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Abstract Spinal cord injury (SCI) results in rapid, severe osteoporosis and an increased risk of lower extremity fractures. Despite the medical complications associated with these fractures, there is no standard of care to prevent osteoporotic fractures following SCI. Functional electrical stimulation‐ (FES‐) assisted rowing is a promising intervention to improve bone health in SCI because of its ability to generate a muscular contraction in conjunction with mechanical loading of the lower extremity long bones. Combination therapy consisting of FES‐rowing plus zoledronic acid (ZA) may be a superior treatment via inhibition of bone resorption and stimulation of new bone formation. We studied participants enrolled in a randomized clinical trial comparing FES‐rowing alone with FES‐rowing plus ZA to improve bone health in SCI. Volumetric CT scans at the distal femur and proximal tibial metaphyses were performed. Bone geometric properties (cortical thickness index [CTI], cortical compressive strength index [CSI], buckling ratio [BR], bending strength index) and mineral (cortical bone volume [CBV], cortical bone mineral density, cortical bone mineral content) indices were determined. In models adjusting for baseline values, we found that the CBV (p = 0.05 to 0.006), the CTI (p = 0.009), and the BR (p = 0.001) at both the distal femoral and proximal tibial metaphyses were greater in the ZA plus rowing group compared with the rowing‐only group. Similarly, there was a significant positive association between the total rowing work completed and the BR at the proximal tibia (p = 0.05). A subgroup analysis of the rowing‐only arm showed that gains in the CSI at the tibial metaphysis varied in a dose‐dependent fashion based on the total amount of exercise performed (p = 0.009). These findings demonstrate that the osteogenic response to FES‐rowing is dose‐dependent. Combination therapy with ZA and FES‐row training has therapeutic potential to improve bone quality, and perhaps reduce fracture risk at the most common fracture site following SCI. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

Research on race homophily in the United States has yet to meaningfully include the growing multiracial population. The present study confronts this challenge by drawing upon recent conceptualizations of race as a multidimensional construct. In aligning this insight with current understandings of homophily, we identify and address several open questions about the origins of race homophily—namely regarding the possibility of peer influence on racial identity and network selection based on multiple facets of race. Data are from 3,036 youth in two large U.S. high schools with sizable proportions of mixed-race students. Using a stochastic actor-oriented model, we find that students choose friends based on similarity across multiple dimensions of racial identity and that peer influence operates to reinforce multiracial youths' racial self-classification rather than to induce change. This points to a system where race homophily arises through multiple selection mechanisms and is reinforced by pressure toward conformity.

Abstract Background The National Institute for Health and Care Excellence (NICE) recommend that men with prostate cancer on androgen deprivation therapy (ADT) are offered twice weekly supervised aerobic and resistance exercise to address side effects of treatment. However, supervised exercise is not routinely offered in standard clinical practice. The STAMINA programme grant for applied research (PGfAR) has been designed to evaluate whether this recommendation can be delivered within standard NHS care. This paper describes how future implementation of NICE recommendations within the NHS was explored during complex intervention development to enable evaluation of a lifestyle intervention. Methods Two stakeholder workshops were conducted to explore factors pertinent to future implementation of the STAMINA Lifestyle intervention (SLI). Normalisation Process Theory (NPT) provided the theoretical framework for discussion and analysis. Stakeholder workshop 1 focussed on intervention coherence and buy-in. Stakeholder workshop 2 explored barriers and facilitators for embedding SLI into the context of the NHS, with delivery partner Nuffield Health, in the future. Results Workshops were attended by healthcare professionals (n = 16), exercise professionals (n = 17), members of public involved in PPI including patients (n = 12), health psychologists (n = 2), clinical commissioners (n = 4), cancer charities (n = 3), a cancer alliance (n = 1) and health economist (n = 1). Stakeholders agreed that professional training packages should emphasise the uniqueness of the SLI and underpinning theory and evidence (Coherence). To further engagement, the use of STAMINA champions and information about the delivery partner were recommended to enhance confidence and knowledge (Cognitive participation). Furthermore, a simple communication (Collective Action) and progress reporting system (Reflexive Monitoring) was suggested to fit into existing infrastructure within the NHS and community partner. Conclusions Application of NPT within two stakeholder workshops enhanced complex intervention development. Context-specific strategies to support implementation of SLI within the context of a trial were proposed, sensed-checked, and considered acceptable. The organisational implications of embedding and sustaining the intervention in preparation for wider NHS roll-out were considered (if proven to be effective) and will be explored in the qualitative component of a process evaluation underpinned by NPT. Trial registration (ISRCTN: 46385239 ). Registered on July 30, 2020.

Abstract Background Chronic obstructive pulmonary disease (COPD) is commonly associated with anxiety/depression which can affect self-management and quality of life. The TANDEM trial evaluated a cognitive behavioural approach intervention targeting COPD-related symptoms of anxiety and/or depression, comprising up to eight one-to-one sessions delivered by respiratory healthcare professionals prior to pulmonary rehabilitation (PR). The intervention showed no improvement in anxiety/depression or uptake/completion of PR. We present patient perspectives of the intervention to help understand these results. Method Semi-structured individual interviews, using a semi-structured topic guide informed by Sekhon’s Theoretical Framework of Acceptability, were conducted with 19 patients between September 2019 and April 2020. The interviews were audio-recorded, transcribed verbatim and analysed thematically. Results The following could have limited the impact of the intervention: (1) The lives of patients were complex and commonly affected by competing comorbidities or other external stressors which they managed through previously adopted long-standing coping strategies. (2) Some patients were reluctant to talk about their mood despite the Facilitators' training and person centred-skills which aimed to enable patients to talk freely about mood. (3) The intervention handouts and ‘home-practice’ were perceived as helpful for some, but not suitable for all. (4) Many patients perceived improvements in their physical and mental health, but this was not sustained due to a mix of personal and external factors, and some did not perceive any benefits. (5) PR non-attendance/non-completion was a result of personal and PR service-related reasons. (6) Discussing COPD and mental health with the Facilitator was a novel experience. Many patients felt that TANDEM could be of benefit if it was offered earlier on/at different time points in the COPD illness journey. Conclusion We found the delivery of TANDEM prior to PR was not helpful for patients with advanced COPD often experiencing other comorbidities, and/or difficult personal/external events. These patients already utilised long-standing coping strategies to manage their COPD. Holistic interventions, that address the impact of COPD in relation to wider aspects of a patients’ life, may be more beneficial. Trial registration ISRCTN Registry 59,537,391. Registration date 20 March 2017.

Abstract Background Between 2015 and 2019 the Chronic Headache Education and Self-management Study (CHESS) developed and tested a supportive self-management approach that aimed to improve outcomes for people with chronic migraine or chronic tension type headache with/without episodic migraine. However, a paucity of qualitative research which explored the lived experiences of people with chronic headache was evidenced. In response, we undertook to explore the experiences of living with chronic headaches of people who participated in the CHESS study. Methods We adopted qualitative methodologies, inviting participants in the CHESS study to participate in semi-structured interviews. In phase 1 (feasibility study), a thematic analysis was conducted. In phase 2 (main CHESS trial), interviews were informed by topic guides developed from our learning from the phase 1 interviews. Pen portrait methodology and thematic analysis was employed allowing us to explore the data longitudinally. Results Phase 1, 15 interviews (10 female) age range 29 to 69 years (median 47 years) revealed the complexities of living with chronic headache. Six overarching themes were identified including the emotional impact and the nature of their headaches. Phase 2, included 66 interviews (26 participants; median age group 50s (range 20s-60s); 20 females. 14 were interviewed at three points in time (baseline, 4 and 12 months) Through an iterative process four overlapping categories of headache impact emerged from the data and were agreed: i) ‘I will not let headaches rule my life’; ii) ‘Headaches rule my life’; iii) ‘Headaches out of control—something needs to change’; and iv) ‘Headaches controlled—not ruling my life’. One of these categories was assigned to each pen portrait at each timepoint. The remaining 12 participants were interviewed at two time points during a year; pen portraits were again produced. Analysis revealed that the headache impact categories developed above held true in this sample also providing some validation of the categories. Conclusions These data give an insight into the complexities of living with chronic headache. Chronic headache is unpredictable, permeating all aspects of an individual’s life; even when an individual feels that their headache is controlled and not interfering, this situation can rapidly change. It shows us that more work needs to be done both medically and societally to help people living with this often-hidden condition. Trial registration ISRCTN79708100

Abstract Background The SPHERe (Supervised Pulmonary Hypertension Exercise Rehabilitation) trial is a multi-centre, pragmatic, randomised controlled trial assessing the clinical and cost-effectiveness of supervised exercise rehabilitation with psychosocial and motivational support compared to best-practice usual care for people with pulmonary hypertension (PH). The original protocol was published in BMC Pulmonary Medicine (accessible online). We randomised our first participant in January 2020. In response to the COVID-19 pandemic, the trial was stopped in March 2020. In person delivery of the SPHERe intervention to a vulnerable population was not possible during the COVID-19 pandemic. We describe here how trial procedures and intervention delivery were adapted in response to the COVID-19 pandemic. Methods Restrictions imposed by the COVID-19 pandemic on the clinically vulnerable PH population meant that trial delivery was changed from a centre-based rehabilitation programme to remotely delivered group online sessions. This led to minor alterations to the eligibility criteria. These changes followed a consultation process with stakeholders and people with PH and were approved by the funder and independent trial committees. Conclusions We describe the modified SPHERe trial protocol in response to restrictions imposed by the COVID-19 pandemic. SPHERe is the first randomised controlled trial to assess the clinical and cost-effectiveness of an online group rehabilitation programme for people with PH compared to usual care. Trial registration ISRCTN no. 10608766. Prospectively registered on 18th March 2019, updated 16th August 2023.

Background 5.4 million people in the UK have asthma, with one third experiencing suboptimal control, leading to co-morbidities and increased healthcare use. A quarter of people with long-term conditions informally access peer support through online health communities (OHCs). However, integrating online peer support into primary care services to facilitate self-management is a new concept.Objectives To develop together with stakeholders the content, delivery, and recruitment strategy of a digital social intervention to promote use of online peer support amongst asthma patients in primary care.Methods Data was collected by qualitative, audio-recorded, one-to-one interviews with clinicians, and focus groups with patients with asthma from East London general practices. The topic guide was informed by patient and public involvement work. Data collected was iterative (i.e. new ideas were added to subsequent interviews and focus groups). Verbatim transcripts were uploaded to NVivo12 and thematically analysed.Results Twenty patients from several ethnicities participated across five focus groups, and three general practitioners and three practice nurses were interviewed. The study’s outputs included: the intervention’s face-to-face content; content of clinician training; patient-facing leaflets/material; and a survey to recruit eligible patients. An intervention consisting of a structured consultation with a primary care clinician followed by OHC engagement, was developed based on three generated themes: ‘introducing OHCs’, describing how clinicians should introduce OHCs; ‘OHC engagement’, describing factors influencing OHC engagement; and ‘clinician training’.Conclusion Findings will assist clinicians in consultations about supporting self-management of patients through OHCs. Future research should evaluate feasibility, effectiveness, and cost-effectiveness of such support.

IntroductionConventional methods for evaluating the management of spasticity, a complex neuromuscular disorder, typically fail to directly measure the muscle forces and loads applied through tendons, which is crucial for accurate diagnostics and treatment. To bridge this gap, we developed a novel modular buckle transducer (BT) designed to measure tendon forces in vivo. This device adjusts to accommodate tendon sizes ranging from 3 mm to 5 mm, maintaining accuracy within this range and avoiding the need for identical tendon calibration.MethodsThis study first presents the mechanical principles for determining tendon tension T using several strain gauges appropriately positioned to allow for varying angles of passage of the tendon through the device. Next, we present a finite element (FE) model that uses multiple linear regression to determine T while varying tendon diameter and lateral placement within the device for several candidate strain gauge locations on the device base plate. Finally, we posit several alternative ways of combining gauge strains.ResultsInitial simulation results demonstrated that this placement facilitates effective pre-implementation calibration, with the device accommodating tendon variations from 3 mm to 5 mm in diameter for a range of gauge placements.DiscussionFuture validation of this technology will involve direct testing on explanted human/equine tendons to verify the practical utility of the BT, aiming to establish a new standard for assessing and managing neuromuscular disorders such as spasticity.

Abstract Background Providing supported self-management for people with asthma can reduce the burden on patients, health services and wider society. Implementation, however, remains poor in routine clinical practice. IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) is a UK-wide cluster randomised implementation trial that aims to test the impact of a whole-systems implementation strategy, embedding supported asthma self-management in primary care compared with usual care. To maximise opportunities for sustainable implementation beyond the trial, it is necessary to understand how and why the IMP2ART trial achieved its clinical and implementation outcomes. Methods A mixed-methods process evaluation nested within the IMP2ART trial will be undertaken to understand how supported self-management was implemented (or not) by primary care practices, to aid interpretation of trial findings and to inform scaling up and sustainability. Data and analysis strategies have been informed by mid-range and programme-level theory. Quantitative data will be collected across all practices to describe practice context, IMP2ART delivery (including fidelity and adaption) and practice response. Case studies undertaken in three to six sites, supplemented by additional interviews with practice staff and stakeholders, will be undertaken to gain an in-depth understanding of the interaction of practice context, delivery, and response. Synthesis, informed by theory, will combine analyses of both qualitative and quantitative data. Finally, implications for the scale up of asthma self-management implementation strategies to other practices in the UK will be explored through workshops with stakeholders. Discussion This mixed-methods, theoretically informed, process evaluation seeks to provide insights into the delivery and response to a whole-systems approach to the implementation of supported self-management in asthma care in primary care. It is underway at a time of significant change in primary care in the UK. The methods have, therefore, been developed to be adaptable to this changing context and to capture the impact of these changes on the delivery and response to research and implementation processes.

Abstract Integrated step‐selection analysis (ISSA) is frequently used to study habitat selection using animal movement data. Methods for incorporating random effects in ISSA have been developed, making it possible to quantify variability among animals in their space‐use patterns. Although it is possible to model variability in both habitat selection and movement parameters, applications to date have focused on the former despite the widely acknowledged and important role that movement plays in determining ecological processes from the individual to ecosystem level. One potential explanation for this omission is the absence of readily available software or examples demonstrating methods for estimating movement parameters in ISSA with random effects. We demonstrated methods for characterizing among‐individual variability in both movement and habitat‐selection parameters using a simulated data set and by fitting two models to an acoustic telemetry data set containing locations of 35 red snapper (Lutjanus campechanus). Movement kernels were assumed to depend on either the type of benthic reef habitat in which the fish was located (model 1) or the distance between the fish's current location and the nearest edge habitat (model 2). In both models, we also quantified habitat selection for different benthic habitat classes and distance to edge habitat, and we allowed for individual variability in movement and habitat‐selection parameters using random effects. The simulation example highlights the benefits of a mixed‐effects specification, namely, we can increase precision when estimating individual‐specific movement parameters by borrowing information across like individuals. In our applied example, we found substantial among‐individual variability in both habitat selection and movement parameters. Nonetheless, most red snapper selected for hardbottom habitat and for locations nearer to edge habitat. They also moved less when in hardbottom habitat. Turn angles were frequently near ± π but were more dispersed when fish were far away from edge habitat. We provide code templates and functions for quantifying variability in movement and habitat‐selection parameters when implementing ISSA with random effects. In doing so, we hope to encourage ecologists conducting ISSA to take full advantage of their ability to model among‐individual variability in both habitat‐selection and movement patterns.

Abstract Background Two million people in the UK are living with or beyond cancer and a third of them report poor quality of life (QoL) due to problems such as fatigue, fear of cancer recurrence, and concerns about returning to work. We aimed to develop and evaluate an intervention based on acceptance and commitment therapy (ACT), suited to address the concerns of cancer survivors and in improving their QoL. We also recognise the importance of exercise and vocational activity on QoL and therefore will integrate options for physical activity and return to work/vocational support, thus ACT Plus (+). Methods We will conduct a multi-centre, pragmatic, theory driven, randomised controlled trial. We will assess whether ACT+ including usual aftercare (intervention) is more effective and cost-effective than usual aftercare alone (control). The primary outcome is QoL of participants living with or beyond cancer measured using the Functional Assessment of Cancer Therapy: General scale (FACT-G) at 52 weeks. We will recruit 344 participants identified from secondary care sites who have completed hospital-based treatment for cancer with curative intent, with low QoL (determined by the FACT-G) and randomise with an allocation ratio of 1:1 to the intervention or control. The intervention (ACT+) will be delivered by NHS Talking Therapies, specialist services, and cancer charities. The intervention consists of up to eight sessions at weekly or fortnightly intervals using different modalities of delivery to suit individual needs, i.e. face-to-face sessions, over the phone or skype. Discussion To date, there have been no robust trials reporting both clinical and cost-effectiveness of an ACT based intervention for people with low QoL after curative cancer treatment in the UK. We will provide high quality evidence of the effectiveness and cost-effectiveness of adding ACT+ to usual aftercare provided by the NHS. If shown to be effective and cost-effective then commissioners, providers and cancer charities will know how to improve QoL in cancer survivors and their families. Trial registration ISRCTN: ISRCTN67900293 . Registered on 09 December 2019. All items from the World Health Organization Trial Registration Data Set for this protocol can be found in Additional file 2 Table S1.

Knowledge of past and present genetic diversity within a breed is critical for the design and optimization of breeding programs as well as the development of strategies for the conservation of genetic resources. The Polypay sheep breed was developed at the U.S. Sheep Experiment Station (USSES) in 1968 with the goal of improving productivity in Western U.S. range flocks. It has since flourished in the more intensively managed production systems throughout the U.S. The genetic diversity of the breed has yet to be documented. Therefore, the primary objective of this study was to perform a comprehensive evaluation of the genetic diversity and population structure of U.S. Polypay sheep using both pedigree- and genomic-based methods. Pedigree data from 193 Polypay flocks participating in the National Sheep Improvement Program (NSIP) were combined with pedigree records from USSES (n = 162,997), tracing back to the breed’s origin. A subset of these pedigreed sheep from 32 flocks born from 2011 to 2023 were genotyped with the GGP Ovine 50K BeadChip containing 51,867 single nucleotide polymorphisms (SNPs). Four subgroups were used for the pedigree-based analyses: 1) the current generation of animals born in 2020–2022 (n = 20,701), 2) the current generation with a minimum of four generations of known ancestors (n = 12,685), 3) only genotyped animals (n = 1,856), and 4) the sires of the current generation (n = 509). Pedigree-based inbreeding for the full population was 2.2%, with a rate of inbreeding of 0.22% per generation. Pedigree-based inbreeding, Wright’s inbreeding, and genomic inbreeding based on runs of homozygosity were 2.9%, 1.3%, and 5.1%, respectively, for the genotyped population. The effective population size ranged from 41 to 249 for the pedigree-based methods and 118 for the genomic-based estimate. Expected and observed heterozygosity levels were 0.409 and 0.403, respectively. Population substructure was evident based on the fixation index (FST), principal component analysis, and model-based population structure. These analyses provided evidence of differentiation from the foundation flock (USSES). Overall, the Polypay breed exhibited substantial genetic diversity and the presence of a population substructure that provides a basis for the implementation of genomic selection in the breed.

Abstract Far infrared (FIR) emission from the Earth's polar regions has become an area of increasing scientific interest and value. FIR emission is important for understanding Earth's radiative balance and improving global climate models, especially in rapidly changing Arctic conditions. Far‐infrared emission from Earth is not currently being monitored from space, except as part of broadband emission channels of Earth radiation budget measurements like those from the CERES project, and only limited measurements in the FIR spectrum exist. The Absolute Radiance Interferometer (ARI), developed as a prototype of the infrared spectrometer for CLARREO at the University of Wisconsin‐Madison, Space Science and Engineering Center, measures absolute spectrally resolved infrared (IR) radiance from 200 to 2,000 cm−1 (or 5–50 μm) at 0.5 cm−1 resolution with high accuracy (

Purpose: The COVID-19 pandemic has brought dramatic changes to the daily lives of U.S. adolescents, including isolation from friends and extended family, transition to remote learning, potential illness and death of loved ones, and economic distress. This study's purpose is to measure changes in adolescents' perceived stress and mood early in the pandemic. Methods: The present study drew from a racially and ethnically diverse sample of high school student participants in an ongoing intervention study in the Midwestern U.S., 128 of whom provided reports of their daily stress and mood both before (December 2017 to March 2020) and during (March-July 2020) the COVID-19 pandemic. We expected to see increases in perceived stress, declines in positive mood states, and increases in negative mood states, with larger impacts on individuals from households with lower parental education levels. Results: Multilevel models revealed increases in perceived stress primarily for adolescents from low/moderate education families during the pandemic. Impacts on mood states also diverged by education: adolescents from low/moderate education households reported feeling more ashamed, caring, and excited than before the pandemic, changes that were not shared by their peers from high education households. Although changes in mood that arose with the onset of the pandemic became less pronounced over time, increased levels of home- and health-related stress stayed high for low/moderate education adolescents. Conclusions: During the COVID-19 period, we observed disparate impacts on adolescents according to household education level, with more dramatic and negative changes in the emotional well-being of adolescents from low/moderate education households.

Abstract Background Pulmonary rehabilitation (PR) is a programme of exercise and education and the most effective treatment for the symptoms and disability associated with chronic obstructive pulmonary disease. However, the benefits of PR are limited by poor uptake and completion. This trial will determine whether using trained volunteer lay health workers, called “PR buddies,” improves uptake and completion of PR and is cost-effective. This trial protocol outlines the methods for evaluating effectiveness, cost-effectiveness, and acceptability. Methods The IMPROVE trial is a pragmatic, open, cluster randomised controlled trial planned in 38 PR services across England and Wales. PR services will be randomised to either intervention arm—offering support from PR buddies to patients with chronic obstructive pulmonary disease—or to usual care as the control arm. PR staff in trial sites randomised to the intervention arm will receive training in recruiting and training PR buddies. They will deliver training to volunteers, recruited from among people who have recently completed PR in their service. The 3-day PR-buddy training programme covers communication skills, confidentiality, boundaries of the PR-buddy role and behaviour change techniques to help patients overcome obstacles to attending PR. An internal pilot will test the implementation of the trial in eight sites (four intervention sites and four in control arm). The primary outcome of the trial is the uptake and completion of PR. A process evaluation will investigate the acceptability of the intervention to patients, PR staff and the volunteer PR buddies, and intervention fidelity. We will also conduct a cost-effectiveness analysis. Discussion Improving outcomes for chronic obstructive pulmonary disease and access to PR are priorities for the UK National Health Service (NHS) in its long-term plan. The trial hypothesis is that volunteer PR buddies, who are recruited and trained by local PR teams, are an effective and cost-effective way to improve the uptake and completion rates of PR. The trial is pragmatic, since it will test whether the intervention can be incorporated into NHS PR services. Information obtained in this trial may be used to influence policy on the use of PR buddies in PR and other similar services in the NHS. Trial registration ISRCTN12658458. Registered on 23/01/2023.

There are few pharmacologic options for the treatment of cognitive deficits associated with traumatic brain injury in pediatric patients. Acetylcholinesterase inhibitors such as donepezil have been evaluated in adult patients after traumatic brain injury, but relatively less is known about the effect in pediatric populations. The goal of this review is to identify knowledge gaps in the efficacy and safety of acetylcholinesterase inhibitors as a potential adjuvant treatment for neurocognitive decline in pediatric patients with traumatic brain injury. Investigators queried PubMed to identify literature published from database inception through June 2023 describing the use of donepezil in young adult traumatic brain injury and pediatric patients with predefined conditions. Based on preselected search criteria, 340 unique papers were selected for title and abstract screening. Thirty-two records were reviewed in full after eliminating preclinical studies and papers outside the scope of the project. In adult traumatic brain injury, we review results from 14 papers detailing 227 subjects where evidence suggests donepezil is well tolerated and shows both objective and patient-reported efficacy for reducing cognitive impairment. In children, 3 papers report on 5 children recovering from traumatic brain injury, showing limited efficacy. An additional 15 pediatric studies conducted in populations at risk for cognitive dysfunction provide a broader look at safety and efficacy in 210 patients in the pediatric age group. Given its promise for efficacy in adults with traumatic brain injury and tolerability in pediatric patients, we believe further study of donepezil for children and adolescents with traumatic brain injury is warranted.

Background Pre-existing cardiovascular disease (CVD) or cardiovascular risk factors have been associated with an increased risk of complications following hospitalisation with COVID-19, but their impact on the rate of recovery following discharge is not known.Objectives To determine whether the rate of patient-perceived recovery following hospitalisation with COVID-19 was affected by the presence of CVD or cardiovascular risk factors.Methods In a multicentre prospective cohort study, patients were recruited following discharge from the hospital with COVID-19 undertaking two comprehensive assessments at 5 months and 12 months. Patients were stratified by the presence of either CVD or cardiovascular risk factors prior to hospitalisation with COVID-19 and compared with controls with neither. Full recovery was determined by the response to a patient-perceived evaluation of full recovery from COVID-19 in the context of physical, physiological and cognitive determinants of health.Results From a total population of 2545 patients (38.8% women), 472 (18.5%) and 1355 (53.2%) had CVD or cardiovascular risk factors, respectively. Compared with controls (n=718), patients with CVD and cardiovascular risk factors were older and more likely to have had severe COVID-19. Full recovery was significantly lower at 12 months in patients with CVD (adjusted OR (aOR) 0.62, 95% CI 0.43 to 0.89) and cardiovascular risk factors (aOR 0.66, 95% CI 0.50 to 0.86).Conclusion Patients with CVD or cardiovascular risk factors had a delayed recovery at 12 months following hospitalisation with COVID-19. Targeted interventions to reduce the impact of COVID-19 in patients with cardiovascular disease remain an unmet need.Trail registration number ISRCTN10980107.

Introduction: Improving ewe longevity is an important breeding and management goal, as death loss and early culling of mature ewes are economic burdens in the sheep industry. Ewe longevity can be improved by selecting for positive reproductive outcomes. However, the breeding approaches for accomplishing this come with the challenge of recording a lifetime trait. Characterizing genetic factors underpinning ewe longevity and related traits could result in the development of genomic selection strategies to improve the stayability of sheep through early, informed selection of replacement ewes.Methods: Towards this aim, a genome-wide association study (GWAS) was performed to identify genetic markers associated with ewe longevity, reproductive, and production traits. Traits evaluated included longevity (i.e., length of time in the flock), parity and the lifetime number of lambs born, lambs born alive, lambs weaned, and weight of lambs weaned. Ewe records from previous studies were used. Specifically, Rambouillet (n = 480), Polypay (n = 404), Suffolk (n = 182), and Columbia (n = 64) breed ewes (N = 1,130) were analyzed against 503,617 SNPs in across-breed and within-breed GWAS conducted with the Bayesian-information and Linkage-disequilibrium Iteratively Nested Keyway (BLINK) model in R.Results: The across-breed GWAS identified 25 significant SNPs and the within-breed GWAS for Rambouillet, Polypay, and Suffolk ewes identified an additional 19 significant SNPs. The most significant markers were rs411309094 (13:22,467,143) associated with longevity in across-breed GWAS (p-value = 8.3E-13) and rs429525276 (2:148,398,336) associated with both longevity (p-value = 6.4E-15) and parity (p-value = 4.8E-15) in Rambouillet GWAS. Significant SNPs were identified within or in proximity (±50 kb) of genes with known or proposed roles in reproduction, dentition, and the immune system. These genes include ALPL, ANOS1, ARHGEF26, ASIC2, ASTN2, ATP8A2, CAMK2D, CEP89, DISC1, ITGB6, KCNH8, MBNL3, MINDY4, MTSS1, PLEKHA7, PRIM2, RNF43, ROBO2, SLCO1A2, TMEM266, TNFRSF21, and ZNF804B.Discussion: This study proposes multiple SNPs as candidates for use in selection indices and suggests genes for further research towards improving understanding of the genetic factors contributing to longevity, reproductive, and production traits of ewes.

Abstract Counter‐wildlife crime (CWC) interventions—those that directly protect target wildlife from illegal harvest/persecution, detect and sanction rule‐breakers, and interdict and control illegal wildlife commodities—are widely applied to address biodiversity loss. This systematic map provides an overview of the literature on the effectiveness of CWC interventions for conserving African, Asian and Latin American wildlife directly threatened by exploitation, including human–wildlife conflicts that trigger poaching. Following our systematic map protocol (Rytwinski, Öckerman, et al., 2021), we compiled peer‐reviewed and grey literature and screened articles using pre‐defined inclusion criteria. Included studies were coded for key variables of interest, from which we produced a searchable database, interactive map and structured heatmaps. A total of 530 studies from 477 articles were included in the systematic map. Most studies were from Africa and Asia (81% of studies) and focused on African and Asian elephants (16%), felids (14%) and turtles and tortoises (11%). Most evaluations of CWC interventions targeted wildlife products (rather than species) and the transfer of those products along the wildlife crime continuum (40% of cases). Population/species outcomes were most commonly measured via indicators of threat reduction (65% of cases) and intermediate outcomes (25%). We identified knowledge clusters where studies investigated the links between (1) patrols and other preventative actions to increase detection and population abundance and (2) information analysis and sharing and wildlife crime/trade levels. However, the effectiveness of most interventions was not rigorously evaluated. Most investigations used post‐implementation monitoring only (e.g. lacking a comparator), and no experimental designs were found. We identified several key knowledge gaps including a paucity of studies by geography (Latin America), taxonomy (plants, birds and reptiles), interventions (non‐patrol‐based CWC interventions) and outcomes (biological and the combination of biological and human well‐being outcomes). Our map reveals an opportunity to improve the rigour and documentation of CWC intervention evaluations, which would enable the evidence‐based selection of effective approaches to improve wildlife conservation and national security.

Artificial reefs can play an important role in marine fisheries management by supplementing or enhancing natural habitats. Despite their increased use in recent years, the choice of structures used at artificial reefs remains largely haphazard due to the lack of information on reef structure performance. Few studies have examined the use of different artificial reef structures by individual fish. From 2021-2022, we acoustically tagged 72 black sea bass (Centropristis striata), 34 gag (Mycteroperca mircrolepis), 27 greater amberjack (Seriola dumerili), nine almaco jack (S. rivoliana), and eight red snapper (Lutjanus campechanus) on four artificial reef complexes near Cape Lookout, North Carolina, U.S. Available artificial reef structures consisted of materials of various sizes and heights made of concrete and metal. We tracked tagged fish using a fine-scale positioning system for ~100 days. Black sea bass exhibited high site fidelity to the artificial structure where we caught them, rarely moving away from that structure. The limited movement resulted in low transition probabilities; we conclude that black sea bass do not select for particular artificial structures. Gag and red snapper moved greater distances away from artificial structures and routinely moved between them. Greater amberjack and almaco jack moved the most within the complexes displaying circling behavior around individual structures and were the only species that regularly moved off the artificial reef complexes. Greater amberjack movements away from artificial sites were most commonly directed to surrounding shipwrecks. Whereas gag, red snapper, almaco jack, and greater amberjack used all available structures, they consistently selected for high relief structures, such as vessels, more than other structures. These results will be useful to managers charged with decisions on what types of structures to place at artificial reef complexes to supplement or enhance habitat for economically important fishes.

Abstract We report the small-signal characterization of a PCSEL device, extracting damping factors and modulation efficiencies, and demonstrating -3 dB modulation bandwidths of up to 4.26 GHz. Based on modelling we show that, by reducing the device width and improving the active region design for high-speed modulation, direct modulation frequencies in excess of 50 GHz are achievable.

Abstract Implementing psychological interventions in healthcare services requires an understanding of the organisational context. We conducted an interview study with UK National Health Service stakeholders to understand the barriers and facilitators for implementing psychological interventions for people with chronic obstructive pulmonary disorder (COPD). We used TANDEM as an exemplar intervention; a psychological intervention recently evaluated in a randomised controlled trial. Twenty participants providing care and/or services to people with COPD were purposively sampled from NHS primary/secondary care, and commissioning organisations. Participants were recruited via professional networks and referrals. Verbatim transcripts of semi-structured interviews were analysed using thematic analysis. Four themes were identified: (1) Living with COPD and emotional distress affects engagement with physical and psychological services; (2) Resource limitations affects service provision in COPD; (3) Provision of integrated care is important for patient well-being; and (4) Healthcare communication can be an enabler or a barrier to patient engagement. People need support with physical and psychological symptoms inherent with COPD and healthcare should be provided holistically. Respiratory healthcare professionals are considered able to provide psychologically informed approaches, but resources must be available for training, staff supervision and service integration. Communication between professionals is vital for clear understanding of an intervention’s aims and content, to facilitate referrals and uptake. There was widespread commitment to integrating psychological and physical care, and support of respiratory healthcare professionals’ role in delivering psychological interventions but significant barriers to implementation due to concerns around resources and cost efficiency. The current study informs future intervention development and implementation.

Abstract Identifying genetic modifiers of familial amyotrophic lateral sclerosis (ALS) may reveal targets for therapeutic modulation with potential application to sporadic ALS. GGGGCC (G4C2) repeat expansions in the C9orf72 gene underlie the most common form of familial ALS, and generate toxic arginine-containing dipeptide repeats (DPRs), which interfere with membraneless organelles, such as the nucleolus. Here we considered senataxin (SETX), the genetic cause of ALS4, as a modifier of C9orf72 ALS, because SETX is a nuclear helicase that may regulate RNA–protein interactions involved in ALS dysfunction. After documenting that decreased SETX expression enhances arginine-containing DPR toxicity and C9orf72 repeat expansion toxicity in HEK293 cells and primary neurons, we generated SETX fly lines and evaluated the effect of SETX in flies expressing either (G4C2)58 repeats or glycine-arginine-50 [GR(50)] DPRs. We observed dramatic suppression of disease phenotypes in (G4C2)58 and GR(50) Drosophila models, and detected a striking relocalization of GR(50) out of the nucleolus in flies co-expressing SETX. Next-generation GR(1000) fly models, that show age-related motor deficits in climbing and movement assays, were similarly rescued with SETX co-expression. We noted that the physical interaction between SETX and arginine-containing DPRs is partially RNA-dependent. Finally, we directly assessed the nucleolus in cells expressing GR-DPRs, confirmed reduced mobility of proteins trafficking to the nucleolus upon GR-DPR expression, and found that SETX dosage modulated nucleolus liquidity in GR-DPR-expressing cells and motor neurons. These findings reveal a hitherto unknown connection between SETX function and cellular processes contributing to neuron demise in the most common form of familial ALS.

Summary: G3BP1/2 are paralogous proteins that promote stress granule formation in response to cellular stresses, including viral infection. The nucleocapsid (N) protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) inhibits stress granule assembly and interacts with G3BP1/2 via an ITFG motif, including residue F17, in the N protein. Prior studies examining the impact of the G3PB1-N interaction on SARS-CoV-2 replication have produced inconsistent findings, and the role of this interaction in pathogenesis is unknown. Here, we use structural and biochemical analyses to define the residues required for G3BP1-N interaction and structure-guided mutagenesis to selectively disrupt this interaction. We find that N-F17A mutation causes highly specific loss of interaction with G3BP1/2. SARS-CoV-2 N-F17A fails to inhibit stress granule assembly in cells, has decreased viral replication, and causes decreased pathology in vivo. Further mechanistic studies indicate that the N-F17-mediated G3BP1-N interaction promotes infection by limiting sequestration of viral genomic RNA (gRNA) into stress granules.

Abstract Opioids have been used to manage pain for thousands of years, but they have significant potential for abuse. Prescription opioids, like oxycodone, are associated with 32% of overdoses, that have reached a total of 75,673 deaths in 2021. A major challenge is maximizing their therapeutic potential while minimizing the negative side effects including opioid use disorder (OUD). The Ketogenic Diet (KD) has been reported to reduce pain and decrease the severity of alcohol use disorder, yet its effects on oxycodone responses remain unknown. KD mice displayed increased oxycodone-induced locomotor activity and enhanced antinociceptive effects of oxycodone, suggesting a dietary effect on opiate sensitivity. Male KD mice exposed to chronic oxycodone exhibited increased naloxone-induced jumps, suggesting a sex-specific effect of diet on opioid withdrawal. Consistent with this, male KD mice self-administered less oxycodone while female KD mice did not differ from controls. Finally, no effect of KD on motivation to obtain oxycodone was observed during a progressive ratio schedule. These data suggest sex-biased effects of KD on responses to opioids that should be considered and potentially leveraged in both clinical pain management and treatment of OUD.

Abstract Background Asthma is a common long-term condition and major public health problem. Supported self-management for asthma that includes a written personalised asthma action plan, supported by regular professional review, reduces unscheduled consultations and improves asthma outcomes and quality of life. However, despite unequivocal inter/national guideline recommendations, supported self-management is poorly implemented in practice. The IMPlementing IMProved Asthma self-management as RouTine (IMP2ART) implementation strategy has been developed to address this challenge. The aim of this implementation trial is to determine whether facilitated delivery of the IMP2ART strategy increases the provision of asthma action plans and reduces unscheduled care in the context of routine UK primary care. Methods IMP2ART is a parallel group, cluster randomised controlled hybrid II implementation trial. One hundred forty-four general practices will be randomly assigned to either the IMP2ART implementation strategy or control group. Following a facilitation workshop, implementation group practices will receive organisational resources to help them prioritise supported self-management (including audit and feedback; an IMP2ART asthma review template), training for professionals and resources to support patients to self-manage their asthma. The control group will continue with usual asthma care. The primary clinical outcome is the between-group difference in unscheduled care in the second year after randomisation (i.e. between 12 and 24 months post-randomisation) assessed from routine data. Additionally, a primary implementation outcome of asthma action plan ownership at 12 months will be assessed by questionnaire to a random sub-group of people with asthma. Secondary outcomes include the number of asthma reviews conducted, prescribing outcomes (reliever medication and oral steroids), asthma symptom control, patients’ confidence in self-management and professional support and resource use. A health economic analysis will assess cost-effectiveness, and a mixed methods process evaluation will explore implementation, fidelity and adaptation. Discussion The evidence for supported asthma self-management is overwhelming. This study will add to the literature regarding strategies that can effectively implement supported self-management in primary care to reduce unscheduled consultations and improve asthma outcomes and quality of life. Trial registration ISRCTN15448074. Registered on 2 December 2019.

We consider a pair of quantum dot-based spin qubits that interact via microwave photons in a superconducting cavity and that are also parametrically driven by separate external electric fields. For this system, we formulate a model for spin qubit entanglement in the presence of mutually off-resonant qubit and cavity frequencies. We show that the sidebands generated via the driving fields enable highly tunable qubit-qubit entanglement using only ac control and without requiring the qubit and cavity frequencies to be tuned into simultaneous resonance. The model we derive can be mapped to a variety of qubit types, including detuning-driven one-electron spin qubits in double quantum dots and three-electron resonant exchange qubits in triple quantum dots. The high degree of nonlinearity inherent in spin qubits renders these systems particularly favorable for parametric drive-activated entanglement. We determine multiple common resonance conditions for the two driven qubits and the cavity and identify experimentally relevant parameter regimes that enable the implementation of entangling gates with suppressed sensitivity to cavity photon occupation and decay. The parametrically driven sideband resonance approach that we describe provides a promising route toward scalability and modularity in spin-based quantum information processing through drive-enabled tunability that can also be implemented in micromagnet-free electron and hole systems for spin-photon coupling.

In recent years, RNA has gained traction both as a therapeutic molecule and as a therapeutic target in several human pathologies. In this review, we consider the approach of targeting RNA using small molecules for both research and therapeutic purposes. Given the primary challenge presented by the low structural diversity of RNA, we discuss the potential for targeting RNA: protein interactions to enhance the structural and sequence specificity of drug candidates. We review available tools and inherent challenges in this approach, ranging from adapted bioinformatics tools to in vitro and cellular high-throughput screening and functional analysis. We further consider two critical steps in targeting RNA/protein interactions: first, the integration of in silico and structural analyses to improve the efficacy of molecules by identifying scaffolds with high affinity, and second, increasing the likelihood of identifying on-target compounds in cells through a combination of high-throughput approaches and functional assays. We anticipate that the development of a new class of molecules targeting RNA: protein interactions to prevent physio-pathological mechanisms could significantly expand the arsenal of effective therapeutic compounds.

Over 1 million Americans are currently living with T1D and improvements in diabetes management have increased the number of adults with T1D living into later decades of life. This growing population of older adults with diabetes is more susceptible to aging comorbidities, including both vascular disease and osteoporosis. Indeed, adults with T1D have a 2- to 3- fold higher risk of any fracture and up to 7-fold higher risk of hip fracture compared to those without diabetes. Recently, diabetes-related vascular deficits have emerged as potential risks factors for impaired bone blood flow and poor bone health and it has been hypothesized that there is a direct pathophysiologic link between vascular disease and skeletal outcomes in T1D. Indeed, microvascular disease (MVD), one of the most serious consequences of diabetes, has been linked to worse bone microarchitecture in older adults with T1D compared to their counterparts without MVD. The association between the presence of microvascular complications and compromised bone microarchitecture indicates the potential direct deleterious effect of vascular compromise, leading to abnormal skeletal blood flow, altered bone remodeling, and deficits in bone structure. In addition, vascular diabetic complications are characterized by increased vascular calcification, decreased arterial distensibility, and vascular remodeling with increased arterial stiffness and thickness of the vessel walls. These extensive alterations in vascular structure lead to impaired myogenic control and reduced nitric-oxide mediated vasodilation, compromising regulation of blood flow across almost all vascular beds and significantly restricting skeletal muscle blood flow seen in those with T1D. Vascular deficits in T1D may very well extend to bone, compromising skeletal blood flow control, and resulting in reduced blood flow to bone, thus negatively impacting bone health. Indeed, several animal and ex vivo human studies report that diabetes induces microvascular damage within bone are strongly correlated with diabetes disease severity and duration. In this review article, we will discuss the contribution of diabetes-induced vascular deficits to bone density, bone microarchitecture, and bone blood flow regulation, and review the potential contribution of vascular disease to skeletal fragility in T1D.

Abstract Background The Chronic Headache Education and Self-Management Study (CHESS) multicentre randomised trial evaluated the impact a group education and self-management support intervention with a best usual care plus relaxation control for people living with chronic headache disorders (tension type headaches or chronic migraine, with or without medication overuse headache). Here we report the process evaluation exploring potential explanations for the lack of positive effects from the CHESS intervention. Methods The CHESS trial included 736 (380 intervention: 356 control) people across the Midlands and London UK. We used a mixed methods approach. Our extensive process evaluation looked at context, reach, recruitment, dose delivered, dose received, fidelity and experiences of participating in the trial, and included participants and trial staff. We also looked for evidence in our qualitative data to investigate whether the original causal assumptions underpinning the intervention were realised. Results The CHESS trial reached out to a large diverse population and recruited a representative sample. Few people with chronic tension type headaches without migraine were identified and recruited. The expected ‘dose‘of the intervention was delivered to participants and intervention fidelity was high. Attendance (“dose received”) fell below expectation, although 261/380 (69%) received at least at least the pre-identified minimum dose. Intervention participants generally enjoyed being in the groups but there was little evidence to support the causal assumptions underpinning the intervention were realised. Conclusions From a process evaluation perspective despite our extensive data collection and analysis, we do not have a clear understanding of why the trial outcome was negative as the intervention was delivered as planned. However, the lack of evidence that the intervention causal assumptions brought about the planned behaviour change may provide some insight. Our data suggests only modest changes in managing headache behaviours and some disparity in how participants engaged with components of the intervention within the timeframe of the study. Moving forwards, we need a better understanding of how those who live with chronic headache can be helped to manage this disabling condition more effectively over time. Trial registration ISRCTN79708100 .

Installations of artificial structures in coastal oceans create de facto habitat for marine life. These structures encompass wide varieties of physical characteristics, reflecting their multiple, diverse purposes and creating a need to understand which characteristics maximize fish habitat. Here, we test how physical characteristics – horizontal area, vertical relief, and spatial isolation – relate to fish density from echosounder surveys over artificial structures like concrete pipes, train boxcars, and ships purposely sunk to function as reefs. Echosounder mapping of 31 artificial reef structures and associated fish across a 200 km linear length of the continental shelf of North Carolina, USA, revealed that structures with greater horizontal area and vertical relief host higher fish densities than smaller, shorter structures. Artificial structure spatial arrangement also relates to fish density, as isolated structures are generally associated with greater localized fish densities than structures closer to one another. Patterns in the relationships between fish density and reef characteristics differed for schooling fish, as there was some evidence that reefs of intermediate area exhibited higher schooling fish density. These results suggest that intentional design and spatial arrangement of marine built structures like artificial reefs relates to and can be deliberately incorporated into siting and deployment decisions to enhance their role as fish habitat.

Epiphytic microalgae are important contributors to the carbon and nutrient cycles yet are often overlooked during ecological surveys. In reef habitats, epiphytes are often found living on host organisms, including seaweeds or corals, and can influence community composition of higher trophic level taxa. Hence, understanding how epiphytes respond to different reef substrate materials can help inform designs of substrates intentionally deployed to form artificial reefs which can encourage high biodiversity and ecological functioning. One such epiphyte, Gambierdiscus spp., is a harmful benthic dinoflagellate which produces toxins that bioaccumulate and cause ciguatera fish poisoning (CFP) when contaminated fish is consumed by humans. CFP is one of the most frequently reported seafood-associated illnesses around the world, occurring most often near tropical reefs. We surveyed the epiphytes amongst 13 natural and artificial reef sites located off the coast of North Carolina to determine the role of the reefs’ foundational substrate (e.g., natural marl, steel or concrete) on structuring the epiphyte community with an emphasis on Gambierdiscus spp. abundance. No Gambierdiscus spp. were detected among the sampled reefs, likely due to suboptimal water temperatures. An ex-situ substrate preference experiment for Gambierdiscus spp. was performed using marl to represent natural rocky reefs, and steel and concrete to represent artificial reefs. Experimental results indicated that Gambierdiscus spp. grew fastest in the presence of marl and density decreased significantly when exposed to steel. However, steel artificial reefs had the highest average epiphyte biomass and species richness amongst the sampled reefs. 18s rRNA gene sequence analysis revealed that natural reefs were more likely to be dominated by dinoflagellates, whereas steel and concrete reefs were dominated by diatoms. We found that epiphyte composition was related to material at a phylum level, but seaweed hosts played a more significant role at the species level. These findings suggest that CFP risk is relatively low on the reefs studied but natural reefs would likely be preferentially colonized by Gambierdiscus spp. should ambient conditions become appropriate.

Mutations in HNRNPH2 cause an X-linked neurodevelopmental disorder with features that include developmental delay, motor function deficits, and seizures. More than 90% of patients with hnRNPH2 have a missense mutation within or adjacent to the nuclear localization signal (NLS) of hnRNPH2. Here, we report that hnRNPH2 NLS mutations caused reduced interaction with the nuclear transport receptor Kapβ2 and resulted in modest cytoplasmic accumulation of hnRNPH2. We generated 2 knockin mouse models with human-equivalent mutations in Hnrnph2 as well as Hnrnph2-KO mice. Knockin mice recapitulated clinical features of the human disorder, including reduced survival in male mice, impaired motor and cognitive functions, and increased susceptibility to audiogenic seizures. In contrast, 2 independent lines of Hnrnph2-KO mice showed no detectable phenotypes. Notably, KO mice had upregulated expression of Hnrnph1, a paralog of Hnrnph2, whereas knockin mice failed to upregulate Hnrnph1. Thus, genetic compensation by Hnrnph1 may counteract the loss of hnRNPH2. These findings suggest that HNRNPH2-related disorder may be driven by a toxic gain of function or a complex loss of HNRNPH2 function with impaired compensation by HNRNPH1. The knockin mice described here are an important resource for preclinical studies to assess the therapeutic benefit of gene replacement or knockdown of mutant hnRNPH2.

Introduction In the UK, approximately 4.3 million adults have asthma, with one-third experiencing poor asthma control, affecting their quality of life, and increasing their healthcare use. Interventions promoting emotional/behavioural self-management can improve asthma control and reduce comorbidities and mortality. Integration of online peer support into primary care services to foster self-management is a novel strategy. We aim to co-design and evaluate an intervention for primary care clinicians to promote engagement with an asthma online health community (OHC). Our protocol describes a ‘survey leading to a trial’ design as part of a mixed-methods, non-randomised feasibility study to test the feasibility and acceptability of the intervention.Methods and analysis Adults on the asthma registers of six London general practices (~3000 patients) will be invited to an online survey, via text messages. The survey will collect data on attitudes towards seeking online peer support, asthma control, anxiety, depression, quality of life, information on the network of people providing support with asthma and demographics. Regression analyses of the survey data will identify correlates/predictors of attitudes/receptiveness towards online peer support. Patients with troublesome asthma, who (in the survey) expressed interest in online peer support, will be invited to receive the intervention, aiming to reach a recruitment target of 50 patients. Intervention will involve a one-off, face-to-face consultation with a practice clinician to introduce online peer support, sign patients up to an established asthma OHC, and encourage OHC engagement. Outcome measures will be collected at baseline and 3 months post intervention and analysed with primary care and OHC engagement data. Recruitment, intervention uptake, retention, collection of outcomes, and OHC engagement will be assessed. Interviews with clinicians and patients will explore experiences of the intervention.Ethics and dissemination Ethical approval was obtained from a National Health Service Research Ethics Committee (reference: 22/NE/0182). Written consent will be obtained before intervention receipt and interview participation. Findings will be shared via dissemination to general practices, conference presentations and peer-reviewed publications.Trial registration number NCT05829265.

IntroductionWheelchair turning biomechanics is an under researched area despite its obvious relevance to functional mobility of wheelchair users. Wheelchair turns might be linked to a higher risk of upper limb injuries due to the increased forces and torques potentially associated with asymmetric movement. Our aim was to obtain a better theoretical understanding of wheelchair turning by biomechanically analyzing turns compared to steady-state straightforward propulsion (SSSFP).MethodsTen able-bodied men received 12-min familiarization and 10 trials (in a random order) of SSSFP and multiple left and right turns around a rectangular course. A Smartwheel was mounted at the right wheel of a standard wheelchair to measure kinetic parameters during SSSFP and of the inner hand during right turns and the outer hand during left turns. A repeated measures ANOVA was used to detect differences across tasks.ResultsTwo strategies were identified: 3% demonstrated roll turns and 97% spin turns. Spin turns consisted of three phases: approach, turning and depart phase. The turning phase was accomplished by increasing peak force (72.9 ± 25.1 N vs. 43.38 ± 15.9 N in SSSFP) of the inner hand, while maintaining high push frequency of the outer hand (1.09 ± 0.20 push/s vs. 0.95 ± 0.13 push/s in SSSFP). Peak negative force and force impulse during the turning phase were much higher than SSSFP, 15.3 ± 15.7 and 4.5 ± 1.7 times higher, respectively.ConclusionThe spin turn strategy might carry an increased risk of upper limb injuries due to higher braking force and requires particular attention by rehabilitation professionals to preserve upper limb function of long-term wheelchair users.

How are attitudes formed in the 21st Century, and who sets the agenda for initial COVID-19 coverage in the United States? We explore these questions using a random sample of 6 million tweets from a population of 224 million tweets collected between January 2020 and June 2020. In conjunction with a content analysis of legacy media such as newspapers, we examine the second-level agendamelding process during the onset of the COVID-19 pandemic in the United States. The findings demonstrate that in the early weeks of the pandemic, public opinion on Twitter about the virus was distinctly different than the coverage of the issue in the traditional media. The attributes used to describe it on social media demonstrate users relying on their past experiences and personal beliefs to talk about the virus. In the 1st week of February, public opinion, traditional media, and social media converged, but traditional media soon becomes the main agenda setter of COVID-19 for 13 weeks. However, for the final 5 weeks of our sample, traditional media are taken over by social media. The findings also show that, except for a few weeks at the onset of the outbreak, Twitter users relied on their personal experiences far less than what statistical models predicted and allowed. Instead, traditional media and social media to shape their opinion of the issue.

Coastal fish communities are under increasing levels of stress associated with climate variation and anthropogenic activities. However, the high degree of behavioral plasticity of many species within these communities allow them to cope with altered environmental conditions to some extent. Here, we combine meteorological information, data from hydroacoustic surveys, and recordings of goliath grouper sound production to examine the response of coastal fish communities to heavy rainfall events in South Florida, USA, that resulted in the release of excess storm water into surrounding estuaries and coastal waters. We observed a nearly 12,000% increase in water column acoustic backscatter following a heavy rainfall event of September 16th, 2015. Interestingly, estimates of school backscatter, a proxy for biomass, increased by 172% with the onset of the perturbation. Schooling fish density also increased by 182%, as did acoustically derived estimates of mean schooling fish length (21%). Following the perturbed period, school backscatter decreased by 406%, along with schooling density (272%), and mean schooling fish length (35%). Hydrophone and hydroacoustic data also revealed that goliath grouper (Epinephelus itajara) spawning aggregations were persistent in the region throughout the duration of the study and continued to exhibit courtship behavior during the perturbed period. Our observations demonstrate the high level of resistance common in coastal species but raises new questions regarding the threshold at which fish communities and reproductive activities are disrupted. As coastal land use continues to increase, and the effects of global climate change become more pronounced, more Before-After Control Impact (BACI) studies will provide improved insight into the overall response of nearshore communities to future perturbations and the cumulative effect of repeated perturbations over extended periods.

Recent research on intergroup contact theory has emphasized the potency of cross-group friendship for reducing prejudice. Evaluating this claim requires consideration of competing friend influence and selection processes. Few studies have jointly tested these mechanisms and often only in limited, majority/minority group contexts. In this study, the authors articulate several mechanisms linking friendships with intergroup attitudes and test them in a diverse U.S. context (two large high schools with significant representations of multiple ethnoracial groups). The analysis involves a longitudinal network model of friendship and attitude coevolution. The findings indicate that ingroup friends influenced intergroup contact attitudes (ICAs) over time, while more open ICAs promoted selection into cross-group friendship. By contrast, effects of cross-group friendships on ICAs were limited to White students with Black friends. These findings suggest that the effect of intergroup contact is overstated in the context of friendship and that more focus should be paid to understanding other friendship dynamics.

Abstract Background SURECAN (SUrvivors’ Rehabilitation Evaluation after CANcer) is a multi-phase study developing and evaluating an Acceptance and Commitment Therapy (ACT) intervention integrated with exercise and work when highly valued (thus we called the intervention ACT+), for people who have completed treatment for cancer but who have low quality of life. We developed a training programme for therapists working in different psychological services to be delivered over 2–3 days. Our aim was to evaluate the extent to which the training could improve therapists’ knowledge and confidence to deliver ACT+ to cancer patients in a trial setting. Methods Three interactive workshops were delivered to 29 therapists from three clinical settings in London and in Sheffield. A mixed-methods approach was used. Questionnaires were designed to assess knowledge and confidence in using ACT+ with people who have low quality of life after cancer treatment. They were self-administered immediately prior to and after each workshop. Open text-based questions were used to elicit feedback about the workshops alongside a satisfaction scale. Semi-structured interviews were conducted with a purposive sample of therapists (n = 12) to explore their views about the training more deeply, and how it might be optimised. Results Quantitative analysis showed that knowledge of ACT, as well as confidence in using the ACT+ intervention in this setting increased significantly after training (28.6 and 33.5% increase in the median score respectively). Qualitative analysis indicated that most therapists were satisfied with the content and structure of the programme, valued the rich resources provided and enjoyed the practice-based approach. Potential barriers/facilitators to participation in the trial and to the successful implementation of ACT+ were identified. For some therapists, delivering a manualised intervention, as well as supporting exercise- and work-related goals as non-specialists was seen as challenging. At the same time, therapists valued the opportunity to be involved in research, whilst training in a new therapy model. Conclusions Training can effectively improve the knowledge and confidence of therapists from different clinical backgrounds to deliver a modified ACT intervention to cancer patients in a trial setting.

Introduction The different factors that contribute to gender differences among patients with vascular dementia (VaD), Alzheimer’s disease (AD), and mixed vascular dementia and Alzheimer’s disease (VDAD) are not fully understood. This study examined gender differences among patients with VaD, AD, and VDAD using demographic and pharmacologic factors. Methods Data was collected from Prisma Health‐Upstate Alzheimer registry from 2016 to 2021 for 6,039 VaD patients, 9,290 AD patients, and 412 VDAD patients. A logistic regression model was used to determine demographic and pharmacological factors that are associated with gender differences in patients with VaD, AD, and VDAD. Results In the adjusted analysis for patients with VaD, increasing age (OR = 1.023, 95% CI, 1.017‐1.029, p< 0.001) and use of aripiprazole (OR = 4.395, 95% CI, 2.880‐6.707, p< 0.001) were more associated with women, whereas use of tobacco (OR = 0.312, 95% CI, 0.278‐0.349, p< 0.001) and galantamine (OR = 0.228, 95% CI, 0.116‐0.449, p< 0.001) were more associated with men. In patients with AD, Black race (OR = 1.747, 95% CI, 1.486‐2.053, p< 0.001) and use of buspirone (OR = 1.541, 95% CI, 1.265‐1.878, p< 0.001) were more associated with women, whereas use of ETOH (OR = 0.627, 95% CI, 0.547‐0.718, p< 0.001) and memantine (OR = 0.882, 95% CI, 0.799‐0.974, p = 0.013) were more associated with men. In patients with VDAD, use of rivastigmine (OR = 3.293, 95% CI, 1.131‐9.585, p = 0.029) was more associated with women, whereas increased length of hospital stay (OR = 0.910, 95% CI, 0.828‐1.000, p = 0.049) was more associated with men. Conclusions Our study revealed that there are gender differences and similarities in the demographic and pharmacological factors of VaD, AD, and VDAD. Future studies can be conducted investigating each of these factors to improve treatment of VaD, AD, and VDADin all patients.

Protected areas (PAs) can help address biodiversity loss by promoting conservation while fostering economic development through sustainable tourism. Nature-based tourism can generate economic benefits for communities in and around PAs; however, its impacts do not lend themselves to conventional impact evaluation tools. We utilize a Monte Carlo simulation approach with econometric estimations using microdata to estimate the full economic impact of nature-based tourism on the economies surrounding three terrestrial and two marine PAs. Simulations suggest that nature-based tourism creates significant economic benefits for communities around PAs, including the poorest households, and many of these benefits are indirect, via income and production spillovers. An additional tourist increases annual real income in communities near the PAs by US$169-$2,400, significantly more than the average tourist's expenditure. Conversely, lost tourism due to the COVID-19 pandemic and economic costs of human-wildlife conflict have disproportionately large negative impacts on local incomes.

Golden-winged Warblers (Vermivora chrysoptera, Parulidae) are declining migrant songbirds that breed in the Great Lakes and Appalachian regions of North America. Within their breeding range, Golden-winged Warblers are found in early successional habitats adjacent to mature hardwood forest, and previous work has found that Golden-winged Warbler habitat preferences are scale-dependent. Golden-winged Warbler Working Group management recommendations were written to apply to large regions of the breeding range, but there may be localized differences in both habitat availability and preferences. Rapid declines at the southernmost extent of their breeding range in Western North Carolina necessitate investigation into landscape characteristics governing distribution in this subregion. Furthermore, with the increase in availability of community science data from platforms such as eBird, it would be valuable to know if community science data produces similar distribution models as systemic sampling data. In this study, we described patterns of Golden-winged Warbler presence in Western North Carolina by examining habitat variables at multiple spatial scales using data from standardized Audubon North Carolina (NC) playback surveys and community science data from eBird. We compared model performance and predictions between Audubon NC and eBird models and found that Golden-winged Warbler presence is associated with sites which, at a local scale (150m), have less mature forest, more young forest, more herb/shrub cover, and more road cover, and at a landscape scale (2500m), have less herb/shrub cover. Golden-winged Warbler presence is also associated with higher elevations and smaller slopes. eBird and Audubon models had similar variable importance values, response curves, and overall performance. Based on variable importance values, elevation, mature forest at the local scale, and road cover at the local scale are the primary variables driving the difference between Golden-winged Warbler breeding sites and random background sites in Western North Carolina. Additionally, our results validate the use of eBird data, since they produce species distribution modeling results that are similar to results obtained from more standardized survey methods.

Abstract We conducted a systematic review on the impacts of natural causes of variation or changes in flow magnitude (resulting from climatic variability and broad‐scale drivers such as climate‐induced change) on fish abundance and biomass in temperate regions. Following our systematic review protocol (Birnie‐Gauvin et al., 2021), we examined commercially published and grey literature originally identified during a recent systematic map process (Rytwinski et al., 2020) and a systematic search update. Articles were screened using an a priori eligibility criteria, with consistency checks performed at the title and abstract, and full text screening stages. All eligible articles were assessed for study validity. A narrative synthesis included all available evidence (300 studies from 219 articles), and meta‐analyses (1863 datasets from 193 studies) were conducted where appropriate. Most studies were conducted in the United States (65%) on genera in the Salmonidae and Leuciscidae families (29% and 28%, respectively), and mainly investigated variation in flow magnitude, followed by droughts and floods. We found that fish abundance and biomass responses to changes in natural flow magnitude were mainly negative, but analyses do not support clear generalizable signals across all contexts (e.g. types of changes in flow magnitude, taxa, locations). When exploring reasons for heterogeneity in effect sizes, we found a detectable effect of intervention type on average fish abundance within the first year of the natural change in flow magnitude, with floods and droughts associated with overall negative responses. However, these patterns were more variable when considering between‐year variation or specific taxonomic responses. Our results suggest that while immediate responses were more apparent and relatively consistent within specific types of natural events, fish populations may recover after such events (i.e. ≥2 years post‐natural event); however, most studies were short in duration (

Background: Gender differences for dementia with Lewy bodies (DLB), usually considered an intermediate disease between Alzheimer disease (AD), Parkinson disease (PD), and Parkinson disease with dementia (PDD), is controversial. The present study investigated gender differences in DLB and PDD using demographic and pharmacologic treatment strategies in a retrospective data analysis. Method: Data of confirmed cases of DLB and PDD between 2015 and 2020 were collected from the PRISMA dementia data-base registry. Data from 7594 PDD patients and 608 DLB patients were analyzed using logistic regression analysis to determine demographic and pharmacologic factors associated with DLB and PDD patients. Result: In the adjusted analysis, central acetylcholinesterase inhibitors (ChEIs) including donepezil, galantamine, rivastigmine were associated with DLB. Second generation antipsychotics (SGAs) such as risperidone (odd ratio(OR)=1.900, 95% confidence interval (CI),1.192–3.030, P = 0.007) was associated with females with DLB while aripiprazole (OR=0.195,95% CI,0.06–0.631, P

Biogeographic assessments aim to determine spatial and temporal distributions of organisms and habitats to help inform resource management decisions. In marine systems, rapid technological advances in sensors employed for biogeographic assessments allow scientists to collect unprecedented volumes of data, yet it remains challenging to visually and intuitively convey these sometimes massive spatial or temporal data as actionable information in geographically relevant maps or virtual models. Here, we provide a case study demonstrating an approach to bridge this data visualization gap by displaying coastal ocean data in a 3D, interactive online format. Our case study documents a workflow that provides resource managers, stakeholders, and the general public with a platform for direct exploration of and interaction with 3D data from hydrographically mapping shipwrecks and marine life on the continental shelf of North Carolina, USA. We simultaneously mapped shipwrecks and their associated fish using echosounders. A multibeam echosounder collected high-resolution multibeam bathymetry of the shipwrecks and detected the broad extent of fish schools. A calibrated splitbeam echosounder detected individual fish and fish schools. After processing the echosounder data, we built an interactive, online 3D data visualization web application complemented by multimedia and story text using ESRI geographic information systems. The freely available visual environment, called “Living Shipwrecks 3D,” allows direct engagement with the biogeographic assessment data in a customizable format. We anticipate that additional interactive 3D data applications can be constructed using a similar workflow allowing seamless exploration of complex spatial data used in biogeographic assessments.

The blood–brain barrier (BBB) is a selective barrier that controls the transport between the blood and neural tissue features and maintains brain homeostasis to protect the central nervous system (CNS). In vitro models can be useful to understand the role of the BBB in disease and assess the effects of drug delivery. Recently, we reported a 3D BBB model with perfusable microvasculature in a Transwell insert. It replicates several key features of the native BBB, as it showed size-selective permeability of different molecular weights of dextran, activity of the P-glycoprotein efflux pump, and functionality of receptor-mediated transcytosis (RMT), which is the most investigated pathway for the transportation of macromolecules through endothelial cells of the BBB. For quality control and permeability evaluation in commercial use, visualization and quantification of the 3D vascular lumen structures is absolutely crucial. Here, for the first time, we report a rapid, non-invasive optical coherence tomography (OCT)-based approach to quantify the microvessel network in the 3D in vitro BBB model. Briefly, we successfully obtained the 3D OCT images of the BBB model and further processed the images using three strategies: morphological imaging processing (MIP), random forest machine learning using the Trainable Weka Segmentation plugin (RF-TWS), and deep learning using pix2pix cGAN. The performance of these methods was evaluated by comparing their output images with manually selected ground truth images. It suggested that deep learning performed well on object identification of OCT images and its computation results of vessel counts and surface areas were close to the ground truth results. This study not only facilitates the permeability evaluation of the BBB model but also offers a rapid, non-invasive observational and quantitative approach for the increasing number of other 3D in vitro models.

With increasing human uses of the ocean, existing seascapes containing natural habitats, such as biogenic reefs or plant-dominated systems, are supplemented by novel, human-made habitats ranging from artificial reefs to energy extraction infrastructure and shoreline installments. Despite the mixture of natural and artificial habitats across seascapes, the distribution and extent of these two types of structured habitats are not well understood but are necessary pieces of information for ocean planning and resource management decisions. Through a case study, we quantified the amount of seafloor in the southeastern US (SEUS; 103,220 km2 in the Atlantic Ocean; 10 – 200 m depth) covered by artificial reefs and natural reefs. We developed multiple data-driven approaches to quantify the extent of artificial reefs within state-managed artificial reef programs, and then drew from seafloor maps and published geological and predictive seafloor habitat models to develop three estimates of natural reef extent. Comparisons of the extent of natural and artificial reefs revealed that artificial reefs account for substantially less habitat (average of two estimates 3 km2;

Rapidly improving gate fidelities for coherent operations mean that errors in state preparation and measurement (SPAM) may become a dominant source of error for fault-tolerant operation of quantum computers. This is particularly acute in superconducting systems, where tradeoffs in measurement fidelity and qubit lifetimes have limited overall performance. Fortunately, the essentially classical nature of preparation and measurement enables a wide variety of techniques for improving quality using auxiliary qubits combined with classical control and post-selection. In practice, however, post-selection greatly complicates the scheduling of processes such as syndrome extraction. Here we present a family of quantum circuits that prepare high-quality |0$\rangle$ states without post-selection, instead using CNOT and Toffoli gates to non-linearly permute the computational basis. We find meaningful performance enhancements when two-qubit gate fidelities errors go below 0.2%, and even better performance when native Toffoli gates are available.