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AbstractHaemorrhagic shock is a leading cause of death worldwide. Blood transfusions can be used to treat patients suffering severe blood loss but donated red blood cells (RBCs) have several limitations that limit their availability and use. To solve the problems associated with donated RBCs, several acellular haemoglobin-based oxygen carriers (HBOCs) have been developed to restore the most important function of blood: oxygen transport. One promising HBOC is the naturally extracellular haemoglobin (i.e. erythrocruorin) of Lumbricus terrestris (LtEc). The goal of this study was to maximise the portability of LtEc by lyophilising it and then testing its stability at elevated temperatures. To prevent oxidation, several cryoprotectants were screened to determine the optimum formulation for lyophilisation that could minimise oxidation of the haem iron and maximise recovery. Furthermore, samples were also deoxygenated prior to storage to decrease auto-oxidation, while resuspension in a solution containing ascorbic acid was shown to partially reduce LtEc that had oxidised during storage (e.g. from 42% Fe3+ to 11% Fe3+). Analysis of the oxygen equilibria and size of the resuspended LtEc showed that the lyophilisation, storage, and resuspension processes did not affect the oxygen transport properties or the structure of the LtEc, even after 6 months of storage at 40 °C. Altogether, these efforts have yielded a shelf-stable LtEc powder that can be stored for long periods at high temperatures, but future animal studies will be necessary to prove that the resuspended product is a safe and effective oxygen transporter in vivo.

Abstract Background Digital interventions are potential tools for reducing and limiting occupational sedentary behaviour (SB) in sedentary desk-based jobs. Given the harmful effects of sitting too much and sitting for too long while working, the aim of this systematic review and meta-analysis was to examine the effectiveness of workplace interventions, that incorporated digital elements, to reduce the time spent in SB in office workers. Methods Randomised control trials that evaluated the implementation of workplace interventions that incorporated digital elements for breaking and limiting SB among desk-based jobs were identified by literature searches in six electronic databases (PubMed, Web of Science, Scopus, CINAHL, PsycINFO and PEDro) published up to 2023. Studies were included if total and/or occupational SB were assessed. Only studies that reported pre- and postintervention mean differences and standard deviations or standard errors for both intervention arms were used for the meta-analysis. The meta-analysis was conducted using Review Manager 5 (RevMan 5; Cochrane Collaboration, Oxford, UK). Risk of bias was assessed using the Standard Quality Assessment Criteria for Evaluating Primary Research Papers from a Variety of Fields QUALSYST tool. Results Nineteen studies were included in the systematic review. The most employed digital elements were information delivery and mediated organisational support and social influences. Multicomponent, information, and counselling interventions measuring total and/or occupational/nonoccupational SB time by self-report or via device-based measures were reported. Multicomponent interventions were the most represented. Eleven studies were included in the meta-analysis, which presented a reduction of 29.9 (95% CI: -45.2, -14.5) min/8 h workday in SB (overall effect: Z = 3.81). Conclusions Multicomponent interventions, using a wide range of digital features, have demonstrated effectiveness in reducing time spent in SB at the workplace among desk-based employees. However, due to hybrid work (i.e., work in the office and home) being a customary mode of work for many employees, it is important for future studies to assess the feasibility and effectiveness of these interventions in the evolving work landscape. Trial registration The review protocol was registered in the Prospero database (CRD42022377366).

Water temperature is an important environmental factor for many ecological processes in coastal ecosystems. Here, we study water temperature dynamics at a set of study sites on the Atlantic coast of Nova Scotia where eelgrass beds are found. The central emphasis is to predict temperature on scales relevant to coastal ecosystem processes using a high-resolution nearshore oceanographic model based on the Finite Volume Community Ocean Model (FVCOM). The model predictions were evaluated against observed temperature time series at six sites for three years from 2017-2019; the evaluation indicates that the model was able to replicate the temperature variation on time scales from hours to seasonal. We also used various biologically tailored temperature metrics relevant to eelgrass condition, including mean seasonal values and variability, daily ranges, growing degree day (GDD), and warm events, to validate the model against time series observations to better understand the temperature regime at the study sites. Frequency resolved Willmott skill scores were >0.7, and the temperature metrics were well predicted with the exception of a bias in GDD at some of the shallow sites. The eelgrass sites have a wide range of temperature conditions. Mean water temperature in the summer differed by more than 7°C between the shallowest and the deepest sites, and the rate of heat accumulation was fastest at shallow sites which had ≥ 12 extreme warm events per year. While the amplitude of the temperature variations within the high frequency band (

Atmospheric methane (CH4) is the second-most-important anthropogenic greenhouse gas and has a 20-year global warming potential 82 times greater than carbon dioxide (CO2). Anthropogenic sources account for ∼ 60 % of global CH4 emissions, of which 20 % come from oil and gas exploration, production and distribution. High-resolution satellite-based imaging spectrometers are becoming important tools for detecting and monitoring CH4 point source emissions, aiding mitigation. However, validation of these satellite measurements, such as those from the commercial GHGSat satellite constellation, has so far not been documented for active leaks. Here we present the monitoring and quantification, by GHGSat's satellites, of the CH4 emissions from an active gas leak from a downstream natural gas distribution pipeline near Cheltenham, UK, in the spring and summer of 2023 and provide the first validation of the satellite-derived emission estimates using surface-based mobile greenhouse gas surveys. We also use a Lagrangian transport model, the UK Met Office's Numerical Atmospheric-dispersion Modelling Environment (NAME), to estimate the flux from both satellite- and ground-based observation methods and assess the leak's contribution to observed concentrations at a local tall tower site (30 km away). We find GHGSat's emission estimates to be in broad agreement with those made from the in situ measurements. During the study period (March–June 2023) GHGSat's emission estimates are 236–1357 kg CH4 h−1, whereas the mobile surface measurements are 634–846 kg CH4 h−1. The large variability is likely down to variations in flow through the pipe and engineering works across the 11-week period. Modelled flux estimates in NAME are 181–1243 kg CH4 h−1, which are lower than the satellite- and mobile-survey-derived fluxes but are within the uncertainty. After detecting the leak in March 2023, the local utility company was contacted, and the leak was fixed by mid-June 2023. Our results demonstrate that GHGSat's observations can produce flux estimates that broadly agree with surface-based mobile measurements. Validating the accuracy of the information provided by targeted, high-resolution satellite monitoring shows how it can play an important role in identifying emission sources, including unplanned fugitive releases that are inherently challenging to identify, track, and estimate their impact and duration. Rapid, widespread access to such data to inform local action to address fugitive emission sources across the oil and gas supply chain could play a significant role in reducing anthropogenic contributions to climate change.

Societal Impact Statement Genetically modified (GM) crops have the potential to address multiple challenges for African smallholder farmers but are limited by several institutional constraints. Public–private partnerships (PPPs) are seen as an organizational fix to one such constraint, bringing privately held intellectual property rights on key crop technologies to African public institutions to develop GM crops for smallholder farmers. Here, a new comprehensive dataset of GM crops in Africa is used to understand the extent and efficacy of PPP‐led GM crop development for smallholder farmers and discuss what might limit their potential in the future. Summary Genetically modified (GM) crops are promoted as a key tool to address multiple challenges in Africa, including the impacts of climate change and food insecurity. Observers have noted, however, significant institutional challenges to achieving such goals, most notably, intellectual property rights (IPR) to key GM traits being held by private companies who have limited incentives to develop those technologies for smallholder farmers. To bridge the gap between privately held IPR and pro‐poor crop breeding, advocates have called for increased funding for institutional innovations such as public–private partnerships (PPPs) to facilitate the transfer of crop technologies from private companies to public research institutes. For the past two decades, donors and firms have invested considerable resources toward PPPs. However, to date, few research efforts have empirically examined the extent and effectiveness of PPPs at the continental scale. This study draws from a new comprehensive dataset on GM crop research and development in Africa to examine whether the anticipated advantages of PPPs have resulted in an improved ability to deliver GM crops to smallholder farmers. We find that although PPP research has focused on crops and traits more relevant for smallholder farmers, many of these efforts have been suspended, with only one crop thus far reaching the hands of farmers. PPPs can address some issues related to GM crop development but still appear constrained by other institutional challenges, which may limit their development, reach, and the achievement of targeted benefits for smallholder farmers.

Background: The Ireland North and South Report Card on Physical Activity (PA) for Children and Adolescents aims to monitor progress in PA participation across a range of internationally established indicators. Methods: Data were collated for 11 indicators and graded following the harmonised Active Healthy Kids Global Alliance report card process. Six representative studies (sample size range n = 898 to n = 15,557) were primarily used in the grading, with many indicators supplemented with additional studies and reports. Data collected since the implementation of COVID-19 public health measures in March 2020 were excluded. Results: Grades were awarded as follows: ‘Overall physical activity’, C-; ‘Organised Sport and Physical Activity’, C; ‘Active Play’, INC; ‘Sedentary Behaviours’, C-; ‘Physical Fitness’, INC; ‘Family and Peers’, D+; ‘School’, C-; ‘Physical Education’, D; ‘Community and Environment’, B+ and ‘Government’, B. Separate grades were awarded for disability as follows; ‘Overall physical activity’, F; ‘Organised Sport and Physical Activity’, D; ‘Sedentary Behaviours’, C-; ‘Family and Peers’, C; ‘School’, C- and ‘Government’, B. ‘Active Play’, ‘Physical Fitness’, ‘Physical Education’ and ‘Community and Environment’ were all graded INC for disability. Since the last report card in 2016, four grades remained the same, three increased (‘Overall physical activity’, ‘School’ and ‘Physical Education’) and two (‘Family and Peers,’ and ‘Government’) were awarded grades for the first time. Conclusion: Grades specific to children and adolescents with disability were generally lower for each indicator. While small improvements have been shown across a few indicators, PA levels remain low across many indicators for children and adolescents.

Geothermal features, such as hot springs and mud volcanoes, host diverse microbial life, including many extremophile organisms. The physicochemical parameters of the geothermal feature, such as temperature, pH, and heavy metal concentration, can influence the alpha and beta diversity of microbial life in these environments, as can spatiotemporal differences between sites and sampling. In this study, water and sediment samples were collected and analyzed from eight geothermal sites at Yellowstone National Park, including six hot springs, a mud volcano, and an acidic lake within the same week in July 2019, and these geothermal sites varied greatly in their temperature, pH, and chemical composition. All samples were processed and analyzed with the same methodology and taxonomic profiles and alpha and beta diversity metrics determined with 16S rRNA sequencing. These microbial diversity results were then analyzed with respect to pH, temperature, and chemical composition of the geothermal features. Results indicated that predominant microbial species varied greatly depending on the physicochemical composition of the geothermal site, with decreases in pH and increases in dissolved heavy metals in the water corresponding to decreases in alpha diversity, especially in the sediment samples. Similarly, sites with acidic pH values had more similar microbial populations (beta diversity) to one another than to relatively neutral or alkaline pH geothermal sites. This study suggests that pH and/or heavy metal concentration is a more important driver for microbial diversity and population profile than the temperature for these sites and is also the first reported microbial diversity study for multiple geothermal sites in Yellowstone National Park, including the relatively new mud volcano Black Dragon’s Caldron, which erupted in 1948.

BackgroundObservational studies have described associations of maternal smoking during pregnancy with intellectual disability (ID) in the exposed offspring. Whether these results reflect a causal effect or unmeasured confounding is still unclear.MethodsUsing a UK-based prospectively collected birth cohort (the Avon Longitudinal Study of Parents and Children) of 13,479 children born between 1991 and 1992, we assessed the relationship between maternal smoking at 18 weeks’ gestation and offspring risk of ID, ascertained through multiple sources of linked information including primary care diagnoses and education records. Using confounder-adjusted logistic regression, we performed observational analyses and a negative control analysis that compared maternal with partner smoking in pregnancy under the assumption that if a causal effect were to exist, maternal effect estimates would be of greater magnitude than estimates for partner smoking if the two exposures suffer from comparable biases.ResultsIn observational analysis, we found an adjusted odds ratio for ID of 0.75 (95% CI = 0.49–1.13) for any maternal smoking and 0.97 (95% CI = 0.71–1.33) per 10-cigarette increase in number of cigarettes smoked per day. In negative control analysis, comparable effect estimates were found for any partner smoking (OR = 0.94; 95% CI = 0.63–1.40) and number of cigarettes smoked per day (OR = 0.94; 95% CI = 0.74–1.20).ConclusionsThe results are not consistent with a causal effect of maternal smoking during pregnancy on offspring ID.

Death may be the only certainty in life, but for palliative care patients and their carers, it is anything but. How long is there left? Will a hospice bed be available? What new loss (big or small), will tomorrow bring? Research suggests that the poor management of uncertainty in palliative care can significantly impact patient outcomes as well as the experience of bereaved families. Social workers cannot mitigate this uncertainty, but they can support individuals to recognise and engage with it. Often, this can create tensions with their personal instinct to remove distress, as well as their professional drive to ‘fix things’. By overcoming these challenges and embracing their ability to find ways forward ‘in the midst of the messy stuff’, they model a constructive mode of behaviour that patients and other multidisciplinary professionals can then mirror.

In this study, we formally examine the association between penis size dissatisfaction and gun ownership in America. The primary hypothesis, derived from the psychosexual theory of gun ownership, asserts that men who are more dissatisfied with the size of their penises will be more likely to personally own guns. To test this hypothesis, we used data collected from the 2023 Masculinity, Sexual Health, and Politics ( MSHAP ) survey, a national probability sample of 1,840 men, and regression analyses to model personal gun ownership as a function of penis size dissatisfaction, experiences with penis enlargement, social desirability, masculinity, body mass, mental health, and a range of sociodemographic characteristics. We find that men who are more dissatisfied with the size of their penises are less likely to personally own guns across outcomes, including any gun ownership, military-style rifle ownership, and total number of guns owned. The inverse association between penis size dissatisfaction and gun ownership is linear; however, the association is weakest among men ages 60 and older. With these findings in mind, we failed to observe any differences in personal gun ownership between men who have and have not attempted penis enlargement. To our knowledge, this is the first study to formally examine the association between penis size and personal gun ownership in America. Our findings fail to support the psychosexual theory of gun ownership. Alternative theories are posited for the apparent inverse association between penis size dissatisfaction and personal gun ownership, including higher levels of testosterone and constructionist explanations.

Nanoporous silver (np-S) was prepared by free corrosion dealloying of a series of Ag–Al thin films containing between 25 and 73 at.% Al. It was found that precursor composition had an important influence on the nanostructures and morphologies of the np-S. In particular the size of the Ag ligaments systematically decreased from 32 to 13 nm as the Al content was increased over the series. In contrast, there was only a weak effect on pore size, which remained in the range 11–15 nm, with the maximum occurring at about 55 at.% Al. There was however a significant increase in the density of the pores as the Al content of the precursor was increased. The electrical resistivity of the np-S increases with the decrease in ligament size, changing from about 3 × 10−8 Ω m for sponges with ligaments of about 32 nm diameter rising to 30 × 10−8 Ω m for the sponge with the 13 nm ligaments. The surface area of the np-S was estimated by the electrochemical capacitance in KNO3 solutions and was estimated to increase by an order of magnitude compared to a smooth Ag surface. There was a systematic change in the optical properties of the sponges, with a trend towards less metallic behaviour as the ligament size decreased and pore density increased. These changes culminated in the sponge prepared from the 73 at.% Al precursor having non-metallic characteristics with regard to visible and near-infrared light. The volume fraction of metal was estimated to be of the order of 40 ± 5%. Prior annealing of the precursor inhibited dealloying.

Objective:. To compare the rates of revision surgery for symptomatic neuromas in patients undergoing primary transtibial amputations with and without targeted muscle reinnervation (TMR). Design:. Retrospective cohort study. Setting:. Level I trauma hospital and tertiary military medical center. Patients/Participants:. Adult patients undergoing transtibial amputations with and without TMR. Intervention:. Transtibial amputation with targeted muscle reinnervation. Main Outcome Measurements:. Reoperation for symptomatic neuroma. Results:. During the study period, there were 112 primary transtibial amputations performed, 29 with TMR and 83 without TMR. Over the same period, there were 51 revision transtibial amputations performed, including 23 (21%) in the patients undergoing primary transtibial amputation at the study institution. The most common indications for revision surgery were wound breakdown/dehiscence (42%, n = 25), followed by symptomatic neuroma 18% (n = 9/51) and infection/osteomyelitis (17%, n = 10) as the most common indications. However, of the patients undergoing primary amputation at the study's institution, there was no difference in reoperation rates for neuroma when comparing the TMR group (3.6%, n = 1/28) and no TMR group (4.0%, n = 3/75) (P = 0.97). Conclusions:. Symptomatic neuroma is one of the most common reasons for revision amputation; however, this study was unable to demonstrate a difference in revision surgery rates for neuroma for patients undergoing primary transtibial amputation with or without targeted muscle reinnervation. Level of Evidence:. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Background Psychiatric comorbidities are common in patients with epilepsy. Reasons for the co-occurrence of psychiatric conditions and epilepsy remain poorly understood.Aim We aimed to triangulate the relationship between epilepsy and psychiatric conditions to determine the extent and possible origins of these conditions.Methods Using nationwide Swedish health registries, we quantified the lifetime prevalence of psychiatric disorders in patients with epilepsy. We then used summary data from genome-wide association studies to investigate whether the identified observational associations could be attributed to a shared underlying genetic aetiology using cross-trait linkage disequilibrium score regression. Finally, we assessed the potential bidirectional relationships using two-sample Mendelian randomisation.Results In a cohort of 7 628 495 individuals, we found that almost half of the 94 435 individuals diagnosed with epilepsy were also diagnosed with a psychiatric condition in their lifetime (adjusted lifetime prevalence, 44.09%; 95% confidence interval (CI) 43.78% to 44.39%). We found evidence for a genetic correlation between epilepsy and some neurodevelopmental and psychiatric conditions. For example, we observed a genetic correlation between epilepsy and attention-deficit/hyperactivity disorder (rg=0.18, 95% CI 0.09 to 0.27, p

The COVID-19 pandemic caused far-reaching societal changes, including significant educational impacts affecting over 1.6 billion pupils and 100 million education practitioners globally. Senior school leaders were at the forefront and were exposed to particularly high demands during a period of "crisis leadership". This occupation were already reporting high work-related stress and large numbers leaving the profession preceding COVID-19. This cross-sectional descriptive study through the international COVID-Health Literacy network aimed to examine the well-being and work-related stress of senior school leaders (n = 323) in Wales (n = 172) and Northern Ireland (n = 151) during COVID-19 (2021-2022). Findings suggest that senior school leaders reported high workloads (54.22±11.30 hours/week), low well-being (65.2% n = 202, mean WHO-5 40.85±21.57), depressive symptoms (WHO-5 34.8% n = 108) and high work-related stress (PSS-10: 29.91±4.92). High exhaustion (BAT: high/very high 89.0% n = 285) and specific psychosomatic complaints (experiencing muscle pain 48.2% n = 151) were also reported, and females had statistically higher outcomes in these areas. School leaders were engaging in self-endangering working behaviours; 74.7% (n = 239) gave up leisure activities in favour of work and 63.4% (n = 202) sacrificed sufficient sleep, which was statistically higher for females. These findings are concerning given that the UK is currently experiencing a "crisis" in educational leadership against a backdrop of pandemic-related pressures. Senior leaders' high attrition rates further exacerbate this, proving costly to educational systems and placing additional financial and other pressures on educational settings and policy response. This has implications for senior leaders and pupil-level outcomes including health, well-being and educational attainment, requiring urgent tailored and targeted support from the education and health sectors. This is particularly pertinent for Wales and Northern Ireland as devolved nations in the UK, who are both implementing or contemplating major education system level reforms, including new statutory national curricula, requiring significant leadership, engagement and ownership from the education profession.

Atmospheric methane (CH4) concentrations are rising, which are expected to lead to a corresponding increase in the global seasonal cycle amplitude (SCA) – the difference between its seasonal maximum and minimum values. The reaction between CH4 and its main sink, OH, is dependent on the amount of CH4 and OH in the atmosphere. The concentration of OH varies seasonally, and due to the increasing burden of CH4 in the atmosphere, it is expected that the SCA of CH4 will increase due to the increased removal of CH4 through a reaction with OH in the atmosphere. Spatially varying changes in the SCA could indicate long-term persistent variations in the seasonal sources and sinks, but such SCA changes have not been investigated. Here we use surface flask measurements and a 3D chemical transport model (TOMCAT) to diagnose changes in the SCA of atmospheric CH4 between 1995–2020 and attribute the changes regionally to contributions from different sectors. We find that the observed SCA decreased by 4 ppb (7.6 %) in the northern high latitudes (NHLs; 60–90∘ N), while the SCA increased globally by 2.5 ppb (6.5 %) during this time period. TOMCAT reproduces the change in the SCA at observation sites across the globe. Therefore, we use it to attribute regions which are contributing to the changes in the NHL SCA, which shows an unexpected change in the SCA that differs from the rest of the world. We find that well-mixed background CH4, likely from emissions originating in, and transported from, more southerly latitudes has the largest impact on the decreasing SCA in the NHLs (56.5 % of total contribution to NHLs). In addition to the background CH4, recent emissions from Canada, the Middle East, and Europe contribute 16.9 %, 12.1 %, and 8.4 %, respectively, to the total change in the SCA in the NHLs. The remaining contributions are due to changes in emissions and transport from other regions. The three largest regional contributions are driven by increases in summer emissions from the Boreal Plains in Canada, decreases in winter emissions across Europe, and a combination of increases in summer emissions and decreases in winter emissions over the Arabian Peninsula and Caspian Sea in the Middle East. These results highlight that changes in the observed seasonal cycle can be an indicator of changing emission regimes in local and non-local regions, particularly in the NHL, where the change is counterintuitive.

The effective separation of ore is based on two fundamental processes: liberation and separability. Liberation involves the reduction of size, yielding smaller particles with enhanced compositional homogeneity. Understanding liberation requires an understanding of rock breakage, as it impacts mineral liberation and helps identify ores suitable for pre-concentration. Non-random breakage, influenced by textural and mineral properties, introduces heterogeneity in mineral distribution across size fractions. Physical attributes, including ore and gangue mineralogy and texture, influence fractionation tendencies during breakage. Notably, the presence of mineralization in veins substantially assists early-stage liberation in mineral processing. The aim of this study is to develop a methodology that allows the prediction of natural fractionation tendencies based on geological, mineralogical, and textural data using Discrete Element Method (DEM) modeling. DEM simulations provide insights into granular material behavior, capturing phenomena such as crack initiation and propagation. The use of DEM, particularly with models such as the Flat Joint Model (FJM), enhances our understanding of rock damage mechanisms. In this paper, DEM is used to predict preferential grade by size deportment, and a numerical model is developed to reflect grade distributions across size fractions. A fragmentation analysis is conducted after rock breakage simulations using DEM to analyze the fragment sizes and grades and calculate the Response Rankings of synthetic specimens.

The impact of cancer cachexia on the colonic microbiota is poorly characterized. This study assessed the effect of two cachectic-producing tumor types on the gut microbiota to determine if a similar dysbiosis could be found. In addition, it was determined if a diet containing an immunonutrient-rich food (walnuts) known to promote the growth of probiotic bacteria in the colon could alter the dysbiosis and slow cachexia. Male Fisher 344 rats were randomly assigned to a semi-purified diet with or without walnuts. Then, within each diet group, rats were further assigned randomly to a treatment group: tumor-bearing ad libitum fed (TB), non-tumor-bearing ad libitum fed (NTB-AL), and non-tumor-bearing group pair-fed to the TB (NTB-PF). The TB group was implanted either with the Ward colon carcinoma or MCA-induced sarcoma, both transplantable tumor lines. Fecal samples were collected after the development of cachexia, and bacteria species were identified using 16S rRNA gene analysis. Both TB groups developed cachexia but had a differently altered gut microbiome. Beta diversity was unaffected by treatment (NTB-AL, TB, and NTB-PF) regardless of tumor type but was affected by diet. Also, diet consistently changed the relative abundance of several bacteria taxa, while treatment and tumor type did not. The control diet increased the abundance of A. Anaeroplasma, while the walnut diet increased the genus Ruminococcus. There were no common fecal bacterial changes characteristic of cachexia found. Diet consistently changed the gut microbiota, but these changes were insufficient to slow the progression of cachexia, suggesting cancer cachexia is more complex than a few gut microbiota shifts.

Abstract Zika virus (ZIKV), an arbovirus transmitted by mosquitoes, was identified as a cause of congenital disease during a major outbreak in the Americas in 2016. Vaccine design strategies relied on limited available isolate sequence information due to the rapid response necessary. The first-generation ZIKV mRNA vaccine, mRNA-1325, was initially generated and, as additional strain sequences became available, a second mRNA vaccine, mRNA-1893, was developed. Herein, we compared the immune responses following mRNA-1325 and mRNA-1893 vaccination and reported that mRNA-1893 generated comparable neutralizing antibody titers to mRNA-1325 at 1/20th of the dose and provided complete protection from ZIKV challenge in non-human primates. In-depth characterization of these vaccines indicated that the observed immunologic differences could be attributed to a single amino acid residue difference that compromised mRNA-1325 virus-like particle formation.

Abstract Seagrass beds inhabit highly heterogeneous temperature regimes that characterize the marine nearshore. Temperature directly influences seagrasses and also provides indirect information on other ecologically relevant environmental variables. Multiple temperature processes operate on seasonal and sub‐seasonal timescales (i.e., hours to months) and include variation from seasonal air–sea heat fluxes, advective heat transport from upwelling and tidal circulation, and daily heating and cooling of shallow waters. Despite this, seagrass–temperature studies typically only examine a single isolated temperature process, often seasonal heating/cooling or marine heatwaves. Furthermore, elucidation of relationships between different short‐term temperature processes and seagrass metrics could provide insights into biologically relevant temperature metrics for seagrasses. Here, we examine the effects of multiple short‐term temperature processes on Zostera marina beds in Atlantic Canada, by describing the seasonal phenology of bed characteristics, plant morphology, and physiology across different temperature regimes and by identifying relationships between different temperature and seagrass metrics. We also include water depth as a proxy for light availability. Four distinct short‐term temperature processes (median temperature, growing degree day [heat accumulation], daily temperature range, and time in the optimal temperature range [5–23°C]) were used to categorize temperature regimes across our study sites as warm and highly variable, or cool and less variable. We found that both temperature regime and light availability were important for leaf area index (LAI) and shoot density, which both decreased with increasing depth yet had the strongest seasonal differences and maximum rates of increase (shoot density) or lowest values and maximum rates of decrease (LAI) in warm and highly variable temperature regimes. These temperature regimes were also associated with seasonal patterns in number of leaves, reduced leaf lengths and number of leaves per shoot, and thinner rhizomes with less carbohydrate storage. Generalized additive models (GAMs) for each seagrass metric using the four temperature processes indicated that while median temperature displayed expected relationships with almost every seagrass metric, inclusion of other temperature processes revealed additional insights not evident from median temperature alone. Our study shows that different sources of short‐term temperature variation influence seagrass properties and that accounting for these will improve our understanding of the temperature–seagrass interaction.

Abstract Background The domestic mite Blomia tropicalis is a major source of allergens in tropical and subtropical regions. Despite its great medical importance, the allergome of this mite has not been sufficiently studied. Only 14 allergen groups have been identified in B. tropicalis thus far, even though early radioimmunoelectrophoresis techniques (27 uncharacterized allergen complexes) and comparative data based on 40 allergen groups officially recognized by the World Health Organization (WHO)/IUIS in domestic astigmatid mites suggest the presence of a large set of additional allergens. Methods Here, we employ a multiomics approach to assess the allergome of B. tropicalis using genomic and transcriptomic sequence data and perform highly sensitive protein abundance quantification. Findings Among the 14 known allergen groups, we confirmed 13 (one WHO/IUIS allergen, Blo t 19, was not found) and identified 16 potentially novel allergens based on sequence similarity. These data indicate that B. tropicalis shares 27 known/deduced allergen groups with pyroglyphid house dust mites (genus Dermatophagoides). Among these groups, five allergen‐encoding genes are highly expressed at the transcript level: Blo t 1, Blo t 5, Blo t 21 (known), Blo t 15, and Blo t 18 (predicted). However, at the protein level, a different set of most abundant allergens was found: Blo t 2, 10, 11, 20 and 21 (mite bodies) or Blo t 3, 4, 6 and predicted Blo t 13, 14 and 36 (mite feces). Interpretation We report the use of an integrated omics method to identify and predict an array of mite allergens and advanced, label‐free proteomics to determine allergen protein abundance. Our research identifies a large set of novel putative allergens and shows that the expression levels of allergen‐encoding genes may not be strictly correlated with the actual allergenic protein abundance in mite bodies.

Food security is recognized as an inherent human right, enshrined within the principles of the Agenda 2030. The Global Report of Food Crises 2022 points out 193 million people facing severe food insecurity across 53 countries, posing challenges to decision-makers and institutions. Among the many causes of food crises, violent conflict, economic shocks, and environmental pressures are the most influential. In this work, we focus primarily on the conflict-related domain. Finding a stable relationship between conflict and food insecurity is complex for several reasons: first, the relationship is mutually reinforcing; second, the full impact of conflict on food insecurity may take time to have an effect; and third, conflict itself is a multidimensional phenomenon and can include multiple types of violent events. This research set out to comparatively assess the impact of different types of violence on self-reported food insecurity in three prominent food crisis contexts: Burkina Faso, Syria, and Yemen. A measure of food-related classifying events was developed using a rules-based approach. The analysis showed that this approach can effectively code and classify food-related conflict in diverse contexts. By refining the search string, it becomes possible to capture food-related conflict in various food systems. Our findings point out that the new-build measure of food-related conflict is more strongly correlated to subsequent self-reported insufficient food consumption than other forms of violence. The results demonstrate that this relationship is robust across a range of data collection windows and across discrete time periods of analysis. In summary, the research suggests that focusing on the use of food and food systems as tactics in conflict can be highly valuable for understanding and addressing food insecurity.

This paper describes the use of a unique spatio-temporally resolved precipitation and temperature dataset to assess the spatio-temporal dynamics of water resources over a period of almost seven decades across the Sierra Nevada mountain range, which is the most southern Alpine environment in Europe. The altitude and geographical location of this isolated alpine environment makes it a good detector of climate change. The data were generated by applying geostatistical co-kriging to significant instrumental precipitation and temperature (minimum, maximum and mean) datasets. The correlation between precipitation and altitude was not particularly high and the statistical analysis yielded some surprising results in the form of mean annual precipitation maps and yearly precipitation time series. These results confirm the importance of orographic precipitation in the Sierra Nevada mountain range and show a decrease in mean annual precipitation of 33 mm per decade. Seasonality, however, has remained constant throughout the period of the study. The results show that previous studies have overestimated the altitudinal precipitation gradient in the Sierra Nevada and reveal its complex spatial variability. In addition, the results show a clear correspondence between the mean annual precipitation and the NAO index and, to a much lesser extent, the WeMO index. With respect to temperature, there is a high correlation between minimum temperature and altitude (coefficient of correlation = −0.84) and between maximum temperature and altitude (coefficient of correlation = −0.9). Thus, our spatial temperature maps were very similar to topographic maps, but the temporal trend was complex, with negative (decreasing) and positive (increasing) trends. A dynamic model of snowfall can be obtained by using the degree-day methodology. These results should be considered when checking the local performance of climatological models.

A nondestructive and rapid classification approach was developed for identifying aflatoxin-contaminated single peanut kernels using field-portable vibrational spectroscopy instruments (FT-IR and Raman). Single peanut kernels were either spiked with an aflatoxin solution (30 ppb–400 ppb) or hexane (control), and their spectra were collected via Raman and FT-IR. An uHPLC-MS/MS approach was used to verify the spiking accuracy via determining actual aflatoxin content on the surface of randomly selected peanut samples. Supervised classification using soft independent modeling of class analogies (SIMCA) showed better discrimination between aflatoxin-contaminated (30 ppb–400 ppb) and control peanuts with FT-IR compared with Raman, predicting the external validation samples with 100% accuracy. The accuracy, sensitivity, and specificity of SIMCA models generated with the portable FT-IR device outperformed the methods in other destructive studies reported in the literature, using a variety of vibrational spectroscopy benchtop systems. The discriminating power analysis showed that the bands corresponded to the C=C stretching vibrations of the ring structures of aflatoxins were most significant in explaining the variance in the model, which were also reported for Aspergillus-infected brown rice samples. Field-deployable vibrational spectroscopy devices can enable in situ identification of aflatoxin-contaminated peanuts to assure regulatory compliance as well as cost savings in the production of peanut products.

Objectives In recent years, ‘deaths of despair’ due to drugs, alcohol and suicide have contributed to rising mid-life mortality in the USA. We examine whether despair-related deaths and mid-life mortality trends are also changing in peer countries, the UK and Canada.Design Descriptive analysis of population mortality rates.Setting The USA, UK (and constituent nations England and Wales, Northern Ireland and Scotland) and Canada, 2001–2019.Participants Full population aged 35–64 years.Outcome measures We compared all-cause and ‘despair’-related mortality trends at mid-life across countries using publicly available mortality data, stratified by three age groups (35–44, 45–54 and 55–64 years) and by sex. We examined trends in all-cause mortality and mortality by causes categorised as (1) suicides, (2) alcohol-specific deaths and (3) drug-related deaths. We employ several descriptive approaches to visually inspect age, period and cohort trends in these causes of death.Results The USA and Scotland both saw large relative increases and high absolute levels of drug-related deaths. The rest of the UK and Canada saw relative increases but much lower absolute levels in comparison. Alcohol-specific deaths showed less consistent trends that did not track other ‘despair’ causes, with older groups in Scotland seeing steep declines over time. Suicide deaths trended slowly upward in most countries.Conclusions In the UK, Scotland has suffered increases in drug-related mortality comparable with the USA, while Canada and other UK constituent nations did not see dramatic increases. Alcohol-specific and suicide mortalities generally follow different patterns to drug-related deaths across countries and over time, questioning the utility of a cohesive ‘deaths of despair’ narrative.

IntroductionNatural products discovered from bacteria provide critically needed therapeutic leads for drug discovery, and myxobacteria are an established source for metabolites with unique chemical scaffolds and biological activities. Myxobacterial genomes accommodate an exceptional number and variety of biosynthetic gene clusters (BGCs) which encode for features involved in specialized metabolism.MethodsIn this study, we describe the collection, sequencing, and genome mining of 20 myxobacteria isolated from rhizospheric soil samples collected in North America.ResultsNine isolates were determined to be novel species of myxobacteria including representatives from the genera Archangium, Myxococcus, Nannocystis, Polyangium, Pyxidicoccus, Sorangium, and Stigmatella. Growth profiles, biochemical assays, and descriptions were provided for all proposed novel species. We assess the BGC content of all isolates and observe differences between Myxococcia and Polyangiia clusters.DiscussionContinued discovery and sequencing of novel myxobacteria from the environment provide BGCs for the genome mining pipeline. Utilizing complete or near-complete genome sequences, we compare the chromosomal organization of BGCs of related myxobacteria from various genera and suggest that the spatial proximity of hybrid, modular clusters contributes to the metabolic adaptability of myxobacteria.

BackgroundResearchers and policy-makers have highlighted that the potential for organized sports to promote health has been underexploited. Sports clubs have limited capacity to promote health due to their voluntary nature and have called for support from their national sports federations. The present article provides guidelines, based on the theoretical principles of health promoting sports clubs and an analysis of practical tools and proven strategies, to support national sports federations to invest in health promotion (HP).MethodsA qualitative iterative study was undertaken, based on five 2-h meetings of a group of 15 international researchers in HP in sports clubs. Notes and minutes from meetings, as well as shared outputs were analyzed based on the health promoting sports club framework.ResultsGuidelines developed for national sports federations to promote health includes a definition of a health promoting sports federation (HPSF), a description of how the settings-based approach to HP adapts to national sports federations, as well as practical applications of health promoting sports club’s intervention strategies. The analysis of existing tools also demonstrated that most tools are centered on a single dimension of health (social, mental, physical, spiritual or community), and often on a specific health topic. Furthermore, they do not cover HP as a continuous long-lasting process, but are generally short-term programs. The HPSF clarifies theoretical concepts, their practical implementation via case studies and outlines intervention components and tools useful for sports federations in their implementation of HP.ConclusionThe guidelines developed in this study are intended to facilitate national sports federations to acknowledge/understand, reinforce/underpin and foster current and further investment in HP.

Abstract Background Increases in serum gamma‐glutamyltransferase (GGT) activity have been reported in Thoroughbred (TB) racehorses and associated with maladaptation to training but the underlying etiology remains unknown. Hypothesis/Objectives Classify the etiology of high GGT syndrome in racing TBs by assessment of pancreatic enzymes, vitamin E concentrations, and both a candidate gene and whole genome association study. We hypothesized that a genetic variant resulting in antioxidant insufficiency or pancreatic dysfunction would be responsible for high GGT syndrome in TBs. Animals A total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity

Abstract Background There has been a growing interest in the association between maternal levels of vitamin D during pregnancy and offspring autism. However, whether any associations reflect causal effects is still inconclusive. Methods We used data from a UK-based pregnancy cohort study (Avon Longitudinal Study of Parents and Children) comprising 7689 births between 1991 and 1992 with maternal blood vitamin D levels recorded during pregnancy and at least one recorded outcome measure, including autism diagnosis and autism-associated traits. The association between each outcome with seasonal and gestational age-adjusted maternal serum 25-hydroxyvitamin D during pregnancy was estimated using confounder-adjusted regression models. Multiple imputation was used to account for missing data, and restricted cubic splines were used to investigate nonlinear associations. Mendelian randomization was used to strengthen causal inference. Results No strong evidence of an association between maternal serum 25-hydroxyvitamin D during pregnancy and any offspring autism-associated outcome was found using multivariable regression analysis (autism diagnosis: adjusted OR = 0.98, 95% CI = 0.90–1.06), including with multiple imputation (autism diagnosis: adjusted OR = 0.99, 95% CI = 0.93–1.06), and no evidence of a causal effect was suggested by Mendelian randomization (autism diagnosis: causal OR = 1.08, 95% CI = 0.46–2.55). Some evidence of increased odds of autism-associated traits at lower levels of maternal serum 25-hydroxyvitamin D was found using spline analysis. Limitations Our study was potentially limited by low power, particularly for diagnosed autism cases as an outcome. The cohort may not have captured the extreme lows of the distribution of serum 25-hydroxyvitamin D, and our analyses may have been biased by residual confounding and missing data. Conclusions The present study found no strong evidence of a causal link between maternal vitamin D levels in pregnancy and offspring diagnosis or traits of autism.

With increased availability of disaggregated conflict event data for analysis, there are new and old concerns about bias. All data have biases, which we define as an inclination, prejudice, or directionality to information. In conflict data, there are often perceptions of damaging bias, and skepticism can emanate from several areas, including confidence in whether data collection procedures create systematic omissions, inflations, or misrepresentations. As curators and analysts of large, popular data projects, we are uniquely aware of biases that are present when collecting and using event data. We contend that it is necessary to advance an open and honest discussion about the responsibilities of all stakeholders in the data ecosystem – collectors, researchers, and those interpreting and applying findings – to thoughtfully and transparently reflect on those biases; use data in good faith; and acknowledge limitations. We therefore posit an agenda for data responsibility considering its collection and critical interpretation.

The transradial approach (TRA) is an effective and safe alternative to transfemoral access for diagnostic neuroangiography and craniocervical interventions. While the technical aspects of supraclavicular intervention are well-described, there are little data on the TRA for thoracolumbar angiography and intervention. The authors describe the feasibility of the TRA for preoperative thoracic tumor embolization, emphasizing technique, device selection, navigation, and catheterization of thoracolumbar segmental arteries. This approach extends the benefits of TRA to spinal interventional neuroradiology.

Objective: We aimed to evaluate and compare the functional characteristics, safety profile and effectiveness of two commonly used ureteral access sheaths (UAS) during flexible ureteroscopy. Methods: After institutional review board approval, patients with proximal ureteral or kidney stones requiring flexible ureteroscopy and UAS were prospectively randomized to group I or group II according to the type of access sheath used. Primary outcome was incidence of intraoperative complications. Results: Eighty-eight patients were enrolled in the study, 44 patients in each group. Sheath size 12/14 FR was used in both cohorts. Median (IQR) stone size was 10 mm (7-13.5) and 10.5 mm (7.37-14) in group I and II respectively (p = 0.915). Nineteen and twenty patients, in group I and II respectively, were pre-stented. Subjective resistance with insertion of the UAS was observed in 9 and 11 patients in group I and II respectively (p = 0.61) while failed insertion was encountered in one patient in group I. Traxer grade 1 ureteral injury was noted in 5 and 6 patients in group I and II respectively while grade 3 injury was seen in 1 patient for both cohorts (p = 0.338). There was less resistance for UAS placement in pre-stented patients (p = 0.0202) but without significant difference in ureteric injury incidence (p = 0.175). Emergency department visits were encountered in 7 (group I) and 5 patients (group II) (p = 0.534). Conclusions: The studied UASs were comparable regarding safety and efficacy in the current study. Pre-stented and dilated ureters had less resistance to insertion although this was not reflected on incidence of ureteric injury.

Lead (Pb) toxicity is a major health problem and bone is the major reservoir. Lead is detrimental to bone, affects bone remodeling and is associated with elderly fractures. Osteocalcin (OC) affects bone remodeling, improves fracture resistance and decreases with age and in some diseases. The effect of lead in osteocalcin depleted bone is unknown and of interest. We compared bone mineral properties of control and Pb exposed (from 2 to 6 months) femora from female adult C57BL6 OC+/+ and OC−/− mice using Fourier Transform Infrared Imaging (FTIRI), Micro-computed tomography (uCT), bone biomechanical measurements and serum turnover markers (P1NP, CTX). Lead significantly increased turnover in OC+/+ and in OC−/− bones producing increased total volume, area and marrow area/total area with decreased BV/TV compared to controls. The increased turnover decreased mineral/matrix vs. Oc+/+ and increased mineral/matrix and crystallinity vs. OC−/−. PbOC−/− had increased bone formation, cross-sectional area (Imin) and decreased collagen maturity compared OC−/− and PbOC+/+. Imbalanced turnover in PbOC−/− confirmed the role of osteocalcin as a coupler of formation and resorption. Bone strength and stiffness were reduced in OC−/− and PbOC−/− due to reduced material properties vs. OC+/+ and PbOC+/+ respectively. The PbOC−/− bones had increased area to compensate for weaker material properties but were not proportionally stronger for increased size. However, at low lead levels osteocalcin plays the major role in bone strength suggesting increased fracture risk in low Pb2+ exposed elderly could be due to reduced osteocalcin as well. Years of low lead exposure or higher blood lead levels may have an additional effect on bone strength.

Glioblastoma multiforme (GBM) is the most common malignant primary brain tumor, known for its poor prognosis and high recurrence rate. Current standard of care includes surgical resection followed by combined radiotherapy and chemotherapy. Although immunotherapies have yielded promising results in hematological malignancies, their successful application in GBM remains limited due to a host of immunosuppressive factors unique to GBM. As a result of these roadblocks, research efforts have focused on utilizing combinatorial immunotherapies that target networks of immune processes in GBM with promising results in both preclinical and clinical trials, although limitations in overcoming the immunosuppressive factors within GBM remain. In this review, we aim to discuss the intrinsic and adaptive immune resistance unique to GBM and to summarize the current evidence and outcomes of engineered and non-engineered treatments targeted at overcoming GBM resistance to immunotherapy. Additionally, we aim to highlight the most promising strategies of targeted GBM immunotherapy combinatorial treatments and the insights that may directly improve the current patient prognosis and clinical care.

Atopic dermatitis is a chronic condition where epidermal barrier dysfunction and cytokine production by infiltrating immune cells exacerbate skin inflammation and damage. A total lipid extract from Macrocystis pyrifera, a brown seaweed, was previously reported to suppress inflammatory responses in monocytes. Here, treatment of human HaCaT keratinocytes with M. pyrifera lipids inhibited tumour necrosis factor (TNF)-α induced TNF receptor-associated factor 2 and monocyte chemoattractant protein (MCP)-1 protein production. HaCaT cells stimulated with TNF-α, interleukin (IL)-4, and IL-13 showed loss of claudin-1 tight junctions, but little improvement was observed following lipid pre-treatment. Three-dimensional cultures of HaCaT cells differentiated at the air–liquid interface showed increased MCP-1 production, loss of claudin-1 tight junctions, and trans-epidermal leakage with TNF-α, IL-4, and IL-13 stimulation, with all parameters reduced by lipid pre-treatment. These findings suggest that M. pyrifera lipids have anti-inflammatory and barrier-protective effects on keratinocytes, which may be beneficial for the treatment of atopic dermatitis or other skin conditions.

Introduction: The aim of this study was to address and enhance our ability to study the clinical outcome of limb salvage (LS), a commonly referenced but ill-defined clinical care pathway, by developing a data-driven approach for the identification of LS cases using existing medical code data to identify characteristic diagnoses and procedures, and to use that information to describe a cohort of US Service members (SMs) for further study. Methods: Diagnosis code families and inpatient procedure codes were compiled and analyzed to identify medical codes that are disparately associated with a LS surrogate population of SMs who underwent secondary amputation within a broader cohort of 3390 SMs with lower extremity trauma (AIS > 1). Subsequently, the identified codes were used to define a cohort of all SMs who underwent lower extremity LS which was compared with the opinion of a panel of military trauma surgeons. Results: The data-driven approach identified a population of n = 2018 SMs who underwent LS, representing 59.5% of the combat-related lower extremity (LE) trauma population. Validation analysis revealed 70% agreement between the data-driven approach and gold standard SME panel for the test cases studied. The Kappa statistic (κ = 0.55) indicates a moderate agreement between the data-driven approach and the expert opinion of the SME panel. The sensitivity and specificity were identified as 55.6% (expert range of 51.8–66.7%) and 87% (expert range of 73.9–91.3%), respectively. Conclusions: This approach for identifying LS cases can be utilized to enable future high-throughput retrospective analyses for studying both short- and long-term outcomes of this underserved patient population.

Closed depressions are scale-invariant landforms that are the most distinctive and characteristic landform in karst terrains at the millimetre-to-kilometre scales. The purpose of this paper is twofold. The first is to raise awareness of the geoheritage and geoeducational asset provided by closed depressions in a high-relief karst massif with the objective of promoting geotourism in the Sierra de las Nieves National Park in Southern Spain, which was declared a national park in 2021. The second is to propose a general, sound methodological approach to achieve the first purpose that can be applied to other national parks and geoparks with karst terrains. This paper identifies the factors that generate geodiversity in closed depressions in karst and, although dissolution is the primary generator in the high relief karst massif analysed, five distinctive types of natural, closed depressions have been recognized and described together with particular cases that deserve consideration. A sixth type of closed depression comprises anthropic closed depressions. Lithology and tectonics are the two main geological factors that determine the different types of natural closed depressions. Closed depressions add value to the geomorphological and hydrogeological diversity of karst terrains, and they can be used at various levels both off-site and on-site for preparing exhibits at a visitor or interpretation centre; as a story resource for guided field tours; and for identifying geosites of special interest for geological itineraries. Generating interpretation methods is an important component of transferring scientific knowledge of, and interest in, karst landscapes to the various types of visitors to the recently declared Sierra de las Nieves National Park in Andalusia, Southern Spain. In addition, an extensive inventory of closed depressions can be used for their identification, mapping, conservation, protection, and management. Such an inventory, which can be obtained efficiently from high spatial resolution digital elevation models, also contributes to the promotion and dissemination of geomorphological science to the general public.

Abstract Background PRAETORIAN is the first randomized controlled trial that demonstrated the noninferiority of subcutaneous ICD (S‐ICD) in comparison with transvenous ICD (TV‐ICD). We retrospectively reviewed electronic records of patients with ICD implanted over the past 6 years, with the primary objective to compare our real‐world single tertiary center experience with the randomized data from the PRAETORIAN study. Methods Seventy S‐ICD patients were compared with 197 TV‐ICD patients, from July 2014 to June 2020 retrospectively, over a median period of 1304 days (296–2451 days). Primary composite endpoints included inappropriate shocks and device‐related malfunctions. Results Patients with S‐ICD implantation were younger than those who received TV‐ICD (mean, 49.7 years vs 63.9 years, p

Introduction: Substance use disorders (SUDs) and addictive behaviours are growing problems which negatively impact health and wellbeing. Occupational therapy can support recovery by facilitating engagement in everyday activities that promote health. To date, the inclusion of occupational therapy in addiction recovery is limited and the evidence base for occupation-focused interventions is lacking. This study explores the impact of an occupational therapy-led intervention on self-reported occupational performance and occupational balance issues for people living with SUDs within an inpatient addiction service. Methodology: A quantitative pre and post-test study was implemented. The Canadian Personal Recovery Outcome Measure (C-PROM) was the sole outcome measure. The C-PROM is a self-report measure which aims to measure personal views of recovery based on rating activity engagement. The cohort of participants were recruited from referrals into 2 inpatient addiction recovery treatment programmes using purposive sampling. Descriptive statistics were run, and a Wilcoxon Signed Rank Test was used to analyse pre and post-test scoring. Results: Sixteen participants (9 male and 7 female) completed the intervention and outcome measure. The majority of participants (31.3%, n = 5) were between 45 and 54 years old. 25% of the sample (n = 4) were in the 35 to 44 age bracket while 18.8% (n = 3) were aged 55 to 64. The majority of participants (68.8%, n = 11) reported substance misuse as their main healthcare concern. The mean score on the C-PROM was significantly higher after participants received the intervention when compared with baseline scoring. Conclusion: Following engagement with an occupational therapist-led intervention participants reported increased engagement in activities and occupational performance. Participants also reported improved occupational balance and increased awareness of personal recovery needs. Further research is required to explore the effectiveness of this intervention in larger samples and to explore the transferability and sustainability of skills post discharge.

Summary: To disseminate through the body, Zika virus (ZIKV) is thought to exploit the mobility of myeloid cells, in particular monocytes and dendritic cells. However, the timing and mechanisms underlying shuttling of the virus by immune cells remains unclear. To understand the early steps in ZIKV transit from the skin, at different time points, we spatially mapped ZIKV infection in lymph nodes (LNs), an intermediary site en route to the blood. Contrary to prevailing hypotheses, migratory immune cells are not required for the virus to reach the LNs or blood. Instead, ZIKV rapidly infects a subset of sessile CD169+ macrophages in the LNs, which release the virus to infect downstream LNs. Infection of CD169+ macrophages alone is sufficient to initiate viremia. Overall, our experiments indicate that macrophages that reside in the LNs contribute to initial ZIKV spread. These studies enhance our understanding of ZIKV dissemination and identify another anatomical site for potential antiviral intervention.

Background Poor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life. Methods Using nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences. Findings Individuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education. Interpretation Our results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

BackgroundThe benefits of real-time continuous glucose monitoring (RT-CGM) are well established for patients with type 1 diabetes (T1D) and patients with insulin-treated type 2 diabetes (T2D). However, the usage and effectiveness of RT-CGM in the context of non–insulin-treated T2D has not been well studied. ObjectiveWe aimed to assess glycemic metrics and rates of RT-CGM feature utilization in users with T1D and non–insulin-treated T2D. MethodsWe retrospectively analyzed data from 33,685 US-based users of an RT-CGM system (Dexcom G6; Dexcom, Inc) who self-identified as having either T1D (n=26,706) or T2D and not using insulin (n=6979). Data included glucose concentrations, alarm settings, feature usage, and event logs. ResultsThe T1D cohort had lower proportions of glucose values in the 70 mg/dl to 180 mg/dl range than the T2D cohort (52.1% vs 70.8%, respectively), with more values indicating hypoglycemia or hyperglycemia and higher glycemic variability. Discretionary alarms were enabled by a large majority in both cohorts. The data sharing feature was used by 38.7% (10,327/26,706) of those with T1D and 10.4% (727/6979) of those with T2D, and the mean number of followers was higher in the T1D cohort. Large proportions of patients with T1D or T2D enabled and customized their glucose alerts. Retrospective analysis features were used by the majority in both cohorts (T1D: 15,783/26,706, 59.1%; T2D: 3751/6979, 53.8%). ConclusionsSimilar to patients with T1D, patients with non–insulin-treated T2D used RT-CGM system features, suggesting beneficial, routine engagement with data by patients and others involved in their care. Motivated patients with diabetes could benefit from RT-CGM coverage.

BackgroundPoor immune function is associated with increased risk for a number of age-related diseases, however, little is known about the impact of early life trauma on immune function in late-life.MethodsUsing nationally representative data from the Health and Retirement Study (n = 5,823), we examined the association between experiencing parental/caregiver death or separation before age 16 and four indicators of immune function in late-life: C-reactive Protein (CRP), Interleukin-6 (IL-6), soluble Tumor Necrosis Factor (sTNFR), and Immunoglobulin G (IgG) response to cytomegalovirus (CMV). We also examined racial/ethnic differences.FindingsIndividuals that identified as racial/ethnic minorities were more likely to experience parental/caregiver loss and parental separation in early life compared to Non-Hispanic Whites, and had poorer immune function in late-life. We found consistent associations between experiencing parental/caregiver loss and separation and poor immune function measured by CMV IgG levels and IL-6 across all racial/ethnic subgroups. For example, among Non-Hispanic Blacks, those that experienced parental/caregiver death before age 16 had a 26% increase in CMV IgG antibodies in late-life (β = 1.26; 95% CI: 1.17, 1.34) compared to a 3% increase in CMV antibodies among Non-Hispanic Whites (β = 1.03; 95% CI: 0.99, 1.07) controlling for age, gender, and parental education.InterpretationOur results suggest a durable association between experiencing early life trauma and immune health in late-life, and that structural forces may shape the ways in which these relationships unfold over the life course.

The precision of temporal multisensory integration is associated with specific aspects of physical functioning in ageing, including gait speed and incidents of falling. However, it is unknown if such an association exists between multisensory integration and grip strength, an important index of frailty and brain health and predictor of disease and mortality in older adults. Here, we investigated whether temporal multisensory integration is associated with longitudinal (eight-year) grip strength trajectories in a large sample of 2,061 older adults (mean age = 64.42 years, SD = 7.20; 52% female) drawn from The Irish Longitudinal Study on Ageing (TILDA). Grip strength (kg) for the dominant hand was assessed with a hand-held dynamometer across four testing waves. Longitudinal k-means clustering was applied to these data separately for sex (male, female) and age group (50–64, 65–74, 75+ years). At wave 3, older adults participated in the Sound Induced Flash Illusion (SIFI), a measure of the precision of temporal audio-visual integration, which included three audio-visual stimulus onset asynchronies (SOAs): 70, 150 and 230 ms. Results showed that older adults with a relatively lower (i.e., weaker) grip strength were more susceptible to the SIFI at the longer SOAs compared to those with a relatively higher (i.e., stronger) grip strength (p

Background: Intellectual disability (ID) describes a neurodevelopmental condition involving impaired cognitive and functional ability. Here, we describe a multisource variable of ID using data from the Avon Longitudinal Study of Parents and Children (ALSPAC). Methods: The multisource indicator variable for ID was derived from i) IQ scores less than 70 measured at age 8 and at age 15, ii) free text fields from parent reported questionnaires, iii) school reported provision of educational services for individuals with a statement of special educational needs for cognitive impairments, iv) from relevant READ codes contained in GP records, iv) international classification of disease diagnoses contained in electronic hospital records and hospital episode statistics and v) recorded interactions with mental health services for ID contained within the mental health services data set. A case of ID was identified if two or more sources indicated ID. A second indicator, labelled as “probable ID”, was created by relaxing the cut off in IQ scores to be less than 85. An indicator variable for known causes of ID was also created to aid in aetiological studies where ID with a known cause may need to be excluded. Results: 158 of 14,370 participants (1.10%) were indicated as having ID by two or more sources and 449 (3.12%) were indicated as having probable ID when the criteria for IQ scores was relaxed to less than 85. There were 476 participants (3.31%) with 1 or fewer sources of available information on ID; these participants had their multisource variable set to missing. The number of cases of ID with known cause was 31 (0.22% of the cohort, 19.6% of those with ID). Conclusions: The multisource variable of ID can be used in future analyses on ID in ALSPAC children.

Variation in the electrical conductivity (EC) of water can reveal environmental disturbance and natural dynamics, including factors such as anthropogenic salinization. Broader application of open source (OS) EC sensors could provide an inexpensive method to measure water quality. While studies show that other water quality parameters can be robustly measured with sensors, a similar effort is needed to evaluate the performance of OS EC sensors. To address this need, we evaluated the accuracy (mean error, %) and precision (sample standard deviation) of OS EC sensors in the laboratory via comparison to EC calibration standards using three different OS and OS/commercial-hybrid (OS/C) EC sensors and data logger configurations and two commercial (C) EC sensors and data logger configurations. We also evaluated the effect of cable length (7.5 m and 30 m) and sensor calibration on OS sensor accuracy and precision. We found a significant difference between OS sensor mean accuracy (3.08%) and all other sensors combined (9.23%). Our study also found that EC sensor precision decreased across all sensor configurations with increasing calibration standard EC. There was also a significant difference between OS sensor mean precision (2.85 μS/cm) and the mean precision of all other sensors combined (9.12 μS/cm). Cable length did not affect OS sensor precision. Furthermore, our results suggest that future research should include evaluating how performance is impacted by combining OS sensors with commercial data loggers as this study found significantly decreased performance in OS/commercial-hybrid sensor configurations. To increase confidence in the reliability of OS sensor data, more studies such as ours are needed to further quantify OS sensor performance in terms of accuracy and precision across different settings and OS sensor and data collection platform configurations.

BackgroundThe COVID-19 pandemic was accompanied by an "infodemic"-an overwhelming excess of accurate, inaccurate, and uncertain information. The social media-based science communication campaign Dear Pandemic was established to address the COVID-19 infodemic, in part by soliciting submissions from readers to an online question box. Our study characterized the information needs of Dear Pandemic's readers by identifying themes and longitudinal trends among question box submissions.MethodsWe conducted a retrospective analysis of questions submitted from August 24, 2020, to August 24, 2021. We used Latent Dirichlet Allocation topic modeling to identify 25 topics among the submissions, then used thematic analysis to interpret the topics based on their top words and submissions. We used t-Distributed Stochastic Neighbor Embedding to visualize the relationship between topics, and we used generalized additive models to describe trends in topic prevalence over time.ResultsWe analyzed 3839 submissions, 90% from United States-based readers. We classified the 25 topics into 6 overarching themes: 'Scientific and Medical Basis of COVID-19,' 'COVID-19 Vaccine,' 'COVID-19 Mitigation Strategies,' 'Society and Institutions,' 'Family and Personal Relationships,' and 'Navigating the COVID-19 Infodemic.' Trends in topics about viral variants, vaccination, COVID-19 mitigation strategies, and children aligned with the news cycle and reflected the anticipation of future events. Over time, vaccine-related submissions became increasingly related to those surrounding social interaction.ConclusionsQuestion box submissions represented distinct themes that varied in prominence over time. Dear Pandemic's readers sought information that would not only clarify novel scientific concepts, but would also be timely and practical to their personal lives. Our question box format and topic modeling approach offers science communicators a robust methodology for tracking, understanding, and responding to the information needs of online audiences.

Background The COVID-19 pandemic was accompanied by an “infodemic”–an overwhelming excess of accurate, inaccurate, and uncertain information. The social media-based science communication campaign Dear Pandemic was established to address the COVID-19 infodemic, in part by soliciting submissions from readers to an online question box. Our study characterized the information needs of Dear Pandemic’s readers by identifying themes and longitudinal trends among question box submissions. Methods We conducted a retrospective analysis of questions submitted from August 24, 2020, to August 24, 2021. We used Latent Dirichlet Allocation topic modeling to identify 25 topics among the submissions, then used thematic analysis to interpret the topics based on their top words and submissions. We used t-Distributed Stochastic Neighbor Embedding to visualize the relationship between topics, and we used generalized additive models to describe trends in topic prevalence over time. Results We analyzed 3839 submissions, 90% from United States-based readers. We classified the 25 topics into 6 overarching themes: ‘Scientific and Medical Basis of COVID-19,’ ‘COVID-19 Vaccine,’ ‘COVID-19 Mitigation Strategies,’ ‘Society and Institutions,’ ‘Family and Personal Relationships,’ and ‘Navigating the COVID-19 Infodemic.’ Trends in topics about viral variants, vaccination, COVID-19 mitigation strategies, and children aligned with the news cycle and reflected the anticipation of future events. Over time, vaccine-related submissions became increasingly related to those surrounding social interaction. Conclusions Question box submissions represented distinct themes that varied in prominence over time. Dear Pandemic’s readers sought information that would not only clarify novel scientific concepts, but would also be timely and practical to their personal lives. Our question box format and topic modeling approach offers science communicators a robust methodology for tracking, understanding, and responding to the information needs of online audiences.

Introduction: Point-of care-ultrasound (POCUS) has become ubiquitous in emergency medicine practice for the management of emergent pathophysiology. There is growing interest in its potential as a diagnostic tool in the prehospital setting. Few studies have examined the feasibility or efficacy of curricula targeted at teaching POCUS to prehospital personnel. Our objective in this study was to investigate a curriculum for the extended focused assessment with sonography in trauma (eFAST) exam in helicopter emergency medical services (HEMS) crews. Methods: This was a pre/post intervention study of HEMS personnel at a tertiary care center. Subjects were administered a pre-intervention written test and an observed structured clinical evaluation (OSCE). Subsequently, they participated in an educational intervention intended to impart proficiency in performing the eFAST. Subjects underwent post-intervention written exams and OSCEs. We analyzed pre- and post-intervention test performance along with the number and quality of practice ultrasound examinations achieved. Results: Sixteen subjects were enrolled (62.5% male, mean age 44.1). After undergoing the intervention, the mean written test score increased 22.1% (t=3.41; P

We introduce a simple extension to the CBDX model to project cohort mortality rates to extreme old age. The proposed approach fits a polynomial to a sample of age effects, uses the fitted polynomial to project the age effects to ages beyond the sample age range, then splices the sample and projected age effects, and uses the spliced age effects to obtain mortality rates for the higher ages. The proposed approach can be used to value financial instruments such as life annuities that depend on projections of extreme old age mortality rates.