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A metal tube-in-manifold packed bed capillary column device, designed to overcome common limitations associated with capillary LC separations, is described. Experimental results of initial packing tests with sub-3 μm core-shell particles demonstrated efficiencies greater than 47,000 plates/m for a separation performed using the column device. Computational fluid dynamics (CFD) modeling of the multicomponent separation used for this work was validated against experimental LC results and the optimized model was able to effectively predict component peak retention times. However, the accuracy of predicted efficiencies requires further refinement. The tube-in-manifold design demonstrates that packed capillary columns with cylindrical cross-sectional channel geometry and ultrahigh pressure, low dead volume fluidic connections are achievable., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: M.K., D. J. C., T. A., and G.S. are employed by IDEX Health & Science, which is the assignee for patents related to the technology described in this work. Partial funding from IDEX Health & Science in support of this project was provided to C.P. and J.P.G. (Rowan University)., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Fluoridoargentates(II) represent a fascinating class of silver(II) compounds with structural and magnetic similarities to cuprate superconductors. However, their synthesis is challenging, leaving their properties largely underexplored and hindering the discovery of new phases. This study introduces mechanochemistry as a novel approach for the synthesis of fluoridoargentates(II), avoiding the use of anhydrous HF or elemental fluorine and employing readily available equipment. Notably, ball milling of commercially available precursors successfully produced the long-sought-after first two examples of binary mixed-valent silver(I,II) phases, Ag I 2 Ag II F 4 (Ag 3 F 4 ) and Ag I Ag II F 3 (Ag 2 F 3 ). While the Ag I 2 Ag II F 4 phase was obtained at room temperature, the Ag I Ag II F 3 phase is metastable and required milling under cryogenic conditions. Characterization by synchrotron powder X-ray and neutron diffraction revealed that Ag I 2 Ag II F 4 crystallizes in the P 2 1 / c space group and is isostructural to β-K 2 AgF 4 . In this crystal structure, [Ag II F 2 F 4/2 ] 2- distorted octahedral units with 4 + 2 coordination, extend parallel to a -crystallographic axis giving a quasi-one-dimensional canted antiferromagnetic character, as shown by magnetic susceptibility. The triclinic perovskite Ag I Ag II F 3 phase adopts the P 1̅ space group, is isostructural to AgCuF 3 and also shows features of a one-dimensional antiferromagnet. This mechanochemical approach, also successfully applied to synthesize β-K 2 AgF 4 , is expected to expand the field of silver(II) chemistry, accelerating the search for silver analogs to cuprate superconductors and potentially extending to other cations in unusual oxidation states.

The synthesis of compounds containing partially deuterated groups such as CD 2 H lacks general methods. These compounds could be important for fine control of metabolic processes in drug discovery, or in the development of multifunctional probes for analysis by complementary spectroscopic techniques. Here, a convenient route to CD 2 H-methyl ketones is reported through coupling of esters with bis[(pinacolato)boryl]methane and trapping with D 2 O.

Rationale : Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive disease characterized by dyspnea and loss of lung function. Transforming growth factor-beta (TGF-β) activation mediated by α v integrins is central to the pathogenesis of IPF. Bexotegrast (PLN 74809) is an oral, once-daily, dual-selective inhibitor of α v β 6 and α v β 1 integrins under investigation for the treatment of IPF. Positron emission tomography (PET) using an α v β 6 -specific PET tracer could confirm target engagement of bexotegrast in the lungs of participants with IPF. Objectives : This Phase 2 study (NCT04072315) evaluated α v β 6 receptor occupancy in the lung, as assessed by changes from baseline in α v β 6 PET tracer uptake, following single dose administration of bexotegrast to participants with IPF. Methods : In this open-label, single-center, single-arm study, adults with IPF received up to 2 single doses of bexotegrast, ranging from 60 to 320 mg with or without background IPF therapy (pirfenidone or nintedanib). At baseline and approximately 4 hours after each orally administered bexotegrast dose, a 60-minute dynamic PET/CT scan was conducted following administration of an α v β 6 -specific PET probe ([ 18 F]FP-R 0 1-MG-F2). α v β 6 receptor occupancy by bexotegrast was estimated from the changes in PET tracer uptake following bexotegrast. Pharmacokinetics, safety, and tolerability of bexotegrast were also assessed. Results : Eight participants completed the study. Total and unbound plasma bexotegrast concentrations increased in a dose-dependent manner, and regional PET volume of distribution (V T ) values decreased in a dose- and concentration-dependent manner. The V T data fit a simple saturation model, producing an unbound bexotegrast EC 50 estimate of 3.32 ng/mL. Estimated maximum receptor occupancy was 35%, 53%, 71%, 88%, and 92% following single 60, 80, 120, 240, and 320-mg doses of bexotegrast, respectively. No treatment-emergent adverse events related to bexotegrast were reported. Conclusions : Dose- and concentration-dependent α v β 6 receptor occupancy by bexotegrast was observed by PET imaging, supporting once-daily 160 to 320 mg dosing to evaluate efficacy in clinical trials of IPF. Trial registration number: NCT04072315 Primary source of funding: Pliant Therapeutics, Inc. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Antarctic toothfish (Dissostichus mawsoni) in the Ross Sea region are believed to spawn predominantly in the northern parts of the Ross Gyre during the austral winter with fluctuations in their recruitment observed. This Lagrangian modelling study attempts to explain these fluctuations and shows how sea-ice drift impacts the buoyant eggs and the overall recruitment of juveniles reaching the Amundsen shelf break. Interannual variations in the Amundsen Sea Low, linked to tropical sea surface temperatures, cause modulations in the sea-ice drift and subsequent recruitment. When the Amundsen Sea Low is weaker, consistent with El Niño conditions, the northward sea-ice drift reduces, and more eggs remain within the Ross Gyre leading to a larger recruitment success. Conversely, recruitment success reduces during La Niña conditions. The sea-ice drift may explain about 80% of the interannual Antarctic toothfish recruitment variability over the period 1975-2016 and is of particular importance during the first year after spawning. These results enable future interannual changes in Antarctic toothfish recruitment success based on remote observations to be anticipated. Our findings suggest that ongoing climate change strengthening of the Amundsen Sea Low, will likely contribute to a long-term toothfish recruitment decline in the Ross Gyre region., (© 2024. The Author(s).)

Background: Procalcitonin (PCT) is a blood marker used to help diagnose bacterial infections and guide antibiotic treatment. PCT testing was widely used/adopted during the COVID-19 pandemic in the UK., Objectives: Primary: to measure the difference in length of early (during first 7 days) antibiotic prescribing between patients with COVID-19 who did/did not have baseline PCT testing during the first wave of the pandemic. Secondary: to measure differences in length of hospital/ICU stay, mortality, total days of antibiotic prescribing and resistant bacterial infections between these groups., Methods: Multi-centre, retrospective, observational, cohort study using patient-level clinical data from acute hospital Trusts/Health Boards in England/Wales. Inclusion: patients ≥16 years, admitted to participating Trusts/Health Boards and with a confirmed positive COVID-19 test between 1 February 2020 and 30 June 2020., Results: Data from 5960 patients were analysed: 1548 (26.0%) had a baseline PCT test and 4412 (74.0%) did not. Using propensity-score matching, baseline PCT testing was associated with an average reduction in early antibiotic prescribing of 0.43 days [95% confidence interval (CI): 0.22-0.64 days, P < 0.001) and of 0.72 days (95% CI: 0.06-1.38 days, P = 0.03] in total antibiotic prescribing. Baseline PCT testing was not associated with increased mortality or hospital/ICU length of stay or with the rate of antimicrobial-resistant secondary bacterial infections., Conclusions: Baseline PCT testing appears to have been an effective antimicrobial stewardship tool early in the pandemic: it reduced antibiotic prescribing without evidence of harm. Our study highlights the need for embedded, rapid evaluations of infection diagnostics in the National Health Service so that even in challenging circumstances, introduction into clinical practice is supported by evidence for clinical utility., Study Registration Number: ISRCTN66682918., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Society for Antimicrobial Chemotherapy.)

Different techniques and devices can achieve haemostasis after endovascular procedures to reduce time to haemostasis and facilitate percutaneous large-bore access. One such device is the Angio-Seal, which accomplishes haemostasis by compressing a collagen plug against the arteriotomy. Multiple complications related to Angio-Seal exist, most commonly acute artery occlusions and rarely infections and endarteritis. We present a case of an adult male (aged 80-85) who developed a groin haematoma associated with Angio-Seal use. Arterial bypass for arterial reconstruction and intravenous antibiotics were required. This case addresses the associated pathologies of Angio-Seal failure and Angio-Seal infection, patient- and device-specific risk factors and measures to treat and prevent these complications (ANGIO-SEAL VIP Vascular Closure Device-6 Fr Terumo Medical, NJ, USA)., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Immunoglobulin E (IgE)-mediated food allergies are the most common type of food allergy, often causing rapid symptoms after exposure to allergens posing a serious health risk and a high impact on patient's and caregiver's quality of life. Omalizumab, a humanized anti-IgE monoclonal antibody, reduces allergic reactions by binding to circulating IgE. Omalizumab has been successfully used in allergic asthma, chronic rhinosinusitis with nasal polyps, and chronic urticaria, and was recently approved for treating IgE-mediated food allergies by the US Food and Drug Administration (FDA). This GA 2 LEN ANACARE Consensus Statement presents our position on the use of omalizumab for treating IgE-mediated food allergies, based on a systematic review and meta-analysis, experience with use for other conditions, and expert consensus achieved via an eDelphi process. Following publication of the recent OUtMATCH study (stage 1) results and subsequent FDA approval, we propose that there is now sufficient evidence to recommend omalizumab as the only drug currently available that can mechanistically reduce IgE-mediated food allergic reactions. We acknowledge that the evidence does not reach the highest level of evidence which would be needed for a guideline recommendation., (© 2024 The Author(s). Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology.)

Metoclopramide, a prokinetic antiemetic with activity at multiple receptor types, may be a useful treatment for renal colic pain. This review investigated whether metoclopramide is an effective analgesic in the management of adults with renal colic.Eligible studies were randomised, quasi-randomised or case-control trials of metoclopramide for the management renal colic pain. Electronic database searches were performed in November 2022. Screening was performed by two authors independently; disagreement was resolved by discussion or by adjudication by a third author. The Cochrane Collaboration Risk of Bias Tool v2.0 was used to assess bias.Two studies were included, enrolling 279 patients. Heterogeneity of primary outcome measurement and comparators rendered meta-analysis inappropriate; a narrative review is presented. Both studies showed some evidence of analgesic effect. The largest study had a low risk of bias in all assessed domains, whilst the smaller study was at a high risk of bias.There is limited evidence that metoclopramide may be an effective analgesic in the management of renal colic, with the highest quality study demonstrating analgesic properties similar to an intravenous non-steroidal anti-inflammatory medication.Protocol registration Prospero (CRD42022346618)., (© 2024. The Author(s).)

Background: Acute aortic syndrome (AAS) requires urgent diagnosis with computed tomographic angiography (CTA). Diagnostic strategies need to weigh the benefits of detecting AAS against the costs of using CTA with a low yield of AAS when the prevalence of AAS is low. We aimed to estimate the cost-effectiveness of diagnostic strategies using clinical probability scoring and D-dimer to select patients with potential symptoms of AAS for CTA., Methods: We developed a decision analytical model to simulate the management of patients attending hospital with possible AAS. We modelled diagnostic strategies that used the Aortic Dissection Detection Risk Score (ADD-RS) and D-dimer to select patients for CTA. We used estimates from our meta-analysis, existing literature and clinical experts to model the consequences of diagnostic strategies on survival, health utility, and health and social care costs. We estimated the incremental cost per quality-adjusted life-years gained by each strategy compared with the next most effective alternative on the efficiency frontier., Results: A strategy based on the Canadian guideline (CTA if ADD-RS>1 or ADD-RS=1 with D-dimer >500 ng/mL) is cost-effective but would result in high rates of CTA if applied to an unselected population (AAS prevalence 0.26%). The strategy is also cost-effective and would result in lower rates of CTA if applied to a more selected population, such as those with a non-zero clinical suspicion of AAS (prevalence 0.61%). For patients currently receiving CTA, using ADD-RS>1 or D-dimer >500 ng/mL to select patients for CTA is cost-effective., Conclusions: A strategy using ADD-RS>1 or ADD-RS=1 with D-dimer >500 ng/mL to select patients for CTA appears cost-effective but primary research is required to evaluate this strategy in practice and determine how suspicion of AAS is identified., Competing Interests: Competing interests: All authors declare funding from NIHR Health Technology Assessment Grant NIHR151853. There are no other competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background and Objectives: Over a million sport-related concussions (SRC) affect children annually in the United States, posing a significant public health concern. Limited data exist on the premorbid risk factors and injury characteristics of SRCs in high school athletes. This study aims to understand acute SRC injury characteristics and describe premorbid risk factors in high school athletes., Methods: Athletes (aged 14-19 years) from 19 central Illinois high schools participating in school-sponsored sports from 2009 to 2023 were included. Sports Concussion Assessment Tool evaluations were performed as part of preseason and postinjury evaluations. Injury characteristics, such as mechanism, setting, and symptoms, were described using all SRCs in the study period. Odds ratios (OR) were computed to determine risk factors using athletes with a baseline Sports Concussion Assessment Tool before SRC and nonconcussed athletes., Results: In total, 4360 athletes were included (3953 without SRC; 407 with ≥1 SRC of whom 168 had a previous baseline). Overall, 24.2% of SRCs occurred in female athletes, and most SRCs occurred in competitions while playing American football (52.3%), soccer (20.4%), and basketball (7.6%). Blow/hit to the head was the most common mechanism. Headache was the most severe symptom (2.55 ± 1.51 [SD]), and symptoms of emotionality and nervousness/anxiety were significantly more severe in female athletes (P < .05). Students with previous concussions (OR 2.64 95% CI [1.81, 3.78]), previous hospitalization for head injury (OR 3.19 95% CI [1.9, 5.14]), headache/migraine disorders (OR 2.23 95% CI [1.29, 3.66]), and learning disabilities (OR 2.69 95% CI [1.47, 4.61]) had greater odds of SRC (P < .05). Lower odds of SRC were seen in athletes identifying as Black or African American (vs White) (OR 0.54 95% CI [0.32, 0.86]) and those attending larger (vs smaller) schools (OR 0.64 95% CI [0.46, 0.88])., Conclusion: Understanding SRC risk factors and characteristics in high school athletes is critical for developing prevention and management programs, guiding neurosurgeons in mitigating SRC risk, and informing return-to-play decisions., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

VMXm joins the suite of operational macromolecular crystallography beamlines at Diamond Light Source. It has been designed to optimize rotation data collections from protein crystals less than 10 µm and down to below 1 µm in size. The beamline has a fully focused beam of 0.3 × 2.3 µm (vertical × horizontal) with a tuneable energy range (6-28 keV) and high flux (1.6 × 10 12  photons s -1 at 12.5 keV). The crystals are housed within a vacuum chamber to minimize background scatter from air. Crystals are plunge-cooled on cryo-electron microscopy grids, allowing much of the liquid surrounding the crystals to be removed. These factors improve the signal-to-noise during data collection and the lifetime of the microcrystals can be prolonged by exploiting photoelectron escape. A novel in vacuo sample environment has been designed which also houses a scanning electron microscope to aid with sample visualization. This combination of features at VMXm allows measurements at the physical limits of X-ray crystallography on biomacromolecules to be explored and exploited., (open access.)

Introduction: In women with cervical incompetence, transvaginal cerclage may help prevent preterm birth. However, training for this procedure poses challenges due to the low number of cases and difficulties in visualizing the operative field. Furthermore, the objective criteria for a successful cerclage procedure are not well-described. Quality assessment relies heavily on self-assessment rather than objective criteria and feedback. To address this issue, training on a simulator may offer a solution. We aimed to objectively assess surgical performance and compare it to the self-assessed performance in transvaginal cerclage procedures., Materials and Methods: During the Nordic Federation of Obstetrics and Gynecology (NFOG) congress in 2023, surgeons proficient in transvaginal cerclage procedures performed a transvaginal cerclage on a simulator. To compare the observed and self-assessed outcomes we obtained measurements on the cerclage height and number of bites from the detachable cervix, and from computed tomography scans we analyzed suture bite depth, reduction of cervix surface area, and whether cerclages had perforated the cervical canal. The same outcomes were self-assessed by each participant after the cerclage procedure. We visualized the continuous paired data in a Bland-Altman plot and compared these data with a paired t-test. Paired binary data was analyzed using McNemars test., Results: 29 participants from eight different nationalities performed one transvaginal cerclage each. The mean height of the cerclage was 26.8 mm (SD 9 mm) and mean depth was 6.5 mm (SD 1.9 mm) across a mean of 4.1 (SD 0.8) bites. The mean reduction of the cervix surface area was 7.6 % (SD 5.9 %). Two sutures perforated the cervical canal. The participants significantly underestimated the height of their cerclage with a mean difference of 6.0 mm (95 % CI 2.1-9.9), (p 0.002), between the observed and the self-assessed height, but otherwise revealed good self-assessment of their performed procedure., Conclusions: Overall, the experienced cerclage surgeons showed a genuine insight into their surgical performance of a transvaginal cerclage. These results could warrant development of a procedural guidelines with objective measures, now reassured that surgeons are capable of self-assessing their procedures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: G. Tydeman and A. H. Shennan are inventors of the simulator. G Tydeman receives personal royalties from Limbs&Things Ltd with A Shennan receiving royalties to his institution. The remaining authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Aims: Glycogenic hepatopathy is associated with significant psychosocial consequences and health costs. Metabolic Dysfunction-Associated Steatotic Liver Disease and glycogenic hepatopathy are frequently confused as "fatty liver" when seen on ultrasonography. We wished to examine liver fat and glycogen content in groups defined based on metabolic and liver disease phenotypes., Methods: This case-control study undertaken in a tertiary hospital used nuclear proton magnetic resonance spectroscopy ( 1 H-MRS) to examine liver fat and glycogen content in five clinical groups, each containing five participants: 1. type 1 diabetes with glycogenic hepatopathy, 2. satisfactorily controlled type 1 diabetes with no liver disease, 3. poorly controlled type 1 diabetes without liver disease, 4. a control group of body mass index- and age-matched individuals without diabetes or liver disease, and 5. hepatic steatosis., Results: Fat content was highest in the hepatic steatosis (median 15.4 %, IQR 10.0-19.3) and glycogenic hepatopathy (median 6.5 %, IQR 4.5-9.1) groups and compared to both of these groups was lower in the control group (median 1.0 %, IQR 0.7-1.1, p 0.002 and 0.022), the T1DM group with satisfactory control (median 0.3 %, IQR 0.2-0.6, p < 0.001 and <0.001), and the T1DM group with poor control without liver disease (median 1.1 %, IQR 0.9-1.1, p 0.001 and 0.012). No participants from the type 1 diabetes poor control, type 1 diabetes satisfactory control or the no diabetes groups had 1 H-MRS-diagnosed hepatic steatosis. 1 H-MRS glycogen content could not be interpreted in the majority of those with glycogenic hepatopathy because of interference from the fat signal., Conclusions: In cases diagnosed with glycogenic hepatopathy there may be significant concomitant fat accumulation, compounding the already elevated cardiovascular risk in this cohort. The technique of 1 H-MRS has not been demonstrated to be useful for diagnosing glycogenic hepatopathy., 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cybersickness remains a major drawback of Virtual Reality (VR) headsets, as a breadth of stationary experiences with visual self-motion can result in visually-induced motion sickness. However, not everybody experiences the same intensity or type of adverse symptoms. Here we propose that prior experience with virtual environments can predict ones degree of cybersickness. Video gaming can enhance visuospatial abilities, which in-turn relate negatively to cybersickness - meaning that consistently engaging in virtual environments can result in protective habituation effects. In a controlled stationary VR experiment, we found that 'VR-naive' video gamers experienced significantly less cybersickness in a virtual tunnel-travel task and outperformed 'VR-naive' non-video gamers on a visual attention task. These findings strongly motivate the use of non-VR games for training VR cybersickness resilience, with future research needed to further understand the mechanism(s) by which gamers become cybersickness resilient - potentially expanding access to VR for even the most susceptible participants.

Background: The optimal dosing strategy for infliximab in steroid-refractory acute severe ulcerative colitis (ASUC) is unknown. We compared intensified and standard dose infliximab rescue strategies and explored maintenance therapies following infliximab induction in ASUC., Methods: In this open-label, multicentre, randomised controlled trial, patients aged 18 years or older from 13 Australian tertiary hospitals with intravenous steroid-refractory ASUC were randomly assigned (1:2) to receive a first dose of 10 mg/kg infliximab or 5 mg/kg infliximab (randomisation 1). Block randomisation was used and stratified by history of thiopurine exposure and study site, with allocation concealment maintained via computer-generated randomisation. Patients in the 10 mg/kg group (intensified induction strategy [IIS]) received a second dose at day 7 or earlier at the time of non-response; all patients in the 5 mg/kg group were re-randomised between day 3 and day 7 (1:1; randomisation 2) to a standard induction strategy (SIS) or accelerated induction strategy (AIS), resulting in three induction groups. Patients in the SIS group received 5 mg/kg infliximab at weeks 0, 2, and 6, with an extra 5 mg/kg dose between day 3 and day 7 if no response. Patients in the AIS group received 5 mg/kg infliximab at weeks 0, 1, and 3, with the week 1 dose increased to 10 mg/kg and given between day 3 and day 7 if no response. The primary outcome was clinical response by day 7 (reduction in Lichtiger score to <10 with a decrease of ≥3 points from baseline, improvement in rectal bleeding, and decreased stool frequency to ≤4 per day). Secondary endpoints assessed outcomes to day 7 and exploratory outcomes compared induction regimens until month 3. From month 3, maintenance therapy was selected based on treatment experience, with use of thiopurine monotherapy, combination infliximab and thiopurine, or infliximab monotherapy, with follow-up as a cohort study up to month 12. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, NCT02770040, and is completed., Findings: Between July 20, 2016, and Sept 24, 2021, 138 patients were randomly assigned (63 [46%] female and 75 [54%] male); 46 received a first dose of 10 mg/kg infliximab and 92 received 5 mg/kg infliximab. After randomisation 1, we observed no significant difference in the proportion of patients who had a clinical response by day 7 between the 10 mg/kg and 5 mg/kg groups (30 [65%] of 46 vs 56 [61%] of 92, p=0·62; risk ratio adjusted for thiopurine treatment history, 1·06 [95% CI 0·94-1·20], p=0·32). We found no significant differences in secondary endpoints including time to clinical response or change in Lichtiger score from baseline to day 7. Two patients who received 10 mg/kg infliximab underwent colectomy in the first 7 days compared with no patients in the 5 mg/kg group (p=0·21). Three serious adverse events occurred in three patients in both the 10 mg/kg group and 5 mg/kg group. After randomisation 2, the proportions of patients with clinical response at day 14 (34 [74%] of 46 in the IIS group, 35 [73%] of 48 in the AIS group, and 30 [68%] of 44 in the SIS group, p=0·81), clinical remission at month 3 (23 [50%], 25 [52%], 21 [48%], p=0·92), steroid-free remission at month 3 (19 [41%], 20 [42%], 18 [41%], p=1·0), endoscopic remission at month 3 (21 [46%], 22 [46%], 21 [48%], p=0·98), and colectomy at month 3 (three [7%] of 45, nine [19%] of 47, five [12%] of 43, p=0·20) were not significantly different between groups. Between day 8 and month 3, the proportion of patients with at least one infectious adverse event possibly related to infliximab was two (4%) of 46 in the IIS group, eight (17%) of 48 in the AIS group, and eight (18%) of 44 in the SIS group (p=0·082). No deaths occurred in the study., Interpretation: Infliximab is a safe and effective rescue therapy in ASUC. In steroid-refractory ASUC, a first dose of 10 mg/kg infliximab was not superior to 5 mg/kg infliximab in achieving clinical response by day 7. Intensified, accelerated, and standard induction regimens did not result in a significant difference in clinical response by day 14 or in remission or colectomy rates by month 3., Funding: Australian National Health and Medical Research Council, Gastroenterology Society of Australia, Gandel Philanthropy, Australian Postgraduate Award, Janssen-Cilag., Competing Interests: Declaration of interests MCC is supported by a Gandel Major Philanthropy Grant and an Australian Postgraduate Award, and has received research funding from Janssen-Cilag. CFDLWS has served as a speaker for DiaSorin, has received educational support from Pfizer, Shire, and Ferring, has received research funding from the Robert C Bulley Charitable Foundation and St Vincent's Hospital Melbourne Research Endowment Fund, and is supported by an Australian National Health and Medical Research Council (NHMRC) Postgraduate Scholarship. DC has received educational support from Viatris and is supported by an NHMRC Postgraduate Scholarship. EKW has served as a consultant, advisory board member, or speaker for AbbVie, Bristol Myers Squibb, Ferring, Janssen, Celltrion, Falk, and Takeda, is supported by an NHMRC Emerging Leadership Level 1 Fellowship, and has received research support from Ferring and Janssen. AP has served as an advisory board member or received speaker fees from AbbVie, Ferring, Janssen, Pfizer, Takeda, and Dr Falk Pharma. BC has served as a consultant, advisory board member, or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, the Helmsley Charitable Trust, the NHMRC, and Takeda. WN has received educational and research support from Pfizer, AbbVie, Janssen, Shire and Ferring. JB has served as a consultant, advisory board member, or speaker for AbbVie, Ferring, Janssen, Celltrion, Chiesi, Janssen, Pfizer, Amgen, GlaxoSmithKline, Bristol Myers Squibb, Microba, Anatara, and Takeda, and has received research support from the NHMRC, United States Department of Defense, AbbVie, Janssen, Ferring, Pfizer, and Takeda. MG has served on the advisory board of Pfizer and AbbVie and has received speaker fees and research grants from Abbvie, Celltrion, Janssen, Pfizer and travel grants from Pfizer. NM has received speaker fees from Takeda and Baxter, and educational support from Baxter. DRVL has received consulting fees from AbbVie and speaker fees for Takeda. NSD reports serving as an advisory board member or speaker for AbbVie, Celltrion, Chiesi, Ferring, Janssen, Eli Lilly, MSD, Pfizer, Takeda, and Shire, and has received research support from AbbVie, Celltrion, The Gastroenterological Society of Australia, and the NHMRC. RWL reports advisory board membership for AbbVie, Aspen, Bristol Myers Squibb, Celgene, Celltrion, Chiesi, Ferring, Glutagen, Hospira, Janssen, Eli Lilly, MSD, Novartis, Pfizer, Prometheus Biosciences, and Takeda, and research grants from the University of Sydney, the McCusker Charitable Foundation, Celltrion, Shire, Janssen, Takeda, Joanna Tiddy grant, the Gastroenterological Society of Australia, the NHMRC, The Gutsy Group, and Pfizer. MPS has received educational grants or research support from Gilead and Celltrion, speaker fees from Janssen, AbbVie, Ferring, Takeda, Pfizer, Shire, Celltrion, Eli Lilly, and Dr Falk Pharma, and has served on advisory boards or received consultancy fees for Janssen, Takeda, Pfizer, Celgene, AbbVie, MSD, Emerge Health, Gilead, Bristol Myers Squibb, Celltrion, and Eli Lilly, and has received travel grants from Pfizer and Dr Falk Pharma. PDC has served as a consultant, advisory board member, or speaker for AbbVie, Baxter, Ferring, Janssen, Celltrion and Emerge Health, and is supported by a NHMRC Emerging Leadership Level 2 Fellowship, and has received research support from AbbVie, Ferring, Janssen and Pfizer. All other authors declare no competing interests., (Crown Copyright © 2024. Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Recent updates have detailed how patients with nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) may be better risk stratified using prognostic scoring systems. Most patients with NLPHL present with early-stage disease and have an indolent disease course. To reflect these differences from classic Hodgkin lymphoma, nomenclature has been updated to recognize nodular lymphocyte-predominant B-cell lymphoma as an alternative to NLPHL. The Global NLPHL One Working Group have published their pivotal dataset in 2024 which challenges the prognostic significance of variant immunoarchitectural (IAP) patterns and proposes a new prognostic scoring system. Key identified prognostic factors include age >45 years, stage III-IV disease, hemoglobin <10.5 g/dL and splenic involvement. After multivariate analysis, variant IAP was not shown to be associated with inferior outcome. As most patients with NLPHL have excellent long-term survival, identifying patients where treatment de-escalation is appropriate will help to minimize toxicity. De-escalation strategies include observation after fully resected stage I disease, active surveillance, anti-CD20 antibody monotherapy, radiotherapy in early-stage disease, and avoiding anthracycline- or bleomycin-containing chemotherapy regimens. Evidence supporting the use of novel therapies remains limited with disappointing results from a recently published study of ibrutinib in patients with relapsed NLPHL. Hopefully, future trials will investigate novel agents such as checkpoint inhibitors, T-cell engaging antibodies and chimeric antigen receptor T-cell therapy.

Objective: To assess whether universal use of every-other-day glucose monitoring in patients with gestational diabetes mellitus (GDM) resulted in similar birth weights and medication use and was preferred by the patient compared with traditional daily glucose monitoring., Methods: This was a noninferiority randomized controlled trial conducted at a single New York City hospital between April 2021 and May 2022. Patients with singleton pregnancies who were diagnosed with GDM after 20 weeks of gestation and had a minimum of 7 days of previous daily blood glucose testing were randomly assigned to test blood glucose values daily or every other day. The primary outcome was neonatal birth weight. We calculated a total sample size of 196 participants needed for noninferiority to be tested, assuming the mean birth weight in the every-other-day group, compared with the daily group, was no higher than the predefined noninferiority margin of 200 g (80% power and one-sided alpha of 0.05). Postrandomization characteristics, including blood glucose values and medication initiation and timing, were recorded. Satisfaction with treatment group was assessed using the validated Oxford Maternity Diabetes Treatment Satisfaction Questionnaire., Results: A total of 197 patients were randomized: 98 in the daily group and 99 in the every-other-day group. Baseline characteristics were similar between groups. The mean neonatal birth weight was similar between groups (mean±SD 3,090±418 g among newborns in the daily group compared with 3,181±482 g among newborns in the every-other-day group). For the primary outcome, the every-other-day group was found to be noninferior to the daily group with an upper confidence limit for the mean difference in mean birth weight of 197 g, which was below the noninferiority margin of 200 g ( P =.046). Postrandomization, there were no significant differences in the number of patients who required medication, the gestational age at which medication was started, or the type of medication used. Average fasting and postprandial glucose values were similar between groups. There was an increase in adherence to treatment group in those randomized to every-other-day blood sugars, but no difference in patient satisfaction., Conclusion: In patients with GDM, testing blood glucose values every other day was as effective as testing daily, without apparent effects on birth weight, medication initiation, or glucose control. Reduced frequency of blood glucose monitoring might help decrease the emotional, physical, and financial burden experienced by patients with GDM., Clinical Trial Registration: ClinicalTrials.gov , NCT04857073., Competing Interests: Financial Disclosure The authors did not report any potential conflicts of interest., (Copyright © 2024 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Background: Evolution of herbicide-resistant weed populations is a major challenge to world food production. Using different herbicides in rotation and/or using different herbicides together as mixtures are strategies that may delay the selection of resistance. This study used simulation modelling to investigate whether mixtures and rotations can delay the selection of both generalist polygenic and specialist monogenic herbicide resistance, and whether these strategies are more likely to lead to the selection of generalist resistance in weed types with varying biological characteristics., Results: Our simulations suggest that well-designed effective herbicide mixtures should delay evolution of both polygenic and monogenic resistance better than rotations and single herbicides across all weed types. Both mixture and rotation strategies increased the likelihood of polygenic resistance compared to single-herbicide use, and the likelihood of polygenic resistance increased as the fecundity and competitiveness of the weed increased. Whether monogenic or polygenic resistance occurred in each case depended most on the relative initial allele frequencies. We did not find that herbicide mixtures were more likely than rotations to lead to the selection of generalist polygenic resistance. The simulated efficacy of mixtures over rotations decreased if components were used at reduced rates or when individual components had already been used solo., Conclusion: Herbicide rotations and particularly well-designed mixtures should delay evolution of both polygenic and monogenic resistance, especially if used as part of an effective integrated weed management programme. However, herbicide mixtures and rotations may also increase the risk that resistance will be generalist polygenic rather than specialist monogenic. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry., (© 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.)

Estimates of ambient background concentrations in surface waters, referred to as natural background concentrations (NBCs) in European guidance documents, may be an important factor in determining whether a monitoring site meets the legally binding Environmental Quality Standard (EQS) when assessing naturally occurring substances. Here, we focus on utilizing routine regulatory surface water monitoring data to provide risk assessors and environmental practitioners with a transparent, implementable, repeatable, and resource-effective approach to estimate NBCs. The methodology does not use additional environmental sampling beyond that which is routine or require advanced statistical methods, or the incorporation of highly specialist, and not always readily accessible, local knowledge. It determines both whether a site is suitable for NBC assessment as well as the identification of suitable surrogate sites and local NBCs using 11 criteria: six for identifying if a site is suitable for NBC correction, and five for identifying suitable surrogate sites for local NBC values. The criteria consider both the extent of any EQS exceedance, after accounting for bioavailability in line with the European guidance and potential anthropogenic impacts at the site, and can be applied in a simple sequential procedure. The method has been applied to derive NBCs for nickel on three case-study countries-Cyprus, France, and Spain-to determine its useability and impact on compliance. The methodology presented addresses a gap in the current guidance regarding the practical and consistent implementation of NBCs and could be applied to other naturally occurring substances in an EQS or Water Quality Guideline compliance assessment process. Integr Environ Assess Manag 2024;20:2128-2141. © 2024 WCA Environment Ltd and NiPERA Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC)., (© 2024 WCA Environment Ltd and NiPERA Inc. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).)

Rationale: The early identification of children with poorly controlled asthma is imperative for optimizing treatment strategies. The analysis of exhaled volatile organic compounds (VOCs) is an emerging approach to identify prognostic and diagnostic biomarkers in pediatric asthma. Objectives: To assess the accuracy of gas chromatography-mass spectrometry-based exhaled metabolite analysis to differentiate between controlled and uncontrolled pediatric asthma. Methods: This study encompassed discovery (SysPharmPediA [Systems Pharmacology Approach to Uncontrolled Paediatric Asthma]) and validation (U-BIOPRED [Unbiased Biomarkers for the Prediction of Respiratory Disease Outcomes] and PANDA [Paediatric-Asthma-Non-Invasive-Diagnostic-Approaches]) phases. First, exhaled VOCs that discriminated degrees of asthma control were identified. Subsequently, outcomes were validated in two independent cohorts. Patients were classified as controlled or uncontrolled on the basis of asthma control test scores and the number of severe attacks in the past year. In addition, the potential of VOCs to predict two or more future severe asthma attacks in SysPharmPediA was evaluated. Measurements and Main Results: Complete data were available for 196 children (SysPharmPediA, n  = 100; U-BIOPRED, n  = 49; PANDA, n  = 47). In SysPharmPediA, after randomly splitting the population into training ( n  = 51) and test ( n  = 49) sets, three compounds (acetophenone, ethylbenzene, and styrene) distinguished between patients with uncontrolled and controlled asthma. The areas under the receiver operating characteristic curves (AUROCCs) for training and test sets were, respectively, 0.83 (95% confidence interval [CI], 0.65-1.00) and 0.77 (95% CI, 0.58-0.96). Combinations of these VOCs resulted in AUROCCs of 0.74 ± 0.06 (U-BIOPRED) and 0.68 ± 0.05 (PANDA). Attack prediction tests resulted in AUROCCs of 0.71 (95% CI, 0.51-0.91) and 0.71 (95% CI, 0.52-0.90) for the training and test sets. Conclusions: Exhaled metabolite analysis might enable asthma control classification in children. This should stimulate the further development of exhaled metabolite-based point-of-care tests in asthma.

Background and Aims: Muscle wasting results in weakness for patients with critical illness. We aim to explore ultrasound-derived rates of change in skeletal muscle in the intensive care unit (ICU) and following discharge to the post-ICU ward., Design: Post hoc analysis of a multicentre randomised controlled trial of functional-electrical stimulated cycling, recumbent cycling, and usual care delivered in intensive care., Method: Participants underwent ultrasound assessment of rectus femoris at ICU admission, weekly in the ICU, upon awakening, ICU discharge, and hospital discharge. The primary outcome was rate of change in rectus femoris cross-sectional area (ΔRF CSA ) in mm 2 /day in the ICU (enrolment to ICU discharge) and in the post-ICU ward (ICU discharge to hospital discharge). Secondary outcomes included rate of change in echo intensity (ΔEI), standard deviation of echo intensity (ΔEI SD ), and the intervention effect on ultrasound measures. Echo intensity is a quantitative assessment of muscle quality. Elevated echo intensity may indicate fluid infiltration, adipose tissue, and reduced muscle quality., Results: 154 participants were included (mean age: 58 ± 15 years, 34% female). Rectus femoris cross-sectional area declined in the ICU (-4 mm 2 /day [95% confidence interval {CI}: -9 to 1]) and declined further in the ward (-9 mm 2 /day [95% CI: -14 to -3]) with a mean difference between ICU and ward of -5 mm 2 /day ([95% CI: -2, to 11]; p = 0.1396). There was a nonsignificant difference in ΔEI between in-ICU and the post-ICU ward of 1.2 ([95% CI: -0.1 to 2.6]; p = 0.0755), a statistically significant difference in ΔEI SD between in-ICU and in the post-ICU ward of 1.0 ([95% CI, 0.5 to 1.5]; p = 0.0003), and no difference in rate of change in rectus femoris cross-sectional area between groups in intensive care (p = 0.411) or at hospital discharge (p = 0.1309)., Conclusions: Muscle wasting occurs in critical illness throughout the hospital admission. The average rate of loss in muscle cross-sectional area does not slow after ICU discharge, even with active rehabilitation., Competing Interests: Conflict of interest The authors declare no potential conflicts of interest with respect to the research, authorship and/or publication of this article., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: Osteophytes are commonly used to diagnose and guide knee osteoarthritis (OA) treatment, but their causes are unclear. Although they are not typically the focus of knee arthroplasty surgeons, they can predict case difficulty and length. Furthermore, their extent and location may yield much information about the knee joint status. The aims of this computed tomography-based study in patients awaiting total or partial knee arthroplasty were to: (1) measure osteophyte volume in anatomical subregions and relative change as total volume increases; (2) determine whether medial and/or lateral OA affects osteophyte distribution; and (3) explore relationships between osteophytes and OA severity., Methods: Data were obtained from 4,928 computed tomography scans. Machine-learning-based imaging analyses enabled osteophyte segmentation and quantification, divided into anatomical regions. Mean three-dimensional joint space narrowing was assessed in medial and lateral compartments. A Bayesian model assessed the uniformity of osteophyte distribution. We correlated femoral osteophyte volumes with B-scores, a validated OA status measure., Results: Total tibial (25%) and femoral osteophyte volumes (75%) within each knee correlated strongly (R 2  = 0.85). Medial osteophytes (65.3%) were larger than lateral osteophytes (34.6%), with similar proportions in both the femur and tibia. Osteophyte growth was found in all compartments, and as total osteophyte volume increased, the relative distribution of osteophytes between compartments did not markedly change. No evidence of variation was found in the regional distribution of osteophyte volume between knees with medial, lateral, both, or no three-dimensional joint space narrowing in the femur or tibia. There was a direct relationship between osteophyte volume and OA severity., Conclusions: Osteophyte volume increased in both medial and lateral compartments proportionally with total osteophyte volume, regardless of OA location. The peripheral position of femoral osteophytes does not appear to contribute to load-bearing. This suggests that osteophytic growth represents a 'whole-knee'/global response. This work may have broad applications for knee OA, both surgically and nonoperatively., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Peripheral blood transcriptomes from 383 patients with newly diagnosed melanoma were subjected to differential gene expression analysis. The hypotheses were that impaired systemic immunity is associated with poorer prognosis (thicker tumors and fewer tumor-infiltrating lymphocytes) and evidence of systemic inflammation (high-sensitivity CRP and fibrinogen levels). Higher fibrinogen levels were associated with thicker primary tumors. In single-gene analysis, high-sensitivity CRP levels were significantly associated with higher blood CD274 expression (coding for PD-L1), but each was independently prognostic, with high-sensitivity CRP associated with increased mortality and higher CD274 protective, independent of age. Pathway analysis identified downregulation of immune cell signaling pathways in the blood of people with thicker tumors and notable upregulation of signal transducer and activator of transcription 1 gene STAT1 in people with brisk tumor-infiltrating lymphocytes. Transcriptomic data provided evidence for increased NF-kB signaling with higher inflammatory markers but with reduction in expression of HLA class II molecules and higher CD274, suggesting that aberrant systemic inflammation is a significant mediator of reduced immune function in melanoma. In summary, transcriptomic data revealed evidence of reduced immune function in patients with thicker tumors and fewer tumor-infiltrating lymphocytes at diagnosis. Inflammatory markers were associated with thicker primaries and independently with death from melanoma, suggesting that systemic inflammation contributes to that reduced immune function., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Importance: More than 150 million people in India need mental health care but few have access to affordable care, especially in rural areas., Objective: To determine whether a multifaceted intervention involving a digital health care model along with a community-based antistigma campaign leads to reduced depression risk and lower mental health-related stigma among adults residing in rural India., Design, Setting, and Participants: This parallel, cluster randomized, usual care-controlled trial was conducted from September 2020 to December 2021 with blinded follow-up assessments at 3, 6, and 12 months at 44 rural primary health centers across 3 districts in Haryana and Andhra Pradesh states in India. Adults aged 18 years and older at high risk of depression or self-harm defined by either a Patient Health Questionnaire-9 item (PHQ-9) score of 10 or greater, a Generalized Anxiety Disorder-7 item (GAD-7) score of 10 or greater, or a score of 2 or greater on the self-harm/suicide risk question on the PHQ-9. A second cohort of adults not at high risk were selected randomly from the remaining screened population. Data were cleaned and analyzed from April 2022 to February 2023., Interventions: The 12-month intervention included a community-based antistigma campaign involving all participants and a digital mental health intervention involving only participants at high risk. Primary health care workers were trained to identify and manage participants at high risk using the Mental Health Gap Action Programme guidelines from the World Health Organization., Main Outcomes and Measures: The 2 coprimary outcomes assessed at 12 months were mean PHQ-9 scores in the high-risk cohort and mean behavior scores in the combined high-risk and non-high-risk cohorts using the Mental Health Knowledge, Attitude, and Behavior scale., Results: Altogether, 9928 participants were recruited (3365 at high risk and 6563 not at high risk; 5638 [57%] female and 4290 [43%] male; mean [SD] age, 43 [16] years) with 9057 (91.2%) followed up at 12 months. Mean PHQ-9 scores at 12 months for the high-risk cohort were lower in the intervention vs control groups (2.77 vs 4.48; mean difference, -1.71; 95% CI, -2.53 to -0.89; P < .001). The remission rate in the high-risk cohort (PHQ-9 and GAD-7 scores <5 and no risk of self-harm) was higher in the intervention vs control group (74.7% vs 50.6%; odds ratio [OR], 2.88; 95% CI, 1.53 to 5.42; P = .001). Across both cohorts, there was no difference in 12-month behavior scores in the intervention vs control group (17.39 vs 17.74; mean difference, -0.35; 95% CI, -1.11 to 0.41; P = .36)., Conclusions and Relevance: A multifaceted intervention was effective in reducing depression risk but did not improve intended help-seeking behaviors for mental illness., Trial Registration: Clinical Trial Registry India: CTRI/2018/08/015355.

Introduction: Competence committees (CCs) centre their work around documentation of trainees' performance; undocumented contributions (i.e. informal, unrecorded material like personal judgements, experiential anecdotes and contextual information) evoke suspicion even though they may play a role in decision making. This qualitative multiple case study incorporates insights from a social practice perspective on writing to examine the use of undocumented contributions by the CCs of two large post-graduate training programmes, one in a more procedural (MP) speciality and the other in a less procedural (LP) one., Methods: Data were collected via observations of meetings and semi-structured interviews with CC members. In the analysis, conversations were organised into triptychs of lead-up, undocumented contribution(s), and follow-up. We then created thick descriptions around the undocumented contributions, drawing on conversational context and interview data to assign possible motivations and significance., Results: We found no instances in which undocumented contributions superseded the contents of a trainee's file or stood in for missing documentation. The number of undocumented contributions varied between the MP CC (six instances over two meetings) and the LP CC (22 instances over three meetings). MP CC discussions emphasised Entrustable Professional Activity (EPA) observations, whereas LP CC members paid more attention to narrative data. The divergent orientations of the CCs-adding an 'advis[ing]/guid[ing]' role versus focusing simply on evaluation-offers the most compelling explanation. In lead-ups, undocumented contributions were prompted by missing and flawed documentation, conflicting evidence and documentation at odds with members' perceptions. Recognising other 'red flags' in documentation often required professional experience. In follow-ups, purposes served by undocumented contributions varied with context and were difficult to generalise; we, therefore, provide deeper analysis of two vignettes to illustrate., Conclusions: Our data suggest undocumented contributions often serve best efforts to ground decisions in documentation. We would encourage CC practices and policies be rooted in more nuanced approaches to documentation., (© 2024 The Author(s). Medical Education published by Association for the Study of Medical Education and John Wiley & Sons Ltd.)

Condoms continue to be used by many gay, bisexual, and other men who have sex with men (GBM) to reduce the risk of HIV transmission. However this is impacted by condom failure events, defined here as condom breakage and slippage. In a prospective, observational cohort study of 343 HIV serodiscordant male couples recruited through high HIV caseload clinics and hospitals between 2012 and 2016 in Australia, Brazil, and Thailand, condom failure rates and associated factors were analysed, including with the study partner versus other sexual partners. There were 717 reported instances of condom failure from an estimated total of 25,831 sex acts with condoms, from over 588.4 participant years of follow up. Of the HIV-negative partners (n = 343) in the study, more than a third (n = 117, 36.7%) reported at least one instance of condom failure with any partner type during study follow-up. Condom failure with their study partner was reported by 91/343 (26.5%) HIV-negative partners, compared with 43/343 (12.5%) who reported condom failure with other partners. In total, there were 86 events where the HIV-negative partner experienced ano-receptive condom failure with ejaculation, representing 12.0% of all failure events. In multivariable analysis, compared to Australia, HIV-negative men in Brazil reported a higher incidence risk rate of condom failure (IRR = 1.64, 95%CI 1.01-2.68, p = 0.046) and HIV-negative men who reported anal sex with other partners reported an increased risk of condom failure compared with men who only had sex with their study partner (IRR = 1.89, 95%CI 1.08-3.33, p = 0.025). Although at least one event of condom failure was reported by a significant proportion of participants, overall condom failure events represented a small proportion of the total condom protected sex acts., (© 2024. The Author(s).)

Background: Elexacaftor/tezacaftor/ivacaftor (ETI), a combination cystic fibrosis transmembrane receptor (CFTR) modulator, has demonstrated improved pulmonary outcomes in individuals with cystic fibrosis (CF). However, ETI's impact on functional endoscopic sinus surgery (FESS) remains unclear., Methods: The TriNetX Analytics Research Network, consisting of 120 million global de-identified electronic medical records, was queried from 2012 to 2023 for subjects with CF who underwent sinus surgery. 1 Patients on ETI prior to FESS (n = 6,056) were propensity score matched to control individuals with CF not on CFTR modulators (n = 37,906) and those on other FDA-approved CFTR modulators (tezacaftor/ivacaftor, lumacaftor/ivacaftor, and ivacaftor) (n = 2437) based on relevant factors. The primary outcome was the absolute risk reduction (ARR) of undergoing FESS. Secondary outcomes included ARR of CF-related pulmonary exacerbations and hospital admission from 0 to 6, 6 to 12, and 12 to 24 months following FESS., Results: ETI use demonstrated a significant ARR for FESS when compared to CF patients not on CFTR modulators (2.12%; 95% confidence interval [CI] 1.5-2.75; p-value < 0.0001) and those on other CFTR modulators (4.7%; 95% CI 3.54-5.85; p-value < 0.0001). No significant differences occurred in secondary outcomes between ETI and non-CFTR modulator groups, except for reduced CF-related pulmonary exacerbations from 0 to 6 months post-FESS. Additionally, a significant reduction in pulmonary exacerbations was observed at all time points and hospital admissions within 6 months following FESS compared to those using other CFTR modulators., Conclusions: In a large dataset, CF patients on ETI demonstrated significantly reduced risk of FESS, pulmonary exacerbations, and hospital admission compared to patients not on CFTR modulators or those on other CFTR modulators, suggesting improved sinonasal disease and overall health status in CF., (© 2024 The Author(s). International Forum of Allergy & Rhinology published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngic Allergy and American Rhinologic Society.)

Objective: Inferior vena cava (IVC) filter placement is associated with important long-term complications. Predictive models for filter-related complications may help guide clinical decision-making but remain limited. We developed machine learning (ML) algorithms that predict 1-year IVC filter complications using preoperative data., Methods: The Vascular Quality Initiative database was used to identify patients who underwent IVC filter placement between 2013 and 2024. We identified 77 preoperative demographic and clinical features from the index hospitalization when the filter was placed. The primary outcome was 1-year filter-related complications (composite of filter thrombosis, migration, angulation, fracture, and embolization or fragmentation, vein perforation, new caval or iliac vein thrombosis, new pulmonary embolism, access site thrombosis, or failed retrieval). The data were divided into training (70%) and test (30%) sets. Six ML models were trained using preoperative features with 10-fold cross-validation (Extreme Gradient Boosting, random forest, Naïve Bayes classifier, support vector machine, artificial neural network, and logistic regression). The primary model evaluation metric was area under the receiver operating characteristic curve (AUROC). Model robustness was assessed using calibration plot and Brier score. Performance was evaluated across subgroups based on age, sex, race, ethnicity, rurality, median Area Deprivation Index, planned duration of filter, landing site of filter, and presence of prior IVC filter placement., Results: Overall, 14,476 patients underwent IVC filter placement and 584 (4.0%) experienced 1-year filter-related complications. Patients with a primary outcome were younger (59.3 ± 16.7 years vs 63.8 ± 16.0 years; P < .001) and more likely to have thrombotic risk factors including thrombophilia, prior venous thromboembolism (VTE), and family history of VTE. The best prediction model was Extreme Gradient Boosting, achieving an AUROC of 0.93 (95% confidence interval, 0.92-0.94). In comparison, logistic regression had an AUROC of 0.63 (95% confidence interval, 0.61-0.65). Calibration plot showed good agreement between predicted/observed event probabilities with a Brier score of 0.07. The top 10 predictors of 1-year filter-related complications were (1) thrombophilia, (2) prior VTE, (3) antiphospholipid antibodies, (4) factor V Leiden mutation, (5) family history of VTE, (6) planned duration of IVC filter (temporary), (7) unable to maintain therapeutic anticoagulation, (8) malignancy, (9) recent or active bleeding, and (10) age. Model performance remained robust across all subgroups., Conclusions: We developed ML models that can accurately predict 1-year IVC filter complications, performing better than logistic regression. These algorithms have potential to guide patient selection for filter placement, counselling, perioperative management, and follow-up to mitigate filter-related complications and improve outcomes., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

This manifesto seeks to challenge dominant narratives about the future of augmentative and alternative communication (AAC). Current predictions are mainly driven by technological developments-technologies usually being developed for different markets-and are often based on ableist assumptions. In online conversations and a discussion panel at the 2023 International Society for Augmentative and Alternative Communication conference, we explored alternative futures by adopting different starting positions. Our case is presented under five headings: questioning the dominance of predictions that artificial intelligence and brain-computer interfaces will define the future of AAC; resisting disability being framed medically, as a problem to be solved, yet acknowledging both the pleasures and pains of being disabled; declaring that people who use AAC-as cyborgs of necessity rather than choice-should have choice and ownership of our technologies; challenging notions of independence as the necessary end goal for disabled bodies and considering interdependence as a human right; imagining alternative futures in which all people who use AAC are accepted and embraced for our communication and self-expression. This manifesto is an invitation for further discussion, and we welcome responses. While our focus is AAC, and three of the authors use AAC, we believe that our stance could be relevant to other disability communities in turn. This paper is about who gets to imagine disability futures and whose voices are left out. It is about how uncritical these futures can be, often presuming values that disabled people, in all their diversity, may not share., Competing Interests: Competing interests: KW is a contractor for PRC-Saltillo an augmentative and alternative communication company. DS is the chairman of the Australian Group Supporting Communication Inclusion (AGSOC). LM, KB and GP have not declared any competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Conventional microporous zeolitic imidazolate frameworks (ZIFs) face limitations in mass transfer and pore accessibility when dealing with large guest molecules. Here, we describe a technique for the synthesis of mesoporous ZIFs (MesoZIFs) using a strategy we term directed reticular chemistry. MesoZIF-8 was prepared through solvent evaporation-induced coassembly of polystyrene- block -poly(ethylene oxide) (PS- b -PEO), ZIF-8 building blocks, and acetic acid (AcOH), followed by amine-facilitated crystallization of ZIF-8 in the interstices of PS- b -PEO micelles. AcOH prevents the fast coordination of ZIF-8 building blocks, avoiding phase separation during coassembly. The employed amine plays a crucial role in neutralizing the crystallization environment and further deprotonating the 2-methlyimizale linker to coordinate with zinc ions. Ink bottle-shaped mesopores with tunable mesopore sizes were created by adjusting the molecular weight of PS- b -PEO. Compared to microporous ZIF-8, MesoZIF-8 exhibited enhanced performance in Knoevenagel condensation reactions involving large reactants and hydrogen storage capacity. With this study, we establish an efficient approach for synthesizing MesoZIFs with highly accessible mesopores to enhance ZIF performance in targeted applications.

Background: While resuscitation guidelines emphasize early vasopressor administration and advanced airway management, their optimal sequence remains unclear. We sought to determine the associations between vasopressor-airway resuscitation sequence and out-of-hospital cardiac arrest (OHCA) outcomes in the Pragmatic Airway Resuscitation Trial (PART)., Methods: We analyzed data from the PART trial. For each patient we determined times of first vasopressor administration (epinephrine or vasopressin), and successful advanced airway insertion (laryngeal tube or endotracheal tube). We classified each case as vasopressor-first or advanced airway-first. We used Generalized Estimating Equations to determine associations between vasopressor-airway sequence and outcomes (72-hour survival, return of spontaneous circulation (ROSC) on emergency department arrival, survival to hospital discharge, hospital survival with favorable neurologic status) and CPR outside of recommended parameters (chest compression fraction <0.8, chest compression rate <100 or >120 per min, or ventilation rate <8 or >12 breaths/min), adjusting for confounders., Results: Of 3,004 patients in the parent trial, we analyzed 2,404, including 1,821 vasopressor-first and 583 advanced airway-first. Median intervention times: ALS arrival-to-vasopressor 8 min (IQR 6-11) and ALS arrival-to-airway 11 min (8-15). Compared with airway-first, vasopressor-first sequence was not associated with 72-hour survival (adjusted OR 0.96; 95% CI: 0.71-1.31), ROSC (0.83; 0.66-1.06), hospital survival (1.09; 0.68-1.73), or hospital survival with favorable neurologic status (0.97; 0.53-1.78). Vasopressor-first sequence was not associated with non-compliance with recommended CPR performance parameters., Conclusions: Vasopressor-airway resuscitation sequence was not associated with OHCA outcomes or CPR quality., 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. Published by Elsevier B.V.)

Background: There is little research done on ground reaction forces (GRF) in terms of 3D impulses after total hip replacement (THR). This study aimed to investigate the GRFs and 3D impulses in four sub-phases of stance during gait in the patients undergoing THR., Methods: A total of 10 pain-free THR patients and 10 healthy people were recruited. This is an observational and retrospective study. The gait data was collected between 2008 and 2014 and analyzed between 2020 and 2024. All the participants were included in the three-dimensional gait analysis. Gait parameters, phase durations, GRFs and impulses' key values during gait were calculated in four sub-phases of stance. Statistical comparisons were performed with generalized linear models including age, gender, body mass index and walking speed as interactive factors., Results: It is found that (1) cadence, walking speed, stride length and step width in THR group were significantly decreased in compared with control group; (2) the THR decreased loading response duration in operative side and pre-swing duration in non-operative side compared with the control group, but the THR's two sides have similar duration proportions in sub-stance phases; (3) the THR group had lower GRFs than the control group in vertical direction but higher in the medial-lateral direction; (4) in operative side, the THR's impulses in loading response phase were lower than the control group in anterior-posterior direction, and (5) in non-operative side, the THR's impulse in pre-swing phase in anterior-posterior direction was higher than the control side., Conclusion: The THR group showed slower walking speeds than the control group. The reasons could be from the decreased impulse in loading response phase, the decreased 2nd peak of GRF and the decreased pre-swing impulse in vertical direction in operative side. Clinicians are suggested to consider the information provided when designing relevant rehabilitation exercises on the related muscles and functions., (© 2024 The Author(s). Orthopaedic Surgery published by Tianjin Hospital and John Wiley & Sons Australia, Ltd.)

This European Academy of Allergy and Clinical Immunology (EAACI) guideline provides recommendations for the management of IgE-mediated food allergy and was developed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Following the confirmation of IgE-mediated food allergy diagnosis, allergen avoidance and dietary advice (with support of a specialised dietitian, if possible) together with the provision of a written treatment plan, education on the recognition of allergic symptoms and prescription of medication including adrenaline using an auto-injector are essential. Patients with significant anxiety and requirement for coping strategies may benefit from support from a clinical psychologist. As immunomodulatory interventions, omalizumab is suggested for treatment of IgE-mediated food allergy in children from the age of 1 and adults; and oral allergen-specific immunotherapy is recommended for children and adolescents with peanut allergy and suggested for milk and egg allergies (generally after 4 years of age for milk and egg). Sublingual and epicutaneous immunotherapy are suggested for peanut allergy but are not yet available at the point of care. Future research into disease modifying treatments for IgE-mediated food allergy are highly needed, with standardised and patient-focused protocols and outcomes., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

Algae such as diatoms and haptophytes have distinct photosynthetic pigments from plants, including a novel set of carotenoids. This includes a primary xanthophyll cycle comprised of diadinoxanthin and its de-epoxidation product diatoxanthin that enables the switch between light harvesting and non-photochemical quenching (NPQ)-mediated dissipation of light energy. The enzyme responsible for the reversal of this cycle was previously unknown. Here, we identified zeaxanthin epoxidase 3 (ZEP3) from Phaeodactylum tricornutum as the candidate diatoxanthin epoxidase. Knocking out the ZEP3 gene caused a loss of rapidly reversible NPQ following saturating light exposure. This correlated with the maintenance of high concentrations of diatoxanthin during recovery in low light. Xanthophyll cycling and NPQ relaxation were restored via complementation of the wild-type ZEP3 gene. The zep3 knockout strains showed reduced photosynthetic rates at higher light fluxes and reduced specific growth rate in variable light regimes, likely due to the mutant strains becoming locked in a light energy dissipation state. We were able to toggle the level of NPQ capacity in a time and dose dependent manner by placing the ZEP3 gene under the control of a β-estradiol inducible promoter. Identification of this gene provides a deeper understanding of the diversification of photosynthetic control in algae compared to plants and suggests a potential target to improve the productivity of industrial-scale cultures., (© 2024 The Author(s). The Plant Journal published by Society for Experimental Biology and John Wiley & Sons Ltd.)

Receptor activity-modifying proteins (RAMPs) modulate the expression and activity of numerous G protein-coupled receptors, primarily those within class B1. These receptors have important physiological roles, including the regulation of food intake, energy metabolism, and glucose homeostasis. Dysregulation of these pathways can lead to obesity and diabetes mellitus, which present an ever-expanding global challenge. Whilst the roles of class B1 receptors and their peptide agonists in obesity and diabetes have been investigated, the contribution of RAMPs is less well understood. This review summarises the results of RAMP knockout studies, highlighting the involvement of these proteins in the incidence of disease. It then moves to discuss how receptor, RAMP, and agonist expression change in disease states, and the benefits (or detriments) of these agonists to the pathways implicated in disease pathophysiology. Whilst much of the data centres around the calcitonin family of receptors, as their interactions with RAMPs are well established, this review then discusses receptors whose roles in obesity and diabetes are well founded, but the significance of whose interactions with RAMPs is more recently emerging. The conclusion of this study of the literature is, however, that the information surrounding RAMPs is conflicting and multifaceted, and more research is required to fully understand their contribution to obesity and diabetes.

A 54-question survey about System Healthcare Infection Prevention Programs (SHIPPs) was sent out to SHEA Research Network participants in August 2023. Thirty-eight United States-based institutions responded (38/93, 41%), of which 23 have SHIPPs. We found heterogeneity in the structure, staffing, and resources for system infection prevention (IP) programs.

Filtration performance of do-it-yourself (DIY) box fan filters deployed across a university campus was assessed over an academic year. Four DIY air filters were constructed from box fans and air filters with a minimum efficiency reporting value (MERV) of 13 and deployed in four spaces (two laboratories that include sources of particles and two offices). They were operated 9 hours daily with a programmable timer and were continuously monitored with power meters. Particle concentrations in the spaces were continuously monitored with low-cost nephelometers. The particle size dependent clean air delivery rate (CADR) and single pass filtration efficiency for each box was measured in a laboratory before deployment and every 10 weeks, for a total of five measurements over 40 weeks. We find that these DIY box fan filters maintain robust performance over time, with each air filter maintaining at least 60% of its initial CADR at the end of the 40 week study even with daily operation in environments with modest particle concentrations. CADR values for particles of 1.0-3.0 μm optical diameter averaged 34% higher than CADR values for 0.35-1.0 μm particles, aligning with MERV 13 filter size-dependent filtration expectations. Reductions in CADR over time were attributed to a reduction in filtration efficiency, likely due to a loss of filter electrostatic charge over time. There was no strong indication that increased resistance due to particle accumulation on filters appreciably decreased flow rates over time for any of the fans. The long-term robustness of DIY box fan air filters demonstrates their validity as a cost-effective, high performance, alternative to portable high efficiency particulate air (HEPA) filters.

Doping of quantum antiferromagnets is an established approach to investigate the robustness of their ground state against the competing phases. Predictions of doping effects on the ground state of the Shastry-Sutherland dimer model are here verified experimentally on Mg-doped SrCu 2 (BO 3 ) 2 . A partial incorporation of Mg 2+ on the Cu 2+ site in the SrCu 2 (BO 3 ) 2 structure leads to a subtle but systematic lattice expansion with the increasing Mg-doping concentration, which is accompanied by a slight decrease in the spin gap, the Curie-Weiss temperature, and the peak temperature of the susceptibility. These findings indicate a doping-induced breaking of Cu 2+ spin-1/2 dimers that is also corroborated by X-band EPR spectroscopy that points to a systematic increase in the intensity of free Cu 2+ sites with increasing Mg-doping concentration. Extending the Mg-doping up to nominal x = 0.10 yielding SrCu 1.9 Mg 0.1 (BO 3 ) 2 , in the magnetization measurements taken up to 35 T, a suppression of the pseudo-1/8 plateau is found along with a clear presence of an anomaly at an onset critical field μ 0 H' C0 ≈ 9 T. The latter, absent in pure SrCu 2 (BO 3 ) 2 , emerges due to the pairwise coupling of liberated Cu 2+ spin-1/2 entities in the vicinity of Mg-doping induced impurities.

The successive dominance of SARS-CoV-2 omicron sublineages presents challenges for vaccination strategies with respect to the antigenic content of boosters. New Zealand's COVID-19 elimination strategy (2020-2021) ensured the major vaccination campaign (Pfizer-BioNTech BNT162b2) was completed pre-omicron in an infection-naive population, providing a unique setting to explore the impact of omicron infection waves on vaccine responses. This study compared neutralising antibodies (NAb) to eight SARS-CoV-2 omicron sublineages 28-days and 11-months after a third dose. Participants (n = 219) were classified by antigen exposure in the intervening 10 months including additional vaccinations and/or infections. Both vaccination and infection boosted NAb levels to all sublineages. Antigenic maps showed infection had a major impact on NAb breadth, despite all participants being vaccinated with an ancestral-based vaccine. While vaccination remains an important tool to boost immunity, the breadth of NAbs observed suggest that attempts to match booster specificity with current circulating variants may not always be necessary., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Graham Le Gros reports financial support was provided by Ministry of Business Innovation and Employment. Graham Le Gros reports financial support was provided by New Zealand Ministry of Health. If there are other authors, they 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 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The COVID-19 pandemic demonstrated the need for respiratory protection against airborne pathogens. Respirator options for children are limited, and existing designs do not consider differences in facial shape or size. We created a dataset of children's facial images from three cohorts, then used geometric morphometric analyses of dense and sparse facial landmark representations to quantify age, sex and ancestry-related variation in shape. We found facial shape and size in children vary significantly with age from ages 2 to 18, particularly in dimensions relevant to respirator design. Sex differences are small throughout most of the age range of our sample. Ancestry is associated with significant facial shape variation in dimensions that may affect respirator fit. We offer guidance on how to our results can be used for the appropriate design of devices such as respirators for pediatric populations. We also highlight the need to consider ancestry-related variation in facial morphology to promote equitable, inclusive products., 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. Published by Elsevier Ltd.)

Background: The Narrative Experiences Online (NEON) Intervention provides self-managed web-based access to mental health recovery narratives (n = 659). We evaluated effectiveness and cost-effectiveness in improving quality of life for adults resident in England with mental health problems and recent psychosis experience., Methods: Prospectively registered pragmatic parallel-group randomised trial controlling for usual care, recruiting from statutory mental health services and through community engagement activities, with a 52-week primary endpoint (ISRCTN11152837). All trial procedures and the NEON Intervention were delivered by an integrated web-application. Randomisation was through an independently generated list (no stratification). Allocation was masked for statistical staff and the Chief Investigator but not participants. Intervention arm participants received immediate NEON Intervention access. Control arm participants received access after completing primary endpoint questionnaires. The primary outcome was quality of life through the Manchester Short Assessment (MANSA). Serious Adverse Events (SAEs) were collected through web-based safety report forms and identified from health service usage data. The primary analysis was by a prospectively described Intention To Treat principle excluding participants who had registered multiple times, with multiple imputation for missing data., Findings: Between 9 March 2020 and 1 March 2021, 739 participants were randomised (intervention:370; control: 369), providing more than 90% power to detect a baseline-adjusted difference of 0.25 in the MANSA score. Mean age was 34.8 years (standard deviation (SD) 12.0), 561 (75.9%) were white British, 443 (59.9%) were female, 609 (82.4%) had accessed specialist care mental health services, and 698 (94.5%) had accessed primary care mental health services. Mean baseline MANSA score was 3.7 for control and intervention arms (SD 0.9 and 1.0). 565 (76.5%) participants provided primary endpoint MANSA data with a mean score of 4.1 (SD 1.0) for both arms. We found no significant difference in Quality of Life between the two arms at the primary endpoint (baseline-adjusted difference 0.07, 95% CI -0.07 to 0.21, p = 0.35). The incremental cost-effectiveness ratio (£110,501 per quality-adjusted life-year (QALY)) exceeded the prospectively defined cost-effectiveness threshold (£30,000 per QALY). 158 (42.8%) control arm and 194 (52.4%) intervention arm participants accessed narratives outside of the NEON Intervention. There were no related serious adverse events (SAEs). 116 unrelated SAEs were reported by control arm participants, and 107 by intervention arm participants., Interpretation: Our findings do not indicate NEON Intervention access for all people with psychosis experience. Future research should consider a) evaluation with current mental health services users; b) optimisation to enable users to find hope-promoting narratives., Funding: National Institute for Health and Care Research (NIHR)., Competing Interests: All authors had financial support from the National Institute for Health and Care Research (NIHR) for the submitted work; Graham Thornicroft had financial support from the UK Medical Research Council for the submitted work; Rachel Elliott had financial support from Abbott Diabetes Care, NHS England, CSL Behring, and Fonds voor Wetenschappelijk Onderzoe for the submitted work; Rachel Elliott is a Trusty of Pharmacy Research UK. Other than these declared interests, no author had financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no author had other relationships or activities that could appear to have influenced the submitted work. Intellectual property rights for the NEON Intervention are owned by the study sponsor, Nottinghamshire Healthcare NHS Foundation Trust, who have responsibility for commercial exploitation., (© 2024 The Authors.)

Rationale: Serum Immunoglobulin G (IgG) deficiency is associated with morbidity in chronic obstructive pulmonary disease (COPD) but it is unclear whether concentrations in the lower end of the normal range still confer risk., Objectives: To determine if levels above traditional cutoffs for serum IgG deficiency are associated with exacerbations among current and former smokers with or at risk for COPD., Measurements and Main Results: Former and current smokers in SPIROMICS (n=1,497) were studied, n=1,026 with and n=471 at risk for COPD. In a subset (n=1,031), IgG subclasses were measured. Associations between total IgG or subclasses and prospective exacerbations were evaluated with multivariable models adjusting for demographics, current smoking, smoking history, FEV 1 % predicted, inhaled corticosteroids, and serum IgA., Results: The 35th percentile (1225 mg/dL in this cohort) of IgG was the best cutoff by Akaike Information Criterion (AIC). Below this, there was increased exacerbation risk (IRR 1.28, 95% CI 1.08-1.51). Among subclasses, IgG1 and IgG2 below 35 th percentile (354 and 105 mg/dL, respectively) were both associated with increased risk of severe exacerbation (IgG1: IRR 1.39, 95% CI 1.06-1.84; IgG2: IRR 1.50, 95% CI 1.14-1.1.97). These associations remained significant when additionally adjusting for history of exacerbations., Conclusions: Lower serum IgG is prospectively associated with exacerbations in individuals with or at risk for COPD. Among subclasses, lower IgG1 and IgG2 are prospectively associated with severe exacerbations. The optimal IgG cutoff was substantially higher than traditional cutoffs for deficiency, suggesting subtle impairment of humoral immunity may be associated with exacerbations.

Introduction: Non-consensual condom removal (NCCR) refers to the act of removing a condom during sex without the other person's permission. It poses physical and psychological risks to women's health. Views and attitudes regarding this sexual practice are not well understood in the UK. This study aimed to explore young people's views on the morality and criminality of NCCR and how their views are affected by negative health outcomes, relationship status, and socio-demographic characteristics., Methods: A quantitative online survey of people aged 18-25 living in the UK was conducted. The survey consisted of two NCCR scenarios, varied by health outcome and relationship status, followed by questions about the morality and criminality of NCCR and respondents' socio-demographic characteristics. Statistical analysis included Chi-square testing and logistic regression modelling., Results: Most of the 1729 respondents considered NCCR to be a violation of consent to sex (97.4%-98.1%), to be wrong (99.3%-99.5%), and to be sexual assault (86.3%-89.2%). Respondents were more likely to support prison time for NCCR if the victim got pregnant (52.1%) (rather than depressed (41.6%)) or was part of a casual hook-up (53.9%) (as opposed to a long-term dating relationship (47.2%). Respondents who were female or non-heterosexual were more likely to view NCCR as sexual assault and support prison as a penalty for NCCR., Conclusion: The majority of young UK adults in this survey considered condom removal during sex without the other person's permission to be a violation of consent, morally wrong, and a form of sexual assault. Support for prison as a penalty was lower. These findings can inform future campaigns on consent in sexual relationships and legislation to provide support for women affected by NCCR., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ezzat 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.)

Background: The COVID-19 pandemic changed the way many industries work, including contact centres, with some employees working from home and new on-site restrictions/measures in place representing even greater challenges for employers around staff engagement and wellbeing. This study aimed to understand the interplay of individual, social, environmental and organisational factors influencing physical activity and sedentary behaviour in UK contact centre employees, how the pandemic impacted these factors, and their relevance for the future of hybrid working., Methods: Individual interviews (n = 33) were conducted with participants (staff working full and part time, on site and from home) from four UK contact centres. A topic guide based on the ecological model was developed to understand current barriers and facilitators to physical activity and (reducing) sedentary behaviour during and outside of working hours. Thematic analysis was carried out using a codebook and a deductive coding approach to identify themes., Results: Three key insights are provided. First, participants felt they were generally sitting more and moving less since the first UK-wide lockdown. Second, factors which negatively impacted on these behaviours were evident across all levels of the ecological model. These included individual and social barriers (e.g., lack of motivation and preferable physical activity options) as well as environmental and organisational barriers (e.g., poor home office setup, back-to-back virtual meetings). There were a mix of new and existing barriers (exacerbated by the pandemic) and several of these were linked to homeworking. Third, organisational support requirements (e.g., homeworking ergonomic support) and existing facilitators (such as the provision of informational support and flexible working arrangements) were identified., Conclusion: Solutions to reduce sedentary behaviours and increase physical activity in contact centres need to address barriers from the individual to the organisational level. Whilst the study was undertaken in the UK, the results are like to be applicable globally., Trial Registration: Clinical trial registration: The trial for the wider project has been registered on the ISRCTN database: http://www.isrctn.com/ISRCTN11580369., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Manner 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.)

Background: D-dimer is the only biomarker currently recommended in guidelines for the diagnosis of acute aortic syndrome (AAS). We undertook a systematic review to determine whether any alternative biomarkers could be useful in AAS diagnosis., Methods: We searched electronic databases (including MEDLINE, EMBASE and the Cochrane Library) from inception to February 2024. Diagnostic studies were eligible if they examined biomarkers other than D-dimer for diagnosing AAS compared with a reference standard test in people presenting to the ED with symptoms of AAS. Case-control studies were identified but excluded due to high risk of bias. Selection of studies, data extraction and risk of bias assessments using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool were undertaken independently by at least two reviewers. We used narrative synthesis to summarise the findings., Results: We identified 2017 citations, included 13 cohort studies (n=76-999), and excluded 38 case-control studies. Methodological quality was variable, with most included studies having unclear or high risk of bias and applicability concerns in at least one item of the QUADAS-2 tool. Only two studies reported biomarkers with sensitivity and specificity comparable to D-dimer (ie, >90% and >50%, respectively). Wang et al reported 99.1% sensitivity and 84.9% specificity for soluble ST2; however, these findings conflicted with estimates of 58% sensitivity and 70.8% specificity reported in another study. Chun and Siu reported 95.6% sensitivity and 56.1% specificity for neutrophil count, but this has not been confirmed elsewhere., Conclusion: There are many potential alternative biomarkers for AAS but few have been evaluated in more than one study, study designs are often weak and reported biomarker accuracy is modest or inconsistent between studies. Alternative biomarkers to D-dimer are not ready for routine clinical use., Prospero Registration Number: CRD42022252121., Competing Interests: Competing interests: SG, AP, ME, MC, GC, RH, MJR, ST and SW all declare funding from NIHR Health Technology Assessment (Grant NIHR151853). There are no other competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: HIV is characterised by high rates of comorbidity with mental health conditions including depression, as such, the detection and treatment of comorbid depression is critical to achieve viral load suppression. This study evaluated the effectiveness of a collaborative care intervention for depression among adults with comorbid depression symptoms receiving ART in primary health care (PHC) facilities., Methods: We conducted a pragmatic cluster-randomised trial in 40 clinics in the North West province of South Africa. PHC clinics were stratified by sub-district and randomised in a 1:1 ratio. Participants were ≥ 18 years, receiving ART, and had depression symptoms indicated by Patient Health Questionnaire-9 (PHQ-9) score ≥ 9. Intervention clinics received: i) supplementary mental health training and clinical communication skills for PHC nurses; ii) workshops for PHC doctors on treating depression; and iii) lay counselling services. Using mixed effects regression models, we assessed co-primary outcomes of PHQ-9 response at 6 months (≥50 % reduction in baseline PHQ-9 score) and viral load suppression at 12 months (viral load<1000 copies/mL)., Results: The intervention had no effect in PHQ-9 response (49 % vs 57 %, risk difference (RD) = -0.08, 95 % CI = -0.19; 0.03, p = 0.184) or viral load suppression (85 % vs 84 %, RD = 0.02, 95 % CI = -0.01; 0.04, p = 0.125). Nurses referred 4298 clinic patients to counsellors, however, only 66/1008 (7 %) of intervention arm participants were referred to counsellors at any point during the study., Limitations: The highly pragmatic approach of this trial limited exposure to the counselling component of the intervention and referral to doctors for initiation of antidepressant treatment was extremely low., Conclusion: The trial showed no effect of a district-based intervention to strengthen collaborative care for depression. The trial revealed the extent of the treatment gap in the context of scaling up mental health services., Trial Registration: ClinicalTrials.gov (NCT02407691); Pan African Clinical Trials Registry (201504001078347)., Competing Interests: Declaration of competing interest All authors declare no competing interests., (Copyright © 2024. Published by Elsevier B.V.)

Background: Research consistently finds poorer health and educational outcomes for children who have experienced out-of-home care relative to the general population. Few studies have explored differences between those in care and those in receipt of intervention from social services but not in care. Children receiving social services interventions often experience Adverse Childhood Experiences (ACEs), and deprivation, which are known to negatively impact outcomes. We aimed to estimate the association of different social services interventions with educational outcomes and hospital admissions, while adjusting for ACEs and deprivation., Methods: We linked retrospective, routinely collected administrative records from health, education, and social care to create a cohort via the Secure Anonymised Information Linkage (SAIL) databank in Wales, UK. We analysed data for children and household members (N = 30,439) across four different groups: [1] no social care intervention; [2] children in need but not in care (CIN); [3] children on the Child Protection Register but not in care (CPR); [4] children in care - i.e. removed from the family home and looked after by the local authority (CLA). Our primary outcome was education outcomes at age 16 years. Secondary outcomes were all cause emergency hospital admissions, and emergency admissions for external causes/injuries., Results: Children in receipt of social services intervention were more likely to not attain the expected level upon leaving statutory education at age 16 after adjusting for ACEs and other characteristics (for children who had been in out-of-home care (conditional OR: 1·76, (95%CI) 1·25 - 2·48), in need (2·51, 2·00-3·15) and those at risk (i.e., on the child protection register) (4·04, 2·44 - 6·68). For all-cause emergency admissions, all social care groups were at greater risk compared to children in the general population (children in care (conditional HR: 1·31, 1·01-1·68), children in need (1·62, 1·38 - 1·90), and children at risk (1·51, 1·11 - 2·04)., Conclusions: All groups receiving social service intervention experience poorer educational and health outcomes than peers in the general population. Children who remain with their home parents or caregivers but are identified as 'in need' or 'at risk' by social care practitioners require further research. Integrated support is needed from multiple sectors, including health, educational and social care., (© 2024. The Author(s).)

Background: Progressive hearing loss is a common problem in the human population with no effective therapeutics currently available. However, it has a strong genetic contribution, and investigating the genes and regulatory interactions underlying hearing loss offers the possibility of identifying therapeutic candidates. Mutations in regulatory genes are particularly useful for this, and an example is the microRNA miR-96, a post-transcriptional regulator which controls hair cell maturation. Mice and humans carrying mutations in miR-96 all exhibit hearing impairment, in homozygosis if not in heterozygosis, but different mutations result in different physiological, structural and transcriptional phenotypes., Methods: Here we present our characterisation of two lines of mice carrying different human mutations knocked-in to Mir96. We have carried out auditory brainstem response tests to examine their hearing with age and after noise exposure and have used confocal and scanning electron microscopy to examine the ultrastructure of the organ of Corti and hair cell synapses. Bulk RNA-seq was carried out on the organs of Corti of postnatal mice, followed by bioinformatic analyses to identify candidate targets., Results: While mice homozygous for either mutation are profoundly deaf from 2 weeks old, the heterozygous phenotypes differ markedly, with only one mutation resulting in hearing impairment in heterozygosis. Investigations of the structural phenotype showed that one mutation appears to lead to synaptic defects, while the other has a much more severe effect on the hair cell stereociliary bundles. Transcriptome analyses revealed a wide range of misregulated genes in both mutants which were notably dissimilar. We used the transcriptome analyses to investigate candidate therapeutics, and tested one, finding that it delayed the progression of hearing loss in heterozygous mice., Conclusions: Our work adds further support for the importance of the gain of novel targets in microRNA mutants and offers a proof of concept for the identification of pharmacological interventions to maintain hearing., (© 2024. The Author(s).)