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From early in the coronavirus disease 2019 (COVID‐19) pandemic, there was interest in using machine learning methods to predict COVID‐19 infection status based on vocal audio signals, for example, cough recordings. However, early studies had limitations in terms of data collection and of how the performances of the proposed predictive models were assessed. This article describes how these limitations have been overcome in a study carried out by the Turing‐RSS Health Data Laboratory and the UK Health Security Agency. As part of the study, the UK Health Security Agency collected a dataset of acoustic recordings, SARS‐CoV‐2 infection status and extensive study participant meta‐data. This allowed us to rigorously assess state‐of‐the‐art machine learning techniques to predict SARS‐CoV‐2 infection status based on vocal audio signals. The lessons learned from this project should inform future studies on statistical evaluation methods to assess the performance of machine learning techniques for public health tasks. [ABSTRACT FROM AUTHOR]

Objectives: Research in adults suggests that intrusive memories and intrusive thoughts (often referred to as intrusive cognitions) are common in members of the general population and are often seen in clinical disorders. However, little is known about the experience of intrusive cognitions in adolescents, particularly in adolescents with major depressive disorder (MDD) and post‐traumatic stress disorder (PTSD). The present study sought to gather fundamental data on these phenomena (i.e., frequency, characteristics and appraisals of intrusive cognitions) in adolescents with MDD and PTSD. Methods: Adolescents aged 11–18 with MDD (n = 11), PTSD (n = 13) and a non‐clinical control group (n = 25) completed structured interviews concerning their intrusive memories and thoughts. Results: Intrusive thoughts were common in all three groups but were particularly frequently experienced in the MDD group. Intrusive memories were expectedly very common in the PTSD group but also experienced by over half of the adolescents with MDD. Both clinical groups reported more negative emotions in response to their intrusive thoughts or memories and appraised these cognitions more negatively than the non‐clinical group. Conclusion: Intrusive memories and thoughts are common experiences in adolescents with MDD and PTSD. Emotions and appraisals relating to these cognitions may be targets for psychological intervention in this age group. However, small sample sizes limit the conclusions that can be drawn. Replication is needed with larger numbers of clinical participants. [ABSTRACT FROM AUTHOR]

This article discusses the progress being made in perinatal mental health research. It emphasizes the importance of addressing perinatal psychiatric and substance use disorders, as they can have negative effects on maternal functioning, obstetrical and neonatal outcomes, and child socioemotional regulation. The special issue highlights the interdisciplinary nature of perinatal psychiatry, which involves various specialties such as obstetrics, neonatology, pediatrics, psychiatry, psychology, epidemiology, and neuroscience. The studies in the issue cover topics such as the risks associated with perinatal psychiatric disorders, the effects of treatments, the role of Mother-Baby units, and the biological aspects of perinatal depression. The research aims to improve treatment strategies, identify risk factors and biomarkers, and understand the underlying pathophysiology of perinatal mental health disorders. [Extracted from the article]

Aim: To assess the association between problematic smartphone usage and anxiety and depression in adolescents. Methods: A cross‐sectional study in five schools in the UK were included. The primary outcome was moderate anxiety (GAD‐7 ≥10) symptoms and secondary outcomes were moderate depression symptoms (PHQ‐9 ≥10) and insomnia. Problematic smartphone usage was assessed using screentime and the Smartphone Addiction Scale. A multi‐level logistic regression was fitted and adjusted Odds Ratio (aOR) with 95% confidence intervals (95% CI) reported. A mediation analysis was conducted. Results: Of the five included schools, 657 adolescents aged 16–18 years were enrolled. The median age was 17.5 years (17–18 [IQR]) and 508 (77.3%) were female. Of these 188 (28.6%) exhibited moderate anxiety and 226 (34.4%) moderate depression symptoms. Almost two thirds (421, 64.1%) have tried to cut down their smartphone use and 81 (12.5%) wanted help to reduce use. Problematic smartphone use was associated with increased anxiety (aOR = 2.03, 95% CI 1.28–3.23); depression (aOR = 2.96, 95% CI 1.80–4.86); and insomnia (aOR = 1.64, 95% CI 1.08–2.50). Screentime was not associated with anxiety (β = 0.99, 95% CI 0.91–1.08); or depression (β = 0.98, 95% CI 0.89–1.07). Problematic smartphone use had a significant direct, indirect and total effect on both anxiety and depression. Conclusion: Problematic smartphone usage was associated with anxiety and depression, independent of screentime. Interventions are needed to reduce problematic use. [ABSTRACT FROM AUTHOR]

Background: Malondialdehyde–acetaldehyde (MAA) adducts lead to generation of anti‐MAA autoantibodies and have been independently identified in inflamed periodontal and rheumatoid arthritis (RA) tissues. This study evaluates serum samples from RA cases and osteoarthritis (OA) controls to quantify associations between periodontal clinical measures, alveolar bone loss (ABL), and anti‐Porphyromonas gingivalis, anti‐Prevotella intermedia, and anti‐Fusobacterium nucleatum antibody concentrations with anti‐MAA antibody concentrations. Methods: Participants (n = 284 RA cases, n = 330 OA controls) underwent periodontal clinical assessments and ABL measurements. Serum immunoglobulin (Ig) A, IgG, and IgM anti‐MAA and serum IgG antibacterial antibody concentrations were quantified by enzyme‐linked immunosorbent assay (ELISA). Analyses utilized simple linear regression and multivariable adjusted models. Results: No significant associations of periodontal clinical measures with serum anti‐MAA were found. Moderate (p = 0.038 and p = 0.036, respectively) and high ABL (p = 0.012 and p = 0.014, respectively) in RA cases (but not in OA) were positively associated with IgG and IgM anti‐MAA. Anti‐P. gingivalis and anti‐P. intermedia antibody concentrations were positively associated with IgA (p = 0.001 for both), IgG (p = 0.007 and p = 0.034, respectively), and IgM anti‐MAA antibody concentrations (p < 0.001 and p = 0.020, respectively), while anti‐F. nucleatum was positively associated with IgG anti‐MAA (p = 0.042), findings that were similar across groups. Conclusions: A positive association was demonstrated between ABL and serum IgG and IgM anti‐MAA antibody concentrations that was unique to RA and not observed in OA. Serum anti‐P. gingivalis, anti‐P. intermedia, and anti‐F. nucleatum antibody concentrations displayed significant associations with anti‐MAA antibody in both groups. These findings suggest MAA may play a role in the interrelationship between the periodontium and RA. [ABSTRACT FROM AUTHOR]

Objective: A comprehensive understanding of coping strategies of patients with advanced diseases can contribute to providing supportive care that meets patients' needs. However, insight into how coping of this population develops over time is lacking. We examined coping strategies of patients with advanced cancer over time and identified distinct trajectories and their predictors. Methods: Data from 675 patients of the control group from the ACTION cluster‐randomized trial were analyzed. Patients with lung or colorectal cancer from six European countries (Belgium, Denmark, Italy, the Netherlands, Slovenia and the United Kingdom) completed questionnaires at baseline, 12 and 20 weeks. Measures included Denial, Acceptance, and Problem‐focused coping (COPE, Brief COPE inventory; scores 4–16 per scale). We used linear mixed models to analyze the data and latent class mixed models to identify stable (within patient change < 2) coping strategies. Results: At baseline, patients reported low use of Denial (6.6) and greater use of Acceptance (12.6) and Problem‐Focused coping (12.2). These scores did not significantly change. We found four distinct trajectories for the use of Denial, three for Acceptance and five for Problem‐Focused coping strategies. Stable trajectories were found in 513 (77%) patients for Denial, 645 (96%) for Acceptance and 602 (91%) for Problem‐Focused coping. All coping strategies were stable in 447 (68%) patients and two were stable in 181 patients (28%). Conclusions: Overall, the use of coping strategies was rather stable in the majority of patients with advanced cancer. However, for each of the coping strategies subgroups of patients reported fluctuating coping trajectories. [ABSTRACT FROM AUTHOR]

A major global catastrophe would likely disrupt trade in liquid fuels. Countries dependent on imported oil products might struggle to sustain industrial agriculture. Island nations importing 100% of refined fuels are particularly vulnerable. Our case study aimed to estimate the agricultural land area and biofuel volumes needed to feed the population of New Zealand in the absence of trade. Results showed that stored diesel would quickly be exhausted with ordinary use (weeks) and even with strict rationing (months). To preserve fuel, we found that farming wheat (requiring as little as 5.4 million liters [L] of diesel per annum) was more fuel‐efficient than potatoes (12.3) or dairy (38.7) to feed the national population under a climate‐as‐usual scenario. In a nuclear winter scenario, with reduced agricultural yields, proportionately greater diesel is needed. The wheat would require 24% of current grain‐cropped land, and the canola crop used as feedstock for the required biofuel would occupy a further 1%–7%. Investment in canola biodiesel or renewable diesel refineries could ensure supply for the bare minimum agricultural liquid fuel needs. Were subsequent analysis to favor this option as part of a fuels resilience response and as a tradeoff for routine food use, expansion in refining and canola cropping before a catastrophe could be encouraged through market mechanisms, direct government investment, or a combination of these. Logistics of biofuel refining scale‐up, post‐catastrophe, should also be analyzed. Further, biodiesel produced in normal times would help the nation meet its emissions reduction targets. Other countries should conduct similar analyses. [ABSTRACT FROM AUTHOR]

Background: Urologic emergencies are common and complications from their management are high. Simulation‐based education (SBE) is a highly effective training method, allowing trainees to learn both technical and nontechnical skills in a safe environment. Training in the management of urological emergencies is limited in many healthcare settings, so we performed a needs assessment for a urological emergencies SBE course in Ethiopia. Methods: This study presents data from a descriptive cross‐sectional, survey‐based survey of consultants and residents in the Ethiopian surgical community. The survey was disseminated using online Google Forms, through social media (WhatsApp), and to colleagues in the College of Surgeons of East, Central and Southern Africa (COSECSA) via email and social media. Results: One hundred‐seven results were received; two were discarded due to incomplete data. Fifty three of the respondents were general surgeons and 38 of the respondents were urologists. Sixty nine respondents strongly agreed that simulation‐based training was important for first‐year surgical residents, whereas twenty‐five respondents agreed and nine respondents strongly disagreed; one respondent disagreed and one was neutral. Eighty seven respondents suggested a 3‐day training course, whereas 17 respondents suggested a two‐day course. More than 80 of the respondents rated training in the management of acute urinary retention, acute scrotum, urethral, and suprapubic catheterization as extreme or very important and 79 respondents wanted education about urologic trauma and Fournier's gangrene. Conclusion: Surgical and urology residents in Ethiopia have expressed a need for, and a strong interest in, simulation‐based urological emergency training. [ABSTRACT FROM AUTHOR]

Background: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied. Objective: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available. Methods: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022. When body mass index (BMI) data were available, normal distribution was assumed and a z score was used to estimate the proportion of obesity. Results categorized by BMI or body weight status were reviewed. Authors were contacted for additional information. Results: Of 148 eligible RCTs with 30174 participants, 144 (97.30%) RCTs did not report the proportion of participants with obesity, while published information regarding BMI was available in 63.51%. Three trials excluded patients based on BMI. Using reported BMI, we estimated the proportion of participants with obesity varied greatly across these trials, ranging from 5.82%–71.9% (median 38.02%, interquartile 29.64%, 49.10%). Patients with obesity were represented in a greater proportion among trials conducted in North America (50.23%) and Asia (44.72%), compared to others (32.16%), p <.001. Subgroup analysis or analysis adjusting for BMI was reported in only 13 (8.78%) RCTs; four (30.77%) of these suggested that BMI or body weight might negatively affect primary outcomes. Conclusion: Obesity is a common comorbidity among AF patients. However, most AF ablation RCTs underreported the proportion of participants with obesity and its impact on the primary outcomes. [ABSTRACT FROM AUTHOR]

The circular economy concept has grown in popularity in recent decades as a potential method to offset the waste produced by the linear economy model. In this study, the authors proposed an update to the ReSOLVE framework that includes social impacts and uses decision variables based on the ECOGRAI methodology to facilitate a system‐wide analysis to support sustainable decision‐making. After the updated framework was outlined, it was employed in a theoretical case study to evaluate the current state of the poultry industry and determine hotspots where circular economy metrics could be implemented to benefit affected stakeholders. While the poultry sector was used as a case study, the proposed framework can be applied with modified indicators in other agricultural sectors. This work demonstrated that decision makers can improve the agriculture sector's high social and environmental impact by applying a framework that integrates ReSOLVE circular economy principles and social impact assessment methods. [ABSTRACT FROM AUTHOR]

The development of lipid nanoparticles (LNP) holds great promise for vaccine and therapeutic applications. However, ineffective transport of nucleic acid cargo from endosomes to the cytosol, termed "endosomal escape," has remained a bottleneck to achieving greater LNP efficacy. Poor understanding of the mechanisms of endosomal escape and a lack of suitable techniques to assess the efficiency of escape have also impeded progress in this field. To address this gap, a modified SNAPSwitch/SNAP‐tag assay is developed to compare the cytosolic delivery capabilities of various LNP formulations, comparing ionizable lipids used in major commercial LNP products. The results show that all the LNP formulations tested exhibited low (<10%) endosomal escape efficiency. Interestingly, a limited correlation is found between the amount of mRNA delivery to the cytosol and protein expression. While endosomal escape of mRNA LNP cargo is necessary for protein expression, subcellular processes after delivery to the cytosol play a critical role in maximising protein expression. These findings challenge existing paradigms and reveal critical parameters for optimizing nucleic acid delivery and therapeutic effectiveness of next‐generation LNP. [ABSTRACT FROM AUTHOR]

Objectives: The purpose of this assessor‐blinded, randomised controlled trial was to determine the effect of computerised cognitive training (CT) on executive function, processing speed and working memory in 61 people with mild‐to‐moderate dementia. Methods: The primary outcomes were forward Digit Span and Trail Making Tests (TMT) at the completion of the 6‐month intervention. Secondary outcomes included cognitive and physical performance, rate of falls, participant and caregiver's quality of life and usability and adherence to the CT program. The study was registered with the Australian and New Zealand Clinical Trials Registry (ACTRN12617000364370). Results: Intervention group (n = 31) participants averaged 81 min of CT per week, and system usability scores were acceptable (participants: 68.8 ± 22.1; caregivers: 79.4 ± 23.5). There were no statistically significant differences in cognitive or physical performance outcomes between the intervention and control groups at 6‐ or 12‐months (between‐group differences [95% CI] for primary outcomes at 6‐months: Forward Digit Span −0.3 [−0.8, 0.3]; TMT‐A 2.7 s [−14.1, 19.5]; TMT‐B −17.1 s [−79.3, 45.2]). At the 12‐month follow‐up reassessment, the intervention group reported significantly more depressive symptoms and had lower caregiver‐rated participant quality of life and higher caregiver quality of life compared to control. Conclusions: This study showed no benefit of the CT program on working memory, processing speed and executive function. Future studies are required to better understand how CT can be used to improve cognitive and physical functioning in older people with mild–moderate dementia. [ABSTRACT FROM AUTHOR]

Background: Repair of sagittal proximal phalanx (P1) and parasagittal metacarpal/metatarsal III (MC/MTIII) fractures has evolved over recent decades from a procedure carried out solely under general anaesthesia, to one commonly performed under standing sedation. To date, standing fracture repair has not been evaluated for large cohorts. Objective s : To determine short‐term (survival to discharge) and long‐term (return to racing) outcomes of horses undergoing standing repair of MC/MTIII and P1 fractures, and to compare pre‐surgical and post‐surgical racing performance. Study design: Single‐centre retrospective cohort study. Methods: Retrospective clinical record review of 245 cases undergoing standing repair of MC/MTIII or P1 fractures, 1 January 2007–30 June 2021. Data on signalment, fracture configuration and complications were collected and full race records were retrieved from the Racing Post Database (www..racingpost.com). Chi‐squared and Mann–Whitney U tests were used to determine any difference in variables between horses that raced after surgery compared to those that did not. McNemar change and Wilcoxon signed‐rank tests were used to compare pre‐ and post‐surgical racing performance, p ≤ 0.05. Results: Ninety‐eight percent [95% confidence interval (CI): 96.2%–99.7%] of horses survived hospital discharge, and 75.1% (95% CI: 68.9%–81.4%) raced after surgery, a median of 241 days later. Horses that raced post‐surgery were significantly less likely to have suffered from complications during hospitalisation than those that did not race again [17.3% (95% CI: 11%–24%) vs. 36.5% (95% CI: 23%–50%), p = 0.005]. Comparing pre‐ and post‐operative racing performance, there was no significant difference in earnings per start [median £628.00, interquartile range (IQR) 115.90–1934.80 vs. £653.20, 51.00–1886.40, p = 0.7] or proportion of horses winning [51% (95% CI: 41%–61%) vs. 54% (95% CI: 44%–64%), p = 0.8] or being placed first–third [77% (95% CI: 68%–85%) vs. 71% (95% CI: 62%–80%, p = 0.5] in at least one race. Main limitations: Retrospective nature of study with reliance on clinical records and public databases, limiting data available for analysis. Conclusions: Standing fracture repair is a viable treatment option for MC/MTIII or P1 fractures that returns horses to the racetrack within an acceptable time frame and is capable of restoring pre‐surgical athletic ability. [ABSTRACT FROM AUTHOR]

AdipoRon is an adiponectin receptor 1, 2 (ADIPOR1 and ADIPOR2) agonist with potential antifibrotic effects. Whether AdipoRon can mitigate joint stiffness in a rabbit model of arthrofibrosis is unknown. We examined the efficacy of intravenous (IV) AdipoRon at mitigating contracture in a rabbit model of knee arthrofibrosis. Fifty‐six female New Zealand White rabbits were divided into three dosing groups: vehicle (dimethyl sulfoxide, DMSO), 2.5 mg/kg AdipoRon, and 5 mg/kg AdipoRon. AdipoRon, in DMSO, was administered IV preoperatively and for 5 days postoperatively (30 rabbits, Aim 1). AdipoRon was again dosed similarly after Kirschner wire (K‐wire) removal at 8 weeks (26 rabbits; Aim 2). The primary outcome of joint passive extension angle (PEA,°) was measured at 8, 10, 12, 16, and 24 weeks following index surgery. At 24 weeks, rabbits were euthanized and limbs were harvested to measure posterior capsular stiffness (N cm/°). In Aim 1, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 16‐week (p < 0.05). In Aim 2, the 5 mg/kg treated rabbits had a significant increase in PEA when compared to controls at 10‐week (p < 0.05). In both aims, no significant differences were observed at later time points. Capsular stiffness was no different in any group. We are the first to report the efficacy of IV AdipoRon in a rabbit model of arthrofibrosis. We identified a significant dose‐dependent decrease in joint PEA at early time points; however, no differences were observed between groups at later time points. Clinical Significance: The present investigation provided the first assessment of AdipoRon's efficacy in mitigating knee stiffness in the current gold standard rabbit model of arthrofibrosis. Results of this investigation provided further evidence as to the potential role of AdipoRon as a preventative for arthrofibrosis in large mammals. [ABSTRACT FROM AUTHOR]

We present ReactionMechanismSimulator.jl (RMS), a modern differentiable software for the simulation and analysis of chemical kinetic mechanisms, including multiphase systems. RMS has already been applied to problems in combustion, pyrolysis, polymers, pharmaceuticals, catalysis, and electrocatalysis. RMS is written in Julia, making it easy to develop and allowing it to take advantage of Julia's extensive numerical computing ecosystem. In addition to its extensive library of optimized analytic Jacobians, RMS can generate and use Jacobians computed using automatic differentiation and symbolically generated analytic Jacobians. RMS is demonstrated to be faster than Cantera and Chemkin in several benchmarks. RMS also implements an extensive set of features for analyzing chemical mechanisms, including a library of easy‐to‐call plotting functions, molecular structure resolved flux diagram generation, crash analysis, traditional sensitivity analysis, transitory sensitivity analysis, and an automatic mechanism analysis toolkit. RMS implements efficient adjoint and parallel forward sensitivity analyses. We also demonstrate the ease of adding new features to RMS. [ABSTRACT FROM AUTHOR]

The growth plate is a cartilage structure at the end of long bones which mediates growth in children. When fractured, the formation of bony repair tissue known as a "bony bar" can occur and cause limb deformities. There are currently no effective clinical solutions for the prevention of the bony bar formation or regeneration of healthy growth plate cartilage after a fracture. This study employs previously developed alginate/chitosan polyelectrolyte complex (PEC) hydrogels as a sustained release vehicle for the delivery of short‐interfering RNA (siRNA). Specifically, the siRNA targets the p38‐MAPK pathway in mesenchymal stem cells (MSCs) to prevent their osteogenic differentiation. In vitro experimental findings show sustained release of siRNA from the hydrogels for 6 months. Flow cytometry and confocal imaging indicate that the hydrogels release siRNA to effectively knockdown GFP expression over a sustained period. MAPK‐14 targeting siRNA was used to knockdown the expression of MAPK‐14 and correspondingly decrease the expression of other osteogenic genes in MSCs in vitro over the span of 21 days. These hydrogels were used in a rat model of growth plate injury to determine whether siMAPK‐14 released from the gels could inhibit bony bar formation. No significant reduction of bony bar formation was seen in vivo at the one concentration of siRNA examined. This PEC hydrogel represents a significant advancement for siRNA sustained delivery, and presents an interesting potential therapeutic delivery system for growth plate injuries and other regenerative medicine applications. [ABSTRACT FROM AUTHOR]

Previous simulations have suggested that O+ outflow plays a role in driving the sawtooth oscillations. This study investigates the role of O+ by identifying the differences in ionospheric outflow between sawtooth and non‐sawtooth storms using 11 years of FAST/Time of flight Energy Angle Mass Spectrograph (TEAMS) ion composition data from 1996 through 2007 during storms driven by coronal mass ejections. We find that the storm's initial phase shows larger O+ outflow during non‐sawtooth storms, and the main and recovery phases revealed differences in the location of ionospheric outflow. On the pre‐midnight sector, a larger O+ outflow was observed during the main phase of sawtooth storms, while non‐sawtooth storms exhibited stronger O+ outflow during the recovery phase. On the dayside, the peak outflow shifts significantly toward dawn during sawtooth storms. This strong dawnside sector outflow during sawtooth storms warrants consideration. Plain Language Summary: A sawtooth event is a convection mode in Earth's magnetosphere, which transports solar wind plasma and energy into the inner magnetosphere and ionosphere. Despite three decades since their discovery, the mechanism behind sawtooth oscillations remains uncertain. One theory suggests that O+ outflow induces sawtooth oscillations through an internal feedback mechanism. In line with this theory, some simulations have generated sawtooth oscillations under steady geomagnetic conditions. Furthermore, previous observations indicate that some, but not all, geomagnetic storms exhibit sawtooth oscillations. This study utilizes data from the FAST/TEAMS instrument (1996–2007) and compares O+ outflow variations during geomagnetic storms with and without sawtooth oscillations. Findings indicate that during the storms' initial phase, sawtooth storms produce less O+ outflow than non‐sawtooth storms. Additionally, non‐sawtooth storms exhibit higher O+ outflow in the dayside during the main phase and in the pre‐midnight sector during the recovery phase, challenging the key role of O+ outflow in driving the feedback mechanism. However, observing large O+ outflow in the dawnside sector of sawtooth events suggests more investigation is needed. Key Points: The intensity and location of O+ outflow during storms are different in storms with and without sawtooth oscillationsThe peak dayside outflow is significantly shifted toward dawn during storms with sawtooth observationsThe nightside picture is mixed; the pre‐midnight O+ outflow is higher in the main phase but lower in the recovery phase of sawtooth storms [ABSTRACT FROM AUTHOR]

The development of novel antivirals is crucial not only for managing current COVID‐19 infections but for addressing potential future zoonotic outbreaks. SARS‐CoV‐2 main protease (Mpro) is vital for viral replication and viability and therefore serves as an attractive target for antiviral intervention. Herein, we report the optimization of a cyclic peptide inhibitor that emerged from an mRNA display selection against the SARS‐CoV‐2 Mpro to enhance its cell permeability and in vitro antiviral activity. By identifying mutation‐tolerant amino acid residues within the peptide sequence, we describe the development of a second‐generation Mpro inhibitor bearing five cyclohexylalanine residues. This cyclic peptide analogue exhibited significantly improved cell permeability and antiviral activity compared to the parent peptide. This approach highlights the importance of optimizing cyclic peptide hits for activity against intracellular targets such as the SARS‐CoV‐2 Mpro. [ABSTRACT FROM AUTHOR]

Objective: To report initial results from the Amyotrophic Lateral Sclerosis (ALS) Identified genetic testing (GT) program on characteristics of individuals tested and frequency of reported disease‐causing variants. Methods: ALS Identified used the Invitae Amyotrophic Lateral Sclerosis panel (Invitae, San Francisco, CA, USA) to assay 22 ALS‐associated genes. Sponsored by Biogen (Cambridge, MA, USA), the program was launched in June 2021 and was available at no charge to individuals ≥18 years in the United States and Puerto Rico with an ALS diagnosis or a known family history of ALS. Deidentified data were available to Biogen. Results: As of 26 October 2023, 998 healthcare professionals ordered the panel at 681 unique care sites. Of 8054 individuals examined, 7483 (92.9%) were reported to have a clinical diagnosis of ALS, while 571 (7.1%) were asymptomatic relatives. Of the individuals with a clinical ALS diagnosis, 57.7% were male (n = 4319) and 42.3% female (n = 3164). Mean (SD) age at diagnosis is 62 (13) years. Out of the 7483 clinically diagnosed individuals, 1810 (24.2%) showed genetic variations in ALS‐associated genes. Among these, 865 individuals (47.8%) carried pathogenic variants, and 44 (2.4%) had likely pathogenic variants, totaling 12.1% of the clinically diagnosed population. Interpretation: Since 2021 there has been robust uptake and sustained use of the ALS Identified program, one of the largest samples of people with ALS to date across the United States, demonstrating the interest and need for genetic ALS testing. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that individuals differ in foraging tactics and this variation is often linked to an individual's behavioural type (BT). Yet, while foraging typically comprises a series of search and handling steps, empirical investigations have rarely considered BT‐dependent effects across multiple stages of the foraging process, particularly in natural settings.In our long‐term sleepy lizard (Tiliqua rugosa) study system, individuals exhibit behavioural consistency in boldness (measured as an individual's willingness to approach a novel food item in the presence of a threat) and aggressiveness (measured as an individual's response to an 'attack' by a conspecific dummy). These BTs are only weakly correlated and have previously been shown to have interactive effects on lizard space use and movement, suggesting that they could also affect lizard foraging performance, particularly in their search behaviour for food.To investigate how lizards' BTs affect their foraging process in the wild, we supplemented food in 123 patches across a 120‐ha study site with three food abundance treatments (high, low and no‐food controls). Patches were replenished twice a week over the species' entire spring activity season and feeding behaviours were quantified with camera traps at these patches. We tracked lizards using GPS to determine their home range (HR) size and repeatedly assayed their aggressiveness and boldness in designated assays.We hypothesised that bolder lizards would be more efficient foragers while aggressive ones would be less attentive to the quality of foraging patches. We found an interactive BT effect on overall foraging performance. Individuals that were both bold and aggressive ate the highest number of food items from the foraging array. Further dissection of the foraging process showed that aggressive lizards in general ate the fewest food items in part because they visited foraging patches less regularly, and because they discriminated less between high and low‐quality patches when revisiting them. Bolder lizards, in contrast, ate more tomatoes because they visited foraging patches more regularly, and ate a higher proportion of the available tomatoes at patches during visits.Our study demonstrates that BTs can interact to affect different search and handling components of the foraging process, leading to within‐population variation in foraging success. Given that individual differences in foraging and movement will influence social and ecological interactions, our results highlight the potential role of BT's in shaping individual fitness strategies and population dynamics. [ABSTRACT FROM AUTHOR]

Levels of dissolved oxygen in open ocean and coastal waters are decreasing (ocean deoxygenation), with poorly understood effects on marine megafauna. All of the more than 1000 species of elasmobranchs (sharks, skates, and rays) are obligate water breathers, with a variety of life‐history strategies and oxygen requirements. This review demonstrates that although many elasmobranchs typically avoid hypoxic water, they also appear capable of withstanding mild to moderate hypoxia with changes in activity, ventilatory responses, alterations to circulatory and hematological parameters, and morphological alterations to gill structures. However, such strategies may be insufficient to withstand severe, progressive, or prolonged hypoxia or anoxia where anaerobic metabolic pathways may be used for limited periods. As water temperatures increase with climate warming, ectothermic elasmobranchs will exhibit elevated metabolic rates and are likely to be less able to tolerate the effects of even mild hypoxia associated with deoxygenation. As a result, sustained hypoxic conditions in warmer coastal or surface‐pelagic waters are likely to lead to shifts in elasmobranch distributions. Mass mortalities of elasmobranchs linked directly to deoxygenation have only rarely been observed but are likely underreported. One key concern is how reductions in habitat volume as a result of expanding hypoxia resulting from deoxygenation will influence interactions between elasmobranchs and industrial fisheries. Catch per unit of effort of threatened pelagic sharks by longline fisheries, for instance, has been shown to be higher above oxygen minimum zones compared to adjacent, normoxic regions, and attributed to vertical habitat compression of sharks overlapping with increased fishing effort. How a compound stressor such as marine heatwaves alters vulnerability to deoxygenation remains an open question. With over a third of elasmobranch species listed as endangered, a priority for conservation and management now lies in understanding and mitigating ocean deoxygenation effects in addition to population declines already occurring from overfishing. [ABSTRACT FROM AUTHOR]

Introduction: Support staff within social care settings have expressed a need for resources to facilitate end‐of‐life care planning with people with intellectual disabilities. This study aimed to co‐design a preliminary toolkit of end‐of‐life care planning approaches and resources that can be implemented in adult social care services for people with intellectual disabilities. Methods: An adapted Experience‐Based Co‐Design process was applied to develop a toolkit for end‐of‐life care planning with people with intellectual disabilities. A co‐design group (the 'All Together Group') met six times from January to October 2023. The group comprised nine people with intellectual disabilities (including four researchers with intellectual disabilities, who also co‐facilitated the workshops), five family members, five intellectual disability support staff including two intellectual disability service managers, and five healthcare professionals. Results: The All Together Group tested resources for and approaches to end‐of‐life care planning with people with intellectual disabilities, based on findings from a scoping review and a focus group study. Easy‐read end‐of‐life care planning forms were deemed overwhelming and complicated, whilst visual and creative approaches were welcomed. Three new visual resources to support illness planning and funeral planning with people with intellectual disabilities were developed: (i) 'When I'm ill' thinking cards; (ii) 'Let's Talk About Funerals' conversation‐starter pictures; and (iii) 'My funeral' planning cards. These three resources, alongside three positively evaluated existing resources, were included in a new toolkit for end‐of‐life care planning with people with intellectual disabilities. Conclusion: Through an iterative, flexible, inclusive, and comprehensive co‐design process, a toolkit of three newly developed and three existing resources was created to facilitate support staff in doing end‐of‐life care planning with people with intellectual disabilities. Following a trialling process with support staff, the final toolkit was made freely available online. Patient or Public Contribution: The research team included four researchers with intellectual disabilities (A.C., D.J., L.J., and R.K.‐B). Researchers with intellectual disability have been part of every step of the research process; from study design to data collection and analysis to dissemination of study findings.Intellectual disability service provider representatives (M.W., N.P., and S.S.) were part of the co‐design group as well. Two of these representatives were also co‐applicants in the overall project (N.P. and S.S.). The co‐design group included people with intellectual disabilities, families, intellectual disability support staff and health and social care professionals. The study was supported by a Research Advisory Group comprising a variety of stakeholders, including people with intellectual disabilities families, intellectual disability researchers, representatives from intellectual disability organisations, and policymakers. Practitioner Points: To facilitate proper and timely end‐of‐life care planning, resources and approaches should be developed together with people with intellectual disabilities and support staff to make sure they are relevant, accessible, and workable in social care practice.People with intellectual disabilities prefer visual and creative approaches to end‐of‐life care planning rather than easy‐read plans and forms.Co‐producing an end‐of‐life care planning toolkit is an iterative, time‐consuming, and complex process, which requires a flexible approach, adapting to the feedback from and needs of co‐design group members. [ABSTRACT FROM AUTHOR]

Aim: Predicting spatial and temporal changes in species distributions is difficult for highly mobile species, making effective management challenging. We aim to understand the seasonal variability in habitat suitability for Atlantic bluefin tuna (Thunnus thynnus; ABFT) by using tracking data to create species distribution models. Location: North‐east Atlantic Ocean. Methods: Forty‐nine ABFT were tagged with pop‐up archival satellite tags along the west coast of Ireland during successive autumns from 2016 to 2021. Four thousand two hundred and sixteen daily locations were used to build a habitat model to describe ABFT environmental preferences and habitat suitability. For each location, 100 'pseudoabsence' locations were simulated using correlated random walks. Results: Tags had a mean retention rate of 237 ± 107 days, resulting in 11,602 cumulative days at liberty, and a mean daily distance travelled of 51 ± 143 km. ABFT showed two primary migration routes from Ireland, travelling to the Bay of Biscay or across the Mid‐Atlantic ridge in the winter. However, in 2019 six individuals travelled northwards towards Iceland, likely in response to a marine heatwave. Eight ABFT entered the Mediterranean in May/June for putative spawning, with six returning to Irish waters a year later. Five environmental covariates best described ABFT habitat, with habitat suitability highest at sea surface temperatures (SST) of 15–18°C, a mixed layer depth between ~200 and 300 m, high relief bathymetric features (i.e. shelf breaks and seamounts) and frontal regions as revealed by non‐linear preferences of eddy kinetic energy and SST standard deviation. Main Conclusions: In the last decade, ABFT have been re‐establishing historic foraging grounds in higher latitudes, for example, Irish and Nordic waters. Our model shows the extent of suitable habitat in these regions and how recent ocean warming may have contributed to northern expansions. Understanding the drivers behind these reappearances is fundamental to successful future management. Achoimre: Aidhm: Tá sé deacair athraithe i ndáileadh ama agus spásdháileadh speiceas atá an‐soghluaiste a thuar, rud a chiallaíonn go bhfuil sé dúshlánach bainistiú éifeachtach a dhéanamh. Tá muid ag iarraidh inathraitheacht shéasúrach in oiriúnacht ghnáthóg an Tuinnín Gorm Atlantach (Thunnus thynnus; TGA) a thuiscint tríd sonraí rianaithe a úsáid chun samhail dháileadh speiceas a chruthú. Suíomh: Oirthuaisceart an Atlantaigh. Modh: Rinneadh clibeadh ar 49 TGA le clibeanna cartlainne a thagann go barr uisce ar chósta iarthar na hÉireann le linn ceithre fhómhair i ndiaidh a chéile ó 2016–2021. Úsáideadh 4216 suíomhanna laethúil chun samhail ghnáthóg a chruthú a rinne cur síos ar roghanna timpeallachta agus oiriúnacht ghnáthóg an TGA. I gcomhair gach suíomh, ionsamhlaíodh 100 suíomhanna bréag‐neamhláithreacht ag úsáid siúlóidí randamacha comhghaolaithe. Torthaí: Bhí meán ráta coinneála de 237 ± 107 lá ag na clibeanna, rud a thug 11,602 lá taifeadta i ndiaidh a chéile agus meán fhad laethúil taistealta de 51 ± 143 km dá bharr. Léirigh TGA dhá phríomhbhealaí imirce ó hÉirinn, ag taisteal go Bá na Bioscáine nó thar Droim an Atlantaigh Láir i rith an gheimhridh. Ach i 2019 thaisteal sé iasc ó thuaidh i dtreo an Íoslainn, is dócha mar gheall ar thonn teasa mara. Chuaigh ocht TGA isteach sa Mheánmhuir i rith mí Bealtaine/mí an Mheitheamh chun uibheacha a sceitheadh de réir dealraimh. Tháinig sé dóibh ar ais go huiscí na hÉireann an bhliain dar gcionn. Déanann cúig athróg timpeallachta an cur síos is fearr ar ghnáthóg an TGA, tá oiriúnacht ghnáthóg is airde ag teocht barr uisce (TBA) de 15–18°C, nuair atá doimhneacht an chisil mheasctha idir ~200 agus 300 m, ag gnéithe bataiméadrach ard‐rilíf (i.e. scoilteanna scairbhe agus tuláin grinnill), agus ag réigiúin frontacha léirithe ag roghanna neamh‐líneacha fuinneamh cinéatach guairneánach agus diall caighdeánach TBA. Príomhchonclúidí: Le leathscór bliain anuas tá TGA tar éis réigiúin sealgaireachta stairiúil a athbhunú in áiteanna le hard‐domhanleithead, ar nós uiscí na hÉireann agus uiscí Nordacha. Taispeánann ár samhail achar an ghnáthóg oiriúnach sna réigiúin seo agus an bhaint féideartha a bhí ag téámh aigéanach le gairid ar leathadh ó thuaidh. Tá sé buntábhachtach na cúiseanna don athfhilleadh seo a thuiscint i gcomhair bainistiú rathúil amach anseo. [ABSTRACT FROM AUTHOR]

Background and aims: Substance use treatment (SUT) has shown to be effective in reducing self‐reported offending; however, the association between SUT completion and criminal justice system (CJS) contact has been underexplored, especially in Latin America. This study aimed to estimate the association between SUT completion status and (1) any subsequent CJS contact and (2) CJS contact leading to imprisonment, at 1, 3 and 5 years post‐discharge, in Chile. Design: Retrospective cohort study using multivariable survival analysis based on linked administrative data from 2010 to 2019. Setting: This study took place in Chile, where SUT is available at no cost through Chile's publicly funded health‐care, and is provided in outpatient and inpatient modalities in public and private centres. Participants: A total of 70 854 individuals received their first SUT from 2010 to 2019. They were mainly males (76.3%), and their main substance used at admission was cocaine paste (39.2%). Measurements SUT completion status included completion, late dropout (≥ 3 months) and early dropout (< 3 months). Outcomes were (1) any CJS contact and (2) CJS contact leading to imprisonment after baseline treatment. We estimated the association between treatment completion and CJS contact through flexible parametric Royston−Parmar models while adjusting for several covariates. Findings Those who completed SUT (27.2%) were less likely to have any CJS contact at 5 years post‐SUT compared with those who dropped out late [with a gap of −9.5%, 95% confidence interval (CI) = −8.7, −10.3] and early (−11.2%, 95% CI = −10.1, −12.3). Also, those who completed SUT were less likely to have CJS contact leading to imprisonment at 5 years post‐SUT compared with those who dropped out late (−2.6%, 95% CI = −2.2, −3.1) and early (−4.0%, 95% CI = −3.3, −4.6). These differences were also observed at 1 and 3 years post‐SUT for each outcome. Conclusions: In Chile, completion of substance use treatment appears to be associated with lower probabilities of both any criminal justice system contact and contact leading to imprisonment. [ABSTRACT FROM AUTHOR]

Background and aims: Substance use treatment (SUT) has shown to be effective in reducing self-reported offending; however, the association between SUT completion and criminal justice system (CJS) contact has been underexplored, especially in Latin America. This study aimed to estimate the association between SUT completion status and (1) any subsequent CJS contact and (2) CJS contact leading to imprisonment, at 1, 3 and 5 years post-discharge, in Chile. Design: Retrospective cohort study using multivariable survival analysis based on linked administrative data from 2010 to 2019. Setting: This study took place in Chile, where SUT is available at no cost through Chile's publicly funded health-care, and is provided in outpatient and inpatient modalities in public and private centres. Participants: A total of 70 854 individuals received their first SUT from 2010 to 2019. They were mainly males (76.3%), and their main substance used at admission was cocaine paste (39.2%). Measurements: SUT completion status included completion, late dropout (≥ 3 months) and early dropout (< 3 months). Outcomes were (1) any CJS contact and (2) CJS contact leading to imprisonment after baseline treatment. We estimated the association between treatment completion and CJS contact through flexible parametric Royston --Parmar models while adjusting for several covariates. Findings: Those who completed SUT (27.2%) were less likely to have any CJS contact at 5 years post-SUT compared with those who dropped out late [with a gap of -9.5%, 95% confidence interval (CI) = -8.7, -10.3] and early (-11.2%, 95% CI = -10.1, -12.3). Also, those who completed SUT were less likely to have CJS contact leading to imprisonment at 5 years post-SUT compared with those who dropped out late (-2.6%, 95% CI = -2.2, -3.1) and early (-4.0%, 95% CI = -3.3, -4.6). These differences were also observed at 1 and 3 years post-SUT for each outcome. Conclusions: In Chile, completion of substance use treatment appears to be associated with lower probabilities of both any criminal justice system contact and contact leading to imprisonment. [ABSTRACT FROM AUTHOR]

Dexmedetomidine is a sedative used in both adults and off‐label in children with considerable reported pharmacokinetic (PK) interindividual variability affecting drug exposure across populations. Several published models describe the population PKs of dexmedetomidine in neonates, infants, children, and adolescents, though very few have been externally evaluated. A prospective PK dataset of dexmedetomidine plasma concentrations in children and young adults aged 0.01‐19.9 years was collected as part of a multicenter opportunistic PK study. A PubMed search of studies reporting dexmedetomidine PK identified five population PK models developed with data from demographically similar children that were selected for external validation. A total of 168 plasma concentrations from 102 children were compared with both population (PRED) and individualized (IPRED) predicted values from each of the five published models by quantitative and visual analyses using NONMEM (v7.3) and R (v4.1.3). Mean percent prediction errors from observed values ranged from −1% to 120% for PRED, and −24% to 60% for IPRED. The model by James et al, which was developed using similar "real‐world" data, nearly met the generalizability criteria from IPRED predictions. Other models developed using clinical trial data may have been limited by inclusion/exclusion criteria and a less racially diverse population than this study's opportunistic dataset. The James model may represent a useful, but limited tool for model‐informed dosing of hospitalized children. [ABSTRACT FROM AUTHOR]

Independent decision making requires forming stable estimates of one's preferences. We assessed whether adolescents learn about their preferences through choice deliberation and whether depressive symptoms disrupt this process. Adolescents aged 11–18 (N = 214; participated 2021–22; Female: 53.9%; White/Black/Asian/Mixed/Arab or Latin American: 26/21/19/9/8%) rated multiple activities, chose between pairs of activities and re‐rated those activities. As expected, overall, participants uprated chosen and downrated unchosen activities (dz =.20). This value refinement through choice was not evident in younger participants but emerged across adolescence. Contrary to our predictions, depressive symptoms were associated with greater value refinement. Despite this, more depressed adolescents reported lower value certainty and choice confidence. The cognitive processes through which choice deliberation shapes preference develop over adolescence, and are disrupted in depression. [ABSTRACT FROM AUTHOR]

Aims: Genetic testing can be used to improve the safety and effectiveness of commonly prescribed medicines—a concept known as pharmacogenetics. This study aimed to quantify members of the UK public's preferences for a pharmacogenetic service to be delivered in primary care in the National Health Service. Methods: Members of the UK population were surveyed via an online panel company. Respondents completed 1 of 2 survey versions, asking respondents to select their preferred pharmacogenetic testing service in the context of a presentation of low mood or pain. A conditional logit model was estimated, before the best functional form for the dataset was identified. Preference heterogeneity was identified via latent class analysis. Coefficients from the final selected models were used to estimate uptake in the context of different hypothetical pharmacogenetic services. Results: Responses from 1993 individuals were included in the analysis. There were no differences observed in preference between the 2 clinical scenarios. Conditional logit analysis, using maximum likelihood estimation, indicated that respondents preferred to have noninvasive tests and wanted their data to be shared between different healthcare organizations to guide future prescribing. There was a preference for regional over national data sharing initiatives, and respondents preferred to have access to their data. Predicted uptake varied considerably, ranging from 51% to >99%, depending on design of the service. Conclusion: This study identifies public preferences for a pharmacogenetic testing service and demonstrates how predicted uptake can be impacted by relatively minor adaptations. This highlights areas for prioritization during development of future pharmacogenetic services. [ABSTRACT FROM AUTHOR]

Adolescence is marked by the onset of puberty, which is associated with an increase in mental health difficulties, particularly in girls. Social and self‐referential processes also develop during this period: adolescents become more aware of others' perspectives, and judgements about themselves become less favourable. In the current study, data from 119 girls (from London, UK) aged 9–16 years were collected at two‐time points (between 2019 and 2021) to investigate the relationship between puberty and difficulties in mental health and emotion regulation, as well as the role of self‐referential and social processing in this relationship. Structural equation modelling showed that advanced pubertal status predicted greater mental health and emotion regulation difficulties, including depression and anxiety, rumination and overall difficulties in emotion regulation, and in mental health and behaviour. Advanced pubertal status also predicted greater perspective‐taking abilities and negative self‐schemas. Exploratory analyses showed that negative self‐schemas mediated the relationships between puberty and rumination, overall emotion regulation difficulties, and depression (although these effects were small and would not survive correction for multiple comparisons). The results suggest that advanced pubertal status is associated with higher mental health and emotion regulation problems during adolescence and that negative self‐schemas may play a role in this association. Research Highlights: This study investigates the relationship between puberty, mental health, emotion regulation difficulties, and social and self‐referential processing in girls aged 9–16 years.Advanced pubertal status was associated with worse mental health and greater emotion regulation difficulties, better perspective‐taking abilities and negative self‐schemas.Negative self‐schemas may play a role in the relationships between advanced pubertal status and depression, and advanced pubertal status and emotion regulation difficulties, including rumination. [ABSTRACT FROM AUTHOR]

Objective: The aim of our study is to better understand the genetic architecture and pathological mechanisms underlying neurodegeneration in idiopathic Parkinson's disease (iPD). We hypothesized that a fraction of iPD patients may harbor a combination of common variants in nuclear‐encoded mitochondrial genes ultimately resulting in neurodegeneration. Methods: We used mitochondria‐specific polygenic risk scores (mitoPRSs) and created pathway‐specific mitoPRSs using genotype data from different iPD case–control datasets worldwide, including the Luxembourg Parkinson's Study (412 iPD patients and 576 healthy controls) and COURAGE‐PD cohorts (7,270 iPD cases and 6,819 healthy controls). Cellular models from individuals stratified according to the most significant mitoPRS were subsequently used to characterize different aspects of mitochondrial function. Results: Common variants in genes regulating Oxidative Phosphorylation (OXPHOS‐PRS) were significantly associated with a higher PD risk in independent cohorts (Luxembourg Parkinson's Study odds ratio, OR = 1.31[1.14–1.50], p‐value = 5.4e‐04; COURAGE‐PD OR = 1.23[1.18–1.27], p‐value = 1.5e‐29). Functional analyses in fibroblasts and induced pluripotent stem cells‐derived neuronal progenitors revealed significant differences in mitochondrial respiration between iPD patients with high or low OXPHOS‐PRS (p‐values < 0.05). Clinically, iPD patients with high OXPHOS‐PRS have a significantly earlier age at disease onset compared to low‐risk patients (false discovery rate [FDR]‐adj p‐value = 0.015), similar to prototypic monogenic forms of PD. Finally, iPD patients with high OXPHOS‐PRS responded more effectively to treatment with mitochondrially active ursodeoxycholic acid. Interpretation: OXPHOS‐PRS may provide a precision medicine tool to stratify iPD patients into a pathogenic subgroup genetically defined by specific mitochondrial impairment, making these individuals eligible for future intelligent clinical trial designs. ANN NEUROL 2024;96:133–149 [ABSTRACT FROM AUTHOR]

Aim: Increasing rates of mental illness among young people, exacerbated by the negative impacts of COVID‐19, has resulted in growing pressure on available psychiatric resources to meet increasing demand. Inpatient units provide specialist care for young people with the most severe and complex mental disorders but are one of the most expensive models of psychiatric care. The aim of this review is to provide an update on the effectiveness of adolescent and youth mental health inpatient units in improving outcomes to inform the most efficacious use of psychiatric resources. Methods: Systematic searches of PubMed, The Cochrane Library, PsycINFO, EMBASE, and Web of Science were conducted for studies published in English between January 2011 to May 2022. Criteria for selection included participants aged 12–25 years who had been admitted to amental health inpatient unit. Studies were excluded if set in substance abuse or disability specific units, outpatient or forensic settings, or assessed novel interventions. Results: 23 studies were identified as meeting inclusion criteria, with most (n = 19) utilizing a pre‐post observational design and reporting improvement across various domains following inpatient treatment. A total of 24 different outcome measures or methods were used meaning a meta‐analysis of results was not possible. There was also a lack of consistency across models of care, lengths of stay, admission policies, and interventions provided. Conclusion: Inpatient units provide positive outcomes for consumers however a clear understanding of clinical significance and comparison to other treatment settings is lacking. [ABSTRACT FROM AUTHOR]

Body size is a fundamental biological trait shaping ecological interactions, evolutionary processes, and our understanding of the structure and dynamics of marine communities on a global scale. Accurately defining a species' body size, despite the ease of measurement, poses significant challenges due to varied methodologies, tool usage, and subjectivity among researchers, resulting in multiple, often discrepant size estimates. These discrepancies, stemming from diverse measurement approaches and inherent variability, could substantially impact the reliability and precision of ecological and evolutionary studies reliant on body size data across extensive species datasets. This study examines the variation in reported maximum body sizes across 69,570 individual measurements of maximum size, ranging from <0.2 μm to >45 m, for 27,271 species of marine metazoans. The research aims to investigate how reported maximum size variations within species relate to organism size, taxonomy, habitat, and the presence of skeletal structures. The investigation particularly focuses on understanding why discrepancies in maximum size estimates arise and their potential implications for broader ecological and evolutionary studies relying on body size data. Variation in reported maximum sizes is zero for 38% of species, and low for most species, although it exceeds two orders of magnitude for some species. The likelihood of zero variation in maximum size decreased with more measurements and increased in larger species, though this varied across phyla and habitats. Pelagic organisms consistently had low maximum size range values, while small species with unspecified habitats had the highest variation. Variations in maximum size within a species were notably smaller than interspecific variation at higher taxonomic levels. Significant variation in maximum size estimates exists within marine species, and partially explained by organism size, taxonomic group, and habitat. Variation in maximum size could be reduced by standardized measurement protocols and improved meta‐data. Despite the variation, egregious errors in published maximum size measurements are rare, and their impact on comparative macroecological and macroevolutionary research is likely minimal. [ABSTRACT FROM AUTHOR]

Background: Oral cavity squamous cell carcinomas (OCSCCs) are relatively common in multiple non‐human primate species but are poorly documented in Goeldi's monkeys. Methods: Four Goeldi's monkeys with OCSCC, from three zoological collections, underwent necropsy with cytology, histopathology, immunohistochemistry, and pan‐herpesvirus PCR analysis. Results: All animals were euthanised and exhibited poor‐to‐emaciated body condition. Three OCSCCs arose from the maxillary oral mucosa and a single OCSCC was primarily mandibular, with bone invasion evident in three cases. Histologically, one OCSCC in situ was diagnosed, whilst the rest were typically invasive OCSCCs. Neoplastic cells were immunopositive for pancytokeratin and E‐cadherin. All examined cases were negative for regional lymph node (RLN) and/or distant metastases, cyclooxygenase‐2 (COX‐2) immunoexpression, and panherpesvirus PCR expression. Conclusions: OCSCCs in Goeldi's monkeys may be deeply invasive, but not readily metastatic. No herpesvirus‐association or COX‐2 expression was evident; the latter suggesting that NSAIDs are unlikely to be a viable chemotherapeutic treatment. [ABSTRACT FROM AUTHOR]

Perioperative anxiety is common in surgical patients and linked to poor outcomes. This multicenter randomized controlled trial assessed the effect of the use of a warm weighted blanket on presurgical anxiety and pain, as well as postsurgical restlessness, nausea, and vomiting. Levels of anxiety and pain were measured in adult patients using a 100‐point visual analog scale before elective surgery. Patients received either a warm weighted blanket (n = 74) or a traditional sheet or nonweighted blanket (n = 74). Patients in the intervention group had significantly lower preoperative anxiety scores (mean [SD] = 26.28 [25.75]) compared to the control group (mean [SD] = 38.73 [30.55], P =.008). However, the intervention had no significant effect on presurgical pain or postsurgical nausea, vomiting, or restlessness. These results suggest that weighted blankets reduce preoperative anxiety in adult patients. [ABSTRACT FROM AUTHOR]

Manganese is an emerging concern in drinking water, due to its potential health and aesthetic effects. Although accurate and sensitive, spectroscopic techniques for Mn2+ detection are costly and not capable of rapid detection. Electrochemical methods, such as cathodic stripping voltammetry, have been intensively explored as portable low‐cost methods for Mn2+ detection. Challenges of reliability and matrix interference are difficult to overcome with current electrochemical methods. Among the interference reagents, Fe2+ is one of the biggest challenges for Mn2+ detection. Herein, a new method based on multiplex chronoamperometry at potentials between 0.9 and 1.4 V by a multichannel potentiostat is explored for its ability for interference resistance and applicability for Mn2+ detection in real drinking water samples. Compared to conventional one‐channel electrochemical techniques, the multiplex method generates a reliable pattern that is unique to the sample components. The interference between Mn2+ and Fe2+ is investigated and the results are promising even at 100:1 Fe2+:Mn2+ concentrations. The detection limit determined for the multiplex method was 25.3 μM, and the optimum recovery rate in a real drinking water sample was 99.8%. [ABSTRACT FROM AUTHOR]

High‐quality forages can benefit from being harvested as baleage when the environmental conditions are not favorable for dry hay production. Currently, it is recommended that baleage should be fed within 9‐months post‐harvest; however, mild winters can reduce the demand for these stored forages. Data are limited on the changes in nutritive value of baleage stored beyond the recommended timepoint. Therefore, the objective was to determine the effect of storage length on nutritive value of forage harvested and stored as baleage. This study evaluated baleage harvested from 2016 to 2018 in Tifton, GA, consisting of either bermudagrass (Cynodon dactylon L. Pers.), or a mixture of bermudagrass and alfalfa (Medicago sativa L.). Baleage was sampled for nutritive value analysis at 6‐weeks and 9‐ and 12‐months post‐harvest, with a subset of bales sampled at 24 months. Regardless of forage, crude protein, total digestible nutrients, and in‐vitro dry matter digestibility at 48 h were not impacted in bales sampled up to 12‐months post‐harvest (p > 0.07). However, acid detergent fiber increased when baleage was stored beyond 6 weeks but did not change from 9 to 12 months (p < 0.01). In the subset of bales stored up to 24‐months post‐harvest, all nutritive value parameters evaluated were negatively impacted (p < 0.01). The prolonged storage period may negatively affect the baleage plastic integrity, resulting in a decline in nutritive value if anaerobic conditions are not maintained. Future research is warranted to evaluate the changes in the fermentation profile of baleage under extended storage conditions. Plain Language Summary: High quality forages can benefit from being harvested as baleage when the environmental conditions are not favorable for dry hay production. Currently, it is recommended that baleage should be fed within 9‐months post‐harvest; however, mild winters can reduce the demand for these stored forages. Data are limited on the changes in nutritive value of baleage stored beyond the recommended timepoint. Therefore, the objective was to determine the effect of storage length on nutritive value of forage harvested and stored as baleage. Baleage was sampled at four timepoints: 6‐weeks and 9‐, 12‐, and 24‐months post‐harvest. Nutritive value of baleage was not negatively impacted for storage up to 12 months. Storage up to 24 months reported a drop in nutritive value likely due to ability to maintain bale integrity. [ABSTRACT FROM AUTHOR]

Ticks produce chemokine‐binding proteins, known as evasins, in their saliva to subvert the host's immune response. Evasins bind to chemokines and thereby inhibit the activation of their cognate chemokine receptors, thus suppressing leukocyte recruitment and inflammation. We recently described subclass A3 evasins, which, like other class A evasins, exclusively target CC chemokines but appear to use a different binding site architecture to control target selectivity among CC chemokines. We now describe the structural basis of chemokine recognition by the class A3 evasin EVA‐ACA1001. EVA‐ACA1001 binds to almost all human CC chemokines and inhibits receptor activation. Truncation mutants of EVA‐ACA1001 showed that, unlike class A1 evasins, both the N‐ and C‐termini of EVA‐ACA1001 play minimal roles in chemokine binding. To understand the structural basis of its broad chemokine recognition, we determined the crystal structure of EVA‐ACA1001 in complex with the human chemokine CCL16. EVA‐ACA1001 forms backbone‐backbone interactions with the CC motif of CCL16, a conserved feature of all class A evasin‐chemokine complexes. A hydrophobic pocket in EVA‐ACA1001, formed by several aromatic side chains and the unique disulfide bond of class A3 evasins, accommodates the residue immediately following the CC motif (the "CC + 1 residue") of CCL16. This interaction is shared with EVA‐AAM1001, the only other class A3 evasins characterized to date, suggesting it may represent a common mechanism that accounts for the broad recognition of CC chemokines by class A3 evasins. [ABSTRACT FROM AUTHOR]

The fast‐growing usage of electronics is creating large amounts of e‐waste (electronic waste), most of which are directly sent into landfills or incinerated as recycling is either impractical or too costly. Therefore, it is believed that degradable, environmentally friendly materials are the solution to this pressing issue. Herein, disintegrable, durable, and highly stretchable strain sensors are developed based on elastic thin films made of sodium carboxymethyl cellulose, glycerol, and polyvinyl alcohol. The polymer thin films show a failure strain up to ≈ 330% and low hysteresis (5.74% at the second cycle) when subjected to 50% cyclic strain, due to the formation of inter or intramolecular hydrogen bonds. Carbon nanofibers with Au thin film are deposited on the elastic thin film, resulting in highly stretchable piezoresistive strain sensors with a maximum gauge factor of 1.7. More interestingly, the as‐developed sensors can be completely broken down in hot water (at ≈ 95 °C) within ≈ 25 min, indicating their remarkable disintegrability. This unique characteristic is expected to contribute to environmental sustainability. The applications of the sensor for joint bending recognition as well as physiological sign measurement have been demonstrated. [ABSTRACT FROM AUTHOR]

Anthropogenic radionuclides 129I and 236U are used to investigate pathways of the Atlantic Water flow in the Canada Basin, estimate transport timescales, and investigate mixing dynamics within the Atlantic Water layer and the overlying Pacific Water. Transit Time Distribution (TTD) model mean ages indicate water takes 25–35 years to reach the Canada Basin from the entrance of the Arctic, with limited lateral and vertical mixing along the core of the Arctic Ocean Boundary Current. Mode ages obtained from the model yield shorter transport times of 20–32 years. These age estimates agree with previous studies using these radionuclides and ventilation tracers in this region, indicating a steady‐state flow of Atlantic Water for the last 15 years. The distribution of the isotopes in the Atlantic layer indicates two pathways Atlantic Water may take into the basin, supported by the distribution of ages in the TTD model. End‐member mixing models indicate that the Pacific Winter water acquires a 20%–40% Atlantic Water signal of the radionuclides, upwelled over short periods, most likely along the shelf and Barrow Canyon region. Plain Language Summary: Man‐made nuclear products are used to trace the path of Atlantic water from the Atlantic Ocean to the Canada Basin in the Arctic, determine its transit time, and how it interacts with itself and Pacific Water that enters through the Bering Strait. The model suggests water takes 25–35 years to flow from the entrance of the Arctic to the Canada Basin, while a second estimate of age suggests slightly shorter transit times. The results of this study show that Atlantic Water flow has not changed significantly in the last 15 years. The distribution of the isotopes and ages also indicates two possible pathways water may take to the basin. An additional finding is that Pacific Winter Water carries a tracer concentration of 20%–40% of Atlantic Water, probably from Atlantic Water upwelling along the shelf, and in the Barrow Canyon region. Key Points: 129I and 236U trace Atlantic sourced water in the Canada BasinUpwelling of tracer labeled Atlantic Water into the Pacific Winter Water distinguishes the layer from Pacific Summer WaterTransit time distributions yield ages of 25–35 years for the core Atlantic Water [ABSTRACT FROM AUTHOR]

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short‐term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data‐driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data‐driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data. Key points: Dynamic cerebral autoregulation is governed by two time constants.The first time constant is the arterial transit time, rather than the traditional 'RC' time constant widely used in previous models.This arterial transit time is approximately 1 s in the brain.The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time.The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model. [ABSTRACT FROM AUTHOR]

Androgen deprivation therapy (ADT) plays an important, integral role in the treatment of prostate cancer; however, it is associated with multiple metabolic and other adverse effects. Making patients aware of these prior to starting ADT and assessing any specific risks during discussions is key to optimising outcomes. A brief checklist for health care professionals to use with patients, such as the one presented here, can aid discussions and facilitate signposting to appropriate specialist services without increasing workload. [ABSTRACT FROM AUTHOR]

With increasing urbanisation, there is a growing disconnect between soil, food, and people, centred around those relying on Western food production models. This 'wicked' problem is challenging sustainable soil use and food insecurity. Knowledge of soils through scientific studies alone are unable to address this problem, and we need to extend the boundaries of soil science for real progress to be made. We present a conceptual framework for understanding the reciprocal connections between soil, food, and people in local food production systems in Aotearoa New Zealand, applying principles and practices from a transdisciplinary research methodology. The resultant Food‐Landscape Networks framework consists of seven factors that support understanding the inherent connections between soil, food, and people. The factors are: soil health, land suitability, climate, productivity, food quality, well‐being, and engagement. These factors have been identified from weaving together mātauraka (the Kāi Tahu mita [dialect] is used in this text, where the 'ng' diagraph is replaced with 'k', e.g., mātauranga = mātauraka) Māori (Māori knowledge, culture, worldview, and values) and soil science using the He Awa Whiria, Braided Rivers, epistemological framework. Mātauraka Māori guides the traditionally reductionist discipline of soil science into a more holistic space, in an Aotearoa New Zealand context. [ABSTRACT FROM AUTHOR]

The efficiency of energy conversion during magnetic reconnection is related to the reconnection rate. While the stable reconnection rate has been studied extensively, its growth between the time of reconnection onset and its peak has not been thoroughly discussed. We use a 2D particle‐in‐cell simulation to examine how the reconnection rate evolves during the growth process and how it relates to changes near the x‐line. We identify three phases of growth: (a) slow quasi‐linear growth, (b) rapid exponential growth, and (c) tapered growth followed by negative growth after the reconnection rate peaks. We associate phase 1 with the breaking of x‐line uniformity by a localized density depletion that changes the in‐plane electric field structure near the neutral line, followed by the expansion of the inflow region and the enhancement of inflow Poynting flux Sz associated with the out‐of‐plane electric field Ey in phase 2. We show how the Hall fields facilitate rapid growth in phase 2 by opening up the exhaust and relieving the electron‐scale bottleneck to allow rapid energy transport across the separatrices. We find that in phase 3, the inflow of electromagnetic energy accumulates until the downstream electromagnetic energy density saturates toward the initial upstream asymptotic value. Finally, we examine how the electron outflow and the downstream ion populations interact in phase 3 and how each species exchanges energy with the local field structures in the exhaust. Key Points: Growth of the reconnection rate characterized by three distinct phasesLocal density depletion initiates slow growth of reconnection rate and changes electrostatic structureReconnection rate stabilizes as downstream magnetic energy density approaches its initial asymptotic value [ABSTRACT FROM AUTHOR]

In this article, one teacher shares her journey using decodable books with her culturally and linguistically diverse students, documenting new understandings and tensions that she has encountered. Four literacy teacher educators augment the teacher's story by connecting it with the current literature on literacy and decodable books. After reading this article, readers will walk away with a stronger understanding of how and when to use decodable books with beginning readers, as well as concrete ideas and resources to support incorporating decodable books into the early grades literacy curriculum. [ABSTRACT FROM AUTHOR]

We propose a holistic approach to define a river corridor as the minimum space needed to sustain key river functions based on an understanding of the desired functions of that corridor and the processes governing channel and floodplain formation. Giving such space is a fundamental nature‐based solution to river management, as it allows the river to use its own energy to maintain flood conveyance and habitat function. The review of existing river corridor concepts shows that these often focus on one or two potential functions of a river corridor and may not be well suited as tools to optimize eco‐geomorphic river function. We argue that evaluating the effects of river corridor width on multiple processes can provide an objective means to optimize delineation in areas where development encroaches onto floodplains and channel migration zones. Key processes are linked to channel migration and include floodplain rejuvenation, emergence of a dynamic patch mosaic of riparian habitat that sustains a functioning large wood cycle, and effects of constriction and confinement on channel dynamics and morphology. Quantification of these processes for an example river shows the most rapid gains for habitat and flood protection values up to the threshold for planform‐controlled conditions and an asymptotically reducing rate of gain in function above that threshold. For the example river, the threshold width approaching that asymptote is substantially more than its constrained condition but much less than the width of the floodplain and channel migration zone, offering a compromise for managing rivers with developed floodplains. This article is categorized under:Engineering Water > Sustainable Engineering of WaterWater and Life > Nature of Freshwater EcosystemsWater and Life > Conservation, Management, and Awareness [ABSTRACT FROM AUTHOR]

1H‐magnetic resonance spectroscopy (MRS) has the potential to improve the noninvasive diagnostic accuracy for paediatric brain tumours. However, studies analysing large, comprehensive, multicentre datasets are lacking, hindering translation to widespread clinical practice. Single‐voxel MRS (point‐resolved single‐voxel spectroscopy sequence, 1.5 T: echo time [TE] 23–37 ms/135–144 ms, repetition time [TR] 1500 ms; 3 T: TE 37–41 ms/135–144 ms, TR 2000 ms) was performed from 2003 to 2012 during routine magnetic resonance imaging for a suspected brain tumour on 340 children from five hospitals with 464 spectra being available for analysis and 281 meeting quality control. Mean spectra were generated for 13 tumour types. Mann–Whitney U‐tests and Kruskal–Wallis tests were used to compare mean metabolite concentrations. Receiver operator characteristic curves were used to determine the potential for individual metabolites to discriminate between specific tumour types. Principal component analysis followed by linear discriminant analysis was used to construct a classifier to discriminate the three main central nervous system tumour types in paediatrics. Mean concentrations of metabolites were shown to differ significantly between tumour types. Large variability existed across each tumour type, but individual metabolites were able to aid discrimination between some tumour types of importance. Complete metabolite profiles were found to be strongly characteristic of tumour type and, when combined with the machine learning methods, demonstrated a diagnostic accuracy of 93% for distinguishing between the three main tumour groups (medulloblastoma, pilocytic astrocytoma and ependymoma). The accuracy of this approach was similar even when data of marginal quality were included, greatly reducing the proportion of MRS excluded for poor quality. Children's brain tumours are strongly characterised by MRS metabolite profiles readily acquired during routine clinical practice, and this information can be used to support noninvasive diagnosis. This study provides both key evidence and an important resource for the future use of MRS in the diagnosis of children's brain tumours. [ABSTRACT FROM AUTHOR]

Mabel Creek Ridge, in the northern Gawler Craton, is a granulite‐facies domain recording early Mesoproterozoic metamorphism, flanked by less metamorphosed rocks and dissected by crustal‐scale divergent structures. The nature of early Mesoproterozoic events is poorly understood due to the lack of basement outcrop. Calculated metamorphic phase diagrams and geochronology are used to decipher the tectonic regime of a potential gneiss dome. Pressure–temperature (P–T) modelling of metapelites from five drill holes across Mabel Creek Ridge suggests it has experienced conditions of ~6.4–7.4 kbar and 800–850°C and the growth of suprasolidus cordierite after garnet indicates subsequent decompression. In situ U–Pb monazite and Lu–Hf garnet geochronology constrains the granulite‐facies metamorphism of Mabel Creek Ridge to ca. 1600–1560 Ma. In contrast, drill hole GOMA DH4 located to the north of Mabel Creek Ridge records conditions of 2.2–5.4 kbar and 710–740°C at ca. 1520 Ma, with no evidence for 1600–1560 Ma metamorphism. Our new P–T pseudosection results and geochronology data from Mabel Creek Ridge and adjacent crust, coupled with the regional seismic and airborne magnetic data, reveal that Mabel Creek Ridge represents a record of early Mesoproterozoic extension in the Gawler Craton, during which thermally perturbed lower crustal rocks were exhumed within a gneiss dome. Early Mesoproterozoic extension took place within a complex geodynamic regime resulting from the interplay between final Nuna convergence along the margin of northeast Australia at ca. 1600 Ma and subduction to the southwest at ca. 1630–1610 Ma. [ABSTRACT FROM AUTHOR]