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Youth mental health interventions in the UK increasingly use goal-setting procedures to shape services and measure outcomes in ways that are intended to be meaningful to service users. This research article questions this premise, departing with the ethnographic observation that many young people do not seem to welcome the invitation or requirement to direct their therapeutic aims and set the terms for service evaluation in the form of goals. I will show that goal-setting procedures are examples of a broader field of complex ethico-political dilemmas navigated by mental health service staff. While wanting to enable young people to be healthy agents, staff are simultaneously critically aware of the risk of imposing normative, unrealistic and unfair expectations onto young people. I propose that these staff are engaged in a specific form of ethico-political practice, which I call ‘nested ethics’. I use this term to describe instances where staff ethically evaluate their own conduct in line with the capacity to enable the ethical life of another person (youth, in this case). Viewing goal-setting processes as an example of an uneasy politics of nested ethics enables a new perspective from which to advance debates about the enablement of service user choice within care provisions.

Background: Over 40 years of research implicates perfectionism in eating disorders in childhood and adolescence. However, the nature of this relationship remains understudied. To address this gap, we performed a systematic review and a meta-analysis to quantify the magnitude of the associations between perfectionism (i.e., unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns) and eating-related symptoms during childhood and adolescence. Methods: The literature search was conducted using five electronic databases in accordance with PRISMA guidelines: MEDLINE, Embase, CINAHL Complete, APA PsycINFO, and EMB Reviews. A total of 904 studies were identified; a total of 126 were included in the systematic review, and 65 in the meta-analysis (N = 29,268). Sensitivity analyses were also carried out to detect potential differences in age and clinical status. Results: All the associations we investigated were both significant and positive. Small effect sizes were found between eating global scores and unidimensional perfectionism, perfectionistic strivings, and perfectionistic concerns (res = 0.19, res = 0.21, res = 0.12, respectively) and remained significant in each age group in both clinical and community samples. Perfectionistic concerns were moderately associated with all eating measures, especially in community samples and samples with a mean age under 14. Conclusions: Psychological interventions specially designed to target perfectionistic concerns in the early stages of development may help prevent the onset or reduce the intensity of eating-related symptoms during childhood and adolescence.

Background: Cardiorespiratory transfusion reactions drive most transfusion-related morbidity and mortality. Transfusion-associated circulatory overload and transfusion-related acute lung injury have established causes, important impacts, mitigation options, and revised definitions, while non-conforming CRTRs fall into a category known as transfusion-associated dyspnea. Though procedures to investigate high-risk febrile transfusion reactions are typically rooted in detecting incompatibility or bacterial contamination, a common standard for examining CRTRs is lacking. CRTRs are further challenged by charting limitations, confounding (or enhanced susceptibility) by comorbidities, and/or overlapping insults. Deeper profiling of CRTRs could improve categorizations, reveal best-value diagnostics, and decipher the nature of (and/or minimize) reactions coded as TAD. Methods: The primary objective of this multi-center study is to reduce uncertainty in final conclusions drawn on CRTRs (cases), defined by dyspnea with objective disturbances and/or significant hemodynamic insults, with/without fever (±F). HRFTRs (controls) represent higher-grade F (T≥39°C or chills/rigors or lower-grade F (≥38°C by +Δ1°C) with non-respiratory effects). Patients (goal: 200) consent to additional sampling (≤24h post-TR) to identify contributing factors in case/control presentations, and in diagnostic groups (TRALI, TACO±F, TAD). Mechanistic axes of interest are cardiorenal, hemolytic, leukoagglutinating, biolipid, vasoactive, and inflammatory. Secondary goals include elucidation of real-life “insult-multiplicity” in CRTRs, tests of greatest yield, and distinguishing features in TRALI/TACO/TAD. Conclusions: A deep systematic CRTR probe may not only reduce diagnostic uncertainty but frame biomarker performance and pathologic signatures in definition-specific CRTRs. The re-classifiability or biology of TAD may be better understood. High-quality, mechanistic, true-to-quantity hemovigilance better exposes burdens and management options. Trial Registration: The trial is registered with ClinicalTrials.gov. with registry number NCT04267029.

BackgroundGiven the recent detection of tetrodotoxin (TTX) in bivalve molluscs but the absence of a full collaborative validation study for TTX determination in a large number of shellfish samples, interlaboratory assessment of method performance was required to better understand current capabilities for accurate and reproducible TTX quantitation using chemical and immunoassay methods.ObjectiveThe aim was to conduct an interlaboratory study with multiple laboratories, using results to assess method performance and acceptability of different TTX testing methods.MethodsHomogenous and stable mussel and oyster materials were assessed by participants using a range of published and in-house detection methods to determine mean TTX concentrations. Data were used to calculate recoveries, repeatability, and reproducibility, together with participant acceptability z-scores.ResultsMethod performance characteristics were good, showing excellent sensitivity, recovery, and repeatability. Acceptable reproducibility was evidenced by HorRat values for all LC–MS/MS and ELISA methods being less than the 2.0 limit of acceptability. Method differences between the LC–MS/MS participants did not result in statistically different results. Method performance characteristics compared well with previously published single-laboratory validated methods and no statistical difference was found in results returned by ELISA in comparison with LC–MS/MS.ConclusionThe results from this study demonstrate that current LC–MS/MS methods and ELISA are on the whole capable of sensitive, accurate, and reproducible TTX quantitation in shellfish. Further work is recommended to expand the number of laboratories testing ELISA and to standardize an LC–MS/MS protocol to further improve interlaboratory precision.HighlightsMultiple mass spectrometric methods and a commercial ELISA have been successfully assessed through an interlaboratory study, demonstrating excellent performance.

This paper explores the formative role of substances of intoxication in the social and scientific establishment of the biological subject in late nineteenth-century Germany. Sourcing the emergence of substances of intoxication as “vital substances” from Brunonianism, this narrative traces their initial significance for Romantic physiology, followed by their rejection from neo-mechanical scientific physiology. Emphasis is placed on late nineteenth-century psychological research on the effects of intoxicants on the mind as the site of a dynamic encounter between theories of the mind and the body, particularly through Kraepelin’s concept of intoxication as model psychosis, and his related research. The biological subject, here, is anti-vitalistic, and, yet, conceptually distinct from neo-mechanism.

Routine chemical venous thromboembolism (VTE) prophylaxis for liver surgery remains controversial, and often delayed post-operatively due to perceived bleeding risk. This study asked whether patients undergoing hepatectomy for colorectal metastases (CRM) were at risk from VTE pre-operatively, and the impact of hepatectomy on that risk.Single-centre prospective observational cohort study of patients undergoing open hepatectomy for CRM, comparing pre-, peri- and post-operative haemostatic variables.Of 336 hepatectomies performed October 2017-December 2019, 60 resections in 57 patients were recruited. There were 28 (46.7%) major resections, with median (interquartile range [IQR]) blood loss 150.0 (76.3-263.7) mls, no blood transfusions, post-operative VTE events or deaths. Patients were prothrombotic pre-operatively (high median factor VIIIC and increased thrombin generation velocity index), an effect exacerbated post-hepatectomy. Major hepatectomies had a significantly greater median drop in Protein C, rise in Factor VIIIC and von Willebrand Factor, versus minor resections (p = 0.001, 0.005, 0.001 respectively). Patients with parenchymal transection times greater than median (40 min), had significantly increased median (IQR) PMBC-TFmRNA expression [1.65(0.93-2.70)2ddCt], versus quicker transections [0.99(0.69-1.28)2ddCt, p = 0.020].Patients with CRM are prothrombotic pre-operatively, an effect exacerbated by hepatectomy, particularly longer, complex resections, suggesting chemical thromboprophylaxis be considered early in the patient pathway.

In many emergency medical services (EMS) systems, a direct medical oversight physician is available to paramedics for mandatory and/or elective consultations. At the time of this study, a clinical support desk (CSD) was being implemented within the medical communications center of a provincial EMS system in addition to the physician resource. The CSD was initially staffed with a registered nurse or an advanced care paramedic. The objective of the current study was to compare CSD "peer to peer" consults versus physician consults with regards to consultation patterns, transport dispositions, and patient safety measures.This retrospective cohort study analyzed 2 months before (September 1 to October 31, 2012) and 2 months after (September 1 to October 31, 2013) implementation of the CSD. In the before period, all clinical consults were fielded by the direct medical oversight physician. In the after period, consults were fielded by the physician, CSD or both. EMS databases were queried, and manual chart review and abstraction of audio recordings were done. Relapses back to EMS within 48 hours of non-transport were measured.1621 consults were included, with 764 consults in the before period and 857 after (p = 0.02). The number of physician consults decreased from 764 before to 464 after (39.2%, p 0.001), with the CSD taking 325 (37.9%) consults. The CSD was consulted more for police custody and trip destination. The physician was consulted more for cease resuscitation and clinical consults prior to medication administration. Overall non-transport rates were 595/764 before (77.9%), and 646/857 after (75.4%) (p = 0.2). Non-transports were 233/325 (71.7%) via the CSD, 364/464 (78.4%) via the physician, and 49/68 (72.1%) when both were involved (p = 0.07). Rate of relapse to EMS was similar before (25/524, 4.8%) and after (26/568, 4.6%) (p = 0.76), and between CSD (12/216, 5.5%) and physician consults (13/325, 4.0%) in the after period (p = 0.41).The introduction of a novel "peer-to-peer" consult program was associated with an increased total number of consults made and reduced call volume for direct medical oversight physicians. There was no change in the patient safety measure studied.

Background: Genome-wide association studies have discovered a link between genetic variants on human chromosome 15q26.1 and increased coronary artery disease (CAD) susceptibility; however, the underlying pathobiological mechanism is unclear. This genetic locus contains the FES (FES proto-oncogene, tyrosine kinase) gene encoding a cytoplasmic protein-tyrosine kinase involved in the regulation of cell behavior. We investigated the effect of the 15q26.1 variants on FES expression and whether FES plays a role in atherosclerosis. Methods and Results: Analyses of isogenic monocytic cell lines generated by CRISPR (clustered regularly interspaced short palindromic repeats)-mediated genome editing showed that monocytes with an engineered 15q26.1 CAD risk genotype had reduced FES expression. Small-interfering-RNA-mediated knockdown of FES promoted migration of monocytes and vascular smooth muscle cells. A phosphoproteomics analysis showed that FES knockdown altered phosphorylation of a number of proteins known to regulate cell migration. Single-cell RNA-sequencing revealed that in human atherosclerotic plaques, cells that expressed FES were predominately monocytes/macrophages, although several other cell types including smooth muscle cells also expressed FES . There was an association between the 15q26.1 CAD risk genotype and greater numbers of monocytes/macrophage in human atherosclerotic plaques. An animal model study demonstrated that Fes knockout increased atherosclerotic plaque size and within-plaque content of monocytes/macrophages and smooth muscle cells, in apolipoprotein E-deficient mice fed a high fat diet. Conclusions: We provide substantial evidence that the CAD risk variants at the 15q26.1 locus reduce FES expression in monocytes and that FES depletion results in larger atherosclerotic plaques with more monocytes/macrophages and smooth muscle cells. This study is the first demonstration that FES plays a protective role against atherosclerosis and suggests that enhancing FES activity could be a potentially novel therapeutic approach for CAD intervention.

After an extended alcohol-drinking history, alcohol use can transition from controlled to compulsive, causing deleterious consequences. Alcohol use can be segregated into two distinct behaviors, alcohol seeking and alcohol taking. Expression of habitual and compulsive alcohol seeking depends on the dorsolateral striatum (DLS), a brain region thought to engage after extended alcohol access. However, it is unknown whether the DLS is also involved in compulsive-like alcohol taking. The purpose of this experiment was to identify whether the DLS gates compulsive-like binge alcohol drinking. To ask this question, we gave adult male and female C57BL/6J mice a binge-like alcohol-drinking history, which we have previously demonstrated to produce compulsive-like alcohol drinking (Bauer, McVey, & Boehm, 2021), or a water-drinking history. We then tested the involvement of the DLS on gating binge-like alcohol drinking and compulsive-like quinine-adulterated alcohol drinking via intra-DLS AMPA receptor antagonism. We hypothesized that pharmacological lesioning of the DLS would reduce compulsive-like quinine-adulterated alcohol (QuA) drinking, but not non-adulterated alcohol drinking, in male and female C57BL/6J mice. Three important findings were made. First, compulsive-like alcohol drinking is significantly blunted in cannulated mice. Because of this, we conclude that we were not able to adequately assess the effect of intra-DLS lesioning on compulsive-like alcohol drinking. Second, we found that the DLS gates binge-like alcohol drinking initially, which replicates findings in our previous work (Bauer, McVey, Germano, Zhang, & Boehm, 2022). However, following an extended alcohol history, the DLS no longer drives this behavior. Finally, alcohol and QuA front-loading is DLS-dependent in alcohol-history mice. Intra-DLS NBQX altered these drinking behaviors without altering ambulatory locomotor activity. These data demonstrate the necessity of the DLS in binge-like alcohol drinking before, but not following, an extended binge-like alcohol-drinking history and in alcohol front-loading in alcohol-history mice.

This article presents a critical review of the current literature to provide a brief update on the contemporary advances in diagnosing and managing N1 penile cancer.Penile squamous cell carcinoma (pSCC) has evolved from being an orphan field for cancer innovation. Advances in the understanding tumour biology have enabled sophisticated diagnostics and predictive modelling to better characterize inguinal disease. Minimally invasive inguinal lymph node dissection is emerging as a technique that reduces morbidity while maintaining oncological safety. Furthermore, robust clinical trials are underway ,which will provide level one evidence to guide treatment decisions. Exciting advances in the field of immune-oncology offer promise as adjuvant therapies. International collaboration and centralisation of care will be essential to driving translational research and equitable evidence-based care.Improving outcomes for men with pSCC remains a global challenge. Radical inguinal lymph node dissection remains the gold standard for diagnosing and curing N1 disease. Although many promising developments are on the horizon, high-level evidence is required to guide therapy.

AFTER 2 years of virtual meetings, the 58th European Association for the Study of Diabetes (EASD) Annual Meeting took a hybrid form, with 7,716 participants onsite in Stockholm, Sweden, as well as 3,291 participants online. The programme of the congress was developed to cover the most recent developments and breaking news relating to diabetes research, covering the latest innovations and developments in the treatment of Type 1 and Type 2 diabetes (T2D), as well as their complications. Through symposia, debates, prize lectures, oral discussion sessions, and a dedicated e-learning track, a range of topics were discussed.

Family-Based Treatment (FBT)-the most widely supported treatment for pediatric eating disorders-transitioned to virtual delivery in many programs due to COVID-19. Using a blended implementation approach, we systematically examined therapist adherence to key components of FBT and fidelity to FBT by videoconferencing (FBT-V), preliminary patient outcomes, and team experiences with our FBT-V implementation approach as well as familial perceptions of FBT-V effectiveness. We examined our implementation approach across four pediatric eating disorder programs in Ontario, Canada, using mixed methods. Participants included therapists (n = 8), medical practitioners (n = 4), administrators (n = 6), and families (n = 5; 21 family members in total). We developed implementation teams at each site, provided FBT-V training, and offered clinical and implementation consultation. Therapists submitted video recordings of their first four FBT-V sessions for fidelity rating, and patient outcomes. Therapists self-reported readiness, attitudes, confidence, and adherence to FBT-V. Focus groups were conducted with each team and family after the first four sessions of FBT-V. Quantitative data were analyzed using repeated measures ANOVA. Qualitative data were analyzed using directed and summative content analysis. Therapists adhered to key FBT components and maintained FBT-V fidelity. Changes in therapists' readiness, attitudes, and confidence in FBT-V over time were not significant. All patients gained weight. Focus groups revealed implementation facilitators/barriers, positives/negatives surrounding FBT-V training and consultation, suggestions for improvement, and effectiveness attributed to FBT-V. Our implementation approach appeared to be feasible and acceptable. Future research with a larger sample is required, furthering our understanding of this approach and exploring how organizational factors influence treatment fidelity.We qualitatively and quantitatively examined the initial implementation (the first four sessions) of Family-Based Treatment (FBT) delivered by videoconferencing (FBT-V) during the COVID-19 pandemic using an evidence-based implementation approach. This included developing implementation teams (consisting of a lead therapist, medical practitioner, and program administrator) at each site, providing FBT-V training to all participants, and offering clinical consultation to all participating therapists and implementation consultation to implementation teams. Therapists were required to submit video recordings of their first four FBT-V sessions. Therapist adherence to key components of FBT as well as fidelity to the FBT-V model, team and family experiences with FBT-V, and preliminary patient outcomes (e.g., weight gain) were examined. Our findings suggest that our implementation approach was feasible and acceptable; therapists adhered to key FBT components and maintained FBT-V fidelity, patients gained weight, and teams and families expressed satisfaction with our intervention. Further research is needed with a larger sample and for a longer duration.

In 1878, Sigmund Freud produced his first scientific publication while a medical student in Vienna, a physiological and histological analysis of Szymon Syrski's claim to have discovered the long-sought testes of the European eel. Though he would eventually come to be known as the father of psychoanalysis, a closer look at Freud's earliest scientific publication demonstrates that he was initially positioned on the cutting edge of neo-mechanistic physiology, and academic Darwinism. Not only was the young Freud a methodologically capable physiologist, he was conceptually grounded by the anti-Lamarckian and anti-Haeckelian Darwinism of his first mentor, Carl Claus. Scholarship on Freud's life and ideas is copious and far-reaching, and yet the stature of his psychoanalytic legacy remains a significant barrier for reappraisals of his early foundations. By analyzing his first publication and the context in which it came to be, this article seeks to revisit the place of Darwin in Freud's earliest scientific work. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Background Abdominal wall hernia (AWH) affects mental health and mental health questions are frequently included within Patient-Reported Outcome Measures (PROMS) for this patient population. However, these questions have not been informed by the subjective lived experiences of mental health in AWH patients. This study is the first to qualitatively examine how AWH affects patients’ mental health. Methods Fifteen patients were interviewed from a purposive sample of AWH patients until no new themes emerged. Interviews explored patient thoughts and experiences of AWH and mental health. Data were examined using Interpretative Phenomenological Analysis (IPA). Results Three key themes pertaining to mental health were identified: “psychological and emotional distress”, “identity disruption” and “coping mechanisms and support systems”. Conclusion Our findings illustrate that AWH is a pathology that can have a significant detrimental impact on people’s mental health. This impact has implications for patient care and can be treated and managed through better psychological support. This support may positively affect AWH patient’s experience and outcomes in terms of quality of life. This paper provides recommendations for improved AWH patient care in regard to mental health.

Funding: This research was part of a larger PhD studentship grant, which was funded by the Scottish Graduate School of Social Science (SGSSS) and the Institute of Chartered Accountants Scotland (ICAS). The UN Guiding Principles on Business and Human (UNGPs) explicitly ask corporations to rely on “external expertise” for policy guidance, human rights due diligence (HRDD), and remedy. The broad conceptualization of expertise in the UNGPs signifies an amorphous, neutral, and largely unregulated community of consultants, human rights institutions, NGOs, impact assessors, and auditors (among other actors). I argue that external experts exert significant governance authority in the business and human rights space. Through empirical analysis of experts orbiting two multinational corporations, I identify experts as knowledge providers, diplomats, critics, and legitimizers in the corporate implementation of the UNGPs. In doing so, this work adds nuanced political dimensions to expert authority in business and human rights, offering evidence of its manifestations and limitations. Finally, I advance some considerations and suggestions for future research, particularly vital in the context of incoming mandatory HRDD legislation. Publisher PDF

The national nursing shortage is affecting hospital leaders in their ability to employ nursing staff. Nursing staffing shortages contribute to extended nurse-to-patient ratios and increased workload for staff. Increased workload contributes to missed nursing care and correlates with increased patient length of stay, readmission rates, patient safety errors, and hospital-acquired infections. Telehealth services have shown initial improvements in care quality outcomes but have not addressed nursing workload or nursing shortages. Telenursing has potential to provide additional nursing support to offset the workloads of bedside nursing staff and break the associated cycle of adverse outcomes. Various definitions of telenursing are present in the literature, but a concept analysis of telenursing has not been published. Understanding the concept of telenursing is necessary to integrate this concept within the context of researching nursing shortages and patient and nurse outcomes in acute care hospitals. The author used Walker and Avant's eight-step procedure to define the concept of telenursing and present a model case, a related case, and a contrary case to describe the telenursing concept. This concept analysis helps to provide clarity around the concept of telenursing and directions for future research. Understanding the concept of telenursing is necessary to integrate this concept within the context of researching nursing shortages, nursing satisfaction, and patient and nurse outcomes in various healthcare settings.

Early detection and management of prostate cancer has evolved over the past decade, with a focus now on harm minimisation and reducing overdiagnosis and overtreatment, given the proven improvements in survival from randomised controlled trials. Multiparametric magnetic resonance imaging (mpMRI) is now an important aspect of the diagnostic pathway in prostate cancer, improving the detection of clinically significant prostate cancer, enabling accurate localisation of appropriate sites to biopsy, and reducing unnecessary biopsies in most patients with normal magnetic resonance imaging scans. Biopsies are now performed transperineally, substantially reducing the risk of post-procedure sepsis. Australian-led research has shown that prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) has superior accuracy in the staging of prostate cancer than conventional imaging (CT and whole-body bone scan). Localised prostate cancer that is low risk (International Society for Urological Pathology [ISUP] grade 1, Gleason score 3 + 3 = 6; and ISUP grade group 2, Gleason score 3 + 4 = 7 with less than 10% pattern 4) can be offered active surveillance, reducing harms from overtreatment. Prostatectomy and definitive radiation remain the gold standard for localised intermediate and high risk disease. However, focal therapy is an emerging experimental treatment modality in Australia in carefully selected patients. The management of advanced prostate cancer treatment has evolved to now include several novel agents both in the metastatic hormone-sensitive and castration-resistant disease settings. Multimodal therapy with androgen deprivation therapy, additional systemic therapy and radiotherapy are often recommended. PSMA-based radioligand therapy has emerged as a treatment option for metastatic castration-resistant prostate cancer and is currently being evaluated in earlier disease states.

Genome-wide association studies have revealed an association between the genetic variant rs17514846 in the FURIN gene and coronary artery disease. We investigated the mechanism through which rs17514846 modulates FURIN expression. An analysis of isogenic monocytic cell lines showed that the cells of the rs17514846 A/A genotype expressed higher levels of FURIN than cells of the C/C genotype. Pyrosequencing showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2′-deoxycytidine increased FURIN expression. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected DNA-protein complex bands that were altered by an anti-MeCP2 antibody. A chromatin immunoprecipitation assay with the anti-MeCP2 antibody showed an enrichment of the DNA sequence containing the rs17514846 site. siRNA-mediated knockdown of MeCP2 caused an increase in FURIN expression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor. The results of our study suggest that DNA methylation inhibits FURIN expression and that the coronary artery disease-predisposing variant rs17514846 modulates FURIN expression and monocyte migration via an allele-specific effect on DNA methylation.

Peer reviewed: True, Funder: Sinneave Family Foundation; FundRef: https://doi.org/10.13039/100012204, Funder: alberta innovates - health solutions; FundRef: https://doi.org/10.13039/501100000145, Funder: Kids Brain Health Network; FundRef: https://doi.org/10.13039/501100015741, Funder: Government of British Columbia, Funder: Autism Speaks; FundRef: https://doi.org/10.13039/100000073, Sibling relationship quality is important for the well-being of children on the autism spectrum and their siblings. Little is known, however, about how varied behavior and abilities of children on the autism spectrum may be associated with parent perceptions of domains of sibling relationship quality. We drew data from a subsample of 119 children on the autism spectrum (ages 10-11 years), participating in an ongoing longitudinal study. We looked at how three clinical characteristics (autism symptoms, behavioral difficulties, and communication ability) related to four areas of parent-reported sibling relationship quality (warmth/closeness, conflict, relative status/power, and rivalry). We also examined whether the strength of the association between behavioral difficulties and parent-reported sibling relationship quality was influenced by communication ability. We found that more severe autism symptoms were associated with less conflict and rivalry, and higher communication ability was associated with more relative status/power. We also found that children on the autism spectrum with more behavioral difficulties and weaker communication ability had less warmth/closeness in their sibling relationships. Our findings highlight that it is important to consider autism symptoms, behavioral difficulties, and communication ability, as well as multiple domains of relationship quality, to better understand how parents view the relationships between autistic children and their siblings. Clinically, methods for improving sibling relationships may include teaching conflict resolution strategies to children on the autism spectrum with stronger communication abilities and their siblings, and fostering sibling connection for those with lower communication abilities.

FOLLOWING the success of the hybrid format at the 2021 European Academy of Allergy and Clinical Immunology (EAACI) congress, it was decided that this year’s annual meeting would be held online, as well as in the remarkable city of Prague, Czechia. With 8,000 participants from 120 countries participating in EAACI 2021, Marek Jutel, EAACI President, and Petr Panzner, EAACI Hybrid Congress Chair 2022 both emphasised the benefits of this flexible format, expanding interaction with experts across the globe and improving the outreach of the impressive scientific programme that was on offer at this year’s event. EAACI have focused on the development of their Digital Congress Platform, providing a seamless transition between the physical and virtual elements of the meeting.

Introduction The Enhanced Assess, Acknowledge, Act (EAAA) Sexual Assault (SA) Resistance Program is a theoretically sound, evidence-based program providing SA resistance education within a positive sexuality framework. It was shown to substantially reduce sexual assault victimization among university women who participate (Senn et al. in New England Journal of Medicine 372(24), 2326-2335, 2015). Staff training can either enhance or impede successful program scale-up and implementation. In this paper, we evaluate the transfer of training to implementation sites (i.e., postsecondary institutions) using a train-the-trainer model. Methods Using pre- and post-training surveys and post-training interviews conducted from 2016 to 2020 with 33 implementation staff members from multiple sites, we answered the following research questions: 1. Did the training meet its overall goal of preparing implementation staff? 2. What training components were perceived to contribute to training effectiveness and implementation staff preparedness? Results Results suggested that our model of training was effective. Competence, confidence, and knowledge and ability increased significantly after training, and most staff perceived the training to be highly useful and effective (especially for preparing them to address EAAA participant issues). Practice and feedback from trainers through active learning techniques were especially important. Although implementation staff reported being well prepared to deliver the training or program, they reported being less prepared for handling other implementation-related activities and issues (that the training was not necessarily designed to address in-depth). Conclusions Our findings suggest a need to enhance existing training on self-care and supporting program facilitators and for ongoing support and reminders from program purveyors to ensure that implementers are making use of existing resources. This study fills important gaps in the literature as few studies have examined the transfer of training for SA prevention programming.

Alternative end joining (alt-EJ) mechanisms, such as polymerase theta-mediated end joining, are increasingly recognized as important contributors to inaccurate double-strand break repair. We previously proposed an alt-EJ model whereby short DNA repeats near a double-strand break anneal to form secondary structures that prime limited DNA synthesis. The nascent DNA then pairs with microhomologous sequences on the other break end. This synthesis-dependent microhomology-mediated end joining (SD-MMEJ) explains many of the alt-EJ repair products recovered following I-SceI nuclease cutting in Drosophila. However, sequence-specific factors that influence SD-MMEJ repair remain to be fully characterized. Here, we expand the utility of the SD-MMEJ model through computational analysis of repair products at Cas9-induced double-strand breaks for 1100 different sequence contexts. We find evidence at single nucleotide resolution for sequence characteristics that drive successful SD-MMEJ repair. These include optimal primer repeat length, distance of repeats from the break, flexibility of DNA sequence between primer repeats, and positioning of microhomology templates relative to preferred primer repeats. In addition, we show that DNA polymerase theta is necessary for most SD-MMEJ repair at Cas9 breaks. The analysis described here includes a computational pipeline that can be utilized to characterize preferred mechanisms of alt-EJ repair in any sequence context.

Introduction: Maintaining functional abilities is critical for optimizing older adults’ well-being and independence. This randomized controlled trial (RCT) pilot examined the feasibility of testing the effects of three commercially available interventions on function-related outcomes in older adults. Methods: Pairs of community-dwelling older adults (N=55, Mage=71.4) were randomized to a 10-week intervention (cognitive-COG, physical-EX, combined exergame-EXCOG, or control-CON). Cognitive, physical, and everyday function were assessed at baseline, immediately post-intervention, and 6-months post-intervention. Feasibility was evaluated using recruitment, enrollment, training adherence, and retention metrics. Variability and patterns of change in functional outcomes were examined descriptively. Results: A total of 208 individuals were screened, with 26% subsequently randomized. Across training arms, 95% of training sessions were completed and 89% of participants were retained at immediate post-test. Variability in functional outcomes and patterns of change differed across study arms. Discussion: Results support a fully powered RCT, with several modifications to the pilot study design, to investigate short- and long-term training impacts.

Crimean–Congo hemorrhagic fever virus (CCHFV) is a widely distributed tickborne zoonotic agent that infects a variety of host species. There is a lack of information on the true geographic distribution of the prevalence and risk of CCHFV in West Africa. A countrywide cross-sectional study involving 1413 extensively managed indigenous small ruminants and cattle at livestock sales markets and in village herds, respectively, was carried out in The Gambia. In sheep, an overall anti-CCHFV antibody prevalence of 18.9% (95% CI: 15.5–22.8%), goats 9.0% (95% CI: 6.7–11.7%), and cattle 59.9% (95% CI: 54.9–64.7%) was detected. Significant variation (p < 0.05) in the prevalence of anti-CCHFV antibodies at sites in the five administrative regions (sheep: 4.8–25.9%; goats: 1.8–17.1%) and three agroecological zones (sheep: 8.9–32.9%; goats: 4.1–18.0%) was also observed. Comparatively, higher anti-CCHFV antibody prevalence was detected in cattle (33.3–84.0%) compared to small ruminants (1.8–8.1%). This study represents the first countrywide investigation of the seroprevalence of CCHFV in The Gambia, and the results suggest potential circulation and endemicity of the virus in the country. These data provide critical information vital to the development of informed policies for the surveillance, diagnosis, and control of CCFHV infection in The Gambia and the region.

BackgroundGenome-wide association studies have revealed an association between the genetic variant rs17514846 on chromosome 15q26.1 and coronary artery disease susceptibility. Studies have shown that rs17514846 influences the expression of the FES Upstream Region (FURIN) gene located at this locus in monocytes. We investigated the mechanism through which rs17514846 modulatesFURINexpression.Methods and ResultsAn analysis of isogenic monocytic cell lines with either the rs17514846 C/C or A/A genotype showed that the cells of the A/A genotype expressed higher levels ofFURINthan cells of the C/C genotype. A pyrosequencing methylation analysis showed that the cytosine (in a CpG motif) at the rs17514846 position on the C allele was methylated. Treatment with the DNA methylation inhibitor 5-aza-2’-deoxycytidine increasedFURINexpression. A bioinformatic analysis indicated that the rs17514846 site might interact with the transcription factor MeCP2 that often functions as a gene repressor by binding to methylated CpG sites. An electrophoretic mobility super-shift assay with a probe corresponding to the DNA sequence at and around the rs17514846 position of the C allele detected two DNA-protein complex bands, which were altered by the addition of an anti-MeCP2 antibody in the assay, whilst these DNA-protein complexes were barely detectable with a probe for the A allele. A chromatin immunoprecipitation assay showed an enrichment of the DNA sequence containing the rs17514846 site in chromatin precipitates pulled down by an anti-MeCP2 antibody. siRNA-mediated knockdown of MeCP2 caused an increase inFURINexpression. Furthermore, MeCP2 knockdown increased monocyte migration and proliferation, and this effect was diminished by a FURIN inhibitor.ConclusionsThe results of our study suggest that DNA methylation inhibitsFURINexpression and that the coronary artery disease predisposing variant rs17514846 modulatesFURINexpression and monocyte migration via an allele-specific effect on DNA methylation.

Background: Multifactorial falls risk assessments (MFRAs) and personalised interventions are recommended practices to reduce risk of falls in hospitals, but there is variation in implementation at practice level, reasons for which have not been explored. The aim of this study was to explore reasons for the variation. Methods: Realist evaluation was used to interrogate how, why and in what contexts falls prevention practices are implemented. Four realist hypotheses about delivery of MFRAs and personalised interventions labelled: Falls Leadership, Facilitation via MFRA tools, Shared responsibility, and Patient participation were tested. Testing was conducted via a multi-site case study in three acute hospitals in older person and orthopaedic wards. Data collection included ethnographic observations (251.25 hours); interviews with staff (n=50), patients and carers aged over 65 (n=31); and clinical record review (n=60). Results: MFRA tools were embedded in nursing practice, located in the Electronic Health Record. Nurses reported that these tools prompted assessment of individual falls risk factors and clinical records indicated that MFRAs and prevention plans were documented with consistency. However, assessment items varied between MFRA tools and competing priorities on nurse time could reduce tool use to a tick-box exercise. Patient supervision, delivered with different levels of intensity by nursing staff, was a key falls prevention intervention. Supervision appeared to constrain the extent to which responsibility for preventing falls was felt to be shared within multidisciplinary teams. Staff interactional skills such as conveying sincerity encouraged patient participation in interventions and understanding patient perspectives enabled personalisation of care in ways that supported their engagement in safety efforts; non-nursing staff and carers helped surface patient perspectives. Conclusions: Organisational policy reflects the MFRA approach. However, to promote reliable delivery of multidisciplinary, personalised interventions, and to help ease the nursing burden, organisations should consider how systems can support clinical teams to work together cohesively to modify individual falls risk factors, and drawing on non-nursing staff and carers to help personalise care in ways that encourage patient participation and engagement in safety efforts.

Vagus nerve signaling is a key component of the gut-brain axis and regulates diverse physiological processes that decline with age. Gut to brain vagus firing patterns are regulated by myenteric intrinsic primary afferent neuron (IPAN) to vagus neurotransmission. It remains unclear how IPANs or the afferent vagus age functionally. Here we identified a distinct ageing code in gut to brain neurotransmission defined by consistent differences in firing rates, burst durations, interburst and intraburst firing intervals of IPANs and the vagus, when comparing young and aged neurons. The aminosterol, squalamine, reverted aged neurons to a young phenotype indicating the age associated changes in neural firing patterns are reversable. In contrast to young neurons sertraline failed to increase firing rates in the aged vagus whereas squalamine was still effective. These results may have implications for improved treatments involving pharmacological and electrical stimulation of the vagus for age-related mood and other disorders.