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OBJECTIVE: Whether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use. METHODS: Participants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months. RESULTS: Of 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5). CONCLUSIONS: ED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

Digitization has facilitated the proliferation of crowd science by lowering the cost of finding individuals with the willingness to participate in science without pay. However, the factors that influence participation and the outcomes of voluntary participation are unclear. We report two findings from a field experiment on the worlds largest crowd science platform that tests how voluntary contributions to science are affected by providing clarifying information on either the desired outcome of a scientific task or the labor requirements for completing the task. First, there is significant heterogeneity in the motivations and ability of contributors to crowd science. Second, both of the information interventions lead to significant decreases in the quantity and increases in the quality of contributions. Combined, our findings are consistent with the information interventions improving match quality between the task and the volunteer. Our findings suggest that science can be democratized by engaging individuals with varying skill levels and motivations with small changes in the information provided to participants.

Workers trained in STEM are generally viewed as essential for innovation-led economic growth. Yet, recent statistics suggest that a majority of STEM undergraduates do not go on to pursue innovation-focused careers in their fields of study. We investigate whether STEM students who do not self-select into innovative tasks are doing so because they are less capable than their peers who do. We find that monetary inducement among STEM students increases aggregate innovative output, but that low-GPA students who were induced significantly underperform relative to low-GPA students who self-selected; however, induced and self-selected high-GPA students perform statistically the same. In contrast, words of encouragement appears to benefit those students with the lowest GPAs. Our results highlight the value of efforts to increase the pool of STEM students who pursue innovative careers and underscore the importance of interventions targeted at specific student subgroups to maximize the returns on those efforts.

BACKGROUND:Information is needed on the safety of adalimumab when used in pregnancy for the treatment of certain autoimmune diseases. METHODS AND FINDINGS:Between 2004 and 2016, the Organization of Teratology Information Specialists Research Center at the University of California San Diego conducted a prospective controlled observational cohort study in 602 pregnant women who had or had not taken adalimumab. Women in the adalimumab-exposed cohort had received at least one dose of the drug in the first trimester for the treatment of rheumatoid arthritis or Crohn's Disease (N = 257). Women in the disease comparison cohort had not used adalimumab in pregnancy (N = 120). Women in the healthy comparison cohort had no rheumatic or inflammatory bowel diseases (N = 225). Women and their infants were followed to one year postpartum with maternal interviews, medical records abstraction, and physical examinations. Study outcomes were major structural birth defects, minor defects, spontaneous abortion, preterm delivery, pre and post-natal growth deficiency, serious or opportunistic infections and malignancies. 42/602 (7.0%) of pregnancies were lost-to-follow-up. 22/221 (10.0%) in the adalimumab-exposed cohort had a live born infant with a major birth defect compared to 8/106 (7.5%) in the diseased unexposed cohort (adjusted odds ratio 1.10, 95% confidence interval [CI] 0.45 to 2.73). Women in the adalimumab-exposed cohort were more likely to deliver preterm compared to the healthy cohort (adjusted hazard ratio [aHR] 2.59, 95% CI 1.22 to 5.50), but not compared to the diseased unexposed cohort (aHR 0.82, 95% CI 0.66 to 7.20). No significant increased risks were noted with adalimumab exposure for any other study outcomes. CONCLUSIONS:Adalimumab exposure in pregnancy compared to diseased unexposed pregnancies was not associated with an increased risk for any of the adverse outcomes examined. Women with rheumatoid arthritis or Crohn's Disease were at increased risk of preterm delivery, irrespective of adalimumab exposure.

Digitization has facilitated the proliferation of crowd science by lowering the cost of finding individuals with the willingness to participate in science without pay. However, the factors that influence participation and the outcomes of voluntary participation are unclear. We report two findings from a field experiment on the world's largest crowd science platform that tests how voluntary contributions to science are affected by providing clarifying information on either the desired outcome of a scientific task or the labor requirements for completing the task. First, there is significant heterogeneity in the motivations and ability of contributors to crowd science. Second, both of the information interventions lead to significant decreases in the quantity and increases in the quality of contributions. Combined, our findings are consistent with the information interventions improving match quality between the task and the volunteer. Our findings suggest that science can be democratized by engaging individuals with varying skill levels and motivations with small changes in the information provided to participants.

Time-dependent data collected in studies of Alzheimer's disease usually has missing and irregularly sampled data points. For this reason time series methods which assume regular sampling cannot be applied directly to the data without a pre-processing step. In this paper we use a random forest to learn the relationship between pairs of data points at different time separations. The input vector is a summary of the time series history and it includes both demographic and non-time varying variables such as genetic data. To test the method we use data from the TADPOLE grand challenge, an initiative which aims to predict the evolution of subjects at risk of Alzheimer's disease using demographic, physical and cognitive input data. The task is to predict diagnosis, ADAS-13 score and normalised ventricles volume. While the competition proceeds, forecasting methods may be compared using a leaderboard dataset selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI) and with standard metrics for measuring accuracy. For diagnosis, we find an mAUC of 0.82, and a classification accuracy of 0.73 compared with a benchmark SVM predictor which gives mAUC = 0.62 and BCA = 0.52. The results show that the method is effective and comparable with other methods.

Workers trained in STEM are generally viewed as essential for innovation-led economic growth. Yet, recent statistics suggest that a majority of STEM undergraduates do not go on to pursue innovation-focused careers in their fields of study. We investigate whether STEM students who do not self-select into innovative tasks are doing so because they are less capable than their peers who do. We find that monetary inducement among STEM students increases aggregate innovative output, but that low-GPA students who were induced significantly underperform relative to low-GPA students who self-selected; however, induced and self-selected high-GPA students perform statistically the same. In contrast, words of encouragement appears to benefit those students with the lowest GPAs. Our results highlight the value of efforts to increase the pool of STEM students who pursue innovative careers and underscore the importance of interventions targeted at specific student subgroups to maximize the returns on those efforts.

Apolipoprotein A-I (ApoA-I), the primary component of high-density lipoprotein (HDL) cholesterol primes β-cells to increase insulin secretion, however, the mechanisms involved are not fully defined. Here, we aimed to confirm ApoA-I receptors in β-cells and delineate ApoA-I-receptor pathways in β-cell insulin output. An LRC-TriCEPS experiment was performed using the INS-1E rat β-cell model and ApoA-I for unbiased identification of ApoA-I receptors. Identified targets, alongside ATP binding cassette transporter A1 (ABCA1) (included control) were silenced in the same cells, and insulin secretion (ELISA) and mitochondrial metabolism (seahorse) were assessed with/without ApoA-I priming. Human β-cell expression data was used to investigate ApoA-I receptor pathways in type 2 diabetes (T2D). Scavenger receptor B1 (SR-BI) and regulator of microtubule dynamics 1 were identified as ApoA-I targets. SR-BI or ABCA1 silencing abolished ApoA-I induced increases in insulin secretion. ApoA-I priming increased mitochondrial OXPHOS, however this was greatly attenuated with SR-BI or ABCA1 silencing. Supporting this, human β-cell expression data investigations found SR-BI and ABCA1 to be correlated with genes associated with mitochondrial pathways. In all, SR-BI and ABCA1 correlated with 73 and 3 genes differentially expressed in T2D, respectively. We confirm that SR-BI and ABCA1 are the primary β-cell ApoA-I receptors and demonstrate that ApoA-I priming enhances β-cell insulin secretion via the upregulation of mitochondrial metabolism through ApoA-I-SR-BI and ApoA-I-ABCA1 pathways. We propose that SR-BI relies on mitochondrial and exocytotic pathways, while ABCA1 depends solely on mitochondrial pathways. Our findings uncover new targets in ApoA-I β-cell mechanism for T2D therapies. [ABSTRACT FROM AUTHOR]

Knowledge of the geographic distribution and connectivity of marine populations is essential for ecological understanding and informing management. Previous works have assessed spatial structure by quantifying exchange using Lagrangian particle-tracking simulations, but their scope of analysis is limited by their use of predefined subpopulations. To instead delineate subpopulations emerging naturally from marine population connectivity, we interpret this connectivity as a network, enabling the use of powerful analytic tools from the field of network theory. The modelling approach presented here uses particle-tracking to construct a transport network, and then applies the community detection algorithm Infomap to identify subpopulations that exhibit high internal connectivity and sparse connectivity with other subpopulations. An established quality metric, the coherence ratio, and a new metric we introduce indicating self-recruitment to subpopulations, dubbed the fortress ratio, are used to interpret community-level exchange. We use the Atlantic sea scallop (Placopecten magellanicus) in the northwest Atlantic as a case study. Results suggest that genetic lineages of P. magellanicus demonstrate spatial substructure that depends on horizontal transport, vertical motility, and suitable habitat. Our results support connectivity previously characterized on Georges Bank and Mid-Atlantic Bight. The Gulf of St. Lawrence genetic lineage is found to consist of five subpopulations that are classified as being a sink, source, permeable, or impermeable using quality metrics. This approach may be applied to other planktonic dispersers and prove useful to management. [ABSTRACT FROM AUTHOR]

COVID-19 convalescent plasma (CCP) was one of the first therapies to receive emergency use authorization for management of COVID-19. We assessed the effectiveness of CCP in a propensity-matched analysis, and whether the presence of antibodies in the recipient at the time of treatment or the titer of antibodies in the administered CCP influenced clinical effectiveness. In an inpatient population within a single large health system, a total of 290 CCP patients were matched to 290 controls. While CCP increased titers of anti-SARS-CoV-2 RBD IgG titers post-CCP (p = <0.0001), no differences in 30-day survival were observed between CCP patients and controls in univariate and multivariate analyses. Survival at 30 days was numerically lower in recipients who were seronegative prior to CCP administration, compared to those with low titer and high titer anti-SARS-CoV-2 RBD IgG, respectively, but did not reach statistical significance (56% vs 82% vs 75%, p = 0.16). Patients who received 2 units of high-titer CCP had numerically better survival versus those who received fewer high-titer units, but this was not statistically significant (p = 0.08). CCP did not improve 30-day survival compared to propensity matched controls. Together these data support that CCP therapy provides limited benefit to hospitalized patients with SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

The present study examined whether people higher in psychopathy experienced less self-reported and psychophysiological nociceptive pressure than people lower in psychopathy. We also examined whether psychopathy affects empathy for others' pain via self-reported and psychophysiological measures. Three hundred and sixty-nine students (18–78 years; M = 26, SD = 9.34) were screened for psychopathic traits using the Youth Psychopathy Inventory (YPI). Stratified sampling was used to recruit 49 adults residing in the highest (n = 23) and lowest (n = 26) 20% of the psychopathy spectrum. Using skin conductance response (SCR) and self-report responses, participants responded to individually adjusted intensities of pneumatic pressure and others' pain images and completed self-reported psychopathy and empathy measures (Triarchic Psychopathy Measure, TriPm; Interpersonal Reactivity Index, IRI). People higher in psychopathy self-reported feeling less nociceptive pressure compared to people lower in psychopathy, yet we did not find any differences in SCR to nociceptive pressure. However, when viewing other people in pain, the high psychopathy group displayed lower SCR and lower self-reported empathy compared to those lower in psychopathy. Our results suggest psychopathic traits relate to problems empathising with others' pain, as well as the perception of nociceptive pressure. We also show support for the theory of dual harm which has been receiving increasing attention. Consequently, psychopathy interventions should focus both on recognising and empathising with the pain of others. [ABSTRACT FROM AUTHOR]

Through our respiratory system, many viruses and diseases frequently spread and pass from one person to another. Covid-19 served as an example of how crucial it is to track down and cut back on contacts to stop its spread. There is a clear gap in finding automatic methods that can detect hand-to-face contact in complex urban scenes or indoors. In this paper, we introduce a computer vision framework, called FaceTouch, based on deep learning. It comprises deep sub-models to detect humans and analyse their actions. FaceTouch seeks to detect hand-to-face touches in the wild, such as through video chats, bus footage, or CCTV feeds. Despite partial occlusion of faces, the introduced system learns to detect face touches from the RGB representation of a given scene by utilising the representation of the body gestures such as arm movement. This has been demonstrated to be useful in complex urban scenarios beyond simply identifying hand movement and its closeness to faces. Relying on Supervised Contrastive Learning, the introduced model is trained on our collected dataset, given the absence of other benchmark datasets. The framework shows a strong validation in unseen datasets which opens the door for potential deployment. [ABSTRACT FROM AUTHOR]

Recombination has essential roles in increasing genetic variability within a population and in ensuring successful meiotic events. The objective of this study is to (i) infer the population-scaled recombination rate (ρ), and (ii) identify and characterize regions of increased recombination rate for the domestic cat, Felis silvestris catus. SNPs (n = 701) were genotyped in twenty-two East Asian feral cats (random bred). The SNPs covered ten different chromosomal regions (A1, A2, B3, C2, D1, D2, D4, E2, F2, X) with an average region size of 850 Kb and an average SNP density of 70 SNPs/region. The Bayesian method in the program inferRho was used to infer regional population recombination rates and hotspots localities. The regions exhibited variable population recombination rates and four decisive recombination hotspots were identified on cat chromosome A2, D1, and E2 regions. As a description of the identified hotspots, no correlation was detected between the GC content and the locality of recombination spots, and the hotspots enclosed L2 LINE elements and MIR and tRNA-Lys SINE elements.

The enzyme cytidine monophospho-N-acetylneuraminic acid hydroxylase is associated with the production of sialic acids on cat red blood cells. The cat has one major blood group with three serotypes; the most common blood type A being dominant to type B. A third rare blood type is known as AB and has an unclear mode of inheritance. Cat blood type antigens are defined, with N-glycolylneuraminic acid being associated with type A and N-acetylneuraminic acid with type B. Blood type AB is serologically characterized by agglutination using typing reagents directed against both A and B epitopes. While a genetic characterization of blood type B has been achieved, the rare type AB serotype remains genetically uncharacterized. A genome-wide association study in Ragdoll cats (22 cases and 15 controls) detected a significant association between blood type AB and SNPs on cat chromosome B2, with the most highly associated SNP being at position 4,487,432 near the candidate gene cytidine monophospho-N-acetylneuraminic acid hydroxylase. A novel variant, c.364C>T, was identified that is highly associated with blood type AB in Ragdoll cats and, to a lesser degree, with type AB in random bred cats. The newly identified variant is probably linked with blood type AB in Ragdoll cats, and is associated with the expression of both antigens (N-glycolylneuraminic acid and N-acetylneuraminic acid) on the red blood cell membrane. Other variants, not identified by this work, are likely to be associated with blood type AB in other breeds of cat.

Why do people prefer one particular COVID-19 vaccine over another? We conducted a pre-registered conjoint experiment (n = 5,432) in France, Germany, and Sweden in which respondents rated the favorability of and chose between pairs of hypothetical COVID-19 vaccines. Differences in effectiveness and the prevalence of side-effects had the largest effects on vaccine preferences. Factors with smaller effects include country of origin (respondents are less favorable to vaccines of Chinese and Russian origin), and vaccine technology (respondents exhibited a small preference for hypothetical mRNA vaccines). The general public also exhibits sensitivity to additional factors (e.g. how expensive the vaccines are). Our data show that vaccine attributes are more important for vaccine preferences among those with higher vaccine favorability and higher risk tolerance. In our conjoint design, vaccine attributes-including effectiveness and side-effect prevalence-appear to have more muted effects among the most vaccine hesitant respondents. The prevalence of side-effects, effectiveness, country of origin and vaccine technology (e.g., mRNA vaccines) determine vaccine acceptance, but they matter little among the vaccine hesitant. Vaccine hesitant people do not find a vaccine more attractive even if it has the most favorable attributes. While the communication of vaccine attributes is important, it is unlikely to convince those who are most vaccine hesitant to get vaccinated.

Personal narratives make up more than half of children's conversations. The ability to share personal narratives helps build and maintain friendships, promotes physical and emotional wellbeing, supports classroom participation, and underpins academic success and vocational outcomes. Although personal narratives are a universal discourse genre, cross-cultural and cross-linguistic research into children's ability to share personal narratives is in its infancy. The current study addresses this gap in the research by developing the Global TALES protocol, a protocol comprising six scripted prompts for eliciting personal narratives in school-age children (excited, worried, annoyed, proud, problem situation, something important). We evaluated its feasibility with 249 ten-year-old children from 10 different countries, speaking 8 different languages, and analyzed researchers' views on the process of adapting the protocol for use in their own country/language. At group-level, the protocol elicited discourse samples from all children, although individual variability was evident, with most children providing responses to all six prompts. When investigating the topics of children's personal narratives in response to the prompts, we found that children from around the world share many commonalities regarding topics of conversation. Once again individual variability was high, indicating the protocol is effective in prompting children to share their past personal experiences without forcing them to focus on one particular topic. Feedback from the participating researchers on the use of the protocol in their own countries was generally positive, although several translation issues were noted. Based on our results, we now invite clinical researchers from around the world to join us in conducting further research into this important area of practice to obtain a better understanding of the development of personal narratives from children across different languages and cultures and to begin to establish local benchmarks of performance.

ObjectiveWhether short-term, low-potency opioid prescriptions for acute pain lead to future at-risk opioid use remains controversial and inadequately characterized. Our objective was to measure the association between emergency department (ED) opioid analgesic exposure after a physical, trauma-related event and subsequent opioid use. We hypothesized ED opioid analgesic exposure is associated with subsequent at-risk opioid use.MethodsParticipants were enrolled in AURORA, a prospective cohort study of adult patients in 29 U.S., urban EDs receiving care for a traumatic event. Exclusion criteria were hospital admission, persons reporting any non-medical opioid use (e.g., opioids without prescription or taking more than prescribed for euphoria) in the 30 days before enrollment, and missing or incomplete data regarding opioid exposure or pain. We used multivariable logistic regression to assess the relationship between ED opioid exposure and at-risk opioid use, defined as any self-reported non-medical opioid use after initial ED encounter or prescription opioid use at 3-months.ResultsOf 1441 subjects completing 3-month follow-up, 872 participants were included for analysis. At-risk opioid use occurred within 3 months in 33/620 (5.3%, CI: 3.7,7.4) participants without ED opioid analgesic exposure; 4/16 (25.0%, CI: 8.3, 52.6) with ED opioid prescription only; 17/146 (11.6%, CI: 7.1, 18.3) with ED opioid administration only; 12/90 (13.3%, CI: 7.4, 22.5) with both. Controlling for clinical factors, adjusted odds ratios (aORs) for at-risk opioid use after ED opioid exposure were: ED prescription only: 4.9 (95% CI 1.4, 17.4); ED administration for analgesia only: 2.0 (CI 1.0, 3.8); both: 2.8 (CI 1.2, 6.5).ConclusionsED opioids were associated with subsequent at-risk opioid use within three months in a geographically diverse cohort of adult trauma patients. This supports need for prospective studies focused on the long-term consequences of ED opioid analgesic exposure to estimate individual risk and guide therapeutic decision-making.

BackgroundCOVID-19 has rapidly emerged as a global public health threat with infections recorded in nearly every country. Responses to COVID-19 have varied in intensity and breadth, but generally have included domestic and international travel limitations, closure of non-essential businesses, and repurposing of health services. While these interventions have focused on testing, treatment, and mitigation of COVID-19, there have been reports of interruptions to diagnostic, prevention, and treatment services for other public health threats.ObjectivesWe conducted a scoping review to characterize the early impact of COVID-19 on HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.MethodsA scoping literature review was completed using searches of PubMed and preprint servers (medRxiv/bioRxiv) from November 1st, 2019 to October 31st, 2020, using Medical Subject Headings (MeSH) terms related to SARS-CoV-2 or COVID-19 and HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition. Empiric studies reporting original data collection or mathematical models were included, and available data synthesized by region. Studies were excluded if they were not written in English.ResultsA total of 1604 published papers and 205 preprints were retrieved in the search. Overall, 8.0% (129/1604) of published studies and 10.2% (21/205) of preprints met the inclusion criteria and were included in this review: 7.3% (68/931) on HIV, 7.1% (24/339) on tuberculosis, 11.6% (26/224) on malaria, 7.8% (19/183) on sexual and reproductive health, and 9.8% (13/132) on malnutrition. Thematic results were similar across competing health risks, with substantial indirect effects of the COVID-19 pandemic and response on diagnostic, prevention, and treatment services for HIV, tuberculosis, malaria, sexual and reproductive health, and malnutrition.DiscussionCOVID-19 emerged in the context of existing public health threats that result in millions of deaths every year. Thus, effectively responding to COVID-19 while minimizing the negative impacts of COVID-19 necessitates innovation and integration of existing programs that are often siloed across health systems. Inequities have been a consistent driver of existing health threats; COVID-19 has worsened disparities, reinforcing the need for programs that address structural risks. The data reviewed here suggest that effective strengthening of health systems should include investment and planning focused on ensuring the continuity of care for both rapidly emergent and existing public health threats.

Evidence concerning the effects of indicators of waterborne pathogens on healthcare systems is of importance for policymaking, future infrastructure considerations and healthcare planning. This paper examines the association between the detection of E. coli in water tests associated with drinking water supplies and the use of healthcare services by older people in Ireland. Uniquely, three sources of data are linked to conduct the analysis. Administrative records of E. coli exceedances recorded from routine water quality tests carried out by Ireland's Environmental Protection Agency are first linked to maps of water systems infrastructure in Ireland. Then, residential addresses of participants of The Irish Longitudinal Study of Ageing (TILDA), a nationally representative survey of over 50-year-olds in Ireland, are linked to the water systems dataset which has the associated water quality monitoring information. Multivariate regression analysis estimates a greater incident rate ratio (IRR) of General Practitioner (GP) visits in the previous year where E. coli is detected in the water supply associated with an older person's residence (Incidence Rate Ratio (IRR) 1.118; [95% Confidence interval (CI): 1.019-1.227]), controlling for demographic and socio-economic factors, health insurance coverage, health, and health behaviours. Where E. coli is detected in water, a higher IRR is also estimated for visits to an Emergency Department (IRR: 1.292; [95% CI: 0.995-1.679]) and nights spent in hospital (IRR: 1.351 [95% CI: 1.004-1.818]).

IntroductionReduced rates of help seeking by those who self-harmed during the COVID-19 pandemic have been reported.ObjectivesTo understand changes in healthcare service contacts for self-harm during the COVID-19 pandemic across primary, emergency and secondary care.MethodsThis retrospective cohort study used routine electronic healthcare data for Wales, United Kingdom, from 2016 to March 14, 2021. Population-based data from primary care, emergency departments and hospital admissions were linked at individual-level. All Welsh residents aged ≥10 years over the study period were included in the study. Primary, emergency and secondary care contacts with self-harm at any time between 2016 and March 14, 2021 were identified. Outcomes were counts, incidence, prevalence and proportion of self-harm contacts relative to all contacts in each and all settings, as well as the proportion of people contacting one or more settings with self-harm. Weekly trends were modelled using generalised estimated equations, with differences between 2020 (to March 2021) and comparison years 2016-2018 (to March 2017-2019) quantified using difference in differences, from which mean rate of odds ratios (μROR) across years was reported.ResultsThe study included 3,552,210 individuals over the study period. Self-harm contacts reduced across services in March and December 2020 compared to previous years. Primary care contacts with self-harm reduced disproportionately compared to non-self-harm contacts (μROR = 0.7, pConclusionsThese findings suggest that those who self-harmed during the COVID-19 pandemic may have been less likely to seek help, and those who did so faced more stringent criteria for admission. Communications encouraging those who self-harm to seek help during pandemics may be beneficial. However, this needs to be supported by maintained provision of mental health services.

Rates of Multimorbidity (also called Multiple Long Term Conditions, MLTC) are increasing in many developed nations. People with multimorbidity experience poorer outcomes and require more healthcare intervention. Grouping of conditions by health service utilisation is poorly researched. The study population consisted of a cohort of people living in Wales, UK aged 20 years or older in 2000 who were followed up until the end of 2017. Multimorbidity clusters by prevalence and healthcare resource use (HRU) were modelled using hypergraphs, mathematical objects relating diseases via links which can connect any number of diseases, thus capturing information about sets of diseases of any size. The cohort included 2,178,938 people. The most prevalent diseases were hypertension (13.3%), diabetes (6.9%), depression (6.7%) and chronic obstructive pulmonary disease (5.9%). The most important sets of diseases when considering prevalence generally contained a small number of diseases, while the most important sets of diseases when considering HRU were sets containing many diseases. The most important set of diseases taking prevalence and HRU into account was diabetes & hypertension and this combined measure of importance featured hypertension most often in the most important sets of diseases. We have used a single approach to find the most important sets of diseases based on co-occurrence and HRU measures, demonstrating the flexibility of the hypergraph approach. Hypertension, the most important single disease, is silent, underdiagnosed and increases the risk of life threatening co-morbidities. Co-occurrence of endocrine and cardiovascular diseases was common in the most important sets. Combining measures of prevalence with HRU provides insights which would be helpful for those planning and delivering services. [ABSTRACT FROM AUTHOR]

We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals' foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual's biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape.

Myotonia congenita (MC) is a skeletal muscle channelopathy characterized by inability of the muscle to relax following voluntary contraction. Worldwide population prevalence in humans is 1:100,000. Studies in mice, dogs, humans and goats confirmed myotonia associated with functional defects in chloride channels and mutations in a skeletal muscle chloride channel (CLCN1). CLCN1 encodes for the most abundant chloride channel in the skeletal muscle cell membrane. Five random bred cats from Winnipeg, Canada with MC were examined. All cats had a protruding tongue, limited range of jaw motion and drooling with prominent neck and proximal limb musculature. All cats had blepharospasm upon palpebral reflex testing and a short-strided gait. Electromyograms demonstrated myotonic discharges at a mean frequency of 300 Hz resembling the sound of a 'swarm of bees'. Muscle histopathology showed hypertrophy of all fiber types. Direct sequencing of CLCN1 revealed a mutation disrupting a donor splice site downstream of exon 16 in only the affected cats. In vitro translation of the mutated protein predicted a premature truncation and partial lack of the highly conserved CBS1 (cystathionine β-synthase) domain critical for ion transport activity and one dimerization domain pivotal in channel formation. Genetic screening of the Winnipeg random bred population of the cats' origin identified carriers of the mutation. A genetic test for population screening is now available and carrier cats from the feral population can be identified.

Physical housing and household composition have an important role in the lives of individuals and drive health and social outcomes, and inequalities. Most methods to understand housing composition are based on survey or census data, and there is currently no reproducible methodology for creating population-level household composition measures using linked administrative data. Using existing, and more recent enhancements to the address-data linkage methods in the SAIL Databank using Residential Anonymised Linking Fields we linked individuals to properties using the anonymised Welsh Demographic Service data in the SAIL Databank. We defined households, household size, and household composition measures based on adult to child relationships, and age differences between residents to create relative age measures. Two relative age-based algorithms were developed and returned similar results when applied to population and household-level data, describing household composition for 3.1 million individuals within 1.2 million households in Wales. Developed methods describe binary, and count level generational household composition measures. Improved residential anonymised linkage field methods in SAIL have led to improved property-level data linkage, allowing the design and application of household composition measures that assign individuals to shared residences and allow the description of household composition across Wales. The reproducible methods create longitudinal, household-level composition measures at a population-level using linked administrative data. Such measures are important to help understand more detail about an individual's home and area environment and how that may affect the health and wellbeing of the individual, other residents, and potentially into the wider community.

Domestic cats have a unique breeding history and can be used as models for human hereditary and infectious diseases. In the current era of genome-wide association studies, insights regarding linkage disequilibrium (LD) are essential for efficient association studies. The objective of this study is to investigate the extent of LD in the domestic cat, Felis silvestris catus, particularly within its breeds. A custom illumina GoldenGate Assay consisting of 1536 single nucleotide polymorphisms (SNPs) equally divided over ten 1 Mb chromosomal regions was developed, and genotyped across 18 globally recognized cat breeds and two distinct random bred populations. The pair-wise LD descriptive measure (r(2)) was calculated between the SNPs in each region and within each population independently. LD decay was estimated by determining the non-linear least-squares of all pair-wise estimates as a function of distance using established models. The point of 50% decay of r(2) was used to compare the extent of LD between breeds. The longest extent of LD was observed in the Burmese breed, where the distance at which r(2) ≈ 0.25 was ∼380 kb, comparable to several horse and dog breeds. The shortest extent of LD was found in the Siberian breed, with an r(2) ≈ 0.25 at approximately 17 kb, comparable to random bred cats and human populations. A comprehensive haplotype analysis was also conducted. The haplotype structure of each region within each breed mirrored the LD estimates. The LD of cat breeds largely reflects the breeds' population history and breeding strategies. Understanding LD in diverse populations will contribute to an efficient use of the newly developed SNP array for the cat in the design of genome-wide association studies, as well as to the interpretation of results for the fine mapping of disease and phenotypic traits.

The cat (Felis silvestris catus) shows significant variation in pelage, morphological, and behavioral phenotypes amongst its over 40 domesticated breeds. The majority of the breed specific phenotypic presentations originated through artificial selection, especially on desired novel phenotypic characteristics that arose only a few hundred years ago. Variations in coat texture and color of hair often delineate breeds amongst domestic animals. Although the genetic basis of several feline coat colors and hair lengths are characterized, less is known about the genes influencing variation in coat growth and texture, especially rexoid - curly coated types. Cornish Rex is a cat breed defined by a fixed recessive curly coat trait. Genome-wide analyses for selection (di, Tajima's D and nucleotide diversity) were performed in the Cornish Rex breed and in 11 phenotypically diverse breeds and two random bred populations. Approximately 63K SNPs were used in the analysis that aimed to localize the locus controlling the rexoid hair texture. A region with a strong signature of recent selective sweep was identified in the Cornish Rex breed on chromosome A1, as well as a consensus block of homozygosity that spans approximately 3 Mb. Inspection of the region for candidate genes led to the identification of the lysophosphatidic acid receptor 6 (LPAR6). A 4 bp deletion in exon 5, c.250_253_delTTTG, which induces a premature stop codon in the receptor, was identified via Sanger sequencing. The mutation is fixed in Cornish Rex, absent in all straight haired cats analyzed, and is also segregating in the German Rex breed. LPAR6 encodes a G protein-coupled receptor essential for maintaining the structural integrity of the hair shaft; and has mutations resulting in a wooly hair phenotype in humans.

Burmese is an old and popular cat breed, however, several health concerns, such as hypokalemia and a craniofacial defect, are prevalent, endangering the general health of the breed. Hypokalemia, a subnormal serum potassium ion concentration ([K(+)]), most often occurs as a secondary problem but can occur as a primary problem, such as hypokalaemic periodic paralysis in humans, and as feline hypokalaemic periodic polymyopathy primarily in Burmese. The most characteristic clinical sign of hypokalemia in Burmese is a skeletal muscle weakness that is frequently episodic in nature, either generalized, or sometimes localized to the cervical and thoracic limb girdle muscles. Burmese hypokalemia is suspected to be a single locus autosomal recessive trait. A genome wide case-control study using the illumina Infinium Feline 63K iSelect DNA array was performed using 35 cases and 25 controls from the Burmese breed that identified a locus on chromosome E1 associated with hypokalemia. Within approximately 1.2 Mb of the highest associated SNP, two candidate genes were identified, KCNH4 and WNK4. Direct sequencing of the genes revealed a nonsense mutation, producing a premature stop codon within WNK4 (c.2899C>T), leading to a truncated protein that lacks the C-terminal coiled-coil domain and the highly conserved Akt1/SGK phosphorylation site. All cases were homozygous for the mutation. Although the exact mechanism causing hypokalemia has not been determined, extrapolation from the homologous human and mouse genes suggests the mechanism may involve a potassium-losing nephropathy. A genetic test to screen for the genetic defect within the active breeding population has been developed, which should lead to eradication of the mutation and improved general health within the breed. Moreover, the identified mutation may help clarify the role of the protein in K⁺ regulation and the cat represents the first animal model for WNK4-associated hypokalemia.

CCN2/Connective Tissue Growth Factor (CTGF) is a matricellular protein that regulates cell adhesion, migration, and survival. CCN2 is best known for its ability to promote fibrosis by mediating the ability of transforming growth factor β (TGFβ) to induce excess extracellular matrix production. In addition to its role in pathological processes, CCN2 is required for chondrogenesis. CCN2 is also highly expressed during development in endothelial cells, suggesting a role in angiogenesis. The potential role of CCN2 in angiogenesis is unclear, however, as both pro- and anti-angiogenic effects have been reported. Here, through analysis of Ccn2-deficient mice, we show that CCN2 is required for stable association and retention of pericytes by endothelial cells. PDGF signaling and the establishment of the endothelial basement membrane are required for pericytes recruitment and retention. CCN2 induced PDGF-B expression in endothelial cells, and potentiated PDGF-B-mediated Akt signaling in mural (vascular smooth muscle/pericyte) cells. In addition, CCN2 induced the production of endothelial basement membrane components in vitro, and was required for their expression in vivo. Overall, these results highlight CCN2 as an essential mediator of vascular remodeling by regulating endothelial-pericyte interactions. Although most studies of CCN2 function have focused on effects of CCN2 overexpression on the interstitial extracellular matrix, the results presented here show that CCN2 is required for the normal production of vascular basement membranes.

The African malaria mosquito Anopheles gambiae sensu stricto continues to play an important role in malaria transmission, which is aggravated by its high degree of anthropophily, making it among the foremost vectors of this disease. In the current study we set out to unravel the strong association between this mosquito species and human beings, as it is determined by odorant cues derived from the human skin. Microbial communities on the skin play key roles in the production of human body odour. We demonstrate that the composition of the skin microbiota affects the degree of attractiveness of human beings to this mosquito species. Bacterial plate counts and 16S rRNA sequencing revealed that individuals that are highly attractive to An. gambiae s.s. have a significantly higher abundance, but lower diversity of bacteria on their skin than individuals that are poorly attractive. Bacterial genera that are correlated with the relative degree of attractiveness to mosquitoes were identified. The discovery of the connection between skin microbial populations and attractiveness to mosquitoes may lead to the development of new mosquito attractants and personalized methods for protection against vectors of malaria and other infectious diseases.

Objectives Proton pump inhibitors (PPIs) are commonly prescribed for prevention and treatment of gastrointestinal conditions or for gastroprotection from other drugs. Research suggests they are linked to increased dementia risk. We use linked national health data to examine the association between PPI use and the development of incident dementia. Methods and findings A population-based study using electronic health-data from the Secure Anonymised Information Linkage (SAIL) Databank, Wales (UK) from 1999 to 2015. Of data available on 3,765,744 individuals, a cohort who had ever been prescribed a PPI was developed (n = 183,968) for people aged 55 years and over and compared to non-PPI exposed individuals (131,110). Those with prior dementia, mild-cognitive-impairment or delirium codes were excluded. Confounding factors included comorbidities and/or drugs associated with them. Comorbidities might include head injury and some examples of medications include antidepressants, antiplatelets and anticoagulants. These commonly prescribed drugs were investigated as it was not feasible to explore all drugs in this study. The main outcome was a diagnosis of incident dementia. Cox proportional hazard regression modelling was used to calculate the Hazard ratio (HR) of developing dementia in PPI-exposed compared to unexposed individuals while controlling for potential confounders. The mean age of the PPI exposed individuals was 69.9 years and 39.8% male while the mean age of the unexposed individuals was 72.1 years and 41.1% male. The rate of PPI usage was 58.4% (183,968) and incident dementia rate was 11.8% (37,148/315,078). PPI use was associated with decreased dementia risk (HR: 0.67, 95% CI: 0.65 to 0.67, p

Parametric kernel methods currently dominate the literature regarding the construction of animal home ranges (HRs) and utilization distributions (UDs). These methods frequently fail to capture the kinds of hard boundaries common to many natural systems. Recently a local convex hull (LoCoH) nonparametric kernel method, which generalizes the minimum convex polygon (MCP) method, was shown to be more appropriate than parametric kernel methods for constructing HRs and UDs, because of its ability to identify hard boundaries (e.g., rivers, cliff edges) and convergence to the true distribution as sample size increases. Here we extend the LoCoH in two ways: "fixed sphere-of-influence," or r-LoCoH (kernels constructed from all points within a fixed radius r of each reference point), and an "adaptive sphere-of-influence," or a-LoCoH (kernels constructed from all points within a radius a such that the distances of all points within the radius to the reference point sum to a value less than or equal to a), and compare them to the original "fixed-number-of-points," or k-LoCoH (all kernels constructed from k-1 nearest neighbors of root points). We also compare these nonparametric LoCoH to parametric kernel methods using manufactured data and data collected from GPS collars on African buffalo in the Kruger National Park, South Africa. Our results demonstrate that LoCoH methods are superior to parametric kernel methods in estimating areas used by animals, excluding unused areas (holes) and, generally, in constructing UDs and HRs arising from the movement of animals influenced by hard boundaries and irregular structures (e.g., rocky outcrops). We also demonstrate that a-LoCoH is generally superior to k- and r-LoCoH (with software for all three methods available at http://locoh.cnr.berkeley.edu).