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Although multiple myeloma (MM) survival has improved following the introduction of proteosome inhibitors, immunomodulatory drugs, and anti-CD38 therapies, patients become refractory to these agents. Real-world outcomes of triple-class exposed patients are limited and were investigated in this study. The Integra Connect Database was used to assess the treatment patterns of triple-class exposed patients with relapsed/refractory MM (RRMM) (January 2016–December 2019). During this period, patients (N = 501) reached triple exposure in a median of three lines of therapy (LOTs) over 995 days. A new LOT was started in a median of 18 (1–691) days after triple exposure; 71% of the patients started a new LOT within 30 days. Throughout the follow-up period, 8% of the patients had a therapy gap greater than 90 days. Following triple exposure, 103/501 patients (21%) received only triple-class agents in subsequent LOTs, while 24 (4.8%) patients received only non–triple-class agents. The median apparent survival from initiation of first therapy after triple exposure was 308 days. These results indicate that recycling of triple-class agents after previous exposure is widespread and prognosis in the RRMM population remains poor, highlighting the continuing unmet need for new agents with novel mechanisms to improve patient outcomes.

Weyl semimetal (WSM), a novel state of quantum matter, hosts Weyl fermions as emergent quasiparticles resulting from the breaking of either inversion or time-reversal symmetry. Magnetic WSMs that arise from broken time-reversal symmetry provide an exceptional platform to understand the interplay between magnetic order and Weyl physics, but few WSMs have been realized. Here, we identify CeAlSi as a new non-centrosymmetric magnetic WSM via angle-resolved photoemission spectroscopy (ARPES) and first-principles, density-functional theory based calculations. Our surface-sensitive vacuum ultraviolet ARPES data confirms the presence of surface Fermi arcs as, the smoking gun evidence for the existence of the Weyl semimetallic state in CeAlSi. We also observe bulk Weyl cones in CeAlSi using bulk-sensitive soft-X-ray ARPES measurements. In addition, Ce 4f at bands are found near the Fermi level, indicating that CeAlSi is a unique platform for investigating exotic quantum phenomena resulting from the interaction of topology, magnetism and electronic correlations., Comment: 12 pages, 4 figures; supplementary information included

This paper examines the role of social capital on livelihood outcomes of households forcibly displaced by the Boko Haram insurgency in Northeast Nigeria. Drawing from in-depth interviews of 21 respondents and a cross-sectional survey of 810 household heads across 12 locations in Northeast Nigeria, the study finds that social capital provides a channel of critical psycho-social support for households. Further, the results of the structural-equation modelling indicate that bridging-linking social capital has a strong positive impact on livelihood outcomes, while the impact of bonding social capital on livelihood outcomes is partially mediated by resilience. The study contributes to recent conversations on the imperative of a triple-nexus strategy by highlighting the unique roles that social capital can play in complementary humanitarian, developmental and peace-building programming, especially in protracted crises and contexts of forced displacement where short-term material and financial interventions may not be adequate. The paper also offers practical and policy recommendations and suggestions for future research on operationalisation of social capital in protracted crises.

GSK2838232 (GSK232) is a novel maturation inhibitor that blocks the proteolytic cleavage of HIV-1 Gag at the junction of capsid and spacer peptide 1 (CA/SP1), rendering newly-formed virions non-infectious. To our knowledge, GSK232 has not been tested against HIV-2, and there are limited data regarding the susceptibility of HIV-2 to other HIV-1 maturation inhibitors. To assess the potential utility of GSK232 as an option for HIV-2 treatment, we determined the activity of the compound against a panel of HIV-1, HIV-2, and SIV isolates in culture. GSK232 was highly active against HIV-1 isolates from group M subtypes A, B, C, D, F, and group O, with IC50 values ranging from 0.25–0.92 nM in spreading (multi-cycle) assays and 1.5–2.8 nM in a single cycle of infection. In contrast, HIV-2 isolates from groups A, B, and CRF01_AB, and SIV isolates SIVmac239, SIVmac251, and SIVagm.sab-2, were highly resistant to GSK232. To determine the role of CA/SP1 in the observed phenotypes, we constructed a mutant of HIV-2ROD9 in which the sequence of CA/SP1 was modified to match the corresponding sequence found in HIV-1. The resulting variant was fully susceptible to GSK232 in the single-cycle assay (IC50 = 1.8 nM). Collectively, our data indicate that the HIV-2 and SIV isolates tested in our study are intrinsically resistant to GSK232, and that the determinants of resistance map to CA/SP1. The molecular mechanism(s) responsible for the differential susceptibility of HIV-1 and HIV-2/SIV to GSK232 require further investigation.

Implementation of the seventh amendment to the EU Cosmetics Directive has driven much research into suitable in vitro alternative assays to support satisfactory risk assessments. One such assay is the reconstructed skin micronucleus (RSMN) assay. First reported in 2006, further development occurred and a standard protocol was published in 2011. To evaluate and optimise the assay at Covance Laboratories, we tested nine chemicals [4-nitrophenol (4-NP), cyclohexanone (CH), 2-ethyl-1,3-hexanediol (2-EHD), methyl methansulfonate (MMS), mitomycin C (MMC), ethyl nitrosourea (ENU), benzo[a]pyrene (BaP), cyclophosphamide (CPA) and vinblastine (VIN)] using the EpiDerm™ 3D skin model (MatTek Corporation®, IVLSL, Bratislava, Slovakia) and compared the data using the standard 48-h treatment regimen and also an emerging 72-h treatment protocol. The EpiDerm™ tissue has reportedly some metabolic capacity but data using 48-h treatments has provided mixed results. Our investigations demonstrate that the two chemicals requiring metabolic activation (BaP and CPA) were negative following the 48-h protocol but were clearly positive following 72-h treatment. Furthermore, Replication Index (RI) data showed higher RI values in vehicle control treatments (indicating increased cell division) across the treatment set following 72-h treatments. A general greater magnitude of micronucleus (MN) induction was also observed following test chemical treatment. These data suggest that the 72-h treatment protocol is more suitable as a standard approach for the detection of clastogenic, aneugenic and metabolically activated chemicals in the RSMN assay. For further assay optimisation, we compare the statistical power of scoring cells from duplicate or triplicate cultures per treatment concentration and provide recommendations.

Introduction Shiga toxin-producing Escherichia coli (STEC) is a zoonotic, foodborne gastrointestinal pathogen that has the potential to cause severe clinical outcomes, including haemolytic uraemic syndrome (HUS). STEC-HUS is the leading cause of renal failure in children and can be fatal. Over the last decade, STEC clonal complex 165 (CC165) has emerged as a cause of STEC-HUS. Gap statement There is a need to understand the pathogenicity and prevalence of this emerging STEC clonal complex in the UK, to facilitate early diagnosis, improve clinical management, and prevent and control outbreaks. Aim The aim of this study was to characterize CC165 through identification of virulence factors (VFs) and antimicrobial resistance (AMR) determinants in the genome and to integrate the genome data with the available epidemiological data to better understand the incidence and pathogenicity of this clonal complex in the UK. Methodology All isolates belonging to CC165 in the archives at the UK public health agencies were sequenced and serotyped, and the virulence gene and AMR profiles were derived from the genome using PHE bioinformatics pipelines and the Centre for Genomic Epidemiology virulence database. Results There were 48 CC165 isolates, of which 43 were STEC, four were enteropathogenic E. coli (EPEC) and one E. coli . STEC serotypes were predominately O80:H2 (n=28), and other serotypes included O45:H2 (n=9), O55:H9 (n=4), O132:H2 (n=1) and O180:H2 (n=1). All but one STEC isolate had Shiga toxin (stx) subtype stx2a or stx2d and 47/48 isolates had the eae gene encoding intimin involved in the intimate attachment of the bacteria to the human gut mucosa. We detected extra-intestinal virulence genes including those associated with iron acquisition (iro) and serum resistance (iss), indicating that this pathogen has the potential to translocate to extra-intestinal sites. Unlike other STEC clonal complexes, a high proportion of isolates (93%, 40/43) were multidrug-resistant, including resistance to aminoglycosides, beta-lactams, chloramphenicol, sulphonamides, tetracyclines and trimethoprim. Conclusion The clinical significance of this clonal complex should not be underestimated. Exhibiting high levels of AMR and a combination of STEC and extra-intestinal pathogenic E. coli (ExPEC) virulence profiles, this clonal complex is an emerging threat to public health.

The TRISCEND study (Edwards EVOQUE Tricuspid Valve Replacement: Investigation of Safety and Clinical Efficacy after Replacement of Tricuspid Valve with Transcatheter Device) is evaluating the safety and performance of transfemoral transcatheter tricuspid valve replacement in patients with clinically significant tricuspid regurgitation (TR) and elevated surgical risk.Transcatheter valve replacement could lead to a paradigm shift in treating TR and improving patient quality of life.In the prospective, single-arm, multicenter TRISCEND study, patients with symptomatic moderate or greater TR, despite medical therapy, underwent percutaneous transcatheter tricuspid valve replacement with the EVOQUE system. A composite rate of major adverse events, echocardiographic parameters, and clinical, functional, and quality-of-life measures were assessed at 30 days.Fifty-six patients (mean age of 79.3 years, 76.8% female, 91.1% TR severe or greater, 91.1% atrial fibrillation, and 87.5% New York Heart Association functional class III or IV) were treated. At 30 days, TR was reduced to mild or less in 98%. The composite major adverse events rate was 26.8% at 30 days caused by 1 cardiovascular death in a patient with a failed procedure, 2 reinterventions after device embolization, 1 major access site or vascular complication, and 15 severe bleeds, of which none were life-threatening or fatal. No myocardial infarction, stroke, renal failure, major cardiac structural complications, or device-related pulmonary embolism were observed. New York Heart Association significantly improved to functional class I or II (78.8%; P 0.001), 6-minute walk distance improved 49.8 m (P 0.001), and Kansas City Cardiomyopathy Questionnaire score improved 19 points (P 0.001).Early experience with the transfemoral EVOQUE system in patients with clinically significant TR demonstrated technical feasibility, acceptable safety, TR reduction, and symptomatic improvement at 30 days. The TRISCEND II randomized trial (NCT04482062) is underway.

Objective: To compare the effectiveness of two commonly used moist dressings, Aquacel and Aquacel Foam (both ConvaTec Ltd., UK), in managing split-thickness skin graft (STSG) donor site wounds. Method: Patients undergoing STSG harvesting for reconstruction were eligible for this quasi-experimental study. After reconstruction surgery, the Aquacel (A) or Aquacel Foam (AF) dressings were applied on the donor site wound. The STSG donor site was assessed by two trained research nurses daily. Clinical outcomes including pain on dressing removal, use of intravenous analgesics, signs and symptoms of wound infection, incidence of exudate leakage and percentage healed were recorded in a standardised form. Cost of the dressing change was retrieved from the hospital billing system. Results: Of 50 patients recruited, 25 received dressing A and 25 received the AF dressing for their STSG donor site wound. The average pain score on dressing removal was significantly lower in the AF dressing group compared with the A dressing group (0.8±0.8 versus 3.1±1.5, respectively (p=0.04)). Regression analysis demonstrated that compared with dressing A, the AF dressing was associated with a lower average pain score (beta: –2.27, standard error: 0.33; pConclusion: In this study, the AF dressing demonstrated superior performance in pain response on dressing removal for STSG donor site wounds compared with dressing A. Large-scale randomised controlled trials should be conducted to confirm the findings.

From mouse to primate, there is a striking discontinuity in our current understanding of the neural coding of motion direction. In non-primate mammals, directionally selective cell types and circuits are a signature feature of the retina, situated at the earliest stage of the visual process1,2. In primates, by contrast, direction selectivity is a hallmark of motion processing areas in visual cortex3,4, but has not been found in the retina, despite significant effort5,6. Here we combined functional recordings of light-evoked responses and connectomic reconstruction to identify diverse direction-selective cell types in the macaque monkey retina with distinctive physiological properties and synaptic motifs. This circuitry includes an ON-OFF ganglion cell type, a spiking, ON-OFF poly-axonal amacrine cell and the starburst amacrine cell, all of which show direction selectivity. Moreover, we found unexpectedly that macaque starburst cells possess a strong, non-GABAergic, antagonistic surround mediated by input from excitatory bipolar cells that is critical for the generation of radial motion sensitivity in these cells. Our findings open a new door to investigation of a novel circuitry that computes motion direction in the primate visual system.

Funder: Royal Society; doi: http://dx.doi.org/10.13039/501100000288, Funder: Trinity College, University of Cambridge; doi: http://dx.doi.org/10.13039/501100000727, Funder: John Fell Fund, University of Oxford; doi: http://dx.doi.org/10.13039/501100004789, We use a deep neural network (NN) to detect and place region-of-interest (ROI) boxes around ultracold atom clouds in absorption and fluorescence images—with the ability to identify and bound multiple clouds within a single image. The NN also outputs segmentation masks that identify the size, shape and orientation of each cloud from which we extract the clouds’ Gaussian parameters. This allows 2D Gaussian fits to be reliably seeded thereby enabling fully automatic image processing. The method developed performs significantly better than a more conventional method based on a standardized image analysis library (Scikit-image) both for identifying ROI and extracting Gaussian parameters.

Journal of Education and Training Studies (JETS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether JETS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 11, Number 1 Akın Metli, Bilkent Erzurum Laboratory School (BELS), TurkeyAlphonce John Amuli, ADEM, TanzaniaChris Mutseekwa, Bindura University of Science Education, ZimbabweFroilan D. Mobo, Philippine Merchant Marine Academy, PhilippineHassan Shaaban, Atomic energy Authority, EgyptHossein Chaharbashloo, Kharazmi University, IranIntakhab Khan, King Abdulaziz University, Saudi ArabiaJohn Cowan, Edinburgh Napier University, UKJohn Mark Asio, Gordon College, PhilippinesKendall Hartley, University of Nevada, USAKeyla Ferrari Lopes, UNICAMP, BrazilLisa Marie Portugal, American College of Education, USAMaria Rosa M. Prado, Faculdades Pequeno Príncipe, BrazilNiveen M. Zayed, MENA College of Management, JordanRichard Penny, University of Washington Bothell, USASadia Batool, Karakoram International University, PakistanSamah El-Sakka, Suez University, EgyptStamatis Papadakis, University of Crete, GreeceThada Jantakoon, Rajabhat Maha Sarakham University, Thailand Robert SmithEditorial AssistantOn behalf of,The Editorial Board of Journal of Education and Training StudiesRedfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USAE-mail 1: jets@redfame.comE-mail 2: jets@redfame.orgURL: http://jets.redfame.com

BACKGROUND There were gaps between guidelines and practice when surgery was the only treatment for aortic stenosis (AS). OBJECTIVES This study analyzed the decision to intervene in patients with severe AS in the EORP VHD (EURObservational Research Programme Valvular Heart Disease) II survey. METHODS Among 2,152 patients with severe AS, 1,271 patients with high-gradient AS who were symptomatic fulfilled a Class I recommendation for intervention according to the 2012 European Society of Cardiology guidelines; the primary end point was the decision for intervention. RESULTS A decision not to intervene was taken in 262 patients (20.6%). In multivariate analysis, the decision not to intervene was associated with older age (odds ratio [OR]: 1.34 per 10-year increase; 95% CI: 1.11 to 1.61; P = 0.002), New York Heart Association functional classes I and II versus III (OR: 1.63; 95% CI: 1.16 to 2.30; P = 0.005), higher age adjusted Charlson comorbidity index (OR: 1.09 per 1-point increase; 95% CI: 1.01 to 1.17; P = 0.03), and a lower transaortic mean gradient (OR: 0.81 per 10-mm Hg decrease; 95% CI: 0.71 to 0.92; P < 0.001). During the study period, 346 patients (40.2%, median age 84 years, median EuroSCORE II [European System for Cardiac Operative Risk Evaluation II] 3.1%) underwent transcatheter intervention and 515 (59.8%, median age 69 years, median EuroSCORE II 1.5%) underwent surgery. A decision not to intervene versus intervention was associated with lower 6-month survival (87.4%; 95% CI: 82.0 to 91.3 vs 94.6%; 95% CI: 92.8 to 95.9; P < 0.001). CONCLUSIONS A decision not to intervene was taken in 1 in 5 patients with severe symptomatic AS despite a Class I recommendation for intervention and the decision was particularly associated with older age and combined comorbidities. Transcatheter intervention was extensively used in octogenarians. (J Am Coll Cardiol 2021;78:2131-2143) (c) 2021 by the American College of Cardiology Foundation.

Introduction: In any health system, choices must be made about the allocation of resources (budget), which are often scarce. Economics has defined frameworks to aid resource allocation, and program budgeting marginal analysis (PBMA) is one such framework. In principle, patient and public values can be incorporated into these frameworks, using techniques such as willingness to pay (WTP). However, this has not been done before, and few formal resource allocation processes have been undertaken in dentistry. This study aimed to undertake a PBMA with embedded WTP values in a national dental setting. Methods: The PBMA process was undertaken by a panel of participant-researchers representing commissioners, dentists, dental public health staff, and academics. The panel reviewed current allocations and generated a set of weighted criteria to evaluate services against. Services to be considered for removal and investment were determined by the panel and wider discussion and then scored against the criteria. Values from a nationally representative WTP survey of the public contributed to the scores for interventions. Final decisions on removal and investment were taken after panel discussion using individual anonymous electronic voting. Results: The PBMA process resulted in recommendations to invest in new program components to improve access to general dentists, care home dentistry, and extra support for dental public health input into local government decisions. Disinvestments were recommended in orthodontics and to remove routine scaling and polishing of teeth. Discussion: The PBMA process was successful in raising awareness of resource allocation issues. Implementation of findings will depend on the ability of decision makers to find ways of operationalizing the decisions. The process illustrates practical aspects of the process that future dental PBMAs could learn from. Knowledge Transfer Statement: This study illustrates a framework for resource allocation in dental health services and will aid decision makers in implementing their own resource allocation systems.

Freezing of gait (FOG) is one of the most disabling gait disorders affecting 80% of patients with Parkinson's disease (PD). Clinical guidelines recommend a behavioral approach for gait rehabilitation, but there is a wide diversity of behavioral modalities.The objective of this network meta-analysis was to compare the effectiveness of different behavioral interventions for FOG management in PD patients.Six databases were searched for randomized controlled trials of behavioral interventions for FOG management among PD patients from 1990 to December 2021. Bayesian network meta-analysis was used to combine both direct and indirect trial evidence on treatment effectiveness, while the surface under the cumulative ranking (SUCRA) score was used to estimate the ranked probability of intervention effectiveness.Forty-six studies were included in the qualitative synthesis. Among, 36 studies (1454 patients) of 72 interventions or control conditions (12 classes) were included in the network meta-analysis, with a mean intervention period of 10.3 weeks. After adjusting for the moderating effect of baseline FOG severity, obstacle training [SMD -2.1; 95% credible interval (Crl): -3.3, -0.86], gait training with treadmill (SMD -1.2; 95% Crl: -2.0, -0.34), action observation training (SMD -1.0; 95% Crl: -1.9, -0.14), conventional physiotherapy (SMD -0.70; 95% Crl: -1.3, -0.12) and general exercise (SMD -0.64; 95% Crl: -1.2, -0.11) demonstrated significant improvement on immediate FOG severity compared to usual care. The SUCRA rankings suggest that obstacle training, gait training on treadmill and general exercises are most likely to reduce FOG severity.Obstacle training, gait training on treadmill, general exercises, action observation training and conventional physiotherapy demonstrated immediate real-life benefits on FOG symptoms among patients with mild-moderate PD. With the promising findings, the sustained effects of high complexity motor training combined with attentional/cognitive strategy should be further explored. Future trials with rigorous research designs using both subjective and objective outcome measures, long-term follow-up and cost-effective analysis are warranted to establish effective behavioral strategies for FOG management.

IntroductionPerinatal depression is common and can often lead to adverse health outcomes for mother and child. Multiple pharmacological and non-pharmacological treatments have been evaluated against usual care or placebo controls in meta-analyses for preventing and treating perinatal depression compared. It is not yet established which of these candidate treatments might be the optimal approach for prevention or treatment.Methods and analysisA systematic review and Bayesian network meta-analyses will be conducted. Eight electronic databases shall be searched for randomised controlled trials that have evaluated the effectiveness of treatments for prevention and/or treatment of perinatal depression. Screening of articles shall be conducted by two reviewers independently. One network meta-analysis shall evaluate the effectiveness of interventions in preventing depression during the perinatal period. A second network meta-analysis shall compare the effectiveness of treatments for depression symptoms in women with perinatal depression. Bayesian 95% credible intervals shall be used to estimate the pooled mean effect size of each treatment, and surface under cumulative ranking area will be used to rank the treatments’ effectiveness.Ethics and disseminationWe shall report our findings so that healthcare providers can make informed decisions on what might be the optimal approach for addressing perinatal depression to prevent cases and improve outcomes in those suffering from depression through knowledge exchange workshops, international conference presentations and journal article publications.PROSPERO registration numberCRD42020200081.

Understanding the environmental factors that affect the production of virulence factors has major implications in evolution and medicine. While spatial structure is important in virulence factor production, observations of this relationship have occurred in undisturbed or continuously disturbed environments. However, natural environments are subject to periodic fluctuations, including changes in physical forces, which could alter the spatial structure of bacterial populations and impact virulence factor production. Using Pseudomonas aeruginosa PA14, we periodically applied a physical force to biofilms and examined production of pyoverdine. Intermediate frequencies of disturbance reduced the amount of pyoverdine produced compared to undisturbed or frequently disturbed conditions. To explore the generality of this finding, we examined how an intermediate disturbance frequency affected pyoverdine production in 21 different strains of P. aeruginosa. Periodic disturbance increased, decreased, or did not change the amount of pyoverdine produced relative to undisturbed populations. Mathematical modeling predicts that interactions between pyoverdine synthesis rate and biofilm density determine the amount of pyoverdine synthesized. When the pyoverdine synthesis rates are high, depletion of the biofilm due to disturbance reduces the accumulation of pyoverdine. At intermediate synthesis rates, production of pyoverdine increases during disturbance as bacteria dispersed into the planktonic state enjoy increased growth and pyoverdine production rates. At low synthesis rates, disturbance does not alter the amount of pyoverdine produced since disturbance-driven access to nutrients does not augment pyoverdine synthesis. Our results suggest that environmental conditions shape robustness in the production of virulence factors and may lead to novel approaches to treat infections. IMPORTANCE Virulence factors are required to cause infections. Previous work has shown that the spatial organization of a population, such as a biofilm, can increase the production of some virulence factors, including pyoverdine, which is produced by Pseudomonas aeruginosa. Pyoverdine is essential for the infection process, and reducing its production can limit infections. We have discovered that periodically changing the spatial structure of a biofilm of P. aeruginosa strain PA14 using a physical force can reduce the production of pyoverdine. A mathematical model suggests that this is due to the disruption of spatial organization. Using additional strains of P. aeruginosa isolated from patients and the environment, we use experiments and modeling to show that this reduction in pyoverdine is due to interactions between biofilm density and the synthesis rate of pyoverdine. Our results identify conditions where pyoverdine production is reduced and may lead to novel ways to treat infections.

Background Age-specific incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination in Asia is lacking. This study aimed to study the clinical characteristics and incidence of acute myocarditis/pericarditis among Hong Kong adolescents following Comirnaty vaccination. Methods This is a population cohort study in Hong Kong that monitored adverse events following immunization through a pharmacovigilance system for coronavirus disease 2019 (COVID-19) vaccines. All adolescents aged between 12 and 17 years following Comirnaty vaccination were monitored under the COVID-19 vaccine adverse event response and evaluation program. The clinical characteristics and overall incidence of acute myocarditis/pericarditis in adolescents following Comirnaty vaccination were analyzed. Results Between 14 June 2021 and 4 September 2021, 33 Chinese adolescents who developed acute myocarditis/pericarditis following Comirnaty vaccination were identified. In total, 29 (87.88%) were male and 4 (12.12%) were female, with a median age of 15.25 years. And 27 (81.82%) and 6 (18.18%) cases developed acute myocarditis/pericarditis after receiving the second and first dose, respectively. All cases are mild and required only conservative management. The overall incidence of acute myocarditis/pericarditis was 18.52 (95% confidence interval [CI], 11.67–29.01) per 100 000 persons vaccinated. The incidence after the first and second doses were 3.37 (95% CI, 1.12–9.51) and 21.22 (95% CI, 13.78–32.28 per 100 000 persons vaccinated, respectively. Among male adolescents, the incidence after the first and second doses were 5.57 (95% CI, 2.38–12.53) and 37.32 (95% CI, 26.98–51.25) per 100 000 persons vaccinated. Conclusions There is a significant increase in the risk of acute myocarditis/pericarditis following Comirnaty vaccination among Chinese male adolescents, especially after the second dose.

Physical activity benefits both physical and mental health. Specific events may augment participation in physical activity at a population level. Parkrun is a popular, free, weekly, timed 5 km run or walk in public spaces located in five continents. However, these events may be distributed inequitably, possibly reinforcing inequities in health. As a prelude to a comprehensive analysis of a larger dataset, we explore a hypothesis that participation in parkrun is influenced by the socio-economic characteristics of both parkrunners and their park. Two parkruns, 4.5 km apart, were selected in the city of Sheffield in the United Kingdom. Defined by indices of multiple deprivation, Castle parkrun is located in an economically deprived neighbourhood and Hallam parkrun is in a prosperous area of the city. Parkrunners were defined by applying these same indices to the neighbourhood of home registration. Results: (i) the prosperous Hallam catchment area produced over five times more parkrun participants than Castle; (ii) compared with Castle, Hallam parkrun attracted more participants from both catchment areas; (iii) consequently, Hallam parkrun had seven times more participants than Castle parkrun. Conclusion: establishing parkruns in deprived areas is a necessary but not sufficient prerequisite for equity of participation in this heath promoting activity.Parkruns are popular, free, weekly, timed 5 km runs or walks in public places across the world. They contribute to both mental and physical health. But they could also increase health inequality. Participants may already have the better health generally associated with above average incomes and home life in attractive neighbourhoods. Our pilot study compares two parkruns in the British city of Sheffield; one located in the city’s poorer East End, the other in the richer West End.

It is economically essential, but challenging, for dairy farmers to manage bovine fertility. Vets can help farmers to improve fertility, and this is cost-effective bringing benefits for production, animal health and welfare, and the environment. However, the extent to which vets are involved in fertility varies considerably between farms, for reasons that are unclear. This study investigated the motivators and barriers that vets perceive when trying to increase their involvement with fertility management on UK dairy farms. Interviews were conducted with 20 vets and four themes identified. The first, “clinical baggage,” highlighted vets' disillusionment due to past experiences of low uptake of their advice by farmers. Consequently, some vets made assumptions about farmer needs and behaviours, and exhibited ageist stereotyping. These issues, along with concerns and fatigue associated with repeatedly offering the same advice which was not acted upon, negatively influenced vets' engagement with farmers. The second theme “stuck in the comfort zone” revealed a loss of enthusiasm by some senior vets, whilst others lacked confidence to engage due to perceived gaps in their knowledge. Vets also reported farmers not perceiving their problems and lack of farm data or facilities, as barriers. The “vet-farmer relationship” theme highlighted building trust and developing strong relationships which were key drivers for vets to proactively engage and to “go the extra mile” for their clients. The final theme “money matters” explored vets' motivations to improve their clients' profitability and included the future sustainability of their own businesses. Our themes provide useful insight into the challenges vets face and provide key areas that can be targeted in future interventions to improve veterinary involvement in fertility management. For example, post-graduate training and support for vets needs to consider factors such as reflection, mentorship, stereotyping, relationships, communication, and leadership skills. This type of postgraduate support is currently limited for vets and requires investment from stakeholders if improvements in production, animal health and welfare, and the environment are to be achieved. Our findings are informative for facilitating veterinary involvement in any disease context, and are relevant for stakeholders including governments, educators, charities, farmer representatives, environmentalists, and veterinary leaders.

Background Social isolation is associated with CHD mortality but evidence of association with incident CHD is mixed. We prospectively examined this association in the Million Women Study (MWS) and UK Biobank (UKB). Methods 481,946 MWS and 456,612 UKB participants reported on social isolation (living alone, little contact with family/friends/groups). Excluding those reporting previous CHD or stroke, participants were followed for incident CHD using linkage to hospital admission and death records. Cox regression yielded relative risks (RR) by 3 levels of social isolation, adjusted for relevant confounders. Results During 7 years follow-up in the MWS and UKB, there were 42,402 first coronary heart disease events in total (of which 1,834 were fatal without an associated hospital admission). After adjustment, social isolation was not associated with hospital admission for first CHD events (combined RR for both studies: RR = 1.01, 95% CI: 0.98–1.04). However, the risk of fatal first CHD events without an associated hospital admission was substantially higher in the most isolated group than the least isolated group (1.86 [1.63–2.12]) This association with fatal first CHD events was driven by the association with living alone. Conclusions Social isolation was not associated with increased risk of first CHD hospital admissions but was associated with increased risk of death from CHD. Key messages Social isolation is likely not a risk factor for developing CHD, but people living alone may be at greater risk of dying from a coronary event than those not living alone.

Excess risk for mortality in hospitalized adults with COVID-19 has been linked to extant chronic conditions, especially obesity (Obes), diabetes (DM) or combination (ObesDM). We investigated dose-response interactions between Elixhauser Comorbidity Index (ECI) and comorbidity ensembles including Obes, DM, ObesDM or Control. Presentation demographics, putative COVID-19 severity markers, and administrative data including ICD-10 codes to measure ECI (AHRQ, v2022.1, 0-38 categories) were extracted under IRB exemption from electronic medical records. Youden's J statistic identified ECI35 prognostic of mortality. Bootstrap Forest (BF) estimated explained variance (EV%) in mortality provided by ECI and comorbidity ensembles including Obes, DM, or ObesDM. Continuous data summarized with median [IQR] were compared using Kruskal-Wallis ANOVA. Discrete data summarized as proportions were compared with chi-squared test. Confounders statistically balanced included age, sex, race, COVID-19 directed treatment and 4-surges of local pandemic. Significant p-value (.013) was Bonferroni corrected. Among 4,275 consecutive COVID-19 patients discharged between March 14, 2020 and September 30, 2021, there were 834 (Obes), 730 (DM), 610 (ObesDM) and 2,101 (Control). Intergroup results are reported using same sequence. Pooled age 69[56-79] years, among 45% females was distributed across Whites (78%), Blacks (10%) and other (12%) races. Additional chronic conditions exhibiting intergroup differences (p Presentation: Sunday, June 12, 2022 12:30 p.m. - 2:30 p.m.

PURPOSE Measuring gliomas is a time-intensive process with significant inter-rater variability in post-surgical residual tumor and resection cavities. This likely contributes to the delayed assessment of progression and in-field recurrences from radiation. Automated segmentation of pre and post-treatment gliomas could reduce inter-rater variability and increase workflow efficiency for routine longitudinal radiographic assessment and treatment planning. We evaluated whether a 3D neural network is comparable to expert assessment of pre and post-treatment diffuse gliomas tissue types and resection cavities. METHODS A retrospective cohort of 647 MRIs of patients with diffuse gliomas (average 55.1 years, 45% female, 396 pre-treatment and 251 post-treatment, median 237 days post-surgery) from The Cancer Imaging Archive were stratified by operation status and tumor grade and randomly split into training (536) and testing (111) samples. T1, T1-post-contrast, T2, and FLAIR images were registered, skull-stripped, and interpolated to 1x1x1. Four classes — edema/infiltrative/post-treatment changes (ED), enhancing tissue (ET), necrotic core (NCR), and resection cavities (RC) — were manually segmented by an expert neuroradiologist. Using these segmentations and the four input image modalities, a nnU-Net, a state-of-the-art 3D U-Net convolutional neural network, was trained to predict segmentations of the four classes. RESULTS Segmentation performance in the test set for the ED, ET, and RC classes was at the level of inter-rater reliability with median Dice scores ranging from 0.85 to 1 and relative volume errors ranging from -0.05 to 0.02. There was a near-perfect correlation between manually segmented and predicted total lesion volumes (r2 values ranging from 0.95 to 0.98 among classes). CONCLUSIONS Accurate, automated volumetric quantification of diffuse glioma tissue volumes may improve response assessment in clinical trials and reduce provider burden and errors in measurement.

Background: Requiring access to sensitive data can be a significant obstacle for the development of health models in the Health Economics & Outcomes Research (HEOR) setting. We demonstrate how health economic evaluation can be conducted with minimal transfer of data between parties, while automating reporting as new information becomes available. Methods: We developed an automated analysis and reporting pipeline for health economic modelling and made the source code openly available on a GitHub repository. The pipeline consists of three parts: An economic model is constructed by the consultant using pseudo data. On the data-owner side, an application programming interface (API) is hosted on a server. This API hosts all sensitive data, so that data does not have to be provided to the consultant. An automated workflow is created, which calls the API, retrieves results, and generates a report. Results: The application of modern data science tools and practices allows analyses of data without the need for direct access – negating the need to send sensitive data. In addition, the entire workflow can be largely automated: the analysis can be scheduled to run at defined time points (e.g. monthly), or when triggered by an event (e.g. an update to the underlying data or model code); results can be generated automatically and then be exported into a report. Documents no longer need to be revised manually. Conclusions: This example demonstrates that it is possible, within a HEOR setting, to separate the health economic model from the data, and automate the main steps of the analysis pipeline.

Journal of Education and Training Studies (JETS) would like to acknowledge the following reviewers for their assistance with peer review of manuscripts for this issue. Many authors, regardless of whether JETS publishes their work, appreciate the helpful feedback provided by the reviewers. Their comments and suggestions were of great help to the authors in improving the quality of their papers. Each of the reviewers listed below returned at least one review for this issue.Reviewers for Volume 10, Number 4 Chris Mutseekwa, Bindura University of Science Education, ZimbabweFathia Lahwal, Elmergib University, LibyaGianpiero Greco, University of Study of Bari, ItalyHelena Reis, Polytechnic Institute of Leiria, PortugalIntakhab Khan, King Abdulaziz University, Saudi ArabiaJohn Cowan, Edinburgh Napier University, UKKendall Hartley, University of Nevada, USAKeyla Ferrari Lopes, UNICAMP, BrazilLisa Marie Portugal, American College of Education, USAMaria Rachel Queiroz, Universidade do Estado da Bahia, BrazilMaria Rosa M. Prado, Faculdades Pequeno Príncipe, BrazilMuhammad Haris Effendi-Hasibuan, Universitas Jambi, IndonesiaMustafa Çakır, Marmara University, TurkeyRichard Penny, University of Washington Bothell, USASandro Sehic, Oneida BOCES, USASenem Seda Şahenk Erkan, Marmara University, TurkeyWong Ken Keong, Inspectorate of School Sabah, MalaysiaYuChun Chen, Louisiana Tech University, USAYuxi Qiu, Florida International University, USA Robert SmithEditorial AssistantOn behalf of,The Editorial Board of Journal of Education and Training StudiesRedfame Publishing9450 SW Gemini Dr. #99416Beaverton, OR 97008, USAE-mail 1: jets@redfame.comE-mail 2: jets@redfame.orgURL: http://jets.redfame.com

The exposure-lag response of air temperature on daily COVID-19 incidence is unclear and there have been concerns regarding the robustness of previous studies. Here we present an analysis of high spatial and temporal resolution using the distributed lag non-linear modelling (DLNM) framework. Utilising nearly two years' worth of data, we fit statistical models to twelve Italian cities to quantify the delayed effect of air temperature on daily COVID-19 incidence, accounting for several categories of potential confounders (meteorological, air quality and non-pharmaceutical interventions). Coefficients and covariance matrices for the temperature term were then synthesised using random effects meta-analysis to yield pooled estimates of the exposure-lag response with effects presented as the relative risk (RR) and cumulative RR (RR