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Postpartum uterine disease in dairy cows affects ovarian function, but it is unclear how the type and timing of disease relates to ovarian function. To explore associations between uterine disease and contemporaneous ovarian function, postpartum uterine health was evaluated in 17 lactating primiparous Holstein cows that ovulated. Ovarian function was assessed by measuring daily hormone concentrations and the diameter of the largest follicle and subsequent corpus luteum. Metritis (≤14 d postpartum) was associated with reduced follicle diameter (P = 0.002) and tended to reduce plasma estradiol concentrations (P = 0.062) from d 7 to 16 postpartum compared to cows without metritis. Metritis was associated with reduced plasma progesterone (P = 0.026) but not corpus luteum diameter from d 17 to 26 postpartum. Endometritis (≥15 d postpartum) was associated with reduced corpus luteum diameter (P = 0.005) but did not alter plasma progesterone from d 17 to 26 postpartum compared to cows without endometritis. To explore longer term effects of uterine infection on luteal function, non-lactating primiparous Holstein cows received an intrauterine infusion of vehicle control (n = 11) or pathogenic Escherichia coli and Trueperella pyogenes to induce endometritis (n = 12) and corpora lutea were recovered on d 16 of the estrous cycle, 146 d after intrauterine infusion. Intrauterine infusion of bacteria had no effect on plasma progesterone or luteal diameter compared to control, and only altered the expression of 2 of 94 candidate genes (NCF1 and TLR9). Taken together, these studies imply that uterine diseases are principally associated with changes to ovarian function at a time contemporaneous with disease., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The majority of patients hospitalised for trauma survive their injuries, with the quality of the survival potentially influenced by early acute hospital rehabilitation. The aim of this study was to review the outcomes of patients managed under an intensive Allied Health Model of Care (AHMOC) compared to a baseline cohort., Methods: The AHMOC was commenced in February 2020 on the Trauma ward at Alfred Health for 12 months. The baseline group included patients admitted to the trauma ward in 2019. All patients who were registered by either the Victorian Orthopaedic Trauma Outcomes Registry (VOTOR) or the Victorian State Trauma Registry (VSTR). The association between the groups (AHMOC and baseline) and outcomes were assessed using logistic (discharge destination, 12-month return to work) and linear (length of stay (LOS)) regression., Results: There were 1644 in the baseline group and 1732 in the AHMOC group, of which 70 % and 76 % respectively were discharged directly home from the acute hospital (p value < 0.001). The trauma ward LOS was 4.0 days for each group (p value 0.77). After accounting for confounders, the adjusted odds of discharge home and RTW at 12 months were 53 % (AOR 1.53 95 % CI 1.29, 1.82) and 65 % (AOR 1.65 95% CI 1.24, 2.21) higher for the AHMOC group compared to baseline, respectively. There was also a 6 % reduction in the LOS in the AHMOC group compared to baseline (Adjusted mean difference 6 %; 95 % CI (0.881, 0.999) p value = 0.050)., Conclusion: This study shows an association between an AHMOC for trauma patients with a focus on early and intensive therapy and improved odds of discharge directly home, as well as improved 12 month return to work outcomes., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Despite uncertain benefit-risk profile near the end of life, antithrombotic therapy (ATT) is prevalent in patients with terminal cancer., Objectives: To examine adherence and persistence with ATT in terminally ill cancer patients and investigate risks of major and clinically relevant bleeding, venous thromboembolism (VTE), and arterial thromboembolism (ATE) by ATT exposure., Methods: Using a Danish nationwide cohort of terminal cancer patients, ATT adherence in the year following terminal illness declaration was measured by the proportion of days covered (PDC) by prescription. Discontinuation was defined as a treatment gap of ≥30 days between prescription renewals. One-year cumulative incidences of bleeding complications, VTE, and ATE were calculated, considering the competing risk of death., Results: During 2013-2022, 86 732 terminally ill cancer patients were identified (median age, 75 years; 47% female; median survival, 57 days). At terminal illness declaration, 37.5% were receiving ATT (66.6% platelet inhibitors, 23.0% direct oral anticoagulants, and 10.4% vitamin K antagonists [VKAs]). The mean PDC with ATT was 88% (SD, 30%), highest among platelet inhibitor users (mean PDC, 89%) and lowest among VKA users (73%). One-year ATT discontinuation incidence was 7.9% (95% CI, 7.7%-8.1%). Most patients continued ATT until death (74.8% platelet inhibitors, 58.8% direct oral anticoagulants, and 61.6% VKAs). Patients receiving ATT had a lower 1-year VTE risk but higher risks of ATE and major bleeding., Conclusion: Despite uncertain benefit-risk profile, most terminally ill cancer patients continue ATT until the end of life. These findings provide insights into current ATT utilization and discontinuation dynamics in the challenging context of terminal illness., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Nicotine has been shown to induce profound physiological and behavioural responses in invertebrate model organisms such as Caenorhabditis elegans and Drosophila melanogaster. Lumbriculus variegatus is an aquatic oligochaete worm which we have previously demonstrated has application within pharmacological research. Herein, we demonstrate the presence of endogenous acetylcholine and cholinesterase activity within L. variegatus and show the time-dependent effects on the sensitivity of L. variegatus to nicotine. We describe the effects of a broad range of concentrations of nicotine (1 μM - 1 mM) on L. variegatus response to tactile stimulation and locomotor activity following acute (10-min) and chronic (24-h) exposure. Here, we show that 10 min of exposure to ≥0.1 mM nicotine reversibly reduces the ability of tactile stimulation to elicit stereotypical movements of body reversal and helical swimming, and locomotor activity in L. variegatus. We also demonstrate that exposure to ≥0.1 mM nicotine for 24 h was toxic to L. variegatus. Chronic low-dose nicotine ≥25 μM similarly inhibits L. variegatus behaviours with 50 μM causing irreversible inhibition of movement. Thus, L. variegatus presents a model for studying the effects of nicotine and further demonstrates the application of the in vivo model L. variegatus for behavioural pharmacology research., (Copyright © 2024. Published by Elsevier Inc.)

Background: A multicentre European randomized control trial - European Uncomplicated Type B Aortic Repair (EU-TBAR) is being developed to compare pre-emptive thoracic endovascular aortic repair (TEVAR) with custom-made devices versus conventional optimal medical therapy. The pretrial set-up is confluent on different pillars, including evaluation of 1) European activity, trends, and governance; 2) outcome reporting; and 3) cost evaluation. This article aimed to demonstrate the observational cross-sectional survey results from participating centers and highlight the risk assessment, activity, practices, and governance of uncomplicated type B aortic dissection (uTBAD)., Methods: This observational cross-sectional European survey used a questionnaire that examined the understanding, risk assessment, local governance oversight, and clinical activity of uTBAD. The data were collected and managed using Research Electronic Data Capture (REDCap)., Results: Out of 43 surveyed surgeons, 37 (86%) responded within a month from 14 European countries. Most reported low annual uTBAD encounters, with autumn being the most common season for cases. Pre-emptive TEVAR was recommended by 43.2% of participants, who favored subacute intervention timing. The Gore TAG was the most used TEVAR device, and custom devices were available for 73% of respondents. Risk factors for uTBAD were ranked, with 'Rapid Aortic Enlargement' deemed most critical. A majority of centers had protocols and multidisciplinary teams, with most having readily available radiology services. Only 45.9% had transfer services to specialized centers., Conclusions: uTBAD remains a misnomer of a dynamic, ongoing disease process requiring early diagnosis and intervention. Pre-emptive TEVAR in high-risk uTBAD is becoming more common, with encouraging results prompting an expansion of indication criteria to a broader uTBAD population managed conservatively. Nevertheless, further evidence is needed through large randomized controlled trials, mainly European collaboratives, to reach a definitive conclusion on the optimum surgical management of uTBAD., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Enzymatically oxygenated phospholipids (eoxPL) from lipoxygenases (LOX) or cyclooxygenase (COX) are prothrombotic. Their generation in arterial disease, and their modulation by cardiovascular therapies is unknown. Furthermore, the Lands cycle acyl-transferases that catalyze their formation are unidentified. eoxPL were measured in platelets and leukocytes from an atherosclerotic cardiovascular disease (ASCVD) cohort and retrieved human arterial thrombi from three anatomical sites. The impact of age, gender, and aspirin was characterized in platelets from healthy subjects administered low-dose aspirin. The role of lysophosphatidylcholine acyltransferase 3 (LPCAT3) in eoxPL biosynthesis was tested using an inhibitor and a cell-free assay. Platelets from ASCVD patients generated lower levels of COX-derived eoxPL but elevated 12-LOX-diacyl forms, than platelets from healthy controls. This associated with aspirin and was recapitulated in healthy subjects by aspirin supplementation. P2Y12 inhibition had no impact on eoxPL. LPCAT3 inhibition selectively prevented 12-LOX-derived diacyl-eoxPL generation. LPCAT3 activity was not directly altered by aspirin. P2Y12 inhibition or aspirin had little impact on eoxPL in leukocytes. Complex aspirin-dependent gender and seasonal effects on platelet eoxPL generation were seen in healthy subjects. Limb or coronary (ST-elevation myocardial infarction, STEMI) thrombi displayed a platelet eoxPL signature while carotid thrombi had a white cell profile. EoxPL are altered in ASCVD by a commonly used cardiovascular therapy, and LPCAT3 was identified as the acyltransferase generating aspirin-sensitive 12-LOX diacyl forms. These changes to the phospholipid composition of blood cells in humans at risk of thrombosis may be clinically significant where the procoagulant membrane plays a central role in driving elevated thrombotic risk., Competing Interests: Conflict of interest P. C. receives research funding from CSL Behring, Haemonetics Corp, Werfen, and consultancy from CSL Behring. The other authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Adjuvant therapy decisions in hormone receptor positive, HER2 negative breast cancer are evolving. Gene panel testing has reduced the number of patients recommended for chemotherapy by up to two thirds. Identifying low risk genomic cases before testing could represent a significant economic impact. Systemic inflammatory indices have shown promise as prognostic markers in early breast cancer. We investigated the utility of four systemic inflammatory indices with the Nottingham Prognostic Index to predict the Oncotype DX® recurrence scores threshold level (low or high score), in women aged 50 and over with node negative invasive ductal carcinoma of the breast., Methods: A retrospective review of 245 patients with Oncotype DX® Recurrence Score testing from 2007 to 2021 were identified. The Nottingham Prognostic Index and systemic inflammatory indices ratios were estimated from histology results and preoperative peripheral blood samples respectively., Results: 22.4% of the cohort had a Recurrence Score in the higher risk group. This group had a greater percentage of grade 3 tumours, progesterone receptor negativity, higher Nottingham Prognostic Scores, and inflammatory indices ratios than the lower risk group. A decision tree incorporating the Neutrophil Lymphocyte Ratio with clinicopathological features showed potential as an indicator of a high Oncotype DX® RS score, such that further investigation is warranted to assess whether Recurrence Score testing could be triaged in certain cohorts of patients. In this study, 38% of patients might be able to avoid genomic testing based on the decision tree analysis., Conclusion: Utility of inflammatory indices with clinicopathological features may help triage gene panel testing., Competing Interests: Disclosure The authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Chest wall injury causes significant morbidity and mortality. There is uncertainty regarding many aspects of clinical care for these patients, including optimal analgesia, acuity of monitoring and surgical fixation. Our aim in this work is to [1] objectively appraise the quality and extent of heterogeneity in UK major trauma centre (MTC) clinical practice guidelines regarding the management of chest wall injury; and [2] narratively summarise clinical and care process recommendations from these guidelines to provide a comparative description of recommendations between institutions., Methods: All major trauma centres in England and Wales were contacted for their institutional clinical practice guidelines relevant to chest wall injury. A literature search was executed seeking eligible supra-regional, national or international consensus documents or guidelines to serve as reference standards. Interrogation of the reference standard guidelines was performed to identify key clinical and care processes against which two blinded assessors judged the clinical validity of institutional clinical practice guidelines as part of the Appraisal of Guidelines for Research & Evaluation II Global Rating Scale (AGREE II-GRS) tool., Results: We received 17 institutional clinical practice guidelines and identified themes of care from seven reference standards identified during our literature search. Four institutional clinical practice guidelines were assessed as high-quality by pre-specified AGREE II-GRS criteria. Guidelines scored highly for the quality of their presentation of information (median (interquartile range [IQR]) AGREE II-GRS Item 5 score 5 (4.5-5.5)); however, the quality of guideline development methodology and the guideline completeness in comprehensively addressing the needs of this population was generally poor (median (IQR) AGREE II-GRS Item 1 methodology score 2.92 (2.33-5.25); AGREE II-GRS Item 3 completeness score 2.63 (1.75-5.25) respectively)., Conclusions: This work highlights the paucity of high-quality local clinical practice guidelines to inform the management of adults with chest wall injury admitted to UK MTCs. Although some degree of variation between local guidelines is acceptable, we have identified substantial heterogeneity in the clinical care recommendations between institutions., Competing Interests: Declaration of competing interest DWH and JGH accept fees for advising in civil, criminal and coronial medicolegal cases. The remaining authors have no conflicts of interest to declare., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this trial was to investigate the impact of early thoracic and shoulder girdle exercises on chronic pain and Health-Related Quality of Life in patients with blunt chest wall trauma, when compared to normal care., Methods: A multi-centre, parallel, randomised controlled trial, in which adult patients presenting to hospital with blunt chest wall trauma were allocated to either control or intervention group. The intervention was an exercise programme consisting of four simple thoracic and shoulder girdle exercises, completed for one week. Outcomes measures included prevalence and severity of chronic pain using the Brief Pain Inventory, health-related quality of life using EQ-5D-5 L, and cost effectiveness, measured at initial presentation and three months post-injury., Results: 360 participants were recruited. Participants' mean age was 63.6 years (standard deviation (SD): 17.9 years) and 213 (59.8 %) were men. After loss-to-follow-up, the survey response rate at three months was 73.0 % (251/344 participants). The primary analysis, for chronic pain prevalence at three months post-injury, found no statistically significant differences between intervention and control groups, with lower rates in the control (intervention: 35/126 (27.8 %), control: 20/117 (17.1 %); adjusted odds ratio 1.862; 95 % CI: 0.892 to 3.893, p = 0.098). There were no statistically significant differences between intervention and control groups for pain severity at three months post-injury, (intervention mean (SD): 2.15 (2.49), control: 1.81 (2.10); adjusted difference 0.196, 95 % CI:0.340 to 0.731; p = 0.473); or Health-Related Quality of Life (intervention mean (SD): 0.715 (0.291), control: 0.704 (0.265); adjusted difference: 0.030; 95 % CI:0.033 to 0.094; p = 0.350). The health economic analysis found the intervention was associated with higher costs compared to normal care., Conclusion: The results of this trial did not support a 'one-size fits all' simple, early exercise programme for patients with blunt chest wall trauma. Future research should consider the impact of a personalised exercise programme, commenced by the patient at least one week post-injury., Competing Interests: Declaration of competing interest There are no conflicts to declare., (Copyright © 2024. Published by Elsevier Ltd.)

In 2021 the European Food Safety Authority (EFSA) concluded that "A concern for genotoxicity of TiO2 particles that may be present in E 171 could therefore not be ruled out.". A detailed review of the genotoxicity of titanium dioxide (TiO 2 ) was subsequently published by Kirkland et al. (2022) using a comprehensive weight of evidence (WoE) approach in which test systems and endpoints were allocated different levels of relevance. At that time only 34 publications met the reliability and quality criteria for being most relevant in the evaluation of genotoxicity, and based on these it was concluded that the existing evidence did not support a direct DNA damaging mechanism for TiO 2 . Recently a number of regulatory opinions have been published, in which papers were cited that described in vitro DNA damage (mainly comet), mode of action, and cellular uptake studies that were not discussed in Kirkland et al. (2022). Furthermore, a number of additional papers have been published recently or have been identified from the regulatory opinions as a result of using extended search criteria. A total of 70 publications not previously reviewed in Kirkland et al. (2022) have been reviewed here, and again show that the published data on the genotoxicity of TiO 2 are inconsistent, often of poor quality, and in some cases difficult to interpret. The cellular uptake studies show some evidence of cytoplasmic uptake, particularly in cells treated in vitro, but there is no convincing evidence of nuclear uptake. In terms of genotoxicity, the conclusions of Kirkland et al. (2022) that existing evidence does not support a direct DNA damaging mechanism for titanium dioxide (including nano forms), and that the main mechanism leading to TiO 2 genotoxicity is most likely indirect damage to DNA through generation of reactive oxygen species (ROS), are still valid., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andreas Czich is a Sanofi employee and may hold shares and or stock options in the company. Stefan Pfuhler is an employee of the Procter and Gamble company who market consumer products that may contain titanium dioxide. Paul Fowler, David Kirkland, Arne Burzlaff, Leon F. Stankowski and Shareen H. Doak report that financial support was provided by Titanium Dioxide Manufacturers Association., (Copyright © 2024. Published by Elsevier Inc.)

This work proposes a modelling framework to analyse flow and pressure distributions throughout the lung of mechanically ventilated COVID-19 patients. The methodology involves: segmentation of the lungs and major airways from patient CT images; a volume filling algorithm that creates a dichotomous airway network in the remaining volume of the lung; an estimate of resistance and compliance within the lung based on Hounsfield unit values from the CT scan; and a computational fluid dynamics model to analyse flow, lung inflation, and pressure throughout the airway network. Mechanically ventilated patients with differing progression and severity of the disease were simulated. The results indicate that the flow distribution within the lung can be significantly affected when there are competing types of lung damage. These competing types are primarily fibrosis-like lung damage that creates higher resistance and lower compliance in that region; and emphysema, which causes a decrease in resistance and increase in compliance. In a patient with severe disease, the model predicted an increase in inflation by 33% in an area affected by emphysema-like conditions. This could increase the risk of alveolar rupture. The framework could readily be adapted to study other respiratory diseases. Early interventions in critical respiratory care could be facilitated through such efficient patient-specific modelling approaches., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Finnafjörður is a small fjord in northeast Iceland, where the planned construction of a large port has the potential to meaningfully change the marine soundscape and ecosystem. In this study, we used one year (2021/22) of passive acoustic recordings to characterize the pre-construction soundscape, including broadband and decidecade sound pressure levels (SPL), frequency-weighted sound exposure levels, seasonal and diel variability and identified regular types of sound. Finnafjörður is relatively quiet with median decidecade levels centered between 25 Hz and 50 kHz of 74.5 to 86.3 dB re 1 μPa. Wind and rain dominate ambient SPL, while anthropogenic sources only occasionally contributed to the soundscape. Regular biological sound sources include humpback whales, toothed whales, and fish. This baseline soundscape description can be used for noise management during port construction, to monitor future changes in the region, and to act as a framework for comprehensive impact assessments as ports are developed globally., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Osteoarthritis (OA) is characterised by the failure of normal biological processes to repair following damage. Traditionally, OA was considered a "wear and tear" disorder; however, it is now a recognised inflammatory condition, preceded by molecular modifications. The aim of this study was to evaluate inflammatory markers among individuals with early knee OA (eKOA) and well-matched asymptomatic controls., Methods: Twenty six eKOA (females, n = 13; age = 60.2 ± 5.4 yrs, height = 1.73 ± 0.11 m, body mass = 77.8 ± 12.8 kg, body fat = 33.9 ± 8.5%) and twenty-three asymptomatic individuals (females, n = 14; age = 59.9 ± 5.5yrs, height = 1.71 ± 0.09 m, body mass = 72.6 ± 11.3 kg, body fat = 30.4 ± 8.2%) were recruited. The Timed Up and Go, and the 6 Minute Walk Tests evaluated physical function in addition to pain specific questionnaires (KOOS and ICOAP). Serum levels of IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-8(CXCL8), IL-10, hsCRP and TNF-α were quantified using a multiplex assay via V-plex®Sector Imager 2400., Results: As hypothesised, only KOOS and EQ-5D-5L metrics differed between the groups for non-blood derived measures (p < 0.04). Only IL-6 was higher in eKOA (P = 0.02; 95% CI = 0.202; by 0.197 pg/mL; 34.5%). Among eKOA, IL-6 did not relate to severity of KOOS pain (P = 0.696, r = -0.088), but had a positive relationship with ICOAP consistent (r = 0.469, P = 0.045) rather than intermittent pain. There was a moderate correlation between 6MWD and IL-8 (r = 0.471, P = 0.012)., Conclusion: Our results illustrate the potential for IL-6 as a biomarker for eKOA, and introduce the proposition for particular consideration in those with consistent pain. Further, for the first time the present data showed greater walking distance in eKOA with lower circulating IL-8. Future work should seek to verify these results and further investigate IL-6 and IL-8 related molecular pathways in eKOA, and their potential relationships with consistent knee pain and physical function., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Abnormal levels of catecholamines can indicate underlying health issues, such as Parkinson's disease, hypertension, and pheochromocytoma. However, it is difficult to accurately differentiate multiple catecholamines using traditional detection methods due to their highly similar structures. Herein, we proposed a carbon-based fluorescent probe with adaptability named spermine that can react with multiple catecholamines to generate polymer carbon dots with distinct fluorescence colors, enabling visual differentiation and quantitative detection of epinephrine, norepinephrine and levodopa. Spermine does not requires synthesis and exhibits excellent biocompatibility, as it naturally exists in bacteria and most animal cells. Additionally, ratiometric fluorescent probes with high sensitivity was constructed to eliminate nonspecific factors in the sample detection process. Furthermore, due to the simplicity of the designed fluorescence detection steps, a convenient paper-based biosensor for visual detection of multiple catecholamines was formed by pre-dropping the probe on the detection layer, which can be integrated into the portable platform and the detection value can directly display on the smartphone. Therefore, the integrated portable platform of the biosensor can differentiate catecholamines types through fluorescent color and intelligently detect the content of catecholamine in the sample., 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 B.V. All rights reserved.)

Introduction: Collecting patient-reported outcomes in a systematic fashion is important to understand recovery trajectories and compare performance between different services and fields of care. These outcomes can be collected through a variety of means, but studies comparing different follow-up methods in patients with a variety of injury types are scarce. This study aimed to compare follow-up data from three injury registries to quantify patient preference for telephone versus online follow-up, determine factors associated with choosing online follow-up, and compare response rates based on the patient's preferred follow-up method., Methods: A registry-based cohort study of adult (≥16 years) patients registered one of three registries from January 2021 to December 2021 was undertaken. Patients who survived to discharge were contacted by telephone and offered the option of telephone or online self-completion at six- and 12-months post-injury using the EQ-5D-5L. The three injury cohorts and telephone/online groups were compared for differences in characteristics, follow-up rates, and data completeness. Multivariable logistic regression models were used to identify predictors of choosing online completion in the three cohorts., Results: Data were retrieved for 8,049 patients. A greater proportion of orthopaedic trauma patients initially opted for online follow-up (41.0 %) compared to major trauma (31.0 %) and burns (24.1 %) patients. Orthopaedic and major trauma patients had increased odds of choosing online follow-up compared to burns patients (adjusted odds ratio [95 % confidence interval] 2.9 [2.2-3.7] and 2.1 [1.6-2.7], respectively). A greater proportion of major trauma patients (69.3 %) and burns patients (64.3 %) completed both follow-ups compared to orthopaedic trauma patients (52.4 %). The overall completion rates for the EQ-5D-5L were high., Conclusions: While follow-up preference and completion were higher for telephone-based follow-ups, the findings suggest a patient's preference for completing post-injury follow-ups differs according to the type of injury they sustained, and that allowing patients a choice of their preferred follow-up method is important. The variety of follow-up methods offered should therefore reflect the needs of different patient groups, which may allow for the development of algorithms or workflow processes. Directing certain patients towards a particular follow-up method could deliver higher and more efficient follow-up rates., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024. Published by Elsevier Ltd.)

Background: Locking plate fixation remains the mainstay of surgical fixation of unstable proximal humerus fractures, however rates of failure remain high. The aim of this study was to identify risk factors that could be used to predict the likelihood of fixation failure., Method: Patients with proximal humerus fractures managed with locking plate fixation between 2010 and 2019 at a Level 1 trauma centre were included. Radiographs were evaluated for parameters that could be used to predict failure of fixation. Pre-operative factors included were the Neer classification, cephalomedullary angle, medial calcar length, disruption of the medial hinge, and anatomical neck fracture. Post-operative factors included the cephalomedullary angle, medial calcar reduction gap, presence of anatomical tuberosity reduction, presence of medial calcar screws, screw distance to articular surface, and number of screws present in the humeral head., Results: There were 189 patients included; 54 % male, mean age 49.9 (intact fixation) group and 56.1 (failure). The rate of fixation failure was 22 %. Factors associated with increased risk of failure following multivariable analysis included increasing age (OR 1.04 per year, CI 1.01-1.07), varus pre-operative cephalomedullary angle (OR 2.84, CI 1.03-7.83), and non-anatomical calcar reduction (OR 2.31, CI 1.05-5.08). The presence of calcar screws was associated with decreased risk of fixation failure (OR 0.30, CI 0.10-0.90). This analysis was used to create a predictive model including the Neer classification, age, pre-operative cephalomedullary angle, post-operative cephalomedullary angle, anatomic reduction of the medial calcar, and presence of medial calcar screws., Conclusion: Rates of locking plate fixation failure in proximal humerus fractures remain high. This study has identified key pre-operative and intra/post-operative factors that can be used to predict the risk of failure. Further work is required to validate this model., Level of Evidence: Level II., Competing Interests: Declaration of competing interest The authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024. Published by Elsevier Ltd.)

Contact with nature can contribute to health and wellbeing, but knowledge gaps persist regarding the environmental characteristics that promote these benefits. Understanding and maximising these benefits is particularly important in urban areas, where opportunities for such contact is limited. At the same time, we are facing climate and ecological crises which require policy and practice to support ecosystem functioning. Policies are increasingly being oriented towards delivering benefits for people and nature simultaneously. However, different disciplinary understandings of environments and environmental quality present challenges to this agenda. This paper highlights key knowledge gaps concerning linkages between nature and health. It then describes two perspectives on environmental quality, based respectively in environmental sciences and social sciences. It argues that understanding the linkages between these perspectives is vital to enable urban environments to be planned, designed and managed for the benefit of both environmental functioning and human health. Finally, it identifies key challenges and priorities for integrating these different disciplinary perspectives., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background and Objective: Information on self-limited epilepsy with centrotemporal spikes (SeLECTS) epidemiology is limited. We aimed to determine the incidence of SeLECTS in children, its association with socioeconomic deprivation and the prevalence of neurodevelopmental comorbidities., Method: We performed a retrospective cohort study (2004-2017) using anonymised, linked, routinely collected, primary care and demographic data for children in Wales. We used primary care diagnosis codes to identify children (aged 0-16 years) with SeLECTS and other epilepsies and to record antiseizure medication (ASM) prescriptions and neurodevelopmental comorbidities. We used a mixed effects Poisson regression model to determine temporal trends of SeLECTS incidence and its association with socioeconomic deprivation., Results: We identified 6,732 children with epilepsy, 186 (3%) with SeLECTS. In 2017, epilepsy and SeLECTS prevalence was 0.55% and 0.02% respectively with corresponding crude incidence of 51.2/100,000/year and 1.1/100,000/year. The incidence of epilepsy in children decreased with decreasing deprivation with an adjusted incidence rate ratio (AIRR) of 0.72 (95% CI 0.64-0.82) in the least deprived compared with the most deprived quintile. The corresponding AIRR for children with SeLECTS was 1.35 (95% CI 0.46-1.99). 34% of children with epilepsy, 18% of children with SeLECTS and 3% of all children in Wales had a neurodevelopmental disorder and or school problems. Half of children with SeLECTS were treated with ASM., Conclusions: We identified a lower than previously reported incidence of SeLECTS, which may be due to under-recording of SeLECTS. There was no change in the incidence of SeLECTS over time, whilst the incidence of childhood epilepsy overall was decreasing. There was no significant association between incidence of SeLECTS and deprivation but the modest sample size needs to be considered. Children with SeLECTS should be screened for neurodevelopmental and or learning comorbidities. Treatment for SeLECTS remains debatable., Competing Interests: Declaration of competing interest The authors do not note any conflict of interests., (Copyright © 2024. Published by Elsevier Ltd.)

Objectives: The study's aim was to explore the prevalence of precarious employment (PE) in Wales prior to the COVID-19 pandemic and examine associations with PE domains across socio-demographics and self-reported health., Study Design: A cross-sectional design was used to explore the prevalence of PE in Wales prior to the COVID-19 pandemic, in February 2020., Methods: Data were collected from a national household survey carried out in May/June 2020, with a sample of 1032 residents in Wales. PE was determined using the Employment Precariousness Scale. Associations between experiencing PE and socio-demographic/health characteristics were examined using Chi-squared tests and logistic regression models (multinomial and binary)., Results: Overall, before the pandemic, one in four respondents (26.5%) was in PE, with the most prevalent domains, wages, and disempowerment being experienced by at least 50% of respondents. Worse perceived treatment at work was twice as likely in those reporting pre-existing conditions (adjusted odds ratio [aOR]: 2.45 95% confidence interval [CI]: [1.33-4.49]), poorer general health (aOR: 2.33 95% CI: [1.22-4.47]), or low mental wellbeing (aOR: 2.81 95% CI: [1.34-5.88]). Those with high wage precariousness were three times more likely to report low mental wellbeing (aOR 3.12 95% CI [1.54-6.32])., Conclusions: The creation and provision of secure, adequately paid job opportunities has the potential to reduce the prevalence of PE in Wales. Targeting such employment opportunities to those people currently unwell would have better population health gains., (Copyright © 2024 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

We know relatively little about the role the neighbourhood built environment plays in promoting young children's physical activity, particularly its longitudinal effect either through repeated exposure to the same environment or through change in exposure by moving from one neighbourhood to another. This study characterised the neighbourhood environment of young children in the PLAYCE cohort study over three timepoints from 2015 to 2023. There were statistically significant differences in built environment attributes between timepoints and across socio-economic status, however they did not represent practically significant differences. These findings inform the analysis approach of subsequent research in the BEACHES Project, an international study examining the role of the built environment on child physical activity and obesity using multiple cohorts., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Despite the surge of interest in psychedelic research in the past decade, largely due to the promise of psychedelics for improving mental health outcomes, there has been comparatively little discussion about the social and environmental consequences of psychedelic drug use. While there is growing evidence to suggest psychedelics could foster a greater connection to the natural world and improve social relationships, such positive repercussions are far from guaranteed. In this commentary, we focus on LSD, psilocybin and especially MDMA, and outline three insights we came to see as crucial to creating beneficial outcomes: 1) the importance of setting and rituals, 2) the establishment of boundaries, and 3) understanding the long-term commitment required. These insights are grounded in the history of psychedelics, which is intimately intertwined with ritualised use, yet the process of commercialisation of these substances threatens to strip away important contextual factors. Creating boundaries around when, how and with whom psychedelics are used have been found to protect recreational users from harm and could also be instrumental in steering commercial interests to align with socio-environmental goals. Finally, far from being a 'quick fix' for social or environmental problems, the use of psychedelics requires sustained engagement to integrate the insights obtained. Whereas we remain optimistic about the transformative potential of psychedelics for social relationships and the environment, we also emphasise the need for a more cautious, considered approach if we are to harness the benefits and minimise the challenges of psychedelic drug use., Competing Interests: Declaration of competing interest The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024. Published by Elsevier B.V.)

Objectives: Tobacco use is one of the greatest public health problems in the world. Prevalence of alcohol and tobacco use among lactating women ranged between 35.9-83.0% and 1.4-6.1%, respectively, in various parts of the world. Both alcohol and nicotine pass quickly into breast milk. The objective of this study is to estimate the prevalence of alcohol and tobacco use in lactating women and its association with having underweight, stunted, and wasted nursing children in India. The study also draws comparisons to identify the common associated socio-economic factors for alcohol and tobacco use among lactating women and having underweight, stunted, and/or wasted children., Study Design: A cross-sectional analytical study involving secondary data from the National Family Health Survey-5., Methods: A cross-sectional analytical study involving secondary data from the National Family Health Survey-5 conducted nationally in community settings in two phases during 2019-2021. Alcohol and tobacco use among lactating women was self-reported, and the nutritional status of children was assess anthropometrically during the survey and categorised into under-weight, stunted, and wasted as per standardised growth charts., Results: prevalence of tobacco use among currently lactating mothers in India was 3.24%. Prevalence of alcohol use among currently lactating mothers was 0.57%. Nursing children of mothers consuming alcohol had significantly higher odds of being wasted [OR = 1.44; (95% CI = 1.07-1.92)]. Richer wealth index {compared to poor, poorer [OR = 0.74; (95% CI = 0.59-0.91)], rich [OR = 0.64; (95% CI = 0.50-0.84)], richer [OR = 0.46; (95% CI = 0.33-0.65)], richest [OR = 0.19; (95% CI = 0.11-0.33)]}, higher education status {compared to illiterate, secondary education [OR = 0.79; (95% CI = 0.63-0.97)], higher education [OR = 0.38; (95% CI = 0.24-0.62)]}, and non-tribal ethnicity [OR = 0.40; (95% CI = 0.33-0.50)] were found to be significantly associated with lower odds of alcohol and tobacco use among lactating mothers. Age, religion, residence, and occupation were also found to be significantly associated., Conclusions: Lactating women with lower education status or belonging to lower income groups needs to be prioritised for further qualitative assessment of alcohol and tobacco use during lactation. Our study reflects the national and state-level prevalence of alcohol and tobacco use among lactating women, which often masks the local and community-level intricacies. There is a need to further explore local and community-level factors affecting alcohol use during lactation and its association with child nutrition., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The impact of new-onset left bundle branch block (N-LBBB) developing after Transcatheter Aortic Valve Replacement (TAVR) on cardiac function and mechanical dyssynchrony is not well defined., Methods: We retrospectively screened all patients who underwent TAVR in our centre between Oct 2018 and Sept 2021 (n = 409). We identified 38 patients with N-LBBB post-operatively (of which 28 were persistent and 10 were transient), and 17 patients with chronic pre-existent LBBB (C-LBBB). We excluded patients requiring pacing post TAVR. For all groups, we retrospectively analysed stored echocardiograms at 3 time points: before TAVR (T0), early after TAVR (T1, 1.2 ± 1.1 days), and late follow-up (T2, 1.5 ± 0.8 years), comparing LV mass and volumes, indices of LV function (LV ejection fraction, LVEF; global longitudinal strain, GLS), and mechanical dyssynchrony indices (systolic stretch index, severity of septal flash)., Results: At baseline (T0), C-LBBB had worse cardiac function, and larger LV volumes and LV mass, compared with patients with N-LBBB. At T1, N-LBBB resulted in mild dyssynchrony and decreased LVEF and GLS. Dyssynchrony progressed at T2 in persistent N-LBBB but not C-LBBB. In both groups however, LVEF remained stable at T2, although individual response was variable. Patients with better LVEF at baseline demonstrated a higher proportion of developing LBBB-induced LV dysfunction at T2. Lack of improvement of LVEF immediately after TAVR predicted deteriorating LVEF at T2. In transient LBBB, cardiac function and most dyssynchrony indices returned to baseline., Conclusions: N-LBBB after TAVR results in an immediate reduction of cardiac function, in spite of only mild dyssynchrony. When LBBB persists, patients with better cardiac function before TAVR are more likely to have LBBB-induced LV dysfunction after TAVR., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Professor Alexander Chase reports a relationship with Abbott and Biosensors that includes: speaking and lecture fees. Professor David Smith reports a relationship with Abbott, Edwards Lifesciences, Biosensors that includes: consulting or advisory and speaking and lecture fees. Dr. Parin Shah reports a relationship with Abbott that includes: speaking and lecture fees. 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 Elsevier Inc. All rights reserved.)

Introduction: Alcohol is commonly detected in patients presenting to hospital after major trauma and is a key preventable risk factor for injury. While it has been suggested that alcohol intoxication at the time of injury results in worse acute patient outcomes, there is currently limited knowledge on the impact of alcohol on health outcomes following hospital discharge. The aim of this study was to examine the relationship between acute pre-injury alcohol exposure and the self-reported health outcomes of survivors of major trauma 12-months post-injury., Methods: Data from the Victorian State Trauma Registry (January 1, 2018 to December 31, 2020) were used to identify major trauma patients who: (1) were aged ≥18 years; (2) survived to 12-months post-injury; and (3) had blood alcohol data available in the registry. Logistic regression analyses were used to examine differences in self-reported health status (EQ-5D) and return to work at 12-months post-injury by blood alcohol concentration (BAC) at the time of presentation to hospital. Analyses were adjusted for potential confounders including a range of demographic, hospital and injury characteristics., Results: A total of 2957 patients met inclusion criteria, of which 857 (29.0 %) had a BAC >0 and 690 (23.3 %) had a BAC ≥0.05 g/100 mL. After adjusting for potential confounders, having any alcohol detected (i.e., BAC >0) was associated with lower odds of reporting problems on the EQ-5D mobility (aOR = 0.72, 95 %CI = 0.53 to 0.99) and usual activities dimensions (aOR = 0.79, 95 %CI = 0.63 to 0.99). Having a BAC ≥0.05 g/100 mL was only associated with lower adjusted odds of reporting problems on the usual activities dimension (aOR = 0.69, 95 %CI = 0.55 to 0.88) of the EQ-5D. Alcohol detection was not associated with the self-care, pain/discomfort or anxiety/depression dimensions of the EQ-5D, or with return to work in adjusted analyses., Conclusion: Acute pre-injury alcohol exposure was not associated with increased reporting of problems on the EQ-5D or with return to work at 12-months post-injury. Further research is needed to understand why patients with alcohol detections were sometimes associated with paradoxically better 12-month post-injury outcomes relative to patients without alcohol detections., Competing Interests: Declaration of competing interest The VSTR is a Department of Health and Human Services, State Government of Victoria and Transport Accident Commission funded project. GL was supported by a Monash University Postgraduate Publications Award. BJG was supported by National Health and Medical Research Council Investigator Grant (L2, ID 2009998). PMD was supported by a National Health and Medical Research Council Senior Research Fellowship (1136090). BB was supported by an Australian Research Council Discovery Future Fellowship (FT210100183)., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Collecting patient-reported outcome measures (PROMs) has been a longstanding priority for the Burns Registry of Australia and New Zealand (BRANZ). An earlier pilot of hospital-led PROM collection encountered low participation rates and high loss to follow-up, indicating consideration for an alternative model was warranted., Aims: To establish the feasibility of implementing centralised long-term PROM collection within the BRANZ., Methods: Two burn services participated in this prospective, longitudinal pilot. PROMs were collected from patients admitted to the services between January and December 2021 who survived to discharge. Follow-up occurred via telephone or online self-completion at three, six, and 12 months post-injury using burn-specific and generic health-related quality-of-life measures., Results: There were 450 patients (423 adult patients [≥ 16 years] and 27 paediatric patients [< 16 years]) who could be contacted and agreed to participate in the follow-ups. Most patients initially opted for telephone rather than online self-completion (n = 305, 67.5 %). No key sociodemographic or injury event factors were associated with specifically opting for online self-completion. The follow-up rates were 81.1 % at three months, 81.9 % at six months, and 77.3 % at 12 months. Data missingness was low (i.e., < 2 %) for all instrument items, excluding the visual analogue scale scores of the 5-Level EuroQoL 5 Dimensions Questionnaire and the two paediatric burn-specific measures., Conclusions: Collecting PROMs from burns patients in the first 12 months after injury via a centralised approach was shown to be feasible, with higher participation rates and low missingness., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Enzyme-induced in-situ fluorescence is crucial for the development of biosensing mechanisms and correlative spectroscopic analysis. Inspired by simple p-aminophenol (AP)-controlled synthesis and the specific catalytic reaction of 4-aminophenyl phosphate (APP) triggered by alkaline phosphatase (ALP), our research proposed a strategy to prepare carbon dots (CDs) as fluorescent signals for ALP detection using AP and 3-aminopropyltrimethoxysilane (APTMS) as the precursors. The further constructed ratiometric fluorescence sensor reduced the detection limit of ALP to 0.075 μU/mL by a significant margin. Considering the need for point-of-care testing (POCT), we chose agarose for the preparation of portable hydrogel sensors so that even untrained personnel can quickly achieve semi-quantitative visual detection of ALP using colorimetric cards. These results demonstrate the practical applicability of ratiometric fluorescence sensing hydrogel pillar arrays, which are important for high-sensitivity, visualization, and portable rapid enzyme activity assays., 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 B.V. All rights reserved.)

River invertebrate communities across Europe have been changing in response to variations in water quality over recent decades, but the underlying drivers are difficult to identify because of the complex stressors and environmental heterogeneity involved. Here, using data from ∼4000 locations across England and Wales, collected over 29 years, we use three approaches to help resolve the drivers of spatiotemporal variation in the face of this complexity: i) mapping changes in invertebrate richness and community composition; ii) structural equation modelling (SEM) to distinguish land cover, water quality and climatic influences; and iii) geographically weighted regression (GWR) to identify how the apparent relationships between invertebrate communities and abiotic variables change across the area. Mapping confirmed widespread increases in richness and the proportion of pollution-sensitive taxa across much of England and Wales. It also revealed regions where pollution-sensitive taxa or overall richness declined, the former primarily in the uplands. SEMs confirmed strong increases in average biochemical oxygen demand and nutrient concentrations related to urban and agricultural land cover, but only a minority of land cover's effect upon invertebrate communities was explained by average water chemistry, highlighting potential factors such as episodic extremes or emerging contaminants. GWR identified strong geographical variation in estimated relationships between macroinvertebrate communities and environmental variables, with evidence that the estimated negative impacts of nutrients and water temperature were increasing through time. Overall the results are consistent with widespread biological recovery of Britain's rivers from past gross organic pollution, whilst highlighting declines in some of the most diverse and least impacted streams. Modelling points to a complex and changing set of drivers, highlighting the multifaceted impacts of catchment land cover and the evolving role of different stressors, with the relationship to gross organic pollution weakening, whilst estimated nutrient and warming effects strengthened., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Ian Vaughan reports financial support was provided by Natural Environment Research Council. 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 Authors. Published by Elsevier B.V. All rights reserved.)

Deep geological repositories (DGRs) stand out as one of the optimal options for managing high-level radioactive waste (HLW) such as uranium (U) in the near future. Here, we provide novel insights into microbial behavior in the DGR bentonite barrier, addressing potential worst-case scenarios such as waste leakage (e.g., U) and groundwater infiltration of electron rich donors in the bentonite. After a three-year anaerobic incubation, Illumina sequencing results revealed a bacterial diversity dominated by anaerobic and spore-forming microorganisms mainly from the phylum Firmicutes. Highly U tolerant and viable bacterial isolates from the genera Peribacillus, Bacillus, and some SRB such as Desulfovibrio and Desulfosporosinus, were enriched from U-amended bentonite. The results obtained by XPS and XRD showed that U was present as U(VI) and as U(IV) species. Regarding U(VI), we have identified biogenic U(VI) phosphates, U(UO 2 )·(PO 4 ) 2, located in the inner part of the bacterial cell membranes in addition to U(VI)-adsorbed to clays such as montmorillonite. Biogenic U(IV) species as uraninite may be produced as result of bacterial enzymatic U(VI) reduction. These findings suggest that under electron donor-rich water-saturation conditions, bentonite microbial community can control U speciation, immobilizing it, and thus enhancing future DGR safety if container rupture and waste leakage occurs., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

The rapid increase in lipidomic studies has led to a collaborative effort within the community to establish standards and criteria for producing, documenting, and disseminating data. Creating a dynamic easy-to-use checklist that condenses key information about lipidomic experiments into common terminology will enhance the field's consistency, comparability, and repeatability. Here, we describe the structure and rationale of the established Lipidomics Minimal Reporting Checklist to increase transparency in lipidomics research., Competing Interests: Conflict of interests Kaddurah-Daouk is an inventor on key patents in the field of metabolomics and hold equity in Metabolon, a biotech company in North Carolina. In addition, she holds patents licensed to Chymia LLC and PsyProtix with royalties and ownership. Kim Ekroos is the owner of Lipidomics Consulting Ltd., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To produce a consensus list of the top 10 signs and symptoms suggestive of adverse drug events (ADEs) for monitoring in residents of long-term care facilities (LTCFs) who use antipsychotics, benzodiazepines, or antidepressants., Design: A 3-round Delphi study., Setting and Participants: Geriatricians, psychiatrists, pharmacologists, general practitioners, pharmacists, nurses, and caregivers from 13 Asia Pacific, European, and North American countries., Methods: Three survey rounds were completed between April and June 2023. In Round 1, participants indicated their level of agreement on a 9-point Likert scale on whether 41 signs or symptoms identified in a systematic review should be routinely monitored. Participants considered signs and symptoms that reduce quality of life or cause significant harm, are observable or measurable by nurses or care workers, and can be assessed at a single time point. Round 1 statements were included in a list for prioritization in Round 3 if ≥ 70% of participants responded ≥7 on the Likert scale. Statements were excluded if ≤ 30% of participants responded ≥7. In Round 2, participants indicated their level of agreement with statements that did not reach initial consensus, plus amended statements based on Round 1 participant feedback. Round 2 statements were included in Round 3 if ≥ 50% of the participants responded ≥7 on the Likert scale. In Round 3, participants prioritized the signs and symptoms., Results: Forty-four participants (93.6%) completed all 3 rounds. Four of 41 signs and symptoms reached consensus for inclusion after Round 1, and 9 after Round 2. The top 10 signs and symptoms prioritized in Round 3 were recent falls, daytime drowsiness or sleepiness, abnormal movements (eg, shaking or stiffness), confusion or disorientation, balance problems, dizziness, postural hypotension, reduced self-care, restlessness, and dry mouth., Conclusions and Implications: The top 10 signs and symptoms provide a basis for proactive monitoring for psychotropic ADEs., Competing Interests: Disclosure B.E.M. is supported by a postgraduate research scholarship funded by Monash University. A.J.C. is supported by an NHMRC Emerging Leadership 1 grant (APP2009633). C.M.B. is supported by a National Institute on Aging Grant (R24AG064025). A.J.C. has received grant funding or consulting funds from the Medical Research Future Fund and Pharmaceutical Society of Australia. J.S.B. has received grant funding or consulting funds from the National Health and Medical Research Council (NHMRC), Medical Research Future Fund, Victorian Government Department of Health and Human Services, Dementia Australia Research Foundation, Yulgilbar Foundation, Aged Care Quality and Safety Commission, Dementia Centre for Research Collaboration, Pharmaceutical Society of Australia, Society of Hospital Pharmacists of Australia, GlaxoSmithKline Supported Studies Programme, Amgen, and several aged care provider organizations unrelated to this work. All grants and consulting funds were paid to the employing institution. M.A.S. receives royalties from UpToDate and honoraria from the American Geriatrics Society. All other co-authors have no real or perceived conflicts of interest to declare., (Copyright © 2024 Post-Acute and Long-Term Care Medical Association. All rights reserved.)

Background: To evaluate survival outcomes of pulmonary resection for isolated metachronous pancreatic cancer metastasis., Methods: A systematic search of electronic data sources and reference lists were conducted. Proportion meta-analysis model was constructed to quantify 1- to 5-year survival after pulmonary resection for isolated metachronous pancreatic cancer metastasis. Random-effects modelling was applied to calculate pooled outcome data., Results: Twenty-four retrospective studies were included reporting a total of 168 patients who underwent pulmonary resection for isolated pancreatic cancer metastasis. The nature of the index pancreatic surgery included 65% pancreaticoduodenectomies, 17.5% distal pancreatectomies, 0.5% total pancreatectomy, and 17% unspecified. Adjuvant chemotherapy was given to 88% of the patients. The median disease-free interval was 35 (8-96) months. The type of pulmonary resection included 54% wedge resections, 26% lobectomies, 4% segmentectomies, 1% pneumonectomies, and 15% unspecified. Pulmonary resection was associated with 1-year survival of 91.1% (95% CI 86.6%-95.5%), 2-year survival of 77.5% (95% CI 68.9%-86.0%), 3-year survival of 65.0% (95% CI 50.7%-79.3%), 4-year survival of 52.0% (95% CI 37.2%-66.9%), and 5-year survival of 37.0% (95% CI 25.0%-49.1%)., Conclusion: Pulmonary resection for isolated pancreatic cancer metastasis is associated with acceptable overall patient survival. We recommend selective pulmonary resection for isolated pulmonary metastasis from pancreatic cancer. Our findings may encourage conduction of better-quality studies in this context to help establishment of definitive treatment strategies., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

The finding of N-nitrosodiethylamine (NDEA) and N-nitrosodimethylamine (NDMA) in marketed drugs has led to implementation of risk assessment processes intended to limit exposures to the entire class of N-nitrosamines. A critical component of the risk assessment process is establishing exposure limits that are protective of human health. One approach to establishing exposure limits for novel N-nitrosamines is to conduct an in vivo transgenic rodent (TGR) mutation study. Existing regulatory guidance on N-nitrosamines provides decision making criteria based on interpreting in vivo TGR mutation studies as an overall positive or negative. However, point of departure metrics, such as benchmark dose (BMD), can be used to define potency and provide an opportunity to establish relevant exposure limits. This can be achieved through relative potency comparison of novel N-nitrosamines with model N-nitrosamines possessing robust in vivo mutagenicity and carcinogenicity data. The current work adds to the dataset of model N-nitrosamines by providing in vivo TGR mutation data for N-nitrosopiperidine (NPIP). In vivo TGR mutation data was also generated for a novel N-nitrosamine impurity identified in sitagliptin-containing products, 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo-[4,3-a]pyrazine (NTTP). Using the relative potency comparison approach, we have demonstrated the safety of NTTP exposures at or above levels of 1500 ng/day., 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 Inc.)

Competing Interests: Declaration of interests PDM is a founding director, patron, and former founding board member of headspace. He is the executive director of Orygen, Australia's National Centre of Excellence in Youth Mental Health and lead agency for five headspace centres across northwest Melbourne. He is a past President of the International Association for Youth Mental Health, and a past President of the IEPA; Early Intervention in Mental Health and of the Schizophrenia International Research Society. S-JB has provided paid expert witness work for UK charities and legal organisations. She is the author of two books related to the brain, education, and learning, for which she receives royalties. She gives talks in schools in the state and private sector, at education conferences, for education organisations, and for other public, private, and third sector organisations (some talks are remunerated). She is a member of the Rethinking Assessment group, the Steering Committee of the Cambridge Centre of Science Policy, the Technical Advisory Group for the UK Government Department of Education's Education and Outcomes Panel-C Study, the Singapore Government National Research Foundation Scientific Advisory Board, and the Singapore Government Human Potential Scientific Advisory Board. She was a member of the Times Education Commission (2021–22). IBH has received honoraria for consultancy and educational activities from Janssen Cilag. He was a member of the Clinical Advisory Group for the evaluation of the Better Access to Psychiatrists, Psychologists and General Practitioners through the Medicare Benefits Schedule initiative, and is a member of Mental Health Reform Advisory Committee (Department of Health). He is the Chief Scientific Advisor to and a 3·2% equity shareholder in InnoWell, which aims to transform mental health services through the use of innovative technologies. FAEA has received honoraria for consultancy from Grand Challenges Canada and is a past member of the World Economic Forum's Global Future Council on Mental Health. AMC is a director of headspace, Australia's National Youth Mental Health Foundation, and the National Education Alliance for Borderline Personality Disorder. AD is the Academic Secretary for the Royal College of Psychiatrists’ Faculty of Child and Adolescent Psychiatry, a research advisory group member of the UK National Society for the Prevention of Cruelty to Children, a member of the UK Trauma Council, and an evidence panel member of the Early Intervention Foundation. TF's research group receives funding for consultancy to Place2Be, a third sector organisation that provides mental health training, support, and interventions to schools across the UK. JH is executive director of Youth Wellness Hubs Ontario and receives funding from Graham Boeckh Foundation and other donors through the Centre for Addiction and Mental Health Foundation. AJ is a trustee of the Samaritans and MQ. She has received fees for lecturing from the Scottish Association of Mental Health. She is an advisory board member of Our Future Health, UK. FK-L's work is the subject of publishing contracts with multiple companies in the EU, Magellan, Cobalt Therapeutics in the USA, and the National Health Service in the UK. Although she has received no remuneration to date, she might receive royalties in the future. She is a non-executive director of Orygen. CK is the founder of Wida, a digital mental health platform. He has received consulting fees from the UN Children's Fund. He has received grants from MQ: Transforming Mental Health in the UK, the Royal Academy of Engineering in the UK, the National Institutes of Health in the USA, the Medical Research Council in the UK, and Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul in Brazil. DR is a Chief Scientific Advisor to headspace, Australia's National Youth Mental Health Foundation. JT receives book royalties from Simon and Schuster, legal consulting fees from Bergman and Little and the Attorney General's office of the State of Tennessee, and honoraria for speaking engagements. EK is the immediate past President of the IEPA: Early Intervention in Mental Health, and during the period of the Commission was the President elect and President. All other authors declare no competing interests.

In response to ongoing coastal urbanization, it is critical to develop effective methods to improve the biodiversity and ecological sustainability of artificial shorelines. Enhancing the topographic complexity of coastal infrastructure through the mimicry of natural substrata may facilitate the establishment of ecosystem engineering species and associated biogenic habitat formation. However, interactions between ecosystem engineers and their substratum are likely determined by organismal size and resource needs, thus making responses to topography highly scale-dependent. Here, we assessed the topographic properties (rugosity, surface area, micro-surface orientations) that underpin the abundance and distribution of two ecosystem engineers (fucoids, limpets) across six spatial scales (1-500 mm). Furthermore, we assessed the 'biogenic' rugosity created by barnacle matrices across fine scales (1-20 mm). Field surveys and 3D scanning, conducted across natural and artificial substrata, showed major effects of rugosity and associated topographic variables on ecosystem engineer assemblages and spatial occupancy, while additional abiotic environmental factors (compass direction, wave exposure) and biotic associations only had weak influences. Natural substrata exhibited ≤67 % higher rugosity than artificial ones. Fucoid-covered patches were predominantly associated with high-rugosity substrata and horizontal micro-surfaces, while homescars of limpets (≥15 mm shell length) predominated on smoother substratum patches. Barnacle-driven rugosity homogenized substrata at scales ≤10 mm. Our findings suggest that scale-dependent rugosity is a key driver of fucoid habitat formation and limpet habitat use, with wider eco-engineering applications for mimicking ecologically impactful topography on coastal infrastructure., 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 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Major burn injury, despite advancements in care and prevention, can have a profound impact on long-term morbidity, affecting quality of life and socioeconomic standing. We aim to explore factors predicting recovery of independence, the expected rate and time in majorly burned patients, and the measures of progress used., Method: A systematic search of four databases (MEDLINE, EMBASE, COCHRANE, CINAHL) was conducted for studies reporting outcomes pertaining to physical ability indicative of independent function in adult (>15 y) cohorts who had suffered a major burn (>20% TBSA) up to 30 years after treatment in a developed specialised burn service. Data extracted included factors affecting rate of and time to achievement of function in five independence domains, as well as the outcome measures used., Results: 21 eligible studies were included comprising 1298 major burns survivors with a combined mean age of 39.6 y and a mean TBSA of 25.8%. The most significant recurring factors impacting recovery of independent function were older age, female gender, burn severity, prolonged ICU and hospital admission, preceding mental health conditions, and post-acute psychological issues. Exercise-based rehabilitation conferred benefits on major burn patients even over 2 years following injury. Discharge to independent living from hospital occurred in 27% to 97% of patients, while reported return to work rates varied from 52% to 80%. Burns Specific Health Scale-Brief, Functional Independence Measure, and Physical Composite Score (SF-36) were the most widely used outcome scoring systems., Conclusion: Major burn survivors have protracted recovery with potential for persistent chronic impairments, remaining consistently below baseline levels of function. Non-modifiable factors such as age and gender, and disease characteristics such as burn size with associated physical, physiological and psychosocial sequelae are contributory. Further research is required to explore achievement of specific milestones of major burn and polytrauma critical care patients, while early targeted rehabilitation addressing physical, psychological, and vocational needs has promising potential benefit., Competing Interests: Conflict of Interest Regarding the manuscript submitted for publication in the Journal of the International Society for Burns Injuries entitled “Recovery of Functional Independence following Major Burn Survival: a Systematic Review”, I confirm no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: It is thought that digit ratios (2D:4D) are a correlate of 1st trimester maternal and foetal sex steroids. Here we consider the relationship of 2D:4D to the former., Method: Digit lengths were directly measured with a calliper at infant age 13 months. Measures of T and E were obtained from mother's blood at 6-8 weeks, 10-11 weeks and 1st trimester means were calculated., Results: There were 69 mother-infant pairs (33 boys). Sex differences in 2D:4D (boysboys) were found. For mothers of girls: there were negative relationships between 2D:4D and T at 6-8 weeks, 10-11 weeks and 1st trimester means. For infants: girls showed more correlations between 2D:4D and hormones than boys. For boys, there was one positive association between 2D:4D and E and two positive associations for E/T. For girls, 2D:4D was negatively related to T (four correlations) and positively related to E/T (four correlations). Considering associations in the total sample and controlling for sex, at 6-8 weeks right and left 2D:4D were positively related to E. At 10-11 weeks, right and left 2D:4D were negatively related to T. For 1st trimester means, 2D:4D's were positively related to E (right and left) and negatively related to T (right)., Conclusion: Infant 2D:4D was correlated with first trimester maternal sex steroids, particularly at 10-11 weeks. The correlations were negative for T, and positive for E and E/T with weaker effects for male infants. The latter pattern may arise because in boys T produced by foetal testes masks the effect of maternal T., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The prostate gland is a complex and heterogeneous organ composed of epithelium and stroma. Whilst many studies into prostate cancer focus on epithelium, the stroma is known to play a key role in disease with the emergence of a cancer-associated fibroblasts (CAF) phenotype associated upon disease progression. In this work, we studied the metabolic rewiring of stromal fibroblasts following differentiation to a cancer-associated, myofibroblast-like, phenotype. We determined that CAFs were metabolically more active compared to normal fibroblasts. This corresponded with a heightened lipogenic metabolism, as both reservoir species and building block compounds. Interestingly, lipid metabolism affects mitochondria functioning yet the mechanisms of lipid-mediated functions are unclear. Data showing oxidised fatty acids and glutathione system are elevated in CAFs, compared to normal fibroblasts, strengthens the hypothesis that increased metabolic activity is related to mitochondrial activity. This manuscript describes mechanisms responsible for the altered metabolic flux and shows that prostate cancer-derived extracellular vesicles can increase basal respiration in normal fibroblasts, mirroring that of the disease-like phenotype. This indicates that extracellular vesicles derived from prostate cancer cells may drive an altered oxygen-dependent metabolism associated to mitochondria in CAFs., 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: People with Intellectual Disabilities (PwID) are twenty times more likely than general population to have epilepsy. Guidance for prescribing antiseizure medication (ASM) to PwID is driven by trials excluding them. Levetiracetam (LEV) is a first-line ASM in the UK. Concerns exist regarding LEV's behavioural and psychological adverse effects, particularly in PwID. There is no high-quality evidence comparing effectiveness and adverse effects in PwID to those without, prescribed LEV., Methods: Pooled casenote data for patients prescribed LEV (2000-2020) at 18 UK NHS Trusts were analysed. Demographics, starting and maximum dose, adverse effects, dropouts and seizure frequency between ID (mild vs. moderate-profound (M/P)) and general population for a 12-month period were compared. Descriptive analysis, Mann-Whitney, Fisher's exact and logistic regression methods were employed., Results: 173 PwID (mild 53 M/P 120) were compared to 200 without ID. Mean start and maximum dose were similar across all groups. PwID (Mild & M/P) were less likely to withdraw from treatment (P = 0.036). No difference was found between ID and non-ID or between ID groups (Mild vs M/P) in LEV's efficacy i.e. >50 % seizure reduction. Significant association emerged between ID severity and psychiatric adverse effects (P = 0.035). More irritability (14.2 %) and aggression (10.8 %) were reported in M/P PwID., Conclusion: PwID and epilepsy have high rates of premature mortality, comorbidities, treatment resistance and polypharmacy but remain poorly researched for ASM use. This is the largest studied cohort of PwID trialled on LEV compared to general population controls. Findings support prescribing of LEV for PwID as a first-line ASM., Competing Interests: Declaration of competing interest RS has received institutional and research support from LivaNova, UCB, Eisai, Veriton Pharma, Bial, Angelini, UnEEG and Jazz/GW pharma outside the submitted work. He holds grants from NIHR AI, SBRI and other funding bodies all outside this work. No other author has any declared conflict of interest to this paper., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)