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A core feature of eating disorders, such as anorexia nervosa, is an overestimation of body size. A key question is whether this overestimation arises solely from body image concerns typical in eating disorders, or if there is an additional perceptual disturbance. To address this question, we applied a two-component model of body size estimation that has been thoroughly replicated in the body image literature concerning healthy individuals. This model shows statistically independent, additive effects on body size estimates of: a) body image concerns, and b) a perceptual component known as contraction bias. Here body image concerns were defined by a principal components analysis (PCA) of psychometric tasks including the: Eating Disorder Examination Questionnaire, Beck Depression Inventory, Body Shape Questionnaire, Rosenberg Self-Esteem Scale, and Sociocultural Attitudes Towards Appearance Questionnaire-4. The PCA identified three components referred to as PSYCH, FAMPEER, and ATHIN. We investigated the influence of age, personal body mass index (BMI), and these three components on body size estimation in 33 women with a current or past history of eating disorders and 100 healthy controls. Low-BMI control participants overestimated their size, while high-BMI controls underestimated their size, exhibiting the expected normal perceptual contraction bias. However, the women with a history of eating disorders showed no evidence of contraction bias, suggesting a different processing of perceptual aspects of body size estimation compared to controls. We discuss two putative mechanisms that can explain these differences in accuracy of personal body size estimation.

BackgroundEndemic African malaria vectors are poorly adapted to typical urban ecologies. However, Anopheles stephensi, an urban malaria vector formerly confined to South Asia and the Persian Gulf, was recently detected in Africa and may change the epidemiology of malaria across the continent. Little is known about the public health implications of An. stephensi in Africa. This study is designed to assess the relative importance of household exposure to An. stephensi and endemic malaria vectors for malaria risk in urban Sudan and Ethiopia.MethodsCase-control studies will be conducted in 3 urban settings (2 in Sudan, 1 in Ethiopia) to assess the association between presence of An. stephensi in and around households and malaria. Cases, defined as individuals positive for Plasmodium falciparum and/or P. vivax by microscopy/rapid diagnostic test (RDT), and controls, defined as age-matched individuals negative for P. falciparum and/or P. vivax by microscopy/RDT, will be recruited from public health facilities. Both household surveys and entomological surveillance for adult and immature mosquitoes will be conducted at participant homes within 48 hours of enrolment. Adult and immature mosquitoes will be identified by polymerase chain reaction (PCR). Conditional logistic regression will be used to estimate the association between presence of An. stephensi and malaria status, adjusted for co-occurrence of other malaria vectors and participant gender.ConclusionsFindings from this study will provide evidence of the relative importance of An. stephensi for malaria burden in urban African settings, shedding light on the need for future intervention planning and policy development.

In the absence of a single comprehensive systematic review of Rational Emotive Behaviour Therapy interventions across all settings, we reviewed the methodological quality, effectiveness and efficacy of Rational Emotive Behaviour Therapy interventions on irrational/rational beliefs. We explored the impact of Rational Emotive Behaviour Therapy on wider outcomes (e.g., mental health) and identified the characteristics of successful interventions. PsycARTICLES, PsycINFO, Scopus, SPORTDiscus, and PubMed were systematically searched up to December 2023 with 162 Rational Emotive Behaviour Therapy intervention studies identified which included a validated measure of irrational/rational beliefs. Where possible, effect size for irrational/rational belief change was reported and data was analysed through a qualitative approach. Using the Mixed Methods Appraisal tool, methodological quality within the Sport and Exercise domain was assessed as good, whilst all other domains were considered low in quality, with insufficient detail provided on intervention characteristics and delivery. Most studies were conducted in the United States, within the Education domain, and assessed irrational beliefs in non-clinical adult samples. Overall, studies reported significant reductions in irrational beliefs, increases in rational beliefs and improvements in mental health outcomes (e.g., depression). More successful interventions were delivered by trained Rational Emotive Behaviour Therapy practitioners, adopted the ABC framework and were longer in duration. We highlight the importance of designing and conducting rigorous future Rational Emotive Behaviour Therapy research to generate clearer insights as to its impact on irrational/rational beliefs and mental health outcomes.

Fracture non-unions affect many patients worldwide, however, known risk factors alone do not predict individual risk. The identification of novel biomarkers is crucial for early diagnosis and timely patient treatment. This study focused on the identification of microRNA (miRNA) related to the process of fracture healing. Serum of fracture patients and healthy volunteers was screened by RNA sequencing to identify differentially expressed miRNA at various times after injury. The results were correlated to miRNA in the conditioned medium of human bone marrow mesenchymal stromal cells (BMSCs) during in vitro osteogenic differentiation. hsa-miR-1246, hsa-miR-335-5p, and miR-193a-5p were identified both in vitro and in fracture patients and their functional role in direct BMSC osteogenic differentiation was assessed. The results showed no influence of the downregulation of the three miRNAs during in vitro osteogenesis. However, miR-1246 may be involved in cell proliferation and recruitment of progenitor cells. Further studies should be performed to assess the role of these miRNA in other processes relevant to fracture healing.

BackgroundGoal 3.2 from the Sustainable Development Goals (SDG) calls for reductions in national averages of Under-5 Mortality. However, it is well known that within countries these reductions can coexist with left behind populations that have mortality rates higher than national averages. To measure inequality in under-5 mortality and to identify left behind populations, mortality rates are often disaggregated by socioeconomic status within countries. While socioeconomic disparities are important, this approach does not quantify within group variability since births from the same socioeconomic group may have different mortality risks. This is the case because mortality risk depends on several risk factors and their interactions and births from the same socioeconomic group may have different risk factor combinations. Therefore mortality risk can be highly variable within socioeconomic groups. We develop a comprehensive approach using information from multiple risk factors simultaneously to measure inequality in mortality and to identify left behind populations.MethodsWe use Demographic and Health Surveys (DHS) data on 1,691,039 births from 182 different surveys from 67 low and middle income countries, 51 of which had at least two surveys. We estimate mortality risk for each child in the data using a Bayesian hierarchical logistic regression model. We include commonly used risk factors for monitoring inequality in early life mortality for the SDG as well as their interactions. We quantify variability in mortality risk within and between socioeconomic groups and describe the highest risk sub-populations.FindingsFor all countries there is more variability in mortality within socioeconomic groups than between them. Within countries, socioeconomic membership usually explains less than 20% of the total variation in mortality risk. In contrast, country of birth explains 19% of the total variance in mortality risk. Targeting the 20% highest risk children based on our model better identifies under-5 deaths than targeting the 20% poorest. For all surveys, we report efficiency gains from 26% in Mali to 578% in Guyana. High risk births tend to be births from mothers who are in the lowest socioeconomic group, live in rural areas and/or have already experienced a prior death of a child.InterpretationWhile important, differences in under-5 mortality across socioeconomic groups do not explain most of overall inequality in mortality risk because births from the same socioeconomic groups have different mortality risks. Similarly, policy makers can reach the highest risk children by targeting births based on several risk factors (socioeconomic status, residing in rural areas, having a previous death of a child and more) instead of using a single risk factor such as socioeconomic status. We suggest that researchers and policy makers monitor inequality in under-5 mortality using multiple risk factors simultaneously, quantifying inequality as a function of several risk factors to identify left behind populations in need of policy interventions and to help monitor progress toward the SDG.

Prediction is often used during language comprehension. However, studies of prediction have tended to focus on L1 listeners in quiet conditions. Thus, it is unclear how listeners predict outside the laboratory and in specific communicative settings. Here, we report two eye-tracking studies which used a visual-world paradigm to investigate whether prediction during a consecutive interpreting task differs from prediction during a listening task in L2 listeners, and whether L2 listeners are able to predict in the noisy conditions that might be associated with this communicative setting. In a first study, thirty-six Dutch-English bilinguals either just listened to, or else listened to and then consecutively interpreted, predictable sentences presented on speech-shaped sound. In a second study, another thirty-six Dutch-English bilinguals carried out the same tasks in clear speech. Our results suggest that L2 listeners predict the meaning of upcoming words in noisy conditions. However, we did not find that predictive eye movements depended on task, nor that L2 listeners predicted upcoming word form. We also did not find a difference in predictive patterns when we compared our two studies. Thus, L2 listeners predict in noisy circumstances, supporting theories which posit that prediction regularly takes place in comprehension, but we did not find evidence that a subsequent production task or noise affects semantic prediction.

Pneumonia, always a major malady, became the main public health and economic disaster of historical proportions with the COVID-19 pandemic. This study was based on a premise that pathology of lung metabolism in inflammation may have features invariant to the nature of the underlying cause. Amino acid uptake by the lungs was measured from plasma samples collected pre-terminally from a carotid artery and vena cava in mice with bleomycin-induced lung inflammation (N = 10) and compared to controls treated with saline instillation (N = 6). In the control group, the difference in concentrations between the arterial and venous blood of the 19 amino acids measured reached the level of statistical significance only for arginine (-10.7%, p = 0.0372) and phenylalanine (+5.5%, p = 0.0266). In the bleomycin group, 11 amino acids had significantly lower concentrations in the arterial blood. Arginine concentration was decreased by 21.1% (p

Antimicrobial resistance (AMR) is a threat to global public health. However, unsatisfactory approaches to directly measuring the AMR burden carried by individuals has hampered efforts to assess interventions aimed at reducing selection for AMR. Metagenomics can provide accurate detection and quantification of AMR genes within an individual person's faecal flora (their gut "resistome"). Using this approach, we aimed to test the hypothesis that differences in antimicrobial use across different hospitals in the United Kingdom will result in observable differences in the resistome of individual patients. Three National Health Service acute Hospital Trusts with markedly different antibiotic use and Clostridioides difficile infection rates collected faecal samples from anonymous patients which were discarded after C. difficile testing over a period of 9 to 15 months. Metagenomic DNA was extracted from these samples and sequenced using an Illumina NovaSeq 6000 platform. The resulting sequencing reads were analysed for taxonomic composition and for the presence of AMR genes. Among 683 faecal metagenomes we found huge variation between individuals in terms of taxonomic diversity (Shannon Index range 0.10-3.99) and carriage of AMR genes (Median 1.50 genes/cell/sample overall). We found no statistically significant differences in diversity (median Shannon index 2.16 (IQR 1.71-2.56), 2.15 (IQR 1.62-2.50) and 2.26 (IQR 1.55-2.51)) or carriage of AMR genes (median 1.37 genes/cell/sample (IQR 0.70-3.24), 1.70 (IQR 0.70-4.52) and 1.43 (IQR 0.55-3.71)) at the three trusts respectively. This was also the case across the sample collection period within the trusts. While we have not demonstrated differences over place or time using metagenomic sequencing of faecal discards, other sampling frameworks may be more suitable to determine whether organisational level differences in antibiotic use are associated with individual-level differences in burden of AMR carriage.

BackgroundCatecholaminergic polymorphic ventricular tachycardia (CPVT) is often a life-threatening arrhythmia disorder with variable penetrance and expressivity. Little is known about the incidence or outcomes of CPVT patients with ≥2 variants.MethodsThe phenotypes, genotypes and outcomes of patients in the Pediatric and Congenital Electrophysiology Society CPVT Registry with ≥2 variants in genes linked to CPVT were ascertained. The American College of Medical Genetics & Genomics (ACMG) criteria and structural mapping were used to predict the pathogenicity of variants (3D model of pig RyR2 in open-state).ResultsAmong 237 CPVT subjects, 193 (81%) had genetic testing. Fifteen patients (8%) with a median age of 9 years (IQR 5-12) had ≥2 variants. Sudden cardiac arrest occurred in 11 children (73%), although none died during a median follow-up of 4.3 years (IQR 2.5-6.1). Thirteen patients (80%) had at least two RYR2 variants, while the remaining two patients had RYR2 variants plus variants in other CPVT-linked genes. Among all variants identified, re-classification of the commercial laboratory interpretation using ACMG criteria led to the upgrade from variant of unknown significance (VUS) to pathogenic/likely pathogenic (P/LP) for 5 variants, and downgrade from P/LP to VUS for 6 variants. For RYR2 variants, 3D mapping using the RyR2 model suggested that 2 VUS by ACMG criteria were P/LP, while 2 variants were downgraded to likely benign.ConclusionsThis severely affected cohort demonstrates that a minority of CPVT cases are related to ≥2 variants, which may have implications on family-based genetic counselling. While multi-variant CPVT patients were at high-risk for sudden cardiac arrest, there are insufficient data to conclude that this genetic phenomenon has prognostic implications at present. Further research is needed to determine the significance and generalizability of this observation. This study also shows that a rigorous approach to variant re-classification using the ACMG criteria and 3D mapping is important in reaching an accurate diagnosis, especially in the multi-variant population.

Increasing attention is being paid to the carbon sequestration and storage services provided by coastal blue carbon ecosystems such as saltmarshes. Sites restored by managed realignment, where existing sea walls are breached to reinstate tidal inundation to the land behind, have considerable potential to accumulate carbon through deposition of sediment brought in by the tide and burial of vegetation in the site. While this potential has been recognised, it is not yet a common motivating factor for saltmarsh restoration, partly due to uncertainties about the rate of carbon accumulation and how this balances against the greenhouse gases emitted during site construction. We use a combination of field measurements over four years and remote sensing to quantify carbon accumulation at a large managed realignment site, Steart Marshes, UK. Sediment accumulated rapidly at Steart Marshes (mean of 75 mm yr-1) and had a high carbon content (4.4% total carbon, 2.2% total organic carbon), resulting in carbon accumulation of 36.6 t ha-1 yr-1 total carbon (19.4 t ha-1 yr-1 total organic carbon). This rate of carbon accumulation is an order of magnitude higher than reported in many other restored saltmarshes, and is somewhat higher than values previously reported from another hypertidal system (Bay of Fundy, Canada). The estimated carbon emissions associated with the construction of the site were ~2-4% of the observed carbon accumulation during the study period, supporting the view that managed realignment projects in such settings may have significant carbon accumulation benefits. However, uncertainties such as the origin of carbon (allochthonous or autochthonous) and changes in gas fluxes need to be resolved to move towards a full carbon budget for saltmarsh restoration.

Colorectal cancer (CRC) is the third-leading cause of cancer-related deaths in the United States and worldwide. Obesity-a worldwide public health concern-is a known risk factor for cancer including CRC. However, the mechanisms underlying the link between CRC and obesity have yet to be fully elucidated in part because of the molecular heterogeneity of CRC. We hypothesized that obesity modulates CRC in a consensus molecular subtype (CMS)-dependent manner. RNA-seq data and associated tumor and patient characteristics including body weight and height data for 232 patients were obtained from The Cancer Genomic Atlas-Colon Adenocarcinoma (TCGA-COAD) database. Tumor samples were classified into the four CMSs with the CMScaller R package; body mass index (BMI) was calculated and categorized as normal, overweight, and obese. We observed a significant difference in CMS categorization between BMI categories. Differentially expressed genes (DEGs) between obese and overweight samples and normal samples differed across the CMSs, and associated prognostic analyses indicated that the DEGs had differing associations on survival. Using Gene Set Enrichment Analysis, we found differences in Hallmark gene set enrichment between obese and overweight samples and normal samples across the CMSs. We constructed Protein-Protein Interaction networks and observed differences in obesity-regulated hub genes for each CMS. Finally, we analyzed and found differences in predicted drug sensitivity between obese and overweight samples and normal samples across the CMSs. Our findings support that obesity impacts the CRC tumor transcriptome in a CMS-specific manner. The possible associations reported here are preliminary and will require validation using in vitro and animal models to examine the CMS-dependence of the genes and pathways. Once validated the obesity-linked genes and pathways may represent new therapeutic targets to treat colon cancer in a CMS-dependent manner.

Background There are few examples of interventions designed to promote physical activity (PA) in adults with Cystic fibrosis (CF). Increasing levels of habitual PA may be more feasible and result in greater compliance than conventional exercise training inventions which give little or no attention to long-term PA behaviour. Despite this there is limited research exploring perceptions of PA among adults with CF. The study aimed to understand the ecological correlates of PA in adults with CF and to involve individuals with CF, their families (where applicable) and clinicians in a formative process to inform the development of an ecological approach to PA promotion in this population. Methods An iterative approach was utilised, whereby findings from earlier phases of the research informed subsequent phases. Semi-structured interviews were conducted to explore patients’ perceptions of PA, devised using the PRECEDE component of the PRECEDE-PROCEED model. Followed by, focus groups to discuss the perceived barriers, facilitators and opportunities for PA participation and how this information could inform the development and delivery of a PA intervention. Separate focus groups were conducted with individuals with CF (n = 11) and their families and CF MDT members. Thematic analysis was used to construct themes. Results Physical and mental wellbeing manifested as both barriers and facilitators of PA. CF is characterised by a progressive decline in physical function, which presents as a number of challenging symptoms and set-backs for an individual with CF. PA represents an opportunity for participants to slow the rate of this decline and manage the symptoms associated with the condition. Enjoyment was an important facilitator of PA. Exercise professionals and family reinforce PA behaviour, particularly during adolescence. Conclusions PA promotion should form part of routine CF care with additional exercise professional support during adolescence.

Cats are known to be affected by hippocampal sclerosis, potentially causing antiseizure drug(s) resistance. In order to lay the foundation for a standardized, systematic classification and diagnosis of this pathology in cats, this prospective study aimed at evaluating normal reference values of cellular densities and the cytoarchitecture of the feline hippocampus. Three transverse sections (head, body and tail) of each left hippocampus were obtained from 17 non-epileptic cats of different brachycephalic and mesocephalic breeds and age classes (range: 3-17 years). Histological (hematoxylin and eosin, Nissl) and immunohistochemical (NeuN, GFAP) staining was performed to investigate neuron and astroglial cell populations, as well as the layer thickness of the pyramidal cell layer and granule cell layer. Significant differences in neuronal density (in CA2-CA4 and the granule cell layer) and layer thickness (in CA1-CA3 and the granule cell layer) were evidenced throughout the longitudinal hippocampal axis (p

Objective We investigated blood samples from fully SARS-CoV2-vaccinated subjects and from previously positive tested patients up to one year after infection with SARS-CoV2, and compared short- and long-term T cell and antibody responses, with a special focus on the recently emerged delta variant (B.1.617.2). Methods and results In 23 vaccinated subjects, we documented high anti-SARS-CoV2 spike protein receptor binding domain (RBD) antibody titers. Average virus neutralization by antibodies, assessed as inhibition of ACE2 binding to RBD, was 2.2-fold reduced for delta mutant vs. wild type (wt) RBD. The mean specific antibody titers were lower one year after natural infection than after vaccination; ACE2 binding to delta mutant vs. wt RBD was 1.65-fold reduced. In an additional group, omicron RBD binding was reduced compared to delta. Specific CD4+ T cell responses were measured after stimulation with peptides pools from wt, alpha, beta, gamma, or delta variant SARS-CoV2 spike proteins by flow cytometric intracellular cytokine staining. There was no significant difference in cytokine production of IFN-γ, TNF-α, or IL-2 between vaccinated subjects. T cell responses to wt or mutant SARS-CoV2 spike were significantly weaker after natural occurring infections compared to those in vaccinated individuals. Conclusion Antibody neutralisation of the delta mutant was reduced compared to wt, as assessed in a novel inhibition assay with a finger prick blood drop. Strong CD4 T cell responses were present against wt and mutant SARS-CoV2 variants, including the delta (B.1.617.2) strain, in fully vaccinated individuals, whereas they were partly weaker 1 year after natural infection. Hence, immune responses after vaccination are stronger compared to those after naturally occurring infection, pointing out the need of the vaccine to overcome the pandemic.

Comparisons of histopathological features and microbiological findings between decedents with respiratory symptoms due to SARS-CoV-2 infection or other causes, in settings with high prevalence of HIV and Mycobacterium tuberculosis (MTB) infections have not been reported. Deaths associated with a positive ante-mortem SARS-CoV-2 PCR test and/or respiratory disease symptoms at Chris Hani Baragwanath Academic Hospital in Soweto, South Africa from 15th April to 2nd November 2020, during the first wave of the South African COVID-19 epidemic, were investigated. Deceased adult patients had post-mortem minimally-invasive tissue sampling (MITS) performed to investigate for SARS-CoV-2 infection and molecular detection of putative pathogens on blood and lung samples, and histopathology examination of lung, liver and heart tissue. During the study period MITS were done in patients displaying symptoms of respiratory disease including 75 COVID-19-related deaths (COVID+) and 42 non-COVID-19-related deaths (COVID-). The prevalence of HIV-infection was lower in COVID+ (27%) than in the COVID- (64%), MTB detection was also less common among COVID+ (3% vs 13%). Lung histopathology findings showed differences between COVID+ and COVID- in the severity of the morphological appearance of Type-II pneumocytes, alveolar injury and repair initiated by SARS-CoV-2 infection. In the liver necrotising granulomatous inflammation was more common among COVID+. No differences were found in heart analyses. The prevalence of bacterial co-infections was higher in COVID+. Most indicators of respiratory distress syndrome were undifferentiated between COVID+ and COVID- except for Type-II pneumocytes. HIV or MTB infection does not appear in these data to have a meaningful correspondence with COVID-related deaths.

ObjectivesThe development of frailty tools from electronically recorded healthcare data allows frailty assessments to be routinely generated, potentially beneficial for individuals and healthcare providers. We wished to assess the predictive validity of a frailty index (FI) derived from interRAI Community Health Assessment (CHA) for outcomes in older adults residing in retirement villages (RVs), elsewhere called continuing care retirement communities.DesignProspective cohort study.Setting and participants34 RVs across two district health boards in Auckland, Aotearoa New Zealand (NZ). 577 participants, mean age 81 years; 419 (73%) female; 410 (71%) NZ European, 147 (25%) other European, 8 Asian (1%), 7 Māori (1%), 1 Pasifika (MethodsinterRAI-CHA FI tool was used to stratify participants into fit (0-0.12), mild (>0.12-0.24), moderate (>0.24-0.36) and severe (>0.36) frail groups at baseline (the latter two grouped due to low numbers of severely frail). Primary outcome was acute hospitalization; secondary outcomes included long-term care (LTC) entry and mortality. The relationship between frailty and outcomes were explored with multivariable Cox regression, estimating hazard ratios (HRs) and 95% confidence intervals (95%CIs).ResultsOver mean follow-up of 2.5 years, 33% (69/209) of fit, 58% (152/260) mildly frail and 79% (85/108) moderate-severely frail participants at baseline had at least one acute hospitalization. Compared to the fit group, significantly increased risk of acute hospitalization were identified in mildly frail (adjusted HR = 1.88, 95%CI = 1.41-2.51, pConclusions and implicationsThe FI derived from interRAI-CHA has robust predictive validity for acute hospitalization, LTC entry and mortality. This adds to the growing literature of use of interRAI tools in this way and may assist healthcare providers with rapid identification of frailty.

Recently, researchers have proposed four superordinate emotion beliefs that supposedly influence emotion regulation and emotion reactivity. Two of these proposed emotion beliefs are captured in the cognitive mediation beliefs questionnaire (CMBQa), namely stimulus-response (S-R) generation beliefs and cognitive mediation (C-M) change beliefs. The remaining two proposed emotion beliefs, C-M generation beliefs and S-R change beliefs, are yet to be operationalised in psychometric form. It is important to validate measurement for all four emotion beliefs in order for them to be used in research and practice. The current paper reports the development and initial validity testing of the CMBQb (studies 1-3), which concerns only C-M generation beliefs and S-R change beliefs, and then tests the four-factor structure of the combined CMBQa (S-R generation, C-M change) and CMBQb (C-M generation, S-R change): the CMBQc (study 4). Some support was found for the four-factor structure of the CMBQc, with factor analyses revealing good fit to the data with a four-factor solution. Also, scores indicating greater C-M generation and change beliefs, and lower S-R generation and change beliefs, were related to more adaptive, and less maladaptive, emotion regulation tendencies. In addition, there was some evidence that greater C-M change beliefs, and lower S-R generation and change belief, were related to better affective and emotion reactivity outcomes. Implications of the CMBQc for research and practice are discussed within the context and emotion regulation science, and cognitive behavioural psychotherapy.

Black and Latinx individuals, and in particular women, comprise an essential health care workforce often serving in support roles such as nursing assistants and dietary service staff. Compared to physicians and nurses, they are underpaid and potentially undervalued, yet play a critical role in health systems. This study examined the impact of the coronavirus disease 2019 (COVID-19) pandemic from the perspective of Black and Latinx health care workers in support roles (referred to here as HCWs). From December 2020 to February 2021, we conducted 2 group interviews (n = 9, 1 group in English and 1 group in Spanish language) and 8 individual interviews (1 in Spanish and 7 in English) with HCWs. Participants were members of a high-risk workforce as well as of communities that suffered disproportionately during the pandemic. Overall, they described disruptive changes in responsibilities and roles at work. These disruptions were intensified by the constant fear of contracting COVID-19 themselves and infecting their family members. HCWs with direct patient care responsibilities reported reduced opportunities for personal connection with patients. Perspectives on vaccines reportedly changed over time, and were influenced by peers' vaccination and information from trusted sources. The pandemic has exposed the stress endured by an essential workforce that plays a critical role in healthcare. As such, healthcare systems need to dedicate resources to improve the work conditions for this marginalized workforce including offering resources that support resilience. Overall working conditions and, wages must be largely improved to ensure their wellbeing and retain them in their roles to manage the next public health emergency. The role of HCWs serving as ambassadors to provide accurate information on COVID-19 and vaccination among their coworkers and communities also warrants further study.

Regular monitoring is an important component of the successful management of pelagic animals of interest to commercial fisheries. Here we provide a biomass estimate for Antarctic krill (Euphausia superba) in the eastern sector of the Commission for the Conservation of Antarctic Marine Living Resources (CCAMLR) Division 58.4.2 (55°E to 80°E; area = 775,732 km2) using data collected during an acoustic-trawl survey carried out in February and March 2021. Using acoustic data collected in day-time and trawl data, areal biomass density was estimated as 8.3 gm-2 giving a total areal krill biomass of 6.48 million tonnes, with a 28.9% coefficient of variation (CV). The inaccessibility of the East Antarctic makes fisheries-independent surveys of Antarctic krill expensive and time consuming, so we also assessed the efficacy of extrapolating smaller surveys to a wider area. During the large-scale survey a smaller scale survey (centre coordinates -66.28°S 63.35°E, area = 4,902 km2) was conducted. We examine how representative krill densities from the small-scale (Mawson box) survey were over a latitudinal range by comparing krill densities from the large-scale survey split into latitudinal bands. We found the small scale survey provided a good representation of the statistical distribution of krill densities within its latitudinal band (KS-test, D = 0.048, p-value = 0.98), as well as mean density (t-test p-value = 0.44), but not outside of the band. We recommend further in situ testing of this approach.

Myeloperoxidase (MPO), oxidative stress (OS), and endoplasmic reticulum (ER) stress are increased in the lungs of rat pups raised in hyperoxia, an established model of bronchopulmonary dysplasia (BPD). However, the relationship between OS, MPO, and ER stress has not been examined in hyperoxia rat pups. We treated Sprague-Dawley rat pups with tunicamycin or hyperoxia to determine this relationship. ER stress was detected using immunofluorescence, transcriptomic, proteomic, and electron microscopic analyses. Immunofluorescence observed increased ER stress in the lungs of hyperoxic rat BPD and human BPD. Proteomic and morphometric studies showed that tunicamycin directly increased ER stress of rat lungs and decreased lung complexity with a BPD phenotype. Previously, we showed that hyperoxia initiates a cycle of destruction that we hypothesized starts from increasing OS through MPO accumulation and then increases ER stress to cause BPD. To inhibit ER stress, we used tauroursodeoxycholic acid (TUDCA), a molecular chaperone. To break the cycle of destruction and reduce OS and MPO, we used N-acetyl-lysyltyrosylcysteine amide (KYC). The fact that TUDCA improved lung complexity in tunicamycin- and hyperoxia-treated rat pups supports the idea that ER stress plays a causal role in BPD. Additional support comes from data showing TUDCA decreased lung myeloid cells and MPO levels in the lungs of tunicamycin- and hyperoxia-treated rat pups. These data link OS and MPO to ER stress in the mechanisms mediating BPD. KYC's inhibition of ER stress in the tunicamycin-treated rat pup's lung provides additional support for the idea that MPO-induced ER stress plays a causal role in the BPD phenotype. ER stress appears to expand our proposed cycle of destruction. Our results suggest ER stress evolves from OS and MPO to increase neonatal lung injury and impair growth and development. The encouraging effect of TUDCA indicates that this compound has the potential for treating BPD.

BackgroundThere is uncertainty around the health impact and economic costs of the recent slowing of the historical decline in cardiovascular disease (CVD) incidence and the future impact on dementia and disability.MethodsPreviously validated IMPACT Better Ageing Markov model for England and Wales, integrating English Longitudinal Study of Ageing (ELSA) data for 17,906 ELSA participants followed from 1998 to 2012, linked to NHS Hospital Episode Statistics. Counterfactual design comparing two scenarios: Scenario 1. CVD Plateau-age-specific CVD incidence remains at 2011 levels, thus continuing recent trends. Scenario 2. CVD Fall-age-specific CVD incidence goes on declining, following longer-term trends. The main outcome measures were age-related healthcare costs, social care costs, opportunity costs of informal care, and quality adjusted life years (valued at £60,000 per QALY).FindingsThe total 10 year cumulative incremental net monetary cost associated with a persistent plateauing of CVD would be approximately £54 billion (95% uncertainty interval £14.3-£96.2 billion), made up of some £13 billion (£8.8-£16.7 billion) healthcare costs, £1.5 billion (-£0.9-£4.0 billion) social care costs, £8 billion (£3.4-£12.8 billion) informal care and £32 billion (£0.3-£67.6 billion) value of lost QALYs.InterpretationAfter previous, dramatic falls, CVD incidence has recently plateaued. That slowdown could substantially increase health and social care costs over the next ten years. Healthcare costs are likely to increase more than social care costs in absolute terms, but social care costs will increase more in relative terms. Given the links between COVID-19 and cardiovascular health, effective cardiovascular prevention policies need to be revitalised urgently.

Here we present vB_BanS-Tsamsa, a novel temperate phage isolated from Bacillus anthracis, the agent responsible for anthrax infections in wildlife, livestock and humans. Tsamsa phage is a giant siphovirus (order Caudovirales), featuring a long, flexible and non-contractile tail of 440 nm (not including baseplate structure) and an isometric head of 82 nm in diameter. We induced Tsamsa phage in samples from two different carcass sites in Etosha National Park, Namibia. The Tsamsa phage genome is the largest sequenced Bacillus siphovirus, containing 168,876 bp and 272 ORFs. The genome features an integrase/recombinase enzyme, indicative of a temperate lifestyle. Among bacterial strains tested, the phage infected only certain members of the Bacillus cereus sensu lato group (B. anthracis, B. cereus and B. thuringiensis) and exhibited moderate specificity for B. anthracis. Tsamsa lysed seven out of 25 B. cereus strains, two out of five B. thuringiensis strains and six out of seven B. anthracis strains tested. It did not lyse B. anthracis PAK-1, an atypical strain that is also resistant to both gamma phage and cherry phage. The Tsamsa endolysin features a broader lytic spectrum than the phage host range, indicating possible use of the enzyme in Bacillus biocontrol.

Spatially restricting cAMP production to discrete subcellular locations permits selective regulation of specific functional responses. But exactly where and how cAMP signaling is confined is not fully understood. Different receptors and adenylyl cyclase isoforms responsible for cAMP production are not uniformly distributed between lipid raft and non-lipid raft domains of the plasma membrane. We sought to determine the role that these membrane domains play in organizing cAMP responses in HEK293 cells. The freely diffusible FRET-based biosensor Epac2-camps was used to measure global cAMP responses, while versions of the probe targeted to lipid raft (Epac2-MyrPalm) and non-raft (Epac2-CAAX) domains were used to monitor local cAMP production near the plasma membrane. Disruption of lipid rafts by cholesterol depletion selectively altered cAMP responses produced by raft-associated receptors. The results indicate that receptors associated with lipid raft as well as non-lipid raft domains can contribute to global cAMP responses. In addition, basal cAMP activity was found to be significantly higher in non-raft domains. This was supported by the fact that pharmacologic inhibition of adenylyl cyclase activity reduced basal cAMP activity detected by Epac2-CAAX but not Epac2-MyrPalm or Epac2-camps. Responses detected by Epac2-CAAX were also more sensitive to direct stimulation of adenylyl cyclase activity, but less sensitive to inhibition of phosphodiesterase activity. Quantitative modeling was used to demonstrate that differences in adenylyl cyclase and phosphodiesterase activities are necessary but not sufficient to explain compartmentation of cAMP associated with different microdomains of the plasma membrane.

Captive cheetahs often demonstrate a high incidence of diseases in which vitamin A imbalances are implicated. These can occur even under controlled and optimised feeding regimens, which is why surveillance of vitamin A status is mandatory in the successful health management of cheetahs. Serum levels of the vitamin do not reflect the true vitamin A status and liver tissue analysis is rather impractical for routine application in large felids. A biomarker for evaluating overt and subclinical vitamin A deficiency in cheetahs is needed. This study evaluates whether increased calvarial bone thickness can be detected on routine skull radiographs of vitamin A deficient cheetahs compared to unaffected animals, and secondly, evaluates whether there is increased bone thickness in clinically sound captive cheetahs in general compared to wild-living controls. Bone thickness in the neuro- and splanchnocranium was measured in 138 skull radiographs. Significant thickening of the parietal bones was found in latero-lateral radiographs of immature cheetahs (< 12 months) with vitamin A deficiency. This finding may allow a presumptive diagnosis of hypovitaminosis A in immature cheetahs. A general difference in skull thickness between free-living and captive cheetahs was not found.

Cats, similar to humans, are known to be affected by hippocampal sclerosis (HS), potentially causing antiepileptic drug (AED) resistance. HS can occur as a consequence of chronic seizure activity, trauma, inflammation, or even as a primary disease. In humans, temporal lobe resection is the standardized therapy in patients with refractory temporal lobe epilepsy (TLE). The majority of TLE patients are seizure free after surgery. Therefore, the purpose of this prospective cadaveric study is to establish a surgical technique for hippocampal resection in cats as a treatment for AED resistant seizures. Ten cats of different head morphology were examined. Pre-surgical magnetic resonance imaging (MRI) and computed tomography (CT) studies of the animals' head were carried out to complete 3D reconstruction of the head, brain, and hippocampus. The resected hippocampal specimens and the brains were histologically examined for tissue injury adjacent to the hippocampus. The feasibility of the procedure, as well as the usability of the removed specimen for histopathological examination, was assessed. Moreover, a micro-CT (mCT) examination of the brain of two additional cats was performed in order to assess temporal vasculature as a reason for possible intraoperative complications. In all cats but one, the resection of the temporal cortex and the hippocampus were successful without any evidence of traumatic or vascular lesions in the surrounding neurovascular structures. In one cat, the presence of mechanical damage (a fissure) of the thalamic surface was evident in the histopathologic examination of the brain post-resection. All hippocampal fields and the dentate gyrus were identified in the majority of the cats via histological examination. The study describes a new surgical approach (partial temporal cortico-hippocampectomy) offering a potential treatment for cats with clinical and diagnostic evidence of temporal epilepsy which do not respond adequately to the medical therapy.

Many apple cultivars are subject to biennial fluctuations in flowering and fruiting. It is believed that this phenomenon is caused by a repressive effect of developing fruit on the initiation of flowers in the apex of proximal bourse shoots. However, the genetic pathways of floral initiation are incompletely described in apple, and the biological nature of floral repression by fruit is currently unknown. In this study, we characterized the transcriptional landscape of bourse shoot apices in the biennial cultivar, 'Honeycrisp', during the period of floral initiation, in trees bearing a high fruit load and in trees without fruit. Trees with high fruit load produced almost exclusively vegetative growth in the subsequent year, whereas the trees without fruit produced flowers on the majority of the potential flowering nodes. Using RNA-based sequence data, we documented gene expression at high resolution, identifying >11,000 transcripts that had not been previously annotated, and characterized expression profiles associated with vegetative growth and flowering. We also conducted a census of genes related to known flowering genes, organized the phylogenetic and syntenic relationships of these genes, and compared expression among homeologs. Several genes closely related to AP1, FT, FUL, LFY, and SPLs were more strongly expressed in apices from non-bearing, floral-determined trees, consistent with their presumed floral-promotive roles. In contrast, a homolog of TFL1 exhibited strong and persistent up-regulation only in apices from bearing, vegetative-determined trees, suggesting a role in floral repression. Additionally, we identified four GIBBERELLIC ACID (GA) 2 OXIDASE genes that were expressed to relatively high levels in apices from bearing trees. These results define the flowering-related transcriptional landscape in apple, and strongly support previous studies implicating both gibberellins and TFL1 as key components in repression of flowering by fruit.

Amnesia is a core diagnostic criterion for Dissociative Identity Disorder (DID), however previous research has indicated memory transfer. As DID has been conceptualised as being a disorder of distinct identities, in this experiment, behavioral tasks were used to assess the nature of amnesia for episodic 1) self-referential and 2) autobiographical memories across identities. Nineteen DID participants, 16 DID simulators, 21 partial information, and 20 full information comparison participants from the general population were recruited. In the first study, participants were presented with two vignettes (DID and simulator participants received one in each of two identities) and asked to imagine themselves in the situations outlined. The second study used a similar methodology but with tasks assessing autobiographical experience. Subjectively, all DID participants reported amnesia for events that occurred in the other identity. On free recall and recognition tasks they presented a memory profile of amnesia similar to simulators instructed to feign amnesia and partial information comparisons. Yet, on tests of recognition, DID participants recognized significantly more of the event that occurred in another identity than simulator and partial information comparisons. As such, results indicate that the DID performance profile was not accounted for by true or feigned amnesia, lending support to the idea that reported amnesia may be more of a perceived than actual memory impairment.

Three studies tested the role of prioritization in solving conflict between multiple goals in different age groups. Study 1 (N = 185 young, middle-aged, older adults) stressed the importance to solve two competing tasks equally well within a short time. Older adults prioritized more than younger adults. However, contrary to our expectations, prioritization led to higher perceived conflict, more negative affect, and less control. Study 2 (N = 117 younger and older adults) found that, using a more lenient instruction, deemphasizing the importance of performing equally well on both tasks, prioritization was no longer associated with perceived goal conflict. Study 3 (N = 721 young, middle-aged, older adults) was an online study using hypothetical scenarios. This study was run to substantiate the potential mechanism underlying the differences between Study 1 and 2 and supported the hypothesized effect of the instructional strictness of pursuing two goals. Thus, when encountering conflicting goals older adults prioritize more than younger adults, but prioritization might not be optimal for solving short-term goal conflict when both conflicting goals are equally important.

BackgroundIdiopathic pulmonary fibrosis (IPF) is a devastating lung disease with limited treatment options in which the telomere shortening is a strong predictive factor of poor prognosis. Mesenchymal stromal cells (MSC) administration is probed in several experimental induced lung pathologies; however, MSC might stimulate fibrotic processes. A therapy that avoids MSC side effects of transformation would be an alternative to the use of living cells. Membranes particles (MP) are nanovesicles artificially generated from the membranes of MSC containing active enzymes involved in ECM regeneration. We aimed to investigate the anti-fibrotic role of MP derived from MSC in an in vitro model of pulmonary fibrosis.MethodsEpithelial cells (A549) and lung fibroblasts, from IPF patients with different telomere length, were co-cultured with MP and TGF-β for 48h and gene expression of major pro-fibrotic markers were analyzed.ResultsAbout 90% of both types of cells effectively took up MP without cytotoxic effects. MP decreased the expression of profibrotic proteins such as Col1A1, Fibronectin and PAI-1, in A549 cells. In fibroblasts culture, there was a different response in the inhibitory effect of MP on some pro-fibrotic markers when comparing fibroblast from normal telomere length patients (FN) versus short telomere length (FS), but both types showed an inhibition of Col1A1, Tenascin-c, PAI-1 and MMP-1 gene expression after MP treatment.ConclusionsMP conserve some of the properties attributed to the living MSC. This study shows that MP target lung cells, via which they may have a broad anti-fibrotic effect.

ObjectivesThere is evidence that emergency department (ED) crowding is associated with increased mortality, however large multicenter studies of high quality are scarce. In a prior study, we introduced a proxy-measure for crowding that was associated with increased mortality. The national registry SVAR enables us to study the association in a more heterogenous group of EDs with more recent data. The aim is to investigate the association between ED crowding and mortality.MethodsThis was an observational cohort study including visits from 14 EDs in Sweden 2015-2019. Crowding was defined as the mean ED-census divided with expected ED-census during the work-shift that the patient arrived. The crowding exposure was categorized in three groups: low, moderate and high. Hazard ratios (HR) for mortality within 7 and 30 days were estimated with a cox proportional hazards model. The model was adjusted for age, sex, triage priority, arrival hour, weekend, arrival mode and chief complaint. Subgroup analysis by county and for admitted patients by county were performed.Results2,440,392 visits from 1,142,631 unique patients were analysed. A significant association was found between crowding and 7-day mortality but not with 30-day mortality. Subgroup analysis also yielded mixed results with a clear association in only one of the three counties. The estimated HR (95% CI) for 30-day mortality for admitted patients in this county was 1.06 (1.01-1.12) in the moderate crowding category, and 1.11 (1.01-1.22) in the high category.ConclusionsThe association between crowding and mortality may not be universal. Factors that influence the association between crowding and mortality at different EDs are still unknown but a high hospital bed occupancy, impacting admitted patients may play a role.

Donation after circulatory death (DCD) has expanded the donor pool for liver transplantation. However, ischemic cholangiopathy (IC) after DCD liver transplantation causes inferior outcomes. The molecular mechanisms of IC are currently unknown but may depend on ischemia-induced genetic reprograming of the biliary epithelium to mesenchymal-like cells. The main objective of this study was to determine if cholangiocytes undergo epithelial to mesenchymal transition (EMT) after exposure to DCD conditions and if this causally contributes to the phenotype of IC. Human cholangiocyte cultures were exposed to periods of warm and cold ischemia to mimic DCD liver donation. EMT was tested by assays of cell migration, cell morphology, and differential gene expression. Transplantation of syngeneic rat livers recovered under DCD conditions were evaluated for EMT changes by immunohistochemistry. Human cholangiocytes exposed to DCD conditions displayed migratory behavior and gene expression patterns consistent with EMT. E-cadherin and CK-7 expressions fell while N-cadherin, vimentin, TGFβ, and SNAIL rose, starting 24 hours and peaking 1-3 weeks after exposure. Cholangiocyte morphology changed from cuboidal (epithelial) before to spindle shaped (mesenchymal) a week after ischemia. These changes were blocked by pretreating cells with the Transforming Growth Factor beta (TGFβ) receptor antagonist Galunisertib (1 μM). Finally, rats with liver isografts cold stored for 20 hours in UW solution and exposed to warm ischemia (30 minutes) at recovery had elevated plasma bilirubin 1 week after transplantation and the liver tissue showed immunohistochemical evidence of early cholangiocyte EMT. Our findings show EMT occurs after exposure of human cholangiocytes to DCD conditions, which may be initiated by upstream signaling from autocrine derived TGFβ to cause mesenchymal specific morphological and migratory changes.

For many years, there has been a trend to breed cats with an increasing degree of brachycephalic head features, which are known to have a severe impact on the animals' health and welfare. The direct relation between different grades of brachycephaly and their negative implications have not been researched in this species. The aim of this study was therefore to establish correlations between the different grades of brachycephaly and reduced upper respiratory airways, exophthalmos of the eye globes and malalignment of the teeth in Persian cats. Sixty-nine Persian cats of various skull dimensions and ten Domestic shorthair cats were recruited for the study. The cats' skulls were examined using three-dimensional reconstructions created from Computed Tomography datasets. Brachycephaly was graded using established craniometric measurements (facial index, cranial index, skull index, craniofacial angle). The flow area of the nasal passageways at different locations, the amount of the eye globe not supported by the bony orbit and the axial deviation of the teeth were quantified and evaluated for a correlation with the grade of brachycephaly. The results of this study clearly show that increased grades of brachycephaly in Persian cats resulted in larger extra-orbital parts of the ocular bulbs. The brachycephalic skull dimension also resulted in a lower height of the naso-osseal aperture, while other areas of the nasal airways were not correlated with the severity of brachycephaly. Persian cats showed a significantly increased occurrence of premolar tooth displacement in the upper jaw with increasing brachycephaly grades. It was interesting to note that the measured values had a broad range and values of some individual Persian cats showed an overlap with those of Domestic shorthair cats.

Archaeological excavations close to St Louis' castle in Sidon, Lebanon have revealed two mass grave deposits containing partially articulated and disarticulated human skeletal remains. A minimum of 25 male individuals have been recovered, with no females or young children. Radiocarbon dating of the human remains, a crusader coin, and the design of Frankish belt buckles strongly indicate they belong to a single event in the mid-13th century CE. The skeletal remains demonstrate a high prevalence of unhealed sharp force, penetrating force and blunt force trauma consistent with medieval weaponry. Higher numbers of wounds on the back of individuals than the front suggests some were attacked from behind, possibly as they fled. The concentration of blade wounds to the back of the neck of others would be compatible with execution by decapitation following their capture. Taphonomic changes indicate the skeletal remains were left exposed for some weeks prior to being collected together and re-deposited in the defensive ditch by a fortified gateway within the town wall. Charring on some bones provides evidence of burning of the bodies. The findings imply the systematic clearance of partially decomposed corpses following an attack on the city, where adult and teenage males died as a result of weapon related trauma. The skeletons date from the second half of the Crusader period, when Christian-held Sidon came under direct assault from both the Mamluk Sultanate (1253 CE) and the Ilkhanate Mongols (1260 CE). It is likely that those in the mass graves died during one of these assaults.

BackgroundEvidence from high-income countries demonstrates that co-morbid mental disorders in people with epilepsy adversely affect clinical and social outcomes. However, evidence from low-income countries is lacking. The objective of this study was to measure the association between co-morbid mental disorders and quality of life and functioning in people with epilepsy.MethodsA facility-based, community ascertained cross-sectional survey was carried out in selected districts of the Gurage Zone, Southern Ethiopia. Participants were identified in the community and referred to primary health care (PHC) clinics. Those diagnosed by PHC workers were recruited. Co-morbid mental disorders were measured using a standardised, semi-structured clinical interview administered by mental health professionals. The main outcome, quality of life, was measured using the Quality of Life in Epilepsy questionnaire (QOLIE-10p). The secondary outcome, functional disability, was assessed using the 12-item World Health Organization Disability Assessment Schedule (WHODAS-2).ResultsThe prevalence of comorbid mental disorders was 13.9%. Comorbid mental disorders were associated with poorer quality of life (Adjusted (Adj.) β -13.27; 95% CI -23.28 to-3.26) and greater disability (multiplier of WHODAS-2 score 1.62; 95% CI 1.05, 2.50) after adjusting for hypothesised confounding factors. Low or very low relative wealth (Adj. β = -12.57, 95% CI -19.94 to-5.20), higher seizure frequency (Adj.β coef. = -1.92, 95% CI -2.83 to -1.02), and poor to intermediate social support (Adj. β coef. = -9.66, 95% CI -16.51 to -2.81) were associated independently with decreased quality of life. Higher seizure frequency (multiplier of WHODAS-2 score 1.11; 95% CI 1.04, 1.19) was associated independently with functional disability.ConclusionCo-morbid mental disorders were associated with poorer quality of life and impairment, independent of level of seizure control. Integrated and comprehensive psychosocial care is required for better health and social outcomes of people with epilepsy.

Microbial communities are of considerable significance for biogeochemical processes, for the health of both animals and plants, and for biotechnological purposes. A key feature of microbial interactions is the exchange of nutrients between cells. Isotope labelling followed by analysis with secondary ion mass spectrometry (SIMS) can identify nutrient fluxes and heterogeneity of substrate utilisation on a single cell level. Here we present a novel approach that combines SIMS experiments with mechanistic modelling to reveal otherwise inaccessible nutrient kinetics. The method is applied to study the onset of a synthetic mutualistic partnership between a vitamin B12-dependent mutant of the alga Chlamydomonas reinhardtii and the B12-producing, heterotrophic bacterium Mesorhizobium japonicum, which is supported by algal photosynthesis. Results suggest that an initial pool of fixed carbon delays the onset of mutualistic cross-feeding; significantly, our approach allows the first quantification of this expected delay. Our method is widely applicable to other microbial systems, and will contribute to furthering a mechanistic understanding of microbial interactions.

The lack of social contact or good social relationships has been linked with cognitive decline and higher risk for Alzheimer's disease and related dementias. One important but unexamined question is how daily social interactions relate to older adults' cognitive function in daily life. The present study examined how changes in daily social interactions related to fluctuations in older adults' performance on mobile cognitive tests from day to day. Using an ecological momentary assessments approach, 312 older adults (aged 70 to 90 years) completed surveys on social interactions and mobile cognitive tests five times a day for 16 consecutive days using smartphones. Multilevel modeling was used for analyses. Results demonstrated that having more daily social interactions, especially more pleasant social interactions, related to better cognitive performance the same day and over the subsequent two days. Cognitive performance, however, did not predict subsequent changes in social interactions across days. At the between-person level, older adults who had more (vs. less) frequent interactions with close partners on average, especially with their friends, had better cognitive performance. Finally, the average levels of social interactions also moderated the within-person associations between daily social interactions and the same-day cognitive performance. In sum, results from this study highlight the importance of having pleasant social interactions and frequent interactions with friends for older adults' cognitive function in daily life, and have important implications for future behavioral interventions targeting certain features of daily social interactions to reduce risk of cognitive decline and Alzheimer's disease and related dementias.

Previous research has demonstrated a lack of neuroplasticity induced by acute exercise in low fit individuals, but the influence of exercise intensity is unclear. In the present study, we assessed the effect of acute high-intensity (HI) or moderate-intensity (MOD) interval exercise on neuroplasticity in individuals with low fitness, as determined by a peak oxygen uptake (VO2peak) test (n = 19). Transcranial magnetic stimulation (TMS) was used to assess corticospinal excitability via area under the motor evoked potential (MEP) recruitment curve before and following training. Corticospinal excitability was unchanged after HI and MOD, suggesting no effect of acute exercise on neuroplasticity as measured via TMS in sedentary, young individuals. Repeated bouts of exercise, i.e., physical training, may be required to induce short-term changes in corticospinal excitability in previously sedentary individuals.

Despite empirical observations suggesting that practitioners value the use of substitutions during soccer match-play, limited research has sought to substantiate such claims. This study used online surveys to assess the perceptions of practitioners within professional soccer about the use and practices of substitutes. Thirty-three practitioners completed one of two surveys (each requiring both open and closed questions to be answered), depending upon whether their primary role related mostly to tactical ('tactical practitioners'; n = 7) or physical ('physical practitioners'; n = 26) aspects of player/team management. Thematic content analysis of responses identified four higher-order themes: 'impact of substitutions', 'planning and communication', 'player preparation and recovery' and 'regulations'. Eighty-five percent of practitioners believed that substitutes are important in determining success during soccer match-play, with the primary justification being the perceived ability of such players to provide a physical and/or tactical impact. However, contextual factors such as the match situation, timing of introduction, and players undergoing adequate pre-pitch-entry preparation, may be important for realising such aims. Although many practitioners believed that there was a need for substitutes to engage in bespoke non-match-day preparations and recovery strategies that differ from starting players, logistical considerations, such as scarcity of resources, often limit their scope. Notwithstanding, 96% of respondents indicated that substitutes frequently perform extra conditioning sessions to account for deficits in high-speed running loads compared with players exposed to a longer period of match-play. Substitutes' pre-match warm-ups are typically led by team staff, however practitioners reported providing varying levels of input with regards to the practices adopted between kick-off and pitch-entry. Uncertainty exists as to the efficacy of current pre-pitch-entry practices, and 100% of practitioners highlighted 'preparatory strategies' as at least a 'moderately important' direction for future research. This study presents novel insights and highlights areas that are considered future research priorities amongst those working in the field.

Two ancient Egyptian child mummies at the University of Tartu Art Museum (Estonia) were, according to museum records, brought to Estonia by the young Baltic-German scholar Otto Friedrich von Richter, who had travelled in Egypt during the early 19th century. Although some studies of the mummies were conducted, a thorough investigation has never been made. Thus, an interdisciplinary team of experts studied the remains using the most recent analytical methods in order to provide an exhaustive analysis of the remains. The bodies were submitted for osteological and archaeothanatological study, radiological investigation, AMS radiocarbon dating, chemical and textile analyses, 3D modelling, entomological as well as aDNA investigation. Here we synthesize the results of one of the most extensive multidisciplinary analyses of ancient Egyptian child mummies, adding significantly to our knowledge of such examples of ancient funerary practices.

Modifying a soccer substitute's pre-pitch-entry activities may represent an opportunity to maximise physical performance and minimise injury-risk following match-introduction. Using a professional team that has previously participated in substitute profiling research, this follow-up case study investigated the effects of a modified match-day protocol that included substitutes; 1) performing a new pre-match warm-up alongside members of the starting team (as opposed to a separate substitute-only warm-up), 2) participating in a staff-led half-time rewarm-up (as opposed to player-led half-time activities), and 3) receiving ongoing education focusing on the efficacy of (re)warm-up activities. English Championship substitutes (n = 15) were monitored using Micro-electromechanical Systems during 13 matches incorporating the modified practices (35 observations). On an individual player basis, data were organised into bouts of warm-up activity (pre-pitch-entry) and five min epochs of match-play (post-pitch-entry). Linear mixed modelling assessed the influence of 'bout' and 'epoch', position, and scoreline. Substitutes performed 3±1 rewarm-up bouts∙player-1∙match-1 between kick-off and pitch-entry, which were shorter (-17.2 to -27.1 min) and elicited less distance (-696 to -1257 m) than the pre-match warm-up (p≤0.001). Compared with previous data, heightened absolute movement responses were observed during the pre-match and staff-led half-time (re)warm-ups, alongside greater relative distances covered during player-led activities performed between kick-off and pitch-entry. Whilst less distance (-10%) was covered during the second versus first five min period following match-introduction, values remained higher than previously reported. Between pitch-entry and the end of the match, the scoreline improved and worsened following 26% and 11% of substitutions, respectively; a favourable record compared with existing observations. Acknowledging the likely contribution from external factors, this case study reports heightened movement profiles and improved match scorelines when pre-pitch-entry practices were modified. Practitioners should note the potential influence of match-day activities on the physical responses of soccer substitutes and, if deemed necessary, consider adapting their pre-pitch-entry routines accordingly.

Computational models of the heart are increasingly being used in the development of devices, patient diagnosis and therapy guidance. While software techniques have been developed for simulating single hearts, there remain significant challenges in simulating cohorts of virtual hearts from multiple patients. To facilitate the development of new simulation and model analysis techniques by groups without direct access to medical data, image analysis techniques and meshing tools, we have created the first publicly available virtual cohort of twenty-four four-chamber hearts. Our cohort was built from heart failure patients, age 67±14 years. We segmented four-chamber heart geometries from end-diastolic (ED) CT images and generated linear tetrahedral meshes with an average edge length of 1.1±0.2mm. Ventricular fibres were added in the ventricles with a rule-based method with an orientation of -60° and 80° at the epicardium and endocardium, respectively. We additionally refined the meshes to an average edge length of 0.39±0.10mm to show that all given meshes can be resampled to achieve an arbitrary desired resolution. We ran simulations for ventricular electrical activation and free mechanical contraction on all 1.1mm-resolution meshes to ensure that our meshes are suitable for electro-mechanical simulations. Simulations for electrical activation resulted in a total activation time of 149±16ms. Free mechanical contractions gave an average left ventricular (LV) and right ventricular (RV) ejection fraction (EF) of 35±1% and 30±2%, respectively, and a LV and RV stroke volume (SV) of 95±28mL and 65±11mL, respectively. By making the cohort publicly available, we hope to facilitate large cohort computational studies and to promote the development of cardiac computational electro-mechanics for clinical applications.

The cocaine vaccine dAd5GNE is comprised of a disrupted serotype 5 adenovirus gene therapy vector covalently conjugated to the cocaine analog GNE. The vaccine evokes a high titer of circulating anti-cocaine antibodies that prevent cocaine from reaching its cognate receptors in the central nervous system. Prior studies have demonstrated the efficacy of dAd5GNE in models of occasional, moderate cocaine use. However, previous studies have not sufficiently evaluated the efficacy of dAd5GNE in models of the repetitive and high-dose "binge" use patterns common in human addicts. In the present study, we evaluated the capacity of dAd5GNE vaccination to protect against "binge" cocaine use and circumstances where vaccinated addicts attempt to override the vaccine. We modeled repetitive daily cocaine use in vaccinated Balb/c mice and African green monkeys, and evaluated high-dose "binge" scenarios in Balb/c mice. In each model of daily use the dAd5GNE vaccine prevented cocaine from reaching the central nervous system. In the high-dose "binge" model, vaccination decreased cocaine-induced hyperactivity and reduced the number of cocaine-induced seizures. Based on this data and our prior data in rodents and nonhuman primates, we have initiated a clinical trial evaluating the dAd5GNE anti-cocaine vaccine as a potential therapy for cocaine addicts who wish to stop cocaine use. If dAd5GNE vaccination is safe and produces high anti-cocaine antibody titers in the clinic, we hypothesize that the vaccine will restrict the access of cocaine to the central nervous system and inhibit cocaine-induced "highs" even in the context of moderate daily and high-dose "binge" use that might otherwise cause a drug-induced overdose.

Accurate quantification and characterization of atherosclerotic plaques with MRI requires high spatial resolution acquisitions with excellent image quality. The intrinsically better signal-to-noise ratio (SNR) at high-field clinical 7T compared to the widely employed lower field strengths of 1.5 and 3T may yield significant improvements to vascular MRI. However, 7T atherosclerosis imaging also presents specific challenges, related to local transmit coils and B1 field inhomogeneities, which may overshadow these theoretical gains. We present the development and evaluation of 3D, black-blood, ultra-high resolution vascular MRI on clinical high-field 7T in comparison lower-field 3T. These protocols were applied for in vivo imaging of atherosclerotic rabbits, which are often used for development, testing, and validation of translatable cardiovascular MR protocols. Eight atherosclerotic New Zealand White rabbits were imaged on clinical 7T and 3T MRI scanners using 3D, isotropic, high (0.63 mm3) and ultra-high (0.43 mm3) spatial resolution, black-blood MR sequences with extensive spatial coverage. Following imaging, rabbits were sacrificed for validation using fluorescence imaging and histology. Image quality parameters such as SNR and contrast-to-noise ratio (CNR), as well as morphological and functional plaque measurements (plaque area and permeability) were evaluated at both field strengths. Using the same or comparable imaging parameters, SNR and CNR were in general higher at 7T compared to 3T, with a median (interquartiles) SNR gain of +40.3 (35.3-80.1)%, and a median CNR gain of +68.1 (38.5-95.2)%. Morphological and functional parameters, such as vessel wall area and permeability, were reliably acquired at 7T and correlated significantly with corresponding, widely validated 3T vessel wall MRI measurements. In conclusion, we successfully developed 3D, black-blood, ultra-high spatial resolution vessel wall MRI protocols on a 7T clinical scanner. 7T imaging was in general superior to 3T with respect to image quality, and comparable in terms of plaque area and permeability measurements.

BackgroundGoal 3.2 from the Sustainable Development Goals (SDG) calls for reductions in national averages of Under-5 Mortality. However, it is well known that within countries these reductions can coexist with left behind populations that have mortality rates higher than national averages. To measure inequality in under-5 mortality and to identify left behind populations, mortality rates are often disaggregated by socioeconomic status within countries. While socioeconomic disparities are important, this approach does not quantify within group variability since births from the same socioeconomic group may have different mortality risks. This is the case because mortality risk depends on several risk factors and their interactions and births from the same socioeconomic group may have different risk factor combinations. Therefore mortality risk can be highly variable within socioeconomic groups. We develop a comprehensive approach using information from multiple risk factors simultaneously to measure inequality in mortality and to identify left behind populations.MethodsWe use Demographic and Health Surveys (DHS) data on 1,691,039 births from 182 different surveys from 67 low and middle income countries, 51 of which had at least two surveys. We estimate mortality risk for each child in the data using a Bayesian hierarchical logistic regression model. We include commonly used risk factors for monitoring inequality in early life mortality for the SDG as well as their interactions. We quantify variability in mortality risk within and between socioeconomic groups and describe the highest risk sub-populations.FindingsFor all countries there is more variability in mortality within socioeconomic groups than between them. Within countries, socioeconomic membership usually explains less than 20% of the total variation in mortality risk. In contrast, country of birth explains 19% of the total variance in mortality risk. Targeting the 20% highest risk children based on our model better identifies under-5 deaths than targeting the 20% poorest. For all surveys, we report efficiency gains from 26% in Mali to 578% in Guyana. High risk births tend to be births from mothers who are in the lowest socioeconomic group, live in rural areas and/or have already experienced a prior death of a child.InterpretationWhile important, differences in under-5 mortality across socioeconomic groups do not explain most of overall inequality in mortality risk because births from the same socioeconomic groups have different mortality risks. Similarly, policy makers can reach the highest risk children by targeting births based on several risk factors (socioeconomic status, residing in rural areas, having a previous death of a child and more) instead of using a single risk factor such as socioeconomic status. We suggest that researchers and policy makers monitor inequality in under-5 mortality using multiple risk factors simultaneously, quantifying inequality as a function of several risk factors to identify left behind populations in need of policy interventions and to help monitor progress toward the SDG.

While the area of plantation forest increased globally between 2010 and 2015, more than twice the area of natural forests was lost over the same period (6.5 million ha natural forest lost per year versus 3.2 million ha plantation gained per year). Consequently, there is an increasing need to understand how plantation land use affects biodiversity. The relative conservation value of plantation forests is context dependent, being influenced by previous land use, management regimes and landscape composition. What is less well understood, and of importance to conservation management, is the consistency of diversity patterns across regions, and the degree to which useful generalisations can be provided within and among bioregions. Here, we analyse forest birds in Ireland, France and Portugal, representing distinct regions across the Atlantic biogeographic area of Europe. We compared taxonomic, functional and phylogenetic diversity of bird communities among conifer plantations and semi-natural oak forests, and assessed correlations between species traits and forest type across these regions. Although bird composition (assessed with NMDS ordination) differed consistently between plantation and oak forests across all three regions, species richness and Shannon diversity did not show a consistent pattern. In Ireland and France, metrics of taxonomic diversity (richness and Shannon diversity), functional diversity, functional dispersion and phylogenetic diversity were greater in oak forests than plantations. However, in Portugal taxonomic and phylogenetic diversity did not differ significantly between forest types, while functional diversity and dispersion were statistically significantly greater in plantations. No single bird trait-forest type association correlated in a consistent direction across the three study regions. Trait associations for the French bird communities appeared intermediate between those in Ireland and Portugal, and when trait correlations were significant in both Ireland and Portugal, the direction of the correlation was always opposite. The variation in response of bird communities to conifer plantations indicates that care is needed when generalising patterns of community diversity and assembly mechanisms across regions.

The aim of this retrospective cross-sectional study was to present comprehensive information about the age-dependent change of skeletal characteristics in captive cheetahs with known age and to assess the benefit of these variables for age estimation in this species. Radiographs of 162 known-age captive and semi-captive cheetahs were retrospectively examined and age-related changes of skull, axial and appendicular skeletal systems were documented. Metric and non-metric variables were used. These parameters were checked for the best correlation with age using a multiple stepwise regression analysis. An overview about the time frames, in which ossification centers appeared and physeal closure occurred is presented. Multiple stepwise regression analysis revealed the status of closure of the coronal suture, the maximum length of the frontal sinus, the condylobasal-, hard palate, and facial length are most significantly correlated with age. Together with the pulp size of the upper canine, these values can be used for an age approximation in cheetahs.

In this study, the morphology of the horse brain (Equus caballus) is decribed in detail using high field MRI. The study includes sagittal, dorsal, and transverse T2-weighted images at 0.25 mm resolution at 3 Tesla and 3D models of the brain presenting the external morphology of the brain. Representative gallocyanin stained histological slides of the same brain are presented. The images represent a useful tool for MR image interpretation in horses and may serve as a starting point for further research aiming at in vivo analysis in this species.

Although we spend much of our waking hours working, the emotional experience of work, versus non-work, remains unclear. While the large literature on work stress suggests that work generally is aversive, some seminal theory and findings portray working as salubrious and perhaps as an escape from home life. Here, we examine the subjective experience of work (versus non-work) by conducting a quantitative review of 59 primary studies that assessed affect on working days. Meta-analyses of within-day studies indicated that there was no difference in positive affect (PA) between work versus non-work domains. Negative affect (NA) was higher for work than non-work, although the magnitude of difference was small (i.e., .22 SD, an effect size comparable to that of the difference in NA between different leisure activities like watching TV versus playing board games). Moderator analyses revealed that PA was relatively higher at work and NA relatively lower when affect was measured using "real-time" measurement (e.g., Experience Sampling Methodology) versus measured using the Day Reconstruction Method (i.e., real-time reports reveal a more favorable view of work as compared to recall/DRM reports). Additional findings from moderator analyses included significant differences in main effect sizes as a function of the specific affect, and, for PA, as a function of the age of the sample and the time of day when the non-work measurements were taken. Results for the other possible moderators including job complexity and affect intensity were not statistically significant.