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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 (

Over the course of a lifetime, the risk of experiencing multiple chronic conditions (multimorbidity) increases, necessitating complex healthcare regimens. Healthcare that manages these requirements in an integrated way has been shown to be more effective than services that address specific diseases individually. One such chronic condition that often accompanies ageing is hearing loss and related symptoms, such as tinnitus. Hearing loss is not only highly prevalent in older adults but is also a leading cause of disability. Accumulating evidence demonstrates an interplay between auditory function and other aspects of health. For example, poorer cardiometabolic health profiles have been shown to increase the risk of hearing loss, which has been attributed to microvascular disruptions and neural degeneration. Additionally, hearing loss itself is associated with significantly increased odds of falling and is a potentially modifiable risk factor for cognitive decline and dementia. Such evidence warrants consideration of new possibilities-a new horizon-for hearing care to develop a holistic, person-centred approach that promotes the overall health and wellbeing of the individual, as well as for audiology to be part of an interdisciplinary healthcare service. To achieve this holistic goal, audiologists and other hearing healthcare professionals should be aware of the range of conditions associated with hearing loss and be ready to make health promoting recommendations and referrals to the appropriate health practitioners. Likewise, healthcare professionals not trained in audiology should be mindful of their patients' hearing status, screening for hearing loss or referring them to a hearing specialist as required.

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

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.

BackgroundGiant cell arteritis (GCA) is a systemic vasculitis that may cause ischemic stroke. Rarely, GCA can present with aggressive intracranial stenoses, which are refractory to medical therapy. Endovascular treatment (EVT) is a possible rescue strategy to prevent ischemic complications in intracranial GCA but the safety and efficacy of EVT in this setting are not well-described.MethodsA systematic literature review was performed to identify case reports and series with individual patient-level data describing EVT for intracranial GCA. The clinical course, therapeutic considerations, and technique of seven endovascular treatments in a single patient from the authors' experience are presented.ResultsThe literature review identified 9 reports of 19 treatments, including percutaneous transluminal angioplasty (PTA) with or without stenting, in 14 patients (mean age 69.6 ± 6.3 years). Out of 12 patients 8 (66.7%) with sufficient data had > 1 pre-existing cardiovascular risk factor. All patients had infarction on MRI while on glucocorticoids and 7/14 (50%) progressed despite adjuvant immunosuppressive agents. Treatment was PTA alone in 15/19 (78.9%) cases and PTA + stent in 4/19 (21.1%). Repeat treatments were performed in 4/14 (28.6%) of patients (PTA-only). Non-flow limiting dissection was reported in 2/19 (10.5%) of treatments. The indications, technical details, and results of PTA are discussed in a single illustrative case. We report the novel use of intra-arterial calcium channel blocker infusion (verapamil) as adjuvant to PTA and as monotherapy, resulting in immediate improvement in cerebral blood flow.ConclusionEndovascular treatment, including PTA with or without stenting or calcium channel blocker infusion, may be effective therapies in medically refractory GCA with intracranial stenosis.

BackgroundIncreases 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/objectivesClassify 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.AnimalsA total of 138 California racing TBs. Amylase: n = 31 affected (serum GGT activity ≥60 IU/L), n = 52 control (serum GGT activity

The current phenomenological study was undertaken, during the COVID-19 pandemic induced school closures, with the purpose to explore successes and challenges of implementing virtual education and collecting suggestions for improving virtual teaching practice. Data was collected using purposive sampling via social media, using open-ended survey. 141 teachers, teaching kindergarten and elementary school, from different regions submitted their responses. In our research findings, three success themes and five major challenges have emerged from the voice of teachers experiencing a rapid and unprepared shift to virtual education. Suggestions for improving digital education revolved around engagement strategies, training, access, school policies and collaboration among teachers. The finding of the research can help in informing areas of focus for reimagining the approach to education for an uncertain future.

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.

Comprehensive knowledge of the distribution of active hydrothermal vent fields along midocean ridges is essential to understanding global chemical and heat fluxes and endemic faunal distributions. However, current knowledge is biased by a historical preference for on-axis surveys. A scarcity of high-resolution bathymetric surveys in off-axis regions limits vent identification, which implies that the number of vents may be underestimated. Here, we present the discovery of an active, high-temperature, off-axis hydrothermal field on a fast-spreading ridge. The vent field is located 750 m east of the East Pacific Rise axis and ∼7 km north of on-axis vents at 9° 50'N, which are situated in a 50- to 100-m-wide trough. This site is currently the largest vent field known on the East Pacific Rise between 9 and 10° N. Its proximity to a normal fault suggests that hydrothermal fluid pathways are tectonically controlled. Geochemical evidence reveals deep fluid circulation to depths only 160 m above the axial magma lens. Relative to on-axis vents at 9° 50'N, these off-axis fluids attain higher temperatures and pressures. This tectonically controlled vent field may therefore exhibit greater stability in fluid composition, in contrast to more dynamic, dike-controlled, on-axis vents. The location of this site indicates that high-temperature convective circulation cells extend to greater distances off axis than previously realized. Thorough high-resolution mapping is necessary to understand the distribution, frequency, and physical controls on active off-axis vent fields so that their contribution to global heat and chemical fluxes and role in metacommunity dynamics can be determined.

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.

ObjectiveTo evaluate the safety and effectiveness of the Flow Redirection Endoluminal Device (FRED) flow diverter in support of an application for Food and Drug Administration approval in the USA.Methods145 patients were enrolled in a prospective, single-arm multicenter trial. Patients with aneurysms of unfavorable morphology for traditional endovascular therapies (large, wide-necked, fusiform, etc) were included. The trial was designed to demonstrate non-inferiority in both safety and effectiveness, comparing trial results with performance goals (PGs) established from peer-reviewed published literature. The primary safety endpoint was death or major stroke (National Institutes of Health Stroke Scale score ≥4 points) within 30 days of the procedure, or any major ipsilateral stroke or neurological death within the first year. The primary effectiveness endpoint was complete occlusion of the target aneurysm with ≤50% stenosis of the parent artery at 12 months after treatment, and in which an alternative treatment of the target intracranial aneurysm had not been performed.Results145 patients underwent attempted placement of a FRED device, and one or more devices were placed in all 145 patients. 135/145 (93%) had a single device placed. Core laboratory adjudication deemed 106 (73.1%) of the aneurysms large or giant. A safety endpoint was experienced by 9/145 (6.2%) patients, successfully achieving the safety PG of 46% aneurysm occlusion was also achieved, with the effectiveness endpoint being met in 80/139 (57.6%) CONCLUSION: As compared with historically derived performance benchmarks, the FRED flow diverter is both safe and effective for the treatment of appropriately selected intracranial aneurysms.Clinical registration numberNCT01801007.

ObjectivesPatients with idiopathic inflammatory myopathies (IIM) have severe vascular involvement, which contributes to disease morbidity and mortality. Paraoxonase-1 (PON1) is a high-density lipoprotein (HDL) associated protein that protects the vascular endothelium from oxidative injury and damage. The current work assessed the functional and genetic determinants of PON1 activity in IIM patients.MethodsA total of 184 IIM patients and 112 healthy controls (HC) were included. PON1 enzyme activity was assessed by paraoxonase, arylesterase and lactonase assays, and the Q192R PON1 single nucleotide polymorphism (SNP) was analysed. Multivariate regression models examined associations of PON1 activity with IIM diagnosis and myositis disease outcomes.ResultsThe arylesterase and lactonase activities of PON1 were significantly lower in IIM patients compared with HC. Higher myositis disease activity, the presence of severe IIM-associated interstitial lung disease (ILD), and the presence of MDA5 or anti-synthetase antibodies were significantly associated with lower PON1 activity. The PON1 Q192R polymorphism was strongly linked to the paraoxonase activity of PON1 in IIM, and patients with the PON1 QQ genotype had better IIM disease outcomes compared with patients with the QR or RR genotypes.ConclusionsThe arylesterase and lactonase activities of PON1 are significantly impaired in IIM patients compared with HC, and inversely associate with IIM disease activity and the presence of severe ILD. The PON1 QQ genotype associates with more favourable disease outcomes in IIM patients. Large prospective studies are needed to further evaluate the role of PON1 and PON1 genetic polymorphisms in the development and propagation of IIM and IIM-ILD.

Background: Spinal epidural arteriovenous fistulas (seAVF) are a rare subset of vascular lesions that are most commonly found in the cervical levels. Unlike spinal dural AVF, seAVF are typically supplied by multiple arteries, including direct branches from the vertebral artery, which increases the risk of nontarget embolization using a transarterial endovascular approach. In these cases, transvenous embolization may be a preferable option, but accessing the cervical epidural venous space, also termed the internal vertebral venous plexus, can be challenging and requires advanced foreknowledge of cervical venous channels. Methods: The authors review salient neurovascular anatomy and present 2 techniques for endovascular access of the cervical epidural space to treat seAVF. Results: The physiology and structure of the cervical internal vertebral venous plexus is briefly reviewed. Next, the authors describe 2 complementary methods for transvenous access to the cervical internal vertebral venous plexus via the jugular vein (cranial‐caudal) and the vertebral vein (caudal‐cranial). The first approach involves retrograde microcatheterization via the jugular bulb and condylar veins. The second approach involves direct antegrade approach via the vertebral vein, arising from the brachiocephalic vein. Both approaches enable stable catheter positioning for coil embolization at remote cervical levels to treat a wide spectrum of seAVF. Conclusions: Accessing the cervical epidural venous space is technically demanding and requires effective planning and knowledge of relevant spinal venous anatomy. These techniques are important tools for safe and effective endovascular treatment of seAVF.

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.

BackgroundDural arteriovenous fistulas (AVF) of the foramen magnum region (FMR) are technically challenging lesions to treat. Transvenous (TV), transarterial (TA), and surgical approaches have been described, but the optimum treatment strategy is not defined.ObjectiveTo report treatment strategies and outcomes for FMR-AVF at a single, high-volume referral center.MethodsA retrospective review from January 2010 to August 2020 identified patients with FMR-AVF at a single referral center. Angiographic features, treatment (observation, endovascular, surgical), and follow-up of angiographic and clinical results were recorded. The technical aspects of TV embolization are then presented in detail.Results29 FMR-AVF were identified in 28 patients. Of these, 24/29 (82.8%) were treated and 5/29 (17.2%) were observed. Treatment was endovascular in 21/24 (87.5%), combined (endovascular+surgical) in 2/24 (8.3%), and surgical in 1/24 (4.2%). Endovascular treatments were 76.2% TV, 14.3% TA, and 9.5% combined TV/TA. Sufficient follow-up data were available for 20/28 (71.4%) with mean follow-up of 16.8 months. No AVF recurrence was seen for TA/TV, combined endovascular/surgical, or surgical groups, and there was one recurrence (7.1%) in the TV group. Symptomatic improvement was seen in all groups: TV (71.4% complete, 28.6% partial), TA (66.7% complete, 33.3% no follow-up), TV+TA (100% partial), endovascular/surgical (100% complete), and surgical (100% partial). Minor non-neurologic complications included 1/14 (7.1%) in the TV group and 1/3 (33.3%) in the TA/TV group.ConclusionEndovascular treatment is safe and effective for most FMR-AVF. TV embolization has a high cure rate with few complications.

Introduction: The “4Ms” model – What Matters, Medication, Mentation, and Mobility – is increasingly gaining attention in age-friendly health systems, yet a feasible approach to identifying what matters to older adults in the emergency department (ED) is lacking. Adapting the “What Matters” questions to the ED setting, we sought to describe the concerns and desired outcomes of both older adult patients seeking ED care and their treating clinicians.Methods: We conducted 46 dyadic semi-structured interviews of cognitively intact older adults and their treating clinicians. We used the “What Matters” conversation guide to explore patients’ 1) concerns and 2) desired outcomes. We then asked analogous questions to each patient’s treating clinician regarding the patient’s priorities. Interviews were professionally transcribed and coded using an inductive approach of thematic analysis to identify emergent themes.Results: Interviews with older adults lasted a mean of three minutes, with a range of 1–8 minutes. Regarding patients’ concerns, five themes emerged from older adults: 1) concern through a family member or outpatient clinician recommendation; 2) no concern, with a high degree of trust in the healthcare system; 3) concerns regarding symptom cause identification; 4) concerns regarding symptom resolution; and 5) concerns regarding preservation of their current status. Regarding desired outcomes, five priority themes emerged among older adults: 1) obtaining a diagnosis; 2) returning to their home environment; 3) reducing or resolving symptoms; 4) maintaining self-care and independence; and 5) gaining reassurance. Responding to what they believed mattered most to older adult patients, ED clinicians believed that older adults were concerned primarily about symptom cause identification and resolution and primarily desired a return to the home environment and symptom reduction.Conclusion: This work identifies concerns and desired outcomes of both older adult patients seeking ED care and their treating clinicians as well as the feasibility of incorporating the “What Matters” questions within ED clinical practice.

Writing is an important skill for communicating knowledge in science, technology, engineering, and mathematics (STEM) and an aid to developing students' communication skills, content knowledge, and disciplinary thinking. Despite the importance of writing, its incorporation into the undergraduate STEM curriculum is uneven. Research indicates that understanding faculty beliefs is important when trying to propagate evidence-based instructional practices, yet faculty beliefs about writing pedagogies are not yet broadly characterized for STEM teaching at the undergraduate level. Based on a nationwide cross-disciplinary survey at research-intensive institutions, this work aims to understand the extent to which writing is assigned in undergraduate STEM courses and the factors that influence faculty members' beliefs about, and reported use of, writing-based pedagogies. Faculty attitudes about the effectiveness of writing practices did not differ between faculty who assign and do not assign writing; rather, beliefs about the influence of social factors and contextually imposed instructional constraints informed their decisions to use or not use writing. Our findings indicate that strategies to increase the use of writing need to specifically target the factors that influence faculty decisions to assign or not assign writing. It is not faculty beliefs about effectiveness, but rather faculty beliefs about behavioral control and constraints at the departmental level that need to be targeted.

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.

IntroductionPoor sleep is prevalent among individuals with social anxiety disorder (SAD) and may negatively affect exposure therapy outcomes. Poor sleep may impair memory and learning, and thus compromise fear extinction learning thought to take place in exposure therapy. We examined poor sleep as a predictor of exposure therapy outcomes for SAD and the moderating role of d-cycloserine (DCS) on this relationship.MethodsParticipants were 152 individuals with a primary diagnosis of SAD. As part of a randomized clinical trial evaluating the efficacy of DCS for enhancing the effects of exposure therapy, they completed self-report baseline measure of sleep quality, and self-report sleep diaries assessing sleep duration (total sleep time [TST]) and sleep quality the nights before and after treatment sessions.ResultsPoorer baseline sleep quality was significantly associated with slower improvement over time and worse symptom outcomes at the end of treatment and follow-up after controlling for baseline symptoms of depression and social anxiety. Greater TST the night before treatment predicted lower SAD symptoms at the next session, after controlling for symptoms at the previous session. There was no relation between prior or subsequent night sleep quality on symptoms at the next session. No associations were moderated by DCS.ConclusionsWe replicated and extended findings indicating that poor sleep quality is associated with poorer exposure therapy outcomes for SAD. Assessing for sleep difficulties before treatment initiation and incorporating sleep interventions into treatment may enhance exposure therapy outcomes for SAD.

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.

Background and purposeAVFs of the foramen magnum region, including fistulas of the marginal sinus and condylar veins, have complex arterial supply, venous drainage, symptoms, and risk features that are not well-defined. The purpose of this study was to present the angioarchitectural and clinical phenotypes of a foramen magnum region AVF from a large, single-center experience.Materials and methodsWe retrospectively reviewed cases from a 10-year neurointerventional data base. Arterial and venous angioarchitectural features and clinical presentation were extracted from the medical record. Venous drainage patterns were stratified into 4 groups as follows: type 1 = unrestricted sinus drainage, type 2 = sinus reflux (including the inferior petrosal sinus), type 3 = reflux involving sinuses and cortical veins, and type 4 = restricted cortical vein outflow or perimedullary congestion.ResultsTwenty-eight patients (mean age, 57.9 years; 57.1% men) had 29 foramen magnum region AVFs. There were 11 (37.9%) type 1, nine (31.0%) type 2, six (20.7%) type 3, and 3 (10.3%) type 4 fistulas. Pulsatile tinnitus was the most frequent symptom (82.1%), followed by orbital symptoms (31.0%), subarachnoid hemorrhage (13.8%), cranial nerve XII palsy (10.3%), and other cranial nerve palsy (6.9%). The most frequent arterial supply was the ipsilateral ascending pharyngeal artery (93.1% ipsilateral, 55.5% contralateral), vertebral artery (89.7%), occipital artery (65.5%), and internal carotid artery branches (48.3%).ConclusionsWe present the largest case series of foramen magnum region AVFs to date and show that clinical features relate to angioarchitecture. Orbital symptoms are frequent when sinus reflux is present. Hemorrhage was only observed in type 3 and 4 fistulas.

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.