Anatomical variation of the aorta in the West of Scotland - A population with high cardiovascular disease burden. Implications for stent design and deployment.

The prevalence and complexity of cardiovascular disease (CVD) in the West of Scotland are high with the aortic arch and abdominal aorta, particularly at increased risk of cardiovascular pathology. Stent deployment can be key in preventing further cardiovascular events, however, current stent design does not account for complex advanced CVD in these areas. This cadaveric study aimed to provide anatomical measurements requested by manufacturers to improve stent design and deployment in this target population. Nine cadavers (six females and three males; age range = 82.7 ± 10.4 years) from the West of Scotland were dissected to expose the aortic arch and abdominal aorta. Digital callipers and protractors were used to collect data on vessel diameters (including taper), branch spacing, angles and presence of collaterals. CVD was present in all cadavers and ranged from mild plaque presence to aortic dissections. One possessed a bovine aortic arch variation. Supra-aortic vessels were approximately equally spaced, but the left common carotid had the most acute branching angle. Angulation of the arch from the coronal plane positively correlated with a deviation of the left subclavian artery (LSA) from the sternal midline (Spearman's coefficient r = 0.82, p = 0.01) which may impact surgical access. The origin of the vertebral artery on the LSA was also highly variable. The diameter of the descending aorta decreased along its length from the aortic hiatus to superior mesenteric by 21 ± 10% indicating a high degree of taper. The artery of Adamkiewicz was present in 33% and additional renal collaterals were present in 22%. 66% had tortuous vessels in the abdominal region. These results highlight the need for more data to aid the refinement of stent-graft design and deployment methods to ensure successful surgical intervention in this population.

Transcriptomic analysis of cutaneous squamous cell carcinoma reveals a multigene prognostic signature associated with metastasis.

BACKGROUND: Metastasis of cutaneous squamous cell carcinoma (cSCC) is uncommon. Current staging methods are reported to have sub-optimal performances in metastasis prediction. Accurate identification of patients with tumors at high risk of metastasis would have a significant impact on management. OBJECTIVE: To develop a robust and validated gene expression profile signature for predicting primary cSCC metastatic risk using an unbiased whole transcriptome discovery-driven approach. METHODS: Archival formalin-fixed paraffin-embedded primary cSCC with perilesional normal tissue from 237 immunocompetent patients (151 nonmetastasizing and 86 metastasizing) were collected retrospectively from four centers. TempO-seq was used to probe the whole transcriptome and machine learning algorithms were applied to derive predictive signatures, with a 3:1 split for training and testing datasets. RESULTS: A 20-gene prognostic model was developed and validated, with an accuracy of 86.0%, sensitivity of 85.7%, specificity of 86.1%, and positive predictive value of 78.3% in the testing set, providing more stable, accurate prediction than pathological staging systems. A linear predictor was also developed, significantly correlating with metastatic risk. LIMITATIONS: This was a retrospective 4-center study and larger prospective multicenter studies are now required. CONCLUSION: The 20-gene signature prediction is accurate, with the potential to be incorporated into clinical workflows for cSCC.

A scaffold-level genome assembly of a minute pirate bug, Orius laevigatus (Hemiptera: Anthocoridae), and a comparative analysis of insecticide resistance-related gene families with hemipteran crop pests.

BACKGROUND: Orius laevigatus, a minute pirate bug, is a highly effective beneficial predator of crop pests including aphids, spider mites and thrips in integrated pest management (IPM) programmes. No genomic information is currently available for O. laevigatus, as is the case for the majority of beneficial predators which feed on crop pests. In contrast, genomic information for crop pests is far more readily available. The lack of publicly available genomes for beneficial predators to date has limited our ability to perform comparative analyses of genes encoding potential insecticide resistance mechanisms between crop pests and their predators. These mechanisms include several gene/protein families including cytochrome P450s (P450s), ATP binding cassette transporters (ABCs), glutathione S-transferases (GSTs), UDP-glucosyltransferases (UGTs) and carboxyl/cholinesterases (CCEs). METHODS AND FINDINGS: In this study, a high-quality scaffold level de novo genome assembly for O. laevigatus has been generated using a hybrid approach with PacBio long-read and Illumina short-read data. The final assembly achieved a scaffold N50 of 125,649 bp and a total genome size of 150.98 Mb. The genome assembly achieved a level of completeness of 93.6% using a set of 1658 core insect genes present as full-length genes. Genome annotation identified 15,102 protein-coding genes - 87% of which were assigned a putative function. Comparative analyses revealed gene expansions of sigma class GSTs and CYP3 P450s. Conversely the UGT gene family showed limited expansion. Differences were seen in the distributions of resistance-associated gene families at the subfamily level between O. laevigatus and some of its targeted crop pests. A target site mutation in ryanodine receptors (I4790M, PxRyR) which has strong links to diamide resistance in crop pests and had previously only been identified in lepidopteran species was found to also be present in hemipteran species, including O. laevigatus. CONCLUSION AND SIGNIFICANCE: This assembly is the first published genome for the Anthocoridae family and will serve as a useful resource for further research into target-site selectivity issues and potential resistance mechanisms in beneficial predators. Furthermore, the expansion of gene families often linked to insecticide resistance may be an indicator of the capacity of this predator to detoxify selective insecticides. These findings could be exploited by targeted pesticide screens and functional studies to increase effectiveness of IPM strategies, which aim to increase crop yields by sustainably, environmentally-friendly and effectively control pests without impacting beneficial predator populations.

A near-chromosome level genome assembly of the European hoverfly, Sphaerophoria rueppellii (Diptera: Syrphidae), provides comparative insights into insecticide resistance-related gene family evolution.

BACKGROUND: Sphaerophoria rueppellii, a European species of hoverfly, is a highly effective beneficial predator of hemipteran crop pests including aphids, thrips and coleopteran/lepidopteran larvae in integrated pest management (IPM) programmes. It is also a key pollinator of a wide variety of important agricultural crops. No genomic information is currently available for S. rueppellii. Without genomic information for such beneficial predator species, we are unable to perform comparative analyses of insecticide target-sites and genes encoding metabolic enzymes potentially responsible for insecticide resistance, between crop pests and their predators. These metabolic mechanisms include several gene families - cytochrome P450 monooxygenases (P450s), ATP binding cassette transporters (ABCs), glutathione-S-transferases (GSTs), UDP-glycosyltransferases (UGTs) and carboxyl/choline esterases (CCEs). METHODS AND FINDINGS: In this study, a high-quality near-chromosome level de novo genome assembly (as well as a mitochondrial genome assembly) for S. rueppellii has been generated using a hybrid approach with PacBio long-read and Illumina short-read data, followed by super scaffolding using Hi-C data. The final assembly achieved a scaffold N50 of 87Mb, a total genome size of 537.6Mb and a level of completeness of 96% using a set of 1,658 core insect genes present as full-length genes. The assembly was annotated with 14,249 protein-coding genes. Comparative analysis revealed gene expansions of CYP6Zx P450s, epsilon-class GSTs, dietary CCEs and multiple UGT families (UGT37/302/308/430/431). Conversely, ABCs, delta-class GSTs and non-CYP6Zx P450s showed limited expansion. Differences were seen in the distributions of resistance-associated gene families across subfamilies between S. rueppellii and some hemipteran crop pests. Additionally, S. rueppellii had larger numbers of detoxification genes than other pollinator species. CONCLUSION AND SIGNIFICANCE: This assembly is the first published genome for a predatory member of the Syrphidae family and will serve as a useful resource for further research into selectivity and potential tolerance of insecticides by beneficial predators. Furthermore, the expansion of some gene families often linked to insecticide resistance and selectivity may be an indicator of the capacity of this predator to detoxify IPM selective insecticides. These findings could be exploited by targeted insecticide screens and functional studies to increase effectiveness of IPM strategies, which aim to increase crop yields by sustainably and effectively controlling pests without impacting beneficial predator populations.

Quantitative estimates of glacial refugia for chimpanzees (Pan troglodytes) since the Last Interglacial (120,000 BP).

Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467° (approximately 5.19 km2 grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km2 of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available.

Child with prolonged leg pain and bruising.

A 12-year-old boy was admitted to the paediatric ward with a 4-month history of worsening pain and bruising to his legs, which had resulted in a progressive reduction in his mobility. He initially had had difficulty weight bearing, which had then progressed further making him wheelchair bound. On examination, there was extensive bruising (figure 1) to his oedematous legs, worse on his right leg compared with his left. His background of autism and 15q13.3 deletion, along with maternal learning difficulties, made deciphering a clear history difficult. However, there was no account of trauma, and he had been afebrile throughout his illness. He had though lost 6 kg in weight but remained clinically stable. He was admitted to the ward for further assessment.

Exploring Participants' Experiences of a Web-Based Program for Bulimia and Binge Eating Disorder: Qualitative Study.

BACKGROUND: Guided cognitive behavioral self-help is a recommended first-line treatment for eating disorders (EDs) such as bulimia nervosa (BN) or binge eating disorder (BED). Online versions of such self-help programs are increasingly being studied in randomized controlled trials (RCTs), with some evidence that they can reduce ED symptoms, although intervention dropout is variable across interventions. However, in-depth research into participants' experiences and views on the acceptability of web-based interventions is limited. OBJECTIVE: This is a qualitative process study of participants' experiences of everyBody Plus, a web-based cognitive behavioral intervention, integrated into a large RCT to aid the interpretation of the main trial's results. To our knowledge, this is the first such study in digital intervention for EDs research to include real-time feedback into the qualitative analysis. This study aims to build upon the emerging literature by qualitatively exploring participants' experiences of a web-based intervention for BN and BED. METHODS: Participants were those who took part in the UK arm of a larger RCT investigating the efficacy of the everyBody Plus intervention. Reflexive thematic analysis was completed on 2 sources of data from the online platform: real-time feedback quotes provided at the end of completing a module on the platform (N=104) and semistructured telephone interview transcripts (n=12). RESULTS: Four main themes were identified. The first theme identified positive and negative user experiences, with a desire for a more customized and personalized intervention. Another theme positively reflected on how flexible and easy the intervention was to embed into daily life, compared with the silo of face-to-face therapy. The third theme identified how the intervention had a holistic impact cognitively, emotionally, interpersonally, and behaviorally. The final theme was related to how the intervention was not a one size fits all and how the perceived usefulness and relevance were often dependent on participants' demographic and clinical characteristics. CONCLUSIONS: Overall, participants reported positive experiences with the use of the everyBody Plus web-based intervention, including flexibility of use and the potential to holistically impact people's lives. The participants also provided valuable suggestions for how similar future web-based interventions could be improved and, in the context of EDs, how programs can be designed to be more inclusive of people by encompassing different demographic and clinical characteristics.

Effects of dietary salt on gene and protein expression in brain tissue of a model of sporadic small vessel disease.

BACKGROUND: The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on cerebral tissue of the stroke-prone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods: Brains from 21-week-old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3-week regime of 1% NaCl in drinking water), were split into two hemispheres and sectioned coronally - one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit. Results: We observed differences in gene and protein expression affecting the acute phase pathway and oxidative stress (ALB, AMBP, APOH, AHSG and LOC100129193, up-regulated in salt-loaded WKY versus WKY, >2-fold), active microglia (increased Iba-1 protein expression in salt-loaded SHRSP versus salt-loaded WKY, p<0.05), vascular structure (ACTB and CTNNB, up-regulated in salt-loaded SHRSP versus SHRSP, >3-fold; CLDN-11, VEGF and VGF down-regulated >2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity (MBP down-regulated in salt loaded WKY rats versus WKY, >2.5-fold). Changes of salt-loading were more pronounced in SHRSP and occurred without an increase in blood pressure in WKY rats. CONCLUSION: Salt exposure induced changes in gene and protein expression in an experimental model of SVD and its parent rat strain in multiple pathways involving components of the glio-vascular unit. Further studies in pertinent experimental models at different ages would help clarify the short- and long-term effect of dietary salt in SVD.

Genes from a translational analysis support a multifactorial nature of white matter hyperintensities.

BACKGROUND AND PURPOSE: White matter hyperintensities (WMH) of presumed vascular origin increase the risk of stroke and dementia. Despite strong WMH heritability, few gene associations have been identified. Relevant experimental models may be informative. METHODS: We tested the associations between genes that were differentially expressed in brains of young spontaneously hypertensive stroke-prone rats and human WMH (using volume and visual score) in 621 subjects from the Lothian Birth Cohort 1936 (LBC1936). We then attempted replication in 9361 subjects from the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE). We also tested the subjects from LBC1936 for previous genome-wide WMH associations found in subjects from CHARGE. RESULTS: Of 126 spontaneously hypertensive stroke-prone rat genes, 10 were nominally associated with WMH volume or score in subjects from LBC1936, of which 5 (AFP, ALB, GNAI1, RBM8a, and MRPL18) were associated with both WMH volume and score (P<0.05); 2 of the 10 (XPNPEP1, P=6.7×10(-5); FARP1, P=0.024) plus another spontaneously hypertensive stroke-prone rat gene (USMG5, P=0.00014), on chromosomes 10, 13, and 10 respectively, were associated with WMH in subjects from CHARGE. Gene set enrichment showed significant associations for downregulated spontaneously hypertensive stroke-prone rat genes with WMH in humans. In subjects from LBC1936, we replicated CHARGE's genome-wide WMH associations on chromosomes 17 (TRIM65 and TRIM47) and, for the first time, 1 (PMF1). CONCLUSIONS: Despite not passing multiple testing thresholds individually, these genes collectively are relevant to known WMH associations, proposed WMH mechanisms, or dementia: associations with Alzheimer's disease, late-life depression, ATP production, osmotic regulation, neurodevelopmental abnormalities, and cognitive impairment. If replicated further, they suggest a multifactorial nature for WMH and argue for more consideration of vascular contributions to dementia.

Comparison of Statistical Methods for Assessing Spatial Correlations Between Maps of Different Arterial Properties.

Assessing the anatomical correlation of atherosclerosis with biomechanical localizing factors is hindered by spatial autocorrelation (SA), wherein neighboring arterial regions tend to have similar properties rather than being independent, and by the use of aggregated data, which artificially inflates correlation coefficients. Resampling data at lower resolution or reducing degrees-of-freedom in significance tests negated effects of SA but only in artificial situations where it occurred at a single length scale. Using Fourier or wavelet transforms to generate autocorrelation-preserving surrogate datasets, and thus to compute the null distribution, avoided this problem. Bootstrap methods additionally circumvented the errors caused by aggregating data. The bootstrap technique showed that wall shear stress (WSS) was significantly correlated with atherosclerotic lesion frequency and endothelial nuclear elongation, but not with the permeability of the arterial wall to albumin, in immature rabbits.

Differential gene expression in multiple neurological, inflammatory and connective tissue pathways in a spontaneous model of human small vessel stroke.

AIMS: Cerebral small vessel disease (SVD) causes a fifth of all strokes plus diffuse brain damage leading to cognitive decline, physical disabilities and dementia. The aetiology and pathogenesis of SVD are unknown, but largely attributed to hypertension or microatheroma. METHODS: We used the spontaneously hypertensive stroke-prone rat (SHRSP), the closest spontaneous experimental model of human SVD, and age-matched control rats kept under identical, non-salt-loaded conditions, to perform a blinded analysis of mRNA microarray, qRT-PCR and pathway analysis in two brain regions (frontal and mid-coronal) commonly affected by SVD in the SHRSP at age five, 16 and 21 weeks. RESULTS: We found gene expression abnormalities, with fold changes ranging from 2.5 to 59 for the 10 most differentially expressed genes, related to endothelial tight junctions (reduced), nitric oxide bioavailability (reduced), myelination (impaired), glial and microglial activity (increased), matrix proteins (impaired), vascular reactivity (impaired) and albumin (reduced), consistent with protein expression defects in the same rats. All were present at age 5 weeks thus predating blood pressure elevation. 'Neurological' and 'inflammatory' pathways were more affected than 'vascular' functional pathways. CONCLUSIONS: This set of defects, although individually modest, when acting in combination could explain the SHRSP's susceptibility to microvascular and brain injury, compared with control rats. Similar combined, individually modest, but multiple neurovascular unit defects, could explain susceptibility to spontaneous human SVD.

Who shouts the loudest? A qualitative study exploring barriers and enablers to implementing a low emission zone in a Northern UK city.

Pollution is a major cause of ill health globally. Low emission zones (LEZ) have been identified as effective in reducing pollution and are increasing in popularity but remain divisive. Understanding what factors help or hinder implementation is important. In the UK, Clean Air Zones (CAZ, a type of LEZ) are being implemented in several cities. We aimed to identify key barriers and enablers to the implementation of a CAZ in real time, as policy was being developed and implemented in a large Northern city in England, UK. Twenty-five semi-structured interviews were conducted with city stakeholders and implementors approximately 6 months before a CAZ charging non-compliant taxis, buses, heavy goods vehicles and vans was launched. Thematic analysis was used to analyse data. Implementers were required to operate within a tight policy framework. Key enablers included: freedom to adapt the framework to local context, financial support, and cross-sector working. A focus on health was felt to be useful in justifying the policy to the public. Key barriers included conflict and opposition from local industry, politicians, and communities. Implementation of air quality policy which involves traffic restrictions remains controversial. The voices which 'shout the loudest' are often those with negative views, and these can create divisive discourse which shape public opinion and damage confidence of implementers. A systems perspective is needed to understand socio-political contexts which can influence implementation success. We provide recommendations to other areas considering implementing a LEZ.

A qualitative study examining the health system's response to COVID-19 in Sierra Leone.

The paper examines the health system's response to COVID-19 in Sierra Leone. It aims to explore how the pandemic affected service delivery, health workers, patient access to services, leadership, and governance. It also examines to what extent the legacy of the 2013-16 Ebola outbreak influenced the COVID-19 response and public perception. Using the WHO Health System Building Blocks Framework, we conducted a qualitative study in Sierra Leone where semi-structured interviews were conducted with health workers, policymakers, and patients between Oct-Dec 2020. We applied thematic analysis using both deductive and inductive approaches. Twelve themes emerged from the analysis: nine on the WHO building blocks, two on patients' experiences, and one on Ebola. We found that routine services were impacted by enhanced infection prevention control measures. Health workers faced additional responsibilities and training needs. Communication and decision-making within facilities were reported to be coordinated and effective, although updates cascading from the national level to facilities were lacking. In contrast with previous health emergencies which were heavily influenced by international organisations, we found that the COVID-19 response was led by the national leadership. Experiences of Ebola resulted in less fear of COVID-19 and a greater understanding of public health measures. However, these measures also negatively affected patients' livelihoods and their willingness to visit facilities. We conclude, it is important to address existing challenges in the health system such as resources that affect the capacity of health systems to respond to emergencies. Prioritising the well-being of health workers and the continued provision of essential routine health services is important. The socio-economic impact of public health measures on the population needs to be considered before measures are implemented.

The integrated molecular and histological analysis defines subtypes of esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) is highly heterogeneous. Our understanding of full molecular and immune landscape of ESCC remains limited, hindering the development of personalised therapeutic strategies. To address this, we perform genomic-transcriptomic characterizations and AI-aided histopathological image analysis of 120 Chinese ESCC patients. Here we show that ESCC can be categorized into differentiated, metabolic, immunogenic and stemness subtypes based on bulk and single-cell RNA-seq, each exhibiting specific molecular and histopathological features based on an amalgamated deep-learning model. The stemness subgroup with signature genes, such as WFDC2, SFRP1, LGR6 and VWA2, has the poorest prognosis and is associated with downregulated immune activities, a high frequency of EP300 mutation/activation, functional mutation enrichment in Wnt signalling and the highest level of intratumoural heterogeneity. The immune profiling by transcriptomics and immunohistochemistry reveals ESCC cells overexpress natural killer cell markers XCL1 and CD160 as immune evasion. Strikingly, XCL1 expression also affects the sensitivity of ESCC cells to common chemotherapy drugs. This study opens avenues for ESCC treatment and provides a valuable public resource to better understand ESCC.

Local genetic adaptation to habitat in wild chimpanzees.

How populations adapt to their environment is a fundamental question in biology. Yet we know surprisingly little about this process, especially for endangered species such as non-human great apes. Chimpanzees, our closest living relatives, are particularly interesting because they inhabit diverse habitats, from rainforest to woodland-savannah. Whether genetic adaptation facilitates such habitat diversity remains unknown, despite having wide implications for evolutionary biology and conservation. Using 828 newly generated exomes from wild chimpanzees, we find evidence of fine-scale genetic adaptation to habitat. Notably, adaptation to malaria in forest chimpanzees is mediated by the same genes underlying adaptation to malaria in humans. This work demonstrates the power of non-invasive samples to reveal genetic adaptations in endangered populations and highlights the importance of adaptive genetic diversity for chimpanzees.

Acceptability and Usability of a Wearable Device for Sleep Health Among English- and Spanish-Speaking Patients in a Safety Net Clinic: Qualitative Analysis.

BACKGROUND: Sleep disorders are common and disproportionately affect marginalized populations. Technology, such as wearable devices, holds the potential to improve sleep quality and reduce sleep disparities, but most devices have not been designed or tested with racially, ethnically, and socioeconomically diverse patients. Inclusion and engagement of diverse patients throughout digital health development and implementation are critical to achieving health equity. OBJECTIVE: This study aims to evaluate the usability and acceptability of a wearable sleep monitoring device-SomnoRing-and its accompanying mobile app among patients treated in a safety net clinic. METHODS: The study team recruited English- and Spanish-speaking patients from a mid-sized pulmonary and sleep medicine practice serving publicly insured patients. Eligibility criteria included initial evaluation of obstructed sleep apnea, which is most appropriate for limited cardiopulmonary testing. Patients with primary insomnia or other suspected sleep disorders were not included. Patients tested the SomnoRing over a 7-night period and participated in a 1-hour semistructured web-based qualitative interview covering perceptions of the device, motivators and barriers to use, and general experiences with digital health tools. The study team used inductive or deductive processes to code interview transcripts, guided by the Technology Acceptance Model. RESULTS: A total of 21 individuals participated in the study. All participants owned a smartphone, almost all (19/21) felt comfortable using their phone, and few already owned a wearable (6/21). Almost all participants wore the SomnoRing for 7 nights and found it comfortable. The following four themes emerged from qualitative data: (1) the SomnoRing was easy to use compared to other wearable devices or traditional home sleep testing alternatives, such as the standard polysomnogram technology for sleep studies; (2) the patient's context and environment, such as family and peer influence, housing status, access to insurance, and device cost affected the overall acceptance of the SomnoRing; (3) clinical champions motivated use in supporting effective onboarding, interpretation of data, and, ongoing technical support; and (4) participants desired more assistance and information to best interpret their own sleep data summarized in the companion app. CONCLUSIONS: Racially, ethnically, and socioeconomically diverse patients with sleep disorders perceived a wearable as useful and acceptable for sleep health. Participants also uncovered external barriers related to the perceived usefulness of the technology, such as housing status, insurance coverage, and clinical support. Future studies should further examine how to best address these barriers so that wearables, such as the SomnoRing, can be successfully implemented in the safety net health setting.

All-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone: a prospective cohort study.

OBJECTIVES: To study the mortality of patients with COVID-19 in Sierra Leone, to explore the factors associated with mortality during the COVID-19 pandemic and to highlight the complexities of treating patients with a novel epidemic disease in a fragile health system. STUDY DESIGN: A prospective single-centre cohort study. Data were extracted from paper medical records and transferred onto an electronic database. Specific indicators were compared between survivors and non-survivors, using descriptive statistics in Stata V.17. STUDY SETTING: The infectious diseases unit (IDU) at Connaught Hospital in Freetown, Sierra Leone PARTICIPANTS: Participants were all patients admitted to the IDU between March and July 2020. AIMS OF STUDY: The primary outcome of the study was to examine the all-cause mortality of hospitalised patients with suspected COVID-19 in Sierra Leone and the secondary outcome measures were to examine factors associated with mortality in patients positive for COVID-19. RESULTS: 261 participants were included in the study. Overall, 41.3% of those admitted to the IDU died, compared with prepandemic in-hospital mortality of 23.8%. Factors contributing to the higher mortality were COVID-19 infection (aOR 5.61, 95% CI 1.19 to 26.30, p=0.02) and hypertension (aOR 9.30, 95% CI 1.18 to 73.27, p=0.03) CONCLUSIONS: This study explores the multiple factors underpinning a doubling in facility mortality rate during the COVID-19 pandemic in Sierra Leone . It provides an insight into the realities of providing front-line healthcare during a pandemic in a fragile health system.

Positioning and early mobilisation in stroke.

Stroke unit care, providing early rehabilitation, improves long-term outcomes for patients following a stroke. Early mobilisation and good positioning are recognised as key aspects of care in stroke units. Nurses working on stroke units have an important role because they are able to implement positioning and early mobilisation strategies 24 hours a day, reducing the risk of complications and improving functional recovery. Patients benefit if nurses work effectively with the therapy team in positioning and early mobilisation. Nurses also need appropriate training and expertise to make best use of specialist equipment.

Population dynamics and genetic connectivity in recent chimpanzee history.

Knowledge on the population history of endangered species is critical for conservation, but whole-genome data on chimpanzees (Pan troglodytes) is geographically sparse. Here, we produced the first non-invasive geolocalized catalog of genomic diversity by capturing chromosome 21 from 828 non-invasive samples collected at 48 sampling sites across Africa. The four recognized subspecies show clear genetic differentiation correlating with known barriers, while previously undescribed genetic exchange suggests that these have been permeable on a local scale. We obtained a detailed reconstruction of population stratification and fine-scale patterns of isolation, migration, and connectivity, including a comprehensive picture of admixture with bonobos (Pan paniscus). Unlike humans, chimpanzees did not experience extended episodes of long-distance migrations, which might have limited cultural transmission. Finally, based on local rare variation, we implement a fine-grained geolocalization approach demonstrating improved precision in determining the origin of confiscated chimpanzees.