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BackgroundThe use of anti-interleukin-5 (IL5) for severe asthma is based on criteria from randomised controlled trials (RCTs), but in real-life patients might not fulfil the eligibility criteria but may benefit from biologics. We aimed to characterise patients starting anti-IL5(R) in Europe and evaluate the discrepancies between initiation of anti-IL5(R) in real life and in RCTs.Materials and methodsWe performed a cross-sectional analysis with data from the severe asthma patients at the start of anti-IL5(R) in the Severe Heterogeneous Asthma Research collaboration Patient-centred (SHARP Central) registry. We compared the baseline characteristics of the patients starting anti-IL5(R) from 11 European countries within SHARP with the baseline characteristics of the severe asthma patients from 10 RCTs (four for mepolizumab, three for benralizumab and three for reslizumab). Patients were evaluated following eligibility criteria from the RCTs of anti-IL5 therapies.ResultsPatients starting anti-IL5(R) in Europe (n=1231) differed in terms of smoking history, clinical characteristics and medication use. The characteristics of severe asthma patients in the SHARP registry differed from the characteristics of patients in RCTs. Only 327 (26.56%) patients fulfilled eligibility criteria of all the RCTs; 24 patients were eligible for mepolizumab, 100 for benralizumab and 52 reslizumab. The main characteristics of ineligibility were: ≥10 pack-years, respiratory diseases other than asthma, Asthma Control Questionnaire score ≤1.5 and low-dose inhaled corticosteroids.ConclusionA large proportion of patients in the SHARP registry would not have been eligible for anti-IL5(R) treatment in RCTs, demonstrating the importance of real-life cohorts in describing the efficacy of biologics in a broader population of patients with severe asthma.

The longhorn beetle fauna of Kentucky has long been overlooked in the literature with revisions and historic publications reporting few records from the state. Here, we document the occurrence of 222 species of Cerambycidae in Kentucky, with 140 new state records. For each species, we summarize its distribution (overall and in the state), the counties, years, and months in which it has been collected, collecting methods, what collections house the specimens, larval host plants, adult flower visitation, chemical lure attraction, recent taxonomic changes, and other pertinent information about the species. Using this dataset, the bias-corrected Chao1 species richness estimator predicted that 241 species should be found in Kentucky, indicating that our sampling is nearly comprehensive. Additionally, we provide a list of 42 species that have been found in at least one neighboring state and the distance from the closest record of the species to Kentucky; among this candidate list are 11 species known from within 50 km of the state. This checklist remedies the historical oversight of Kentucky cerambycid diversity in the literature, and we hope it will serve as a resource for future collectors, particularly the information on chemical lure attraction, which has not been summarized to this extent for any other state to date.

Early-life adversities during development (e.g., child abuse and neglect) are linked to multiple behavioral and cognitive dysfunctions, such as attention deficit/hyperactivity disorder (ADHD) and anxiety disorders, which have high comorbidity. However, the impact of adversities during adolescence, a crucial period in early life for these disorders, is understudied. Using a chronic unpredictable stress (CUS) model in rats, we investigated whether adversities in adolescence could lead to increased anxiety and ADHD-like symptoms in adulthood.Mid- to late-adolescent (5-7-week-old) male and female Sprague-Dawley rats underwent a mild CUS procedure for 2 weeks. Various stressors were applied in an unpredictable way. Rats of both sexes were then trained with a 2-choice reaction time (2-CRT) task during adulthood, which are designed to detect ADHD-like symptoms, including increased impulsivity and lapse of attention. In addition, an open field test was conducted to examine if CUS resulted in a persistent increase in anxiety-like behavior during adulthood.Both male and female rats with CUS exposure travelled shorter distances in the open field and spent less time in the center zone, indicating increased anxiety. In the 2-CRT task, rats of both sexes with CUS exposure showed increased impulsivity. Augmented lapses of attention were observed in female but not male rats.Chronic unpredictable stress during adolescence increases anxiety and leads to ADHD-like symptoms in both male and female rats in adulthood. The deficits are more severe in females than in males. These observations support that adversities during adolescence persistently increase anxiety, which is comorbid with attention deficits.

Introduction Health professionals in rural settings encounter a wide range of medical conditions requiring broad knowledge for their clinical practice. This creates the need for ongoing continuing professional development (CPD). In this study, we explored the barriers that health professionals in a rural healthcare context faced participating in CPD activities and their preferences regarding educational strategies to overcome these challenges. Methods This mixed-methods (exploratory sequential) study in a community hospital in rural Mexico includes 22 interviews, 3 focus groups, 40 observational hours, and a questionnaire of healthcare staff. Results Despite low engagement with CPD activities (67% not motivated), all participants expressed interest and acknowledged the importance of learning for their practice. Barriers to participating include a disparity between strategies used (lecture-based) and their desire for practical learning, institutional barriers (poor leadership engagement, procedural flaws, and lack of resources), and collaboration barriers (adverse interprofessional education environment, ineffective teamwork, and poor communication). Additional barriers identified were inconvenient scheduling of sessions (75%), inadequate classrooms (65%), high workload (60%), ineffective speakers (60%), and boring sessions (55%). Participants’ preferred learning strategies highlighted activities relevant to their daily clinical activities (practical workshops, simulations, and case analysis). The questionnaire had an 18% response rate. Discussion The barriers to CPD in this rural setting are multifactorial and diverse. A strong interest to engage in context-specific active learning strategies highlighted the need for leadership to prioritize interprofessional education, teamwork, and communication to enhance CPD and patient care. Thes

Artificial intelligence (AI) is increasingly reshaping brand and marketing communications. While significant research has been conducted on the impact of AI in other fields, there is little empirical evidence on how artificial intelligence is affecting the customer journey. This research study seeks to answer, “How is artificial intelligence influencing both organizational content strategy and the related customer journey?” To answer this, the authors employed mixed-methods qualitative research via a content analysis of industry publications, a series of in-depth customer interviews, and a case study content analysis of two organizations that are using AI to varying degrees within their content strategy. This study found that many publications agree AI will play a future role as creative assistant in content development, that consumer perceptions about AI and cognitive dissonance impact levels of adoption to some extent, and that companies in different geographical locations may have different levels of AI adoption along innovation stages.

Choice behavior requires animals to evaluate both short- and long-term advantages and disadvantages of all potential alternatives. Impulsive choice is traditionally measured in laboratory tasks by utilizing delay discounting (DD), a paradigm that offers a choice between a smaller immediate reward, or a larger more delayed reward. This study tested a large sample of Heterogeneous Stock (HS) male (n = 896) and female (n = 898) rats, part of a larger genetic study, to investigate whether measures of reward maximization overlapped with traditional models of delay discounting via the patch depletion model using a Sequential Patch Depletion procedure. In this task, rats were offered a concurrent choice between two water “patches” and could elect to “stay” in the current patch or “leave” for an alternative patch. Staying in the current patch resulted in decreasing subsequent reward magnitudes, whereas the choice to leave a patch was followed by a delay and a resetting to the maximum reward magnitude. Based on the delay in a given session, different visit durations were necessary to obtain the maximum number of rewards. Visit duration may be analogous to an indifference point in traditional DD tasks. While differences in traditional DD measures (e.g., delay gradient) have been detected between males and females, these effects were small and inconsistent. However, when examining measures of reward maximization, females made fewer patch changes at all delays and spent more time in the patch before leaving for the alternative patch compared to males. This pattern of choice resulted in males having a higher rate of reinforcement than females. Consistent with this, there was some evidence that females deviated from the optimal more, leading to less reward. Measures of reward maximization were only weakly associated with traditional DD measures and may represent distinctive underlying processes. Taken together, females performance differed from males with regard to reward maximization that were not observed utilizing traditional measures of DD, suggesting that the patch depletion model was more sensitive to modest sex differences when compared to traditional DD measures in a large sample of HS rats.

Background: Smoking is the leading preventable cause of death; however, small-area estimates for detailed smoking status are limited. We developed multilevel small-area estimate mixed models to generate county-level estimates for six smoking status categories: current, some days, every day, former, ever, and never.Method: Using 2012 Behavioral Risk Factor Surveillance System (BRFSS) data (our sample size = 405,233 persons), we constructed and fitted a series of multilevel logistic regression models and applied them to the U.S. Census population to generate county-level prevalence estimates. We mapped the estimates by sex and aggregated them into state and national estimates. We conducted comparisons for internal consistency with BRFSS states' estimates using Pearson correlation coefficients, and external validation with the 2012 National Health Interview Survey current smoking prevalence.Results: Correlation coefficients ranged from 0.908 to 0.982, indicating high internal consistency. External validation indicated complete agreement (prevalence = 18.06%). We found large variations in current and former smoking status between and within states and by sex. County prevalence of former smokers was highest among men in the Northeast, North, and West. Utah consistently had the lowest smoking prevalence.Conclusions: Our models, which include demographic and geographic characteristics, provide reliable estimates that can be applied to multiple category outcomes and any demographic group. County and state estimates may help understand the variation in smoking prevalence in the United States and provide information for control and prevention.Impact: Detailed county and state smoking category estimates can help identify areas in need of tobacco control and prevention and potentially allow planning for health care. Cancer Epidemiol Biomarkers Prev; 25(10); 1402–10. ©2016 AACR.

Supplementary Methods and Materials

Power analyses are often used to determine the number of animals required for a genome-wide association study (GWAS). These analyses are typically intended to estimate the sample size needed for at least 1 locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real data set that consisted of 3,173 male and female adult N/NIH heterogeneous stock rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in subsamples of the full data set. The subsampling analysis was conducted for 4 traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03), and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we subsampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.

Power analyses are often used to determine the number of animals required for a genome wide association analysis (GWAS). These analyses are typically intended to estimate the sample size needed for at least one locus to exceed a genome-wide significance threshold. A related question that is less commonly considered is the number of significant loci that will be discovered with a given sample size. We used simulations based on a real dataset that consisted of 3,173 male and female adult N/NIH heterogeneous stock (HS) rats to explore the relationship between sample size and the number of significant loci discovered. Our simulations examined the number of loci identified in sub-samples of the full dataset. The sub-sampling analysis was conducted for four traits with low (0.15 ± 0.03), medium (0.31 ± 0.03 and 0.36 ± 0.03) and high (0.46 ± 0.03) SNP-based heritabilities. For each trait, we sub-sampled the data 100 times at different sample sizes (500, 1,000, 1,500, 2,000, and 2,500). We observed an exponential increase in the number of significant loci with larger sample sizes. Our results are consistent with similar observations in human GWAS and imply that future rodent GWAS should use sample sizes that are significantly larger than those needed to obtain a single significant result.

Background The safety, effectiveness, and cost-effectiveness of molnupiravir, an oral antiviral medication for SARS-CoV-2, has not been established in vaccinated patients in the community at increased risk of morbidity and mortality from COVID-19. We aimed to establish whether the addition of molnupiravir to usual care reduced hospital admissions and deaths associated with COVID-19 in this population. Methods PANORAMIC was a UK-based, national, multicentre, open-label, multigroup, prospective, platform adaptive randomised controlled trial. Eligible participants were aged 50 years or older—or aged 18 years or older with relevant comorbidities—and had been unwell with confirmed COVID-19 for 5 days or fewer in the community. Participants were randomly assigned (1:1) to receive 800 mg molnupiravir twice daily for 5 days plus usual care or usual care only. A secure, web-based system (Spinnaker) was used for randomisation, which was stratified by age (vs ≥50 years) and vaccination status (yes vs no). COVID-19 outcomes were tracked via a self-completed online daily diary for 28 days after randomisation. The primary outcome was all-cause hospitalisation or death within 28 days of randomisation, which was analysed using Bayesian models in all eligible participants who were randomly assigned. This trial is registered with ISRCTN, number 30448031. Findings Between Dec 8, 2021, and April 27, 2022, 26 411 participants were randomly assigned, 12 821 to molnupiravir plus usual care, 12 962 to usual care alone, and 628 to other treatment groups (which will be reported separately). 12 529 participants from the molnupiravir plus usual care group, and 12 525 from the usual care group were included in the primary analysis population. The mean age of the population was 56·6 years (SD 12·6), and 24 290 (94%) of 25 708 participants had had at least three doses of a SARS-CoV-2 vaccine. Hospitalisations or deaths were recorded in 105 (1%) of 12 529 participants in the molnupiravir plus usual care group versus 98 (1%) of 12 525 in the usual care group (adjusted odds ratio 1·06 [95% Bayesian credible interval 0·81–1·41]; probability of superiority 0·33). There was no evidence of treatment interaction between subgroups. Serious adverse events were recorded for 50 (0·4%) of 12 774 participants in the molnupiravir plus usual care group and for 45 (0·3%) of 12 934 in the usual care group. None of these events were judged to be related to molnupiravir. Interpretation Molnupiravir did not reduce the frequency of COVID-19-associated hospitalisations or death among high-risk vaccinated adults in the community. Funding UK National Institute for Health and Care Research

The remarkable archaeological record of Neolithic Orkney has ensured that these islands play a prominent role in narratives of European late prehistory, yet knowledge of the subsequent Bronze Age is comparatively poor. The Bronze Age settlement and cemetery at the Links of Noltland, on the island of Westray, offers new evidence, including aDNA, that points to a substantial population replacement between the Late Neolithic and Bronze Age. Focusing on funerary practice, the authors argue for interconnecting identities centred on household and community, patrilocality and inheritance. The findings prompt a reconsideration of the Orcadian Bronze Age, with wider implications for population movement and the uptake of cultural innovations more widely across prehistoric north-western Europe.

Teaching is a critical skill in the medical profession, yet has only recently gained recognition as a core skill for medical students and trainees. Student-as-teacher (SAT) programs provide medical students formal teaching instruction with opportunities for practice. While efforts to determine how SAT courses should be taught are ongoing, the authors' review of SAT programs in medical schools' curricula shows they are diverse and often developed by faculty and trainees who advocate for formal teacher training at their institutions, rather than by medical school leadership. Consequently, there is significant heterogeneity among known SAT programs with regard to content, format, and evaluation methods. As efforts are underway to create guidelines and competency frameworks for SAT programs, medical educators must engage in open and critical discussion about the optimal content and organization for SAT educational experiences, emphasizing outcomes-based value and curricular and experiential consistency across programs. The authors describe an innovative SAT elective at Harvard Medical School (HMS), discuss research supporting curricular content and decisions, and emphasize potential implications for the conception and implementation of SAT programs at other institutions. The HMS SAT course is a year-long, elective, longitudinal curriculum built on a community of practice model and comprising 5 key components: Fundamentals of Medical Education seminar series, teaching field experiences, teaching observations, final educational product, and self-reflection. This 5-component theoretically justified model covers essential topics of SAT programming, providing students a comprehensive educational skills training curriculum. Medical educators developing SAT courses must identify common core competencies and curricular activities to implement SAT programs informed by the perspective of local stakeholders and institutional needs. Further growth of SAT programs in medical education offers opportunities for collaboration and coordination among medical educators, institutions, and licensing and accreditation bodies, to further develop consistent guidelines for teaching medical education skills to future medical educators.

The associations between swimming and cycling abilities and fitness levels in 9-11-year-old children were examined. A cross-sectional study involving 2258 children (50.7% boys; aged 10.52 ± 0.6 years) from 33 schools across Wales, participated in Swan/BridgeLinx health, fitness, and lifestyle programmes between 2013-2019. Health and fitness data were collected; namely body composition, cardiorespiratory fitness, muscular strength, flexibility, power, and speed using standardised measures. Children completed an online survey collecting data on swimming and cycling abilities and sports club attendance. Multivariate multilevel regressions were used to examine the associations between measures. The ability to swim and cycle was significantly (p 0.05) associated with all components of fitness when accounting for age, body mass index (BMI), deprivation, gender, and sports club attendance. Boys outperformed girls with significant interactions between swimming, cycling and cardiorespiratory fitness for gender by swim (p = 0.001) and gender by cycle (p = 0.015). The gender by cycle interaction significantly predicted grip strength and power (p 0.05). Swimming and cycling are important "milestones" in the journey of motor development and are associated with higher levels of fitness. These activities should be promoted to allow for an optimal development of motor skills, fitness, and health.

Purpose: The University of Maine Speech Therapy Telepractice Program provides speech therapy telepractice services to children with communication disorders at the International School Suva (ISS), Fiji. This partnership has fostered international engagement and multicultural experiences for graduate student clinicians in the Department of Communication Sciences and Disorders while filling a need for speech therapy services in Fiji. Despite infrastructure, scheduling, and COVID-19 issues, the benefits of this partnership have far outweighed the challenges. Clinical observations of the ISS children's responses have revealed excellent progress toward achieving therapy goals. Parents and school personnel have also reported a high degree of satisfaction with our services. The program has encouraged our graduate students to be resilient, out-of-the-box thinkers as they research a variety of multicultural issues and apply this new knowledge to the clinical programs of their clients. Conclusions: This article highlights the partnership between The University of Maine, Speech Therapy Telepractice Training Program and the ISS, Fiji, as an example for other academic programs that are interested in establishing international telepractice partnerships. A description of the telepractice clinical procedures and technology for service provision at the ISS is included, along with a discussion of the challenges and benefits for providing international speech therapy telepractice services. Two case examples illustrate the complexity of providing services to multilingual children with different cultural backgrounds.

Over the past three decades, electrohydraulic extracorporeal shock wave therapy (ESWT) as a treatment modality for equine orthopaedic disorders has sparked exponential interest among practitioners, but its clinical applications are quickly evolving and a current review highlighting modernised equine clinical use is lacking. The objective of this review is to summarise the most current ESWT technology, evidence for its use, proposed mechanisms of action and clinical applications in horses while also highlighting the areas requiring further investigation. The three ways to generate a shock wave are through electrohydraulic, electromagnetic or piezoelectric mechanisms, but over the last decade, electrohydraulic systems have predominated due to the ability to focus and control a therapeutic waveform. Shock waves' primary physical effect is believed to be via mechanotransduction leading to cellular activation and downstream signalling. Experimentally, ESWT's effects on osseous, connective tissue and wound healing via various mechanisms of action have been reported both in the human and veterinary literature. Clinical trials have investigated ESWT's orthopaedic application including osteoarthritis, thoracolumbar pain, navicular syndrome, tendinopathy and proximal suspensory desmopathy, with its concomitant use with biologics representing an area of active research. Direct ESWT protocol comparisons in terms of long-term efficacy with variables of energy, depth and exposed tissue types are still lacking with evidence-based recommendations being largely anecdotal. Technical advancements to facilitate the safe and judicious use of ESWT include human and equine hearing protection, light sedation and/or patient restraint. Efforts to ensure the safe and judicious use of ESWT and its analgesic effects are ongoing.

Background: Some children with asthma experience exacerbations despite long-acting beta2-agonist (LABA) treatment. While this variability is partly caused by genetic variation, no genome-wide study until now has investigated which genetic factors associated with risk of exacerbations despite LABA use in children with asthma. We aimed to assess whether genetic variation was associated with exacerbations in children treated with LABA from a global consortium. Methods: A meta-analysis of genome-wide association studies (meta-GWAS) was performed in 1,425 children and young adults with asthma (age 6-21 years) with reported regular use of LABA from six studies within the PiCA consortium using a random effects model. The primary outcome of each study was defined as any exacerbation within the past 6 or 12 months, including at least one of the following: 1) hospital admissions for asthma, 2) a course of oral corticosteroids or 3) emergency room visits because of asthma. Results: Genome-wide association results for a total of 82 996 common single nucleotide polymorphisms (SNPs, MAF ≥1%) with high imputation quality were meta-analysed. Eight independent variants were suggestively (P-value threshold ≤5 × 10−6) associated with exacerbations despite LABA use. Conclusion: No strong effects of single nucleotide polymorphisms (SNPs) on exacerbations during LABA use were identified. We identified two loci (TBX3 and EPHA7) that were previously implicated in the response to short-acting beta2-agonists (SABA). These loci merit further investigation in response to LABA and SABA use.

Purpose: We aim to compare the incidence of corneal epithelial defects after laser for retinopathy of prematurity (ROP) with and without the use of postoperative erythromycin ointment. Methods: In this retrospective observational cohort study, a total of 100 infants (200 eyes) consecutively treated with laser for ROP between 2012 and 2018. The primary outcome was presence or absence of corneal epithelial defect using fluorescein on bedside examination within the first week following laser for ROP. Additional data assessed included: the use of postoperative prophylactic erythromycin ointment for 1 week, postoperative day on which examination using fluorescein occurred, presence of corneal opacity, gender, birth weight, and gestation age. The presence or absence of postoperative corneal epithelial defects was compared between eyes receiving postoperative erythromycin ointment or not using a Fisher's exact test. Results: Postoperative corneal epithelial defects were more common in eyes which did not receive postoperative erythromycin (7 of 40 eyes; 17.5%), compared to eyes which did receive erythromycin (1 of 160 eyes; 0.6%; P < 0.0001). Postoperative bedside examinations with fluorescein were performed within 2 days of surgery on 136 of 200 of eyes (68%). Corneal opacities were noted in 3 of 200 eyes (1.5%). Conclusion: We observed less corneal epithelial defects in eyes which received postoperative erythromycin ointment for 1 week after laser for ROP than in those which did not. While multiple variables may influence the presence or absence of postoperative corneal epithelial defects following laser for ROP, consideration for postoperative lubricating ointment following laser for ROP seems reasonable.

The history of the British Isles and Ireland is characterized by multiple periods of major cultural change, including the influential transformation after the end of Roman rule, which precipitated shifts in language, settlement patterns and material culture1. The extent to which migration from continental Europe mediated these transitions is a matter of long-standing debate2–4. Here we study genome-wide ancient DNA from 460 medieval northwestern Europeans—including 278 individuals from England—alongside archaeological data, to infer contemporary population dynamics. We identify a substantial increase of continental northern European ancestry in early medieval England, which is closely related to the early medieval and present-day inhabitants of Germany and Denmark, implying large-scale substantial migration across the North Sea into Britain during the Early Middle Ages. As a result, the individuals who we analysed from eastern England derived up to 76% of their ancestry from the continental North Sea zone, albeit with substantial regional variation and heterogeneity within sites. We show that women with immigrant ancestry were more often furnished with grave goods than women with local ancestry, whereas men with weapons were as likely not to be of immigrant ancestry. A comparison with present-day Britain indicates that subsequent demographic events reduced the fraction of continental northern European ancestry while introducing further ancestry components into the English gene pool, including substantial southwestern European ancestry most closely related to that seen in Iron Age France

Background: The Global Matrix 4.0 on physical activity (PA) for children and adolescents was developed to achieve a comprehensive understanding of the global variation in children’s and adolescents’ (5–17 y) PA, related measures, and key sources of influence. The objectives of this article were (1) to summarize the findings from the Global Matrix 4.0 Report Cards, (2) to compare indicators across countries, and (3) to explore trends related to the Human Development Index and geo-cultural regions. Methods: A total of 57 Report Card teams followed a harmonized process to grade the 10 common PA indicators. An online survey was conducted to collect Report Card Leaders’ top 3 priorities for each PA indicator and their opinions on how the COVID-19 pandemic impacted child and adolescent PA indicators in their country. Results: Overall Physical Activity was the indicator with the lowest global average grade (D), while School and Community and Environment were the indicators with the highest global average grade (C+). An overview of the global situation in terms of surveillance and prevalence is provided for all 10 common PA indicators, followed by priorities and examples to support the development of strategies and policies internationally. Conclusions: The Global Matrix 4.0 represents the largest compilation of children’s and adolescents’ PA indicators to date. While variation in data sources informing the grades across countries was observed, this initiative highlighted low PA levels in children and adolescents globally. Measures to contain the COVID-19 pandemic, local/international conflicts, climate change, and economic change threaten to worsen this situation.

Autorzy: Abe K., Adrich P., Aihara H., Akutsu, R., Alekseev I., Ali A. , Ameli F., Anghel I., Anthony L. H. V., Antonova M. , Araya A., Asaoka Y., Ashida Y., Aushev V., Ballester F., Bandac I., Barbi M., Barker G. J., Barr G., Batkiewicz-Kwasniak M., Bellato M., Berardi V., Bergevin M., Bernard L., Bernardini E., Berns L., Bhadra S., Bian J., Blanchet A., Blaszczyk F. d. M., Blonde A., Boiano A., Bolognesi S., Bonavera L., Booth N., Borjabad S., Boschi, T., Bose D., Boyd S . B., Bozza C., Bravar A., Bravo-Berguño D., Bronner C., Brown L., Bubak Arkadiusz, Buchowicz A., Buizza Avanzini M., Cafagna F. S., Calabria N. F., Calvo-Mozota J. M., Cao S., Cartwright S.L., Carroll A., Catanesi M. G., Cebriàn, S., Chabera M., Chakraborty, S., Checchia C., Choi J.H., Choubey S., Cicerchia M., Coleman J., Collazuol G., Cook L., Cowan G., Cuen-Rochin, S., Danilov M., Díaz López G., De la Fuente E., de Perio P., De Rosa G., Dealtry T., Densham C. J., Dergacheva A., Deshmukh N., Devi M. M., Di Lodovico F., Di Meo, P., Di Palma I., Doyle T. A., Drakopoulou E., Drapier O., Dumarchez J., Dunne P., Dziewiecki M., Eklund L., El Hedri S., Ellis J., Emery S., Esmaili A., Esteve R., Evangelisti A., Feely M., Fedotov S., Feng J., Fernandez P., Fernández-Martinez E., Ferrario P., Ferrazzi,B., Feusels T., Finch A., Finley C., Fiorentini A., Fiorillo G., Fitton M., Frankiewicz K., Friend M., Fujii Y., Fukuda Y., Galinski G., Gao J., Garde C., Garfagnini A., Garode S., Gialanella L., Giganti C., Gomez-Cadenas J.J., Gonin M., González-Nuevo J., Gorin A., Gornea R., Gousy-Leblanc V. Gramegna F. Grassi M. Grella G. Guigue M. Gumplinger P. Hadley D.R. Harada M., Hartfiel B., Hartz M., Hassani S., Hastings N.C., Hayato Y., Hernando-Morata J.A., Herrero V., Hill J., Hiraide K., Hirota S., Holin A., Horiuchi S., Hoshina K., Hultqvist K., Iacob F., Ichikawa A.K., Idrissi Ibnsalih W., Iijima T., Ikeda M., Inomoto M., Inoue K., Insler J., Ioannisian A., Ishida T., Ishidoshiro K., Ishino H., Ishitsuka M., Ito H., Ito S., Itow Y., Iwamoto K., Izmaylov A., Izumi N., Izumiyama S., Jakkapu M., Jamieson B., Jang H.I., Jang J.S., Jenkins S.J., Jeon S.H., Jiang M., Jo H.S., Jonsson P., Joo K.K., Kajita T., Kakuno H., Kameda J., Kano Y., Kalaczynski P., Karlen D., Kasperek J., Kataoka Y., Kato A., Katori T., Kazarian N., Kearns E., Khabibullin M., Khotjantsev A., Kikawa T., Kekic M., Kim J.H., Kim J.Y., Kim S.B., Kim S.Y., King S., Kinoshita T., Kisiel Jan, Klekotko A., Kobayashi T., Koch L., Koga M., Koerich L., Kolev N., Konaka A., Kormos L.L., Koshio Y., Korzenev A., Kotsar Y., Kouzakov K.A., Kowalik K.L., Kravchuk L., Kryukov A.P., Kudenko Y., Kumita T., Kurjata R., Kutter T., Kuze M., Kwak K., La Commara M., Labarga L., Lagoda J., Lamers James J., Lamoureux M., Laveder M., Lavitola L., Lawe M., Learned J.G., Lee J., Leitner R., Lezaun V., Lim I.T., Lindner T., Litchfield R.P., Long K.R., Longhin A., Loverre P., Lu X., Ludovici L., Maekawa Y., Magaletti L., Magar K., Mahn K., Makida Y., Malek M., Malinský M., Marchi T., Maret L., Mariani C., Marinelli A., Martens K., Marti L., Martin J.F. Martin D., Marzec J., Matsubara T., Matsumoto R., Matsuno S., Matusiak M., Mazzucato E., McCarthy M., McCauley N., McElwee J., McGrew C., Mefodiev A., Medhi A., Mehta P., Mellet L., Menjo H., Mermod P., Metelko C., Mezzetto M., Migenda J., Migliozzi P., Mijakowski P., Miki S., Miller E.W., Minakata H., Minamino A., Mine S., Mineev O., Mitra A., Miura M., Moharana R., Mollo C.M., Mondal T., Mongelli M., Monrabal F., Moon D.H., Moon C.S., Mora F.J., Moriyama S., Mueller Th.A., Munteanu L., Murase K., Nagao Y., Nakadaira T., Nakagiri K., Nakahata M., Nakai S., Nakajima Y., Nakamura K., Nakamura KI., Nakamura H., Nakano Y., Nakaya T., Nakayama S., Nakayoshi K., Nascimento Machado L., Naseby C.E.R., Navarro-Garcia B., Needham M., Nicholls T., Niewczas K., Nishimura Y., Noah E., Nova F., Nugent J.C., Nunokawa H., Obrebski W., Ochoa-Ricoux J.P., O’Connor E., Ogawa N., Ogitsu T., Ohta K., Okamoto K., O’Keeffe H.M., Okumura K., Onishchuk Y., Orozco-Luna F., Oshlianskyi A., Ospina N., Ostrowski M., O’Sullivan E., O’Sullivan L., Ovsiannikova T., Oyama Y., Ozaki H., Pac M.Y., Paganini P., Palladino V., Paolone V., Pari M., Parsa S., Pasternak J., Pastore C., Pastuszak G., Patel D.A., Pavin M., Payne D., Peña-Garay C., Pidcott C., Pinzon Guerra E., Playfer S., Pointon B.W., Popov A., Popov B., Porwit Kamil, Posiadala-Zezula M., Poutissou J.M., Pozimski J., Pronost G., Prouse N.W., Przewlocki P., Quilain B., Quiroga A.A., Radicioni E., Radics B., Rajda P.J., Renner J., Rescigno M., Retiere F., Ricciardi G., Riccio C., Richards B., Rondio E., Rose H.J., Roskovec B., Roth S., Rott C., Rountree S.D., Rubbia A., Ruggeri A.C., Ruggles C., Russo S., Rychter A., Ryu D., Sakashita K., Samani S., Sánchez F., Sánchez M.L., Sanchez M.C., Sano S., Santos J.D., Santucci G., Sarmah P., Sashima I., Sato K., Scott M., Seiya Y., Sekiguchi T., Sekiya H., Seo J.W., Seo S.H., Sgalaberna D., Shaikhiev A., Shan Z., Shaykina A., Shimizu I., Shin C.D., Shinoki M., Shiozawa M., Sinnis G., Skrobova N., Skwarczynski K., Smy M.B., Sobczyk J., Sobel H.W., Soler F. J. P., Sonoda Y., Spina R., Spisso B., Spradlin B., Stankevich K.L., Stawarz L., Stellacci S.M., Stopa K., Studenikin A.I., Suárez Gómez S.L., Suganuma T., Suvorov S., Suwa Y., Suzuki A.T., Suzuki S.Y., Suzuki Y., Svirida D., Svoboda R., Taani M., Tada M., Takeda A., Takemoto Y., Takenaka A., Taketa A., Takeuchi Y., Takhistov V., Tanaka H., Tanaka H.A., Tanaka H.I., Tanaka M., Tashiro T., Thiesse M., Thompson L.F., Toledo J., Tomatani-Sánchez A.K., Tortone G., Tsui K.M., Tsukamoto T., Tzanov M., Uchida Y., Vagins M.R., Valder S., Valentino V., Vasseur G., Vijayvargi A., Vilela C., Vinning W. G. S., Vivolo D., Vladisavljevic T., Vogelaar R.B., Vyalkov M.M., Wachala T., Walker J., Wark D., Wascko M.O., Wendell R.A., Wilkes R.J., Wilking M.J., Wilson M.R., Wronka S., Xia J., Xie Z., Xin T., Yamaguchi Y., Yamamoto K., Yanagisawa C., Yano T., Yen S., Yershov N., Yeum D.N., Yokoyama M., Yonenaga M., Yoo J., Yu I., Yu M., Zakrzewski T., Zaldivar B., Zalipska J., Zaremba K., Zarnecki G., Ziembicki M., Zietara K., Zito M., Zsoldos S., Core-collapse supernovae are among the most magnificent events in the observable universe. They produce many of the chemical elements necessary for life to exist and their remnants-neutron stars and black holes-are interesting astrophysical objects in their own right. However, despite millennia of observations and almost a century of astrophysical study, the explosion mechanism of core-collapse supernovae is not yet well understood. Hyper-Kamiokande is a next-generation neutrino detector that will be able to observe the neutrino flux from the next galactic core-collapse supernova in unprecedented detail. We focus on the first 500 ms of the neutrino burst, corresponding to the accretion phase, and use a newly-developed, high-precision supernova event generator to simulate Hyper-Kamiokandeʼs response to five different supernova models. We show that Hyper-Kamiokande will be able to distinguish between these models with high accuracy for a supernova at a distance of up to 100 kpc. Once the next galactic supernova happens, this ability will be a powerful tool for guiding simulations toward a precise reproduction of the explosion mechanism observed in nature.

Background/ObjectiveAcute appendicitis is predominantly managed with appendectomy, but can be treated non-operatively, leading to recurrence risk. Non-operative management has been more common since the COVID-19 pandemic affected the feasibility of performing surgery. This case-control study analyzed non-operatively managed patients in order to identify clinical and radiological factors associated with recurrence risk. MethodsOver 12 months, 48 adults with CT-proven acute appendicitis managed non-operatively were identified, and followed up for at least 6 further months to assess them for recurrence (reattendance to hospital more than 14 days after discharge and after symptom resolution, requiring treatment for appendicitis). Clinical and CT data were collected and a Cox regression survival analysis was performed to produce hazards ratios. ResultsOf the 48 patients, 12 (25%) experienced a recurrence up until the end of the follow-up period, 8 of whom were then treated operatively. On the univariate analysis, greater recurrence risk was observed in patients with diabetes mellitus, higher pulse rate (on admission and maximum value during admission), lower white cell count and neutrophils and appendiceal wall thinning on CT. On the multivariate analysis, diabetes mellitus (hazards ratio=7.72, p=0.021) and higher pulse rate (hazards ratio=1.08, p=0.018) were associated with statistically significant greater recurrence risk. ConclusionsDiabetes mellitus and higher pulse rate on admission are associated with greater recurrence risk of acute appendicitis managed non-operatively. No CT findings were associated with greater risk. Clinicians should therefore consider diabetes mellitus and pulse rate when making decisions on appendicitis management, during the COVID-19 pandemic and beyond.

Background: Invasive procedures are a core aspect of pulmonary and critical care practice. Procedures performed in the intensive care unit can be divided into high-risk, low-volume (HRLV) procedures and low-risk, high-volume (LRHV) procedures. HRLV procedures include cricothyroidotomy, pericardiocentesis, Blakemore tube placement, and bronchial blocker placement. LRHV procedures include arterial line placement, central venous catheter placement, thoracentesis, and flexible bronchoscopy. Despite the frequency and importance of procedures in critical care medicine, little is known about the similarities and differences in procedural training between different Pulmonary and Critical Care Medicine (PCCM) and Critical Care Medicine (CCM) training programs. Furthermore, differences in procedural training practices for HRLV and LRHV procedures have not previously been described. Objective: To assess procedural training practices in PCCM and CCM fellowship programs in the United States, and compare differences in training between HRLV and LRHV procedures. Methods: A novel survey instrument was developed and disseminated to PCCM and CCM program directors and associate program directors at PCCM and CCM fellowship programs in the United States to assess procedural teaching practices for HRLV and LRHV procedures. Results: The survey was sent to 221 fellowship programs, 168 PCCM and 34 CCM, with 70 unique respondents (31.7% response rate). Of the procedural educational strategies assessed, each strategy was used significantly more frequently for LRHV versus HRLV procedures. The majority of respondents (51.1%) report having no dedicated training for HRLV procedures versus 6.9% reporting no dedicated training for any LRHV procedure (P