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Abstract Monitoring sleep and activity through wearable devices such as wrist-worn actigraphs has the potential for long-term measurement in the individual’s own environment. Long periods of data collection require a complex approach, including standardized pre-processing and data trimming, and robust algorithms to address non-wear and missing data. In this study, we used a data-driven approach to quality control, pre-processing and analysis of longitudinal actigraphy data collected over the course of 1 year in a sample of 95 participants. We implemented a data processing pipeline using open-source packages for longitudinal data thereby providing a framework for treating missing data patterns, non-wear scoring, sleep/wake scoring, and conducted a sensitivity analysis to demonstrate the impact of non-wear and missing data on the relationship between sleep variables and depressive symptoms. Compliance with actigraph wear decreased over time, with missing data proportion increasing from a mean of 4.8% in the first week to 23.6% at the end of the 12 months of data collection. Sensitivity analyses demonstrated the importance of defining a pre-processing threshold, as it substantially impacts the predictive value of variables on sleep-related outcomes. We developed a novel non-wear algorithm which outperformed several other algorithms and a capacitive wear sensor in quality control. These findings provide essential insight informing study design in digital health research.

Abstract Contrafreeloading—working to access food that could be freely obtained—is rarely exhibited and poorly understood. Based on data from Grey parrots (Psittacus erithacus), researchers proposed a correlation between contrafreeloading and play: that contrafreeloading is more likely when subjects view the task as play. We tested that hypothesis by subjecting a relatively more playful parrot species, the kea (Nestor notabilis), to the same experimental tasks. Experiment 1 presented eight kea with container pairs holding more- or less-preferred free or enclosed food items, and examined three types of contrafreeloading: calculated (working to access preferred food over less-preferred, freely available food); classic (working to access food identical to freely available food); and super (working to access less-preferred food over preferred, freely available food). At the group level, the kea behaved similarly to the Greys: They significantly preferred calculated contrafreeloading, performed classic contrafreeloading at chance, and significantly failed to super contrafreeload. However, overall kea engaged in more contrafreeloading than Greys. Experiment 2 examined a potentially more ecologically relevant task, a choice between shelled and unshelled walnuts. No kea contrafreeloaded for nuts, whereas two of five Greys significantly preferred nut contrafreeloading and one chose at chance. We examine proximate and adaptive explanations for the performances of these differentially playful parrot species to further elucidate the role of play in contrafreeloading.

The genotype of an individual is an important predictor of their immune function, and subsequently, their ability to control or avoid infection and ultimately contribute offspring to the next generation. However, the same genotype, subjected to different intrinsic and/or extrinsic environments, can also result in different phenotypic outcomes, which can be missed in controlled laboratory studies. Natural wildlife populations, which capture both genotypic and environmental variability, provide an opportunity to more fully understand the phenotypic expression of genetic variation. We identified a synonymous polymorphism in the high-affinity Immunoglobulin E (IgE) receptor (GC and non-GC haplotypes) that has sex-dependent effects on immune gene expression, susceptibility to infection, and reproductive success of individuals in a natural population of field voles (Microtus agrestis). We found that the effect of the GC haplotype on the expression of immune genes differed between sexes. Regardless of sex, both pro-inflammatory and anti-inflammatory genes were more highly relatively expressed in individuals with the GC haplotype than individuals without the haplotype. However, males with the GC haplotype showed a stronger signal for pro-inflammatory genes, while females showed a stronger signal for anti-inflammatory genes. Furthermore, we found an effect of the GC haplotype on the probability of infection with a common microparasite, Babesia microti, in females – with females carrying the GC haplotype being more likely to be infected. Finally, we found an effect of the GC haplotype on reproductive success in males – with males carrying the GC haplotype having a lower reproductive success. This is a rare example of a polymorphism whose consequences we are able to follow across immunity, infection, and reproduction for both males and females in a natural population.

Abstract Tooling is associated with complex cognitive abilities, occurring most regularly in large-brained mammals and birds. Among birds, self-care tooling is seemingly rare in the wild, despite several anecdotal reports of this behaviour in captive parrots. Here, we show that Bruce, a disabled parrot lacking his top mandible, deliberately uses pebbles to preen himself. Evidence for this behaviour comes from five lines of evidence: (i) in over 90% of instances where Bruce picked up a pebble, he then used it to preen; (ii) in 95% of instances where Bruce dropped a pebble, he retrieved this pebble, or replaced it, in order to resume preening; (iii) Bruce selected pebbles of a specific size for preening rather than randomly sampling available pebbles in his environment; (iv) no other kea in his environment used pebbles for preening; and (v) when other individuals did interact with stones, they used stones of different sizes to those Bruce preened with. Our study provides novel and empirical evidence for deliberate self-care tooling in a bird species where tooling is not a species-specific behaviour. It also supports claims that tooling can be innovated based on ecological necessity by species with sufficiently domain-general cognition.

Abstract Naïve individuals of some bird species can rapidly solve vertical string-pulling tasks with virtually no errors. This has led to various hypotheses being proposed which suggest that birds mentally simulate the effects of their actions on strings. A competing embodied cognition hypothesis proposes that this behaviour is instead modulated by perceptual-motor feedback loops, where feedback of the reward moving closer acts as an internal motivator for functional behaviours, such as pull-stepping. To date, the kea parrot has produced some of the best performances of any bird species at string-pulling tasks. Here, we tested the predictions of the four leading hypotheses for the cognition underpinning bird string-pulling by presenting kea with a horizontal connectivity task where only one of two loose strings was connected to the reward, both before and after receiving perceptual-motor feedback experience. We find that kea fail the connectivity task both before and after perceptual-motor feedback experience, suggesting not only that kea do not mentally simulate their string-pulling actions, but also that perceptual-motor feedback alone is insufficient in eliciting successful performance in the horizontal connectivity task. This suggests a more complex interplay of cognitive factors underlies this iconic example of animal problem-solving.

Abstract Persistence of wild Pacific oyster, Magallana gigas, also known as Crassostrea gigas, has been increasingly reported across Northern European waters in recent years. While reproduction is inhibited by cold waters, recent warm summer temperature has increased the frequency of spawning events. Although correlation between the increasing abundance of Pacific oyster reefs in Northern European waters and climate change is documented, persistence of wild populations may also be influenced by external recruitment from farmed populations and other wild oyster populations, as well as on competition for resources with aquaculture sites. Our understanding of the combined impact of the spawning frequency, external recruitment, and competition on wild population persistence is limited. This study applied an age-structured model, based on ordinary differential equations, to describe an oyster population under discrete temperature-related dynamics. The impact of more frequent spawning events, external recruitment, and changes in carrying capacity on Pacific oyster density were simulated and compared under theoretical scenarios and two case studies in Southern England. Results indicate that long term persistence of wild oyster populations towards carrying capacity requires a high frequency of spawning events but that in the absence of spawning, external recruitment from farmed populations and other wild oyster populations may act to prevent extinction and increase population density. However, external recruitment sources may be in competition with the wild population so that external recruitment is associated with a reduction in wild population density. The implications of model results are discussed in the context of wild oyster population management.

Introduction Neurodegenerative and psychiatric disorders (NPDs) confer a huge health burden, which is set to increase as populations age. New, remotely delivered diagnostic assessments that can detect early stage NPDs by profiling speech could enable earlier intervention and fewer missed diagnoses. The feasibility of collecting speech data remotely in those with NPDs should be established.Methods and analysis The present study will assess the feasibility of obtaining speech data, collected remotely using a smartphone app, from individuals across three NPD cohorts: neurodegenerative cognitive diseases (n=50), other neurodegenerative diseases (n=50) and affective disorders (n=50), in addition to matched controls (n=75). Participants will complete audio-recorded speech tasks and both general and cohort-specific symptom scales. The battery of speech tasks will serve several purposes, such as measuring various elements of executive control (eg, attention and short-term memory), as well as measures of voice quality. Participants will then remotely self-administer speech tasks and follow-up symptom scales over a 4-week period. The primary objective is to assess the feasibility of remote collection of continuous narrative speech across a wide range of NPDs using self-administered speech tasks. Additionally, the study evaluates if acoustic and linguistic patterns can predict diagnostic group, as measured by the sensitivity, specificity, Cohen’s kappa and area under the receiver operating characteristic curve of the binary classifiers distinguishing each diagnostic group from each other. Acoustic features analysed include mel-frequency cepstrum coefficients, formant frequencies, intensity and loudness, whereas text-based features such as number of words, noun and pronoun rate and idea density will also be used.Ethics and dissemination The study received ethical approval from the Health Research Authority and Health and Care Research Wales (REC reference: 21/PR/0070). Results will be disseminated through open access publication in academic journals, relevant conferences and other publicly accessible channels. Results will be made available to participants on request.Trial registration number NCT04939818.

Abstract Executive function plays a critical role in regulating behaviour. Behaviour which directs attention towards the correct solution leads to increased executive function performance in children, but it is unknown how other animals respond to such scaffolding behaviour. Dogs were presented with an A-not-B detour task. After learning to go through gap A to obtain the reward, the barrier was reversed, and the dogs had to inhibit their learned response and enter through gap B on the opposite side. Failure to do so is known as the perseveration error. In test trials, dogs taking part in one of two scaffolding conditions, a pointing condition, where the experimenter pointed to the new gap, and a demonstration condition, where the experimenter demonstrated the new route, were no less likely to commit the perseveration error than dogs in a control condition with no scaffolding behaviour. Dogs’ lack of responsiveness to scaffolding behaviour provides little support for suggestions that simple social learning mechanisms explains scaffolding behaviour in humans. Instead, our results suggest that the theory of natural pedagogy extends to the development of executive function in humans. This suggests that human children’s predisposition to interpret ostensive-communicative cues as informative may be an innate, species-specific adaptation.

Objectives Paediatric cancer is a leading cause of death for children. Children in low-income and middle-income countries (LMICs) were four times more likely to die than children in high-income countries (HICs). This study aimed to test the hypothesis that the COVID-19 pandemic had affected the delivery of healthcare services worldwide, and exacerbated the disparity in paediatric cancer outcomes between LMICs and HICs.Design A multicentre, international, collaborative cohort study.Setting 91 hospitals and cancer centres in 39 countries providing cancer treatment to paediatric patients between March and December 2020.Participants Patients were included if they were under the age of 18 years, and newly diagnosed with or undergoing active cancer treatment for Acute lymphoblastic leukaemia, non-Hodgkin’s lymphoma, Hodgkin lymphoma, Wilms’ tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas or neuroblastomas, in keeping with the WHO Global Initiative for Childhood Cancer.Main outcome measure All-cause mortality at 30 days and 90 days.Results 1660 patients were recruited. 219 children had changes to their treatment due to the pandemic. Patients in LMICs were primarily affected (n=182/219, 83.1%). Relative to patients with paediatric cancer in HICs, patients with paediatric cancer in LMICs had 12.1 (95% CI 2.93 to 50.3) and 7.9 (95% CI 3.2 to 19.7) times the odds of death at 30 days and 90 days, respectively, after presentation during the COVID-19 pandemic (p

Importance and objectiveThe aim of this pragmatic, embedded, adaptive trial was to measure the effectiveness of the subcutaneous anti-IL-6R antibody sarilumab, when added to an evolving standard of care (SOC), for clinical management of inpatients with moderate to severe COVID-19 disease.DesignTwo-arm, randomized, open-label controlled trial comparing SOC alone to SOC plus sarilumab. The trial used a randomized play-the-winner design and was fully embedded within the electronic health record (EHR) system.Setting5 VA Medical Centers.ParticipantsHospitalized patients with clinical criteria for moderate to severe COVID-19 but not requiring mechanical ventilation, and a diagnostic test positive for SARS-CoV-2.InterventionsSarilumab, 200 or 400 mg subcutaneous injection. SOC was not pre-specified and could vary over time, e.g., to include antiviral or other anti-inflammatory drugs.Main outcomes and measuresThe primary outcome was intubation or death within 14 days of randomization. All data were extracted remotely from the EHR.ResultsAmong 162 eligible patients, 53 consented, and 50 were evaluated for the primary endpoint of intubation or death. This occurred in 5/20 and 1/30 of participants in the sarilumab and SOC arms respectively, with the majority occurring in the initial 9 participants (3/4 in the sarilumab and 1/5 in the SOC) before the sarilumab dose was increased to 400 mg and before remdesivir and dexamethasone were widely adopted. After interim review, the unblinded Data Monitoring Committee recommended that the study be stopped due to concern for safety: a high probability that rates of intubation or death were higher with addition of sarilumab to SOC (92.6%), and a very low probability (3.4%) that sarilumab would be found to be superior.Conclusions and relevanceThis randomized trial of patients hospitalized due to respiratory compromise from COVID-19 but not mechanical ventilation found no benefit from subcutaneous sarilumab when added to an evolving SOC. The numbers of patients and events were too low to allow definitive conclusions to be drawn, but this study contributes valuable information about the role of subcutaneous IL-6R inhibition in the treatment of hospitalized COVID-19 patients. Methods developed and piloted during this trial will be useful in conducting future studies more efficiently.Trial registrationClinicaltrials.gov-NCT04359901; https://clinicaltrials.gov/ct2/show/NCT04359901?cond=NCT04359901&draw=2&rank=1.

Introduction Childhood cancers are a leading cause of non-communicable disease deaths for children around the world. The COVID-19 pandemic may have impacted on global children’s cancer services, which can have consequences for childhood cancer outcomes. The Global Health Research Group on Children’s Non-Communicable Diseases is currently undertaking the first international cohort study to determine the variation in paediatric cancer management during the COVID-19 pandemic, and the short-term to medium-term impacts on childhood cancer outcomes.Methods and analysis This is a multicentre, international cohort study that will use routinely collected hospital data in a deidentified and anonymised form. Patients will be recruited consecutively into the study, with a 12-month follow-up period. Patients will be included if they are below the age of 18 years and undergoing anticancer treatment for the following cancers: acute lymphoblastic leukaemia, Burkitt lymphoma, Hodgkin lymphoma, Wilms tumour, sarcoma, retinoblastoma, gliomas, medulloblastomas and neuroblastomas. Patients must be newly presented or must be undergoing active anticancer treatment from 12 March 2020 to 12 December 2020. The primary objective of the study was to determine all-cause mortality rates of 30 days, 90 days and 12 months. This study will examine the factors that influenced these outcomes. χ2 analysis will be used to compare mortality between low-income and middle-income countries and high-income countries. Multilevel, multivariable logistic regression analysis will be undertaken to identify patient-level and hospital-level factors affecting outcomes with adjustment for confounding factors.Ethics and dissemination At the host centre, this study was deemed to be exempt from ethical committee approval due to the use of anonymised registry data. At other centres, participating collaborators have gained local approvals in accordance with their institutional ethical regulations. Collaborators will be encouraged to present the results locally, nationally and internationally. The results will be submitted for publication in a peer-reviewed journal.

The Caribbean is a genetically diverse region with heterogeneous admixture compositions influenced by local island ecologies, migrations, colonial conflicts, and demographic histories. The Commonwealth of Dominica is a mountainous island in the Lesser Antilles historically known to harbor communities with unique patterns of migration, mixture, and isolation. This community-based population genetic study adds biological evidence to inform post-colonial narrative histories in a Dominican horticultural village. High density single nucleotide polymorphism data paired with a previously compiled genealogy provide the first genome-wide insights on genetic ancestry and population structure in Dominica. We assessed family-based clustering, inferred global ancestry, and dated recent admixture by implementing the fastSTRUCTURE clustering algorithm, modeling graph-based migration with TreeMix, assessing patterns of linkage disequilibrium decay with ALDER, and visualizing data from Dominica with Human Genome Diversity Panel references. These analyses distinguish family-based genetic structure from variation in African, European, and indigenous Amerindian admixture proportions, and analyses of linkage disequilibrium decay estimate admixture dates 5-6 generations (~160 years) ago. African ancestry accounts for the largest mixture components, followed by European and then indigenous components; however, our global ancestry inferences are consistent with previous mitochondrial, Y chromosome, and ancestry marker data from Dominica that show uniquely higher proportions of indigenous ancestry and lower proportions of African ancestry relative to known admixture in other French- and English-speaking Caribbean islands. Our genetic results support local narratives about the community's history and founding, which indicate that newly emancipated people settled in the steep, dense vegetation along Dominica's eastern coast in the mid-19th century. Strong genetic signals of post-colonial admixture and family-based structure highlight the localized impacts of colonial forces and island ecologies in this region, and more data from other groups are needed to more broadly inform on Dominica's complex history and present diversity.

The investigation of prosocial behavior is of particular interest from an evolutionary perspective. Comparisons of prosociality across non-human animal species have, however, so far largely focused on primates, and their interpretation is hampered by the diversity of paradigms and procedures used. Here, we present the first systematic comparison of prosocial behavior across multiple species in a taxonomic group outside the primate order, namely the bird family Corvidae. We measured prosociality in eight corvid species, which vary in the expression of cooperative breeding and colonial nesting. We show that cooperative breeding is positively associated with prosocial behavior across species. Also, colonial nesting is associated with a stronger propensity for prosocial behavior, but only in males. The combined results of our study strongly suggest that both cooperative breeding and colonial nesting, which may both rely on heightened social tolerance at the nest, are likely evolutionary pathways to prosocial behavior in corvids.

Abstract Background Health behaviors directly impact the health of individuals, and populations. Since individuals tend to engage in multiple unhealthy behaviors such as smoking, excessive alcohol use, physical inactivity, and eating an unhealthy diet simultaneously, many large community-based interventions have been implemented to reduce the burden of disease through the modification of multiple health behaviors. Smoking cessation can be particularly challenging as the odds of becoming dependent on nicotine increase with every unhealthy behavior a smoker exhibits. This paper presents a protocol for a rapid realist review which aims to identify factors associated with effectively changing tobacco use and target two or more additional unhealthy behaviors. Methods An electronic literature search will be conducted using the following bibliographic databases: MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, Social Science Abstracts, Social Work Abstracts, and Web of Science. Two reviewers will screen titles and abstracts for relevant research, and the selected full papers will be used to extract data and assess the quality of evidence. Throughout this process, the rapid realist approach proposed by Saul et al., 2013 will be used to refine our initial program theory and identify contextual factors and mechanisms that are associated with successful multiple health behavior change. Discussion This review will provide evidence-based research on the context and mechanisms that may drive the success or failure of interventions designed to support multiple health behavior change. This information will be used to guide curriculum and program development for a government funded project on improving smoking cessation by addressing multiple health behaviors in people in Canada. Systematic review registration PROSPERO CRD42017064430

Resumen: Se presenta el caso de un varón de 74 años intervenido de doble bypass coronario, recambio valvular aórtico y sustitución de aorta ascendente que, a los 10 meses tras la cirugía, comienza con clínica de insuficiencia cardíaca congestiva. A partir de una imagen obtenida mediante ecocardiografía transtorácica, donde se observó el paso de suero fisiológico agitado desde la aorta a cavidades derechas, se realizó el diagnóstico de presunción de un probable pseudoaneurisma sobre la prótesis de aorta ascendente que fistulizaba a cavidades derechas, y que fue confirmado posteriormente por angiotomografía computarizada y resonancia magnética. El paciente fue reintervenido y evolucionó favorablemente.La aparición de una fístula aorto-auricular derecha es una complicación muy poco frecuente tras cirugías sobre la válvula aórtica y aorta ascendente. La ecocardiografía desempeña un papel fundamental en la valoración del paciente con enfermedad cardiovascular, siendo la prueba de imagen de elección para el seguimiento de los pacientes sometidos a recambio valvular. Abstract: Here is reported a clinical case of a 74 year old man who underwent coronary artery bypass grafting, aortic valve replacement and replacement of ascending aorta who, ten months after surgery, presented with congestive heart failure. A transthoracic echocardiogram was performed and showed the passage of bubbles of agitated physiological saline solution from the aorta to the right atrium. Based on these findings a probable pseudoaneurism formation on the prosthesis of ascending aorta that fistulized to right atrium was suspected. It was later confirmed by computerised angiography and magnetic resonante imaging. The patient was re-operated and evolved favourably.The occurrence of an aortic-right atrial fistula represents a rare complication after surgery over the aortic valve and ascending aorta. Echocardiography plays a fundamental role in the assessment of patients with cardiovascular disease being the gold-standard test for the on-going study of patients who have undergone heart valve replacement. Palabras clave: Pseudoaneurisma, Aorta ascendente, Aurícula derecha, Fístula aorto-atrial derecha, Keywords: Pseudoaneurism, Ascending aorta, Right atrium, Aortic right atrial fistula

Abstract Background Alcohol and substance use results in significant human and economic cost globally and is associated with economic costs of £21 billion and £15billion within the UK, respectively, and trends for use are not improving. Pharmacological interventions are well researched, but relapse rates across interventions for substance and alcohol use disorders are as high as 60–90%. Physical activity may offer an alternative or adjunct approach to reducing rates of alcohol and substance use that is associated with few adverse side effects, is easily accessible, and is potentially cost-effective. Through psychological, behavioural, and physiological mechanisms, physical activity may offer benefits in the prevention, reduction, and treatment of alcohol and substance use across the lifespan. Whilst physical activity is widely advocated as offering benefit, no systematic review exists of physical activity (in all forms) and its effects on all levels of alcohol and substance use across all ages to help inform policymakers, service providers, and commissioners. Methods The objectives of this mixed methods systematic review are to describe and evaluate the quantitative and qualitative research obtained by a diverse search strategy on the impact of physical activity and its potential to: 1. Reduce the risk of progression to alcohol and/or substance use (PREVENTION) 2. Support individuals to reduce alcohol and/or substance use for harm reduction (REDUCTION), and 3. Promote abstinence and relapse prevention during and after treatment for an alcohol and/or substance use disorder (TREATMENT). With the input of key stakeholders, we aim to assess how what we know can be translated into policy and practice. Quantitative, qualitative, service evaluations, and economic analyses will be brought together in a final narrative synthesis that will describe the potential benefits of physical activity for whom, in what conditions, and in what form. Discussion This review will provide details of what is known about physical activity and the prevention, reduction, and treatment of alcohol and/or substance use. The synthesised findings will be disseminated to policymakers, service providers, and commissioners in the UK. Systematic review registration PROSPERO number: CRD42017079322 .

The ability to make profitable decisions in natural foraging contexts may be influenced by an additional requirement of tool-use, due to increased levels of relational complexity and additional work-effort imposed by tool-use, compared with simply choosing between an immediate and delayed food item. We examined the flexibility for making the most profitable decisions in a multi-dimensional tool-use task, involving different apparatuses, tools and rewards of varying quality, in 3-5-year-old children, adult humans and tool-making New Caledonian crows (Corvus moneduloides). We also compared our results to previous studies on habitually tool-making orangutans (Pongo abelii) and non-tool-making Goffin's cockatoos (Cacatua goffiniana). Adult humans, cockatoos and crows, but not children and orangutans, did not select a tool when it was not necessary, which was the more profitable choice in this situation. Adult humans, orangutans and cockatoos, but not crows and children, were able to refrain from selecting non-functional tools. By contrast, the birds, but not the primates tested, struggled to attend to multiple variables-where two apparatuses, two tools and two reward qualities were presented simultaneously-without extended experience. These findings indicate: (1) in a similar manner to humans and orangutans, New Caledonian crows and Goffin's cockatoos can flexibly make profitable decisions in some decision-making tool-use tasks, though the birds may struggle when tasks become more complex; (2) children and orangutans may have a bias to use tools in situations where adults and other tool-making species do not.

Freshwater cyanobacteria blooms represent a risk to ecological and human health through induction of anoxia and release of potent toxins; both conditions require water management to mitigate risks. Many cyanobacteria taxa may produce microcystins, a group of toxic cyclic heptapeptides. Understanding the relationships between the abiotic drivers of microcystins and their occurrence would assist in the implementation of targeted, cost-effective solutions to maintain safe drinking and recreational waters. Cyanobacteria and microcystins were measured by flow cytometry and liquid chromatography coupled to tandem mass spectrometry in two interconnected reservoirs varying in age and management regimes, in southern Britain over a 12-month period. Microcystins were detected in both reservoirs, with significantly higher concentrations in the southern lake (maximum concentration >7 µg L−1). Elevated microcystin concentrations were not positively correlated with numbers of cyanobacterial cells, but multiple linear regression analysis suggested temperature and dissolved oxygen explained a significant amount of the variability in microcystin across both reservoirs. The presence of a managed fishery in one lake was associated with decreased microcystin levels, suggestive of top down control on cyanobacterial populations. This study supports the need to develop inclusive, multifactor holistic water management strategies to control cyanobacterial risks in freshwater bodies.

[This corrects the article DOI: 10.1371/journal.pone.0206181.].

The composition of the mammalian gut microbiota can be influenced by a multitude of environmental variables such as diet and infections. Studies investigating the effect of these variables on gut microbiota composition often sample across multiple separate populations and habitat types. In this study we explore how variation in the gut microbiota of the house mouse (Mus musculus domesticus) on the Isle of May, a small island off the east coast of Scotland, is associated with environmental and biological factors. Our study focuses on the effects of environmental variables, specifically trapping location and surrounding vegetation, as well as the host variables sex, age, body weight and endoparasite infection, on the gut microbiota composition across a fine spatial scale in a freely interbreeding population. We found that differences in gut microbiota composition were significantly associated with the trapping location of the host, even across this small spatial scale. Sex of the host showed a weak association with microbiota composition. Whilst sex and location could be identified as playing an important role in the compositional variation of the gut microbiota, 75% of the variation remains unexplained. Whereas other rodent studies have found associations between gut microbiota composition and age of the host or parasite infections, the present study could not clearly establish these associations. We conclude that fine spatial scales are important when considering gut microbiota composition and investigating differences among individuals.

Island biotas have disproportionately influenced the history and development of evolutionary biology, but understanding their genesis and evolution across geological timescales has been hindered by a poor fossil record. Here we augment the insular Eocene (~43 Ma) mammalian fauna known from the Pontide terrane of central Anatolia by describing two new metatherian taxa (stem marsupials) from the Lülük Member of the Uzunçarşıdere Formation in the Orhaniye Basin. Geological and paleontological data indicate that the Pontide terrane was an island on the northern margin of Neotethys during the middle Eocene. Reflecting its geodynamic context in a region of active tectonic convergence, the Eocene Pontide terrane hosted a unique combination of Laurasian and Gondwanan mammals, including an anachronistic radiation of pleuraspidotheriids (archaic ungulates) that went extinct on the European mainland ~13 Ma earlier. Most of the mammalian clades occupying the Pontide terrane colonized it by dispersal across marine barriers rather than being stranded there through vicariance. Endemic radiations of pleuraspidotheriid ungulates and polydolopimorphian metatherians on the Pontide terrane reveal that in situ diversification was an important factor contributing to faunal assembly and evolution. The insular fauna that arose on the Pontide terrane is highly analogous to that of modern Sulawesi, which evolved under strikingly similar geological conditions. Illustrating the ephemeral nature of insular biotas across macroevolutionary timescales, the demise of the Pontide fauna coincided with paleogeographic changes enabling more cosmopolitan taxa to reach it for the first time. The high level of endemism shown by the mammalian fauna of the Uzunçarşıdere Formation eliminates the Pontide terrane as a potential early Eocene dispersal corridor between western Europe and India.

BACKGROUND:The Philippine government has an extensive network of 513 Animal Bite Treatment Centers (ABTCs) to supply rabies post exposure prophylaxis (PEP), reaching over 1 million bite victims in 2016. The network was evaluated using a review of existing national and provincial data, key informant interviews and surveys in sample ABTCs to determine the cost-effectiveness of this network in preventing human rabies deaths. METHODOLOGY AND PRINCIPAL FINDINGS:One urban and one rural ABTC in each of three selected provinces were studied in more detail. PEP delivery generally followed national guidance based on best practices, but there was evidence of operational challenges in supplying all ABTCs with adequate biologics and recently trained staff. Funding was contributed by different levels of government and in some clinics, patients paid for a significant fraction of the total cost. From a health provider perspective including both fixed and variable costs, the average PEP course delivered cost USD 32.91 /patient across urban ABTCs (with higher patient throughput) and USD 57.21 /patient across rural ABTCs. These costs suggests that PEP provision in the Philippines cost USD 37.6 million in 2016, with a cost per life saved of USD 8,290. An analysis of the 2,239 suspected rabies deaths from 2008 to 2016 showed no significant decline, and from 2014-16 an average of 8,534 years of life were lost annually. The incidence of rabies deaths from 2014-16 was not clearly related to the provision of ABTCs (per 100,000 population) or human population density, but deaths were more common in higher income provinces. CONCLUSIONS/SIGNIFICANCE:In the context of comprehensive rabies control (including dog vaccination and public awareness) ways to reduce this high expenditure on PEP should be explored, to most cost-effectively reach the elimination of human rabies deaths. This paper is accompanied by another containing data on the operation of ABTCs network from a patient perspective.

BACKGROUND:The Philippines has built an extensive decentralised network of Animal Bite Treatment Centers (ABTCs) to help bite victims receive timely rabies post-exposure prophylaxis (PEP) at little cost. This study surveyed patients in the community and at ABTCs of three provinces to assess animal bite/scratch incidence, health-seeking behaviour and PEP-related out-of pocket expenses (OOPE). METHODOLOGY AND PRINCIPAL FINDINGS:During community surveys in 90 barangays (neighbourhoods), 53% of households reported at least one animal bite /scratch injury over the past 3 years, similar across urban and rural barangays. Overall bite/scratch incidences in 2016-17 were 67.3, 41.9 and 48.8 per 1,000 population per year for Nueva Vizcaya, Palawan and Tarlac respectively. Incidences were around 50% higher amongst those under 15 years of age, compared to -those older than 15. Household awareness of the nearest ABTCs was generally over 80%, but only 44.9% sought proper medical treatment and traditional remedies were still frequently used. The proportion of patients seeking PEP was not related to the distance or travel time to the nearest ABTC. For those that did not seek medical treatment, most cited a lack of awareness or insufficient funds and almost a third visited a traditional healer. No deaths from bite/scratch injuries were reported. A cohort of 1,105 patients were interviewed at six ABTCs in early 2017. OOPE varied across the ABTCs, from 5.53 USD to 37.83 USD per patient, primarily dependent on the need to pay for immunization if government supplies had run out. Overall, 78% of patients completed the recommended course, and the main reason for non-completion was a lack of time, followed by insufficient funds. Dog observation data revealed that 85% of patients were not truly exposed to rabies, and education in bite prevention might reduce provoked bites and demand for PEP. An accompanying paper details the ABTC network from the health provider's perspective.

Aesop’s Fable tasks—in which subjects drop objects into a water-filled tube to raise the water level and obtain out-of-reach floating rewards —have been used to test for causal understanding of water displacement in both young children and non-human animals. However, a number of alternative explanations for success on these tasks have yet to be ruled out. One hypothesis is that subjects may respond to perceptual-motor feedback: repeating those actions that bring the reward incrementally closer. Here, we devised a novel, forced-choice version of the Aesop’s Fable task to assess whether subjects can solve water displacement tasks when this type of feedback is removed. Subjects had to select only one set of objects, or one type of tube, into which all objects were dropped at once, and the effect the objects had on the water level was visually concealed. In the current experiment, fifty-five 5–9 year old children were tested in six different conditions in which we either varied object properties (floating vs. sinking, hollow vs. solid, large vs. small and too large vs. small objects), the water level (high vs. low) and/or the tube size (narrow vs. wide). We found that children aged 8–9 years old were able to solve most of the water displacement tasks on their first trial, without any opportunity for feedback, suggesting that they mentally simulated the results of their actions before making a choice. Children aged 5–7 years solved two conditions on their first trial (large vs. small objects and high- vs. low-water levels), and learnt to solve most of the remaining conditions over five trials. The developmental pattern shown here is comparable to previous studies using the standard Aesop’s Fable task, where eight year olds are typically successful from their first trial and 5–7 year olds learn to pass over five trials. Thus, our results indicate that children do not depend on perceptual-motor feedback to solve these water displacement tasks. The forced-choice paradigm we describe could be used comparatively to test whether or not non-human animals require visual feedback to solve water displacement tasks.

BACKGROUND:Evidence suggests obesity exerts a negative impact on cognition. Major Depressive Disorder (MDD) is also linked to problems in cognitive functioning. Obesity is highly prevalent in individuals with MDD and is linked to a failure to return to a full level of functioning. The study's objective was to investigate the effect of obesity on cognitive impairment in participants with MDD. METHODS:This study compared cognitive performance in obese individuals with MDD and two control populations (obese individuals without a psychiatric illness and non-obese controls). A standardized battery of neuropsychological tests specifically designed to assess performance in declarative memory, executive functioning, processing speed and attention was administered. Mood ratings, physical measurements, nutritional and health questionnaires were also completed. RESULTS:We observed a consistent pattern across measures of memory, executive functioning, attention and processing speed. Whereas healthy controls performed better than both bariatric groups across the majority of measures administered, bariatric controls tended to outperform bariatric MDD patients. LIMITATIONS:The overall sample size of our study was small and thus largely explorative in nature. However, it provides compelling results (while controlling for extraneous variables such as medication load, nutritional status and common metabolic comordidities) that strongly urges for further investigation and study replication with larger sample sizes. CONCLUSIONS:We found obesity has a subtle impact on cognition in obese individuals, and when obesity is present in individuals with MDD, this impact may be significant. It is important to minimize all modifiable variables that can add to cognitive burden in this population.

[This corrects the article DOI: 10.1371/journal.pone.0169168.].

Cooperation between individuals is one of the defining features of our species. While other animals, such as chimpanzees, elephants, coral trout and rooks also exhibit cooperative behaviours, it is not clear if they think about cooperation in the same way as humans do. In this study we presented the kea, a parrot endemic to New Zealand, with a series of tasks designed to assess cooperative cognition. We found that keas were capable of working together, even when they had to wait for their partner for up to 65 seconds. The keas also waited for a partner only when a partner was actually needed to gain food. This is the first demonstration that any non-human animal can wait for over a minute for a cooperative partner, and the first conclusive evidence that any bird species can successful track when a cooperative partner is required, and when not. The keas did not attend to whether their partner could actually access the apparatus themselves, which may have been due to issues with task demands, but one kea did show a clear preference for working together with other individuals, rather than alone. This preference has been shown to be present in humans but absent in chimpanzees. Together these results provide the first evidence that a bird species can perform at a similar level to chimpanzees and elephants across a range of collaborative tasks. This raises the possibility that aspects of the cooperative cognition seen in the primate lineage have evolved convergently in birds.