Wild sheep and many primitive domesticated breeds have two coats: coarse hairs covering shorter, finer fibres. Both are shed annually. Exploitation of wool for apparel in the Bronze Age encouraged breeding for denser fleeces and continuously growing white fibres. The Merino is regarded as the culmination of this process. Archaeological discoveries, ancient images and parchment records portray this as an evolutionary progression, spanning millennia. However, examination of the fleeces from feral, two-coated and woolled sheep has revealed a ready facility of the follicle population to change from shedding to continuous growth and to revert from domesticated to primitive states. Modifications to coat structure, colour and composition have occurred in timeframes and to sheep population sizes that exclude the likelihood of variations arising from mutations and natural selection. The features are characteristic of the domestication phenotype: an assemblage of developmental, physiological, skeletal and hormonal modifications common to a wide variety of species under human control. The phenotypic similarities appeared to result from an accumulation of cryptic genetic changes early during vertebrate evolution. Because they did not affect fitness in the wild, the mutations were protected from adverse selection, becoming apparent only after exposure to a domestic environment. The neural crest, a transient embryonic cell population unique to vertebrates, has been implicated in the manifestations of the domesticated phenotype. This hypothesis is discussed with reference to the development of the wool follicle population and the particular roles of Notch pathway genes, culminating in the specific cell interactions that typify follicle initiation. The changes in fleece traits are consistent with the observations of Darwin , who not8.et al., One aspect of the evolution of the fleece not previously addressed has been the effect of the domestication process itself, beginning at the capture of animals from the wild and introducing them to an environment created by humans. The pioneering work of the Soviet scientist Dmitry Belayev, using wild silver foxes, demonstrated that by selecting individuals for a single behavioural trait (tameness), an array of seemingly unrelated developmental, physiological, hormonal and skeletal modifications were induced Belayev, , 1979. Iet al., et al., et al.  in which the only common denominator was that of being brought under human control (Trut , et al.  to descr9.The genetic and developmental mechanisms underlying domestication have been widely canvassed. The observations suggested that mutations with equivalent effects were present in the same genes. The phenotypic similarities in such a range of species seemed likely to result from a gradual accumulation of cryptic genetic changes early during vertebrate evolution. The implications are that the mutations, because they did not affect fitness in the wild, were not exposed to adverse selection. Their frequencies were therefore inherited unchanged, becoming increasingly buffered against alterations as species diverged. Their accumulated effects only became apparent following exposure to a human environment.et al. (et al., et al., Wilkins et al.  postulat et al., . Differe et al., , NCCs miet al., et al., et al., et al., It was proposed that the domesticated phenotype developed as a consequence of deficits in proliferation or migratory capacities of the NCCs, resulting in lower densities at their final destinations (Wilkins 10.et al., et al., et al., et al., et al., We propose that, in the sheep, rather than failing to migrate, NCCs are redirected to fates that include an increased commitment to hair follicle morphogenesis. There is evidence to support this view. NCCs are found in epidermal and dermal compartments of the skin and hair follicles, together with NC-derived cells (Fernandes et al., et al., et al., et al., et al., et al., et al., et al., Previously, we have shown that both follicle density and fibre diameter in the sheep are determined at follicle initiation (Moore 11.Primitive sheep and the modern Merino are generally regarded as occupying either end of a range of fibre-producing breeds. However, examination of the nature of the fleece and its ready adaptability suggest that the differences are less striking than their similarities. The development and types of follicles initiated are essentially identical, and similar growth cycles are present, albeit to varying degrees. The rapidity and apparent facility with which a follicle population may convert from shedding to continuous growth and revert from domesticated to feral states argue that the apparent differences are simply stages in a spectrum of types, ranging from coarse fibres and two coats to fine and continuously growing. The random appearance of primitive traits in modern flocks then becomes a not unexpected occurrence. A labile process appears to be in play.Domestication has emerged as a dynamic feature of the evolution of sheep breeds. Within this environment, modifications to the coat structure and composition have occurred in timeframes and to sheep population sizes that exclude evolutionary variations arising from random mutations and natural selection. The fact that these changes occur so consistently and, from available evidence, rapidly, points to an accumulation of a suite of genetic changes that only achieved phenotypic expression through exposure to an environment managed by humans. The involvement of NCCs in follicle morphogenesis is a working hypothesis that provides a single, coherent and essentially consistent rationale for the appearance of changes in coat structure, characteristics and composition associated with a domesticated phenotype.Seemingly, the Merino has access to an extensive wardrobe. What it is wearing at any particular time is a consequence of two competing and unrelenting environmental forces: one natural, the other human.


Bioelectric signals provide an extraordinary opportunity to discover and quantify a wealth of phenomena associated with the organs that generate them. In addition, they provide extensive potentially valuable information for medical doctors (MDs), physiotherapists (PTs), occupational therapists (OTs), and movement scientists (MSs), for functional diagnosis, patient path management, evaluation of patient recovery and progress, and to document or quantify the effectiveness of treatments/trainings.Clinical researchers and engineers have expected that such information would be highly welcomed by clinicians because of the evidence that such information would add to their rehabilitative activity. This has not been the case for surface EMG (sEMG), a fact that motivated this Frontiers project, as well as the publication of a number of tutorials and consensus papers –5, and sCampanini, Disselhorst-Klug et al., while results of interviews are presented in Manca et al., Feldner et al., and Cappellini et al. as well as the situation in specific countries , and teaching/communication experiences . Specific clinical applications concerning neurorehabilitation, gait analysis, sport, kinesiology, exoskeletons, occupational medicine, and ergonomics, are discussed in Cappellini et al., Agostini et al., Felici and Del Vecchio, Goffredo et al., Medved et al., Steele et al., Pilkar et al., Campanini, Cosma et al., Ranavolo et al., and Disselhorst-Klug and Williams.This Frontiers Project presents 18 contributions from 7 countries and 80 authors  who are highly respected experts in the many fields of sEMG. The general problem is addressed in Ranavolo et al.; Martin and Acosta-Sojo). These “quantities” are not easy to measure. The focus on the clinical impact of quantitative assessments of movement and of the so called “hard sciences” to the rehabilitation field is relatively recent . Proper interpretation of sEMG requires both technical and clinical competencies. Should these two different types of expertise be merged into a single professional expert, or in two distinct professional figures?Manca et al. indicate that, in reply to their questionnaire, “… the professional figure of ‘human motion analyst’ was put forward by some respondents as a possible reference to manage sEMG assessments in the clinical setting.” Some interviewees in the work of Cappellini et al. made similar propositions.Some universities . Other authors propose that practical experience working with sEMG should be embedded into education in the form of workshops or course placements to effectively promote its use, and outline a basic tutorial which could be used as a tool for teaching or self-guided learning . A new medical degree addressing technological issues,The alternative option of integrating technical knowledge into the training of PTs, OTs, MSs, and other health operators, finds approval but few implementation efforts. A research group integrating clinicians from Brazil and Chile promoted a Winter School to integrate knowledge about sEMG into the background of clinical operators . Lack of time seems to be one of the main reasons behind this barrier (see the section below).Some contradictions are linked to the fact that (as opposed to ECG) visual analysis and interpretation of sEMG is not easy. However, improper muscle coordination and timing  can be readily detected visually. Nonetheless, the interpretation of this information requires a thorough comprehension of biomechanics, of the existing boundaries to movement consequent to pathology and, more generally, several years of expertise  as well as insufficient education/practice during refresher courses (reported by 20/28), and inadequate education and training of PTs and MDs on sEMG (reported by 17/28). This is another vicious cycle since adequate education, in turn, reduces time for learning and clinical application.Difficult interpretation of sEMG without specific education/training was reported by 21 out of 28 interviewees .Most clinical research studies involving sEMG have been carried out by engineers and life-scientists in research centers, on small groups of 10–50 subjects. Larger clinical trials are few because they must be carried out within health institutions where engineers are rarely present and clinical operators may lack the competence, the support, and the time to carry them out , but the initial effort of the SENIAM project  and its Disselhorst-Klug and Williams) along with the contribution to clinical decision-making . Scientific societies should address this issue.On another related issue, the number of publications about methodologies for sEMG analysis is overwhelming and confusing. Twenty-four years ago Hodges and Bui  tested 2Feldner et al.; Martin and Acosta-Sojo). The application and connection of electrodes is indicated as time-consuming. This is no longer true with the use of wireless systems but knowledge about proper electrode positioning is required to promote time saving .Only a few insurance companies reimburse basic sEMG examinations. Institutional stakeholders should outline the fact that muscle assessment for proper treatment selection would likely generate savings, rather than cost increases  would reduce the weight of ineffective therapies, increase insurance profits, and reduce costs for national health systems.Furthermore, in stroke patients “surface EMG would supply information for better assessment of deficits as well as rehabilitation progress and/or efficacy” . In theSeveral negative factors, inconsistencies, and contradictions are outlined in the project. On the one hand, rehabilitation clinicians; (a) recognize the value and need for formal education to enable more rigorous and clear evidence highlighting the benefits of sEMG; and (b) assert that the opportunities to pursue it are inadequate due to administrative and time resource limitations. On the other hand, many textbooks  and the Removing administrative obstacles is equally important to lighten the workload of clinical operators, leaving time for applying and investigating more recent and well-documented techniques. Doing so would promote experience-based technical improvements, prime virtuous cycles incrementing knowledge, applications, market, and reducing the commercial prices of devices.Introducing new professional figures such as rehabilitation engineers or clinical technologists (see text footnote 1), alongside clinical operators, would substantially reduce (but would not eliminate) the need for technical training of the latter. As rehabilitation technology is rapidly developing, such figures will become necessary very shortly and early training of these operators is certainly appropriate. The clinical responsibilities of these two professional figures should be defined soon. Finally, a common language for proper communication must be available on both sides to understand the information carried by sEMG.All authors contributed equally to the preparation 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.


Mental imagery is a multimodal cognitive simulation process that enables us to represent perceptual information in our minds in the absence of actual sensory input  and MIP? Thirdly, how do cognitive representations of covertly rehearsed skills change during MIP? Finally, what aspects of MI skills change over time as a function of MIP? Before addressing these issues, however, we must consider how MIP effects are typically explained.Motor simulation theory (MST; Jeannerod, In the traditional MIP paradigm, participants in the cognitive rehearsal condition receive a scripted sequence of instructions designed to help them to see and feel the target skill in their imagination. Surprisingly, little is known about how people translate such verbal or written instructions into procedural skill representations. Nevertheless, sport psychology researchers like Holmes and Collins  and WillWM is a cognitive system that stores and manipulates currently relevant information for short periods of time (D'Esposito and Postle, In sport, expert performers are adept at prioritizing specific contextual and motor-relevant information in order to anticipate opponents' offensive plays (e.g., see Murphy et al., A key tenet of modern cognitive psychology is the assumption that human behavior is causally related to “mental representations”—knowledge structures in memory that correspond to objects of thought. Accordingly, Schack and Ritter  cognitivWhat effect does MIP have on mental representation development in skill learners? Frank et al.  investigThere is evidence to suggest that MIP can improve MI ability (Rodgers et al., Although at first glance, thinking and action appear to lie at opposite ends of the behavioral spectrum, cognition and action are elaborately interconnected (Rosenbaum et al., 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.


As the authors of the article “Viewpoint: WHO World Mental Health Surveys International College Student Initiative: Implementation issues in low‐ and middle‐income countries” (LMICs) have pointed out, the university system and the number of students are rapidly growing and changing in LMICs (Evans‐Lacko & Thornicroft, Although racism is known to have a causal link with morbidity, disability, and mortality, this issue is not commonly addressed in public health or mental health agendas (Bailey et al., Likewise, South Africa has an ongoing challenge to reconcile a society strongly harmed by racism. At the end of the apartheid system, the early 1990s started a process of liberation; however, in what is known as the Soudien Report, a Ministerial Committee on Transformation and Social Cohesion and the Elimination of Discrimination in Public Higher Education still found discrimination based on gender and race to be endemic in public higher education institutions (Soudien et al., We support Evans‐Lacko and Thornicraft's  contentiHigher education systems in Brazil and South Africa leave black students and academics with experiences of alienation, limiting a healthy experience of belonging for black students within their campuses. Nonetheless, racist experiences among students have also been acknowledged as an issue in other large LMICs (Laruelle,


The effect of long‐term chemical fertilization on plant‐microorganisms and microbe‐microbe interactions. In fact, in order to feed the growing world population, current estimates indicate that our global agricultural output will need to be increased by at least 50% by 2050 (Muller et al., et al., et al., et al., et al., et al., et al., et al., The interactions between plants and non‐pathogenic bacteria have been largely studied, and the advantages that both partners obtain from such association have been explored in different model systems (Berg and Koskella, et al., et al., et al., et al., et al., et al., et al. (et al., (in silico analysis revealed that long‐term fertilization not only reduced the interactions between soil microbes but also the complexity of the networks between plants and functional microbial communities. Thus, while five plant species showed an association with microbial functional genes in unfertilized soils, only one plant species showed a connection with microbial functional groups in long‐term fertilized soils. Finally, the authors showed that carbon and nitrogen contents in soil were the main parameters that modulate plant and microbe networks. They further highlighted that functional microbial communities play an important role in plant diversity (Huang et al., The emergence of the above‐mentioned next‐generation green revolution aimed at developing sustainable alternatives to improve crop production is also reflected in the increasing number of articles that are focused on investigating the composition of soil microbiota and how soil treatments alter bacterial soil communities. Among them, there is a remarkable number of studies that investigate the impact of long‐term fertilization, chemical or organic, on the diversity of plants and microorganisms. In general, these studies reveal that chemical fertilization reduces the diversity of plants and microorganisms as well as negatively impacts plant–microbe interactions and the soil microbiome’s capacity to contribute to soil nutrient cycling (Pierik , et al.  recently(et al.,  found thet al., et al., et al., et al., et al. (Anthropogenic changes in natural ecosystems are dramatically affecting global diversity. In particular, the soil microbiome plays a key role in modulating plant diversity as well as nutrient retention and recycling (Geisen , et al. . ConsequNone declared.


Dear Editor,As the evidence base for the efficacy of physical exercise for cognition in older adults is mounting, efforts to detect the most efficacious exercise settings are critical for clinical translation and guidelines development. Chen et al.  conducten = 3008 (Table 2) to 7023 in the overall model, (b) underestimation of standard error and thus overestimation of precision, and (c) assigning excessive weight to studies that reported multiple outcomes regardless of their actual sample size, which bias not only the pooled effect estimates but also investigations of small-study effect (‘publication bias’). Although Chen et al.    are unliThird, it is not clear to us why the authors chose to include only studies published since 2003, i.e., after the publication of Colcombe and Kramer’s seminal meta-analysis in this area . In theiLike many in the exercise science and sports medicine community, we were encouraged by Chen et al.’s  positive


Blood flow restriction (BFR) training is a bourgeoning exercise modality which promotes increases in skeletal muscle mass and strength during resistance exercise Sato, . In pracSpranger et al.  offered Several studies in young, healthy individuals have shown that BFR-RE exacerbates cardiovascular responses. Downs et al.  reportedWhile caution is warranted even in healthy individuals, the primary concern of Spranger et al.  specificA few studies have employed BFR-RE in populations with cardiovascular disease with generally favorable conclusions. However, these conclusions were drawn despite the fact that either hemodynamics were not assessed in the study (Madarame et al., Patterson et al. , profferPatterson et al.  intend fThe 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.


Telomere attrition is increased in various disorders and is therefore a potential biomarker for diagnosis and/or prognosis of these disorders. The contribution of telomere attrition in the pathogenesis of neurodegenerative disorders is yet to be fully elucidated. We are reviewing the current knowledge regarding the telomere biology in two common neurodegenerative disorders, Alzheimer’s disease (AD), and Parkinson’s disease (PD). Furthermore, we are discussing future prospective of telomere research in these disorders. The majority of studies reported consistent evidence of the accelerated telomere attrition in AD patients, possibly in association with elevated oxidative stress levels. On the other hand in PD, various studies reported contradictory evidence regarding telomere attrition. Consequently, due to the low specificity and sensitivity, the clinical benefit of telomere length as a biomarker of neurodegenerative disease development and progression is not yet recognized. Nevertheless, longitudinal studies in large carefully selected cohorts might provide further elucidation of the complex involvement of the telomeres in the pathogenesis of neurodegenerative diseases. Telomere length maintenance is a complex process characterized by environmental, genetic, and epigenetic determinants. Thus, in addition to the selection of the study cohort, also the selection of analytical methods and types of biological samples for evaluation of the telomere attrition is of utmost importance. Telomeres are tandemly repeated nucleotide sequences at the end of the linear chromosomes. Their main function is maintaining genomic stability by protecting chromosomal ends from degradation and end-to-end fusion  is considered as a surrogate marker for other cells as well. In elderly patients, TL in leukocytes is significantly shorter compared to skin, synovial tissue  method enables measurement of all individual telomeres per metaphase , type and amount of sample required, accuracy, reproducibility, robustness, throughput, and technical skills required. Terminal Restriction Fragment (TRF) analysis using Southern blot (Harley et al., The selection of a method should be made with consideration of their advantages and disadvantages. For larger epidemiology and population studies qPCR is the most practical choice while q-FISH and STELA are more appropriate for studies with fewer samples or when more accurate and specific measurements are required (Aubert et al., During embryonic brain development, most cells express telomerase, while after birth, the activity in most cells quickly declines to undetectable levels (Wright et al., Studies of the relationship between TL and cognitive performance have led to inconsistent results. While TL was reported in cognitive decline in elderly people and suggested to be a possible biomarker of cognitive aging (Kljajevic, post-mortem study in neuropsychiatric disorders reported a highly significant difference in TL in different brain regions, where telomere were the longest in substantia nigra and the shortest in the dorsolateral prefrontal cortex (Mamdani et al., LTL has been proposed as a surrogate marker for the central nervous system TL (Daniali et al., Telomere attrition has been investigated in many neurodegenerative disorders (Eitan et al., AD is a slowly progressing neurodegenerative disease and a common cause of dementia in the elderly worldwide (Prince et al., Amyloid-beta deposition and advanced age are the major risk factors for AD development, and both have been associated with the activation of microglia (Flanary et al., Oxidative stress can trigger chronic inflammation and contribute to neuronal dysfunction and cell death in AD (Mhatrea et al., Studies of TL in patients with AD are inconsistent. Their major observations along with the characteristics of the study cohorts and methods are summarized in Guan et al.  publisheLukens et al., 2009, reported a direct correlation between TL in leukocytes and cerebellum, but cerebellum TLs were not significantly different in AD patients (Lukens et al., A few studies investigated TLs in brain tissue. The data regarding the involvement of telomere attrition in AD progression is contradictory and needs further elucidation. The common characteristic of all these studies but one (Honig et al., Parkinson’s disease is characterized by both motor and non-motor features (Kalia and Lang, substantia nigra were also reported in PD patients (Hudson et al., Studies of TLs in patients with PD showed contradictory results and are summarized in The majority of the studies reported no significant telomere attrition in PD . A SwediReported studies evaluating TL in PD are very heterogeneous regarding the study population, sample type, TL detection method, and the cohort size. Even though telomere attrition was observed in only two studies with 30 or fewer participants and different sample types (Maeda et al., Studies of telomere dynamics in AD and PD have provided inconclusive results. Currently, the telomere attrition is believed to be associated with AD (Forero et al., Smith et al., using an umbrella review approach where findings were derived by examining the epidemiological credibility of the evidence, pointed out several weaknesses in reporting relationship between TL and different disorders (Smith et al., The clinical benefit of TLs as a biomarker of neurodegenerative diseases is questionable due to its low specificity and sensitivity. Telomere shortening is not present only in neurodegenerative diseases, but also in a vast amount of other diseases and different demographic factors may contribute to telomere attrition. A recent study by Different study designs, methods for TL measurement, and tissues in which TLs are investigated may contribute to the variability between studies. Moreover, although qPCR is the most commonly used method in TL measurement, there are still inconsistencies in recent reports. Recently, Lin et al. carefully evaluated all critical steps in qPCR telomere length assay and provided guidance and recommendations for each step based on current knowledge (Lin et al., post mortem studies of TLs in different brain cells are needed to fully evaluate the LTL as the appropriate surrogate marker for the central nervous system.One of the most important aspects is the selection of the representative tissue that corresponds to the pathological processes in the affected tissue, such as the brain in neurodegenerative diseases. The discrepancy in TL in different brain regions (Mamdani et al., The number of subjects to show statistical significance between two groups is a crucial factor and must be calculated taking into account high inter- and intra-variability in TLs. In most reported studies, the sample size was relatively small, which may be the cause for statistical insignificance. Furthermore, classification of the patients into subgroups, such as progression rate, disease stage, etc. may be beneficial to show statistical significance, but it requires an even larger total sample size. In this view, the longitudinal studies in carefully selected cohorts may provide more reliable results since a smaller sample size is needed (Aviv et al., To conclude, longitudinal studies in carefully selected cohorts and sample types are required to elucidate the complex role the telomeres may have in the pathogenesis of neurodegenerative diseases and possible targets for intervention with a final goal to possibly prevent or delay neurodegenerative diseases. Furthermore, the integration of various experimental and clinical data might improve the strength of such studies. Additionally, standardized protocols for TL measurements addressing sample types and methods might be beneficial since and would enable a more relevant comparison of results from different laboratories.TL and EK wrote the manuscript. VD revised the manuscript. KT conceptualized, wrote, and revised the manuscript. All authors reviewed and approved the final 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.


People suffering from neurological conditions such as Parkinson's disease, stroke, and brain injury encounter and endure numerous situations in their daily lives that cause excess disability and restrict full participation in their meaningful activities.Neuroscience and rehabilitation science are complementary disciplines, engaged in the exploration of the human Central Nervous System (CNS) and the amelioration of functional disability. There is often, however, a lack of discourse between these disciplines, which precludes opportunities for meaningful exchange and synergistic collaboration to improve the lives of people who suffer from a disability.The goal of this current theme issue was to foster original research papers in neuroscience and rehabilitation science that may serve to address the existing disconnect between disciplines. This platform offered an opportunity for a meaningful exchange of ideas, findings, and practices toward ultimately promoting knowledge, improving clinical practice, and reducing performance deficits and participation restrictions for people with neurological ailments and diseases. This broader, biopsychosocial approach to understanding rehabilitation and recovery from neurological deficits, embraces the concept that true understanding of recovery and living with a chronic condition, goes beyond knowledge of disease mechanisms. Social determinants and secondary disease sequelae may have a significant impact on functional performance and participation.The initial call for papers invited researchers and practitioners to submit research papers on the topic of “Performance and Participation Outcomes for Individuals with Neurological Conditions.” This focused topic recognized the need for a more comprehensive and integrative perspective in research and practice to address this disconnect between neuroscience and rehabilitation. This perspective should thus reveal neglected key domains, as well as incorporate a range of components intricately involved in human performance, such as motor, sensory, cognitive, and emotional components. Such integration may serve to significantly enhance the functional outcomes for persons suffering from any of the range of neurological conditions.The theme call aimed at addressing these respective issues by soliciting original research papers, review articles, or meta-analyses, covering topics ranging from basic research to translational studies anchored in neuroscience or rehabilitation.Schliep et al.;Valè et al.;Wang, Wang et al.; and Sul et al. addressed the need for greater understanding of prognostic indicators of recovery such as lesion location, behavioral characteristics, EMG assessment in motor disorders, and the initiation of swallowing in disorders of consciousness. Performance outcomes and their contributors was the focus of Fasoli and Adans-Dester, Ranford et al., Yael et al., and McCambridge et al.. The vast majority of the papers included in this special issue cluster around the multifactorial outcome of participation: Rotenberg et al., Malone et al., Yosef et al., Wang, Chan et al., Toglia et al., Erler et al., Nicholas et al., and Cattaneo et al..The encouraging response to our call yielded 22 submitted papers that underwent a peer-review process. Ultimately, 16 papers were adjudged to favorably meet the theme call objectives and scientific standards. As this special issue was designed to organize our thinking around outcome, rather than disease, we provide a classification of the articles by their primary outcome focus. We categorized the papers as addressing prognostic indicators of recovery (4 articles), performance (4 articles), or participation (8 articles). The breadth of neurological conditions and methodological approaches in this issue is astounding. Although broad in scope, our focus on the larger outcomes of people with neurological conditions, we believe, enables us to glean principles for maximizing performance and participation at the highest conceptual level. One of the most striking themes that emerged from this collection, for example, is that cognitive and emotional factors are of utmost importance for the performance of motor-intensive activities and participation in life activities that are motorically-demanding in diseases classically thought of as diseases of the motor system. Moreover, social support is a major predictor of resumption of pre-disease activities.Of course, putting the focus on outcome introduces factors that are outside the purview of neurological science and will not replace studies focused on disease mechanisms that foster new treatment approaches aimed at treating or curing disease. The vast majority of the patients living with these neurological conditions will be doing just that—living with their chronic conditions. Our hope is that a more holistic scientific treatment of factors predicting outcome will advance our rehabilitation attempts to promote better living for people with neurological conditions.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.


Mitochondria are indispensable for energy metabolism and are essential for the regulation of many cellular processes in healthy as well as in transformed cells. Mitochondria in malignant cells differ structurally and functionally from those in normal cells, which make them a promising target for anticancer therapy. Mitochondria in cancer cells are characterized by reactive oxygen species (ROS) overproduction, which promotes cancer development by inducing genomic instability, modifying gene expression and participating in signaling pathways. Additionally, the pleiotropic roles of mitochondrial ROS in the regulation of anticancer immunity are now coming to light. The involvement of mitochondria in cancer cell metabolic reprogramming as well as in the anticancer immune response has been utilized for designing novel mitochondria-targeted anticancer agents. However, we are still far from an in depth understanding of the role played by mitochondria in cancer development. Therefore, the main aim of this Special Issue was to collect novel findings and ideas from scientists involved in basic research as well as in translational studies in the field of mitochondria and cancer. Hguen and Pandey  discusseAnother interesting point in gender-related anticancer treatment is the topic of the review of Stakisaitis et al.: “The Importance of Gender-Related Anticancer Research on Mitochondrial regulator Sodium Dichloroacetate in Preclinical Studies In Vivo” . The revJeena et al.  hypothesAutophagy is a key node for the regulation of ROS levels as well as for the ROS-dependent cellular regulation. Therefore, such regulation could be a potential target mechanism for cancer treatment. Based on this idea, Sanches-Ávarez et al.  recognizThe drug resistance, without question, is a huge barrier in the struggle against cancer. As previously mentioned, it is important to know the structural differences between normal and cancer cells. Moscheni et al.  also conFinally, Meng et al.  in theirSummarizing, a small but high quality spectrum of reviews and original papers from this issue provides an insight into new research directions linked to an extremely important topic “Mitochondria and Cancer”. I hope all readers of this Special Issue enjoy taking a closer look into a subject of this compendium.


Figure 1 legend and should read:In the original article Albert et al. Figure 1. Previously published sets of transcriptomic data (Florio et al., The authors apologize for this error and state that this does not change the scientific conclusions of the article in any way. The original article has been updated.


Biological invasions are a global consequence of an increasingly connected world and the rise in human population size. The numbers of invasive alien species – the subset of alien species that spread widely in areas where they are not native, affecting the environment or human livelihoods – are increasing. Synergies with other global changes are exacerbating current invasions and facilitating new ones, thereby escalating the extent and impacts of invaders. Invasions have complex and often immense long‐term direct and indirect impacts. In many cases, such impacts become apparent or problematic only when invaders are well established and have large ranges. Invasive alien species break down biogeographic realms, affect native species richness and abundance, increase the risk of native species extinction, affect the genetic composition of native populations, change native animal behaviour, alter phylogenetic diversity across communities, and modify trophic networks. Many invasive alien species also change ecosystem functioning and the delivery of ecosystem services by altering nutrient and contaminant cycling, hydrology, habitat structure, and disturbance regimes. These biodiversity and ecosystem impacts are accelerating and will increase further in the future. Scientific evidence has identified policy strategies to reduce future invasions, but these strategies are often insufficiently implemented. For some nations, notably Australia and New Zealand, biosecurity has become a national priority. There have been long‐term successes, such as eradication of rats and cats on increasingly large islands and biological control of weeds across continental areas. However, in many countries, invasions receive little attention. Improved international cooperation is crucial to reduce the impacts of invasive alien species on biodiversity, ecosystem services, and human livelihoods. Countries can strengthen their biosecurity regulations to implement and enforce more effective management strategies that should also address other global changes that interact with invasions. I.(1)et al. . However, in the second call, besides stressing the need to respond to indirect drivers of biodiversity loss , Ripple et al.  addresseet al. . IAS are et al., . The rec(2)et al., et al., et al., et al., et al., et al., Alien species (as opposed to native species) are those whose presence in a region is attributable to human actions, deliberate or inadvertent, that enabled them to overcome biogeographical barriers (Richardson (3)i) appraise the current state of biological invasions in marine, freshwater, and terrestrial ecosystems; (ii) show that current societal responses are insufficient to address impacts of IAS on ecosystems, biodiversity, and human well‐being and to mitigate future risks; and (iii) argue that a warning to humanity regarding the threats posed by IAS is both timely and relevant to complement other focused papers pointing to current threats to nature and the importance of nature for humans  Where do we stand? (ii) Why should we care? (iii) What tools are available to deal with these problems? (iv) What comes next? We treat these questions separately and then provide recommendations for policy, management, and research.To support global initiatives addressing the loss of biodiversity and ecosystem services, this paper presents a comprehensive global overview of a major environmental change – invasion by alien species. We (II.(1)et al., et al., et al., et al., et al., et al., et al., et al., et al., et al., www.iucngisd.org), which contains profiles of key IAS, and the Global Register of Introduced and Invasive Alien Species , and NEMESIS (https://invasions.si.edu/nemesis) exemplify cross‐taxonomic initiatives that have produced such databases for particular regions , and the aliens also reach much higher abundances  have led to established alien populations  as a well‐known reptile example et al., via anthropogenic corridors ; or unaided spread from other invaded regions. The intentional pathways ‘escape’ and ‘release’ are most important for plants and vertebrates, whereas for invertebrates, algae, fungi, and microorganisms, unintentional ‘contaminant’ and ‘stowaway’ transport pathways prevail; representation of these pathways differs only slightly among marine, freshwater, and terrestrial environments  of the CBD calls for urgent action by the Parties (i.e. signatory States) to identify and prioritize alien species pathways and to implement measures to manage pathways to prevent alien species introduction and establishment CBD, . Six broet al., Bufo marinus; Shanmuganathan et al., Historically, many species were deliberately released for economic, recreational, or aesthetic benefits Lever, . Althouget al., et al., et al., Ornamental plants have escaped from gardens for centuries  between the Atlantic and Pacific Oceans. As with ocean plastic rafting, we have yet to fully grasp the short‐ and long‐term consequences of the disappearance of the ice‐bound Arctic, which has long formed an impassable barrier between oceans and continents  migrating from the UK to Spain, or the currant‐lettuce aphid (Nasonovia ribisnigri), dispersing on wind currents from New Zealand to Tasmania and subsequently throughout Australia. This unaided pathway poses major challenges for international regulation as well as biosecurity measures within individual countries et al., et al., et al., et al., et al., et al., et al., et al., 2017) or indirectly through other variables, such as the movement of particular commodities, eutrophication, or the intensity of anthropogenic disturbance et al., et al., et al., et al., The acceleration of alien species introductions and invasions has been highlighted for several regions et al., www.protectedplanet.net); they are a key component of the societal response to environmental degradation 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., Given the many pressing environmental issues, one must ask how prominently biological invasions should feature in political and public agendas? The magnitude and variety of impacts of IAS provide an unambiguous reason for much more urgent attention to be given to invasions. Research on invasion impacts has developed rapidly over the past decade , four mammals , one crayfish (Procambarus clarkii), the varroa mite (Varroa destructor), and four plants   and insects . One must also consider that native species, even if not yet driven to local or global extinction, often suffer from population declines attributable to IAS, and many now exist only as remnant populations et al., et al., et al., Mnemiopsis leidyi, which led to the abandonment of anchovy fisheries in parts of the Black Sea because clogging of nets by this species made fishing impractical  injuring fishermen in the eastern Mediterranean  threatening outdoor activities and causing costs associated with the nuisance of large colonies near homes in parts of Australia et al., et al., Invasion biologists and policy‐makers generally agree that efficient responses to biological invasions require prioritizing measures to prevent the arrival of potentially invasive alien species, the timely management of incursions, and effective management of those already established  by 2050 . The ongoing process of maintaining the list relies on collaboration between scientists and policymakers. The European example highlights the key components required to establish robust and sustainable policies for dealing with biological invasions et al., et al., et al., https://www.ippc.int) of the UN Food and Agriculture Organization as the international standard‐setting body for border biosecurity. Because import quarantines can be cited as unfair barriers to free trade, the IPPC provides rules by which national plant protection organizations can implement biosecurity practices. The IPPC also sets standards that are harmonized among countries to limit the spread of invasive alien species while promoting free trade. Under IPPC guidelines, each country is able to select a level of predetermined risk when implementing biosecurity practices, but this selection must be justified based on the best available science and uniformly applied .The term ‘biosecurity’ refers to measures to prevent and manage biological invasions Hulme, a. A clo(3)et al., et al., et al., et al., Petromyzon marinus) with an eye towards control in the Laurentian Great Lakes  when the insect attacks the plant   of the bee to express dsRNA sequences of varroa mite genes, thus entraining the mite's RNAi (ribonucleid acid interference) mechanism, killing the mite. Gene‐silencing for control of invasive populations is also under study for plants  into cells to destabilize messenger RNA, has been studied especially for applications to human health and agriculture, but with much research also aimed at getting targeted invasive species to eat substances including dsRNA . Other invasive animals targeted by current projects entailing use of transgenes include the Channel catfish , common carp (Cyprinus carpio), and Pacific oyster (Crassostrea gigas)  and GBIRd for invasive rodents (www.geneticbiocontrol.org).Recognition that CRISPR‐Cas9  gene‐editing technology, usually together with transgenes, could aid in management or eradication of invasive alien species (Esvelt (4)et al., et al., et al., et al., et al., The importance of early‐warning and rapid‐response initiatives, and concurrently the need for surveillance to inform such approaches, is widely recognized. Most countries do not implement integrated national invasive alien species surveillance programs. Also, many IAS that can affect biodiversity and ecosystems adversely do not fulfil the criteria for inclusion under government‐funded schemes. Engaging volunteers in surveillance and monitoring is a low‐cost, large‐scale, and long‐term option , but also through non‐linearities and synergisms with other components of global change. Unlike some other components of global change, biological invasions can be effectively managed and mitigated. We suggest the following priorities to ensure progress in dealing effectively with the many dimensions of biological invasions.(1)et al., et al., et al., et al., Acacia). The forthcoming assessment of IAS as part of IPBES will play a crucial role in this endeavour. This first comprehensive assessment will address past and future trends in the spread, pathways, evolutionary change, and distribution of invasive alien species, and gaps in existing knowledge; direct and indirect drivers responsible for their introduction, spread, abundance, and dynamics; global environmental, economic, and social impacts of invasive alien species; the effectiveness of past and current programmes and tools for the global, national, and local prevention and management and future options for the prevention and management of invasive alien species; and analysis of possible support tools for decision makers. A number of overarching themes are also being developed to guide the assessment including interactions of IAS with climate change. The IPBES assessment will bring together more than 70 experts spanning diverse disciplines. The completed assessment is expected to be presented in 2023 to the 10th session of the IPBES Plenary composed of representatives from 132 member states.National capacities to respond to invasions differ among countries (Early (2)et al., et al., i) high‐risk pathways, activities, and/or societal sectors that use alien species  to prevent introduction, (ii) newly arrived species for removal to prevent further spread, and (iii) vulnerable habitats/native species to monitor and impede invasions from impacting them. Managing invasions is difficult and often expensive, but emerging evidence shows that even expensive interventions, especially related to prevention, generally result in net benefits et al., et al., Protected areas are an important part of global efforts to conserve biodiversity. Nevertheless, integrated efforts involving science, management, and policy for dealing with IAS in protected areas are insufficient. The extent and overall impact of invasive species in protected areas is increasing worldwide, especially for invasive plants, despite some notable successes in dealing with such invasions (Shackleton (4)et al., et al., conditio sine qua non in the quest for comprehensive solutions to deal with biological invasions. Overcoming knowing–doing gaps et al., et al., et al., et al., Despite numerous correlative bioclimatic models predicting that many alien species will likely become more widespread as a result of climate change, there is a dearth of empirical data that clearly link shifts in alien species distributions with changes in temperature or precipitation. Analysis of long‐term and large‐scale spatial data on alien species distributions is urgently needed to disentangle how they correlate with climate variables and other aspects of global change, such as intensified land use and transformation, pollution, and propagule pressure (Bellard VII.(1) Biological invasions are a major driver of ecosystem degradation. The number of invasive alien species is increasing rapidly with no evidence that either the rate of species introduction or the emergence of new invasive species is slowing down.(2) Islands and coastal mainland areas are hotspots of invasions, but ecosystems in all biomes throughout the world are increasingly affected. Although boundaries of protected areas provide some resistance to invasions, even the most isolated and well‐managed reserves are experiencing pressure from invasive alien species.(3) The global escalation in biological invasions is attributed to the increase in the number of pathways of introduction and spread of species, and particularly the volume of traffic (and therefore species) along these pathways. Emerging pathways are creating new categories of invasions, such as plastics providing rafts for transport of organisms across oceans.(4) Interactions with other drivers of global change are exacerbating current biological invasions and facilitating new ones, thereby greatly escalating the extent and impacts of invaders. Although biological invasions are sometimes symptoms (or ‘passengers’) of other human‐mediated change, they are themselves often key drivers of change.(5) Invasions have complex and often immense long‐term direct and indirect impacts, many of which manifest decades or more after invasions commence, when the invaders are established and extend across large geographic ranges. Invasive alien species break down biogeographic realms, affect native species richness and abundance, increase the risk of native species extinction, affect the genetic composition of native populations, change native animal behaviour, alter phylogenetic diversity across communities, and modify trophic networks. Many invasions alter ecosystem functioning and the delivery of ecosystem services, thereby adversely impacting human livelihoods. All these types of impacts are accelerating and predicted to increase in the future, often following non‐linear trajectories. Despite advances in understanding impacts of biological invasions, little is known about the impacts of alien pathogens  and associated emerging infectious diseases on biodiversity and ecosystems.(6) Strategies to reduce future invasions are in place in many countries but are often implemented ineffectively. Unlike some other facets of global environmental change, with sufficient foresight and resources many biological invasions can be managed and mitigated. There is increasing evidence of successful long‐term and large‐scale management of established invaders, such as the eradication of mammals on increasingly large islands and biological control of weeds across continental areas. In many countries, however, invasions receive inadequate attention. Management approaches must be objectively prioritized by accounting for feasibility and considering invasion debt . Engaging people from diverse stakeholder groups is essential to enhance understanding of biological invasions and inform decision‐making including effective implementation of biosecurity.(7) Multidisciplinary collaborations and integrated approaches through international cooperation are critical to reduce the impacts of invasive alien species, including alien pathogens, on biodiversity, ecosystem services, and human livelihoods. Countries must strengthen their biosecurity regulations to implement and enforce effective management strategies that address invasions in tandem with other facets of global change.VIII.P.P., J.P. and L.C.F. were supported by EXPRO grant no. 19‐28807X (Czech Science Foundation) and long‐term research development project RVO 67985939 (Czech Academy of Sciences). S.B. was supported through the 2017‐2018 Belmont Forum and joint call for research proposals, under the BiodivScen ERA‐Net COFUND programme, and by the Swiss National Science Foundation . F.E. was supported by a grant from the Austrian Science Foundation FWF (grant I 3757‐B29). L.C.F. acknowledges South African National Parks, the DSI‐NRF Centre of Excellence for Invasion Biology, Stellenbosch University, and the National Research Foundation of South Africa (Grant Numbers IFR2010041400019 and IFR160215158271). P.E.H. was supported through grant C09X1611 “Winning against Wildings” from the New Zealand Ministry of Business, Innovation and Employment. J.M.J. was supported by the Deutsche Forschungsgemeinschaft  and the Belmont Forum‐BiodivERsA projects InvasiBES and AlienScenarios with the national funder German Federal Ministry of Education and Research . A.M.L. was supported by EVA4.0, No. CZ.02.1.01/0.0/0.0/16_019/0000803 financed by OP RDE and by the USDA Forest Service. A.P. was funded by CONICYT AFB‐170008 and Fondecyt 1180205. D.M.R. acknowledges support from the DSI‐NRF Centre of Excellence for Invasion Biology and the Oppenheimer Memorial Trust (grant 18576/03). H.E.R. was supported by the Natural Environment Research Council award number NE/R016429/1 as part of the UK‐SCAPE programme Delivering National Capability. M.v.K. was supported by the Deutsche Forschungsgemeinschaft (DFG: grant 264740629). M.V. was supported by the Belmont Forum‐BiodivERsA project InvasiBES (PCI2018‐092939) funded by the Spanish Ministerio de Ciencia, Innovación y Universidades. H.S. was supported by Belmont Forum‐BiodivERsA with the national funder German Federal Ministry of Education and Research . D.S. was supported by the Nancy Gore Hunger Professorship in Environmental Studies at the University of Tennessee.


We are very glad to hear from Maertens and Blot , and theIn the study reported by Mahmoodpoor et al. in 2013 [In another study published by Monsel et al. in 2016 , in ordeIn most of the studies included by us, the polyvinylchloride (PVC) cuffs were used, and many other studies suggested that polyurethane- (PU-) tapered cuffs showed no benefits on microaspiration reduction. Thus, only PVC cuffs in Philippart's study reported in 2014  were incIn Mahmoodpoor's study reported in 2017 , the tapOur study only included the published studies but not the unpublished studies.Finally, we believe that we share with Maertens and Blot  the opin


Increasing rates of male infertility have led to a greater need for relevant model systems to gain further insight into male fertility and its failings. Spermatogenesis and hormone production occur within distinct regions of the testis. Defined by specialized architecture and a diverse population of cell types, it is no surprise that disruption of this highly organized microenvironment can lead to infertility. To date, no robust in vitro system has facilitated full spermatogenesis resulting in the production of fertilization‐competent human spermatozoa. Here, we review a selection of current in vitro systems available for modelling the human testis microenvironment with focus on the progression of spermatogenesis and recapitulation of the testis microenvironment. Additionally, CSF‐1, produced by Leydig cells, has been demonstrated to promote self‐renewal of SSCs which is perhaps unsurprising given their proximity to the SSC niche  supplementation  to generate rat testicular organoids in vitro (Alves‐Lopes et al., et al., et al., et al., et al., Alternative dynamic culture approaches have been described in an attempt to promote germ cell differentiation in vitro. Using a bioreactor system, Perrard and colleagues report differentiation of morphologically mature spermatozoa from spermatogonia in human seminiferous tubule fragments enclosed in porous chitosan hydrogel tubes immersed in culture medium (Perrard A functioning somatic microenvironment is crucial for the process of spermatogenesis. When considering in vitro modelling of the human testis with the intent of generating mature spermatozoa, this must be a primary consideration. Studies that have made the most progress have either exploited the intrinsic microenvironment using testis tissue fragments or encapsulated dissociated cells within a supportive matrix to generate a 3D structure. In the effort to replicate human spermatogenesis in vitro, future focus should be on maintaining the functional niche or, in the case of immature tissue, maturation of the niche to support spontaneous spermatogenesis.


Lancet Psychiatry position paper on multidisciplinary research priorities for the coronavirus disease 2019 (COVID-19) pandemic (Holmes et al., et al., et al., Older adults have been identified as a “population of interest” by the recent et al., et al., Learning from history is a helpful starting point. Even as far back as the 1918–1919 “Spanish” influenza pandemic, there has been discussion of an increase in rate of psychosis and suicide at that time Harris, . The impet al., et al., The very recent history of providing mental health services to older adults in China during the COVID-19 pandemic has been challenging, with the “digital divide,” quarantines, and restrictions on movement having significant impact (Yang Older adults living with dementia in the COVID-19 world have experienced reduced access to support and activities. These changes have caused distress and exacerbated behavioral and psychological symptoms of dementia. We have seen community-dwelling older adults with dementia referred due to inability to understand and retain information about social distancing, with relatives fearing they will be at risk of contracting COVID-19 or receiving penalties from law enforcement agencies. A concerning development is the increasing media discussion about the relative worth of human lives based on age and remaining life expectancy which could divide generations and challenge established ethical values.et al., et al., Our response to COVID-19 for older adults can borrow general mental health recommendations from historic pandemic influenza preparedness initiatives including a focus on strengthening social networks and community support, communication networks, directive leadership and stress management (Douglas Lancet Psychiatry, It is heartening to see the relative increase in attention being paid to mental health by governments, researchers, and clinicians for those affected by COVID-19, when compared to previous pandemics (


The discovery that a considerable fraction of the eukaryotic proteins lacks a well-defined three-dimensional structure in their native state has revolutionised our general understanding of proteins. In fact, the dogma sequence determines structure determines function constituted, until recently, the foundations of our description of the protein universe. Consequently, it is not surprising that the early years of the intrinsically disordered proteins (IDPs) field have seen some scepticism. In fact, the experimental finding that some proteins did not display a well-ordered structure in isolation was merely considered as an artefact, assuming that the crowded environment of the cell could in fact reshape the native state. Thus, disorder was very far from being considered as a key player in orchestrating some of the molecular events controlling cell biology.Life, a collection of articles is presented with the specific focus of describing the “Functions, Regulation and Dysfunction of Intrinsically Disordered Proteins”. Lermyte et al [The recent collaborative efforts between experimentalists and theoreticians, however, have contributed in catalysing a revolution in the protein universe and protein disorder has gradually acquired a central role in molecular biology. In this issue of te et al  providedte et al  review ate et al  used kinIn the study of IDPs, molecular dynamics simulations (MD) have made fundamental contributions. In this issue, Sullivan and Weinzierl  used MD In the context of αS interactions, Burmann and co-workers  reviewedThe onset and development of neurodegenerative diseases such as Parkinson’s and Alzheimer’s are inherently associated to the insurgence of oxidative stress in the neurons. The excessive production of free radicals and reactive oxygen species (ROS) have been associated to the mechanisms leading to neuronal death, review by Abramov et al.  IntracelThe main conformational transition of IDPs involved in neurodegenerative diseases involves the formation of fibrillar aggregates with common structural topologies (cross-β spine) and showing peculiar mechanical properties at a microscopic level that make them stronger than steel. Scollo and La Rosa  reviewedIn summary, we have assembled a collection of articles that study and discuss different aspects of this intriguing class of proteins. More remains to be discovered in the IDP universe, and this elusive state poses the challenges for the next decades to overcome the limitations of current techniques in vitro and in vivo that have mostly been tailored to study structurally defined systems.


The Food and Agriculture Organization of the United Nations has recently estimated that the world equid population exceeds 110 million (FAOSTAT 2017). Working equids  remain essential to ensure the livelihood of poor communities around the world. In many developed countries, the equine industry has a significant economical weight, with around 7 million horses in Europe alone. The close relationship between humans and equids, and the fact that the athlete horse is the terrestrial mammal that travels the most worldwide after humans, are important elements to consider in the transmission of pathogens and diseases, amongst equids and to other species. The potential effect of climate change on vector ecology and vector-borne diseases is also of concern for both human and animal health.With this Special Issue, which assembles a collection of communications, research articles, and reviews, we intend to explore our understanding of a panel of equine viruses, looking at their pathogenicity, their importance in terms of welfare and potential association with diseases, their economic importance and impact on performance, and how their identification can be helped by new technologies and methods. Beyond their potential risk to other species, including humans, equine viruses may also represent an interesting model for reproducing virus infection in the host species.orbivirus AHS virus (AHSV), induces a very high mortality rate that can exceed 95% in its most severe form. This disease mostly occurs in southern African countries, but its transmission by Culicoides biting midges is of great concern in the current context of global warming and its consequence on displacement of vector populations. In the absence of treatment, prevention is essential, and Dennis et al. also provide a comprehensive review of the different vaccine strategies and technologies available and in current development against AHSV. While live attenuated and inactivated AHSV vaccines have played a role to reduce the impact and occurrence of AHS in affected areas, the number of AHSV serotypes in circulation and their lack of DIVA markers  is a drawback that leads to the development of a new generation of vaccines, such as poxvirus-vectored or reverse genetics vaccines. Lecollinet et al. [Flaviridae family , Saint Louis encephalitis virus (SLEV), and Murray Valley encephalitis virus (MVEV)) or the alphaviruses from the Togaviridae family . In relation to VEEV, Rusnak et al. [Dennis et al.  contribut et al.  reviewedt et al. . A commut et al.  and an at et al. ). The MLt et al. . Lecollik et al.  presenteEqcopivirus by the authors, with no specific and/or statistical association with disease. Equine parvovirus-hepatitis was also the subject of the article from Meister et al. [Altan et al.  have user et al. , which rr et al.  identifir et al. , who repr et al.  developer et al.  shed somFinally, Fatima et al.  investigWe hope this Special Issue helps to highlight the diversity of equine viruses and their importance, in terms of welfare and/or economic impact, to equids and humans.


To develop a diabetes education model based on individual beliefs, knowledge and risk awareness, aimed at migrants with type 2 diabetes, living in Sweden.Type 2 diabetes is rapidly increasing globally, particularly affecting migrants living in developed countries. There is ongoing debate about what kind of teaching method gives the best result, but few studies have evaluated different methods for teaching migrants. Previous studies lack a theoretical base and do not proceed from the individuals’ own beliefs about health and illness, underpinned by their knowledge, guiding their health-related behaviour.A diabetes education model was developed to increase knowledge about diabetes and to influence self-care among migrants with type 2 diabetes. The model was based on literature review, on results from a previous study investigating knowledge about diabetes, on experience from studies of beliefs about health and illness, and on collaboration between researchers in diabetes care and migration and health and staff working in a multi-professional diabetes team.This is a culturally appropriate diabetes education model proceeding from individual beliefs about health and illness and knowledge, conducted in focus-group discussions in five sessions, led by a diabetes specialist nurse in collaboration with a multi-professional team, and completed within three months. The focus groups should include 4–5 persons and last for about 90 min, in the presence of an interpreter. A thematic interview guide should be used, with broad open-ended questions and descriptions of critical situations/health problems. Discussions of individual beliefs based on knowledge are encouraged. When needed, healthcare staff present at the session answer questions, add information and ensure that basic principles for diabetes care are covered. The diabetes education model is tailored to both individual and cultural aspects and can improve knowledge about type 2 diabetes, among migrants and thus increase self-care behaviour and improve health. A physician should also attend this session. At the third session the participants discuss their individual beliefs about why diabetes-related short- and long-term complications occur, how they affect the body and particularly how they can be prevented. A podiatrist should also attend this session, with whom the participants have the opportunity to discuss daily foot care and how to prevent ‘the diabetic foot’. During the fourth session, diet and eating habits are discussed, and the participants discuss their individual beliefs about how they should eat in relation to type 2 diabetes, thus, principles for dietary adjustment. A dietician should also attend the session. The fifth and last session is planned to summarise beliefs about how to achieve good glycaemic control and the complex relation between diet, exercise, medication and awareness/knowledge. Thus the effects of exercise, diet and medication are also discussed, and how to assess blood glucose control. At this session, the whole diabetes team is present, in order to contribute to a holistic picture of the management and to answer any of the participants’ questions. In addition, during the sessions, booklets are handed out in the participants’ native language, concerning diabetes-related complications and self-care.The content of this article is unique since it describes a culturally appropriate health diabetes education model based on individual beliefs about health and illness and knowledge conducted in focus-group discussions guided by a semi-structured interview guide in five sessions, led by a diabetes specialist nurse in collaboration with a multi-professional team, and completed in three months.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., Despite a previously expressed need, culturally tailored diabetes education models for migrants are lacking  (Krueger and Casey, et al., et al., This education model is led by a nurse specialised in diabetes care who acts as a moderator, promoting interaction and discussions between the participants in the group. The diabetes specialist nurse provides support with new knowledge when knowledge gaps are found. This means that, by focussing on the participants’ individual beliefs and knowledge about health and illness, that is, internal resources, the diabetes specialist nurse will use the educative and supportive nursing system in facilitating learning about diabetes and self-management, and thereby improve a person’s self-agency Orem, . Furtheret al., et al., et al., 2003; 2005; The education model described here has been developed to achieve the goal of a culturally appropriate programme, which is to develop culturally and linguistically appropriate services that function within the context of the cultural beliefs, behaviour and needs presented by an ethnic group (Attridge It has been found that migrants have difficulties assimilating knowledge about diabetes in existing education models offered by health care. Therefore a culturally appropriate diabetes education model has been developed, conducted in a focus-group discussion based on the participants’ individual beliefs about health and illness and their knowledge about diabetes and diabetes care and experiences of self-care. The education model is therefore both individually and culturally tailored and intended to improve knowledge about type 2 diabetes among migrants and thus increase self-care behaviour and improve health.It is a strength that many aspects, from both a scientific and clinical perspective, and a theoretical base were considered when this education model was developed in collaboration with a multi-professional diabetes team. Further, this education model ought to be appropriate for several population groups considering that it is based on the participants’ individual beliefs about health and illness and can be implemented at different phases during the illness trajectory and thus be delivered at various times. However, one limitation might be that the model is not tested yet, which is the next step in the research process. Then an evaluation from the users’ perspective will also be included to further revise the model.


We recently completed the Special Issue on ‘Plant Virus Epidemiology and Control’. As editors, we decided not to offer vouchers to scientists that submit to this issue. This action had an effect on the number of papers received and accepted. We received a total of 19 papers and we accepted four. The study of Kinoti et al.  providesThe study of Tahzima et al.  focuses The study of Dall et al.  deals wiThe fourth paper, the study of Alazem et al. , exploreViruses.Overall, the three editors are very satisfied with the quality of the published papers and we are looking forward to additional high-impact plant virus epidemiology and control papers being submitted to


Enemy‐risk effects, often referred to as non‐consumptive effects (NCEs), are an important feature of predator–prey ecology, but their significance has had little impact on the conceptual underpinning or practice of biological control. We provide an overview of enemy‐risk effects in predator–prey interactions, discuss ways in which risk effects may impact biocontrol programs and suggest avenues for further integration of natural enemy ecology and integrated pest management. Enemy‐risk effects can have important influences on different stages of biological control programs, including natural enemy selection, efficacy testing and quantification of non‐target impacts. Enemy‐risk effects can also shape the interactions of biological control with other pest management practices. Biocontrol systems also provide community ecologists with some of the richest examples of behaviourally mediated trophic cascades and demonstrations of how enemy‐risk effects play out among species with no shared evolutionary history, important topics for invasion biology and conservation. We conclude that the longstanding use of ecological theory by biocontrol practitioners should be expanded to incorporate enemy‐risk effects, and that community ecologists will find many opportunities to study enemy‐risk effects in biocontrol settings. We provide a synthetic review of enemy‐risk effects in biological control of arthropod pests. We provide a conceptual overview of enemy‐risk effects, review the current body of literature documenting risk effects in biocontrol systems and describe in detail ways in which risk effects may impact the implementation of biocontrol programs. Pseudacteon spp. parasitoids lay eggs in adult worker ants, the resulting parasitoid larvae completing their development in the heads of their host ants, which fall off as the larvae develop (hence their common name: decapitating flies).The red imported fire ant, Pseudacteon spp. in the native ranges of the fire ants concluded, however, that they were poor candidates for effective biological control, because they achieved very low rates of parasitism , including within‐generation changes in behaviour , the consequences for the individual prey/host (e.g. reduced growth rate) or the consequences at the prey/host population level (e.g. increased emigration). Referring to all three levels as NCEs reduces the important distinctions between them, we advocate for a more explicit framework Fig. , and cleBehavioural shifts are a commonly studied trait responses in arthropods, and are generally the most rapid and reversible. Examples include changes in time spent feeding  is often a result of reduced foraging effort . This can make physiological shifts difficult to categorise within the framework shown in Fig. et al., et al., Morphological shifts are generally slower to appear and more difficult to reverse than behavioural or even physiological shifts. They have been less described in terrestrial arthropods, but thoroughly studied in systems such as Daphnia pulex, where predator cues trigger production of carapace protrusions that decrease vulnerability to predation  with the effect of constrained predators  or predator cues (NCEs only) on prey. A meta‐analysis of these experiments found that the importance of NCEs was highly variable, but on average roughly the same magnitude as CEs  and the perception of risk upon detection (e.g. perceived risk may be lower if a refuge is nearby). Response to risk can be highly state dependent; a starving organism may be more likely to accept higher risk to avoid starvation, and a larger, faster individual may assess risk differently than a smaller, more vulnerable organism. In some cases, it can take a combination of multiple cues to trigger a response  if prey are energy stressed (hungry), resources or mates are abundant but more accessible only if prey show little anti‐predator response, or if prey have high reproductive value  increases mortality from another enemy  history with enemies (or specific enemies) often exhibit much weaker anti‐enemy responses and thus suffer heavy mortality (strong CEs) when novel enemies appear  separating NCEs and CEs to improve predictions of pest population dynamics see Box , (2) conBox 4et al., A central difference between CEs and NCEs is their consequences for natural enemy reproduction  for mass‐rearing and release. Finally, after classical biocontrol agents are released and established, it is important to evaluate efficacy, including effects on targets and non‐targets. The methods used in each of these stages of assessment are overlapping, and different methods can be complementary  population density as the primary response variables Table , therebyet al., et al., et al., Recent research on prey responses to exotic enemies emphasises the importance of prey’s eco‐evolutionary experience (EEE) with enemies , are often used to predict pest movement and abundance within a patchy habitat, but the inclusion of mobile enemies and prey perception of enemies can drastically alter those predictions  and heterozygotes (RS) are killed on Bt plants. Only the rare resistant homozygotes (RR) can survive. The ‘refuge’ refers to a planted block of non‐Bt plants, which are expected to produce relatively large numbers of SS individuals. The rare RR homozygotes surviving on Bt plants are then expected to mate with one of the abundant SS individuals developing in the refuge, and the offspring (genotype RS) are subsequently killed on the Bt crops, removing R alleles from the population. In this way, the models suggest, resistance can be dramatically delayed  additive, independent effects; (2) greater than additive, or synergistic effects; or (3) less than additive, or disruptive effects , then total predation may be less than expected when both predators are present (Vance‐Chalcraft and Soluk, et al.  showed tet al., et al., et al., Insect herbivores face the dual challenge of well‐defended host plants and natural enemies Polis, . It has 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., Natural enemies express a broad array of responses to their own predators. A common response is to move away from areas where predator risk is perceived; this may be measured experimentally as shorter patch residency times (Nakashima and Senoo, et al., et al., et al., et al., et al., per capita reproductive output, perhaps as a consequence of reduced expression of costly anti‐predator defences (Van Veen et al. et al. What influence these responses have on the overall success of biological control is uncertain. Much of the literature is framed around the idea that anti‐enemy behaviour of intraguild prey ameliorate the impact of IGP, potentially facilitating the coexistence of multiple natural enemies, and presumably enhancing the suppression of pest populations. In the short‐term, however, anti‐predator responses that reduce potential IGP or cannibalism often results in reduced overall consumption of prey (Sih et al., et al., et al., Interactions between top‐down and bottom‐up pressures have received much attention in broader natural enemy ecology, but specific breakdown of CEs and NCEs has been less common (but see Kaplan and Thaler, et al., et al., Bottom‐up effects do not always affect anti‐enemy behaviours simply by changing the cost‐benefit ratio of those behaviours. Additive effects may be possible if pests respond to plant defences and enemy risk in qualitatively different ways. For example, phytohormones have been shown to reduce aphid population growth, while natural enemies induce the production of winged morphs (Kaplan and Thaler, per capita consumptive rates and NCEs. The interactions between plant defences and natural enemies are numerous, including risk effect pathways and others not discussed here, which have been more thoroughly reviewed elsewhere (Pappas et al., Finally, many biocontrol agents are omnivorous, meaning plant defences may affect their fitness directly. If high‐quality plants increase omnivorous enemy populations, consumption of prey may increase. However, high‐quality plants may also reduce the omnivore’s need to forage for prey, reducing The study of enemy‐risk effects has advanced greatly in the past two decades, developing into a more fully realised field, incorporating theoretical frameworks, many experimental methods and even predictive models. However, the field of biological control is still catching up to broader natural enemy ecology, and the incorporation of enemy‐risk effects into the biocontrol framework is still in its infancy. There is a significant body of research documenting the importance of risk effects in biocontrol systems, but there is much room to grow beyond this. We have outlined several areas in which risk effect literature may provide insight into biocontrol practice, and hope that further studies will investigate specific interactions between enemy‐risk effects and IPM programs more thoroughly.Community ecologists likewise can find, in biological control systems, rich examples where the consequences of risk effects play out in well‐characterised predator–prey systems, including both coevolved versus novel predator–prey associations. Agricultural systems provide ideal settings for examining both the shorter‐ and the longer term consequences of risk effects, on both smaller and larger spatial scales. Opportunities exist to examine how risk effects shape trophic cascades, the distributions of prey populations in space and even microevolutionary responses to plant defensive traits.One of the most crucial aspects of the merging of the fields will be broadly considering biocontrol of arthropods as an inherently behavioural issue. A focus on preventing unwanted and damaging pest behaviour, whether through killing pests or changing their behaviour, broadens the scope of interactions that may be utilised in biological control. The historical focus on population density is no longer sufficient in light of research demonstrating the importance of enemy‐risk effects and how they can cascade to the level of plants.Studies of risk effects in biocontrol systems should also include more holistic studies of the numerous interactions, either synergistic or antagonistic, between pest behaviour and broader IPM practices. Studies in this area can simultaneously investigate core ecological concepts and provide more concrete suggestions for biocontrol practitioners.Finally, we recognise that it may not be feasible to investigate all possible enemy‐risk effects in a given agroecosystem when attempting to predict the effects of a biocontrol agent, which is why we propose the incorporation of theory and predictive models from risk effect research into biocontrol decision‐making processes. By considering the evolutionary history of the pest, bottom‐up effects of the crop and spatiotemporal dynamics of the agroecosystem, pest management programs may be able to predict the relative importance of various types of risk effects and how they may interact with management practices. Just as other detailed aspects of pest and agent biology are incorporated into management decisions, we advocate for the inclusion of enemy‐risk effect knowledge as well.All the authors discussed ideas and structure, wrote sections of the manuscript, reviewed literature and contributed substantially to revisions.https://publons.com/publon/10.1111/ele.13601.The peer review history for this article is available at Supplementary MaterialClick here for additional data file.


In Amazonia, human activities that occurred hundreds of years ago in the pre‐European era can leave long‐lasting effects on the forests – termed ecological legacies. These legacies include the intentional or nonintentional enrichment or depletion of certain species. The persistence of these legacies through time varies by species, and creates complex long‐term trajectories of post‐disturbance succession that affect ecosystem processes for hundreds of years. Most of our knowledge of Amazonian biodiversity and carbon storage comes from a series of several hundred forest plots, and we only know the disturbance history of four of them. More empirical data are needed to determine the degree to which past human activities and their ecological legacies affect our current understanding of Amazonian forest ecology. The type and intensity of human disturbance (e.g. clear cut versus forest burning) affect the trajectory of the ecological legacy in Amazonian systems on decadal timescales (e.g. Mesquita 3Bertholettia excelsa (Brazil Nut), Bactris gasipaes  and other edible plants were enriched in the pre‐European era, and their abundances have remained artificially high ever since (i.e. for hundreds of years) (Fig. et al., et al., et al., c. 1100 forest plots in Amazonia, there were higher richnesses and abundances of domesticated tree species in locations that were closest to known pre‐European archaeological sites (Levis et al., et al., Most studies of ecological legacies on Amazonian forest composition have focused on the enrichment and long‐term persistence of useful species. It has been suggested that Cecropia or Trema (Fig. Ficus and Pilea, have longer life spans and can persist for centuries, but eventually decrease in abundance (Åkesson et al., et al., et al., Ecological legacies following disturbances may not always be persistent, as is the case with early successional taxa, such as ema Fig. . Mid‐ toIriartea deltoidea, which occurs in higher abundances where there is little to no evidence of human activity compared with areas containing past fire and cultivation (Bush & McMichael, et al., Iriartea deltoidea usually recovers c. 100 yr after site abandonment and often reaches abundances higher than before the disturbance (Fig. Iriartea deltoidea is currently the sixth most common tree species in Amazonia (ter Steege et al., et al., Ecological legacies in Amazonia can also include the depletion of species by people Fig. . The mosnce Fig. . IriarteWettinia is a genus of mid‐successional palms that has a similar, nonpersistent, negative response to human disturbance like I. deltoidea. Wettinia, however, does not seem to have the recovery overshoot that has been documented in Iriartea (Fig. et al., Euterpe includes the first and seventh most common tree species in Amazonia (ter Steege et al., Euterpe species are useful for their fruit, but their abundances do not seem to shift drastically in response to low levels of human disturbance (Fig. et al., Palms are disproportionately abundant in Amazonia compared with other tree families, and have varying degrees of responses to human disturbances. 4et al., et al., et al., Amazonia provides a significant input to global carbon and climate models, and is believed to sequester more carbon than it releases (i.e. is a carbon sink; e.g. Aragao et al., c. 60 yr after abandonment, and this process can happen for over 100 yr (Fig. et al., et al., Old growth forests typically contain high amounts of biomass, but have relatively low productivity and mortality rates Fig. . Landscaet al., et al., Bertholettia excelsa in southwestern Amazonia, which may be related to past human enrichment (Fig. et al., et al., It is possible that the decline of the Amazonian carbon sink and slowing down of productivity observed in the last 30 yr (Brienen ent Fig. , play a 5et al., et al., et al., There are several knowledge gaps and debatable aspects regarding ecological legacies in Amazonian forests. The first concerns the timing and intensity of the disturbance that created the ecological legacy. Most research has focused on linking pre‐European human activities with modern vegetation, but the impacts of the last 400 yr of postcolonial activities are also beginning to be considered (McMichael et al., et al., The time since the last major disturbance is almost unknown in the forest plots used to study biodiversity and carbon dynamics. The time since the last fire has been published in only four out of the hundreds of surveyed forest plots (Fig. 2 concentrations (Koch et al., et al., et al., 14C dating (Heijink et al., et al., The spatial extent of these past human activities and ecological legacies into less well‐studied and less accessible regions of the forest also remains unknown and is highly debated. Some have argued that the extent of site abandonment and subsequent forest regrowth after European arrival was so great that it caused a global decrease in COet al., et al., The integration of ecological, palaeoecological, and archaeological data are crucial to understanding the long‐term ecology and ecological legacies in Amazonian forests. Archaeologists and palaeoecologists are beginning to collect complementary datasets (Mayle & Iriarte, et al., et al., et al., Advancements in techniques of looking into the past are pushing the boundaries of what can be learned from ecological, palaeoecological and archaeological datasets. One example is by extracting dendrochronological, isotopic and genetic information from living trees, and using that information as time capsules of past human and climatic change (Caetano‐Andrade


Health-related fear is a normal and common response in the face of the global pandemic of COVID-19. Children and young people are frequently being exposed to messages about the threat to health, including from the media and authorities. Whilst for most, their anxiety will be proportionate to the threat, for some, existing pre-occupation with physical symptoms and illness will become more problematic. There is a growing body of evidence that health anxiety may occur in childhood, however much of the literature is taken from research using adult samples. This practitioner review aims to give an overview of the assessment and treatment of health-related worries in children and young people in the context of the COVID-19 pandemic. This review is based on the limited existing evidence in this population and the more substantial evidence base for treating health anxiety in adults. We consider the adaptations needed to ensure such interventions are developmentally appropriate. For most, anxiety will be a proportionate and adaptive response to the threat posed by the virus, motivating individuals to engage in sensible, precautionary health behaviours Taylor, . HoweverThere are both individual and systematic factors that may render children and young people particularly vulnerable to health-related worries in the context of COVID-19. It is important to acknowledge that there are key differences in the presentation of anxiety between children and adolescents  and multi-informant  approach to assessment is recommended  or health threat information . As children and young people are less likely to scrutinise the quality and relevance of incoming information, a threat response may be triggered at a lower threshold than adults. Cognitions might typically centre on the risk and likelihood of becoming ill with COVID-19, alongside thoughts of how catastrophic this could be (i.e. ultimately death of self/parent). Behaviours resulting from these health-related fears would be strategically aimed at reducing both distress and risk of contracting COVID-19, with the unintended consequence of increasing anxiety through prevention of disconfirmation, e.g. symptom checking, overly restrictive practices, excessive handwashing. This process also serves to increase the perception of worrying physical sensations, through symptom hypervigilance for example, or interoceptive experience of physiological arousal associated with anxiety. This further acts as a health-related stimulus, elevating anxiety and perceived health risk, and so the cycle continues. This is particularly problematic due to the limited ability that children may have to understand and express their own emotions, therefore the experience of emotions themselves may be perceived as threatening.Within this adapted formulation we also present key mechanisms between the parent and child that may contribute to the maintenance of distress, albeit inadvertently. Illness beliefs in the anxious parent trigger safety-seeking strategies that are designed to keep both themselves, and the child, emotionally and physically safe. However, parental safety-seeking behaviours, and the anxieties that underpin them, are likely to raise salience of the health threat to the child. This in turn drives the child’s own safety-seeking behaviours, which also seek to reduce distress and threat to physical health. Parental safety-seeking behaviours are also likely to influence the child’s behaviours without an explicit cognitive route, e.g. parent repeatedly checks for signs of illness, this behaviour is repeated by the child, learned via modelling and reinforced by the absence of negative consequences. This, within a societal context of public health messages that everyone must stay home in order to be safe and keep others safe, and with schools and workplaces closed, may lead to intensifying difficult dynamics within the family home.et al., et al., et al.  to high-intensity interventions (nine to 20 face-to-face sessions: Creswell , et al.  conducte (et al.  conducteet al., et al., et al., et al., et al., et al., CBT is effective in treating HA in adults (Cooper et al. (We propose that formulation-driven CBT for health-related worries and HA is probably the best treatment available for children and young people with HA. This will be most effective if adapted to be developmentally appropriate. Creswell et al.  suggest et al., The aim of CBT for HA is to reduce distress, reduce unhelpful safety-seeking behaviours and enable consideration of alternative explanations of physical sensations that are being misinterpreted as signs of disease (Daniels and Loades, et al., As with adult HA interventions and good practice in CBT for children and young people (Fuggle There is a qualitative difference to a child’s thinking processes compared with an adult, and they will have a different understanding of illness and disease.Reassurance seeking will often be directed to adults in the child’s life such as parents, caregivers and teachers rather than health professionals.Maintaining factors will be inextricably linked to the beliefs and psychosocial functioning of parents.While there are differences between HA in adults and in those aged under 18, it is also important to consider that there are also likely to be developmental differences between children and young people (Waite and Creswell, et al., et al., et al., et al., Rask  outlineset al., et al., Creswell and colleagues  suggest et al. (et al., et al., et al., et al., et al., et al., Dalton et al.  indicateIn the absence of online HA-specific interventions for children and young people, adapting existing online evidence-based programmes for anxiety to address health-related worries relevant to COVID-19 specifically may hold promise. The adaptations needed would include specific content about coronaviruses and COVID-19, and about concerns children and young people may have about the health threat to adults as well as to themselves. This would need to acknowledge the ongoing uncertainty about COVID-19 and to include a focus on coping with this uncertainty, as well as uncertainty about how long disease containment measures will be in place and how they will be lifted. Content and techniques, including practical exercises, would need to consider physical distancing and disease containment measures. Specific suggestions about how to seek social support and to maintain social contact within these limitations may also be helpful. Further research is needed to establish if existing transdiagnostic programmes, delivered online, are effective in the pandemic context at reducing health-related worries.In the context of a global pandemic, some degree of health-related fear is normal and adaptive. However, for a minority of children and young people, this health-related fear may become particularly distressing. It may interfere substantially with their functioning and persist over time, in a way that we recognise in HA. For these children and young people, adopting a multi-informant approach to assessment, including using existing HA scales to complement clinical interview, could help to establish the extent of their HA. An individualised formulation of the problem, including the cognitive, behavioural and emotional components, based on the CBT model, should be developed. Consideration of developmental factors such as cognitive ability, emotional literacy, intergenerational transmission of beliefs and parental modelling or reinforcement of behaviours, is an important part of the formulation. Adapting existing evidence-based HA treatments for adults and offering these to children and young people may be most helpful. More research is needed to establish age-appropriate diagnostic criteria and standardised tools for assessment of HA in younger children, and to evaluate developmentally appropriate treatment intervention/programmes.