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Childhood wellbeing is essential for positive outcomes in adulthood, as is academic attainment. Schools play a pivotal role in laying the foundations for children to live well. However, research investigating the relationship between wellbeing and attainment has relied on conceptualisations of wellbeing that are too broad (i.e. overall and domain-general wellbeing) or samples spanning large age ranges (thereby overlooking developmental differences). Additionally, the role of mindset, a potentially co-occurring psychological state of both wellbeing and attainment, has been neglected. This study therefore investigated the wellbeing-attainment relationship in 942 children aged 9-11 (447 male, M[subscript age] = 10.5; 495 female, M[subscript age] = 10.6) across 17 schools in England (UK). Structural equation models distinguished between overall wellbeing, life satisfaction, and eudaimonia, examining associations of each with children's attainment on standardised tests, accounting for mindsets, achievement goals, and sociodemographic factors. Results indicated lower life satisfaction was significantly associated with higher attainment on average, and in English and Mathematics, while eudaimonia was not significantly related to attainment. Overall wellbeing was negatively associated with Mathematics attainment only. A growth mindset was "positively" associated, while a fixed mindset was "negatively" associated, with wellbeing. In turn, a growth mindset was significantly "positively" associated, while a fixed mindset was "negatively" associated, with attainment. Implications for policy and practice are discussed.

The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimers opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

Our previous study identified 52 antiplasmodial peptaibols isolated from fungi. To understand their antiplasmodial mechanism of action, we conducted phenotypic assays, assessed the in vitro evolution of resistance, and performed a transcriptome analysis of the most potent peptaibol, HZ NPDG-I. HZ NPDG-I and 2 additional peptaibols were compared for their killing action and stage dependency, each showing a loss of digestive vacuole (DV) content via ultrastructural analysis. HZ NPDG-I demonstrated a stepwise increase in DV pH, impaired DV membrane permeability, and the ability to form ion channels upon reconstitution in planar membranes. This compound showed no signs of cross resistance to targets of current clinical candidates, and 3 independent lines evolved to resist HZ NPDG-I acquired nonsynonymous changes in the P. falciparum multidrug resistance transporter, pfmdr1. Conditional knockdown of PfMDR1 showed varying effects to other peptaibol analogs, suggesting differing sensitivity.

BACKGROUND: Postoperative delirium is a common problem affecting admitted patients that decreases patient satisfaction and increases the cost and complexity of care. The purpose of this study was to use the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database to compare rates and risk factors of postoperative delirium for total hip arthroplasty (THA) and hemiarthroplasty patients indicated for osteoarthritis or proximal femur fracture. METHODS: The 2021 NSQIP database was queried for patients using Current Procedural Terminology (CPT) codes for THA and hemiarthroplasty and ICD-10 codes for osteoarthritis or proximal femur fracture. Demographic, past medical history, preoperative labs, and functional status data were recorded. Procedural data were also collected. Finally, postoperative outcomes and complications were reviewed. RESULTS: Overall, 16% of patients had postoperative delirium. Delirium patients were older on average (82.4 years vs. 80.7 years, p

BackgroundThe purpose of this study was to investigate the relationship between preoperative aspartate aminotransferase-to-platelet ratio index (APRI) and postoperative complications following total hip arthroplasty (THA).MethodsAll THA for osteoarthritis patients from 2007 to 2020 within the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) database were included in this study. Subjects were subsequently divided into cohorts based on APRI. Four groups, including normal range, some liver damage, significant fibrosis, and cirrhosis groups, were created. Comparisons between groups were made for demographics, past medical history, and rate of major and minor complications. Other outcomes included readmission, reoperation, discharge destination, mortality, periprosthetic fracture, and postoperative hip dislocation. Multivariate logistic regression analysis was performed to determine the role of preoperative APRI in predicting adverse outcomes. Statistical significance was set at p

Abstract Background Anxiety disorders are among the most prevalent mental health concerns affecting children and adolescents. Despite their high prevalence, statistics indicate that fewer than 25% of individuals in this demographic seek professional assistance for their condition. Consequently, there is a pressing need to develop innovative interventions aimed at improving treatment accessibility. Objectives This study aims to assess the effectiveness of Internet-delivered Cognitive Behavioral Therapy (iCBT) for adolescents with anxiety, with a specific emphasis on involving parents in the treatment process. Methods The study is structured as a parallel three-armed randomized controlled trial, comparing Internet-delivered Cognitive Behavioral Therapy (iCBT) with planned feedback, iCBT with on-demand feedback, and a waitlist control group, each group including 56 participants. Participants in the two iCBT conditions will undergo a 14-week treatment regimen, while those in the waitlist control group will wait for 14 weeks before starting iCBT with planned feedback. Additionally, participants in the iCBT groups will be randomly assigned to receive a booster session or not. The study design is factorial including two factors: type of therapist feedback (factor 1) and booster or no booster (factor 2). The study population comprises adolescents aged between 12 and 17 years, residing in Denmark, diagnosed with an anxiety disorder according to DSM-5 criteria. The primary outcome measures are the Youth Online Diagnostic Assessment and the Spence Children’s Anxiety Scale. Assessments will occur at baseline, post-treatment, and at 3-, 6-, and 12-month follow-ups post-treatment. Discussion The findings of this study are anticipated to contribute to improving the accessibility of evidence-based treatments for adolescents with anxiety. Trial registration The study is registered at clinicalTrials.gov, under protocol ID 22/59602. The Initial release was the 16.10.2023, first posted due to technical problems 16.04.2024. https://clinicaltrials.gov/study/NCT06368557?locStr=Odense,%20Denmark&country=Denmark&city=Odense&page=2&rank=13 .

Abstract Background Improving health equity and access to the highest possible standard of health care is a key issue of social accountability. Centretown Community Health Centre in Ottawa, Canada has iteratively developed a program to target and serve marginalized and complex populations since 1999. The program implementation was evaluated using a validated implementation framework. Methods Quantitative and qualitative data were collected through a health records extraction (n = 570), a client complexity assessment tool (n = 74), semi-structured interviews with clients and key stakeholders (n = 41), and a structured client satisfaction survey (n = 30). Data were analyzed using descriptive statistics and inductive thematic analysis. Results Five hundred and seventy unique clients were seen between November 1–30, 2021. A third of clients (34%) did not have a provincial health card for access to universal health care services, and most (68%) were homeless or a resident of rooming houses. Most clients who reported their income (92%) were at or below Canada’s official poverty line. The total mean complexity score for clients seen over a one-month period (n = 74) was 16.68 (SD 6.75) where a total score of at least 13 of 33 is perceived to be a threshold for client biopsychosocial complexity. Clients gained the majority of their total score from the Social support assessment component of the tool. Clients (n = 31) and key informants (n = 10) highlighted the importance of building relationships with this population, providing wrap-around care, and providing low-barrier care as major strength to the Urban Health program (UH). Key areas for improvement included the need to: i) increase staff diversity, ii) expand program hours and availability, and iii) improve access to harm reduction services. Clients appeared to be highly satisfied with the program, rating the program an average total score of 18.50 out of 20. Conclusions The program appears to serve marginalized and complex clients and seems well-received by the community. Our findings have relevance for other health care organizations seeking to better serve marginalized and medically and socially complex individuals and families in their communities.

This study examined the association between internalizing and externalizing mental health and prosociality across four developmental transitions. The effects of parent-child interactions on mental health and prosociality were also explored. The data from a community sample of 10,703 children on mental health, prosociality, child maltreatment, parent-child relationships, parental mental health, and socioeconomic status were derived from the Millennium Cohort Study to cover the developmental periods from early childhood to late adolescence (ages 5, 7, 11, 14, 17). Adjusting for covariates, latent trait-state-occasion and cross-lag modeling were deployed. The results indicated that internalizing and externalizing mental health symptoms, and prosociality were more trait-like throughout adolescence. Only within-person increase in externalizing symptoms predicted decrease in subsequent within-person prosociality from middle childhood to late adolescence. Parent-child conflict and maltreatment had deleterious effects on children's prosociality and mental health. Mental health professionals should screen for both possible mental health problems and deficits in prosociality. Interventions aiming to improve the quality of parent--child relationships could be beneficial for the development of child mental health and prosociality.

PURPOSE: The purpose of this study was to identify modifiable medical comorbidities, laboratory markers and flaws in perioperative management that increase the risk of acute dislocation in total hip arthroplasty (THA) patients. METHODS: All THA with primary indications of osteoarthritis from 2007 to 2020 were queried from the National Surgical Quality Improvement Program (NSQIP) database. Demographic data, preoperative laboratory values, recorded past medical history, operative details as well as outcome and complication information were collected. The study population was divided into two cohorts: non-dislocation and dislocation patients. Statistics were performed to compare the characteristics of both cohorts and to identify risk factors for prosthetic dislocation (α

Background: Rural general surgeons perform many procedures outside the conventional scope of the specialty. Unique to British Columbia, the Rural Practice Subsidiary Agreement (RSA) formally defines rurality in the province. Our goal is to understand the scope of practice for BC's rural general surgeons and whether it has been affected over time by changing privileging guidelines. Methods: Medical Services Plan (MSP) data were collected from 2011 to 2021 for procedures billed by general surgeons in communities defined by the RSA as rural. We categorized codes from the MSP based on surgical specialty. For each community, we calculated the totals for these categories considering what other surgical specialties were present as well as changes over time. Results: From 2011 to 2021, 222 905 procedures were performed in 23 rural communities in BC. Colonoscopies were the most frequently performed procedure (n = 80114, 35.9%), followed by colorectal (n = 23891, 10.7%) and hernia procedures (n = 20 911, 9.4%). The most common unconventional procedures were plastic surgeries (n = 8077, 3.6%). Classification within the RSA did not significantly influence the percentage of unconventional general surgery procedures performed (p = 0.4). When another surgical specialty was present, there was often a decrease in the number of that specialty's procedures performed by general surgeons. Over the past decade, rural general surgeons performed fewer unconventional general surgery procedures (p < 0.001). Conclusion: General surgeons working in rural communities perform a variety of procedures based on resources, community need, and access to other specialists. Over the last decade, this appears to have been influenced by new privileging guidelines. Understanding the scope of rural general surgery can inform training opportunities and, as there is a migration away from rural surgeons performing as many unconventional procedures, can elucidate the implications on patients and communities. Contexte : En r gion rurale, les chirurgiens g n ralistes effectuent beaucoup d'interventions sortant du cadre conventionnel de pratique de leur sp cialit . La Colombie-Britannique est actuellement la seule province avoir mis en place l'entente Rural Practice Subsidiary Agreement (RSA), qui d finit officiellement la ruralit dans la province. Notre objectif est de mieux d limiter le champ de pratique des chirurgiens g n ralistes exer ant en milieu rural en Colombie-Britannique et de d terminer s'il a t affect dans le temps par l' volution des directives concernant l'octroi de privil ges. M thodes : Des donn es du r gime d'assurance maladie de la province (Medical Services Plan, ou MSP) pour la p riode de 2011 2021 ont t recueillies pour les interventions factur es par des chirurgiens g n ralistes dans les communaut s d sign es rurales selon la RSA. Nous avons class les codes du MSP selon la sp cialit chirurgicale. Pour chaque collectivit , nous avons calcul les totaux pour ces cat gories, tout en tenant compte des autres sp cialit s chirurgicales pr sentes et des changements dans le temps. R sultats : De 2011 2021, 222 905 interventions ont t effectu es dans 23 collectivit s rurales en Colombie-Britannique. La colonoscopic tait l'intervention la plus courante (n = 80 114, 35,9%), suivie des chirurgies colorectales (n = 23 891, 10,7%) et des r parations de hernies (n = 20 911, 9,4%). Parmi les interventions non classiques, la chirurgie plastique occupait le premier rang (n = 8077, 3,6%). La classification selon la RSA n'a pas eu d'influence significative sur le pourcentage de chirurgies g n rales non classiques effectu es (p = 0,4). Lorsqu'un prestataire d'une autre sp cialit chirurgicale tait pr sent, on observait souvent une baisse du nombre d'interventions de cette sp cialit effectu es par les g n ralistes. Au cours de la derni re d cennie, les chirurgiens g n ralistes en milieu rural ont effectu moins d'interventions de chirurgie g n rale non classiques (p < 0,001). Conclusion : Dans les collectivit s rurales, les chirurgiens g n ralistes effectuent un ventail d'interventions qui varie selon les ressources, les besoins communautaires, et l'acc s d'autres sp cialistes. Durant la derni re d cennie, cette diversit semble avoir t influenc e par les nouvelles directives concernant l'octroi de privil ges. En connaissant le champ de pratique des chirurgiens g n ralistes en milieu rural, on peut guider les occasions de formation et, alors que les g n ralistes effectuent de moins en moins d'interventions non classiques, mieux comprendre ce que cela signifie pour la patient le et les collectivit s., For Canadians in rural, remote, and northern settings, access to specialty surgical care is more challenging than in urban communities. Although the Canada Health Act states that its primary objective [...]

Smallholders play a key role in specialty coffee production. Implementing industrial ecology coffee (IEC) practices is crucial for sustainable coffee production (SCP), aiming to add value, achieve zero waste, and respect the environment. For that purpose, this study used life cycle assessment (LCA) to assess the environmental impact of coffee production, specifically focusing on the global warming potential (GWP) of dry methods (DMs). Data were collected from pilot plant operations in Bondowoso, Indonesia, covering the process from cherry beans (CBs) to coffee powder (CP). A unique aspect of this study is assessing the impact of the DMs: Natural, Anaerobic, Hydro honey, Lactic, and Carbonic Maceration, which were often overlooked in previous research. Observations and experimental results served as primary data for input calculations in LCA. As a result, it was found that for the studied DMs, inputting 150 kg per batch of CBs produced approximately 22.4–22.8 kg of CP. The LCA revealed that for one kg of CP produced by the DMs, GWP ranged from 0.676 kg to 1.168 kg of CO2-eq, with Natural being the least polluting and Lactic having the highest environmental impact. This study also suggests potential improvements in by-products for novel food and fuel applications.

Abstract The full-length prefusion-stabilized SARS-CoV-2 spike (S) is the principal antigen of COVID-19 vaccines. Vaccine efficacy has been impacted by emerging variants of concern that accumulate most of the sequence modifications in the immunodominant S1 subunit. S2, in contrast, is the most evolutionarily conserved region of the spike and can elicit broadly neutralizing and protective antibodies. Yet, S2’s usage as an alternative vaccine strategy is hampered by its general instability. Here, we use a simulation-driven approach to design S2-only immunogens stabilized in a closed prefusion conformation. Molecular simulations provide a mechanistic characterization of the S2 trimer’s opening, informing the design of tryptophan substitutions that impart kinetic and thermodynamic stabilization. Structural characterization via cryo-EM shows the molecular basis of S2 stabilization in the closed prefusion conformation. Informed by molecular simulations and corroborated by experiments, we report an engineered S2 immunogen that exhibits increased protein expression, superior thermostability, and preserved immunogenicity against sarbecoviruses.

Abstract Background Past empirical evidence on the longitudinal relations between emotional mental health symptoms and parent-child close relationships has produced mixed and inconclusive results. Some studies suggest a unidirectional relation, whereas other studies point toward a bidirectional association. Additionally, most of the past research has been carried out with adolescent samples, rather than children. Hence, this study aimed to estimate the longitudinal relations between children’s trait emotional difficulties and trait parent-child closeness, accounting for the time-invariant and time-varying state components of each factor. Methods Participants were 7,507 children (ages 3 years, 5 years, 7 years, and 9 years) from the Growing Up in Ireland cohort. Α bivariate stable trait, autoregressive trait, and state (STARTS) model was estimated using Bayesian structural equation modelling. Results The STARTS model revealed that children’s emotional difficulties and parent-child closeness were relatively stable across time, and these overarching traits were strongly negatively correlated. Children’s earlier trait emotional difficulties predicted later trait parent-child closeness and vice versa between 3 years and 5 years, and between 5 years and 7 years, but these effects disappeared between 7 years and 9 years. At all pairs of time points, state emotional difficulties and state parent-child closeness were weakly negatively correlated. Conclusions Overall, the results suggest that early and middle childhood are critical stages for improving parent-child relationships and reducing children’s emotional difficulties. Developing close parent-child relationships in childhood appears to be a key factor in reducing children’s subsequent emotional difficulties. Children who face greater than usual emotional difficulties tend to be more withdrawn and less receptive to close parent-child relationships and this could serve as an important screening indicator.

Abstract Respirovirus 3 is a leading cause of severe acute respiratory infections in vulnerable human populations. Entry into host cells is facilitated by the attachment glycoprotein and the fusion glycoprotein (F). Because of its crucial role, F represents an attractive therapeutic target. Here, we identify 13 F-directed heavy-chain-only antibody fragments that neutralize recombinant respirovirus 3. High-resolution cryo-EM structures of antibody fragments bound to the prefusion conformation of F reveal three distinct, previously uncharacterized epitopes. All three antibody fragments bind quaternary epitopes on F, suggesting mechanisms for neutralization that may include stabilization of the prefusion conformation. Studies in cotton rats demonstrate the prophylactic efficacy of these antibody fragments in reducing viral load in the lungs and nasal passages. These data highlight the potential of heavy-chain-only antibody fragments as effective interventions against respirovirus 3 infection and identify neutralizing epitopes that can be targeted for therapeutic development.

Abstract Background Most people want to remain at home as they age. Ageing in place – remaining at home and connected to the community – is a national and international policy priority; however, to better understand how policy might be implemented, a more nuanced understanding is required about older adults’ lived experiences of ageing in place, especially the experiences of those aged 80 and above. Objective To describe and explore the social processes which enable ageing in place from the perspective of community-dwelling older people (80+). Methods Forty-six respondents (80–100+ years) participated in the first wave of a longitudinal qualitative study set in North East England. Semi-structured interviews were conducted in participants’ homes between June 2022 and January 2023. Interviews were analysed using reflexive thematic analysis. Results Participants positioned their homes as a place of freedom and as the antithesis of a ‘care home’. Remaining in place was important for all participants; a key priority for them was to remain physically active to enable this. However, many participants faced significant hurdles to remaining in place. These were primarily related to health and mobility issues. Some participants were able to overcome such barriers by drawing on financial resources and available social networks. Conclusion The home is central to understanding older peoples’ (80+) experiences of ageing. In a socio-political context which promotes ageing in place, the social factors shaping experiences of ageing in place must be considered. This involves attending to the challenges of later life, particularly health and especially mobility and physical function. Currently, those with resources (social and economic) are better equipped to respond to such challenges, thus potentially exacerbating widening inequalities in ageing. By foregrounding the perspectives of those ageing in place alongside social factors shaping their experiences, our study has important implications for policy and health and social care. We show that a more equitable allocation of resources is vital to fulfil the ageing in place policy agenda. Furthermore, we highlight a need to recognise commitments to ageing in place displayed by people aged 80 and above, especially when remaining in place becomes difficult to achieve.

Māori, as substantial stakeholders in the fishery sector, must play a major role in any imagined or proposed transition to a blue economy. This paper provides the results from a project examining how to indigenise the blue economy in Aotearoa New Zealand, outlining the underlying theory and providing results from five case studies. The paper explores three key thematic constraints identified in consultation with the Māori fishing sector, namely: centralisation of power; quota fragmentation; and product commodification. It concludes that there is a need to focus on: redressing the imbalance between iwi and hapū by providing quota for hapū while providing wrap around financial and capacity support, incorporating local experts in decision making, and creating community clusters; overcoming fragmentation through joint ventures and hybrid governance structures and a focus on quota optimisation; and increasing market differentiation through research, innovation, and branding and marketing initiatives.