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Aim: This study aimed to examine the transition process of paediatric rheumatology patients from the Monash Children's Hospital (MCH) in Melbourne in order to identify areas that could be improved., Methods: Retrospective review of clinical data from the rheumatology database of paediatric rheumatology patients eligible for transition between January 2015 and September 2020., Results: One hundred and sixty-five patients were included; 57 patients were transitioned. Of patients transitioned to an adult service, 38 (88%) were on medication and 14 (33%) had active disease. All patients transitioned to the general practitioner (GP) had inactive disease off medication. Juvenile idiopathic arthritis (JIA) (non-systemic) was the most common diagnosis in patients transitioned. The mean age at which transition was first discussed was 18.0 years; the first referral was made at a mean of 18.3 years. The mean age at the first adult appointment was 18.5 years. Thirty-nine (91%) patients had a referral completed and 8 (19%) had a transfer letter. Thirteen (93%) patients transferred to the GP had a transfer letter. Transfer documents to an adult public rheumatology service rated 4.3 for quality, compared to 5.5 to the GP. Transfer of care was confirmed in 40 (93%) patients transitioned to an adult service; however, correspondence was available for only 3 (7%)., Conclusion: Although the transition process at MCH was adequate, it could be improved through earlier discussion of the process and improved referrals and documentation. A readiness-to-transfer checklist and a young adult clinic have the potential to improve the process of transition to adult rheumatology care., (© 2024 Paediatrics and Child Health Division (The Royal Australasian College of Physicians).)

Quantitative Systems Pharmacology (QSP) modeling is increasingly applied in the pharmaceutical industry to influence decision making across a wide range of stages from early discovery to clinical development to post-marketing activities. Development of standards for how these models are constructed, assessed, and communicated is of active interest to the modeling community and regulators but is complicated by the wide variability in the structures and intended uses of the underlying models and the diverse expertise of QSP modelers. With this in mind, the IQ Consortium conducted a survey across the pharmaceutical/biotech industry to understand current practices for QSP modeling. This article presents the survey results and provides insights into current practices and methods used by QSP practitioners based on model type and the intended use at various stages of drug development. The survey also highlights key areas for future development including better integration with statistical methods, standardization of approaches towards virtual populations, and increased use of QSP models for late-stage clinical development and regulatory submissions., Competing Interests: Declarations Competing interests The authors declare no competing interests. Conflict of interest The authors declare no competing interests., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Men who have sex with men (MSM) living with HIV tend to experience a range of mental health issues, in particular generalised anxiety disorder (GAD), often caused and maintained by psychosocial variables including HIV stigma, discrimination, self-esteem issues, substance abuse and loneliness. This is particularly problematic in countries like Nigeria where same sex activity is illegal and can result in up to 14 years imprisonment. An important psychological variable that may contribute to the experience of GAD are metacognitive beliefs. Participants ( N  = 311) completed measures to examine the relationship between these variables. Results indicated that metacognition was associated with, and significantly predicted, GAD in this population. Moderation analysis showed that the effect of HIV stigma on GAD was explained by the proposed interaction with metacognition. Findings suggest that metacognition may be an important variable in explaining GAD symptoms in MSM living with HIV in Nigeria., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Syncope is a frequent reason for hospitalization from the emergency department (ED), but the benefit of hospitalization is unclear. This systematic review and meta-analysis (SRMA) aims to cohere and synthesize the best current evidence regarding the potential benefit of hospitalization for ED syncope patients for developing an evidence-based ED syncope management guideline., Methods: We conducted a SRMA according to the patient-intervention-control-outcome (PICO) framework: In patients 16 years of age or older who present to the ED with syncope (population), does hospitalization (intervention) or direct ED discharge (comparison) improve short-term outcomes (outcome)? The primary outcome was a composite of all adverse events as defined by individual studies, up to 30 days. Two reviewers independently assessed articles for inclusion and methodological quality. We measured heterogeneity among included studies with I-squared statistic and used GRADE criteria to assess the quality of evidence., Results: Our search strategy identified 2140 publications and included 18 publications (510,545 participants) in the analysis. All studies reported higher rates of adverse events in hospitalized patients (0.7%-43.8%) compared to discharged patients (0%-3.7%). Our meta-analysis detected considerable statistical heterogeneity. The GRADE assessment for all adverse events and all-cause mortality revealed risk ratios of >5 favoring ED discharge for both outcomes at a median follow-up of 30 days. However, point estimates are limited by serious risk of bias, inconsistency, imprecision, indirectness, and publication bias., Conclusions: Due to the uncertainty of the available evidence, this SRMA's findings do not support a recommendation for or against hospitalizing patients presenting to ED with syncope. However, discharging low-risk patients with syncope from the ED is associated with a low risk of short-term adverse events., (© 2025 Society for Academic Emergency Medicine.)

In drug development, quantitative systems pharmacology (QSP) models are becoming an increasingly important mathematical tool for understanding response variability and for generating predictions to inform development decisions. Virtual populations are essential for sampling uncertainty and potential variability in QSP model predictions, but many clinical efficacy endpoints can be difficult to capture with QSP models that typically rely on mechanistic biomarkers. In oncology, challenges are particularly significant when connecting tumor size with time-to-event endpoints like progression-free survival while also accounting for censoring due to consent withdrawal, loss in follow-up, or safety criteria. Here, we expand on our prior work and propose an extended virtual population selection algorithm that can jointly match tumor burden dynamics and progression-free survival times in the presence of censoring. We illustrate the core components of our algorithm through simulation and calibration of a signaling pathway model that was fitted to clinical data for a small molecule targeted inhibitor. This methodology provides an approach that can be tailored to other virtual population simulations aiming to match survival endpoints for solid-tumor clinical datasets., (© 2024 Pfizer, Inc. and Vantage Research Inc. CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objectives: To determine whether daily provision of a high protein, high energy meal for 12-weeks to under-nourished older adults living independently in the community can improve physical, physiological, and psychological outcomes., Design: A randomised crossover trial., Setting: Participant homes within a 15-mile radius to meal supplier; Dartmoor Community Kitchen Hub., Participants: Fifty-six community dwelling older adults (82 ± 7 years, 70% female) were randomised (stratified for baseline mini nutritional assessment (MNA) score and cohabiting or living alone) to receive 12-weeks of meal provision followed by 12-weeks no intervention (meals first group, n = 28), or, 12-weeks without intervention followed by 12-weeks of meal provision intervention (meals second group, n = 28)., Intervention: A daily high protein and high energy home-delivered meal for 12-weeks. Each meal contained >50% daily protein requirements (0.6 g kg -1 of the recommended 1.2 g kg -1 .day -1 , ∼42 g protein per meal) and >40% daily energy requirements (∼715 kcal)., Measurements: Physical, physiological and psychological health (including MNA score, body composition, hand grip strength, self-esteem, and depression) were evaluated in participants' homes before and after each 12-week period (baseline, 12-weeks, and 24-weeks). The effect of meal provision was assessed by t-test then effects were combined using meta-analysis. Retention of any meal provision effect after cessation of meal delivery was quantified as change from the end of the meal intervention versus 12-weeks follow-up via paired t-test., Results: The meal intervention significantly increased MNA score with a medium effect size (MNA: pooled Cohen's D = 0.74, p < 0.001). Energy and protein intake increased significantly during the control period where participants were asked to maintain their habitual diet in the meals second group (energy intake: increase = 252 kcal [95% CI 36-487 kcal], t(22) = 2.408, p = 0.025, protein intake: increase = 0.20 g kg -1 [95% CI 0.04-0.357 g kg -1 ], t(22) = 2.629, p = 0.015), which confounded the principle of a randomised crossover design analysis. When the control effect in those in the meals second group was removed from the analysis, the effect of the meal provision was much greater (meal provision significantly improved energy and protein intakes (311 kcal D = 0.52 (95% CI 0.22 to 0.82), p < 0.001; 0.24 g kg -1 D = 0.52 (0.19-0.81), p < 0.001, respectively), MNA score (2.6 points D = 1.14 (0.78-1.50), p < 0.001), and handgrip strength (1.5 kg D = 0.36 (0.06-0.66), p = 0.02), but did not change levels of depression or self-esteem). Twelve weeks after meal removal, the following % of the meal effect was retained: 68% for MNA score, 27% for negative mood score, 15% for daily energy intake, 6% for daily protein intake and 0% for handgrip strength., Conclusion: Provision of high protein, high energy meals to community dwelling older adults for 12-weeks improved nutritional status and handgrip strength, indicative of reduced frailty risk. Benefits were not retained upon withdrawal of the intervention, suggesting a need for sustained interventions in this cohort to meet nutritional needs. Home-delivered meals offer a popular, and scalable intervention for community dwelling older adults to prevent malnutrition, promote health and sustain high quality independent living thus reducing the burden of ageing and frailty on health and social care systems., (Crown Copyright © 2024. Published by Elsevier Masson SAS. All rights reserved.)

Bacterial social interactions play crucial roles in various ecological, medical, and biotechnological contexts. However, predicting these interactions from genome sequences is notoriously difficult. Here, we developed bioinformatic tools to predict whether secreted iron-scavenging siderophores stimulate or inhibit the growth of community members. Siderophores are chemically diverse and can be stimulatory or inhibitory depending on whether bacteria have or lack corresponding uptake receptors. We focused on 1928 representative Pseudomonas genomes and developed an experimentally validated coevolution algorithm to match encoded siderophore synthetases to corresponding receptor groups. We derived community-level iron interaction networks to show that siderophore-mediated interactions differ across habitats and lifestyles. Specifically, dense networks of siderophore sharing and competition were observed among environmental and nonpathogenic species, while small, fragmented networks occurred among human-associated and pathogenic species. Together, our sequence-to-ecology approach empowers the analyses of social interactions among thousands of bacterial strains and offers opportunities for targeted intervention to microbial communities.

Background: Nipple-sparing mastectomy (NSM) has become increasingly popular in recent years. However, the impact of prepectoral versus subpectoral implant reconstruction on nipple position, clinical outcomes, and patient-reported outcomes (PROs) after NSM remains unknown., Objective: We hypothesized that prepectoral reconstruction would lead to a more anatomic nipple position and improved clinical outcomes and PROs as compared to subpectoral reconstruction following NSM., Methods: Surgical characteristics, complications, and PROs in NSM patients with implant-based reconstruction from 2018 to 2021 were prospectively collected. Nipple displacement from baseline was analyzed using three-dimensional (3D) surface imaging., Results: 216 patients underwent 391 NSMs, separated into subpectoral (n = 96) and prepectoral (n = 120) cohorts. There were no differences in demographic and comorbidities between cohorts. Prepectoral showed a greater incidence of short-term return to OR (21% vs 10%, p=0.026). 3D analysis for 96 patients and 175 nipple positions were conducted. Compared to preoperative baseline, 3D imaging at 12 months postoperatively showed that the subpectoral cohort had greater straight-line distance between the nipples (23.1 mm vs 17.3 mm, p<0.001) and more lateral nipple displacement (9.2 mm vs 6.1 mm, p<0.001) as compared to the prepectoral cohort. Regression analysis found no relationship between incision pattern and nipple displacement. No postoperative differences were seen in PROs., Conclusions: Subpectoral NSM reconstruction was found to have more lateralized nipple displacement as compared to prepectoral patients, regardless of incision pattern used. Nipple displacement after NSM can play a significant role in postoperative aesthetic appearance and should be considered when deciding implant plane., (© The Author(s) 2025. Published by Oxford University Press on behalf of The Aesthetic Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Approximately 10% of patients with syncope have serious or life-threatening causes that may not be apparent during the initial emergency department (ED) assessment. Consequently, researchers have developed clinical decision rules (CDRs) to predict adverse outcomes and risk stratify ED syncope patients. This systematic review and meta-analysis (SRMA) aims to cohere and synthesize the best current evidence regarding the methodological quality and predictive accuracy of CDRs for developing an evidence-based ED syncope management guideline., Methods: We conducted a systematic literature search according to the patient-intervention-control-outcome question: In patients 16 years of age or older who present to the ED with syncope for whom no underlying serious/life-threatening condition was found during the index ED visit (population), are risk stratification tools (intervention), better than unstructured clinical judgment (i.e., usual care; comparison), for providing accurate prognosis and aiding disposition decision for outcomes within 30 days (outcome)? Two reviewers independently assessed articles for inclusion and methodological quality. We performed statistical analysis using Meta-DiSc. We used GRADEPro GDT software to determine the certainty of the evidence and create a summary of the findings (SoF) tables., Results: Of 2047 publications obtained through the search strategy, 31 comprising 13 CDRs met the inclusion criteria. There were 13 derivation studies (17,578 participants) and 24 validation studies (14,845 participants). Only three CDRs were validated in more than two studies. The San Francisco Syncope Rule (SFSR) was validated in 12 studies: positive likelihood ratio (LR+) 1.15-4.70 and negative likelihood ratio (LR-) 0.03-0.64. The Canadian Syncope Risk Score (CSRS) was validated in five studies: LR+ 1.15-2.58 and LR- 0.05-0.50. The Osservatorio Epidemiologico sulla Sincope nel Lazio (OESIL) risk score was validated in five studies: LR+ 1.16-3.32 and LR- 0.14-0.46., Conclusions: Most CDRs for ED adult syncope management have low-quality evidence for routine clinical practice use. Only three CDRs (SFSR, CSRS, OESIL) are validated by more than two studies, with significant overlap in operating characteristics., (© 2024 The Author(s). Academic Emergency Medicine published by Wiley Periodicals LLC on behalf of Society for Academic Emergency Medicine.)

Glaucoma is the leading cause of irreversible blindness with early detection and intervention critical to slowing disease progression. However, half of those affected are undiagnosed. This is largely due to the early stages of disease being asymptomatic; current population-based screening measures being unsupported; and a lack of current efficient prediction models. Research investigating polygenic risk scores (PRS) for glaucoma have shown predictive ability to identify individuals at higher risk. Potential clinical applications include identification of high-risk individuals, resulting in earlier diagnosis and treatment to prevent glaucoma blindness, and adjusted monitoring for low-risk individuals. However, the psychological impact of receiving glaucoma PRS is unknown. There is a critical need to evaluate risk information communication and assess the impact of receiving results, to support clinical implementation of glaucoma PRS testing. In this prospective study, 300 individuals from the GRADE (Genetic Risk Assessment of Degenerative Eye disease) study will be recruited to investigate the psychosocial impact of disclosing polygenic risk results for glaucoma. GRADE aimed to apply PRS testing on 1,000 unexamined individuals aged 50 years or older from the general population and examine a subset of these individuals to assess the clinical validity of PRS to detect glaucoma. In this study, individuals each from the bottom decile (10%), top decile (10%), and middle (45-55%) of the PRS distributions will be invited to receive research glaucoma PRS results. Participants who choose to receive their results will complete up to four questionnaires (prior to receiving their results, and subsequently two-weeks, six- and 12-months after receiving their result). The questionnaires will include health belief model measures and assess glaucoma anxiety, general anxiety and depression, test-related distress, decisional regret, and recall and understanding of results. This research will provide guidance for the implementation of polygenic risk testing into clinical practice and inform delivery strategies., Competing Interests: JEC is a co-inventor on a patent application for the use of genetic risk scores in predicting glaucoma risk and hold equity in Seonix Pty Ltd., (Copyright: © 2024 Maxwell et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Therapeutic nucleic acids (TNAs) including antisense oligonucleotides (ASOs) and small interfering RNA (siRNA) have emerged as promising treatment strategies for a wide variety of diseases, offering the potential to modulate gene expression with a high degree of specificity. These small, synthetic nucleic acid-like molecules provide unique advantages over traditional pharmacological agents, including the ability to target previously "undruggable" genes. Despite this promise, several biological barriers severely limit their clinical efficacy. Upon administration, TNAs primarily enter cells through endocytosis, becoming trapped inside membrane-bound vesicles known as endosomes. Studies estimate that only 1-2% of TNAs successfully escape endosomal compartments to reach the cytosol, and in some cases the nucleus, where they bind target mRNA and exert their therapeutic effect. Endosomal entrapment and inefficient nuclear localization are therefore critical bottlenecks in the therapeutic application of TNAs. This review explores the current understanding of TNA endosomal escape and nuclear transport along with strategies aimed at overcoming these challenges, including the use of endosomal escape agents, peptide-TNA conjugates, non-viral delivery vehicles, and nuclear localization signals. By improving both endosomal escape and nuclear localization, significant advances in TNA-based therapeutics can be realized, ultimately expanding their clinical utility.

Study Objective: We performed a systematic review and Bayesian network meta-analysis to determine which pharmacologic therapies are relatively more effective and safer for migraine in adult patients who present to the emergency department (ED)., Methods: We searched MEDLINE, Embase, and Web of Science from inception to February 9, 2024. Eligible studies were randomized controlled trials that enrolled adult participants presenting to ED with migraine and compared one pharmacologic therapy to another or placebo. Outcomes were as follows: 1) adequate pain relief at 2 hours, 2) change in pain intensity at 1 hour, 3) need for rescue drug at 2 hours, and 4) significant adverse reaction. We extracted data according to PRISMA-network meta-analysis and appraised trials using Cochrane RoB 2. For dichotomous outcomes, we performed Bayesian network meta-analysis to calculate odds ratios with 95% credible intervals; for continuous outcomes, we performed frequentist network meta-analysis to calculate mean differences with 95% confidence intervals. We assessed confidence using Confidence in Network Meta-analysis. We used Surface under the cumulative ranking curve (SUCRA) to rank agents., Results: Chlorpromazine intravenous (IV)/intramuscular (IM) (SUCRA=87.3%) was most likely to be superior for "adequate pain relief at 2 hours" (24 trials; n=2,361); metoclopramide IV-ibuprofen IV (SUCRA=94.6%) was most likely to be superior for "need for rescue drug" (not needing rescue drug) at 2 hours (27 trials; n=2,942); dexamethasone IV (SUCRA=79.5%) was most likely to be superior for "significant adverse reaction" (not causing adverse reaction) (22 trials; n=2,450). The network for change in pain intensity demonstrated statistically significant incoherence at the overall level. Confidence in network meta-analysis estimates (certainty of evidence) varied and was mostly "low" or "very low," limiting the validity of the probabilistic analyses., Conclusions: According to Bayesian network meta-analysis, ibuprofen IV is definitely among the least effective for adequate pain relief; chlorpromazine IV/IM is definitely among the most effective; valproate IV is definitely among the least effective, and ketorolac IV/IM is possibly among the least effective as single agents. The relative safety of the pharmacologic therapies cannot be determined with sufficient certainty., (Copyright © 2024 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

Restless legs syndrome (RLS) is a neurological disorder that can have a profound effect on sleep and quality of life. Idiopathic RLS is associated with brain iron insufficiency despite normal peripheral iron stores. There is, however, a five- to six-fold increase in prevalence of RLS in patients with iron deficiency anemia (IDA). Several open-label trials have demonstrated symptomatic improvement in RLS following treatment of IDA using oral or intravenous iron supplementation. To date, there have been no randomized double-blind controlled trials of intravenous iron compared with oral iron for the treatment of RLS patients with IDA. In the current study, oral ferrous sulfate and ferumoxytol were compared for efficacy and speed of response for treatment of RLS occurring in patients with IDA. The planned recruitment for this study was 70 patients with RLS and IDA, to be randomly assigned 1:1 to oral or intravenous iron, using double-blind, double-dummy procedures. At Week 6, the primary outcomes of Clinical Global Impression-Improvement score and change from baseline in the International Restless Legs Syndrome Study Group rating scale score were assessed. Due to challenges, performing the clinical trial during the COVID-19 pandemic, final-week data were found missing for 30 patients. As a result, in order to maintain the prespecified statistical analysis, an additional 30 patients were recruited. Both IV and oral iron were associated with a marked improvement in RLS symptoms, with no statistically significant difference between treatment groups. No serious adverse events were observed in either treatment group., (© 2024 Wiley Periodicals LLC.)

Rationale: Accelerated decline in lung function contributes to the development of chronic respiratory disease. Despite evidence for a genetic component, few genetic associations with lung function decline have been identified., Objectives: To evaluate genome-wide associations and putative downstream functionality of genetic variants with lung function decline in diverse general population cohorts., Methods: We conducted genome-wide association study (GWAS) analyses of decline in the forced expiratory volume in the first second (FEV 1 ), forced vital capacity (FVC), and their ratio (FEV 1 /FVC) in participants across six cohorts in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium and the UK Biobank. Genotypes were imputed to TOPMed (CHARGE cohorts) or Haplotype Reference Consortium (HRC) (UK Biobank) reference panels, and GWAS analyses used generalized estimating equation models with robust standard error. Models were stratified by cohort, ancestry, and sex, and adjusted for important lung function confounders and genotype principal components. Results were combined in cross-ancestry and ancestry-specific meta-analyses. Selected top variants were tested for replication in two independent COPD-enriched cohorts., Measurements and Main Results: Our discovery analyses included 52,056 self-reported White (N=44,988), Black (N=5,788), Hispanic (N=550), and Chinese American (N=730) participants with a mean of 2.3 spirometry measurements and 8.6 years of follow-up. Functional mapping of GWAS meta-analysis results identified 361 distinct genome-wide significant (p<5E-08) variants in one or more of the FEV 1 , FVC, and FEV 1 /FVC decline phenotypes, which overlapped with previously reported genetic signals for several related pulmonary traits. Of these, 8 variants, or 20.5% of the variant set available for replication testing, were nominally associated (p<0.05) with at least one decline phenotype in COPD-enriched cohorts (White [N=4,778] and Black [N=1,118]). Using the GWAS results, gene-level analysis implicated 38 genes, including eight ( XIRP2 , GRIN2D , SATB1 , MARCHF4 , SIPA1L2 , ANO5 , H2BC10 , and FAF2 ) with consistent associations across ancestries or decline phenotypes. Annotation class analysis revealed significant enrichment of several regulatory processes for corticosteroid biosynthesis and metabolism. Drug repurposing analysis identified 43 approved compounds targeting eight of the implicated 38 genes., Conclusions: Our multi-ancestry GWAS meta-analyses identified numerous genetic loci associated with lung function decline. These findings contribute knowledge to the genetic architecture of lung function decline, provide evidence for a role of endogenous corticosteroids in the etiology of lung function decline, and identify drug targets that merit further study for potential repurposing to slow lung function decline and treat lung disease., Competing Interests: COMPETING INTERESTS BMP serves on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. No other others have competing interests to declare.

Background: Warmblood horses are a popular breed around the world for equestrian sports. Previous studies have investigated ocular findings in other breeds of horses; however, no studies exist for the Warmblood breed., Objectives: To determine the prevalence of ocular abnormalities in a convenience sample of Warmblood horses in South Africa and to determine if the prevalence of lens and chorioretinal lesions increase with age., Study Design: Descriptive, observational study., Methods: Warmblood horses underwent a full ophthalmic examination which included a Schirmer tear test (STT), tonometry, fluorescein dye testing, slit lamp biomicroscopy and indirect ophthalmoscopy. Age was categorised into three groups namely <8 years old, 8-13 years old and 14+ years old for statistical analysis. Prevalence of lens and chorioretinal lesions were compared between age categories., Results: One hundred and four horses (208 eyes) were examined. The age range was 5 months to 30 years (mean 11 years, standard deviation [SD] 6 years). Ocular pathology was noted in 125 eyes (60.1%) and 79 horses (76%). The highest number of lesions were noted in the choroid and retina, iris and lens. Chorioretinal lesions were seen in 100 eyes (48.1%) and in 65 horses (62.5%). Iridial lesions were seen in 19 eyes (9.1%) and 12 horses (11.5%). Cataracts were seen in 19 eyes (9.1%) and in 13 horses (12.5%). The presence of total chorioretinal lesions (eye level [p = 0.002]; horse level [p = 0.004]), focal chorioretinal lesions (eye level [p = 0.004]; horse level [p = 0.008]) and cataract (eye [p = 0.03]; horse level [p = 0.02]) were all shown to statistically increase with age., Main Limitations: A small sample size and limited geographic area., Conclusions: There was a high prevalence of ocular pathology in this population of Warmblood horses in South Africa. This reiterates the importance of an ocular examination as a part of routine health checks, as well as during prepurchase examinations., (© 2024 The Author(s). Equine Veterinary Journal published by John Wiley & Sons Ltd on behalf of EVJ Ltd.)

Liver disease is a major, and increasing, cause of death in the UK. The UK Chronic Liver Failure network (UK-CLIF) was developed as a multi-stakeholder network with the aim to advance cirrhosis research, with emphasis on geographical areas of high disease prevalence or limited research activity. The process involved network development through dissemination and snowball sampling techniques, with monitoring of network development and connections between participants, developed over two online meetings. Network membership included representatives from patients, carers, clinicians, researchers, R&D professionals, industry representatives, and the third sector. Subsequently, two facilitated in-person workshops were conducted with network participants. World Café methodology and participant dot voting was used to develop areas of priority and consensus in: (i) research infrastructure for cirrhosis clinical trials, (ii) clinical factors affecting research delivery, and (iii) research priorities for future trials. Thematic analysis demonstrated that the need for patient-centric trial materials, a lack of resource for clinicians to participate in research, and variability in the standard of inpatient care for cirrhosis, were barriers for cirrhosis clinical trials. Future activities for UK-CLIF include participation in a process of quality standard setting for inpatient care for cirrhosis, and coordination of a James Lind Alliance Priority Setting Partnership to develop research questions for liver cirrhosis., Competing Interests: Competing interests: RA is National Specialist Advisor and Chair of the Clinical Reference Group for Hepatobiliary & Pancreas for NHS England. RJ is founder of Yaqrit Ltd. and co-founder of Hepyx Ltd. and Cyberliver Ltd. GM is co-founder of Hepyx Ltd., (Copyright: © 2024 Crisp H et al.)

We investigated the mechanism of action of an arylsulfonamide with whole-cell activity against Mycobacterium tuberculosis . We newly synthesized the molecule and confirmed it had activity against both extracellular and intracellular bacilli. The molecule had some activity against HepG2 cells but maintained some selectivity. Bacterial cytological profiling suggested that the mechanism of action was via disruption of cell wall synthesis, with similarities to an inhibitor of the mycolic acid exporter MmpL3. The compound induced expression from the IniB promoter and caused a boost in ATP production but did not induce reactive oxygen species. A mutation in MmpL3 (S591I) led to low-level resistance. Taken together, these data confirm the molecule targets cell wall biosynthesis with MmpL3 as the most probable target., Competing Interests: The authors declare no conflict of interest.

Background: Livestock markets are critical intermediaries in the movement of cattle and sheep between herds and to abattoirs. Disease prevention strategies promoting Cleansing & Disinfection (C&D) of vehicles moving animals from markets are in place in Scotland to reduce the risk of widespread transmission of pathogens within the livestock industry. However, little is known about how market users implement C&D on their vehicles and how these may differ between sectors of the industry., Methods: An online questionnaire was completed by 72 Scottish market users to investigate C&D practices on livestock transport vehicles. Respondents were grouped based on their farming activities and biosecurity practices were compared between commercial and non-commercial users., Results: The results showed a lower-than-expected use of brush or disinfectant and a shorter-than-expected time spent on C&D. Particularly, 43.6 % of respondents spent less than 30 min to C&D their vehicle, with no significant differences between respondents from commercial and non-commercial sectors (P = 0.75). Overall, we found little differences in C&D practices and level of training between sectors, highlighting the industrywide deficit in biosecurity knowledge., Conclusions: These results highlight a need to improve the messaging and awareness on good C&D practices on transport vehicles. Regular training on C&D practices is recommended, particularly for commercial livestock transport., Competing Interests: Declaration of competing interest The authors of this research paper have no financial or personal interests that could have influenced this paper., (Copyright © 2024. Published by Elsevier Ltd.)

BackgroundNon-university hospitals are the major provider of inpatient care in Germany, serving 89% of acute care hospital beds. Although surveillance data on antimicrobial use in hospitals are widely available, data on prescription quality are rare.AimWe aimed to provide an in-depth analysis of antimicrobial prescribing patterns and quality in southwest German non-university hospitals.MethodsDuring 2021, we performed three point prevalence surveys (PPS) in 10 non-university hospitals, representing ca 10% of hospital beds in the federal state of Baden-Württemberg (11 million inhabitants). Demographic and clinical information were collected. We assessed the overall performance of 14 validated process quality indicators (QI) covering infection diagnostics, antimicrobial therapy and documentation.ResultsOf 8,560 patients analysed, 2,861 (33%) received at least one antimicrobial. Most (2,789, 80%) antimicrobial prescriptions were for therapeutic indications. Most frequently prescribed agents were beta-lactam/beta-lactamase inhibitors (1,120, 40%) in therapeutic and cefuroxime (269, 37%) in prophylactic indications. According to the World Health Organization's Access, Watch, Reserve classification, the Access-to-Watch ratio was 0.73. Overall adherence to QIs was low and varied substantially (27-93%), with documentation, possible streamlining and switching to oral therapy exhibiting the lowest fulfilment rates (< 50%).ConclusionThe results indicate a need to improve antimicrobial prescribing quality in non-university hospitals. The high prevalence of antimicrobial use in our setting underlines the demand for sustainable antimicrobial stewardship programmes in this sector. Our QI-based PPS approach can be used to identify key targets for future antimicrobial stewardship interventions. The results indicate a need for further legislation on antimicrobial stewardship.

Context: In kidney therapy (KT) decisions, goal-concordant decision-making is recognized to be important, yet alignment with patients' goals during dialysis initiation is not always achieved., Objectives: To explore older patients' and caregivers' hopes, goals, and fears related to KT and communication of these elements with members of their health care team., Methods: The study included patients aged ≥75 years with an estimated glomerular filtration rate ≤25 mL/min/1.73 m2 and their caregivers enrolled in a palliative care intervention for KT decision-making. Patients and caregivers were asked open-ended questions about their hopes, goals, and fears related to KT decisions. A survey assessed if patients shared their goals with members of their health care team. Qualitative data underwent content analysis, supplemented by demographic descriptive statistics., Results: The mean age of patients (n = 26) was 82.7 (±5.7) years, and caregivers (n = 15) had a mean age of 66.4 (±13.7) years. Among the participants, 13 patients and 11 caregivers were women, and 20 patients and 12 caregivers were White. Four themes emerged: (1) Maintaining things as good as they are by avoiding dialysis-related burdens; (2) seeking longevity while avoiding dialysis; (3) avoiding pain, symptoms, and body disfigurement; and (4) deferring decision-making. Patients rarely had shared their goals with the key members of their health care team., Conclusion: Patients and caregivers prioritize maintaining quality of life, deferring decision-making regarding dialysis, and avoiding dialysis-related burdens. These goals are often unshared with their family and health care teams. Given our aging population, urgent action is needed to educate clinicians to actively explore and engage with patient goals in KT decision-making., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background:  Experiential learning through simulation allows students to apply didactic knowledge to real-world situations. Tabletop simulation allows for the exploration of a variety of topics, including cybersecurity in health care. Due to its low frequency, yet high-risk nature, simulation is a perfect educational modality to practice responding to a cybersecurity attack. As such, the authors designed and executed a tabletop cybersecurity simulation consisting of a prebriefing, four rounds of injects detailing potential cybersecurity breaches that students must address, and structured debriefings that included input from cybersecurity content experts. This simulation was performed in 2018, 2019, 2022, and 2023, during graduate Health Informatics (HI) students' residential visits., Objective:  The simulation allowed opportunities for HI students to apply knowledge of cybersecurity principles to an unfolding tabletop simulation containing injects of scenarios they may encounter in the real world., Methods:  Survey data were used to assess the students' perceptions of the simulation. Topics assessed included overall satisfaction, teamwork and communication, and length of the event. Additionally, in 2022 and 2023, data were collected on psychological safety and whether to include them in future HI residential visits., Results:  Eighty-eight graduate HI students took part in the cybersecurity simulation over four annual residential visits. Most students were satisfied with the event, found it valuable, and could see it impacting their future practice as informaticists. Additionally, students indicated high levels of psychological safety. Multiple students requested that additional simulations be incorporated into the curriculum., Conclusion:  A tabletop cybersecurity simulation was utilized to allow HI students the ability to apply knowledge related to cybersecurity breaches to real-world examples. The simulation's best practices of prebriefing, psychological safety, and structured debriefing with expert feedback were emphasized in the simulation's design and implementation. Students found the simulation valuable and worth including in the curriculum., Competing Interests: None declared., (Thieme. All rights reserved.)

Undesired coupling to the surrounding environment destroys long-range correlations in quantum processors and hinders coherent evolution in the nominally available computational space. This noise is an outstanding challenge when leveraging the computation power of near-term quantum processors 1 . It has been shown that benchmarking random circuit sampling with cross-entropy benchmarking can provide an estimate of the effective size of the Hilbert space coherently available 2-8 . Nevertheless, quantum algorithms' outputs can be trivialized by noise, making them susceptible to classical computation spoofing. Here, by implementing an algorithm for random circuit sampling, we demonstrate experimentally that two phase transitions are observable with cross-entropy benchmarking, which we explain theoretically with a statistical model. The first is a dynamical transition as a function of the number of cycles and is the continuation of the anti-concentration point in the noiseless case. The second is a quantum phase transition controlled by the error per cycle; to identify it analytically and experimentally, we create a weak-link model, which allows us to vary the strength of the noise versus coherent evolution. Furthermore, by presenting a random circuit sampling experiment in the weak-noise phase with 67 qubits at 32 cycles, we demonstrate that the computational cost of our experiment is beyond the capabilities of existing classical supercomputers. Our experimental and theoretical work establishes the existence of transitions to a stable, computationally complex phase that is reachable with current quantum processors., (© 2024. The Author(s).)

Objective:  This proof-of-concept study assessed how confidently an artificial intelligence (AI) model can determine the sex of a fetus from an ultrasound image., Study Design:  Analysis was performed using 19,212 ultrasound image slices from a high-volume fetal sex determination practice. This dataset was split into a training set (11,769) and test set (7,443). A computer vision model was trained using a transfer learning approach with EfficientNetB4 architecture as base. The performance of the computer vision model was evaluated on the hold out test set. Accuracy, Cohen's Kappa and Multiclass Receiver Operating Characteristic area under the curve (AUC) were used to evaluate the performance of the model., Results:  The AI model achieved an Accuracy of 88.27% on the holdout test set and a Cohen's Kappa score 0.843. The ROC AUC score for Male was calculated to be 0.896, for Female a score of 0.897, for Unable to Assess a score of 0.916, and for Text Added a score of 0.981 was achieved., Conclusion:  This novel AI model proved to have a high rate of fetal sex capture that could be of significant use in areas where ultrasound expertise is not readily available., Key Points: · This is the first proof-of-concept AI model to determine fetal sex.. · This study adds to the growing research in ultrasound AI.. · Our findings demonstrate AI integration into obstetric care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Background: To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published., Methods: Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics., Results: Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis., Conclusion: Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years., (© 2024 The Authors. International Journal of Rheumatic Diseases published by Asia Pacific League of Associations for Rheumatology and John Wiley & Sons Australia, Ltd.)

Background: Dialysis is often initiated in the United States without exploring patients' preferred decision-making style, and conservative kidney management (CKM) is infrequently presented. To improve kidney therapy (KT) decision-making, research on nephrologists' comfort with various decision-making styles, attitudes towards CKM, and reports of patients' lived experiences with KT decision-making is needed., Methods: We surveyed 28 nephrologists and 58 of their patients aged ≥75 years. The nephrologist survey was designed to gauge their comfort levels with decision-making styles and attitudes towards CKM. The patient survey assessed experiences in making KT decisions., Results: The average age of nephrologists was 43 years, and that of patients was 82 years. Nephrologists rated themselves as comfortable with various decision styles: paternalistic (60.7%), shared decision-making (92.8%), and patient-driven decision-making (67.8%). Nearly 57% of nephrologists felt challenged or were neutral in determining CKM's suitability, and 39% reported difficulties in discussing CKM with patients or were neutral. Only 38 % of patients recalled discussing CKM with their nephrologists, and a minority reported discussing CKM-related topics such as life expectancy (24.7%), quality of life (QOL) (45.1%), and end-of-life care (17.5%)., Conclusions: Most nephrologists displayed comfort with various decision-making styles; however, many described difficulties in guiding patients toward CKM. In contrast, patients reported gaps in vital aspects of KT decision-making and CKM choices, such as discussions of life expectancy, QOL, and end-of-life care. Raising awareness of blind spots in decision-making skills and educating nephrologists in KT decision-making to include CKM and other person-centered aspects of care are needed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: Emergency department (ED)-initiated buprenorphine has proven efficacy, but many patients are reluctant to begin this treatment. This study evaluated SafetyNet, a program using a 2-person, recovery coach and paramedic (RCP) intervention postoverdose to reduce subsequent opioid overdose, engage patients in medications for opioid use disorder (MOUD), and reduce illicit drug use., Methods: We conducted a prospective nonrandomized study in individuals who experienced opioid overdoses, received naloxone, but subsequently declined buprenorphine initiation in the ED. Each participant was followed by an RCP team that performed a brief negotiation interview (BNI) to motivate engagement in treatment, peer-recovery coaching to encourage recovery-related activities, and health education around medical concerns by trained paramedics. Participants were followed-up at 30 and 180 days. The primary hypothesized outcome was reduction in overdose events; the secondary hypothesized outcomes were engagement in MOUD and reduction in opioid positive urine tests., Results: Eighty-one patients were enrolled and received BNIs; 45 (56%; 95% CI: 44-67) had at least 1 follow-up encounter. Twenty participants (25%; 95% CI: 16-36) had at least 1 overdose during follow-up. Fifty-five participants (68%; 95% CI: 57-78) were confirmed to have engaged in some form of medication treatment. Differences in subsequent overdose events ( P  = .95), engagement in MOUD ( P  = .49), and rates of opioid-positive urine toxicology rates within 30 days ( P  = .44) and between 31 and 180 days ( P  = .46) were not significantly different when comparing those who did and did not follow-up., Conclusion: There were no differences in rates of subsequent overdose, MOUD engagement, or positive urine toxicology screens in our intervention. However, 68% of participants engaged in outpatient MOUD, a treatment associated with fewer overdose events, particularly fatal ones. Substantial limitations occurred due to the COVID pandemic, and sample size estimates were not met. Further research is needed to investigate potential benefits of the SafetyNet program., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Pantalon is cofounder of Center for Progressive Recovery, LLC, a digital behavioral health and training company focused on recovery coaching.

Background: Incidental findings are unrelated to a patient's complaint, found on diagnostic imaging, such as point-of-care ultrasound (POCUS). Incidental findings represent potential harms to patients and may lead to increased patient anxiety and health care costs related to downstream testing and surveillance., Study Objectives: In this study, we aimed to calculate the rate of incidental renal cysts found by POCUS. Further, we hoped to describe how emergency physicians relay the findings to patients. Lastly, we hoped to examine if patients suffered harms in the 12 months following identification of an incidental renal cyst., Methods: From our single-center, academic emergency department (ED), we reviewed renal POCUS images from 1000 consecutive adult ED patients to determine if there was a renal cyst. Next, we performed manual chart review to determine if patients were informed of the incidental renal cyst or suffered any patient harms., Results: We found the prevalence of renal cysts to be 6.5% (95% confidence interval: 4.9%-8.4%). Those with cysts were more likely to be older compared to those without (63 ± 14 vs. 49 ± 15 years of age). Only 8% of patients had evidence that they were informed of their incidental renal cyst. No patients received a biopsy or were diagnosed with renal cell carcinoma or polycystic kidney disease., Conclusion: Incidental renal cysts are common and are more likely to be found in older adults. In our study, physicians infrequently informed patients of their incidental finding., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Morel-Lavallée lesion is an internal degloving injury seen after a traumatic force. These lesions are frequently missed on initial presentation, leading to a delay in diagnosis and increased morbidity. We present a case of a 52-year-old male who suffered an injury to his right thigh and was ultimately diagnosed with a Morel-Lavallée lesion after the third emergency department visit. Point-of-care ultrasound (POCUS) assisted with making the diagnosis and expediting proper care., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Androgen deprivation therapy (ADT) is a front-line treatment for prostate cancer. In some men, their tumors can become refractory leading to the development of castration-resistant prostate cancer (CRPC). This causes tumors to regrow and metastasize, despite ongoing treatment, and impacts negatively on patient survival. ADT is known to stimulate the accumulation of immunosuppressive cells like protumoral tumor-associated macrophages (TAMs), myeloid-derived suppressor cells and regulatory T cells in prostate tumors, as well as hypofunctional T cells. Protumoral TAMs have been shown to accumulate around tumor blood vessels during chemotherapy and radiotherapy in other forms of cancer, where they drive tumor relapse. Our aim was to see whether such perivascular (PV) TAMs also accumulate in ADT-treated prostate tumors prior to CRPC, and, if so, whether selectively inducing them to express a potent immunostimulant, interferon beta (IFNβ), would stimulate antitumor immunity and delay CRPC., Methods: We used multiplex immunofluorescence to assess the effects of ADT on the distribution and activation status of TAMs, CD8+T cells, CD4+T cells and NK cells in mouse and/or human prostate tumors. We then used antibody-coated, lipid nanoparticles (LNPs) to selectively target a STING agonist, 2'3'-cGAMP (cGAMP), to PV TAMs in mouse prostate tumors during ADT., Results: TAMs accumulated at high density around blood vessels in response to ADT and expressed markers of a protumoral phenotype including folate receptor-beta (FR-β), MRC1 (CD206), CD169 and VISTA. Additionally, higher numbers of inactive (PD-1-) CD8+T cells and reduced numbers of active (CD69+) NK cells were present in these PV tumor areas. LNPs coated with an antibody to FR-β selectively delivered cGAMP to PV TAMs in ADT-treated tumors, where they activated STING and upregulated the expression of IFNβ. This resulted in a marked increase in the density of active CD8+T cells (along with CD4+T cells and NK cells) in PV tumor areas, and significantly delayed the onset of CRPC. Antibody depletion of CD8+T cells during LNP administration demonstrated the essential role of these cells in delay in CRPC induced by LNPs., Conclusion: Together, our data indicate that targeting a STING agonist to PV TAMs could be used to extend the treatment window for ADT in prostate cancer., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Robust delay induced oscillations, common in nature, are often modeled by delay-differential equations (DDEs). Motivated by the success of phase-amplitude reductions for ordinary differential equations with limit cycle oscillations, there is now a growing interest in the development of analogous approaches for DDEs to understand their response to external forcing. When combined with Floquet theory, the fundamental quantities for this reduction are phase and amplitude response functions. Here, we develop a framework for their construction that utilizes the method of harmonic balance.

Background: Textured implants have been linked to breast implant-associated anaplastic large-cell lymphoma (BIA-ALCL). Patients who undergo explantation have options for reconstruction, but data on safety and patient-reported outcomes (PROs) are limited. The purpose of this study was to classify complications and PROs in patients opting for surgical management of textured implants., Methods: Complication rates and BREAST-Q scores were compared between (1) asymptomatic patients who underwent conversion from textured to smooth implants ( n = 224), (2) symptomatic patients who underwent conversion from textured to smooth implants ( n = 83), (3) patients who underwent explantation without replacement ( n = 44), and (4) patients who underwent replacement with autologous reconstruction ( n = 33). Linear regression examined PROs controlling for clinical and surgical variables., Results: Overall complication rates in 384 patients (637 implants) differed across groups ( P = 0.034), with the highest rate (25%) in patients who underwent explantation without replacement. These patients were specifically more impacted by minor complications, notably seroma. Capsulectomy extent did not significantly impact complications. Asymptomatic and symptomatic smooth implant patients had improvements in Satisfaction with Breasts ( P < 0.05). Autologous reconstruction patients had significant improvements in Satisfaction with Breasts sustained after 3 months postoperatively ( P < 0.01) and Sexual Well-being sustained after 6-months postoperatively ( P < 0.05). Patients who underwent removal without replacement had lower Physical Well-being of the Chest scores at 1 year or more than the other groups., Conclusions: Replacement of textured implants with smooth implants or flaps is safe and is associated with improved satisfaction with breasts and quality of life. The degree of capsulectomy does not appear to impact the incidence of perioperative complications., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Purpose: To investigate bacterial contamination of indirect ophthalmoscopes and condensing lenses used in three UK veterinary referral centers, and the impact of an implemented cleaning protocol., Methods: Bacteriology samples from 10 indirect ophthalmoscopes and 10 condensing lenses were taken at each center (n = 30 T0), before initiating one of three cleaning frequencies (every 2 weeks/once weekly/daily) for 28 days. The most contaminated indirect ophthalmoscope and condensing lens from each center were re-sampled 30 min prior to (T1; n = 9) and 30 min after (T2; n = 9) the final clean. Sensitivity testing was completed using MIC., Results: Seventy-three isolates representing 15 different bacterial populations (genus/species) were cultured from 36 of 48 (75%) swabs tested. The most frequently cultured isolates were Staphylococcus spp. 30%, Micrococcus 22%, and Bacillus 14%. Pseudomonas aeruginosa, Pantoea, and Staphylococcus pseudintermedius demonstrated resistance to >50% of antibiotics against which they were tested. Eighty-three percent of T0 samples (54 isolates across 11 species, median 2 isolates/swab), all T1 samples (15 isolates across 8 species, median 2 isolates/swab), and 22% of T2 samples (4 isolates across 4 species, median 0 isolates/swab) were contaminated. Head contact points were most contaminated irrespective of time point. A T1 sample was 57 times more likely (95% CI: 2.4-1376) to have a positive culture than a T2 sample (p = .01)., Conclusions: Baseline contamination was high, representing a potential source of nosocomial infection in ophthalmic patients and handlers of diagnostic equipment. No center implemented a cleaning protocol prior to this study. Routine cleaning reduces bacterial contamination., (© 2023 American College of Veterinary Ophthalmologists.)

Background: This study aimed to determine the clinical impact of wound management technique on surgical site infection (SSI), hospital length of stay (LOS), and mortality in emergent colorectal surgery., Methods: A prospective observational study (2021-2023) of urgent or emergent colorectal surgery patients at 15 institutions was conducted. Pediatric patients and traumatic colorectal injuries were excluded. Patients were classified by wound closure technique: skin closed (SC), skin loosely closed (SLC), or skin open (SO). Primary outcomes were SSI, hospital LOS, and in-hospital mortality rates. Multivariable regression was used to assess the effect of wound closure on outcomes after controlling for demographics, patient characteristics, intensive care unit admission, vasopressor use, procedure details, and wound class. A priori power analysis indicated that 138 patients per group were required to detect a 10% difference in mortality rates., Results: In total, 557 patients were included (SC, n = 262; SLC, n = 124; SO, n = 171). Statistically significant differences in body mass index, race/ethnicity, American Society of Anesthesiologist scores, EBL, intensive care unit admission, vasopressor therapy, procedure details, and wound class were observed across groups. Overall, average LOS was 16.9 ± 16.4 days, and rates of in-hospital mortality and SSI were 7.9% and 18.5%, respectively, with the lowest rates observed in the SC group. After risk adjustment, SO was associated with increased risk of mortality (OR, 3.003; p = 0.028) in comparison with the SC group. Skin loosely closed was associated with increased risk of superficial SSI (OR, 3.439; p = 0.014), after risk adjustment., Conclusion: When compared with the SC group, the SO group was associated with mortality but comparable when considering all other outcomes, while the SLC was associated with increased superficial SSI. Complete skin closure may be a viable wound management technique in emergent colorectal surgery., Level of Evidence: Therapeutic/Care Management; Level III., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

We present a genome assembly from a culture of Marvania coccoides (CCAP 251/1B) (Chlorophyta; Trebouxiophyceae; Chlorellales; Chlorellaceae). The genome sequence is 22.3 megabases in span. Most of the assembly is scaffolded into 13 chromosomal pseudomolecules. The mitochondrial and plastid genome assemblies have lengths of 49.04 kilobases and 99.87 kilobases in length, respectively., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Allen R et al.)

Purpose: Currently, 1 in 5 college students struggle with suicidal ideation while 7% to 44% engage in nonsuicidal self-injury. Illinois has one of the highest teenage and college student suicide rates in the United States. This pilot study assessed suicide ideation and self-harm behaviors at a public Illinois university. This is the first study to use 5 standardized psychological instruments to investigate these 2 crises in freshmen college students who are all required to reside in dormitories. The main hypothesis was to determine if the independent effects of freshmen students' depression, Five-Factor Model, and Reasons for Living affected the dependent variables, self-harm behaviors and suicide ideation. Methods: Forty first-year college dormitory students completed the Beck Depression Inventory-II, Scale of Suicidal Ideation, Five-Factor Model, Inventory of Statements About Self-Injury, and Reasons for Living Scale in person. Results: Participants were 18 to 19 years old, predominantly female (65%), and non-White (62%). Forty percent reported self-harm behaviors and 19% reported suicidal ideation. The top reasons for contemplated suicide attempts included the inability to solve problems (33%) and attention/revenge (28%). Students experienced high levels of anxiety (55%), self-consciousness (43%), and depression (18%). Depression was associated with suicide ideation (β   = 0.05, P  = .006), while neuroticism and openness were associated with self-harm behaviors ( aOR  = 3.36, P  = .02, aOR  = 0.48, P  = .047, respectively). Ninety-five percent reported "responsibility to family" as a Reason for Living. Conclusions: Preliminary evidence necessitates an examination of self-harm and suicide ideation among all freshmen, investigating both risk and protective factors. In the future, a prevention intervention should be implemented campus-wide (and eventually nationwide) for all first-year dormitory students to enhance their mental well-being., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Background: Recent data suggest disparities in receipt of regional anesthesia prior to breast reconstruction. We aimed to understand factors associated with block receipt for mastectomy with immediate tissue expander (TE) reconstruction in a high-volume ambulatory surgery practice with standardized regional anesthesia pathways., Patients and Methods: Patients who underwent mastectomy with immediate TE reconstruction from 2017 to 2022 were included. All patients were considered eligible for and were offered preoperative nerve blocks as part of routine anesthesia care. Interpreters were used for non-English speaking patients. Patients who declined a block were compared with those who opted for the procedure., Results: Of 4213 patients who underwent mastectomy with immediate TE reconstruction, 91% accepted and 9% declined a nerve block. On univariate analyses, patients with the lowest rate of block refusal were white, non-Hispanic, English speakers, patients with commercial insurance, and patients undergoing bilateral reconstruction. The rate of block refusal went down from 12 in 2017 to 6% in 2022. Multivariable logistic regression demonstrated that older age (p = 0.011), Hispanic ethnicity (versus non-Hispanic; p = 0.049), Medicaid status (versus commercial insurance; p < 0.001), unilateral surgery (versus bilateral; p = 0.045), and reconstruction in earlier study years (versus 2022; 2017, p < 0.001; 2018, p < 0.001; 2019, p = 0.001; 2020, p = 0.006) were associated with block refusal., Conclusions: An established preoperative regional anesthesia program with blocks offered to all patients undergoing mastectomy with TE reconstruction can result in decreased racial disparities. However, continued differences in age, ethnicity, and insurance status justify future efforts to enhance preoperative educational efforts that address patient hesitancies in these subpopulations., (© 2024. Society of Surgical Oncology.)

Purpose: The available evidence to determine which antidysrhythmic drug is superior for pharmacologic cardioversion of recent-onset (onset within 48 h) atrial fibrillation (AF) is uncertain. We aimed to identify the safest and most effective agent for pharmacologic cardioversion of recent-onset AF in the emergency department., Methods: We searched MEDLINE, Embase, and Web of Science from inception to February 21, 2023 (PROSPERO: CRD42018083781). Eligible studies were randomized controlled trials that enrolled adult participants with AF ≤ 48 h, compared a guideline-recommended antidysrhythmic drug with another antidysrhythmic drug or a different formulation of the same drug or placebo and reported specific adverse events. The primary outcome was immediate, serious adverse event - cardiac arrest, sustained ventricular tachydysrhythmia, atrial flutter 1:1 atrioventricular conduction, hypotension, and bradycardia. Additional analyses included the outcomes of conversion to sinus rhythm within 4 h and 24 h. We extracted data according to PRISMA-NMA and appraised trials using Cochrane RoB 2. We performed Bayesian network meta-analysis (NMA) using a Markov Chain Monte Carlo method with random-effect model and vague prior distribution to calculate odds ratios with 95% credible intervals. We assessed confidence using CINeMA. We used surface under the cumulative ranking curve (SUCRA) to rank agent(s)., Results: The systematic review initially identified 5545 studies. Twenty-five studies met eligibility criteria, and 22 studies (n = 3082) provided data for NMA, which demonstrated that vernakalant (SUCRA = 70.9%) is most likely to be safest. Additional effectiveness NMA demonstrated that flecainide (SUCRA = 89.0%) is most likely to be superior for conversion within 4 h (27 studies; n = 2681), and ranolazine-amiodarone IV (SUCRA 93.7%) is most likely to be superior for conversion within 24 h (24 studies; n = 3213). Confidence in the NMA estimates is variable and limited mostly by within-study bias and imprecision., Conclusions: Among guideline-recommended antidysrhythmic drugs, the combination of digoxin IV and amiodarone IV is definitely among the least safe for cardioversion of recent onset AF; flecainide, vernakalant, ibutilide, propafenone, and amiodarone IV are definitely among the most effective for cardioversion within 4 h; flecainide is definitely among the most effective for cardioversion within 24 h. Further, randomized controlled trials with predetermined and strictly defined, hemodynamic adverse event outcomes are recommended., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

As massively parallel sequencing is implemented in forensic genetics, an understanding of sequence data must accompany these advancements, that is, accurate modeling of data for proper statistical analysis. Allelic drop-out, a common stochastic effect seen in genetic data, is often modeled in statistical analysis of STR results. This proof-of-concept study sequenced several serial dilutions of a standard sample ranging from 4 ng to 7.82 pg to evaluate allelic drop-out trends on a select panel of autosomal STRs using the ForenSeq™ DNA Signature Prep Kit, Primer Set A on the Illumina MiSeq FGx. Parameters assessed included locus, profile, and run specific information. A majority of the allelic drop-out occurred in DNA concentrations less than 31.25 pg. Statistical results indicated a need for locus-specific modeling based on STR descriptors, like simple versus compound repeat patterns. No correlation was seen between average read count of scored alleles and allelic drop-out at a locus. A statistical correlation was observed between the amount of allelic drop-out and the starting amount of DNA in a sample, average read count of a sample, and total read count generated on a flow cell. This study supports using common allelic drop-out factors used in fragment length analysis on sequenced STRs while including additional locus, sample, and run specific information. Results demonstrate multiple factors that can be considered when developing probability of allelic drop-out models for sequenced autosomal STRs including locus-specific analysis, total read count of a profile, and total read count sequenced on a flow cell., (© 2024 American Academy of Forensic Sciences.)

Background: The COVID-19 vaccine was initially offered to frontline health care workers (HCWs), due to the high risk of contracting COVID-19 through occupational exposure to patients. Low HCW vaccine uptake can impact overall community-level vaccine uptake. This study used the Diffusion of Innovation (DOI) Theory to understand factors related to COVID-19 vaccine uptake in HCWs., Methods: We surveyed Pennsylvanian HCWs (excluding Philadelphia) from August 2022 to February 2023. Survey questions inquired about demographics, COVID-19 vaccination status, reasons for receiving/declining the COVID-19 vaccine, and sources of information about the vaccine., Results: Participants (n = 3,490) were 85% female, 89% White, and 93% (n = 3,255) reported receiving at least one dose of a COVID-19 vaccine. HCWs were categorized into adopter categories of the DOI Theory: innovators (56%), early adopters (9%), early majority (11%), late majority (7%), and laggards (17%). The major reason that prompted participants to get the vaccine was to protect them against COVID-19 infection (78%), while the major reason for declining the vaccine was due to concern about possible side effects from the vaccine (78%)., Conclusions: We applied the DOI Theory to characterize adopters and identify factors related to COVID-19 vaccine uptake in HCWs. As updated COVID-19 vaccines are approved for the United States market, our findings may be used to improve vaccine education and communication among HCWs to support vaccine uptake., (Copyright © 2024 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Understanding universal aspects of quantum dynamics is an unresolved problem in statistical mechanics. In particular, the spin dynamics of the one-dimensional Heisenberg model were conjectured as to belong to the Kardar-Parisi-Zhang (KPZ) universality class based on the scaling of the infinite-temperature spin-spin correlation function. In a chain of 46 superconducting qubits, we studied the probability distribution of the magnetization transferred across the chain's center, [Formula: see text]. The first two moments of [Formula: see text] show superdiffusive behavior, a hallmark of KPZ universality. However, the third and fourth moments ruled out the KPZ conjecture and allow for evaluating other theories. Our results highlight the importance of studying higher moments in determining dynamic universality classes and provide insights into universal behavior in quantum systems.

Background: Prepectoral implant placement for postmastectomy breast reconstruction has increased in recent years. Benefits of prepectoral reconstruction may include lack of animation deformities and reduced postoperative pain, but its complication profile is currently unclear. This study aimed to examine the complication profile of prepectoral tissue expanders (TEs) to determine factors associated with TE loss., Methods: A retrospective review was performed to identify all patients who underwent immediate prepectoral TE reconstruction from January 2018 to June 2021. The decision to use the prepectoral technique was based on mastectomy skin quality and patient comorbidities. Patient demographics, comorbidities, and operative details were evaluated. Outcomes of interest included TE loss, seroma, hematoma, infection/cellulitis, mastectomy skin flap necrosis requiring revision, and TE exposure. Logistic regression analysis was performed to identify factors associated with TE loss., Results: The study identified 1225 TEs. The most frequent complications were seroma (8.7%, n = 106), infection/cellulitis (8.2%, n = 101), and TE loss (4.2%, n = 51). Factors associated with TE loss in the univariate analysis included ethnicity, history of smoking, body mass index, mastectomy weight, and neoadjuvant chemotherapy. In the multivariate regression analysis, only mastectomy weight had a positive association with TE loss (odds ratio, 1.001; p = 0.016)., Conclusion: Prepectoral two-stage breast reconstruction can be performed safely with an acceptable early complication profile. The study data suggest that increasing mastectomy weight is the most significant factor associated with TE loss. Further research examining the quality of the soft tissue envelope and assessing patient-reported outcomes would prove beneficial., (© 2024. Society of Surgical Oncology.)

Objective: We explore relationships between barriers and facilitators experienced by users to understand dynamic interactions in sociotechnical systems and improve a mobile phone-based augmented reality application that teaches users about the contents of a standardized pediatric code cart., Background: Understanding interactions between performance obstacles and facilitators can provide guidance to (re)designing sociotechnical systems to improve system outcomes. Clinicians should know about contents and organization of code carts, and an augmented reality mobile application may improve that knowledge but changes the sociotechnical system in which they learn. Prior work identified barriers and facilitators impacting the use of this application-participants described dimensions together, indicating interactions that are explored in the current study., Method: We conducted four focus groups (number of clinicians = 18) and two interviews with clinicians who used the application. We performed a secondary analysis of focus group data exploring interactions between previously identified barriers and facilitators to application use. We used epistemic network analysis to visualize these interactions., Results: Work system barriers interacted with barriers and facilitators interacted with facilitators to amplify cumulative negative or positive impact, respectively. Facilitators balanced barriers, mitigating negative impact. Facilitators also exacerbated barriers, worsening negative impact., Conclusion: Barriers and facilitators interact and can amplify, balance, and exacerbate each other-notably, positives are not always positive. To obtain desired outcomes, interactions must be further considered in sociotechnical system design, for example, the potential improvements to the application we identified.