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Background: Imlunestrant is a next-generation, brain-penetrant, oral selective estrogen-receptor (ER) degrader that delivers continuous ER inhibition, even in cancers with mutations in the gene encoding ERα ( ESR1 )., Methods: In a phase 3, open-label trial, we enrolled patients with ER-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer that recurred or progressed during or after aromatase inhibitor therapy, administered alone or with a cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor. Patients were assigned in a 1:1:1 ratio to receive imlunestrant, standard endocrine monotherapy, or imlunestrant-abemaciclib. Primary end points were investigator-assessed progression-free survival with imlunestrant as compared with standard therapy among patients with ESR1 mutations and among all patients and with imlunestrant-abemaciclib as compared with imlunestrant among all patients who had undergone randomization concurrently., Results: Overall, 874 patients underwent randomization, with 331 assigned to imlunestrant, 330 to standard therapy, and 213 to imlunestrant-abemaciclib. Among 256 patients with ESR1 mutations, the median progression-free survival was 5.5 months with imlunestrant and 3.8 months with standard therapy. The estimated restricted mean survival time at 19.4 months was 7.9 months (95% confidence interval [CI], 6.8 to 9.1) with imlunestrant and 5.4 months (95% CI, 4.6 to 6.2) with standard therapy (difference, 2.6 months; 95% CI, 1.2 to 3.9; P<0.001). In the overall population, the median progression-free survival was 5.6 months with imlunestrant and 5.5 months with standard therapy (hazard ratio for progression or death, 0.87; 95% CI, 0.72 to 1.04; P = 0.12). Among 426 patients in the comparison of imlunestrant-abemaciclib with imlunestrant, the median progression-free survival was 9.4 months and 5.5 months, respectively (hazard ratio, 0.57; 95% CI, 0.44 to 0.73; P<0.001). The incidence of grade 3 or higher adverse events was 17.1% with imlunestrant, 20.7% with standard therapy, and 48.6% with imlunestrant-abemaciclib., Conclusions: Among patients with ER-positive, HER2-negative advanced breast cancer, treatment with imlunestrant led to significantly longer progression-free survival than standard therapy among those with ESR1 mutations but not in the overall population. Imlunestrant-abemaciclib significantly improved progression-free survival as compared with imlunestrant, regardless of ESR1 -mutation status. (Funded by Eli Lilly; EMBER-3 ClinicalTrials.gov number, NCT04975308.)., (Copyright © 2024 Massachusetts Medical Society.)

Rationale: The measurement of cough frequency is widely used in clinical trials, typically expressed as the number of explosive cough sounds per hour. However, this measure does not capture the clustering of coughs into bouts. Coughing bouts contribute to perceived cough severity and the physical complications of coughing, but an agreed standard definition of cough bouts is lacking. The objectives of the present study were to explore the impact of different definitions of cough bouts on the parameters generated, their relationships with reported cough severity and influence of age and gender in refractory chronic cough (RCC)., Methods: We analysed 24-h acoustic recordings and concurrent cough severity visual analogue scales from 91 RCC patients (62% female, median (interquartile range) age 60.0 (54-67.0) years). A custom-built algorithm calculated cough bouts, defined by the intervals between explosive cough sounds. Bouts defined by inter-cough intervals from ≤0.5 to ≤10 s (0.5 s increments) were explored, and parameters including number of bouts, median/maximum bout length and total bout duration calculated., Measurements and Main Results: Using inter-cough intervals of >3 s to define cough bouts made little difference to cough bout parameters. Correlations between cough severity and bout parameters were weak but most likely to be significant when single coughs were removed. Cough-free time/total time spent coughing tended to have more influence on cough severity than the average cough bout length, irrespective of the interval used., Conclusion: These analyses favour definitions of cough bouts utilising inter-cough intervals of ≤3 s and the exclusion of single coughs from cough bout analysis., Competing Interests: Conflict of interest: K. McGuinness invented the VitaloJAK filtering algorithm that has been licensed by Manchester University NHS Foundation Trust (MFT) and the University of Manchester to Vitalograph Ltd and Vitalograph Ireland (Ltd). MFT receives royalties that may be shared with K. McGuinness as the inventor and the clinical division in which J.A. Smith works. The remaining authors have nothing to disclose., (Copyright ©The authors 2024.)

Aims: The aim of this audit was to assess and improve the completeness and accuracy of the National Joint Registry (NJR) dataset for arthroplasty of the elbow., Methods: It was performed in two phases. In Phase 1, the completeness was assessed by comparing the NJR elbow dataset with the NHS England Hospital Episode Statistics (HES) data between April 2012 and April 2020. In order to assess the accuracy of the data, the components of each arthroplasty recorded in the NJR were compared to the type of arthroplasty which was recorded. In Phase 2, a national collaborative audit was undertaken to evaluate the reasons for unmatched data, add missing arthroplasties, and evaluate the reasons for the recording of inaccurate arthroplasties and correct them., Results: Phase 1 identified 5,539 arthroplasties in HES which did not match an arthroplasty on the NJR, and 448 inaccurate arthroplasties from 254 hospitals. Most mismatched procedures (3,960 procedures; 71%) were radial head arthroplasties (RHAs). In Phase 2, 142 NHS hospitals with 3,640 (66%) mismatched and 314 (69%) inaccurate arthroplasties volunteered to assess their records. A large proportion of the unmatched data (3,000 arthroplasties; 82%) were confirmed as being missing from the NJR. The overall rate of completeness of the NJR elbow dataset improved from 63% to 83% following phase 2, and the completeness of total elbow arthroplasty data improved to 93%. Missing RHAs had the biggest impact on the overall completeness, but through the audit the number of RHAs in the NJR nearly doubled and completeness increased from 35% to 70%. The accuracy of data was 94% and improved to 98% after correcting 212 of the 448 inaccurately recorded arthroplasties., Conclusion: The rate of completeness of the NJR total elbow arthroplasty dataset is currently 93% and the accuracy is 98%. This audit identified challenges of data capture with regard to RHAs. Collaboration with a trauma and orthopaedic trainees through the British Orthopaedic Trainee Association improved the completeness and accuracy of the NJR elbow dataset, which will improve the validity of the reports and of the associated research., Competing Interests: Z. Hamoodi reports research fellowship funding from Royal College of Surgeons, National Joint Registry, and The John Charnley Trust, related to this study. A. Sayers is senior statistician on the HQIP/NJR Lot 2 contract. M. R. Whitehouse is the principal investigator for the HQIP/NJR Lot 2 contract to provide statistical support, analysis and associated services to the NJR, related to this study, and reports multiple grants or contracts from the NIHR and Ceramtec, royalties or licenses from Taylor & Frances, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Heraeus, all of which are unrelated to this study. A. C. Watts reports royalties or licenses and patents planned, issued or pendingfrom Adler, consulting fees from Medartis, payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Medartis, Stryker, and Arthrex, all of which are unrelated to this study, and is also a member of the editorial boards of the National Joint Registry and The Bone & Joint Journal., (© 2024 The British Editorial Society of Bone & Joint Surgery.)

Purpose: To estimate the prevalence, distribution, and co-occurrence of mental ill-health and substance use among gender and sexuality diverse young people relative to their cisgender and heterosexual peers in Australia using population-level, nationally representative data., Methods: We utilised Wave 8 (2018) data from the Longitudinal Study of Australian Children (N = 3037, M age = 18.4) collected via an assessment protocol comprising interviews, direct observations, and assessments (on average 60 min per survey occasion). Weighted prevalence ratios and logistic regression models adjusted for demographic confounders were used to estimate the prevalence and distribution of mental ill-health (psychological distress, past 12-month self-harm thoughts and behaviours, past 12-month suicidal ideation, planning, attempt/s) and substance use outcomes (past 12-month cigarette, alcohol, and marijuana use) across gender identity (trans vs. cisgender), sexuality (gay/lesbian, bisexual, queer [those identifying with an 'other' sexuality identity that is not 'gay', 'lesbian', 'bisexual', or 'heterosexual'] vs. heterosexual) and sexuality diversity status (sexuality diverse vs heterosexual) subgroups. Sex-stratified prevalence rates and accompanying adjusted logistic regression models were also used to assess mental ill-health and substance use disparities by sexuality diversity status. Adjusted multinominal logistic regression models were used to test disparities in co-occurring outcomes by sexuality identity) sexuality status sub-groups, and Fisher's Exact Test of Independence for co-occurring disparities by gender identity (due to small sample size). All analyses used Wave 8 sample weights and adjusted for postcode-level clustering., Results: Among gender and sexuality diverse participants, 59 - 64% reported high or very high levels of psychological distress, 28 - 46% reported past 12-month self-harm ideation or attempts, and 26 - 46% reported past 12-month suicidal ideation, planning, or behaviour. We found significant disparities in high/very high levels of psychological distress, self-harm behaviours and suicidal behaviours among trans participants (adjusted odds ratios (aORs) ranged from 3.5 to 5.5) and sexuality diverse participants (aORs ranged from 3.5 to 3.9), compared with cisgender and heterosexual participants, respectively. Highest disparities in any past 12-month self-harm and suicidal behaviours appeared most pronounced among trans participants and queer participants compared with their cisgender, heterosexual counterparts. Minor differences by sex among sexuality diverse participants were observed for select mental ill-health outcomes. Sexuality diverse participants, and particularly sexuality diverse females, were significantly more likely to report past 12-month cigarette use and past 12-month marijuana use (adjusted odds ratio (aORs) ranging 1.4-1.6). Trans young people were at significantly elevated risk of mental ill-health in co-occurrence with cigarette and marijuana use compared with their cisgender peers (Fisher's Exact Test of Independence p < 0.05 for all), whereas sexuality diverse young people were at greater risk of co-occurring mental ill-health and cigarette co-use and marijuana co-use, compared with their non-sexuality diverse peers (adjusted multinomial odds ratios (aMORs) ranging 2.2-6.0)., Conclusion: Mental ill-health, substance use, and their co-occurrence disproportionately affects gender and sexuality diverse young people in Australia. Further research should study the longitudinal development of these disparities through adolescence, with close attention to the social, embodied contexts of substance use among LGBTQ + young people with the view to building LGBTQ + affirming models of harm reduction., (© 2024. The Author(s).)

Purpose: Age- and disease-related changes in oropharyngeal anatomy and physiology may be identified through quantitative videofluoroscopic measures of pharyngeal area and dynamics. Pixel-based measures of nonconstricted pharyngeal area (PhAR) are typically taken during oral bolus hold tasks or on postswallow rest frames. A recent study in 87 healthy adults reported mean postswallow PhAR of 62%(C2-4) 2 , (range: 25%-135%), and significantly larger PhAR in males. The fact that measures were taken after initial bolus swallows without controlling for the presence of subsequent clearing swallows was identified as a potential source of variation. A subset of study participants had completed a protocol including additional static nonswallowing tasks, enabling us to explore variability across those tasks, taking sex differences into account., Method: Videofluoroscopy still shots were analyzed for 20 healthy adults (10 males, 10 females, M age = 26 years) in head-neutral position, chin-down and chin-up positions, a sustained /a/ vowel vocalization, and oral bolus hold tasks (1-cc, 5-cc). Trained raters used ImageJ software to measure PhAR in %(C2-4) 2 units. Measures were compared to previously reported mean postswallow PhAR for the same participants: (a) explorations of sex differences; (b) pairwise linear mixed-model analyses of variance (ANOVAs) of PhAR for each nonswallowing task versus postswallow measures, controlling for sex; and (c) a combined mixed-model ANOVA to confirm comparability of the subset of tasks showing no significant differences from postswallow measures in Step 2., Results: Overall, PhAR measures were significantly larger in male participants; however, most pairwise task comparisons did not differ by sex. No significant differences from postswallow measures were seen for 5-cc bolus hold, chin-down and chin-up postures, and the second (but not the first) of two repeated head neutral still shots. PhAR during a 5-cc bolus hold was most similar to postswallow measures: mean ± standard deviation of 51 ± 13%(C2-4) 2 in females and 64 ± 16%(C2-4) 2 in males., Conclusions: PhAR is larger in men than in women. Oral bolus hold tasks with a 5-cc liquid bolus yield similar measures to those obtained from postswallow rest frames.

Background: Mental ill-health and substance use bear significant public health burden on young people. Prevention is key. Trauma-informed approaches to prevention of mental ill-health and substance use demonstrate significant promise, yet it is unclear how well existing approaches work for young people targeting mental ill-health and substance use. This review aimed to assess the effectiveness, feasibility, and acceptability of trauma-informed mental ill-health and/or substance use prevention programs for young people., Methods: We searched the PsycINFO, CINAHL, Embase, MEDLINE, and Cochrane Library reference databases for peer-reviewed studies of trauma-informed mental ill-health and/or substance use prevention programs for young people published between 2013 and 2022. Studies in any language were included and reference lists of included articles were scanned for additional studies of relevance., Results: In total, 30 studies were included in this review, comprising five randomized controlled trials (RCTs), seven non-RCTs, 10 quasi-experimental designs, and eight qualitative studies. Among the 30 studies, 27 unique trauma-informed prevention interventions were detailed. Eighteen studies reported statistically significant decreases in mental ill-health, and two studies reported significant decreases in substance use outcomes among participants, up to 6 months following the interventions. Most preventative interventions with statistically significant effects were selective (rather than universal or indicated) in their approach (n = 10, 55%). Broad acceptability and feasibility of trauma-informed prevention programs was observed among studies reporting this information though most quantitative studies were at high risk of bias and/or did not include a control group, whilst qualitative studies tended to report research conducted without a priori research aims., Discussion: This review synthesizes for the first-time evidence on the effectiveness (or efficacy), feasibility, and acceptability of trauma-informed mental ill-health and/or substance use programs for young people, especially for those exposed to traumatic or adverse experiences. While there are promising efficacy outcomes, further research conducting rigorous, well-powered RCTs is required for large-scale evaluation and scaling of the potential preventative benefits of such programs., (© 2024 Foundation for Professionals in Services to Adolescents.)

Background: Air pollution exposure during pregnancy has been associated with numerous adverse pregnancy, birth, and child health outcomes. One proposed mechanism underlying these associations is maternal immune activation and dysregulation. We examined associations between PM 2.5 and NO 2 exposure during pregnancy and immune markers within immune function groups (TH1, TH2, TH17, Innate/Early Activation, Regulatory, Homeostatic, and Proinflammatory), and examined whether those associations changed across pregnancy., Methods: In a pregnancy cohort study (n = 290) in Rochester, New York, we measured immune markers (using Luminex) in maternal plasma up to 3 times during pregnancy. We estimated ambient PM 2.5 and NO 2 concentrations at participants' home addresses using a spatial-temporal model. Using mixed effects models, we estimated changes in immune marker concentrations associated with interquartile range increases in PM 2.5 (2.88 μg/m 3 ) and NO 2 (7.82 ppb) 0-6 days before blood collection, and assessed whether associations were different in early, mid, and late pregnancy., Results: Increased NO 2 concentrations were associated with higher maternal immune markers, with associations observed across TH1, TH2, TH17, Regulatory, and Homeostatic groups of immune markers. Furthermore, the largest increases in immune markers associated with each 7.82 ppb increase in NO 2 concentration were in late pregnancy (e.g., IL-23 = 0.26 pg/ml, 95% CI = 0.07, 0.46) compared to early pregnancy (e.g., IL-23 = 0.08 pg/ml, 95% CI = -0.11, 0.26)., Conclusions: Results were suggestive of NO 2 -related immune activation. Increases in effect sizes from early to mid to late pregnancy may be due to changes in immune function over the course of pregnancy. These findings provide a basis for immune activation as a mechanism for previously observed associations between air pollution exposure during pregnancy and reduced birthweight, fetal growth restriction, and pregnancy complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Introduction: Breast cancer is the most common malignancy worldwide. The disease is more severe in younger women and often confers a poorer prognosis. This study aimed to profile a cohort of young women with breast cancer and address whether aspects of their tumour biology were related to their long-term outcomes., Methods: The records of consecutive women aged 40 and under with a diagnosis of breast cancer at a single centre between 1 January 2010 and 30 December 2015 were analysed and a profile was created. They were followed up until 19 July 2023 (median 112 months, range 4-161), and the impact of oestrogen positivity (ER+), human epidermal growth factor 2 positivity (HER2+), tumour grade, axillary lymph node metastases and Ki67 value on overall survival and disease-free interval (DFI) was investigated., Results: One hundred and sixty-four patients were included. Younger patients typically presented with large, high-grade tumours with axillary lymph node metastases, and 83.2% of the cohort were alive at 5 years. ER+ tumours appeared to have a better 5-year survival: ER+/HER2- 86.3%, ER+/HER2+ 88.5%, ER-/HER2+ 71.4%, and triple-negative (ER-/HER2-) 70.8%. However, neither the log-rank test nor the Cox regression model found a significant effect of ER status and long-term survival (P = 0.485 and P = 0.158 respectively)., Discussion: Young patients with breast cancer have a lower 5-year survival than the UK average for all ages, and patients in this single-centre study with ER+ tumours appeared to have better short-term but similar longer-term outcomes compared to ER- breast cancer., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Background/Objectives: This study assessed the effects of formulation components on the long-term stability of a previously described tetraethyl orthosilicate-based drug delivery system. Early stability studies of a product concept are crucial not only to provide information on the overall system stability and individual components' contributions to it, but also to identify opportunities for dosage form optimization and to define its use case. Methods: We assessed the time-dependent thixogel properties-specifically, mechanical strength, thixotropy, release of model drug, and dry substance-in both real-time and accelerated shelf-life determination set-ups. Results: Our findings indicate that the concentration and molecular weight of hyaluronic acid, one of the main constituents of the investigated thixotropic systems, are key determinants of formulation stability. We further showed that changes in both of these parameters reflect on the drug release properties and stiffness of the formulation and could inform subsequent product development based on several use cases. Conclusions: Overall, this study provides an understanding of some key factors that would need to be considered prior to and in the final product development process of thixogels in preparation for commercialization.

Introduction: The diagnosis of asthma is often based on characteristic patterns of symptoms in the absence of an alternative explanation, resulting in over and under diagnosis. Therefore, diagnostic guidelines usually recommend including confirmation of variable airflow obstruction. Some recommend using a sequence of objective tests; however the tests used, the specific cut-off values and the specified order are yet to be validated. We aimed to determine the optimal cut-off values and series of investigations to diagnose asthma. We also explore the potential for novel tests of small airways function and biomarkers, which could be incorporated into future diagnostic pathways., Methods and Analysis: The Rapid Access Diagnostics for Asthma study is an observational study of 300 symptomatic patients with 'clinician-suspected asthma' and healthy controls (aged ≥3 to <70 years), recruited from primary and secondary care in Greater Manchester, UK. Symptomatic participants will undergo four core visits and one optional visit. Participants will complete two baseline visits and undergo a series of established (spirometry, bronchodilator reversibility, exhaled nitric oxide, home peak flow monitoring and bronchial challenge testing) and novel tests. Following visit 2, participants will receive monitored medium-dose inhaled corticosteroid therapy for 6-8 weeks, after which they will return for repeat testing. Patients will be diagnosed with asthma by 'expert panel' opinion (minimum two respiratory specialists) on review of all data (excluding novel tests) pre and post treatment. Healthy controls will attend two visits to establish reference intervals and calculate repeatability coefficients for novel tests where there is a lack of evidence on what threshold constitutes a 'normal' set of values. The primary end point is to determine the optimum diagnostic pathway for diagnosing asthma., Ethics and Dissemination: The study was approved by Greater Manchester East Research Ethics Committee (18/NW/0777). All participants or parents/guardians are required to provide written informed consent and children to provide written assent. The results will be published in peer-review journals and disseminated widely at conferences and with the help of Asthma and Lung UK (www.asthmaandlung.org.uk)., Trial Registration Number: ISRCTN11676160., Competing Interests: Competing interests: CM has received grants from NIHR, Asthma UK, Innovate UK, Moulton Charitable Foundation, GSK and MRC; travel grants from Sanofi and lecture fees from Novartis, GSK and Sanofi. AngS has received grants from NIHR, Asthma UK, Innovate UK, Moulton Charitable Foundation, GSK and MRC. SF reports personal fees from AstraZeneca, Chiesi, GlaxoSmithKline, Novartis and Teva and grants and personal fees from Boehringer Ingelheim. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Front-of-pack nutrition labelling (FOPNL) on packaged foods is recommended by the World Health Organization to promote healthier diets. Our aim was to assess uptake of Australia's FOPNL, the Health Star Rating (HSR), overall and by HSR score received (0.5 (less healthy) to 5.0 (more healthy) in 0.5 increments) after ten years of voluntary implementation. In a sample of 21,197 products, we found HSR uptake of 37% overall in 2023. Uptake was unevenly distributed, with 24% of products with an HSR ≤ 3 displaying the label, compared to 53% of products scoring ≥3.5 (p < 0.001). Low HSR uptake on poorly rated products demonstrates that most food manufacturers will only display FOPNL where marketing value exists in a voluntary system. Poor and uneven HSR uptake limits consumers' ability to meaningfully use the label to compare and choose healthier products. Government action is urgently required to make the HSR system mandatory., (© 2024. The Author(s).)

Objective: We aimed to investigate the prevalence of sleep disturbances and associated factors among Ukrainians 1 year after Russia's full-scale invasion., Methods: Quota sampling was used to collect online survey data from 2364 adults living in Ukraine aged 18 to 79 years from April 5, 2023, to May 15, 2023. Short sleep duration was defined as sleep duration ≤6 hours and long sleep duration as ≥9 hours. Insomnia was assessed by the Insomnia Symptom Questionnaire., Results: The prevalences of short sleep duration, long sleep duration, and insomnia were 39.4%, 6.9%, and 38.5%, respectively. Short sleep duration and insomnia were both more likely in females (short sleep duration: adjusted odds ratio [aOR] = 1.44; insomnia: aOR = 2.17), individuals with depression (short sleep duration: aOR = 1.61; insomnia: aOR = 7.76), affected by the 2014 Russian invasion (short sleep duration: aOR = 1.37; insomnia: aOR = 1.78), and with more trauma events (short sleep duration: quartile 3 [Q3] versus Q1: aOR = 1.88; Q4 versus Q1: aOR = 1.83; insomnia: Q3 versus Q1: aOR = 2.14; Q4 versus Q1: aOR = 2.32). Insomnia was more likely in Ukrainians with posttraumatic stress disorder (aOR = 2.95), anxiety (aOR = 4.57), and loneliness (aOR = 1.67). Essential public service was associated with short sleep duration (aOR = 1.64). Short sleep duration and insomnia were associated with lower quality of life in physical, psychological, and environmental domains. Insomnia was associated with the social relationships domain., Conclusions: Sleep health among Ukrainian adults 1 year into the war is concerning, with more than one-third reporting inadequate sleep or insomnia. More studies are needed on impacts and interventions for sleep health during and after the war., (Copyright © 2024 by the American Psychosomatic Society.)

Purpose: Ibrutinib is a first-in-class inhibitor of Bruton tyrosine kinase. We previously reported the safety and short-term antitumor activity of ibrutinib in 20 patients with relapsed or refractory (r/r) primary central nervous system (CNS) lymphoma (PCNSL) or secondary CNS lymphoma (SCNSL)., Patients and Methods: We enrolled 26 additional patients with r/r PCNSL/SCNSL into the dose-expansion cohort of the trial into a combined cohort of 46 patients (31 with PCNSL and 15 with SCNSL). Patients received ibrutinib at 560 or 840 mg daily in the dose-escalation cohort and ibrutinib at 840 mg daily in the expansion cohort. The median follow-up was 49.9 and 62.1 months for patients with PCNSL and SCNSL, respectively. We sequenced DNA from available tumor biopsies and cerebrospinal fluid collected before and during ibrutinib therapy., Results: Tumor responses were observed in 23/31 (74%) patients with PCNSL and 9/15 (60%) patients with SCNSL, including 12 complete responses in PCNSL and 7 in SCNSL. The median progression-free survival (PFS) for PCNSL was 4.5 months [95% confidence interval (CI), 2.8-9.2] with 1-year PFS at 23.7% (95% CI, 12.4%-45.1%). The median duration of response in the 23 PCNSL responders was 5.5 months. The median PFS in SCNSL was 5.3 months (95% CI, 1.3-14.5) with a median duration of response of 8.7 months for the 9 responders. Exploratory biomarker analysis suggests that mutations in TBL1XR1 may be associated with a long-term response to ibrutinib in PCNSL (P = 0.0075). Clearance of ctDNA from cerebrospinal fluid was associated with complete and long-term ibrutinib responses., Conclusions: Our study confirms single-agent activity of ibrutinib in r/r CNS lymphoma and identifies molecular determinants of response based on long-term follow-up., (©2024 American Association for Cancer Research.)

We aimed to assess the mental health of adults living in Ukraine one year after onset of the Russo-Ukrainian war, along with quality of life and coping strategies. Quota sampling was used to collect online survey data from 2364 adults aged 18-79 years living in Ukraine from April 5, 2023 to May 15, 2023. Among adults living in Ukraine, 14.4 % had probable post-traumatic stress disorder (PTSD), another 8.9 % had complex PTSD (CPTSD), 44.2 % had probable depressive disorder, 23.1 % had anxiety disorder and 38.6 % showed significant loneliness. In adjusted models, the number of trauma events experienced during the war showed a dose-response association with PTSD/CPTSD and was associated with depressive disorder and anxiety disorder. Quality of life domains, particularly physical quality of life, were negatively associated with PTSD/CPTSD, depressive disorder, anxiety disorder, and number of trauma events. Maladaptive coping was positively associated with depressive disorder, anxiety disorder, PTSD/CPTSD and loneliness. All quality of life domains were positively associated with using adaptive coping strategies. Mental health disorders are highly prevalent in adults living in Ukraine one year into the war. Policy and services can promote adaptive coping strategies to improve mental health and quality of life for increased resilience during war., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier B.V.)

Background: Generalized anxiety disorder (GAD)-characterised by excessive and uncontrollable worry-is the most frequently diagnosed anxiety disorder during pregnancy and the postpartum period. Identification of GAD often relies on assessment of its cardinal feature, pathological worry. The Penn State Worry Questionnaire (PSWQ) is the most robust measure of pathological worry to date but has not been extensively evaluated for use during pregnancy and the postpartum period. This study evaluated the internal consistency, construct validity, and diagnostic accuracy of the PSWQ in a sample of pregnant and postpartum women with and without a principal GAD diagnosis., Methods: One hundred forty-two pregnant and 209 postpartum women participated in this study. Sixty-nine pregnant and 129 postpartum participants met criteria for a principal diagnosis of GAD., Results: The PSWQ demonstrated good internal consistency and converged with measures assessing similar constructs. Pregnant participants with principal GAD scored significantly higher on the PSWQ than those with no psychopathology and postpartum participants with principal GAD scored significantly higher than those with principal mood disorders, other anxiety and related disorders, and no psychopathology. A cut-off score of 55 and 61 or greater was determined for detecting probable GAD during pregnancy and the postpartum period, respectively. Screening accuracy of the PSWQ was also demonstrated., Conclusions: This study underscores the robustness of the PSWQ as a measure of pathological worry and probable GAD and supports its use in the detection and monitoring of clinically significant worry symptoms during pregnancy and postpartum period.

Women who use violence represent one of the fastest growing groups within the Australian prisoner population, including Aboriginal women who are more likely to be incarcerated than non-Aboriginal women for violent crimes. Many incarcerated women report histories of adverse childhood experiences (ACEs) and intimate partner violence. This exploratory study examines baseline data from a sample of 167 women in 3 Western Australia women's prisons enrolled in a gender-specific violent behavior program. It describes their exposure to intimate partner violence, head injury, and childhood adversities. Overall, 94% of women had experienced at least one childhood adversity (median 6), and 94% reported being a victim of physical violence by a current or former intimate partner. Aboriginal women were more likely than non-Aboriginal women to report that a family member was incarcerated as a child ( p  = .001). There was an association between an increased number of ACEs and head injury with a loss of consciousness ( p  = .008). Overall, these results present a harrowing picture of childhood exposure to adversity and violence in adulthood. Successful rehabilitation of women incarcerated for violent crimes should be cognizant of the histories of extreme violence endured by most of these women., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Previous research has shown a robust association between different childhood and adolescent vulnerabilities and youth offending. However, these investigations have primarily focused on youths from high-income Western countries. Consequently, the generalizability of these findings to better inform global justice policies remains uncertain. This study aimed to address this gap by examining the relationship between individual, familial, and contextual vulnerabilities and criminal versatility during young adulthood, accounting for sociodemographic factors and cross-national differences. Data were derived from a diverse sample of 4,182 young adults (67% female; mean age = 18.96; SD  = 0.81) residing in 10 countries across 5 continents who participated in the International Study of Pro/Antisocial Behavior in Young Adults . The Psychosocial and Family Vulnerability Questionnaire and the Adverse Childhood Experiences questionnaire were used to assess social and family adversity, and past-year criminal diversity was measured with the Criminal Variety Index. Results indicate that child maltreatment, substance abuse, and delinquent peers are global risk factors for criminal variety. Moreover, they are independent across males and females and among youths living in countries that are ranked differently on the Human Development Index (HDI). In addition, some childhood vulnerabilities showed different predictive ability across sexes (e.g., school failure), and across countries ranked differently on the HDI (e.g., family dysfunction). These findings suggest that certain childhood factors contribute to criminal behavior through transcultural mechanisms. Moreover, they highlight the importance of developing evidence-based policies that focus on transcultural risk factors to globally prevent criminal behavior., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Purpose: A combined body weight loss and upper body/arm exercise programme is a potential strategy for managing Breast cancer related lymphoedema (BCRL), but there is limited data on the best method for delivery or its potential efficacy., Methods: Fifty-seven women with overweight/obesity and BCRL were randomised to a 12 week supervised (n = 12) or home-based combined weight loss and upper body/arm exercise programme (n = 16), a home-based upper-body arm exercise only programme (n = 17) or standard care (n = 12). Primary outcomes were uptake, retention and changes in weight and change in Relative Arm Volume Increase (RAVI) using analysis of covariance (ANCOVA)., Results: Sixteen percent of women invited joined the study and 49 completed the trial (85% retention). Reductions in weight occurred in the supervised and home-based weight control and exercise programmes; Mean (95% CI) change compared to standard care - 1.68 (- 4.36 to - 1.00), - 2.47(- 4.99 to - 0.04) Kg. Reductions in perometer assessed RAVI were seen in the supervised and home-based combined weight control and arm exercise groups and the weight stable home-based arm exercise only group: mean (95% CI) change compared to standard care - 2.4 (- 5.0 to + 0.4),- 1.8 (- 4.3 to + 0.7), - 2.5(- 4.9 to - 0.05)%., Conclusion: Women with BCRL and overweight and obesity engaged in diet and exercise weight loss programmes. Both weight loss/arm exercise programmes led to modest changes in weight and BCRL. Comparable reductions in BCRL were reported in the weight stable group undertaking arm exercise only. The independent and combined effects of weight loss and exercise on BCRL need further study., Trial Registration: ISRCTN86789850 https://doi.org/10.1186/ISRCTN86789850 , registered 2011., (© 2024. The Author(s).)

Background: COVID-19 saw an increase in child mental health presentations internationally. Clinicians analogised the exponential increase in anorexia nervosa to a 'tsunami' or 'outbreak', raising parallel concerns regarding medical and psychological risks (Marsh in The Guardian, 2021; Leask in NZ Herald, 2021; Monteleone et al. in Eat Weight Disord 26(8):2443-2452, 2021) . It is unclear whether Ireland emulated this picture of increased referrals with increased medical compromise., Aims: This paper examines both rates and clinical profiles of child eating disorder presentations in the Republic of Ireland (ROI), across different clinical settings., Methods: Following ethical approval, retrospective chart reviews were conducted in a community eating disorder service and in two paediatric hospital settings. The time frame of the different studies ranged from January 2016 to December 2022., Results: Community eating disorder services saw significantly higher referral rates post COVID-19 (3.78/month vs. 2.31/month, p = 0.02), with a shorter duration of illness (4.8 months vs. 7.4 months, p = 0.001), but no significant difference in ideal body weight % (IBW%) at referral (85.32% vs. 83.7%, p = 0.1). Both paediatric hospitals witnessed significantly increased referrals post-COVID-19 (hospital 1; 4.38/month vs. 1.93/month, p = 0.0001; hospital 2; 2.8/month vs. 0.92/month, p < 0.0001), but no significant difference in IBW% at assessment (hospital 1; 82.7% vs. 81.39%, p = 0.673; hospital 2; 81.5% vs. 83%, p = 0.563). There was no significant difference in clinical profile, management, or duration of hospital stay., Conclusions: This study supports the growing consensus of a pandemic specific increase in eating disorder referrals to both medical and psychiatry services. However, there was little to indicate a change in clinical profile or severity. Ongoing monitoring of referrals is necessary to ensure adequate service availability and expertise., (© 2024. The Author(s).)

Wheat (Triticum aestivum) is an important crop worldwide, contributing to about one third of the global caloric intake. In June 2021, leaves with bacterial blight symptoms, including yellow and necrotic lesions running parallel to veins, were found in several fields across five counties in eastern Colorado (Weld, Morgan, Sedgwick, Baca, and Kit Carson). Plants exhibiting these symptoms were scattered throughout fields, but symptoms appeared consistent across counties. To determine the causal agent and complete Koch's postulates, a 1 cm2 symptomatic leaf area was excised and macerated in 0.5 mL of sterilized water from four field samples. The lysate was spread on yeast extract dextrose calcium carbonate medium (YDC agar, 1% yeast extract, 2% dextrose, 2% calcium carbonate, 1.5% agar) to isolate bacteria. Single colonies of yellow, mucoid morphology were selected and streaked on new YDC plates. Isolate genomic DNA was extracted (Zymo Research Quick-DNA Fungal/Bacterial Miniprep Kit, #D6005), and ~30 ng of gDNA was used to amplify the 16S rRNA, gyrB, and rpoB genes of all four isolates (Barret et al., 2015; Delétoile et al., 2009; Krawczyk et al., 2020; Ogier et al., 2019). Amplified PCR products were cleaned (Zymo DNA Clean & Concentrator kit, #D4033) and Sanger sequenced, and all sequences have been deposited in NCBI (16S rRNA: OR707336, OR707337, OR707338, OR707339), (gyrB: PP407951, PP407952, PP407953, PP407954), (rpoB: PP407955, PP407956, PP407957, PP407958). A BLAST search against whole genomes identified one isolate from Kit Carson county (CO314) and two isolates from Baca county (CO316 and CO317) as Pantoea agglomerans with 100% identity for the 16S rRNA, gyrB, and rpoB genes, and one isolate from Weld county (CO315) was 100% identical to Pantoea allii for all three genes. To complete Koch's postulates and confirm Pantoea sp. as the causal disease agents, isolates were grown as lawns on DifcoTM Nutrient Agar (NA) medium (48h, 28℃), suspended in 10 mM MgCl2 using a final optical density of 0.1 (~109 colony forming units per milliliter (CFU/mL)), and syringe-infiltrated into the entire leaf area of 10-day-old wheat seedling leaves (var. Hatcher). Treatments of 10mM MgCl2 and a field isolate that does not cause symptoms, identified as Pseudomonas synxantha by 16S rRNA and gyrB sequencing, were negative controls. Inoculated wheat plants were transferred to a growth chamber (22℃, 90% relative humidity). Symptoms developed 14 days post inoculation (dpi), with the most severe appearing 21 dpi. Each of the four Pantoea isolates were re-isolated from symptomatic leaves by grinding them in a Tissue Lyser II (Qiagen) with two metal beads and diluting with 0.4 mL of sterile water. A 20 µL sample of each isolate was plated on NA (24h, 28℃). The colonies appeared phenotypically identical to the original isolates, and Sanger sequencing confirmed the identities of the isolates. To our knowledge, this is the first report of P. agglomerans causing disease in wheat in the United States, and the first report of P. allii as a wheat disease-causing agent. This report is consistent with previous communications showing P. agglomerans causing wheat disease in China (Gao et al., 2023), and P. ananatis in Poland (Krawczyk et al., 2020). The growing numbers of reports of Pantoea spp. as pathogens in recent years suggests increasing novel disease emergence on cereals worldwide.

Objective: The pharyngeal swallow typically begins within 400 ms following the arrival of a liquid bolus in the pharynx. By contrast, processed food particles aggregate in the valleculae prior to swallow initiation. With solid foods, swallow reaction time (SRT), the interval between bolus passing the ramus of mandible and hyoid burst onset (HYB) can be subdivided into components of vallecular aggregation time (VAT) and the subsequent end of aggregation to hyoid burst interval (EOA-to-HYB). However, expected durations of these timing measures remain unclear. We aimed to study bolus aggregation in healthy swallowing for International Dysphagia Diet Standardisation Initiative Food Levels 5 (minced and moist [MM5]), 6 (soft and bite-sized [SB6]), and 7 (regular [RG7]). Understanding typical patterns and durations of vallecular aggregation with solids in healthy swallowing will inform the identification of impaired swallow timing in patient populations., Design: Twenty healthy adults (10 males, M age = 28 years, range: 23-55 years) swallowed two boluses each of MM5, SB6, and RG7 foods in videofluoroscopy. Blinded duplicate ratings determined bolus location at swallow onset, SRT, VAT, and EOA-to-HYB. Texture-based differences were measured using Friedman's tests. Bolus location was at/above the valleculae at swallow onset for 85% of boluses, with no differences by texture. SRT, VAT, and EOA-to-HYB did not vary by texture, with overall median values (interquartile range) of 99 ms (-66 to 743 ms) for SRT, 347 ms (66 to 891 ms) for VAT, and -132 ms (-231 to -83 ms) for EOA-to-HYB., Conclusions: These data corroborate prior evidence that it is not unusual for food particles to aggregate in the valleculae prior to swallow initiation in healthy swallowing. However, durations of vallecular aggregation are typically < 1 s in healthy adults.

Background: Intermediaries are health-related workers who facilitate connections to local physical activities. Intermediaries deliver interventions by receiving referrals, conducting assessments, connecting referred individuals to activities and/or services in the community, and following up with them over time. However, it is unclear whether individuals who are referred to physical activities by an intermediary improve their physical activity levels, and what their perspectives and experiences are of participating in this intervention. To date there has been a lack of studies investigating the effect of this intervention on physical activity using appropriate outcome measures., Methods: This will be a mixed methods pilot feasibility study. Participants will be individuals referred or self-referred to an intermediary and connected to local physical activities. Participants will be recruited through two types of intermediary services in Ireland; social prescribing and local sports partnerships. A total of 30 participants will be recruited (15 per service). Baseline demographic information will be taken upon enrolment to the study and three questionnaires will be completed: the International Physical Activity Questionnaire - Short Form, Self-Efficacy for Exercise Scale and Short Warwick Edinburgh Mental Well-being Scale. The questionnaires will be repeated after 12 weeks and in addition semi-structured interviews will be carried out to explore intervention content and delivery, as well as acceptability of the intervention and evaluation design., Discussion: This overall aim of this proposed study is to investigate the feasibility of an intervention delivered by an intermediary to improve physical activity and health-related outcomes of community-dwelling individuals., Registration: ClinicalTrials.gov (NCT06260995)., Competing Interests: 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., (© 2024 The Authors.)

In rich false memory studies, familial informants often provide information to support researchers in planting vivid memories of events that never occurred. The goal of the current study was to assess how effectively we can retract these false memories via debriefing - i.e., to what extent can we put participants back the way we found them? We aimed to establish (1) what proportion of participants would retain a false memory or false belief following debriefing, and (2) whether richer, more detailed memories would be more difficult to retract. Participants (N = 123) completed a false memory implantation protocol as part of a replication of the "Lost in the Mall" study (Loftus & Pickrell, Psychiatric Annals, 25, 720-725, 1995). By the end of the protocol, 14% of participants self-reported a memory for the fabricated event, and a further 52% believed it had happened. Participants were then fully debriefed, and memory and belief for the false event were assessed again. In a follow-up assessment 3 days post-debriefing, the false memory rate had dropped to 6% and false belief rates also fell precipitously to 7%. Moreover, virtually all persistent false memories were found to be nonbelieved memories, where participants no longer accepted that the fabricated event had occurred. Richer, more detailed memories were more resistant to correction, but were still mostly retracted. This study provides evidence that participants can be "dehoaxed", and even very convincing false memories can be retracted., (© 2024. The Author(s).)

The glucagon-like peptide-1 receptor (GLP-1R) agonists reduce glycated hemoglobin in patients with type 2 diabetes. Mounting evidence indicates that the potential of GLP-1R agonists, mimicking a 30 amino acid ligand, GLP-1, extends to the treatment of neurodegenerative conditions, with a particular focus on Alzheimer's disease (AD). However, the mechanism that underlies regulation of GLP-1R availability in the brain with AD remains poorly understood. Here, using whole transcriptome RNA-Seq of the human postmortem caudate nucleus with AD and chronic hydrocephalus (CH) in the elderly, we found that GLP-1R and select mRNAs expressed in glucose dysmetabolism and dyslipidemia were significantly altered. Furthermore, we detected human RNA indicating a deficiency in doublecortin (DCX) levels and the presence of ferroptosis in the caudate nucleus impacted by AD. Using the genome data viewer, we assessed mutability of GLP-1R and 39 other genes by two factors associated with high mutation rates in chromosomes of four species. Surprisingly, we identified that nucleotide sizes of GLP-1R transcript exceptionally differed in all four species of humans, chimpanzees, rats, and mice by up to 6-fold. Taken together, the protein network database analysis suggests that reduced GLP-1R in the aged human brain is associated with glucose dysmetabolism, ferroptosis, and reduced DCX+ neurons, that may contribute to AD., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Barrett, Ivey, Cunningham, Coffman, Pemberton, Lee, Patra, Day, Lee and Shim.)

Purpose: This study was guided by three research aims: firstly, to examine the longitudinal trends of health-related quality of life (HR-QoL) among gender and sexuality diverse (LGBTQA2S+) young people through adolescence (ages 14-19); secondly, to assess longitudinal associations between poor mental health and HR-QoL among LGBTQA2S+ young people through adolescence; and thirdly, to examine differences in HR-QoL among LGBTQA2S+ young people during early adolescence (ages 14 and 15) depending on select school-, peer-, and parent-level factors., Methods: This study used three of nine available waves of data from a large population-level, probability sample-based, longitudinal cohort study, namely the K' cohort: children aged 4-5 years old at time of study enrolment followed-up biennially (~ 61% retention rate). HR-QoL weighted means and standard deviations were calculated using Child Health Utility 9D (CHU-9D) scores for LGBTQA2S+ participants at ages 14 and 15 (Wave 6), ages 16 and 17 (Wave 7), and ages 18 and 19 (Wave 8). To strategically identify policy-relevant modifiable behavioural factors suitable for prevention and early intervention, non-parametric Wilcoxon signed-rank tests tested differences in mean CHU-9D ranks at ages 14 and 15 (Wave 6) between groups (gender identity: trans vs. cis; identity-level sexuality: gay, lesbian, bisexual, or other diverse sexuality vs. heterosexual; group-level sexuality: sexually diverse vs. not sexually diverse) and selected school factors (school acceptance, belonging, freedom of expression), peer factors (peer relationship quality, trust, respect), and family factors (parental acceptance, understanding, trust), with Hedge's g correction statistics computed for effect sizes. Longitudinal associations between gender, sexuality, and poor mental health (depressive symptoms, anxiety, symptoms, self-harm thoughts/behaviour, and suicidal thoughts/behaviour) and HR-QoL were tested using mixed-effects models with random intercepts and random slopes for nested clustering (participants within postcodes)., Results: HR-QoL disparities disproportionately affecting LGBTQA2S+ groups relative to their cisgender, heterosexual peers, were well-established by age 14 to 15 relatively steeper reductions in HR-QoL were observed throughout adolescence among all LGBTQA2S+ groups, with HR-QoL widening the most for trans participants. Poor mental health was significantly associated with HR-QoL declines. LGBTQA2S+ participants with positive school- and parent factors related to feelings of acceptance, belonging, and freedom of self-expression, reported significantly higher HR-QoL during early adolescence., Conclusion: Evidence-based public health policy responses are required to address the dire HR-QoL inequities among LGBTQA2S+ young people, particularly trans young people. Prioritising the promotion of school- and family-based interventions which foster LGBTQA2S+ inclusivity, acceptance, and a sense of belonging from early adolescence through young adulthood, represents a feasible, evidence-based, and cost-effective response to address these HR-QoL disparities., (© 2024. The Author(s).)

Switching between similar food and beverage products may reduce greenhouse gas emissions (GHGe). Here, using consumer data linked to 23,550 product-specific GHGe values, we estimated annual GHGe attributable to product purchases consumed at home in Australia and calculated reductions from specific switches. Potential changes to mean Health Star Rating, mean energy density and the proportion of ultraprocessed foods purchased were assessed. Approximately 31 million tonnes of GHGe were attributable to products consumed at home in 2019, the three highest contributors of GHGe being 'meat and meat products' (49%), 'dairy' (17%) and 'non-alcoholic beverages' (16%). Switching higher-emission products for 'very similar' lower-emission products could reduce total emissions by 26%. Switches to 'less similar' lower-emission products could lead to a 71% reduction. Switches had little impact on the average Health Star Rating, energy density of purchases and proportion of ultraprocessed foods purchased. Directing manufacturing and marketing towards lower-environmental-impact products and signposting such options to consumers are key., (© 2024. The Author(s).)

Introduction: Connecting inactive individuals to local physical activity (PA) and exercise, via intermediaries (professionals who can facilitate and support connections to non-medical services) may be an effective method to tackle physical inactivity. Evidence regarding the processes of intermediaries, the profile of people referred, how connections to local PA and exercise are made and outcomes of these connections is lacking., Methods: This scoping review followed guidelines from the Joanna Briggs Institute. Searches of four electronic databases (Embase, Medline, Web of Science, CINAHL) and an extensive grey literature search were conducted from inception to June 2022. Full-text studies which reported on community-dwelling adults (population), and the processes of intermediaries (concept) when connecting to local PA and exercise (context) were considered for inclusion. A logic model was created to map processes to outcomes. Evidence advances and gaps were identified., Results: N = 28 studies were identified. Participants referred to an intermediary were older, female, and with poorer health. Where possible, the processes of referral, assessment, follow-up and discharge by intermediaries were described, as well as the local PA and exercise services used. Short-term PA outcomes appeared positive after working with intermediaries, but many studies were poorly described, and the review was not designed to examine effectiveness of this intervention., Discussion/conclusion: Many aspects of the processes were poorly described. More robust studies evaluating the processes of intermediaries are needed, as well as further exploration of the optimum processes in improving PA outcomes., Competing Interests: The authors have no competing interests to declare., (Copyright: © 2024 The Author(s).)

Background: Urinary CXCL10/creatinine (uCXCL10/Cr) is proposed as an effective biomarker of subclinical rejection in pediatric kidney transplant recipients. This study objective was to model implementation in the clinical setting., Methods: Banked urine samples at a single center were tested for uCXCL10/Cr to validate published thresholds for rejection diagnosis (>80% specificity). The positive predictive value (PPV) for rejection diagnosis for uCXCL10/Cr-indicated biopsy was modeled with first-positive versus two-test-positive approaches, with accounting for changes associated with urinary tract infection (UTI), BK and CMV viremia, and subsequent recovery., Results: Seventy patients aged 10.5 ± 5.6 years at transplant (60% male) had n = 726 urine samples with n = 236 associated biopsies (no rejection = 167, borderline = 51, and Banff 1A = 18). A threshold of 12 ng/mmol was validated for Banff 1A versus no-rejection diagnosis (AUC = 0.74, 95% CI = 0.57-0.92). The first-positive test approach (n = 69) did not resolve a clinical diagnosis in 38 cases (55%), whereas the two-test approach resolved a clinical diagnosis in the majority as BK (n = 17/60, 28%), CMV (n = 4/60, 7%), UTI (n = 8/60, 13%), clinical rejection (n = 5/60, 8%), and transient elevation (n = 18, 30%). In those without a resolved clinical diagnosis, PPV from biopsy for subclinical rejection is 24% and 71% (p = .017), for first-test versus two-test models, respectively. After rejection treatment, uCXCL10/Cr level changes were all concordant with change in it-score. Sustained uCXCL10/Cr after CMV and BK viremia resolution was associated with later acute rejection., Conclusions: Urinary CXCL10/Cr reliably identifies kidney allograft inflammation. These data support a two-test approach to reliably exclude other clinically identifiable sources of inflammation, for kidney biopsy indication to rule out subclinical rejection., (© 2024 The Authors. Pediatric Transplantation published by Wiley Periodicals LLC.)

Objective: Evidence suggests that young adults (aged 18-34) were disproportionately impacted by the COVID-19 pandemic, but little is known about their longer-term mental health changes beyond the early pandemic period. This article investigates heterogeneous trajectories of mental health among Australian young adults across 2 years of the pandemic and identifies a broad range of associated risk and protective factors., Method: Young adults ( N = 653, M age = 27.8 years) from the longitudinal Alone Together Study were surveyed biannually between July 2020 and June 2022. Measures assessed anxiety (7-item Generalised Anxiety Disorder scale) and depression (9-item Patient Health Questionnaire) symptoms at Waves 1-4, as well as demographic, psychological, adversity and COVID-19 factors at baseline., Results: Four and three distinct trajectories of anxiety and depressive symptoms, respectively, were identified through growth mixture modelling. The proportion of participants in each anxiety trajectory were Asymptomatic (45.9%), Mild Stable (17.9%), Moderate-Severe Stable (31.1%) and Initially Severe/Recovering (5.1%). For depression, Mild Stable (58.3%), Moderate-Severe Stable (30.5%) and Reactive/Recovering (11.2%). Baseline factors associated with severe symptom trajectories included a lifetime mental health disorder, pre-pandemic stressful events, identifying as LGBTQIA+ and/or female, and experiencing one or more infection-control measures. Higher household income was protective., Conclusion: Most young adults demonstrated stable trajectories of low or high symptoms during the pandemic, with smaller groups showing initially severe or reactive symptoms followed by marked improvements over time. Vulnerable subgroups (gender- or sexuality-diverse, those with prior adversity or pre-existing mental ill-health) may face ongoing impacts and require targeted psychosocial supports to assist their mental health recovery post-COVID-19 and in the event of future crises., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship and/or publication of this article.

Background: The Andago is an electromechanical gait trainer providing dynamic body weight support while simultaneously enabling over ground walking. The aim of this study was to compare the effects of the Andago with over ground walking on selected gait parameters, during a single gait reeducation session in a post-acute rehabilitation population., Methods: Twenty-seven participants (mean age 78 yrs. (SD = 9.2), female 55.6% (n = 15)) undergoing rehabilitation for neurological (51.8%, n = 14), orthopedic (33.3%, n = 9), and medical conditions (14.8%, n = 4) completed the study. This was a single group, cross sectional, repeated measures study. Participants completed a 10-meter walk test (10MWT) and a 20-minute gait reeducation session under two conditions: i) harnessed in the Andago with body weight support or ii) using their normal walking pattern. Walking speed, steps taken, distance walked, rest breaks, Borg ratings of perceived exertion, and fear of falling were compared over both conditions., Results: Walking speed was significantly slower with the Andago (10MWT mean difference 0.12 (95% CI 0.03-0.20), eta squared 0.24, p = .008; 20-min gait mean difference 0.04 (95% CI 0.00-0.09), eta squared 0.15, p = .049). During the 20-minute gait reeducation session, step count, distance walked, and duration of walking was similar over both conditions, however participants recorded less rest breaks and fear of falling at minutes 10 and 20 in favor of the Andago., Conclusion: Gait parameters measured during a single gait reeducation session in the Andago, in a mixed cohort of predominately older rehabilitation patients, appear comparable to conventional over ground training, other than walking speed which was reduced.

Introduction: Perfluoroalkyl substances (PFAS) are synthetic chemicals used in industrial and consumer goods that are widely detected in human populations and are associated with adverse health outcomes, including perinatal health risks and child health. One mechanism of influence may be the impact of PFAS exposure on placental structure and function., Objectives: The objective of this study is to investigate the relationship between maternal prenatal exposure to PFAS and measures of placental vascularization, and to assess whether changes in vascularization play a role in mediating the impact of PFAS on birth outcomes., Methods: Using data from a prospective cohort study, we examined associations between second trimester PFAS (individually and as mixtures using Bayesian kernel machine regression) and placental arterial vasculature in term placentae (N = 158); secondarily we evaluated the degree to which alterations in placental arterial vasculature explained associations between PFAS exposure and birth outcomes. Placental arterial vasculature features were collected from arterial tracings of each placental image., Results: In both linear regression and mixture models, natural log-transformed perfluorooctanoic acid concentrations were negatively associated with surface vasculature, indexed by the mean distance from arterial end point to perimeter (β = -0.23, 95% CI: -0.41, -0.041); additionally, maximum arterial tortuosity was negatively associated with placental weight (β = -0.19, 95% CI: -0.34, -0.051). There were no reliable differences in effect by fetal sex., Discussion: The findings provide some of the first evidence of PFAS exposure shaping a key measure of placental vascular function, which may underlie the impact of PFAS on perinatal and child health risks., Competing Interests: Declaration of competing interest None, (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: Exposure to endocrine disrupting chemicals (EDCs), such as phthalates, can negatively impact maternal and child health, contributing to impaired fetal growth, preterm birth, and pregnancy complications, as well as increased downstream risks of cardiometabolic disease and breast cancer. Notably, women of color (WOC) are the largest consumers of personal care products, which are a common source of EDC exposure., Methods: The Let's Reclaim Our Ancestral Roots (Let's R.O.A.R) Pilot Study developed an educational intervention delivered during pregnancy to promote reduced use of phthalate-containing hair care products (HCPs). This mixed-methods study included: (1) a quantitative analysis and (2) a qualitative analysis of the educational sessions and the semi-structured focus groups to evaluate the factors that influenced the hair care practices and product choices of WOC at various stages of life, including their current pregnancy (hereafter referred to as the hair journey). During the sessions, participants learned about EDCs (with a focus on phthalates), the unequal burden of exposure for WOC, adverse implications of exposure, and exposure reduction strategies. Focus group sessions provided insight into participants' hair journeys from childhood to the current pregnancy and explored factors during their hair product selection process. All sessions were transcribed and imported into NVivo Version 12 for coding and thematic analysis., Results: A total of 46 individuals were enrolled in the study, and 31 participated in an educational session. This current work synthesizes the qualitative analysis of this study. We identified two important life stages (before and after gaining agency over hair care practices and product choices) and three dominant themes related to HCP use: (1) products that impacted the hair journey, which involved all mentions of hair products, (2) factors that influenced the hair journey, which included individuals or entities that shaped participants' hair experiences, and (3) the relationship between hair and sense of self, where sense of self was defined as the alignment of one's inner and outer beauty., Conclusion: The themes intersected and impacted the participants' hair journey. Cultural integration was a sub-theme that overlapped within the dominant themes and participants discussed the effect of traditions on their hair experiences., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Vilfranc, Houghton, Tsui, Barrett, Llanos, Pennell, Walker, Martinez, Morton, Shepard, Terry and McDonald.)

Background: Weight and health behaviours impact on breast cancer risk. We describe trends in weight and health behaviours in women at entry to a specialist breast cancer family history clinic in Manchester, UK, and changes after clinic entry., Methods: Questionnaires were completed at clinic entry (1987-2019, n = 10,920), and updated in 2010-11 (n = 3283). Clinic entry characteristics were compared between joining periods 1989-98, 1999-2008 and 2009-18. Partial Least Squares analysis characterised trends in weight, smoking and alcohol intake by age at entry, year of entry and birth year. Weight changes were compared over time, between joining periods., Results: Obesity at clinic entry increased from 10.6% in 1989-98 to 20.5% in 2009-18. Alcohol intake above recommendations and smoking prevalence decreased from 20.1% to 13.8% and 33.5% to 16.1% respectively. Weight gain was median 9.7 (IQR 1.4-20.6) % between age 20 and clinic entry (mean duration 11.9 ± 5.6 years) and a further 4.5 (0.0-12.5) % between clinic entry and 2010-11 (31.1 ± 10.4 years). Weight gain between age 20 and clinic entry was highest in the most recent joining period., Conclusions: Obesity and weight gain are common in women attending a breast cancer family history clinic suggesting a need for weight management advice and support., (© 2024. The Author(s).)

Generalized anxiety disorder (GAD) is a leading mental health concern during pregnancy and the postpartum (perinatal) period. People with GAD engage in problematic behaviors to manage their distress. However, the extent of GAD behaviors during the perinatal period may not be adequately captured by the Worry Behaviors Inventory (WBI), the most comprehensive measure of GAD behaviors to date. We evaluated the structure of the initial WBI item-pool and then evaluated the internal consistency, construct validity, and predictive utility of the Perinatal Revised WBI (WBI-PR) in a sample of 214 perinatal women with and without GAD. A two-factor, 10-item scale was supported, and some of the retained items differed from the original WBI. Internal consistency of the WBI-PR was acceptable, and evidence of construct validity was demonstrated. The WBI-PR predicted GAD diagnostic status both alone and beyond existing generalized anxiety and depression symptoms. Implications of these findings are discussed., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Noise-induced hearing loss affects roughly 430 million people worldwide. Current treatment options often require invasive medical procedures, and to date, there are no FDA-approved drug therapies. While the causes can be diverse, noise induced hearing loss is unequivocally associated with oxidative stress and inflammation, and subsequent damage to the inner ear structures. Several studies have shown that various antioxidants such as glutathione, cysteine, and methionine can be used to mitigate oxidative damage from reactive oxygen species; however, these studies relied on invasive or systemic drug delivery methods. This study focused on the development and characterization of a novel series of antioxidant compounds that would be suitable for non or minimally invasive topical inner ear delivery and could mitigate reactive oxygen species associated cellular damage. Specifically, a series of covalent conjugates were synthesized by using hyaluronan as a drug carrier, and methionine, cysteine or glutathione as antioxidant drugs. The conjugates were tested for their ability to readily permeate though in vitro round window membrane and tympanic membrane permeation models, as well as their in vitro internalization into cochlear cells. Our data revealed interdependence between the molecular weight of the hyaluronan carrier, and the tissue and cellular membrane permeation capacity. Subsequent screening of the adequately sized conjugates in in vitro acellular assays revealed the strongest antioxidant activity for the cysteine and glutathione conjugates. These oxidative stress protective effects were further confirmed in cellular in vitro assays. Collectively, the data herein showcase the potential value of these conjugates as therapeutics against oxidative-stress-mediated cellular damage specific to noise-induced hearing loss., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Arrigali, Veit, Birru, Van Tine, Sandau, Barrett-Catton, Tonnerre and Serban.)

Background: This review evaluated the existing literature exploring the effects of arts-inclusive programs (AIPs) on the mental health and wellbeing of young children. AIPs include activities, programs, or interventions containing creative arts., Methods: Literature searches were conducted across three databases (SCOPUS, psycINFO, and ERIC). The search was restricted to studies reporting outcomes of children 0-6 years., Results: Nine studies were included in the review (3,671 participants). Three key themes were identified: music-related ( n  = 4); artmaking ( n  = 3); and storytelling/drama ( n  = 2). All included studies reported positive outcomes on children's wellbeing following engagement in AIPs., Discussion: This review found emerging evidence demonstrating positive impacts of arts engagement on the wellbeing of children aged 0-6. However, most studies were low quality and used varying outcome measures. The review is one of the first to highlight the lack of high-quality studies on the relationship between AIPs and wellbeing in young children.

There is a substantial need of effective drugs for the treatment of hearing loss, which affects nearly 500 million individuals globally. Hearing loss can be the result of intense or prolonged noise exposure, ototoxic drugs, infections, and trauma, which trigger inflammatory signaling cascades that lead to irreversible damage to cochlear structures. To address this, we developed and characterized a series of covalent conjugates of anti-inflammatory drugs to hyaluronic acid (HA), for potential use as topical ototherapeutics. These conjugates were tested in in vitro assays designed to mirror physiological processes typically observed with acoustic trauma. Intense noise exposure leads to macrophage recruitment to the cochlea and subsequent inflammatory damage to sensory cells. We therefore first tested our conjugates' ability to reduce the release of inflammatory cytokines in macrophages. This anti-inflammatory effect on macrophages also translated to increased cochlear cell viability. In our initial screening, one conjugate, ibuprofen-HA, demonstrated significantly higher anti-inflammatory potential than its counterparts. Subsequent cytokine release profiling of ibuprofen-HA further confirmed its ability to reduce a wider range of inflammatory markers, to a greater extent than its equivalent unconjugated drug. The conjugate's potential as a topical therapeutic was then assessed in previously developed tympanic and round window membrane tissue permeation models. As expected, our data indicate that the conjugate has limited tympanic membrane model permeability; however, it readily permeated the round window membrane model and to a greater extent than the unconjugated drug. Interestingly, our data also revealed that ibuprofen-HA was well tolerated in cellular and tissue cytocompatibility assays, whereas the unconjugated drug displayed significant cytotoxicity at equivalent concentrations. Moreover, our data highlighted the importance of chemical conjugation of ibuprofen to HA; the conjugate had improved anti-inflammatory effects, significantly reduced cytotoxicity, and is more suitable for therapeutic formulation. Overall, this work suggests that ibuprofen-HA could be a promising safe and effective topical ototherapeutic for inflammation-mediated cochlear damage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 Birru, Veit, Arrigali, Van Tine, Barrett-Catton, Tonnerre, Diaz and Serban.)

Introduction: Population-level, nationally representative data on the prevalence of minority stressors and traumatic events, mental ill-health effects, and the preventative utility of school climate, among gender and sexuality diverse young people in Australia, is significantly lacking. In this study, we estimated the prevalence and distribution of minority stressors and traumatic events among young people by sexuality identity (gay/lesbian, bisexual, other sexuality, heterosexual), sexuality diversity (sexuality diverse, not sexuality diverse), and gender identity (transgender, cisgender) and assessed associations with mental ill-health and the moderating role of school climate factors., Methods: Using Wave 8 (2018) follow-up data from a population-level, nationally representative longitudinal cohort study, the sample comprised 3037 young people aged 17-19 years in Australia. Prevalence ratios for minority stressors and traumatic events were calculated for gender and sexuality diverse categories using logistic regression models. Linear regression models were used to test associations between traumatic events and minority stressors, and mental ill-health. Multivariate linear regression tested school climate factors as effect modifier between minority stressors and mental ill-health among sexuality diverse young people., Results: Rates of traumatic events and minority stressors were highest among bisexual and gay/lesbian young people and were significantly associated with mental ill-health among all gender and sexuality diverse young people. Highest mental ill-health effects were observed among trans young people. Among sexuality diverse young people, positive and negative feelings toward school climate were associated with decreased and increased mental ill-health, respectively. After accounting for sexuality diversity, positive overall school climate appeared protective of mental ill-health effects of sexuality-based discrimination., Discussion: Minority stressors, traumatic events, and associated mental ill-health are prevalent among gender and sexuality diverse young people in Australia, especially trans, bisexual, and gay/lesbian young people. Promotion of affirmative, safe, and inclusive school climate demonstrates significant promise for the prevention and early intervention of mental ill-health among gender and sexuality diverse young people., (© 2023 The Authors. Journal of Adolescence published by Wiley Periodicals LLC on behalf of Foundation for Professionals in Services to Adolescents.)

Many aspects of the activity of a medical laboratory have to be documented so as to facilitate the maintenance of the ongoing quality of service. As a consequence, many documents, forms and reports are generated. The retention time for each of these has to be specified. In addition to medical laboratory reports as part of the patient's medical record, the medical laboratory has to retain many documents and specimens according to national legislation or guidance from professional organizations, if these exist. If not, the laboratory management needs to define a retention schedule, which shall define the storage conditions and period of storage, according to ISO 15189:2022 requirements for retention of general quality management documents and records. The EFLM Working Group on Accreditation and ISO/CEN standards provides here a proposal on retention periods of documentation and specimens based on a failure-mode-effects-analysis (FMEA) risk-based approach, a concept of risk reduction that has become an integral part of modern standards., Competing Interests: Competing interests: The authors state no conflict of interest., (© 2024 the author(s), published by De Gruyter, Berlin/Boston.)

Issue: Across the United States, the majority of medical schools teach physical examination using some form of peer physical examination (PPE). The process of being physically exposed in the presence of colleagues can be uncomfortable and cause students distress for myriad reasons ranging from religious and cultural practices to body dysmorphia and previous trauma experiences. This is especially problematic in educational systems which offer no other options, or make PPE a requirement of the curriculum. Evidence: Across all U.S. medical schools, trainees spent a median of 59 hours teaching physical examination skills. Of this time, 30% is dedicated to PPE practice. Despite this prevalence, there are data that show some students find this uncomfortable, especially women. Literature on best practices around PPE highlights voluntary participation, informed consent, and an available alternative to learning physical xamination skills. These are not uniformly available in all learning environments. There are little data around the impact of PPE on students who have experienced or are experiencing sexual trauma. Authors have drawn conclusions about the potential for harm given the prevalence of sexual mistreatment in US higher education. Implications: Our medical school policy required students to participate in PPE practice, undressing for the exams wearing only shorts (and a sports bra for women) an and a hospital gown. Students who could not participate in this practice for reasons ranging from mobility to religious beliefs had to seek individual formal accommodations to be exempt, putting the onus of change on potentially vulnerable individuals. We evaluated the policy around PPE, and concluded that the school's requirements could be harmful and isolating, as they required students to disclose their personal vulnerabilities while seeking exemptions from being examined by peers. At our institution, a group of students instead advocated for the school to review the policy and create a PPE procedure that was safer and more inclusive while supporting student learning. Our experience emphasized the potential for students to advocate for change, while also highlighting the need for greater research in the field of trauma-informed curricular design for medical education.

Xanthomonas translucens, the causal agent of bacterial leaf streak disease (BLS) in cereals, is a re-emerging pathogen that is becoming increasingly destructive across the world. While BLS has caused yield losses in the past, there is anecdotal evidence that newer isolates may be more virulent. We observed that two X. translucens isolates collected from two sites in Colorado, USA, are more aggressive on current wheat and barley varieties compared to older isolates, and we hypothesize that genetic changes between recent and older isolates contribute to the differences in isolate aggressiveness. To test this, we phenotyped and genetically characterized two X. translucens isolates collected from Colorado in 2018, which we designated CO236 (from barley) and CO237 (from wheat). Using pathovar-specific phenotyping and PCR primers, we determined that CO236 belongs to pathovar translucens (Xtt) and CO237 belongs to pathovar undulosa (Xtu). We sequenced the full genomes of the isolates using Oxford Nanopore long-read sequencing, and compared their whole genomes against published X. translucens genomes. This analysis confirmed our pathovar designations for Xtt CO236 and Xtu CO237, and showed that, at the whole-genome level, there were no obvious genomic structural changes between Xtt CO236 and Xtu CO237 and other respective published pathovar genomes. Focusing on pathovar undulosa (Xtu CO237), we then compared putative type III effectors among all available Xtu isolate genomes and found that they were highly conserved. However, there were striking differences in the presence and sequence of various transcription activator-like effectors between Xtu CO237 and published undulosa genomes, which correlate with isolate virulence. Here, we explore the potential implications of the differences in these virulence factors, and provide possible explanations for the increased virulence of recently emerged isolates.

Introduction: Within undergraduate medical education, there is a gap between students' understanding of anatomy and application of that knowledge within surgical specialties. The integration of drawing, in conjunction with traditional learning, has been shown to increase retention and understanding of information. Currently, no educational curriculum integrates drawing to aid in medical students' understanding of surgical pelvic anatomy. We anticipated that the utilization of drawing anatomy in an OB/GYN clerkship would enhance students' ability to explain surgical pelvic anatomy and pelvic pathology., Methods: At the beginning of the OB/GYN clerkship, third-year medical students participated in an interactive, 1.5-hour session requiring them to draw pelvic anatomy, present their work, and explain topics related to pelvic surgery and pathology to the other clerkship students. At the end of their clinical rotation, the students were invited to complete a five-item survey to assess long-term retention and understanding of concepts presented in the session. Frequencies and percentages were calculated for all categorical/ordinal variables to describe survey participants and question responses., Results: Thirty-seven of 44 respondents (84%) reported that the anatomy interactive session prepared them for the surgical portion of the OB/GYN clinical rotation. Thirty-five respondents (80%) reported that drawing the pelvic structures helped their understanding of pelvic pathology; 33 respondents (75%) reported they had a thorough understanding of pelvic anatomy after taking the OB/GYN anatomy interactive educational session ( p < .001)., Discussion: Our session shows that integrating drawing and anatomy increases students' ability to discuss pelvic pathology and surgical anatomy., (© 2023 Adkins et al.)

Background: Interprofessional education (IPE) has been promoted as a breakthrough in healthcare because of the impact when professionals work as a team. However, despite its inception dating back to the 1960s, its science has taken a long time to advance. There is a need to theorize IPE to cultivate creative insights for a nuanced understanding of IPE. This study aims to propose a research agenda on social interaction by understanding the measurement scales used and guiding researchers to contribute to the discussion of social processes in IPE., Method: This quantitative research was undertaken in a cross-institutional IPE involving 925 healthcare students (Medicine, Nursing, Social Work, Chinese Medicine, Pharmacy, Speech Language Pathology, Clinical Psychology, Food and Nutritional Science and Physiotherapy) from two institutions in Hong Kong. Participants completed the Social Interaction Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6). We applied a construct validation approach: within-network and between-network validation. We performed confirmatory factors analysis, t-test, analysis of variance and regression analysis., Results: CFA results indicated that current data fit the a priori model providing support to within-network validity [RMSEA=.08, NFI=.959, CFI=.965, IFI=.965, TLI=.955]. The criteria for acceptable fit were met. The scales were invariant between genders, across year levels and disciplines. Results indicated that social interaction anxiety and social phobia negatively predicted behavioural engagement ( F  = 25.093, p <.001, R 2 =.065) and positively predicted behavioural disaffection ( F  = 22.169, p <.001, R 2 =.057) to IPE, suggesting between-network validity., Conclusions: Our data provided support for the validity of the scales when used among healthcare students in Hong Kong. SIAS-6 and SPS-6 have sound psychometric properties based on students' data in Hong Kong. We identified quantitative, qualitative and mixed methods research designs to guide researchers in getting involved in the discussion of students' social interactions in IPE.Key MessagesThe Social Anxiety Scale (SIAS-6) and Social Phobia Scale (SPS-6) scales have sound psychometric properties based on the large-scale healthcare students' data in IPE in Hong Kong.Social interaction anxiety and social phobia negatively predicted students' behavioural engagement with IPE and positively predicted behavioural disaffection. The scales are invariant in terms of gender, year level and discipline.Quantitative, qualitative and mixed methods studies are proposed to aid researchers to contribute in healthcare education literature using the SIAS-6 and SPS-6.