared to studies that used diagnostic interviews (Fisher et al., Most of the studies used self-reporting screening instruments. As screening instruments can merely identify symptomatic people or people with a probable psychiatric disorder, results from screening instruments are not equivalent to disorder prevalence. Using screening instruments can result in an overestimation of disorder prevalence, as could be shown for depression screening among people living with HIV in sub-Saharan Africa Tsai, . ParticuSelf-reported results are prone to reporting bias and may be influenced by social desirability, so results have to be interpreted with caution. Where sensitive issues are concerned, there is a considerable risk of underreporting. Most studies used convenience sampling which has an impact on the representativeness of the data. As the vast majority of studies were cross-sectional, no causal relationships can be derived from the results. Most of the studies did not use control groups, which makes it difficult to differentiate between HIV-related mental health risks and risks that adolescents share with their peers from the same community.et al., et al., et al., et al., et al., et al., et al., et al., et al. (The majority of standardized screening instruments and diagnostic interviews in use in the field of child and adolescent mental health today were developed in high-income settings. Questions developed and tested in high-income settings may be inappropriate when used in a low-resource setting, which can lead to an over- or underestimation of prevalence (Sweetland , et al.  have shoThe number of databases that were searched was limited due to time and capacity restrictions, though the most important ones were included. Because we focused on peer-reviewed articles only, EMBASE and conference websites were not searched. The inclusion of studies in other languages than English may have led to additional findings. Because of our focus on adolescents aged 10–19, publications employing a broader age than 10–19, reporting prevalence data for children and adolescents or for adolescents and young people up to the age of 24 may have been missed. Due to publication bias, studies that found a high prevalence of mental health problems may be overrepresented. As the review was conducted within an adolescent mental health promotion project in South Africa and Zambia, both countries were included in the search terms which might have led to an overrepresentation of studies from these two countries. Furthermore, the results presented here are a subsection of a larger systematic review and the comparability of the findings to the general sub-Saharan adolescent population, as well as other high-risk groups, can only be commented on once the other sections of the review have been published. Lastly, the review was limited to the period 2008 and 2019 and so studies published before and after this period, which may be informative, were excluded.This review updates and synthesizes evidence on the prevalence of mental health problems among HIV-positive adolescent populations in sub-Saharan Africa. Mental health problems are highly prevalent in this population and need to be addressed within regular HIV care settings. Poor mental health can be associated with non-adherence to ART and with other risk behaviors, leading to poorer physical outcomes and a higher risk of HIV transmission. Health care professionals working with HIV-positive adolescents should be enabled to recognize mental health problems and respond to them in an appropriate, non-discriminatory way to ensure the best possible outcomes.


Swift medically led scientifically informed responses to the Covid-19 epidemic nationally have been demonstrably superior to other, non-scientific approaches. In forensic psychiatry and across all psychiatric services, urgent and clinically led responses have underlined redundancies and confusions in the governance of mental health services and a vacuum in policy makers. For the future, a greater emphasis on services for patients with schizophrenia and other severe, enduring mental disorders must aim at reducing standardised mortality ratios, managing risk of violence and improving hard outcomes such as symptomatic remission, functional recovery and forensic recovery of autonomy. This will require more use of information technology at service level and at national level where Scandinavian-style population-based data linkage research must now become legally sanctioned and necessary. A national research and development centre for medical excellence in forensic psychiatry is urgently required and is complimentary to and different from quality management. The aim of forensic psychiatrists is to manage the COVID-19 crisis in secure hospitals and prisons to prevent clusters where possible, to provide effective medical assessment and treatment where necessary, whilst continuing to manage the mental health and violence risk posed by the vulnerable and stigmatised patients we serve. It is essential to evaluate and research organisational and service responses to this crisis and to continue to develop research in this field to improve ‘hard’ outcomes, mortality and functional recovery (Kennedy et al. et al.Forensic psychiatry occupies the interface between psychiatry and the law. It is a subspecialty within psychiatry, which provides specialist treatment to the most severely mentally ill. Like other tertiary referral services aiming to reduce mortality and manage risk such as oncology or obstetrics, forensic psychiatry is a national service because it requires a critical mass and minimum level of activity to maintain both effectiveness and efficiency (Amato et al. et al. et al. et al. et al. et al. et al. et al. In recent years, driven by new population needs, forensic psychiatry services have begun to develop new subspecialties within forensic psychiatry including forensic psychiatry for those with intellectual and developmental disabilities (Gulati et al. et al. et al. et al. et al. et al. et al. et al. et al. et al. Forensic psychiatry in Ireland and Europe is at a turning point. At the beginning of 2020, the National Forensic Mental Health Service was in the advanced stages of preparing to move to the new forensic hospital in Portrane, Dublin (Kennedy, et al. et al. et al. Forensic psychiatrists are trained to give expert evidence and to be cross-examined on their evidence rationally and rigorously in the formal setting of a court of law Kenny, . The difCountries such as Ireland which have relatively low Covid-19 death rates are generally those with leaders who have quickly acted on expert advice – complex, imperfect, tolerant of diversity and capable of compromise. Ireland has done very well in this crisis, so far. This contrasts with populist leaderships who had ‘enough of experts; and promised simple solutions to complex questions, perfect solutions, winner take all deals and an inability to make pragmatic compromises, with an intolerance of other points of view. Ireland has performed well by following expert advice concerning how to manage the Covid-19 epidemic so far. For the next steps in the COVID-19 crisis, as well as any future pandemics, success will depend on accepting the necessity of expertise, recognising scientific facts about epidemiology, and distinguishing experts from pundits (Collins & Evans, The Irish Government appointed a stellar list of academic and professional leaders to produce the Fitzgerald report to examine the needs for acute hospital beds (Department of Health, et al. et al. et al. et al. et al. The teaching hospitals benefit from their boards, ensuring governance that is medically responsible, patient centred and able to maintain an arms-length protection from cyclical austerity policies and the consequences of confusion about the nature of expertise. These teaching hospitals have world class research-driven programmes for translational medicine with traditions of excellence and patient-centred values that are still intact. Psychiatry, however, has been almost entirely subsumed by the directly managed public sector and this sector (Department of Health, How has the Covid-19 crisis tested our services and our preparedness? The spread of the Covid-19 pandemic to Ireland impacted everyone including patients detained in confined places such as prisons and secure psychiatric wards. The onset of the national emergency was sharp, as was governmental and public recognition. During the initial weeks, fire fighting became the order of the day. Clinicians had to rapidly reassess how to practice safely and effectively from day to day. The switch to remote working by phone and video improved efficiencies and generated new risks. There have been many outstanding examples of nimble and adaptable behaviour. Telemedicine has been implemented almost everywhere including the courts. Meetings are leaner, more driven by the agenda and the need to reach practical decisions quickly. Triage has become rigorous and effective.et al. et al. et al. et al. The chronic shortage of acute and intensive care beds in general medicine was solved in Ireland by taking the large number of private hospital beds into the public system, a political act that exposed our collective tolerance of ‘normal’ trolley queues. This has not yet benefitted forensic psychiatry where severely mentally ill people in prison have prolonged waiting times for admission to hospital. Triage was already invented and rigorously applied by necessity (Flynn In forensic psychiatry, court appearances by patients transferred overnight to telepresence (Day & Cleary, et al. et al. et al. et al. et al. et al. et al. Forensic psychiatrists have long since established that the busiest acute psychiatric units are remand prisons (Lenihan To meet the needs of this vulnerable prisoner group, the National Forensic Mental Health Service and Irish Prison Service worked together to develop a system of telemedicine to provide video-link mental health clinics for the prisons service, to support prisoners and the prison primary healthcare teams. Triage is completed by forensic psychiatry nurses and psychiatrists in cooperation with IPS nurses. When a prisoner requires an in-person review, this is now conducted in a closed, screened visitor area of the prison to prevent transmission of Covid-19 from either the hospital team to the prison or vice versa. These arrangements are safe, efficient, prompt and will likely continue.et al. Older prisoners are a uniquely vulnerable group. Older prisoners have a health age similar to elders in the community that are 10 years their senior (Davoren et al. et al. The National Forensic Mental Health Service is working very closely with colleagues in the Irish Prison Service to deliver the best possible service, whilst acknowledging the challenge of providing safe and effective care to such a vulnerable unwell group at this time. It has never been more pressing to provide humane drug-free prisons and enough acute, sub-acute, medium-term and long-term secure forensic hospital places, with decant wards and surge capacity (McManus et al. et al. et al. 2018, et al. et al. et al. et al. et al. et al. et al. The Covid-19 emergency has led to rapid changes in working practices in psychiatry (European Centre for Disease Control and Prevention, This is an idea that has at last found its moment. As with every other employer, the National Forensic Mental Health service must pay greater attention to promoting employee safety. Public health information is made available to increase awareness of the new risks associated with Covid-19. Training in the donning and removal of PPE and hand washing is the new normal. Support must also be made available for impacted employees. For the future, there should be a return to investing in career development – every trainee should be able to register for a higher degree relevant to their practice. This would be a real stimulus to the knowledge culture and economy of medicine and health professions.et al. et al. et al. et al. There will be no return to the old normality. It may take longer than expected to achieve sufficient population immunity through vaccination or exposure. There will likely be further, lesser epidemics and there may be more deadly ones. The universal recognition of medical need and medical leadership in the face of deadly illnesses needs to be kept in the forefront of policy and practice when the increased and increasing mortality of the severely mentally ill has been missed by lay policy makers until now (Crump Shared office space is already a thing of the past. Telemedicine may replace most but not all prison in-reach and outpatient clinics, and hospital practice will benefit from leaner, more focused patient reviews. Training for psychiatrists will likely revert to the model of valuing preliminary years of training in general medicine or general practice. Out-patient and hospital work will be far more efficient through the liberation of clinicians from administrative burdens and a greater task orientation towards achieving clinical goals. Formal productivity monitoring through the use of electronic clinical management systems will drive further reform of the deployment of all health professionals. Waiting lists will be managed through the deployment of senior clinicians to this key decision-making function, with re-medicalisation of assessment and neuropharmacological management.et al. Forensic psychiatry needs a governance structure in which medical leaders (Ham, et al.et al. et al. et al. et al. Prior to the Covid-19 pandemic, there was tolerance for a homeless, mentally ill and substance misusing population who cycle between psychiatric and addiction services, prisons and street services Maxmen, . They reet al. et al. et al. The future can be bright for patients in forensic psychiatry services. A new hospital will replace the 1850s Dundrum buildings in 2020. New teaching and research programmes will be an intrinsic part of the new hospital (Kennedy


Current human-induced climate warming poses a threat to many organisms Somero, . SpeciesIn recent decades there has been a boom in studies that use genome-wide sequencing (Savolainen et al., Logan and Cox suggest that there is moderate heritability for upper thermal tolerance and, hence, the potential for heat tolerance to evolve. However, this may also be constrained by unfavorable genetic correlations with other thermal performance traits. They also suggest that the plastic response of the transcriptome depends on the magnitude of thermal shifts. Rodrigues and Beldade also study genomics and transcriptomics of plasticity, which are usually assumed to have the potential to enhance thermal adaptation. However, more research is needed because high phenotypic plasticity may be maladaptive in warmer and more variable future climates (Kreyling et al., Drosophila Genetic Reference Panel (DGRP, Mackay et al., Lecheta et al. found that heat tolerance is less variable than cold tolerance, with ~50% more identified genes affecting the latter. These results reinforce that heat tolerance is more constrained than cold tolerance (Araújo et al., Sørensen et al. studied D. simulans populations after 20 generations of experimental evolution under predictable or unpredictable thermal fluctuations. The strongest response involved unpredictable fluctuations, and the genes under selection were distinct from the genes that are important for the adaptive plastic response under predictive thermal fluctuations. Other studies have shown that constant and fluctuating temperatures induce different plastic and evolutionary responses (Botero et al., Using a genome-wide association study and transcriptomic profiling in lines from the Zwoinska et al. found that males are more affected than females when flies were exposed at high sublethal temperatures. At the same time, they did not find additive genetic variance for reproductive performance at these temperatures. Similar results were obtained for the egg-to-adult viability assessed at different temperatures in D. melanogaster (Kristensen et al., Zwoinska et al. the power to map the genetic variants of relatively small effects may be reduced due to the low line number. Thus more studies, using several populations or more DGRP lines are needed.A potential limitation of studies on the evolution of heat tolerance is that most ignore the possible negative impacts of sublethal temperatures on oogenesis and spermatogenesis. This could lead to a higher vulnerability to climate warming in many organisms than is currently thought (David et al., Drosophila subobscura are remarkably consistent worldwide and highly correlated with environmental temperature, respond to seasonal changes and frequency shifts shortly after a heatwave (Balanyà et al., Karageorgiou et al. focused on the breakpoints of a particular inversion that shows cyclic seasonal changes and speculate that this might be partly due to antagonistic pleiotropic effects on reproduction and immunity resulting from a position effect affecting the expression of functional genes located at the breakpoints.Few studies have demonstrated that adaptive evolution is occurring as a consequence of climate change. Latitudinal and long-term trends in the frequency of inversions in Mazzucco et al. focussed on the endosymbiont Wolbachia infecting D. melanogaster lines evolved in cold and hot environments, and found that these dynamics cannot be straightforwardly linked to temperature, making it difficult to predict the impact of climate change.An important ingredient in a warming world is the ecological and evolutionary implications of parasite-host dynamics and prevalence. Cortés et al. summarize some of the tools available to reveal the genetic consequences of climate change, but there are some shortcomings to linking fitness relevant genes with environmental factors; e.g., those related to data reporting as highlighted by Waldvogel et al. This is important, as genotype-environment associations can be a key ingredient in forecasting the response of natural populations to climatic variation.A goal of genome-wide analyses is to detect and understand the signatures left by natural selection on the genome. Alcorta et al. shed light on the genomic features and taxonomy of thermophilic cyanobacteria living in hot springs. These features included genome reduction, changes in GC content, coding density, and size of biosynthetic gene clusters.Relevant insights into the genetic basis of thermal evolution can come from studying the adaptations of organisms that live in extreme natural environments. Using a metagenomics approach, The contributions to this Research Topic add to our understanding of thermal adaptation and its multifactorial nature, and highlight the challenges that are still ahead of us in striving for a deeper understanding of adaptation to expected higher and more variable future temperatures. As shown in this Research Topic, increased knowledge should be brought about by complementary approaches comprising different levels of biological organization and their interaction, using a variety of methodologies and study organisms.All authors listed have made a substantial, direct and intellectual contribution to the work, and approved it for publication. All authors contributed to the writing of the editorial.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.