The macroevolutionary singularity of snakes.

Snakes and lizards (Squamata) represent a third of terrestrial vertebrates and exhibit spectacular innovations in locomotion, feeding, and sensory processing. However, the evolutionary drivers of this radiation remain poorly known. We infer potential causes and ultimate consequences of squamate macroevolution by combining individual-based natural history observations (>60,000 animals) with a comprehensive time-calibrated phylogeny that we anchored with genomic data (5400 loci) from 1018 species. Due to shifts in the dynamics of speciation and phenotypic evolution, snakes have transformed the trophic structure of animal communities through the recurrent origin and diversification of specialized predatory strategies. Squamate biodiversity reflects a legacy of singular events that occurred during the early history of snakes and reveals the impact of historical contingency on vertebrate biodiversity.

Virtual endocasts of Clevosaurus brasiliensis and the tuatara: Rhynchocephalian neuroanatomy and the oldest endocranial record for Lepidosauria.

Understanding the origins of the vertebrate brain is fundamental for uncovering evolutionary patterns in neuroanatomy. Regarding extinct species, the anatomy of the brain and other soft tissues housed in endocranial spaces can be approximated by casts of these cavities (endocasts). The neuroanatomical knowledge of Rhynchocephalia, a reptilian clade exceptionally diverse in the early Mesozoic, is restricted to the brain of its only living relative, Sphenodon punctatus, and unknown for fossil species. Here, we describe the endocast and the reptilian encephalization quotient (REQ) of the Triassic rhynchocephalian Clevosaurus brasiliensis and compare it with an ontogenetic series of S. punctatus. To better understand the informative potential of endocasts in Rhynchocephalia, we also examine the brain-endocast relationship in S. punctatus. We found that the brain occupies 30% of its cavity, but the latter recovers the general shape and length of the brain. The REQ of C. brasiliensis (0.27) is much lower than S. punctatus (0.84-1.16), with the tuatara being close to the mean for non-avian reptiles. The endocast of S. punctatus is dorsoventrally flexed and becomes more elongated throughout ontogeny. The endocast of C. brasiliensis is mostly unflexed and tubular, possibly representing a more plesiomorphic anatomy in relation to S. punctatus. Given the small size of C. brasiliensis, the main differences may result from allometric and heterochronic phenomena, consistent with suggestions that S. punctatus shows peramorphic anatomy compared to Mesozoic rhynchocephalians. Our results highlight a previously undocumented anatomical diversity among rhynchocephalians and provide a framework for future neuroanatomical comparisons among lepidosaurs.

Therapeutic games to reduce anxiety and depression in young people: A systematic review and exploratory meta-analysis of their use and effectiveness.

OBJECTIVE: The development of serious games for mental wellbeing is a topic of growing interest. The increase in acceptance of games as a mainstream entertainment medium combined with the immersive qualities of games provides opportunities for meaningful support and intervention in mental wellbeing. METHOD: We conducted a systematic review and exploratory meta-analysis to examine if aspects of the interventions influenced outcomes as measured via overall effect sizes. We employed a multilevel meta-analytic approach to accommodate the interdependency of effect sizes (18 effect sizes from 14 studies, with 2027 participants). RESULTS: Overall, the main effect for gaming interventions on any outcome variable was small to medium sized, d = .35 (confidence interval [.23, 47], p < .001). Results revealed that the only significant moderator was the nature of the intervention. Specifically, only interventions that included a rational emotional behavioural focus significantly predicted an improvement in depression and/or anxiety in participants. CONCLUSION: The findings reveal promising effects for therapeutic games for mental health, but replications are needed, alongside the addressing of methodological and procedural concerns.

Development of the ARENA training programme for resilient performance in defense and security settings.

Defense and Security Personnel (DSP) often have to operate in the presence of stressful demands. Prior research has identified factors and processes associated with DSP being able to perform resiliently in demanding situations and settings. The aim of the present study was to develop a resilient performance training programme for UK defense and security operators. An intervention mapping (IM) method was used to guide the development of the programme. Typically, IM follows six sequential phases. In the present work, these phases were shaped by insights from prior research (e.g. systematic review and end user interviews), the input of a dedicated working group (N = 13) and from practitioner focus groups. During the IM process, the importance of programme flexibility was emphasized by practitioners. As such, the enAbling REsilieNt performAnce (ARENA) training programme was designed to be agile and include both face-to-face training and online learning modules. Theoretical behavior change principles, closely aligned to findings of earlier work on resilient defense and security performance, were used to underpin programme content and delivery. Future research should seek to gather data on the impact of the ARENA programme, in the targeted biological, psychological and social factors that previously been associated with resilient performances.

Profiles of resilient psychosocial function during three isolated ski expeditions in the High Arctic.

To successfully complete a Polar expedition individuals and teams must respond resiliently to the environmental, psychological, and social demands they face. In this study we examined profiles of resilient function in seven people from three expeditions in the High Arctic. Using a structured daily diary, participants reported on experiences of physical health (morning and evening), affect, team cohesion, performance, and potential explanatory factors including sleep, demand appraisals, events, and coping strategies. Notable intra- and inter-individual variability was observed in daily reports and all profiles could be interpreted as representing resilient function. A number of significant relationships were found between markers of resilient physical and psychosocial function and potential explanatory variables. For example, there was much more daily variability in an individual's reporting of positive affect than prior research might imply, and what prior research designs could capture. Further, while negative affect tended to remain low and stable, our findings reveal that even minor and infrequent increases in negative emotions were significantly associated with other variables in the network. Finally, across the expedition period individual coping resources consistently exceeded demands, suggesting that individuals viewed the expedition as a challenge and not a threat. More broadly, these findings inform efforts to monitor, and maintain resilience when operating in Polar and other extreme settings.

Swab pooling enables rapid expansion of high-throughput capacity for SARS-CoV-2 community testing.

BACKGROUND: The challenges of rapid upscaling of testing capacity were a major lesson from the COVID-19 pandemic response. The need for process adjustments in high-throughput testing laboratories made sample pooling a challenging option to implement. OBJECTIVE: This study aimed to evaluate whether pooling samples at source (swab pooling) was as effective as qRT-PCR testing of individuals in identifying cases of SARS-CoV-2 in real-world community testing conditions using the same high-throughput pipeline. METHODS: Two cohorts of 10 (Pool10: 1,030 participants and 103 pools) and 6 (Pool6: 1,284 participants and 214 pools) samples per pool were tested for concordance, sensitivity, specificity, and Ct value differences with individual testing as reference. RESULTS: Swab pooling allowed unmodified application of an existing high-throughput SARS-Cov-2 testing pipeline with only marginal loss of accuracy. For Pool10, concordance was 98.1% (95% Confidence interval: 93.3-99.8%), sensitivity was 95.7% (85.5-99.5%), and specificity was 100.0% (93.6-100.0%). For Pool6, concordance was 97.2% (94.0-99.0%), sensitivity was 97.5% (93.7-99.3%), and specificity was 96.4% (87.7-99.6%). Differences of outcomes measure between pool size were not significant. Most positive individual samples, which were not detected in pools, had very low viral concentration. If only individual samples with a viral concentration > 400 copies/ml (i.e. Ct value < 30) were considered positive, the overall sensitivity of pooling increased to 99.5%. CONCLUSION: The study demonstrated high sensitivity and specificity by swab pooling and the immediate capability of high-throughput laboratories to implement this method making it an option in planning of rapid upscaling of laboratory capacity for future pandemics.

Microchromosome fusions underpin convergent evolution of chameleon karyotypes.

Evolutionary shifts in chromosome compositions (karyotypes) are major drivers of lineage and genomic diversification. Fusion of ancestral chromosomes is one hypothesized mechanism for the evolutionary reduction of the total chromosome number, a frequently implied karyotypic shift. Empirical tests of this hypothesis require model systems with variable karyotypes, known chromosome features, and a robust phylogeny. Here we used chameleons, diverse lizards with exceptionally variable karyotypes ($2n=20\text{-}62$), to test whether chromosomal fusions explain the repeated evolution of karyotypes with fewer chromosomes than ancestral karyotypes. Using a multidisciplinary approach including cytogenetic analyses and phylogenetic comparative methods, we found that a model of constant loss through time best explained chromosome evolution across the chameleon phylogeny. Next, we tested whether fusions of microchromosomes into macrochromosomes explained these evolutionary losses using generalized linear models. Multiple comparisons supported microchromosome fusions as the predominant agent of evolutionary loss. We further compared our results to various natural history traits and found no correlations. As such, we infer that the tendency of microchromosomes to fuse was a quality of the ancestral chameleon genome and that the genomic predisposition of ancestors is a more substantive predictor of chromosome change than the ecological, physiological, and biogeographical factors involved in their diversification.

"Make it the done thing": an exploration of attitudes towards rest breaks, productivity and wellbeing while working from home.

OBJECTIVE: Taking regular rest breaks while working positively impacts productivity and wellbeing. While home and hybrid working styles have become a popular choice for employees, the impact of, and perceptions towards, taking breaks while working at home is poorly understood. The current research aimed to explore attitudes towards taking rest breaks while working from home and capture levels of breaks taken, wellbeing and productivity in a sample of UK white-collar workers. METHODS: A mixed method approach was applied where self-report data from an online survey were gathered from individuals (N = 140) from one organisation. Open-ended questions regarding attitudes and perceptions towards rest break behaviours were obtained. Further quantitative measures included the number of breaks taken while working from home, levels of productivity (measured by the Health and performance Presenteeism subscale) and mental wellbeing (measured by the Short Warwick-Edinburgh Mental wellbeing scale). Both quantitative and qualitative analysis approaches were applied. RESULTS: Qualitative responses indicated two overarching themes (1) Personal and (2) Organisational sat above four further themes including Movement outside, Structure of home working, Home environment and Digital presence. Additionally, quantitative findings indicated that the number of breaks taken outside was associated with positive changes in wellbeing. CONCLUSION: Employers could aim to support employees working from home in taking outside breaks through flexible working patterns, authentic leadership, and a change in company social norms around break behaviours. Such organisational changes could help to improve workforce productivity and wellbeing.

Conservative versus Surgical Management of Fifth Metatarsal Diaphyseal Fractures: A Retrospective Review.

BACKGROUND: Historically, distal fifth metatarsal diaphyseal fractures have been treated with conservative management, with only limited research evaluating surgical treatment of these fractures. This study was performed to compare surgical versus conservative treatment of distal fifth metatarsal diaphyseal fractures in athletes and nonathletes. METHODS: A retrospective review of 53 patients with surgical or conservative treatment of isolated fifth metatarsal diaphyseal fractures was performed. Data recorded included age, sex, tobacco use, diagnosis of diabetes mellitus, time to clinical union, time to radiographic union, athletic versus nonathletic status, time to return to full activity, surgical fixation method, and complications. RESULTS: Patients treated surgically had a mean clinical union time of 8.2 weeks, radiographic union time of 13.5 weeks, and return to activity time of 12.9 weeks. Patients treated conservatively had a mean clinical union time of 16.3 weeks, radiographic union time of 25.2 weeks, and return to activity time of 20.7 weeks. Delayed unions and nonunions occurred in 27.0% of patients (10 of 37) treated conservatively and in none in the surgical group. CONCLUSIONS: Surgical treatment significantly decreased time to radiographic union, clinical union, and return to activity by an average of 8 weeks compared with conservative treatment. We suggest that surgical treatment of distal fifth metatarsal fractures is a viable option that may significantly decrease the patient's time to clinical union, radiographic union, and return to activity.

Multiple pathways to herbivory underpinned deep divergences in ornithischian evolution.

The extent to which evolution is deterministic is a key question in biology,1,2,3,4,5,6,7,8,9 with intensive debate on how adaptation6,10,11,12,13 and constraints14,15,16 might canalize solutions to ecological challenges.4,5,6 Alternatively, unique adaptations1,9,17 and phylogenetic contingency1,3,18 may render evolution fundamentally unpredictable.3 Information from the fossil record is critical to this debate,1,2,11 but performance data for extinct taxa are limited.7 This knowledge gap is significant, as general morphology may be a poor predictor of biomechanical performance.17,19,20 High-fiber herbivory originated multiple times within ornithischian dinosaurs,21 making them an ideal clade for investigating evolutionary responses to similar ecological pressures.22 However, previous biomechanical modeling studies on ornithischian crania17,23,24,25 have not compared early-diverging taxa spanning independent acquisitions of herbivory. Here, we perform finite-element analysis on the skull of five early-diverging members of the major ornithischian clades to characterize morphofunctional pathways to herbivory. Results reveal limited functional convergence among ornithischian clades, with each instead achieving comparable performance, in terms of reconstructed patterns and magnitudes of functionally induced stress, through different adaptations of the feeding apparatus. Thyreophorans compensated for plesiomorphic low performance through increased absolute size, heterodontosaurids expanded jaw adductor muscle volume, ornithopods increased jaw system efficiency, and ceratopsians combined these approaches. These distinct solutions to the challenges of herbivory within Ornithischia underpinned the success of this diverse clade. Furthermore, the resolution of multiple solutions to equivalent problems within a single clade through macroevolutionary time demonstrates that phenotypic evolution is not necessarily predictable, instead arising from the interplay of adaptation, innovation, contingency, and constraints.1,2,3,7,8,9,18.

A systematic review of resilient performance in defence and security settings.

A narrative systematic literature review was conducted to explore resilient performance in defence and security settings. A search strategy was employed across a total of five databases, searching published articles from 2001 onwards that assessed performance and optimal function in relation to resilience, in defence and security personnel. Following narrative synthesis, studies were assessed for quality. Thirty-two articles met inclusion criteria across a range of performance domains, including, but not limited to, course selection, marksmanship, land navigation, and simulated captivity. Some of the key findings included measures of mental toughness, confidence, and a stress-is-enhancing mindset being positively associated with performance outcomes. There was mixed evidence for the predictive value of biomarkers, although there was some support for cortisol, dehydroepiandrosterone sulfate (DHEA-S) and neuropeptide-y (NPY), and vagal reactivity. Interventions to improve resilient performance were focused on mindfulness or general psychological skills, with effects generally clearer on cognitive tasks rather than direct performance outcomes in the field. In sum, no single measure, nor intervention was consistently associated with performance over a range of domains. To inform future work, findings from the present review have been used to develop a framework of resilient performance, with the aim to promote theoretically informed work.

Middle Jurassic fossils document an early stage in salamander evolution.

Salamanders are an important group of living amphibians and model organisms for understanding locomotion, development, regeneration, feeding, and toxicity in tetrapods. However, their origin and early radiation remain poorly understood, with early fossil stem-salamanders so far represented by larval or incompletely known taxa. This poor record also limits understanding of the origin of Lissamphibia (i.e., frogs, salamanders, and caecilians). We report fossils from the Middle Jurassic of Scotland representing almost the entire skeleton of the enigmatic stem-salamander Marmorerpeton. We use computed tomography to visualize high-resolution three-dimensional anatomy, describing morphologies that were poorly characterized in early salamanders, including the braincase, scapulocoracoid, and lower jaw. We use these data in the context of a phylogenetic analysis intended to resolve the relationships of early and stem-salamanders, including representation of important outgroups alongside data from high-resolution imaging of extant species. Marmorerpeton is united with Karaurus, Kokartus, and others from the Middle Jurassic-Lower Cretaceous of Asia, providing evidence for an early radiation of robustly built neotenous stem-salamanders. These taxa display morphological specializations similar to the extant cryptobranchid "giant" salamanders. Our analysis also demonstrates stem-group affinities for a larger sample of Jurassic species than previously recognized, highlighting an unappreciated diversity of stem-salamanders and cautioning against the use of single species (e.g., Karaurus) as exemplars for stem-salamander anatomy. These phylogenetic findings, combined with knowledge of the near-complete skeletal anatomy of Mamorerpeton, advance our understanding of evolutionary changes on the salamander stem-lineage and provide important data on early salamanders and the origins of Batrachia and Lissamphibia.

Clade-wide variation in bite-force performance is determined primarily by size, not ecology.

Performance traits are tightly linked to the fitness of organisms. However, because studies of variation in performance traits generally focus on just one or several closely related species, we are unable to draw broader conclusions about how and why these traits vary across clades. One important performance trait related to many aspects of an animal's life history is bite-force. Here, we use a clade-wide phylogenetic comparative approach to investigate relationships between size, head dimensions and bite-force among lizards and tuatara (lepidosaurs), using the largest bite-force dataset collated to date for any taxonomic group. We test four predictions: that bite-force will be greater in larger species, and for a given body size, bite-force will be greatest in species with acrodont tooth attachment, herbivorous diets, and non-burrowing habits. We show that bite-force is strongly related to body and head size across lepidosaurs and, as predicted, larger species have the greatest bite-forces. Contrary to our other predictions, tooth attachment, diet and habit have little predictive power when accounting for size. Herbivores bite more forcefully simply because they are larger. Our results also highlight priorities for future sampling to further enhance our understanding of broader evolutionary patterns.

Comparative cranial biomechanics in two lizard species: impact of variation in cranial design.

Cranial morphology in lepidosaurs is highly disparate and characterised by the frequent loss or reduction of bony elements. In varanids and geckos, the loss of the postorbital bar is associated with changes in skull shape, but the mechanical principles underlying this variation remain poorly understood. Here, we sought to determine how the overall cranial architecture and the presence of the postorbital bar relate to the loading and deformation of the cranial bones during biting in lepidosaurs. Using computer-based simulation techniques, we compared cranial biomechanics in the varanid Varanus niloticus and the teiid Salvator merianae, two large, active foragers. The overall strain magnitude and distribution across the cranium were similar in the two species, despite lower strain gradients in V. niloticus In S. merianae, the postorbital bar is important for resistance of the cranium to feeding loads. The postorbital ligament, which in varanids partially replaces the postorbital bar, does not affect bone strain. Our results suggest that the reduction of the postorbital bar impaired neither biting performance nor the structural resistance of the cranium to feeding loads in V. niloticus Differences in bone strain between the two species might reflect demands imposed by feeding and non-feeding functions on cranial shape. Beyond variation in cranial bone strain related to species-specific morphological differences, our results reveal that similar mechanical behaviour is shared by lizards with distinct cranial shapes. Contrary to the situation in mammals, the morphology of the circumorbital region, calvaria and palate appears to be important for withstanding high feeding loads in these lizards.

Targeting DNA Damage Response and Replication Stress in Pancreatic Cancer.

BACKGROUND & AIMS: Continuing recalcitrance to therapy cements pancreatic cancer (PC) as the most lethal malignancy, which is set to become the second leading cause of cancer death in our society. The study aim was to investigate the association between DNA damage response (DDR), replication stress, and novel therapeutic response in PC to develop a biomarker-driven therapeutic strategy targeting DDR and replication stress in PC. METHODS: We interrogated the transcriptome, genome, proteome, and functional characteristics of 61 novel PC patient-derived cell lines to define novel therapeutic strategies targeting DDR and replication stress. Validation was done in patient-derived xenografts and human PC organoids. RESULTS: Patient-derived cell lines faithfully recapitulate the epithelial component of pancreatic tumors, including previously described molecular subtypes. Biomarkers of DDR deficiency, including a novel signature of homologous recombination deficiency, cosegregates with response to platinum (P < .001) and PARP inhibitor therapy (P < .001) in vitro and in vivo. We generated a novel signature of replication stress that predicts response to ATR (P < .018) and WEE1 inhibitor (P < .029) treatment in both cell lines and human PC organoids. Replication stress was enriched in the squamous subtype of PC (P < .001) but was not associated with DDR deficiency. CONCLUSIONS: Replication stress and DDR deficiency are independent of each other, creating opportunities for therapy in DDR-proficient PC and after platinum therapy.

Disparities in the analysis of morphological disparity.

Analyses of morphological disparity have been used to characterize and investigate the evolution of variation in the anatomy, function and ecology of organisms since the 1980s. While a diversity of methods have been employed, it is unclear whether they provide equivalent insights. Here, we review the most commonly used approaches for characterizing and analysing morphological disparity, all of which have associated limitations that, if ignored, can lead to misinterpretation. We propose best practice guidelines for disparity analyses, while noting that there can be no 'one-size-fits-all' approach. The available tools should always be used in the context of a specific biological question that will determine data and method selection at every stage of the analysis.

Precision Oncology in Surgery: Patient Selection for Operable Pancreatic Cancer.

OBJECTIVE: We aimed to define preoperative clinical and molecular characteristics that would allow better patient selection for operative resection. BACKGROUND: Although we use molecular selection methods for systemic targeted therapies, these principles are not applied to surgical oncology. Improving patient selection is of vital importance for the operative treatment of pancreatic cancer (pancreatic ductal adenocarcinoma). Although surgery is the only chance of long-term survival, 80% still succumb to the disease and approximately 30% die within 1 year, often sooner than those that have unresected local disease. METHOD: In 3 independent pancreatic ductal adenocarcinoma cohorts (total participants = 1184) the relationship between aberrant expression of prometastatic proteins S100A2 and S100A4 and survival was assessed. A preoperative nomogram based on clinical variables available before surgery and expression of these proteins was constructed and compared to traditional measures, and a postoperative nomogram. RESULTS: High expression of either S100A2 or S100A4 was independent poor prognostic factors in a training cohort of 518 participants. These results were validated in 2 independent patient cohorts (Glasgow, n = 198; Germany, n = 468). Aberrant biomarker expression stratified the cohorts into 3 distinct prognostic groups. A preoperative nomogram incorporating S100A2 and S100A4 expression predicted survival and nomograms derived using postoperative clinicopathological variables. CONCLUSIONS: Of those patients with a poor preoperative nomogram score, approximately 50% of patients died within a year of resection. Nomograms have the potential to improve selection for surgery and neoadjuvant therapy, avoiding surgery in aggressive disease, and justifying more extensive resections in biologically favorable disease.

Research priorities for the COVID-19 pandemic and beyond: A call to action for psychological science.

The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) that has caused the coronavirus disease 2019 (COVID-19) pandemic represents the greatest international biopsychosocial emergency the world has faced for a century, and psychological science has an integral role to offer in helping societies recover. The aim of this paper is to set out the shorter- and longer-term priorities for research in psychological science that will (a) frame the breadth and scope of potential contributions from across the discipline; (b) enable researchers to focus their resources on gaps in knowledge; and (c) help funders and policymakers make informed decisions about future research priorities in order to best meet the needs of societies as they emerge from the acute phase of the pandemic. The research priorities were informed by an expert panel convened by the British Psychological Society that reflects the breadth of the discipline; a wider advisory panel with international input; and a survey of 539 psychological scientists conducted early in May 2020. The most pressing need is to research the negative biopsychosocial impacts of the COVID-19 pandemic to facilitate immediate and longer-term recovery, not only in relation to mental health, but also in relation to behaviour change and adherence, work, education, children and families, physical health and the brain, and social cohesion and connectedness. We call on psychological scientists to work collaboratively with other scientists and stakeholders, establish consortia, and develop innovative research methods while maintaining high-quality, open, and rigorous research standards.