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Tendinopathy is a common age-related disease which causes significant morbidity for both human athletes and performance horses. In the latter, the superficial digital flexor tendon is an excellent model for human tendinopathies because it is a functional homologue of the human Achilles tendon and a primary site of injuries with strong similarities to the human disease. Corticosteroids have been previously used clinically to treat tendinopathic inflammation, but they upregulate the p53-p21 axis with concomitant reductions in cell proliferation and collagen synthesis in human tenocytes. This phenotype is consistent with the induction of cellular senescence in vitro and in vivo and probably represents an important clinical barrier to their effective use. Because of the many differences in senescence mechanisms between species, this study aimed to evaluate these mechanisms after corticosteroid treatment in equine tenocytes. Exposure to clinically reflective levels of dexamethasone for 48 hours drove equine tenocytes into steroid induced senescence (SIS). This was characterised by permanent growth arrest and upregulation of p53, the cyclin dependent kinase inhibitors p21waf and p16ink4a as well as the matrix degrading enzymes MMP1, MMP2 and MMP13. SIS also induced a distinctive equine senescence associated secretory phenotype (eSASP) characterised by enhanced secretion of IL-8 and MCP-1. Preincubation with resveratrol or the potent SIRT1 activator SRT1720 prevented SIS in equine tenocytes, while treatment with the non-SIRT1 activating resveratrol analogue V29 was equally protective against SIS, consistent with a novel, as yet uncharacterised SIRT1-indendent mechanism which has relevance for the development of future preventative and therapeutic strategies., Competing Interests: NO authors have competing interests., (Copyright: © 2024 Heidari et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

This study aimed to evaluate the effect of discrete passages of play on locomotor demands of international men's and women's rugby sevens matches and their relationship with winning or losing. Thirteen men's and thirteen women's international rugby sevens players wore 10 Hz Global Positioning Systems during twelve Tokyo Olympic games matches (966 observations; 507 for men, 459 for women). Discrete ball-in-play periods were categorised as: 'Single-phase defence', 'single-phase attack', 'multi-phase defence', 'multi-phase attack', 'multi-phase defence to attack', or 'multi-phase attack to defence'. Relative total distance, alongside high-speed (>5.0 m∙s-1), acceleration (>3 m∙s-2), and deceleration (>3 m∙s-2) distances were recorded for each passage. Separately for men and women, linear mixed models examined the effect of passage type and match outcome (win or loss) on locomotor demands, whilst controlling for opposition ranking. In men, relative total distance ranged from 137 m∙min-1 to 174 m∙min-1 for 'multi-phase defence to attack' and 'multi-phase attack', respectively. In women, 'multi-phase attack' elicited the lowest relative total distance (118 m∙min-1), whereas the greatest values (186 m∙min-1) were recorded for 'single-phase defence'. For men, there were significant interactions between match outcome and passage type for relative total (p<0.001) and high-speed (p = 0.006) distance. During 'multi-phase attack', relative total distance was greater for wins versus losses (174 vs 138 m.min-1, p = 0.024). However, for 'single-phase defence', relative total distance was lower for wins (128 vs 164 m.min-1, p<0.001). For women, there were significant interactions between match outcome and passage type for relative total (p = 0.036), high-speed (p = 0.003), and deceleration (p = 0.015) distances. Locomotor responses were influenced by passage type and match result for men and women. Knowing the demands of each passage type may inform training drills targeted at developing match-play-specific physical, technical, and tactical adaptations. Understanding how passages differ between matches won and lost could also inform team technical/tactical preparation including selection., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Hills et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Young women who are not in education, employment, or training (NEET) experience poorer health and social outcomes compared to non-NEET young women and to NEET young men, especially in deprived areas with intersecting inequalities. The evidence on effective public health approaches is scarce. Interventions that target hope, which NEET young women notably lack, offer a promising theory-driven and intuitive means to prevent mental health problems and improve social outcomes. Hope can be defined as a goal-focused mindset comprising self-agency (motivation and self-belief) and pathways (identifying routes to achieving goals). Hope is implicated in a variety of evidence-based psychosocial interventions for young people, but is not directly targeted by existing prevention programmes for NEET populations. The current study used a phased qualitative research design and participatory methods to model a hope-focused intervention for NEET young women. Phase 1 investigated population needs and intervention parameters through semi-structured interviews with 28 key informants living or working in disadvantaged coastal communities in South-East England. The sample comprised eight NEET young women, four family members, and 16 practitioners from relevant support organisations. Phase 2 refined intervention parameters and outcomes through co-design sessions with four NEET young women, followed by a theory of change workshop with 10 practitioners. The resulting intervention model is articulated as a mentor-supported, in-person psychosocial intervention that builds hope by enhancing positive sense of self and time spent in meaningful activities, before explicitly teaching the skills needed to identify, set, and pursue personally meaningful goals., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Berry et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Objectives: The post-medieval period in Europe saw a dramatic increase in metabolic bone disease related to vitamin D deficiency (VDD). Recent paleopathological work has utilized interglobular dentin (IGD) as a proxy for poor vitamin D status during development, while enamel peptide analysis allows the identification of chromosomal sex in non-adult remains. Here we explore the relationship between sex, the presence of IGD, and macroscopic markers of VDD in an industrial era assemblage from Northeast England., Materials and Methods: 25 individuals (9 females, 9 males, 9 unknown sex) from the cemetery site at Coach Lane, North Shields (1711-1857) were selected for paleopathological analysis, histological assessment of IGD, and enamel peptide determination of chromosomal sex., Results: Ground tooth sections from 21 individuals were of suitable quality for detection of IGD, and enamel peptide analysis confirmed the chromosomal sex of ten individuals. Sixteen individuals (76.1%) exhibited ≥1 episode of IGD. Nine of these (42.8%) exhibited >1 episode and four (19%) exhibited ≥4 episodes in regular intervals. Male sex was significantly associated with the presence of IGD (p = 0.0351; 100% males vs. 54.5% females). Females were more likely to exhibit macroscopic evidence of VDD (45.5% females vs 30% males) but this was not statistically significant., Discussion and Conclusions: Periods of poor mineral metabolism during childhood appear much more prevalent at Coach Lane than macroscopic evidence suggests. Evidence of seasonal IGD episodes indicates that northern latitude played a major role in poor VD status in the Northeast of England. The significant association of IGD with male sex may be due to sex-related differences in dentinal mineralization or a higher risk of poor VD status in males aged <5 years. More work is needed to establish an evidence-based threshold for pathological levels of IGD before the presence of this feature can confidently be used as a biomarker for poor VD status., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Snoddy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Young people living with type 1 diabetes (T1D) navigate daily complex diabetes related tasks as they take on increasing (and eventually full) responsibility for managing their condition, in addition to developing their lives as independent adults. Alongside the need for careful day-to-day diabetes management, the psychosocial burden and mental health impact and stigma are well recognised. Despite advances in psychological care, many young people with diabetes still experience a greater mental health burden than those without diabetes. This study aims to develop a brief and simple intervention for young people with T1D that will support their wellbeing day to day, as required, and grow their ability to live confidently with their condition that requires lifelong meticulous management. Insights gained in this participatory study will guide the development and focus of the intervention which may involve a toolkit containing self-guided resources or which could be a series of recommendations on how to design a healthcare service with a support network that is tailored to the needs of young people. This study will consist of qualitative research and collaboration with young people with T1D and their siblings, friends, and peers to co-create a testable intervention. In Part 1, research interviews will be conducted with young people (16-24 years old) with T1D and, where possible, their siblings/peers to understand the day-to-day challenges of type 1 and what a novel intervention should address. Thematic analysis of interviews will inform the generation of a prototype intervention to take into part two, focus group discussions. Focus groups with (i) young people with T1D and, separately (ii) carers (comprising parents, carers, teachers, specialist nurses). Collaborative principles will be used to review, redesign and evolve the intervention to meet user needs. A blend of narrative and thematic analysis will inform the findings and report. Insights from Parts 1 and 2 will shape a user-defined and formatively analysed brief and simple intervention and future study design ready for pilot testing. The aim of this part of the research is to maximise acceptability and usability of a testable intervention by the target population. To aim of the future intervention will be to demonstrate effectiveness in helping young adults to live well with T1D., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Howland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Child labour is the most common form of child abuse in the world today, with almost half of child workers employed in hazardous industries. The large-scale employment of children during the rapid industrialisation of the late 18th and early 19th centuries in England is well documented. During this period, the removal of pauper children from workhouses in cities to work as apprentices in rural mills in the North of England was commonplace. Whilst the experiences of some of these children have been recorded historically, this study provides the first direct evidence of their lives through bioarchaeological analysis. The excavation of a rural churchyard cemetery in the village of Fewston, North Yorkshire, yielded the skeletal remains of 154 individuals, including an unusually large proportion of children aged between 8 to 20 years. A multi-method approach was undertaken, including osteological and palaeopathological examination, stable isotope and amelogenin peptide analysis. The bioarchaeological results were integrated with historical data regarding a local textile mill in operation during the 18th-19th centuries. The results for the children were compared to those obtained from contemporaneous individuals of known identity (from coffin plates) of comparable date. Most of the children exhibited distinctive 'non-local' isotope signatures and a diet low in animal protein when compared to the named local individuals. These children also showed severe growth delays and pathological lesions indicative of early life adversity, as well as respiratory disease, which is a known occupational hazard of mill work. This study has provided unique insights into the harrowing lives of these children; born into poverty and forced to work long hours in dangerous conditions. This analysis provides a stark testimony of the impacts of industrial labour on the health, growth and mortality risk of children, with implications for the present as well as our understanding of the past., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Gowland et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Despite undeniable hardship, the onset of the COVID-19 pandemic also saw an outpour of community solidarity and mutual aid towards those in need. This study explored why people participated in mutual aid during the pandemic as well as the factors that contributed to continued involvement and/or its decline. We conducted remote interviews with 17 people in South-east England who had been involved in volunteering and local community mutual aid support groups during the first UK lockdown from March to May 2020. Using thematic analysis, we identified two themes: 1) The emergence of social groups and their psychosocial effects, and 2) Enduring connections and barriers to continued participation. Participants often reported an emergent shared identity, preferring the localised nature of these groups and the associated mutual nature of support. They also reported intentions to continue providing such support, should the need arise again, and any barriers to continued involvement in mutual aid were better explained by structural and systemic issues, rather than individual motivational factors., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Cocking et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Social science research is key for understanding and for predicting compliance with COVID-19 guidelines, and this research relies on survey data. While much focus is on the survey question stems, less is on the response alternatives presented that both constrain responses and convey information about the assumed expectations of the survey designers. The focus here is on the choice of response alternatives for the types of behavioral frequency questions used in many COVID-19 and other health surveys. We examine issues with two types of response alternatives. The first are vague quantifiers, like "rarely" and "frequently." Using data from 30 countries from the Imperial COVID data hub, we show that the interpretation of these vague quantifiers (and their translations) depends on the norms in that country. If the mean amount of hand washing in a country is high, it is likely "frequently" corresponds to a higher numeric value for hand washing than if the mean in the country is low. The second type are sets of numeric alternatives and they can also be problematic. Using a US survey, respondents were randomly allocated to receive either response alternatives where most of the scale corresponds to low frequencies or where most of the scale corresponds to high frequencies. Those given the low frequency set provided lower estimates of the health behaviors. The choice of response alternatives for behavioral frequency questions can affect the estimates of health behaviors. How the response alternatives mold the responses should be taken into account for epidemiological modeling. We conclude with some recommendations for response alternatives for behavioral frequency questions in surveys., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2022 Wright et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Introduction: This study aims to investigate the health-related quality of life and coping strategies among COVID-19 survivors in Bangladesh., Methods: This is a cross-sectional study of 2198 adult, COVID-19 survivors living in Bangladesh. Data were collected from previously diagnosed COVID-19 participants (confirmed by an RT-PCR test) via door-to-door interviews in the eight different divisions in Bangladesh. For data collection, Bengali-translated Brief COPE inventory and WHO Brief Quality of Life (WHO-QoLBREF) questionnaires were used. The data collection period was from October 2020 to March 2021., Results: Males 72.38% (1591) were more affected by COVID-19 than females 27.62% (607). Age showed significant correlations (p<0.005) with physical, psychological and social relationships, whereas gender showed only a significant correlation with physical health (p<0.001). Marital status, occupation, living area, and co-morbidities showed significant co-relation with all four domains of QoL (p<0.001). Education and affected family members showed significant correlation with physical and social relationship (p<0.001). However, smoking habit showed a significant correlation with both social relationship and environment (p<0.001). Age and marital status showed a significant correlation with avoidant coping strategies (p<0.001); whereas gender and co-morbidities showed a significant correlation with problem-focused coping strategies (p<0.001). Educational qualification, occupation and living area showed significant correlation with all three coping strategies(p<0.001)., Conclusion: Survivors of COVID-19 showed mixed types of coping strategies; however, the predominant coping strategy was avoidant coping, followed by problem-focused coping, with emotion-focused coping reported as the least prevalent. Marital status, occupation, living area and co-morbidities showed a greater effect on QoL in all participants. This study represents the real scenario of nationwide health-associated quality of life and coping strategies during and beyond the Delta pandemic., Competing Interests: The authors declare that they have no competing interests regarding publication of this journal., (Copyright: © 2022 Hossain et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

In Thailand, 17% of the population lives by the coast, approximately 11 million people. A combination of coastal erosion, sea level rise and coastal land subsidence are critical issues threatening the livelihoods of coastal communities. Thailand has invested a lot of money and installed conservation policies to restore and protect coastal mangroves and realign or replenish their beaches. This study assessed the use of the toolkit Coastsat to digitise a time series of shoreline positions from open access satellite images between 1990 and 2019 along 560 km of coastline in the provinces of Krabi and Nakhon Si Thammarat (NST). Based on these digitised shorelines and the use of the software Digital Shoreline Analysis System (DSAS), it was possible to identify shoreline change, which varied between -66 to +16.4 m/y in the mangroves of NST and -22.2 to +10.6 m/year on its sandy beaches. Shoreline change rates along the Krabi coast varied -34.5 to +21.7 m/year in the mangroves and -4.1 to +4 m/year on sandy beaches. Analysis of the spatial and temporal variations of the shoreline position during the survey period reveals a linkage between extreme weather conditions and coastal erosion along the NST coast while that linkage is less clear along the Krabi coast. CoastSat delivers crucial and accurate time series shoreline data over extensive areas that are vital to coastal managers and researchers in a completely remote manner, which is key with the presence of COVID-19 travel bans., Competing Interests: The authors have declared that no competing interests exist.

Shopping behaviour in response to extreme events is often characterized as "panic buying" which connotes irrationality and loss of control. However, "panic buying" has been criticized for attributing shopping behaviour to people's alleged psychological frailty while ignoring other psychological and structural factors that might be at play. We report a qualitative exploration of the experiences and understandings of shopping behaviour of members of the public at the onset of the COVID-19 pandemic. Through a thematic analysis of semi-structured interviews with 23 participants, we developed three themes. The first theme addresses people's understandings of "panic buying". When participants referred to "panic buying" they meant observed product shortages (rather than the underlying psychological processes that can lead to such behaviours), preparedness behaviours, or emotions such as fear and worry. The second theme focuses on the influence of the media and other people's behaviour in shaping subsequent shopping behaviours. The third theme addresses the meaningful motivations behind increased shopping, which participants described in terms of preparedness; some participants reported increased shopping behaviours as a response to other people stockpiling, to reduce their trips to supermarkets, or to prepare for product shortages and longer stays at home. Overall, despite frequently using the term 'panic', the irrationalist connotations of "panic buying" were largely absent from participants' accounts. Thus, "panic buying" is not a useful concept and should not be used as it constructs expected responses to threat as irrational or pathological. It can also facilitate such behaviours, creating a self-fulfilling prophecy., Competing Interests: The authors declare that there are no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The subjective experience of fatigue impairs an individual's ability to sustain physical endurance performance. However, precise understanding of the specific role perceived fatigue plays in the central regulation of performance remains unclear. Here, we examined whether the subjective intensity of a perceived state of fatigue, pre-induced through prior upper body activity, differentially impacted performance and altered perceived effort and affect experienced during a sustained, isometric contraction in lower body. We also explored whether (cardiac) interoception predicted the intensity of experienced perceptual and affective responses and moderated the relationships between constructs during physical activity., Methods: Using a repeated-measures study design, thirty male participants completed three experimental conditions, with the intensity of a pre-induced state of fatigue manipulated to evoke moderate (MOD), severe (SEV) and minimal (control; CON) intensity of perceptions prior to performance of the sustained contraction., Results: Performance of the sustained contraction was significantly impaired under a perceived state of fatigue, with reductions of 10% and 14% observed in the MOD and SEV conditions, respectively. Performance impairment was accompanied by greater perceived effort and more negative affective valence reported during the contraction. However, effects were limited to comparisons to CON, with no difference evident between the two experimental trials (i.e. MOD vs. SEV). Individuals' awareness of their accuracy in judging resting heartbeats was shown to predict the subjective intensity of fatigue experienced during the endurance task. However, interoception did not moderate the relationships evident between fatigue and both perceived effort and affective valence., Conclusions: A perceived state of fatigue limits endurance performance, influencing both how effortful activity is perceived to be and the affective experience of activity. Though awareness of interoceptive representations of bodily states may be important to the subjective experience of fatigue, interoception does not modulate the relationships between perceived fatigue and other perceptual (i.e. effort) and affective constructs., Competing Interests: The authors have declared that no competing interests exist.

Comparison of the severity, frequency and self-reporting of pollution incidents by water and sewerage companies is made difficult by differences in environmental and operational conditions. In England, the deterioration in pollution incident performance makes it important to investigate common trends that could be addressed to improve pollution management. This study presents the first external analysis of available national pollution incident data, obtained through Environmental Information Regulations 2004 requests to the English Environment Agency. The study aimed to assess and compare the pollution incident performance of water and sewerage companies in England. Results indicated that there were significant variations in numbers of pollution incidents reported and the severity of the impact on the water environment for different asset types (operational property). There were significant positive relationships between the self-reporting percentages and total numbers of reported pollution incidents per 10,000 km sewer length for pumping stations and sewage treatment works. These results indicate that in at least these asset types, an estimated 5% of pollution incidents could go unreported. Pollution events that go unreported can lead to more severe impacts to the water environment, so rapid and consistent reporting of incidents is crucial for limiting damage. The results have significance for the water industry internationally, because the issues presented here are not restricted to England. In the short-term, research should focus on investigating best practice and standardising reporting of pollution incidents, so that an accurate baseline of the number of pollution incidents occurring can be determined., Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests; NM is employed by Southern Water Services Ltd. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The funding provided by the commercial source Southern Water Services Ltd does not alter our adherence to all PLOS ONE policies on sharing data and materials.

Little is known of the properties of the sarsen stones (or silcretes) that comprise the main architecture of Stonehenge. The only studies of rock struck from the monument date from the 19th century, while 20th century investigations have focussed on excavated debris without demonstrating a link to specific megaliths. Here, we present the first comprehensive analysis of sarsen samples taken directly from a Stonehenge megalith (Stone 58, in the centrally placed trilithon horseshoe). We apply state-of-the-art petrographic, mineralogical and geochemical techniques to two cores drilled from the stone during conservation work in 1958. Petrographic analyses demonstrate that Stone 58 is a highly indurated, grain-supported, structureless and texturally mature groundwater silcrete, comprising fine-to-medium grained quartz sand cemented by optically-continuous syntaxial quartz overgrowths. In addition to detrital quartz, trace quantities of silica-rich rock fragments, Fe-oxides/hydroxides and other minerals are present. Cathodoluminescence analyses show that the quartz cement developed as an initial <10 μm thick zone of non-luminescing quartz followed by ~16 separate quartz cement growth zones. Late-stage Fe-oxides/hydroxides and Ti-oxides line and/or infill some pores. Automated mineralogical analyses indicate that the sarsen preserves 7.2 to 9.2 area % porosity as a moderately-connected intergranular network. Geochemical data show that the sarsen is chemically pure, comprising 99.7 wt. % SiO2. The major and trace element chemistry is highly consistent within the stone, with the only magnitude variations being observed in Fe content. Non-quartz accessory minerals within the silcrete host sediments impart a trace element signature distinct from standard sedimentary and other crustal materials. 143Nd/144Nd isotope analyses suggest that these host sediments were likely derived from eroded Mesozoic rocks, and that these Mesozoic rocks incorporated much older Mesoproterozoic material. The chemistry of Stone 58 has been identified recently as representative of 50 of the 52 remaining sarsens at Stonehenge. These results are therefore representative of the main stone type used to build what is arguably the most important Late Neolithic monument in Europe., Competing Interests: Three of the authors (JMH, MRP and NW) are employed by commercial companies (Petroclays Ltd, Vidence Inc. and Gatan UK, respectively). This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Water safety planning is an approach to ensure safe drinking-water access through comprehensive risk assessment and water supply management from catchment to consumer. However, its uptake remains low in rural areas. Participatory mapping, the process of map creation for resource management by local communities, has yet to be used for rural water safety planning. In this mixed methods study, to evaluate the validity of participatory mapping outputs for rural water safety planning and assess community understanding of water safety, 140 community members in Siaya County, Kenya, attended ten village-level participatory mapping sessions. They mapped drinking-water sources, ranked their safety and mapped potential contamination hazards. Findings were triangulated against a questionnaire survey of 234 households, conducted in parallel. In contrast to source type ranking for international monitoring, workshop participants ranked rainwater's safety above piped water and identified source types such as broken pipes not explicitly recorded in water source typologies often used for formal monitoring. Participatory mapping also highlighted the overlap between livestock grazing areas and household water sources. These findings were corroborated by the household survey and subsequent participatory meetings. However, comparison with household survey data suggested participatory mapping outputs omitted some water sources and landscape-scale contamination hazards, such as open defecation areas or flood-prone areas. In follow-up visits, participant groups ranked remediation of rainwater harvesting systems as the most acceptable intervention to address hazards. We conclude that participatory mapping can complement other established approaches to rural water safety planning by capturing informally managed source use and facilitating community engagement., Competing Interests: The authors have declared that no competing interests exist.

The objective of this scoping review was to map the evidence on measurement properties of body composition tools to assess whole-body and regional fat and fat-free mass in adults with SCI, and to identify research gaps in order to set future research priorities. Electronic databases of PubMed, EMBASE and the Cochrane library were searched up to April 2020. Included studies employed assessments related to whole-body or regional fat and/or fat-free mass and provided data to quantify measurement properties that involved adults with SCI. All searches and data extractions were conducted by two independent reviewers. The scoping review was designed and conducted together with an expert panel (n = 8) that represented research, clinical, nutritional and lived SCI experience. The panel collaboratively determined the scope and design of the review and interpreted its findings. Additionally, the expert panel reached out to their professional networks to gain further stakeholder feedback via interactive practitioner surveys and workshops with people with SCI. The research gaps identified by the review, together with discussions among the expert panel including consideration of the survey and workshop feedback, informed the formulation of future research priorities. A total of 42 eligible articles were identified (1,011 males and 143 females). The only tool supported by studies showing both acceptable test-retest reliability and convergent validity was whole-body dual-energy x-ray absorptiometry (DXA). The survey/workshop participants considered the measurement burden of DXA acceptable as long as it was reliable, valid and would do no harm (e.g. radiation, skin damage). Practitioners considered cost and accessibility of DXA major barriers in applied settings. The survey/workshop participants expressed a preference towards simple tools if they could be confident in their reliability and validity. This review suggests that future research should prioritize reliability and validity studies on: (1) DXA as a surrogate 'gold standard' tool to assess whole-body composition, regional fat and fat-free mass; and (2) skinfold thickness and waist circumference as practical low-cost tools to assess regional fat mass in persons with SCI, and (3) females to explore potential sex differences of body composition assessment tools. Registration review protocol: CRD42018090187 (PROSPERO)., Competing Interests: The authors have declared that no competing interests exist.

The neural representation of a 'biological self' is linked theoretically to the control of bodily physiology. In an influential model, selfhood relates to internal agency and higher-order interoceptive representation, inferred from the predicted impact of efferent autonomic nervous activity on afferent viscerosensory feedback. Here we tested if an altered representation of physical self (illusory embodiment of an artificial hand) is accompanied by sustained shifts in autonomic activity. Participants (N = 37) underwent procedures for induction of the rubber hand illusion (synchronous stroking of own unseen hand and observed stroking of artificial hand) and a control condition (asychronous stroking). We recorded electrocardiography, electrodermal activity, and a non-invasive measure of multiunit skin sympathetic nerve activity (SKNA) from the chest. We compared these autonomic indices between task conditions, and between individuals who did and did not experience the illusion. Bayes factors quantified the strength of evidence for and against null hypotheses. Observed proprioceptive drift and subjective reports confirmed the efficacy of the synchronous (vs asynchronous) condition in inducing illusory hand ownership. Stringent discriminant analysis classified 24/37 individuals as experiencing the rubber hand illusion. Surprisingly, heart rate, heart rate variability, electrodermal activity, and SKNA measures revealed no autonomic differences between synchronous vs asynchronous conditions, nor between individuals who did or did not experience the rubber hand illusion. Bayes factors indicated substantial evidence for no physiological differences. In contrast to earlier reports, our autonomic data show the absence of a reliable change in physiological state during the rubber hand illusion. More encompassing perturbations of self-experience, for example in full body illusions, may nevertheless be coupled to, or facilitated by, changes in efferent autonomic activity and afferent viscerosensory feedback. Our findings suggest that such changes in bodily physiology are not sustained as an obligatory component of the rubber hand illusion., Competing Interests: The authors have declared that no competing interests exist.

The COVID-19 pandemic has created enormous global demand for personal protective equipment (PPE). Face shields are an important component of PPE for front-line workers in the context of the COVID-19 pandemic, providing protection of the face from splashes and sprays of virus-containing fluids. Existing face shield designs and manufacturing procedures may not allow for production and distribution of face shields in sufficient volume to meet global demand, particularly in Low and Middle-Income countries. This paper presents a simple, fast, and cost-effective curved-crease origami technique for transforming flat sheets of flexible plastic material into face shields for infection control. It is further shown that the design could be produced using a variety of manufacturing methods, ranging from manual techniques to high-volume die-cutting and creasing. This demonstrates the potential for the design to be applied in a variety of contexts depending on available materials, manufacturing capabilities and labour. An easily implemented and flexible physical-digital parametric design methodology for rapidly exploring and refining variations on the design is presented, potentially allowing others to adapt the design to accommodate a wide range of ergonomic and protection requirements., Competing Interests: The authors of this manuscript have read the journal’s policy and have the following competing interests: we disclose here that HappyShield is our CE-marked design, which we have released open source on https://happyshield.github.io/en/, licensed under the Creative Commons “Attribution-NonCommercial-ShareAlike 4.0 International” License (CC BY-NC-SA 4.0). We do not intend to gain financially from the release of this face shield design. A disclaimer for the design is provided at https://happyshield.github.io/en/. All others producing face shields based on the designs presented in this paper remain responsible for undergoing any necessary testing and obtaining any necessary approvals before manufacturing and distributing face shields. No patent application has been made for this design. No further modified versions of the design are currently under active development. Any future versions of the design presented in this paper developed by the authors will also be released open-source under the CC BY-NC-SA 4.0 license. This does not alter our adherence to PLOS ONE policies on sharing data and materials. The funding that supported this work is listed in the acknowledgements.

Cognitive behavioural therapy (CBT) which includes Exposure and Response (ERP) is a highly effective, gold standard treatment for Obsessive-Compulsive Disorder (OCD). Nonetheless, not all patients with OCD significantly benefit from CBT. This has generated interest in the potential benefits of Mindfulness-Based Interventions (MBIs), either integrated with CBT, to enhance engagement with ERP tasks, or delivered as a stand-alone, first-line or therapy to augment CBT. This paper reports on two qualitative studies that involved a thematic analysis of interview data with participants in a 10-week Mindfulness-Based ERP (MB-ERP) course (study 1) and a 9-week Mindfulness-Based Cognitive Therapy course adapted for OCD (MBCT-OCD) (study 2). Whilst MB-ERP integrated a mindfulness component into a standard ERP protocol, MBCT-OCD adapted the psychoeducational components of the standard MBCT for depression protocol to suit OCD, but without explicit ERP tasks. Three common main themes emerged across MB-ERP and MBCT-OCD: 'satisfaction with course features', 'acceptability of key therapeutic tasks 'and 'using mindfulness to respond differently to OCD'. Sub-themes identified under the first two main themes were mostly unique to MB-ERP or MBCT-OCD, with the exception of '(struggles with) developing a mindfulness practice routine' whilst most of the sub-themes under the last main theme were shared across MB-ERP and MBCT-OCD participants. Findings suggested that participants generally perceived both MBIs as acceptable and potentially beneficial treatments for OCD, in line with theorised mechanisms of change., Competing Interests: CS is Research Lead for Sussex Mindfulness Centre and has received NIHR and other research funding to evaluate mindfulness-based interventions. TL, KC, LL, CR, AMJ and EF have received research funding to evaluate mindfulness-based interventions.

In urban areas green roofs provide important environmental advantages in regard to biodiversity, storm water runoff, pollution mitigation and the reduction of the urban heat island effect. There is a paucity of literature comparing different types of green roof substrates and their contributions to ecosystem services or their negative effects. This study investigated if there was a difference between sedum and wildflower green roof substrate properties (soil organic matter (SOM), potassium (K) and phosphorus (P) concentrations and pH values) of 12 green roofs in the city of Brighton & Hove. One hundred substrate samples were collected (50 from sedum roof substrates and 50 from wildflower roof substrates) and substrate properties were investigated using standard protocols. Comparisons were made between substrate characteristics on both types of roof substrate with a series of multiple linear regressions. Sedum roofs displayed significantly higher values of SOM, P and pH. There were significant positive relationships between SOM and K concentrations, SOM and P concentrations, pH and K concentrations and pH and P concentrations on sedum roofs. This study concluded that sedum roof substrates are more favourable for plant water use efficiency and also contained a significantly higher percentage of SOM than wildflower roofs. However, higher concentrations of P in sedum roof substrates may have implications in regard to leachates., Competing Interests: The authors have declared that no competing interests exist.

Background: Comorbid depression is common among patients with diabetes and has severe health consequences, but often remains unrecognized. Several questionnaires are used to screen for depression. A systematic review and meta-analysis regarding the diagnostic accuracy of depression questionnaires in adults with diabetes is unavailable. Our aim was to conduct a systematic review and meta-analysis to evaluate the diagnostic accuracy of depression questionnaires in adults with type 1 or type 2 diabetes., Methods: PubMed, Embase and PsycINFO were searched from inception to 28 February 2018. Studies were included when the diagnostic accuracy of depression questionnaires was assessed in a diabetes population and the reference standard was a clinical interview. Data extraction was performed by one reviewer and checked by another. Two reviewers independently conducted the quality assessment (QUADAS-2). Diagnostic accuracy was pooled in bivariate random effects models. The main outcome was diagnostic accuracy, expressed as sensitivity and specificity, of depression questionnaires in an adult diabetes population. This study is reported according to PRISMA-DTA and is registered with PROSPERO (CRD42018092950)., Results: A total 6,097 peer-reviewed articles were screened. Twenty-one studies (N = 5,703 patients) met the inclusion criteria for the systematic review. Twelve different depression questionnaires were identified, of which the CES-D (n = 6 studies) and PHQ-9 (n = 7 studies) were the most frequently evaluated. Risk of bias was unclear for multiple domains in the majority of studies. In the meta-analyses, five (N = 1,228) studies of the CES-D (≥16), five (N = 1,642) of the PHQ-9 (≥10) and four (N = 822) of the algorithm of the PHQ-9 were included in the pooled analysis. The CES-D (≥16) had a pooled sensitivity of 85.0% (95%CI, 71.3-92.8%) and a specificity of 71.6% (95%CI, 62.5-79.2%); the PHQ-9 (≥10) had a sensitivity of 81.5% (95%CI, 57.1-93.5%) and a specificity of 79.7% (95%CI, 62.1-90.4%). The algorithm for the PHQ-9 had a sensitivity of 60.9% (95%CI, 52.3-90.8%) and a specificity of 64.0% (95%CI, 53.0-93.9%)., Conclusions: This review indicates that the CES-D had the highest sensitivity, whereas the PHQ-9 had the highest specificity, although confidence intervals were wide and overlapping. The algorithm for the PHQ-9 had the lowest sensitivity and specificity. Given the variance in results and suboptimal reporting of studies, further high quality studies are needed to confirm the diagnostic accuracy of these depression questionnaires in patients with diabetes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: To test the accuracy, validity, reliability and sensitivity of an alternative method for the measure of TMS-assessed voluntary activation (VATMS) in the knee extensors., Methods: Ten healthy males (24 ± 5 years) completed a neuromuscular assessment protocol before and after a fatiguing isometric exercise: two sets of five contractions (50%, 62.5%, 75%, 87.5%, 100% Maximal Voluntary Contraction; MVC) with superimposed TMS-evoked twitches for calculation of VATMS using either the first 5 stimulations (1x5C) or all 10 (2x5C). This was performed on two separate occasions (between-day reliability). Accuracy and validity were compared with a routinely used protocol [i.e. 50%, 75%, and 100% of MVC (1x3C) performed three times (3x3C)]., Results: 95% confidence interval for estimated resting twitch, a key determinant of VATMS, was similar between 1x5C, 2x5C, and 3x3C but improved by six-fold when compared to 1x3C (P<0.05). In a fresh state, potentiated twitch force was unchanged following 1x5C but decreased following 2x5C (P<0.05). A recovery was found post-exercise but was smaller for 1x5C compared to 2x5C (P<0.05), with no difference between the latter two (P>0.05). Absolute reliability was strong enough for both 1x5C and 2x5C to depict a true detectable change in the sample's VATMS following the fatiguing exercise (TEM < 3% at rest, <9% post-exercise) but 2x5C was marginally more sensitive to individual's changes from baseline., Conclusion: Both 1x5C and 2x5C provide reliable measures of VATMS. However, 1x5C may hold stronger internal validity. Both protocols allow detection of 'true' changes in sample's means but not individual scores following a fatiguing isometric exercise., Competing Interests: The authors have declared that no competing interests exist.

The AbsA1-AbsA2 two component signalling system of Streptomyces coelicolor has long been known to exert a powerful negative influence on the production of the antibiotics actinorhodin, undecylprodiginine and the Calcium-Dependent Antibiotic (CDA). Here we report the analysis of a ΔabsA2 deletion strain, which exhibits the classic precocious antibiotic hyper-production phenotype, and its complementation by an N-terminal triple-FLAG-tagged version of AbsA2. The complemented and non-complemented ΔabsA2 mutant strains were used in large-scale microarray-based time-course experiments to investigate the effect of deleting absA2 on gene expression and to identify the in vivo AbsA2 DNA-binding target sites using ChIP-on chip. We show that in addition to binding to the promoter regions of redZ and actII-orfIV AbsA2 binds to several previously unidentified sites within the cda biosynthetic gene cluster within and/or upstream of SCO3215-SCO3216, SCO3217, SCO3229-SCO3230, and SCO3226, and we relate the pattern of AbsA2 binding to the results of the transcriptomic study and antibiotic phenotypic assays. Interestingly, dual 'biphasic' ChIP peaks were observed with AbsA2 binding across the regulatory genes actII-orfIV and redZ and the absA2 gene itself, while more conventional single promoter-proximal peaks were seen at the CDA biosynthetic genes suggesting a different mechanism of regulation of the former loci. Taken together the results shed light on the complex mechanism of regulation of antibiotic biosynthesis in Streptomyces coelicolor and the important role of AbsA2 in controlling the expression of three antibiotic biosynthetic gene clusters., Competing Interests: We have the following interests. Richard A. Lewis is affiliated to Demuris Ltd. and Andrzej Kierzek to Certara. There are no patents, products in development or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

This paper presents the first empirical investigation that compares Euler and linear diagrams when they are used to represent set cardinality. A common approach is to use area-proportional Euler diagrams but linear diagrams can exploit length-proportional straight-lines for the same purpose. Another common approach is to use numerical annotations. We first conducted two empirical studies, one on Euler diagrams and the other on linear diagrams. These suggest that area-proportional Euler diagrams with numerical annotations and length-proportional linear diagrams without numerical annotations support significantly better task performance. We then conducted a third study to investigate which of these two notations should be used in practice. This suggests that area-proportional Euler diagrams with numerical annotations most effectively supports task performance and so should be used to visualize set cardinalities. However, these studies focused on data that can be visualized reasonably accurately using circles and the results should be taken as valid within that context. Future work needs to determine whether the results generalize both to when circles cannot be used and for other ways of encoding cardinality information., Competing Interests: AD’s employment by Bloomberg does not alter our adherence to PLOS ONE policies on sharing data and materials.

Objective: To investigate trends in the incidence of imported malaria in the UK between 2005 and 2016., Design: Analysis of longitudinal electronic health records (EHRs) in The Health Improvement Network (THIN) primary care database., Setting: UK primary care., Participants: In total, we examined 12,349,003 individuals aged 0 to 99 years., Outcome Measure: The rate of malaria recordings in THIN was calculated per year between 2005 and 2016. Rate ratios exploring differences by age, sex, location of general practice, socioeconomic status and ethnicity were estimated using multivariable Poisson regression., Results: A total of 1,474 individuals with a first diagnosis of malaria were identified in THIN between 2005 and 2016. The incidence of recorded malaria followed a decreasing trend dropping from a rate of 3.33 in 2005 to 1.36 cases per 100,000 person years at risk in 2016. Multivariable Poisson regression showed that adults of working age (20 to 69 years), men, those registered with a general practice in London, higher social deprivation and non-white ethnicity were associated with higher rates of malaria recordings., Conclusion: There has been a decrease in the number of malaria recordings in UK primary care over the past decade. This decrease exceeds the rate of decline reported in national surveillance data; however there are similar associations with age, sex and deprivation. Improved geographic information on the distribution of cases and the potential for automation of case identification suggests that EHRs could provide a complementary role for investigating malaria trends over time., Competing Interests: The authors have declared that no competing interests exist.

Ebola and cholera treatment centres (ETC and CTC) generate considerable quantities of excreta that can further the transmission of disease amongst patients and health workers. Therefore, approaches for the safe handling, containment and removal of excreta within such settings are needed to minimise the likelihood of onward disease transmission. This study compared the performance and suitability of three chlorine-based approaches (0.5% HTH, NaDCC and NaOCl (domestic bleach)) and three lime-based approaches (10%, 20% and 30% Ca(OH)2). The experiments followed recent recommendations for Ebola Treatment Centres. Three excreta matrices containing either raw municipal wastewater, or raw municipal wastewater plus 10% or 20% (w/v) added faecal sludge, were treated in 14 litre buckets at a ratio of 1:10 (chlorine solutions or lime suspensions: excreta matrix). The effects of mixing versus non-mixing and increasing contact time (10 and 30 mins) were also investigated. Bacterial (faecal coliforms (FC) and intestinal enterococci (IE)) and viral (somatic coliphages (SOMPH), F+specific phages (F+PH) and Bacteroides fragilis phages (GB-124PH)) indicators were used to determine the efficacy of each approach. Lime-based approaches provided greater treatment efficacy than chlorine-based approaches, with lime (30% w/v) demonstrating the greatest efficacy (log reductions values, FC = 4.75, IE = 4.16, SOMPH = 2.85, F+PH = 5.13 and GB124PH = 5.41). There was no statistical difference in efficacy between any of the chlorine-based approaches, and the highest log reduction values were: FC = 2.90, IE = 2.36, SOMPH = 3.01, F+PH = 2.36 and GB124PH = 0.74. No statistical difference was observed with respect to contact time for any of the approaches, and no statistical differences were observed with respect to mixing for the chlorine-based approaches. However, statistically significant increases in the efficacy of some lime-based approaches were observed following mixing. These findings provide evidence and practical advice to inform safe handling and containment of excreta and ensure more effective health protection in future emergency settings., Competing Interests: The authors have declared that no competing interests exist.

The ability to produce creative solutions is a key part of expert performance. The aim of this study was to identify the visual search behaviors that underpin superior creative performance of skilled soccer players during simulated 11-a-side match play. Players (N = 44) were required to interact with a representative life-size video-based simulation of attacking situations whilst in possession of the ball. Clips were occluded at a key moment and they were required to play the ball in response to each situation presented. Moreover, they were required to name other additional actions they could execute for each situation. Creative performance on the task was measured using the three criteria of originality, flexibility, and fluency of decisions. Visual search behaviors were examined using a portable eye-movement registration system. Players were classified as most- (n = 11) or least-creative (n = 11) based on their performance on the representative task. The most-creative players produced more appropriate, original, flexible, and fluid decisions compared to least-creative players. The creativity-based differences in judgment were underpinned by differences in visual search strategy. Most-creative players employed a broader attentional focus including more fixations of shorter duration and towards more informative locations of the display compared with least-creative players. Moreover, most-creative players detected teammates in threatening positions earlier in the attacking play. Creative performance is underpinned by different underlying visual processes when compared to less-creative performance, which appears to be crucial in facilitating more creative solutions., Competing Interests: The authors have declared that no competing interests exist.

Globally there are many examples of synanthropic carnivores exploiting growth in urbanisation. As carnivores can come into conflict with humans and are potential vectors of zoonotic disease, assessing densities in suburban areas and identifying factors that influence them are necessary to aid management and mitigation. However, fragmented, privately owned land restricts the use of conventional carnivore surveying techniques in these areas, requiring development of novel methods. We present a method that combines questionnaire distribution to residents with field surveys and GIS, to determine relative density of two urban carnivores in England, Great Britain. We determined the density of: red fox (Vulpes vulpes) social groups in 14, approximately 1km2 suburban areas in 8 different towns and cities; and Eurasian badger (Meles meles) social groups in three suburban areas of one city. Average relative fox group density (FGD) was 3.72 km-2, which was double the estimates for cities with resident foxes in the 1980's. Density was comparable to an alternative estimate derived from trapping and GPS-tracking, indicating the validity of the method. However, FGD did not correlate with a national dataset based on fox sightings, indicating unreliability of the national data to determine actual densities or to extrapolate a national population estimate. Using species-specific clustering units that reflect social organisation, the method was additionally applied to suburban badgers to derive relative badger group density (BGD) for one city (Brighton, 2.41 km-2). We demonstrate that citizen science approaches can effectively obtain data to assess suburban carnivore density, however publicly derived national data sets need to be locally validated before extrapolations can be undertaken. The method we present for assessing densities of foxes and badgers in British towns and cities is also adaptable to other urban carnivores elsewhere. However this transferability is contingent on species traits meeting particular criteria, and on resident responsiveness., Competing Interests: The authors have declared that no competing interests exist.

Children nowadays, particularly in urban areas, are more disconnected from nature than ever before, leading to a large-scale "extinction of experience" with the natural world. Yet there are many potential benefits from children interacting with nature first-hand, including via outdoor learning opportunities. Urban environmental education programmes typically aim to increase awareness and knowledge of local biodiversity and to promote positive attitudes and behaviour towards the environment. However, limited research has been conducted evaluating to what extent these interventions achieve their goals. Here, we explore and assess the influence of a six-week bird-feeding and monitoring project conducted within school grounds ("Bird Buddies") on individual awareness, knowledge and attitudes towards birds by primary school children. This initiative was conducted across eight (sub-)urban primary schools within Brighton and Hove (UK), with 220 participating children (aged 7 to 10). Via pre- and post-project questionnaires, we found evidence for enhanced awareness of local biodiversity, alongside significant gains in both bird identification knowledge and attitudes, which were greatest for children with little prior exposure to nature. Many children expressed a keenness to continue improving the environmental value of their school grounds and to apply elements of the project at home. Student project evaluation scores were consistently positive. Mirroring this, participating teachers endorsed the project as a positive learning experience for their students. One year after the project, several schools were continuing to feed and watch birds. Collectively, the findings from this study highlight the multiple benefits that can be derived from engagement with a relatively short outdoor environmental activity. We therefore believe that such interventions, if repeated locally/longer term, could enhance children's experience with nature in urban settings with combined positive environmental impact.

East Coast Fever (ECF) is the most economically important production disease among traditional beef cattle farmers in Zambia. Despite the disease control efforts by the government, donors, and farmers, ECF cases are increasing. Why does ECF oscillate over time? Can alternative approaches such as systems thinking contribute solutions to the complex ECF problem, avoid unintended consequences, and achieve sustainable results? To answer these research questions and inform the design and implementation of ECF interventions, we qualitatively investigated the influence of dynamic socio-economic, cultural, and ecological factors. We used system dynamics modelling to specify these dynamics qualitatively, and an innovative participatory framework called spatial group model building (SGMB). SGMB uses participatory geographical information system (GIS) concepts and techniques to capture the role of spatial phenomenon in the context of complex systems, allowing stakeholders to identify spatial phenomenon directly on physical maps and integrate such information in model development. Our SGMB process convened focus groups of beef value chain stakeholders in two distinct production systems. The focus groups helped to jointly construct a series of interrelated system dynamics models that described ECF in a broader systems context. Thus, a complementary objective of this study was to demonstrate the applicability of system dynamics modelling and SGMB in animal health. The SGMB process revealed policy leverage points in the beef cattle value chain that could be targeted to improve ECF control. For example, policies that develop sustainable and stable cattle markets and improve household income availability may have positive feedback effects on investment in animal health. The results obtained from a SGMB process also demonstrated that a "one-size-fits-all" approach may not be equally effective in policing ECF in different agro-ecological zones due to the complex interactions of socio-ecological context with important, and often ignored, spatial patterns.

Unlike the fibroblast-like cells formed upon monolayer culture of human mesenchymal stem cells, the natural stem cell niche of the bone marrow and other types of tissues favours the formation of 3-dimensional (3D) cell clusters. The structuring and biological activity of these clusters are regulated by the contacts established by cells with both the basement membrane and neighbour cells and results in their asymmetric division and the consequent maintenance of both a stem population and a committed progeny. The present work demonstrates the potential of a synthetic substrate to mimic the stem cell niche in vitro. The side amino groups of a linear Poly-L-lysine were modified with hyperbranched poly-(ϵ-lysine) peptides, named as dendrons, tethered with the laminin-mimicking sequence, YIGSR. These dendrons presented the YIGSR sequence at the uppermost molecular branching ensuring a controlled spacing of the bioligand. When used to coat the surface of tissue culture plates in a serum-free in vitro cell culture system, the substrate was able to mimic the most relevant features of the basement membrane of the stem cell niche, i.e. the mesh structure of Collagen Type IV and the availability of laminin bioligands relevant to integrin biorecognition. The substrate biomimetic properties were tested for their ability to support the formation of human bone marrow mesenchymal stem cells (hMSCs) 3D spheroids similar to those observed in the natural stem cell niches and their ability to maintain stem cell pluripotency markers. These features were related to the substrate-specific expression and localisation of (i) cell adhesion receptors (i.e. β-integrin and N-cadherin), (ii) transcription factors of pluripotency markers and cytoskeleton protein and (iii) regulators of cell migration throughout cell culture passages 2 to 4. The results clearly demonstrate the formation of 3D spheroids starting from the asymmetric division of substrate-adhering spread cells, the clustering of relevant integrins and the expression of specific intracellular pathways controlling cytoskeleton formation suggesting their potential use as a substrate for the handling of stem cells prior to transplantation procedures.

The loss of unimproved grassland has led to species decline in a wide range of taxonomic groups. Agricultural intensification has resulted in fragmented patches of remnant grassland habitat both across Europe and internationally. The monitoring of remnant patches of this habitat is critically important, however, traditional surveying of large, remote landscapes is a notoriously costly and difficult task. The emergence of small-Unmanned Aircraft Systems (sUAS) equipped with low-cost multi-spectral cameras offer an alternative to traditional grassland survey methods, and have the potential to progress and innovate the monitoring and future conservation of this habitat globally. The aim of this article is to investigate the potential of sUAS for rapid detection of threatened unimproved grassland and to test the use of an Enhanced Normalized Difference Vegetation Index (ENDVI). A sUAS aerial survey is undertaken at a site nationally recognised as an important location for fragmented unimproved mesotrophic grassland, within the south east of England, UK. A multispectral camera is used to capture imagery in the visible and near-infrared spectrums, and the ENDVI calculated and its discrimination performance compared to a range of more traditional vegetation indices. In order to validate the results of analysis, ground quadrat surveys were carried out to determine the grassland communities present. Quadrat surveys identified three community types within the site; unimproved grassland, improved grassland and rush pasture. All six vegetation indices tested were able to distinguish between the broad habitat types of grassland and rush pasture; whilst only three could differentiate vegetation at a community level. The Enhanced Normalized Difference Vegetation Index (ENDVI) was the most effective index when differentiating grasslands at the community level. The mechanisms behind the improved performance of the ENDVI are discussed and recommendations are made for areas of future research and study.

Objective: Hypoxia is known to induce pancreatic beta cell dysfunction and apoptosis. Changes in Programmed Cell Death Gene 4 (PDCD4) expression have previously been linked with beta cell neogenesis and function. Our aim was to investigate the effects of hypoxia on cell viability, PDCD4 expression and subcellular localisation., Methods: MIN6 beta cells and ARIP ductal cells were exposed to 1% (hypoxia) or 21% O2 (normoxia) for 12 or 24 hours. MTT assay, HPI staining, scanning electron microscopy, western blotting and immunocytochemistry analyses were performed to determine the effect of hypoxia on cell viability, morphology and PDCD4 expression., Results: 24 hour exposure to hypoxia resulted in ~70% loss of beta cell viability (P<0.001) compared to normoxia. Both HPI staining and SEM analysis demonstrated beta cell apoptosis and necrosis after 12 hours exposure to hypoxia. ARIP cells also displayed hypoxia-induced apoptosis and altered surface morphology after 24 hours, but no significant growth difference (p>0.05) was observed between hypoxic and normoxic conditions. Significantly higher expression of PDCD4 was observed in both beta cells (P<0.001) and ductal (P<0.01) cells under hypoxic conditions compared to controls. PDCD4 expression was localised to the cytoplasm of both beta cells and ductal cells, with no observed effects of hypoxia, normoxia or serum free conditions on intracellular shuttling of PDCD4., Conclusion: These findings indicate that hypoxia-induced expression of PDCD4 is associated with increased beta cell death and suggests that PDCD4 may be an important factor in regulating beta cell survival during hypoxic stress.

Background: The recent obesity epidemic in children also showed an increase in the prevalence of hypertension. As blood pressure (BP) is associated with (long-chain) polyunsaturated fatty acids (LC PUFA), genetic variation in desaturase enzymes being involved in the synthesis of LC PUFA may be associated with BP. This study aimed to investigate the direct effects (independent of mediating variables) and indirect effects (mediated through intermediate variables) of a common variant in the FADS1 gene, rs174546, known to affect delta-5 desaturase (D5D) activity on PUFA level, body mass index (BMI) and BP., Methods: A subsample of the IDEFICS (Identification and prevention of dietary- and lifestyle-induced health effects in children and infants) baseline survey including 520 children aged 2 to <10 years from six European countries was included. The association between rs174546 (T

Heat treatment was one of the first transformative technologies in the southern African Middle Stone Age (MSA), with many studies in the Cape coastal zone of South Africa identifying it as an essential step in the preparation of silcrete prior to its use in stone tool manufacture. To date, however, no studies have investigated whether heat treatment is necessary for all silcrete types, and how geographically widespread heat treatment was in the subcontinent. The aim of this study is to investigate experimentally whether heat treatment continued further north into the Kalahari Desert of Botswana and northernmost South Africa, the closest area with major silcrete outcrops to the Cape. For this we analyse the thermal transformations of silcrete from both regions, proposing a comprehensive model of the chemical, crystallographic and 'water'-related processes taking place upon heat treatment. For the first time, we also explore the mobility of minor and trace elements during heat treatment and introduce a previously undescribed mechanism-steam leaching-causing depletion of a limited number of elements. The results of this comparative study reveal the Cape and Kalahari silcrete to respond fundamentally differently to heat treatment. While the former can be significantly improved by heat, the latter is deteriorated in terms of knapping quality. These findings have important implications for our understanding of the role of fire as a technical solution in MSA stone tool knapping, and for the extension of its use in southern Africa. Silcrete heat treatment-at least in the form we understand it today-may have been a strictly regional phenomenon, confined to a narrow zone along the west and south coast of the Cape. On the basis of our findings, silcrete heat treatment should not be added as a new trait on the list of behaviours that characterise the MSA of the southern African subcontinent.

Objective: Anticipation of opponent actions, through the use of advanced (i.e., pre-event) kinematic information, can be trained using video-based temporal occlusion. Typically, this involves isolated opponent skills/shots presented as trials in a random order. However, two different areas of research concerning representative task design and contextual (non-kinematic) information, suggest this structure of practice restricts expert performance. The aim of this study was to examine the effect of a sequential structure of practice during video-based training of anticipatory behavior in tennis, as well as the transfer of these skills to the performance environment., Methods: In a pre-practice-retention-transfer design, participants viewed life-sized video of tennis rallies across practice in either a sequential order (sequential group), in which participants were exposed to opponent skills/shots in the order they occur in the sport, or a non-sequential (non-sequential group) random order., Results: In the video-based retention test, the sequential group was significantly more accurate in their anticipatory judgments when the retention condition replicated the sequential structure compared to the non-sequential group. In the non-sequential retention condition, the non-sequential group was more accurate than the sequential group. In the field-based transfer test, overall decision time was significantly faster in the sequential group compared to the non-sequential group., Conclusion: Findings highlight the benefits of a sequential structure of practice for the transfer of anticipatory behavior in tennis. We discuss the role of contextual information, and the importance of representative task design, for the testing and training of perceptual-cognitive skills in sport.

Background and Aims: Neuromedin U (NMU) is a hypothalamic neuropeptide with important roles in several metabolic processes, recently suggested as potential therapeutic target for obesity. We analysed the associations between NMU gene variants and haplotypes and body mass index (BMI) in a large sample of European children., Methods and Results: From a large European multi-center study on childhood obesity, 4,528 children (2.0-9.9 years, mean age 6.0±1.8 SD; boys 52.2%) were randomly selected, stratifying by age, sex and country, and genotyped for tag single nucleotide polymorphisms (SNPs; rs6827359, T:C; rs12500837, T:C; rs9999653,C:T) of NMU gene, then haplotypes were inferred. Regression models were applied to estimate the associations between SNPs or haplotypes and BMI as well as other anthropometric measures. BMI was associated with all NMU SNPs (p<0.05). Among five haplotypes inferred, the haplotype carrying the minor alleles (CCT, frequency = 22.3%) was the only associated with lower BMI values (beta = -0.16, 95%CI:-0.28,-0.04, p = 0.006; z-score, beta = -0.08, 95%CI:-0.14,-0.01, p = 0.019) and decreased risk of overweight/obesity (OR = 0.81, 95%CI:0.68,0.97, p = 0.020) when compared to the most prevalent haplotype (codominant model). Similar significant associations were also observed using the same variables collected after two years' time (BMI, beta = -0.25, 95%CI:-0.41,-0.08, p = 0.004; z-score, beta = -0.10, 95%CI:-0.18,-0.03, p = 0.009; overweight/obesity OR = 0.81, 95%CI:0.66,0.99, p = 0.036). The association was age-dependent in girls (interaction between CCT haplotypes and age, p = 0.008), more evident between 7 and 9 years of age. The CCT haplotype was consistently associated with lower levels of fat mass, skinfold thickness, hip and arm circumferences both at T0 and at T1, after adjustment for multiple testing (FDR-adjusted p<0.05)., Conclusions: This study shows an association between a NMU haplotype and anthropometric indices, mainly linked to fat mass, which appears to be age- and sex-specific in children. Genetic variations within or in linkage with this haplotype should be investigated to identify functional variants responsible for the observed phenotypic variation.

There is contradictory evidence surrounding the role of critical cues in the successful anticipation of penalty kicks in soccer. In the current study, skilled and less-skilled soccer goalkeepers were required to anticipate when viewing penalty kicks that were both spatially (full body; hip region) and temporally (-160 ms, -80 ms before, foot-ball contact) occluded. The skilled group outperformed the less-skilled group in all conditions. Participants performed better in the full body condition when compared to hip region condition. Performance in the hip only condition was significantly better than chance for the skilled group across all occlusion conditions. However, the less-skilled group were no better than chance in the hip condition for the early occlusion points when predicting direction and height. Later temporal occlusion conditions were associated with increased performance both in the correct response and correct direction analyses, but not for correct height. These data suggest that postural information solely from the hip region may be used by skilled goalkeepers to make accurate predictions of penalty kick direction, however, information from other sources are needed in order to make predictions of height. Findings demonstrate how the importance of anticipation cues evolve over time, which has implications for the design of training programs to enhance perceptual-cognitive skill., Competing Interests: The authors have declared that no competing interests exist.

Run-of-river (ROR) hydroelectric power (HEP) schemes are often presumed to be less ecologically damaging than large-scale storage HEP schemes. However, there is currently limited scientific evidence on their ecological impact. The aim of this article is to investigate the effects of ROR HEP schemes on communities of invertebrates in temperate streams and rivers, using a multi-site Before-After, Control-Impact (BACI) study design. The study makes use of routine environmental surveillance data collected as part of long-term national and international monitoring programmes at 22 systematically-selected ROR HEP schemes and 22 systematically-selected paired control sites. Five widely-used family-level invertebrate metrics (richness, evenness, LIFE, E-PSI, WHPT) were analysed using a linear mixed effects model. The analyses showed that there was a statistically significant effect (p<0.05) of ROR HEP construction and operation on the evenness of the invertebrate community. However, no statistically significant effects were detected on the four other metrics of community composition. The implications of these findings are discussed in this article and recommendations are made for best-practice study design for future invertebrate community impact studies., Competing Interests: This research was co-funded by the Natural Environment Research Council (http://www.nerc.ac.uk/) and the Environment Agency (https://www.gov.uk/government/organisations/environment-agency) under grant reference NE/M019810/1. Only GSB received the funding for this work. The Environment Agency had a role in the original collection of the routine surveillance monitoring data used in this study, though it was not collected specifically for the purposes of this study. The study was designed by GSB and it was his decision to publish the work. HGO (an employee of the Environment Agency funding body) did contribute towards the preparation of the manuscript. JCG is employed by Precima Inc. (https://www.precima.com/). The funder provided support in the form of salaries for authors [JCG], but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. This commercial affiliation does not alter our adherence to PLOS ONE policies on sharing data and materials(as detailed online in our guide for authors http://www.PLOSone.org/static/editorial.action#competing). The specific roles of these authors are articulated in the ‘author contributions’ section.

The World Health Organisation Quality of Life (WHOQOL) questionnaires are widely used around the world and can claim strong cross-cultural validity due to their development in collaboration with international field centres. To enhance conceptual equivalence of quality of life across cultures, optional national items are often developed for use alongside the core instrument. The present study outlines the development of national items for the New Zealand WHOQOL-BREF. Focus groups with members of the community as well as health experts discussed what constitutes quality of life in their opinion. Based on themes extracted of aspects not contained in the existing WHOQOL instrument, 46 candidate items were generated and subsequently rated for their importance by a random sample of 585 individuals from the general population. Applying importance criteria reduced these items to 24, which were then sent to another large random sample (n = 808) to be rated alongside the existing WHOQOL-BREF. A final set of five items met the criteria for national items. Confirmatory factor analysis identified four national items as belonging to the psychological domain of quality of life, and one item to the social domain. Rasch analysis validated these results and generated ordinal-to-interval conversion algorithms to allow use of parametric statistics for domain scores with and without national items., Competing Interests: The authors have declared that no competing interests exist.

The potential environmental impacts of large-scale storage hydroelectric power (HEP) schemes have been well-documented in the literature. In Europe, awareness of these potential impacts and limited opportunities for politically-acceptable medium- to large-scale schemes, have caused attention to focus on smaller-scale HEP schemes, particularly run-of-river (ROR) schemes, to contribute to meeting renewable energy targets. Run-of-river HEP schemes are often presumed to be less environmentally damaging than large-scale storage HEP schemes. However, there is currently a lack of peer-reviewed studies on their physical and ecological impact. The aim of this article was to investigate the effects of ROR HEP schemes on communities of fish in temperate streams and rivers, using a Before-After, Control-Impact (BACI) study design. The study makes use of routine environmental surveillance data collected as part of long-term national and international monitoring programmes at 23 systematically-selected ROR HEP schemes and 23 systematically-selected paired control sites. Six area-normalised metrics of fish community composition were analysed using a linear mixed effects model (number of species, number of fish, number of Atlantic salmon-Salmo salar, number of >1 year old Atlantic salmon, number of brown trout-Salmo trutta, and number of >1 year old brown trout). The analyses showed that there was a statistically significant effect (p<0.05) of ROR HEP construction and operation on the number of species. However, no statistically significant effects were detected on the other five metrics of community composition. The implications of these findings are discussed in this article and recommendations are made for best-practice study design for future fish community impact studies.

Consistent individual differences in animal performance drive individual fitness under variable environmental conditions and provide the framework through which natural selection can operate. Underlying this concept is the assumption that individuals will display consistent levels of performance in fitness-related traits and interest has focused on individual variation and broad sense repeatability in a range of behavioural and physiological traits. Despite playing a central role in maintenance and growth, and with considerable inter-individual variation documented, broad sense repeatability in rates of protein synthesis has not been assessed. In this study we show for the first time that juvenile flounder Platichthys flesus reared under controlled environmental conditions on the same plane of nutrition for 46 days maintain consistent whole-animal absolute rates of protein synthesis (As). By feeding meals containing 15N-labelled protein and using a stochastic end-point model, two non-terminal measures of protein synthesis were made 32 days apart (d14 and d46). As values (mass-corrected to a standard mass of 12 g) showed 2- to 3-fold variation between individuals on d14 and d46 but individuals showed similar As values on both days with a broad sense repeatability estimate of 0.684 indicating significant consistency in physiological performance under controlled experimental conditions. The use of non-terminal methodologies in studies of animal ecophysiology to make repeat measures of physiological performance enables known individuals to be tracked across changing conditions. Adopting this approach, repeat measures of protein synthesis under controlled conditions will allow individual ontogenetic changes in protein metabolism to be assessed to better understand the ageing process and to determine individual physiological adaptive capacity, and associated energetic costs of adaptation, to global environmental change.

Aim: To appraise the Diabetes Self-Management Questionnaire (DSMQ)'s measurement of diabetes self-management as a statistical predictor of glycaemic control relative to the widely used SDSCA., Methods: 248 patients with type 1 diabetes and 182 patients with type 2 diabetes were cross-sectionally assessed using the two self-report measures of diabetes self-management DSMQ and SDSCA; the scales were used as competing predictors of HbA1c. We developed a structural equation model of self-management as measured by the DSMQ and analysed the amount of variation explained in HbA1c; an analogue model was developed for the SDSCA., Results: The structural equation models of self-management and glycaemic control showed very good fit to the data. The DSMQ's measurement of self-management showed associations with HbA1c of -0.53 for type 1 and -0.46 for type 2 diabetes (both P < 0.001), explaining 21% and 28% of variation in glycaemic control, respectively. The SDSCA's measurement showed associations with HbA1c of -0.14 (P = 0.030) for type 1 and -0.31 (P = 0.003) for type 2 diabetes, explaining 2% and 10% of glycaemic variation. Predictive power for glycaemic control was significantly higher for the DSMQ (P < 0.001)., Conclusions: This study supports the DSMQ as the preferred tool when analysing self-reported behavioural problems related to reduced glycaemic control. The scale may be useful for clinical assessments of patients with suboptimal diabetes outcomes or research on factors affecting associations between self-management behaviours and glycaemic control.

There are strong genetic components to cardiorespiratory fitness and its response to exercise training. It would be useful to understand the differences in the genomic profile of highly trained endurance athletes of world class caliber and sedentary controls. An international consortium (GAMES) was established in order to compare elite endurance athletes and ethnicity-matched controls in a case-control study design. Genome-wide association studies were undertaken on two cohorts of elite endurance athletes and controls (GENATHLETE and Japanese endurance runners), from which a panel of 45 promising markers was identified. These markers were tested for replication in seven additional cohorts of endurance athletes and controls: from Australia, Ethiopia, Japan, Kenya, Poland, Russia and Spain. The study is based on a total of 1520 endurance athletes (835 who took part in endurance events in World Championships and/or Olympic Games) and 2760 controls. We hypothesized that world-class athletes are likely to be characterized by an even higher concentration of endurance performance alleles and we performed separate analyses on this subsample. The meta-analysis of all available studies revealed one statistically significant marker (rs558129 at GALNTL6 locus, p = 0.0002), even after correcting for multiple testing. As shown by the low heterogeneity index (I2 = 0), all eight cohorts showed the same direction of association with rs558129, even though p-values varied across the individual studies. In summary, this study did not identify a panel of genomic variants common to these elite endurance athlete groups. Since GAMES was underpowered to identify alleles with small effect sizes, some of the suggestive leads identified should be explored in expanded comparisons of world-class endurance athletes and sedentary controls and in tightly controlled exercise training studies. Such studies have the potential to illuminate the biology not only of world class endurance performance but also of compromised cardiac functions and cardiometabolic diseases.

Introduction: The characterization of the hyperbolic power-time (P-tlim) relationship using a two-parameter model implies that exercise tolerance above the asymptote (Critical Power; CP), i.e. within the severe intensity domain, is determined by the curvature (W') of the relationship., Purposes: The purposes of this study were (1) to test whether the amount of work above CP (W>CP) remains constant for varied work rate experiments of high volatility change and (2) to ascertain whether W' determines exercise tolerance within the severe intensity domain., Methods: Following estimation of CP (208 ± 19 W) and W' (21.4 ± 4.2 kJ), 14 male participants (age: 26 ± 3; peak VO2: 3708 ± 389 ml.min(-1)) performed two experimental trials where the work rate was initially set to exhaust 70% of W' in 3 ('THREE') or 10 minutes ('TEN') before being subsequently dropped to CP plus 10 W., Results: W>CP for TEN (104 ± 22% W') and W' were not significantly different (P>0.05) but lower than W>CP for THREE (119 ± 17% W', P<0.05). For both THREE (r = 0.71, P<0.01) and TEN (r = 0.64, P<0.01), a significant bivariate correlation was found between W' and tlim., Conclusion: W>CP and tlim can be greater than predicted by the P-tlim relationship when a decrement in the work rate of high-volatility is applied. Exercise tolerance can be enhanced through a change in work rate within the severe intensity domain. W>CP is not constant.

Few studies have explored the factors associated with long-term maintenance of exercise following cardiac rehabilitation. The present study used auto-photography and interviews to explore the factors that influence motivation and continued participation in physical activity among post cardiac rehabilitation patients. Twenty-three semi-structured interviews were conducted alongside participant-selected photographs or drawings with participants that had continued participation in physical activity for at least two years following the cardiac rehabilitation programme. Participants were recruited from circuit training classes in East Sussex in the UK. Thematic content analysis revealed seven main themes: fear of death and ill health avoidance, critical incidents, overcoming aging, social influences, being able to enjoy life, provision of routine and structure, enjoyment and psychological well-being. Fear of death, illness avoidance, overcoming aging, and being able to enjoy life were powerful motives for continued participation in exercise. The social nature of the exercise class was also identified as a key facilitator of continued participation. Group-based exercise suited those that continued exercise participation post cardiac rehabilitation and fostered adherence.

Chimpanzees of the Sonso community, Budongo Forest, Uganda were observed eating clay and drinking clay-water from waterholes. We show that clay, clay-rich water, and clay obtained with leaf sponges, provide a range of minerals in different concentrations. The presence of aluminium in the clay consumed indicates that it takes the form of kaolinite. We discuss the contribution of clay geophagy to the mineral intake of the Sonso chimpanzees and show that clay eaten using leaf sponges is particularly rich in minerals. We show that termite mound soil, also regularly consumed, is rich in minerals. We discuss the frequency of clay and termite soil geophagy in the context of the disappearance from Budongo Forest of a formerly rich source of minerals, the decaying pith of Raphia farinifera palms.

Runners are often categorized as forefoot, midfoot or rearfoot strikers, but how much and why do individuals vary in foot strike patterns when running on level terrain? This study used general linear mixed-effects models to explore both intra- and inter-individual variations in foot strike pattern among 48 Kalenjin-speaking participants from Kenya who varied in age, sex, body mass, height, running history, and habitual use of footwear. High speed video was used to measure lower extremity kinematics at ground contact in the sagittal plane while participants ran down 13 meter-long tracks with three variables independently controlled: speed, track stiffness, and step frequency. 72% of the habitually barefoot and 32% of the habitually shod participants used multiple strike types, with significantly higher levels of foot strike variation among individuals who ran less frequently and who used lower step frequencies. There was no effect of sex, age, height or weight on foot strike angle, but individuals were more likely to midfoot or forefoot strike when they ran on a stiff surface, had a high preferred stride frequency, were habitually barefoot, and had more experience running. It is hypothesized that strike type variation during running, including a more frequent use of forefoot and midfoot strikes, used to be greater before the introduction of cushioned shoes and paved surfaces.

Airway mucin secretion studies have focused on goblet cell responses to exogenous agonists almost to the exclusion of baseline mucin secretion (BLMS). In human bronchial epithelial cell cultures (HBECCs), maximal agonist-stimulated secretion exceeds baseline by ~3-fold as measured over hour-long periods, but mucin stores are discharged completely and require 24 h for full restoration. Hence, over 24 h, total baseline exceeds agonist-induced secretion by several-fold. Studies with HBECCs and mouse tracheas showed that BLMS is highly sensitive to mechanical stresses. Harvesting three consecutive 1 h baseline luminal incubations with HBECCs yielded equal rates of BLMS; however, lengthening the middle period to 72 h decreased the respective rate significantly, suggesting a stimulation of BLMS by the gentle washes of HBECC luminal surfaces. BLMS declined exponentially after washing HBECCs (t1/2 = 2.75 h), to rates approaching zero. HBECCs exposed to low perfusion rates exhibited spike-like increases in BLMS when flow was jumped 5-fold: BLMS increased >4 fold, then decreased within 5 min to a stable plateau at 1.5-2-fold over control. Higher flow jumps induced proportionally higher BLMS increases. Inducing mucous hyperplasia in HBECCs increased mucin production, BLMS and agonist-induced secretion. Mouse tracheal BLMS was ~6-fold higher during perfusion, than when flow was stopped. Munc13-2 null mouse tracheas, with their defect of accumulated cellular mucins, exhibited similar BLMS as WT, contrary to predictions of lower values. Graded mucous metaplasia induced in WT and Munc13-2 null tracheas with IL-13, caused proportional increases in BLMS, suggesting that naïve Munc13-2 mouse BLMS is elevated by increased mucin stores. We conclude that BLMS is, [i] a major component of mucin secretion in the lung, [ii] sustained by the mechanical activity of a dynamic lung, [iii] proportional to levels of mucin stores, and [iv] regulated differentially from agonist-induced mucin secretion.