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Extracellular matrix (ECM) stiffness is fundamental in cell division, movement and differentiation. The stiffness that cells sense is determined not only by the elastic modulus of the ECM material but also by ECM geometry and cell density. We hypothesized that these factors would influence cell traction-induced matrix deformations and cellular differentiation in bone marrow stromal cells (BMSCs). To achieve this, we cultivated BMSCs on polyacrylamide hydrogels that varied in elastic modulus and geometry and measured cell spreading, cell-imparted matrix deformations and differentiation. At low cell density BMSCs spread to a greater extent on stiff compared with soft hydrogels, or on thin compared with thick hydrogels. Cell-imparted matrix deformations were greater on soft compared with stiff hydrogels or thick compared with thin hydrogels. There were no significant differences in osteogenic differentiation relative to hydrogel elastic modulus and thickness. However, increased cell density and/or prolonged culture significantly reduced matrix deformations on soft hydrogels to levels similar to those on stiff substrates. This suggests that at high cell densities cell traction-induced matrix displacements are reduced by both neighbouring cells and the constraint imposed by an underlying stiff support. This may explain observations of the lack of difference in osteogenic differentiation as a function of stiffness.

Frontal bone fractures are amongst the most common facial fractures and surgical management, which has traditionally involved access via a coronal flap, can result in unsightly scarring, alopecia, paraesthesia, facial nerve weakness and temporal hollowing. Alternative approaches include use of endoscopically-assisted surgery, often through the eyebrow, which minimises the risk of unsightly scarring but may also sacrifice access in the process. In this technical note, we discuss a surgical technique for open reduction and internal fixation of fractures of the bone overlying the frontal sinus and supra-orbital rim, which the authors have not found in the literature, which involves the making of a "zig-zag" incision through the eyebrow in a trichophytic manner which reduces the risk of unsightly scarring whilst simultaneously allowing for sufficient surgical access to the fracture site., 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 Masson SAS. All rights reserved.)

Matrix stiffening by lysyl oxidase-like 2 (LOXL2)-mediated collagen cross-linking is proposed as a core feedforward mechanism that promotes fibrogenesis. Failure in clinical trials of simtuzumab (the humanized version of AB0023, a monoclonal antibody against human LOXL2) suggested that targeting LOXL2 may not have disease relevance; however, target engagement was not directly evaluated. We compare the spatial transcriptome of active human lung fibrogenesis sites with different human cell culture models to identify a disease-relevant model. Within the selected model, we then evaluate AB0023, identifying that it does not inhibit collagen cross-linking or reduce tissue stiffness, nor does it inhibit LOXL2 catalytic activity. In contrast, it does potently inhibit angiogenesis consistent with an alternative, non-enzymatic mechanism of action. Thus, AB0023 is anti-angiogenic but does not inhibit LOXL2 catalytic activity, collagen cross-linking, or tissue stiffening. These findings have implications for the interpretation of the lack of efficacy of simtuzumab in clinical trials of fibrotic diseases., Competing Interests: Declaration of interests M.G.J., D.E.D., and Y.W. acknowledge grants from Boehringer Ingelheim. D.E.D. is co-founder of, shareholder in, and consultant to Synairgen Research Ltd. M.G.J. acknowledges consultancy fees from Skyhawk Therapeutics. J.J.W.R., K.L., and P.D.M. are current employees of Synairgen Research Ltd. L.R. acknowledges grants from Boehringer Ingelheim and consultancy fees from Biogen, Celgene, Boehringer Ingelheim, Roche, Pliant Therapeutics, BMS, CSL Behring, FibroGen, Veracyte, and Chiesi., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Spasticity is a potentially debilitating symptom of various acquired and congenital neurologic pathologies that, without adequate treatment, may lead to long-term disability, compromise functional independence, and negatively impact mental health. Several conservative as well as non-nerve targeted surgical strategies have been developed for the treatment of spasticity, but these may be associated with significant drawbacks, such as adverse side effects to medication, device dependence on intrathecal baclofen pumps, and inadequate relief with tendon-based procedures. In these circumstances, patients may benefit from nerve-targeted surgical interventions such as (i) selective dorsal rhizotomy, (ii) hyperselective neurectomy, and (iii) nerve transfer. When selecting the appropriate surgical approach, preoperative patient characteristics, as well as the risks and benefits of nerve-targeted surgical intervention, must be carefully evaluated. Here, we review the current evidence on the efficacy of these nerve-targeted surgical approaches for treating spasticity across various congenital and acquired neurologic pathologies., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Kagome vanadates AV 3 Sb 5 display unusual low-temperature electronic properties including charge density waves (CDW), whose microscopic origin remains unsettled. Recently, CDW order has been discovered in a new material ScV 6 Sn 6 , providing an opportunity to explore whether the onset of CDW leads to unusual electronic properties. Here, we study this question using angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy (STM). The ARPES measurements show minimal changes to the electronic structure after the onset of CDW. However, STM quasiparticle interference (QPI) measurements show strong dispersing features related to the CDW ordering vectors. A plausible explanation is the presence of a strong momentum-dependent scattering potential peaked at the CDW wavevector, associated with the existence of competing CDW instabilities. Our STM results further indicate that the bands most affected by the CDW are near vHS, analogous to the case of AV 3 Sb 5 despite very different CDW wavevectors., (© 2024. The Author(s).)

Objective: This case series explored the integration of smartwatches in a community mental health service to support severe mental illness (SMI) management and intervention. We examined whether biometric data provided by smartwatches could help to predict relapse and inform treatment decisions., Method: Four Australian SMI outpatients of mixed diagnoses (age range = 19-24) were selected from a prior study. Clinicians accessed patients' biometric data (activity, sleep, heart rate, and electrodermal activity) through smartwatches., Results: Changes in circadian rhythm and electrodermal activity preceded hospitalization in two cases. Additionally, smartwatch data was effectively used to guide targeted interventions, improving patient treatment outcomes., Conclusion: Integrating smartwatches in community mental health services offers promise as adjunct tools for SMI management. However, ethical considerations on data privacy and technology reliance require further evaluation. Additionally, as this is a small case series, randomized controlled trials with larger sample sizes are required to provide evidence for generalisability of results., (© 2024 The Authors. Early Intervention in Psychiatry published by John Wiley & Sons Australia, Ltd.)

Background and Purpose: Symptomatic arrhythmia is common following radiotherapy for non-small cell lung cancer (NSCLC), frequently resulting in morbidity and hospitalization. Modern treatment planning technology theoretically allows sparing of cardiac substructures. Atrial fibrillation (AF) comprises the majority of post-radiotherapy arrhythmias, but efforts to prevent this cardiotoxicity have been limited as the causative cardiac substructure is not known. In this study we investigated if incidental radiation dose to the pulmonary veins (PVs) is associated with AF., Material and Methods: A single-centre study of patients completing contemporary (chemo)radiation for NSCLC, with modern planning techniques. Oncology, cardiology and death records were examined, and AF events were verified by a cardiologist. Cardiac substructures were contoured on planning scans for retrospective dose analysis., Results: In 420 eligible patients with NSCLC treated with intensity-modulated (70%) or 3D-conformal (30%) radiotherapy with a median OS of 21.8 months (IQR 10.8-35.1), there were 26 cases of new AF (6%). All cases were grade 3 except two cases of grade 4. Dose metrics for both the left (V55) and right (V10) PVs were associated with the incidence of new AF. Metrics remained statistically significant after accounting for the competing risk of death and cardiovascular covariables for both the left (HR 1.02, 95%CI 1.00-1.03, p = 0.005) and right (HR 1.01 (95%CI 1.00-1.02, p = 0.033) PVs., Conclusion: Radiation dose to the PVs during treatment of NSCLC was associated with the onset of AF. Actively sparing the PVs during treatment planning could reduce the incidence of AF during follow-up, and screening for AF may be warranted for select cases., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Those studying neural systems within the brain have historically assumed that lower-level processes in the spinal cord act in a mechanical manner, to relay afferent signals and execute motor commands. From this view, abstracting temporal and environmental relations is the province of the brain. Here we review work conducted over the last 50 years that challenges this perspective, demonstrating that mechanisms within the spinal cord can organize coordinated behavior (stepping), induce a lasting change in how pain (nociceptive) signals are processed, abstract stimulus-stimulus (Pavlovian) and response-outcome (instrumental) relations, and infer whether stimuli occur in a random or regular manner. The mechanisms that underlie these processes depend upon signal pathways (e.g., NMDA receptor mediated plasticity) analogous to those implicated in brain-dependent learning and memory. New data show that spinal cord injury (SCI) can enable plasticity within the spinal cord by reducing the inhibitory effect of GABA. It is suggested that the signals relayed to the brain may contain information about environmental relations and that spinal cord systems can coordinate action in response to descending signals from the brain. We further suggest that the study of stimulus processing, learning, memory, and cognitive-like processing in the spinal cord can inform our views of brain function, providing an attractive model system. Most importantly, the work has revealed new avenues of treatment for those that have suffered a SCI., 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 Grau, Hudson, Johnston and Partipilo.)

Background: Peripheral nerve injury or post-block neurological dysfunction (PBND) are uncommon but a recognized complications of peripheral nerve blocks (PNB). A broad range of its incidence is noted in the literature and hence a critical appraisal of its occurrence is needed., Objective: In this review, we wanted to know the pooled estimates of PBND and further, determine its pooled estimates following various PNB over time. Additionally, we also sought to estimate the incidence of PBND with or without US guidance., Evidence Review: A literature search was conducted in six databases. For the purposes of the review, we defined PBND as any new-onset sensorimotor disturbances in the distribution of the performed PNB either attributable to the PNB (when reported) or reported in the context of the PNB (when association with a PNB was not mentioned). Both prospective and retrospective studies which provided incidence of PBND at timepoints of interest (>48 hours to <2 weeks; >2 weeks to 6 weeks, 7 weeks to 5 months, 6 months to 1 year and >1 year durations) were included for review. Incidence data were used to provide pooled estimates (with 95% CI) of PBND at these time periods. Similar estimates were obtained to know the incidence of PBND with or without the use of US guidance. Additionally, PBND associated with individual PNB were obtained in a similar fashion with upper and lower limb PNB classified based on the anatomical location of needle insertion., Findings: The overall incidence of PBND decreased with time, with the incidence being approximately 1% at <2 weeks' time (Incidence per thousand (95% CI)= 9 (8; to 11)) to approximately 3/10 000 at 1 year (Incidence per thousand (95% CI)= 0. 3 (0.1; to 0.5)). Incidence of PBND differed for individual PNB with the highest incidence noted for interscalene block., Conclusions: Our review adds information to existing literature that the neurological complications are rarer but seem to display a higher incidence for some blocks more than others. Use of US guidance may be associated with a lower incidence of PBND especially in those PNBs reporting a higher pooled estimates. Future studies need to standardize the reporting of PBND at various timepoints and its association to PNB., Competing Interests: Competing interests: RVS: receives consultation fees from CIVCO Ltd and the relationship is currrent., (© American Society of Regional Anesthesia & Pain Medicine 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Empirical analyses have demonstrated that individuals exposed to severe air pollution in utero have worse health outcomes during childhood. However, there is little evidence on the long-term health impacts of air pollution exposure. The objective of this paper is to estimate the effect of in utero exposure to the Great London Smog of 1952 (GLS) on five health outcomes identified through a scoping review to be those most likely affected: respiratory, circulatory, neoplasms, mental health, and nervous system conditions. We use the GLS, an extreme air pollution event in December 1952, as a quasi-natural experiment to estimate the effect of exposure to air pollution in utero on adulthood health. Data from the UK Biobank is analysed for a cohort of participants born from December 1952 to July 1956. Differences in health outcomes between adults exposed and not exposed to the GLS due to their birth dates, born inside and outside London, were explored. Our primary focus is hospitalization events between 1997 and 2020 (corresponding to ages 40 to 69), as recorded in linked administrative data from the National Health Service (NHS). Specifically, the five primary outcomes are binary variables indicating that the individual had at least one hospitalization where the main cause of hospitalization is related to respiratory, circulatory, neoplasms, mental health, or nervous system conditions. The analytical sample comprised 36,281 individuals. A positive effect on adulthood hospitalizations due to respiratory conditions was observed. If exposed to the GLS in utero, the probability of at least one respiratory health-related hospitalization between 1997 and 2020 increased by 2.58 percentage points (95% CI 0.08, 4.30, p = 0.03), a 23% increase relative to the sample mean. Small effects were found for all other outcomes, suggesting that these conditions were not affected by the GLS. We do not find heterogeneous effects by sex or childhood socioeconomic status. This study found that a 5-day pollution exposure event while in utero significantly increased respiratory-related hospitalizations at ages 40 to 69 but had no impact on hospitalizations due to circulatory, neoplasms, mental health, and nervous system conditions., (© 2023. The Author(s).)

The Asian community - the second largest non-European ethnic community in New Zealand - plays an important role in combatting the COVID-19 pandemic, evidenced by their active advocation for border control and mass masking. Despite the long history of racial discrimination against the Asian population, the Asian community has experienced certain degrees of racial discrimination associated with the stigmatisation as the cause of the COVID-19 outbreak in New Zealand. Based on data from a quantitative online survey with 402 valid responses within the Asian communities across New Zealand and the in-depth interviews with 19 Asian people in Auckland, New Zealand, this paper will illustrate Asian people's experience of racial discrimination and stigmatisation during the pandemic in the country. The survey shows that since the outbreak of COVID-19, under a quarter of the participants reported experiencing discrimination, and a third reported knowing an immediate contact who had experienced discrimination. However, when looking beyond their immediate social circle, an even higher proportion reported noticing racism and stigmatisation through the traditional or social media due to COVID-19. Major variations of the degree of racial discrimination experienced are determined by three demographic variables: ethnicity, age, and region. The in-depth interviews largely echoed the survey findings and highlighted a strong correlation between the perceived racial discrimination among the local Asian community and the stigmatisation associated with COVID-19. These findings are important for improving the way we manage future pandemics and other disasters within the context of the UN Sendai Framework for Disaster Risk Reduction., (© 2022. The Author(s).)

Extreme heat negatively impacts cognition, learning, and task performance. With increasing global temperatures, workers may therefore be at increased risk of work-related injuries and illness. This study estimates the effects of temperature on worker health using records spanning 1985-2020 from an Australian mandatory insurance scheme. High temperatures are found to cause significantly more claims, particularly among manual workers in outdoor-based industries. These adverse effects have not diminished across time, with the largest effect observed for the 2015-2020 period, indicating increasing vulnerability to heat. Within occupations, the workers most adversely affected by heat are female, older-aged and higher-earning. Finally, results from firm-level panel analyses show that the percentage increase in claims on hot days is largest at "safer" firms., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Radiation cardiotoxicity is a dose-limiting toxicity and major survivorship issue for patients with non-small cell lung cancer (NSCLC) completing curative-intent radiotherapy, however patients' cardiovascular baseline is not routinely optimised prior to treatment. In this study we examined the impact of statin therapy on overall survival and post-radiotherapy cardiac events., Methods: Patients treated between 2015-2020 at a regional center were identified. Clinical notes were interrogated for baseline patient, tumor and cardiac details, and both follow-up cancer control and cardiac events. Three cardiologists verified cardiac events. Radiotherapy planning scans were retrieved for application of validated deep learning-based autosegmentation. Pre-specified Cox regression analyses were generated with varying degrees of adjustment for overall survival. Fine and Gray regression for the risk of cardiac events, accounting for the competing risk of death and cardiac covariables was undertaken., Results: Statin therapy was prescribed to 59% of the 478 included patients. The majority (88%) of patients not prescribed a statin had at least one indication for statin therapy according to cardiovascular guidelines. In total, 340 patients (71%) died and 79 patients (17%) experienced a cardiac event. High-intensity (HR 0.68, 95%CI 0.50-0.91, p = 0.012) and medium-intensity (HR 0.70, 95%CI 0.51-0.97, p = 0.033) statin therapy were associated with improved overall survival after adjustment for patient, cancer, treatment, response and cardiovascular clinical factors. There were no consistent differences in the rate or grade of cardiac events according to statin intensity., Conclusions: Statin therapy is associated with improved overall survival in patients receiving curative-intent radiotherapy for NSCLC, and there is evidence of a dose-response relationship. This study highlights the importance of a pre-treatment cardiovascular risk assessment in this cohort. Further studies are needed to examine if statin therapy is cardioprotective in patients undergoing treatment for NSCLC with considerable incidental cardiac radiation dose and a low baseline cardiac risk., 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 © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The aim of this study is to evaluate the change in incidence rate of shoulder arthroplasty, indications, and surgeon volume trends associated with these procedures between January 2003 and April 2021 in the province of Nova Scotia, Canada., Methods: A total of 1,545 patients between 2005 and 2021 were analyzed. Patients operated on between 2003 and 2004 were excluded due to a lack of electronic records. Overall, 84.1% of the surgeries (n = 1,299) were performed by two fellowship-trained upper limb surgeons, with the remainder performed by one of the 14 orthopaedic surgeons working in the province., Results: Total shoulder arthroplasty (TSA) was the most frequent procedure (32.17%; n = 497), followed by stemmed hemiarthroplasty (SHA) (27.7%; n = 428). The most frequent indication for primary shoulder arthroplasty was degenerative osteoarthritis (58.1%; n = 882), followed by acute proximal humerus fracture in 15.11% (n = 245), and rotator cuff arthropathy in 14.18% (n = 220). The overall rate of revision was 7.7% (2.8% to 11.2%). The number of TSAs and reverse shoulder arthroplasties (RSAs) has been increasing since 2016. The amount of revision cases is proportional to the number of operations performed in the same year throughout the study period., Conclusion: The incidence of shoulder arthroplasty in the Maritime Provinces has increased over the last 16 years. Revision rates are similar the those found in other large database registries. Reverse shoulder arthroplasty prevalence has increased since 2016., Competing Interests: None declared., (© 2023 Author(s) et al.)

Non-communicable diseases (NCDs) disproportionately affect people in low- and middle-income countries (LMICs), yet context-specific evidence on policies that impact NCD risk factors is lacking. We estimate the impact of a massive Indonesian primary school expansion program in the 1970s on NCD risk factors in later life using data from two surveys with very large sample sizes. We find that in non-Java regions of Indonesia, the program led to significant increases in the likelihood of overweight and high waist circumference among women, but not among men. The increase for women can be partly explained by increased consumption of high-calorie packaged and take-away meals. We find no meaningful impacts on high blood pressure for either sex. Despite the increase in body weight, the program had a negligible impact on diabetes and cardiovascular disease diagnosis. It led to an improvement in women's self-reported health outcomes in their early-40s, but these benefits largely disappeared once they reached their mid-40s., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Dementia prevalence is projected to rise steeply in coming decades, producing tremendous burdens on families, and health and social services. Motivated by the need for further robust evidence on modifiable risk factors, we investigate the relationship between cognitive activity at work and later-life dementia. Using data from the US Health and Retirement Study matched to the O*NET occupational database, we find that a one standard deviation increase in the cognitive activity associated with one's longest held occupation is associated with a 0.9 percentage point reduction in (predicted) dementia, or a 24% reduction relative to the mean. This relationship is consistently found across model specifications and robustness tests. When controlling for individual fixed-effects we find that the association between dementia and work cognitive activity increases with age. Overall, our results provide some evidence in support of the inclusion of cognitive activity at work as a recognized modifiable risk factor for dementia., (© 2023 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Aim: Asians are the second largest and fastest growing non-European population in New Zealand but are under-researched in terms of their COVID-19 pandemic response. The paper aims to illustrates Asians' risk perceptions and knowledge of COVID-19, and self-protection practices to avoid infection and prevent community transmission., Subject and Methods: An online survey was used to collect data and received 402 valid responses. Data analyses included: 1) a descriptive analysis by using Chi -square tests and a Kruskal-Wallis rank sum tests to explore associations between responses and the four demographic variables (i.e. age, gender, country of origin/ethnicity, and region); and 2) a correlation analysis between different survey objectives., Results: The descriptive analysis of the survey found that while ethnicity (within the Asian category) was the most influential variable that resulted in varying responses to many questions, gender and age were other two important variables in influencing the answering patterns. The correlation analysis found a positive correlation between the perceived 'dangerousness' of COVID-19 and respondents' overall compliance behaviour to New Zealand authorities' recommendations to prevent spread of COVID-19., Conclusion: The majority of the respondents provided correct answers to the questions about the vulnerable populations, symptoms, asymptomatic transmission and potential sequelae of COVID-19; however, their understanding of the availability of a cure for, and the incubation period of COVID-19 was not consistent with the official information. The research also found that the higher perceived dangerousness of COVID-19, the better compliance to self-protection practices among the surveyed population., Competing Interests: Conflict of interestThe authors have no relevant financial or non-financial conflict of interests to disclose. Submission declaration and verification: The work has not published previously and submitted to any other journal., (© The Author(s) 2023.)

Bulk filter feeding has enabled gigantism throughout evolutionary history. The largest animals, extant rorqual whales, utilize intermittent engulfment filtration feeding (lunge feeding), which increases in efficiency with body size, enabling their gigantism. The smallest extant rorquals (7-10 m minke whales), however, still exhibit short-term foraging efficiencies several times greater than smaller non-filter-feeding cetaceans, raising the question of why smaller animals do not utilize this foraging modality. We collected 437 h of bio-logging data from 23 Antarctic minke whales (Balaenoptera bonaerensis) to test the relationship of feeding rates (λ f ) to body size. Here, we show that while ultra-high nighttime λ f (mean ± s.d.: 165 ± 40 lunges h -1 ; max: 236 lunges h -1 ; mean depth: 28 ± 46 m) were indistinguishable from predictions from observations of larger species, daytime λ f (mean depth: 72 ± 72 m) were only 25-40% of predicted rates. Both λ f were near the maxima allowed by calculated biomechanical, physiological and environmental constraints, but these temporal constraints meant that maximum λ f was below the expected λ f for animals smaller than ~5 m-the length of weaned minke whales. Our findings suggest that minimum size for specific filter-feeding body plans may relate broadly to temporal restrictions on filtration rate and have implications for the evolution of filter feeding., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

The krill surplus hypothesis of unlimited prey resources available for Antarctic predators due to commercial whaling in the 20th century has remained largely untested since the 1970s. Rapid warming of the Western Antarctic Peninsula (WAP) over the past 50 years has resulted in decreased seasonal ice cover and a reduction of krill. The latter is being exacerbated by a commercial krill fishery in the region. Despite this, humpback whale populations have increased but may be at a threshold for growth based on these human-induced changes. Understanding how climate-mediated variation in prey availability influences humpback whale population dynamics is critical for focused management and conservation actions. Using an 8-year dataset (2013-2020), we show that inter-annual humpback whale pregnancy rates, as determined from skin-blubber biopsy samples (n = 616), are positively correlated with krill availability and fluctuations in ice cover in the previous year. Pregnancy rates showed significant inter-annual variability, between 29% and 86%. Our results indicate that krill availability is in fact limiting and affecting reproductive rates, in contrast to the krill surplus hypothesis. This suggests that this population of humpback whales may be at a threshold for population growth due to prey limitations. As a result, continued warming and increased fishing along the WAP, which continue to reduce krill stocks, will likely impact this humpback whale population and other krill predators in the region. Humpback whales are sentinel species of ecosystem health, and changes in pregnancy rates can provide quantifiable signals of the impact of environmental change at the population level. Our findings must be considered paramount in developing new and more restrictive conservation and management plans for the Antarctic marine ecosystem and minimizing the negative impacts of human activities in the region., (© 2023 The Authors. Global Change Biology published by John Wiley & Sons Ltd. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

The Paleocene-Eocene Thermal Maximum (PETM) was an abrupt global warming event associated with a large injection of carbon into the ocean-atmosphere system, as evidenced by a diagnostic carbon isotope excursion (CIE). Evidence also suggests substantial hydrologic perturbations, but details have been hampered by a lack of appropriate proxies. To address this shortcoming, here we isolate and measure the isotopic composition of hydroxyl groups (OH - ) in clay minerals from a highly expanded PETM section in the North Sea Basin, together with their bulk oxygen isotope composition. At this location, we show that hydroxyl O- and H-isotopes are less influenced than bulk values by clay compositional changes due to mixing and/or inherited signals and thus better track hydrologic variability. We find that clay OH - hydrogen-isotope values (δ 2 H OH ) decrease slowly prior to the PETM and then abruptly by ∼8‰ at the CIE onset. Coincident with an increase in relative kaolinite content, this indicates increased rainfall and weathering and implies an enhanced hydrologic cycle response to global warming, particularly during the early stages of the PETM. Subsequently, δ 2 H OH returns to pre-PETM values well before the end of the CIE, suggesting hydrologic changes in the North Sea were short-lived relative to carbon-cycle perturbations., (© 2022. The Author(s).)

Recent recommendations describe a set of core anatomical structures to identify on ultrasound for the performance of basic blocks in ultrasound-guided regional anesthesia (UGRA). This project aimed to generate consensus recommendations for core structures to identify during the performance of intermediate and advanced blocks. An initial longlist of structures was refined by an international panel of key opinion leaders in UGRA over a three-round Delphi process. All rounds were conducted virtually and anonymously. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for "block view" (which visualizes the block site and is maintained for needle insertion/injection). A "strong recommendation" was made if ≥75% of participants rated any structure as "definitely include" in any round. A "weak recommendation" was made if >50% of participants rated it as "definitely include" or "probably include" for all rounds, but the criterion for strong recommendation was never met. Structures which did not meet either criterion were excluded. Forty-one participants were invited and 40 accepted; 38 completed all three rounds. Participants considered the ultrasound scanning for 19 peripheral nerve blocks across all three rounds. Two hundred and seventy-four structures were reviewed for both orientation scanning and block view; a "strong recommendation" was made for 60 structures on orientation scanning and 44 on the block view. A "weak recommendation" was made for 107 and 62 structures, respectively. These recommendations are intended to help standardize teaching and research in UGRA and support widespread and consistent practice., Competing Interests: Competing interests: AD, YG, CG, LFV-V, TV, and MW are members of the Executive Board of the ESRA. NME, RKG, and MR are members of the Board of Directors of the ASRA. ERM, SM, and ESS sit on ASRA Committees. TA, AG, NH, DFJ, RJK, AJRM, AP, MPS, AT, LT, SW, and JW are members of the Board of RA-UK. KEB is the Scientific Officer for the Difficult Airway Society. JSB, DBSL, AJRM, DP, and AT declare honoraria and/or research funding from Intelligent Ultrasound. JAN is a Senior Scientific Advisor for Intelligent Ultrasound. AP declares honoraria from GE Healthcare, Butterfly Net, Sintetica UK, and Pacira., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The biogeochemical fluxes that cycle oxygen (O 2 ) play a critical role in regulating Earth's climate and habitability. Triple-oxygen isotope (TOI) compositions of marine dissolved O 2 are considered a robust tool for tracing oxygen cycling and quantifying gross photosynthetic O 2 production. This method assumes that photosynthesis, microbial respiration, and gas exchange with the atmosphere are the primary influences on dissolved O 2 content, and that they have predictable, fixed isotope effects. Despite its widespread use, there are major elements of this approach that remain uncharacterized, including the TOI dynamics of respiration by marine heterotrophic bacteria and abiotic O 2 sinks such as the photochemical oxidation of dissolved organic carbon (DOC). Here, we report the TOI fractionation for O 2 utilization by two model marine heterotrophs and by abiotic photo-oxidation of representative terrestrial and coastal marine DOC. We demonstrate that TOI slopes associated with these processes span a significant range of the mass-dependent domain (λ = 0.499 to 0.521). A sensitivity analysis reveals that even under moderate productivity and photo-oxidation scenarios, true gross oxygen production may deviate from previous estimates by more than 20% in either direction. By considering a broader suite of oxygen cycle reactions, our findings challenge current gross oxygen production estimates and highlight several paths forward to better understanding the marine oxygen and carbon cycles., (© The Author(s) 2022. Published by Oxford University Press on behalf of the National Academy of Sciences.)

Billions of people live in urban poverty, with many forced to reside in disaster-prone areas. Research suggests that such disasters harm child nutrition and increase adult morbidity. However, little is known about impacts on mental health, particularly of people living in slums. In this paper we estimate the effects of flood disasters on the mental and physical health of poor adults and children in urban Indonesia. Our data come from the Indonesia Family Life Survey and new surveys of informal settlement residents. We find that urban poor populations experience increases in acute morbidities and depressive symptoms following floods, that the negative mental health effects last longer, and that the urban wealthy show no health effects from flood exposure. Further analysis suggests that worse economic outcomes may be partly responsible. Overall, the results provide a more nuanced understanding of the morbidities experienced by populations most vulnerable to increased disaster occurrence., (© 2022 The Authors. Health Economics published by John Wiley & Sons Ltd.)

Although gigantic body size and obligate filter feeding mechanisms have evolved in multiple vertebrate lineages (mammals and fishes), intermittent ram (lunge) filter feeding is unique to a specific family of baleen whales: rorquals. Lunge feeding is a high cost, high benefit feeding mechanism that requires the integration of unsteady locomotion (i.e., accelerations and maneuvers); the impact of scale on the biomechanics and energetics of this foraging mode continues to be the subject of intense study. The goal of our investigation was to use a combination of multi-sensor tags paired with UAS footage to determine the impact of morphometrics such as body size on kinematic lunging parameters such as fluking timing, maximum lunging speed, and deceleration during the engulfment period for a range of species from minke to blue whales. Our results show that, in the case of krill-feeding lunges and regardless of size, animals exhibit a skewed gradient between powered and fully unpowered engulfment, with fluking generally ending at the point of both the maximum lunging speed and mouth opening. In all cases, the small amounts of propulsive thrust generated by the tail were unable to overcome the high drag forces experienced during engulfment. Assuming this thrust to be minimal, we predicted the minimum speed of lunging across scale. To minimize the energetic cost of lunge feeding, hydrodynamic theory predicts slower lunge feeding speeds regardless of body size, with a lower boundary set by the ability of the prey to avoid capture. We used empirical data to test this theory and instead found that maximum foraging speeds remain constant and high (∼4 m s -1 ) across body size, even as higher speeds result in lower foraging efficiency. Regardless, we found an increasing relationship between body size and this foraging efficiency, estimated as the ratio of energetic gain from prey to energetic cost. This trend held across timescales ranging from a single lunge to a single day and suggests that larger whales are capturing more prey-and more energy-at a lower cost., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology.)

Background: Apprenticeships are a common pathway for young people transitioning into the workforce. Apprentices often face many employment-related challenges and have high levels of psychological distress, drug and alcohol use, and suicidal ideation. Little is known about the attitudes of apprentices toward using smartphone apps to support their mental health and the content that would engage them., Objective: This study explored (1) apprentices' interest in using an app to support their mental health and (2) the healthy coping strategies used to manage their mental well-being in the face of workplace challenges, in order to inform future app content., Methods: A mixed methods study was conducted with 54 apprentices (50/54 male, 93%) with a mean age of 22.7 (SD 5.7) years. Participants completed a survey on preferred ways of using an app to support mental health. Across 8 focus groups, participants were asked to describe healthy strategies they used to cope with occupational stressors., Results: Only 11% (6/54) of participants currently used a well-being app, but there was high interest in using an app to support their friends (47/54 participants, 87%) and develop self-help strategies to manage or prevent mental health issues (42/54 participants, 78%). Four major types of coping behaviors were identified: (1) social connection for disclosure, advice, and socializing; (2) pleasurable activities, such as engaging in hobbies, time-outs, and developing work-life separation; (3) cognitive approaches, including defusing from thoughts and cognitive reframing; and (4) self-care approaches, including exercise, a healthy diet, and getting adequate sleep., Conclusions: There is interest among apprentices to use an app with a positive well-being focus that helps them to develop self-management skills and support their friends. Apprentices utilized a range of healthy behaviors to cope with workplace stressors that can be incorporated into mental health apps to improve uptake and engagement. However, many of the preferred coping strategies identified are not those focused on by currently available apps, indicating the need for more targeted digital interventions for this group., (©Isabella Choi, Katherine Petrie, Rochelle Einboden, Daniel Collins, Rose Ryan, David Johnston, Samuel B Harvey, Nicholas Glozier, Alexis Wray, Mark Deady. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 18.08.2022.)

A defining pathological feature of human lung fibrosis is localized tissue heterogeneity, which challenges the interpretation of transcriptomic studies that typically lose spatial information. Here we investigate spatial gene expression in diagnostic tissue using digital profiling technology. We identify distinct, region-specific gene expression signatures as well as shared gene signatures. By integration with single-cell data, we spatially map the cellular composition within and distant from the fibrotic niche, demonstrating discrete changes in homeostatic and pathologic cell populations even in morphologically preserved lung, while through ligand-receptor analysis, we investigate cellular cross-talk within the fibrotic niche. We confirm findings through bioinformatic, tissue, and in vitro analyses, identifying that loss of NFKB inhibitor zeta in alveolar epithelial cells dysregulates the TGFβ/IL-6 signaling axis, which may impair homeostatic responses to environmental stress. Thus, spatially resolved deconvolution advances understanding of cell composition and microenvironment in human lung fibrogenesis., Competing Interests: Declaration of interests D.E.D. is co-founder of, shareholder in, and consultant to Synairgen Research Ltd. D.E.D., M.G.J., and Y.W. acknowledge grants from Boehringer Ingelheim., (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)

The triple oxygen isotope composition (Δ' 17 O) of sulfate minerals is widely used to constrain ancient atmospheric p O 2 / p CO 2 and rates of gross primary production. The utility of this tool is based on a model that sulfate oxygen carries an isotope fingerprint of tropospheric O 2 incorporated through oxidative weathering of reduced sulfur minerals, particularly pyrite. Work to date has targeted Proterozoic environments (2.5 billion to 0.542 billion years ago) where large isotope anomalies persist; younger timescale records, which would ground ancient environmental interpretation in what we know from modern Earth, are lacking. Here we present a high-resolution record of the [Formula: see text]O and Δ' 17 O in marine sulfate for the last 130 million years of Earth history. This record carries a Δ' 17 O close to 0o, suggesting that the marine sulfate reservoir is under strict control by biogeochemical cycling (namely, microbial sulfate reduction), as these reactions follow mass-dependent fractionation. We identify no discernible contribution from atmospheric oxygen on this timescale. We interpret a steady fractional contribution of microbial sulfur cycling (terrestrial and marine) over the last 100 million years, even as global weathering rates are thought to vary considerably.

Background/importance: There is heterogeneity among the outcomes used in regional anesthesia research., Objective: We aimed to produce a core outcome set for regional anesthesia research., Methods: We conducted a systematic review and Delphi study to develop this core outcome set. A systematic review of the literature from January 2015 to December 2019 was undertaken to generate a long list of potential outcomes to be included in the core outcome set. For each outcome found, the parameters such as the measurement scale, timing and definitions, were compiled. Regional anesthesia experts were then recruited to participate in a three-round electronic modified Delphi process with incremental thresholds to generate a core outcome set. Once the core outcomes were decided, a final Delphi survey and video conference vote was used to reach a consensus on the outcome parameters., Results: Two hundred and six papers were generated following the systematic review, producing a long list of 224 unique outcomes. Twenty-one international regional anesthesia experts participated in the study. Ten core outcomes were selected after three Delphi survey rounds with 13 outcome parameters reaching consensus after a final Delphi survey and video conference., Conclusions: We present the first core outcome set for regional anesthesia derived by international expert consensus. These are proposed not to limit the outcomes examined in future studies, but rather to serve as a minimum core set. If adopted, this may increase the relevance of outcomes being studied, reduce selective reporting bias and increase the availability and suitability of data for meta-analysis in this area., Competing Interests: Competing interests: EA received grants from the Swiss Academy for Anaesthesia Research, Lausanne, Switzerland; B. Braun Medical AG, Sempach, Switzerland; and the Swiss National Science Foundation to support his clinical research. EA has also received an honorarium from B. Braun Medical AG Switzerland, Sintetica Ltd UK and MSD AG Switzerland. BF declares honoraria from B. Braun, Sintetica, Brain Therapeutics and Hospitality Medovate. ERM chairs the American Society of Anaesthesiologists Committee on Regional Anesthesia and Acute Pain Medicine. He is a former director of the American Society of Regional Anesthesia and Pain Medicine (ASRA). TA, AG, NH, DFJ, AJRM, AP, MPS, LT, SW, JW are members of the Board of Regional Anaesthesia UK (RA-UK). KE-B declares honoraria from GE Healthcare, Ambu, Fisher and Paykel, Edwards Lifesciences. AJRM declares honoraria and/or research funding from Intelligent Ultrasound. PM is a board member of European Diploma in Regional Anaesthesia (EDRA) and declares honoraria from B. Braun Medical and Medovate. AP declares honoraria from GE Healthcare, Butterfly Net, Sintetica UK and Pacira. KR was the President of the British Association of Day Surgery., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Antarctic humpback whales forage in summer, coincident with the seasonal abundance of their primary prey, the Antarctic krill. During the feeding season, humpback whales accumulate energy stores sufficient to fuel their fasting period lasting over six months. Previous animal movement modelling work (using area-restricted search as a proxy) suggests a hyperphagic period late in the feeding season, similar in timing to some terrestrial fasting mammals. However, no direct measures of seasonal foraging behaviour existed to corroborate this hypothesis. We attached high-resolution, motion-sensing biologging tags to 69 humpback whales along the Western Antarctic Peninsula throughout the feeding season from January to June to determine how foraging effort changes throughout the season. Our results did not support existing hypotheses: we found a significant reduction in foraging presence and feeding rates from the beginning to the end of the feeding season. During the early summer period, feeding occurred during all hours at high rates. As the season progressed, foraging occurred mostly at night and at lower rates. We provide novel information on seasonal changes in foraging of humpback whales and suggest that these animals, contrary to nearly all other animals that seasonally fast, exhibit high feeding rates soon after exiting the fasting period., (© 2022 The Authors.)

Aim: To provide an up-to-date review of thunderstorm asthma (TA), identifying causative factors, and to discuss implications for management of TA in New Zealand., Methods: A literature search was carried out to identify articles that investigate the characteristics and causative factors of TA. Nine electronic databases were searched, yielding 372 articles, reduced to 30 articles after screening for duplication and relevance., Results: TA is globally rare, with 29 reported events since 1983, but is expected to increase in frequency as Earth warms. Triggers include both pollen (particularly ryegrass pollen) and fungal spores. Individual risk factors include outdoor exposure, sensitivity to triggering allergens and history of seasonal allergic rhinitis. History of asthma is not a strong risk factor but is associated with severity of outcome. Limited data on demographic characteristics suggests that individuals aged between 20 and 60 and (in Australasia) of Asian/Indian ethnicity are at higher risk. A single TA event has been reported in New Zealand to date, but much of New Zealand may be at risk of future events given that ryegrass pastures are widely distributed, and summer thunderstorms can occur anywhere., Conclusions: We recommend developing rapidly deployable public messaging to support the health emergency management response to future TA events, together with the instigation of routine aeroallergen monitoring., Competing Interests: Nil.

Despite their enormous size, whales make their living as voracious predators. To catch their much smaller, more maneuverable prey, they have developed several unique locomotor strategies that require high energetic input, high mechanical power output and a surprising degree of agility. To better understand how body size affects maneuverability at the largest scale, we used bio-logging data, aerial photogrammetry and a high-throughput approach to quantify the maneuvering performance of seven species of free-swimming baleen whale. We found that as body size increases, absolute maneuvering performance decreases: larger whales use lower accelerations and perform slower pitch-changes, rolls and turns than smaller species. We also found that baleen whales exhibit positive allometry of maneuvering performance: relative to their body size, larger whales use higher accelerations, and perform faster pitch-changes, rolls and certain types of turns than smaller species. However, not all maneuvers were impacted by body size in the same way, and we found that larger whales behaviorally adjust for their decreased agility by using turns that they can perform more effectively. The positive allometry of maneuvering performance suggests that large whales have compensated for their increased body size by evolving more effective control surfaces and by preferentially selecting maneuvers that play to their strengths., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

There is no universally agreed set of anatomical structures that must be identified on ultrasound for the performance of ultrasound-guided regional anesthesia (UGRA) techniques. This study aimed to produce standardized recommendations for core (minimum) structures to identify during seven basic blocks. An international consensus was sought through a modified Delphi process. A long-list of anatomical structures was refined through serial review by key opinion leaders in UGRA. All rounds were conducted remotely and anonymously to facilitate equal contribution of each participant. Blocks were considered twice in each round: for "orientation scanning" (the dynamic process of acquiring the final view) and for the "block view" (which visualizes the block site and is maintained for needle insertion/injection). Strong recommendations for inclusion were made if ≥75% of participants rated a structure as "definitely include" in any round. Weak recommendations were made if >50% of participants rated a structure as "definitely include" or "probably include" for all rounds (but the criterion for "strong recommendation" was never met). Thirty-six participants (94.7%) completed all rounds. 128 structures were reviewed; a "strong recommendation" is made for 35 structures on orientation scanning and 28 for the block view. A "weak recommendation" is made for 36 and 20 structures, respectively. This study provides recommendations on the core (minimum) set of anatomical structures to identify during ultrasound scanning for seven basic blocks in UGRA. They are intended to support consistent practice, empower non-experts using basic UGRA techniques, and standardize teaching and research., Competing Interests: Competing interests: AD, CL, EM, LFV-V, TV, and MW are members of the Executive Board of the European Society of Regional Anaesthesia & Pain Therapy (ESRA). NE, SK, SM, SN, and MAR are members of the Board of Directors of the American Society of Regional Anesthesia & Pain Medicine (ASRA). AG, NH, DFJ, RJK, AJRM, AP, MPS, AT, LT, SW, JW are members of the Board of Regional Anaesthesia UK (RAUK). WH-G is the Vice-President of the Royal College of Anaesthetists. JSB, DBSL, AJRM, DP & AT declare honoraria and/or research funding from Intelligent Ultrasound. JAN is a Senior Scientific Advisor for Intelligent Ultrasound Limited. AP declares consultancy fees for B Braun Medical UK and honoraria from GE Healthcare, Butterfly Net Inc, Sintetica UK Ltd, and Pacira., (© American Society of Regional Anesthesia & Pain Medicine 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: There is evidence that depression can be prevented; however, traditional approaches face significant scalability issues. Digital technologies provide a potential solution, although this has not been adequately tested. The aim of this study was to evaluate the effectiveness of a new smartphone app designed to reduce depression symptoms and subsequent incident depression amongst a large group of Australian workers., Methods: A randomized controlled trial was conducted with follow-up assessments at 5 weeks and 3 and 12 months post-baseline. Participants were employed Australians reporting no clinically significant depression. The intervention group (N = 1128) was allocated to use HeadGear, a smartphone app which included a 30-day behavioural activation and mindfulness intervention. The attention-control group (N = 1143) used an app which included a 30-day mood monitoring component. The primary outcome was the level of depressive symptomatology (PHQ-9) at 3-month follow-up. Analyses were conducted within an intention-to-treat framework using mixed modelling., Results: Those assigned to the HeadGear arm had fewer depressive symptoms over the course of the trial compared to those assigned to the control (F3,734.7 = 2.98, p = 0.031). Prevalence of depression over the 12-month period was 8.0% and 3.5% for controls and HeadGear recipients, respectively, with odds of depression caseness amongst the intervention group of 0.43 (p = 0.001, 95% CI 0.26-0.70)., Conclusions: This trial demonstrates that a smartphone app can reduce depression symptoms and potentially prevent incident depression caseness and such interventions may have a role in improving working population mental health. Some caution in interpretation is needed regarding the clinical significance due to small effect size and trial attrition.Trial Registration Australian and New Zealand Clinical Trials Registry (www.anzctr.org.au/) ACTRN12617000548336.

Spinal cord injuries (SCIs) are often the result of traumatic accidents, which also produce multiple other injuries (polytrauma). Nociceptive input from associated injuries has been shown to significantly impair recovery post-SCI. Historically, work in our laboratory has focused exclusively on male animals; however, increasing incidence of SCI in females requires research to determine whether pain (nociceptive) input poses the same risk to their recovery. Some animal studies have shown that females demonstrate greater tissue preservation and better locomotor recovery post-SCI. Given this, we examined the effect of sex on SCI recovery in two pain models-intermittent electrical stimulation (shock) to the tail or capsaicin injection to the hindpaw. Female rats received a lower thoracic contusion injury and were exposed to noxious stimulation the next day. The acute effect of noxious input on cardiovascular function, locomotor performance, and hemorrhage were assessed. Treatment with capsaicin or noxious electrical stimulation disrupted locomotor performance, increased blood pressure, and disrupted stepping. Additional experiments examined the long-term consequences of noxious input, demonstrating that both noxious electrical stimulation and capsaicin impair long-term recovery in female rats. Interestingly, injury had a greater effect on behavioral performance when progesterone and estrogen were low (metestrus). Conversely, nociceptive input led to a greater disruption in locomotor performance and produced a greater rise in blood pressure in animals injured during estrus., Competing Interests: No competing financial interests exist., (© Rachel E. Baine et al., 2022; Published by Mary Ann Liebert, Inc.)

Prior research shows that economic downturns are associated with increases in mental illness. However, we know little about whose mental health is most negatively affected. Is it the young or old, men or women, employed or non-employed, rich or poor? Using an 18-year panel dataset of Australians, we contribute to this understanding by estimating the impact of changes in unemployment on mental health, separately by population subgroups. Our mental health measure captures psychological distress and emotional difficulties, which are often missed by infrequent event indicators such as suicides. We find that young women suffer most during economic downturns. Men and women of older ages are not significantly affected. The effects for young women are driven by those in insecure employment, and those from low socioeconomic backgrounds. Our results suggest that public health programs should emphasize the mental health of young women during economic downturns., (© 2021 John Wiley & Sons Ltd.)

Mechanisms for sharing information in a disaster situation have drastically changed due to new technological innovations throughout the world. The use of social media applications and collaborative technologies for information sharing have become increasingly popular. With these advancements, the amount of data collected increases daily in different modalities, such as text, audio, video, and images. However, to date, practical Disaster Response (DR) activities are mostly depended on textual information, such as situation reports and email content, and the benefit of other media is often not realised. Deep Learning (DL) algorithms have recently demonstrated promising results in extracting knowledge from multiple modalities of data, but the use of DL approaches for DR tasks has thus far mostly been pursued in an academic context. This paper conducts a systematic review of 83 articles to identify the successes, current and future challenges, and opportunities in using DL for DR tasks. Our analysis is centred around the components of learning, a set of aspects that govern the application of Machine learning (ML) for a given problem domain. A flowchart and guidance for future research are developed as an outcome of the analysis to ensure the benefits of DL for DR activities are utilized., (© The Author(s), under exclusive licence to Springer Nature Singapore Pte Ltd 2021.)

Background: The introduction of developmentally adapted criteria for posttraumatic stress disorder (PTSD) has improved the identification of ≤6-year-old children with clinical needs. Across two studies, we assess predictors of the development of PTSD in young children (PTSD-YC), including the adult-led acute stress disorder (ASD) diagnosis, and provide proof of principle for cognitive-focused therapy for this age range, with the aim of increasing treatment options for children diagnosed with PTSD-YC., Method: Study 1 (N = 105) assessed ASD and PTSD-YC diagnosis in 3- to 8-year-old children within one month and at around three months following attendance at an emergency room. Study 2 (N = 37) was a preregistered (www.isrctn.com/ISRCTN35018680) randomized controlled early-phase trial comparing CBT-3M, a cognitive-focused intervention, to treatment-as-usual (TAU) delivered within the UK NHS to 3- to 8-year-olds diagnosed with PTSD-YC., Results: In Study 1, the ASD diagnosis failed to identify any young children. In contrast, prevalence of acute PTSD-YC (minus the duration requirement) was 8.6% in the first month post-trauma and 10.1% at 3 months. Length of hospital stay, but no other demographic or trauma-related characteristics, predicted development of later PTSD-YC. Early (within one month) diagnosis of acute PTSD-YC had a positive predictive value of 50% for later PTSD-YC. In Study 2, most children lost their PTSD-YC diagnosis following completion of CBT-3M (84.6%) relative to TAU (6.7%) and CBT-3M was acceptable to recipient families. Effect sizes were also in favor of CBT-3M for secondary outcome measures., Conclusions: The ASD diagnosis is not fit for purpose in this age-group. There was a strong and encouraging signal of putative efficacy for young children treated using a cognitive-focused treatment for PTSD, and a larger trial of CBT-3M is now warranted., (© 2021 The Authors. Journal of Child Psychology and Psychiatry published by John Wiley & Sons Ltd on behalf of Association for Child and Adolescent Mental Health.)

Enhancing population resilience to adverse events is now a policy priority. Accordingly, there have been calls for more evidence on the determinants of resilience. We answer this call by identifying financial and non-financial resources associated with psychological resilience during the COVID-19 pandemic. Using longitudinal survey data, psychological resilience is measured by comparing distress reported pre-COVID-19 with distress reported during the outbreak and initial lockdown in April 2020. Methodologically, we compare differences in resilience and resources between people with identical gender, ethnicity, health, parenthood status, education, employment status, and region of residence (all measured pre-2020). We also provide estimates from within-household comparisons. Surprisingly, income, savings, and debt levels did not affect the likelihood of psychologically resilient outcomes. Cognitive ability, religiosity, and neighborhood social capital also had no protective effect. In contrast, we find robust evidence that non-cognitive skills, measured by self-efficacy, strongly protected against psychological distress. Self-efficacy also dampened the increase in distress caused by large earnings shocks. These findings support investments in non-cognitive skills that modify the damage-function from adverse events., (© 2021 John Wiley & Sons Ltd.)

Nociceptive input diminishes recovery and increases lesion area after a spinal cord injury (SCI). Recent work has linked these effects to the expansion of hemorrhage at the site of injury. The current article examines whether these adverse effects are linked to a pain-induced rise in blood pressure (BP) and/or flow. Male rats with a low-thoracic SCI were treated with noxious input (electrical stimulation [shock] or capsaicin) soon after injury. Locomotor recovery and BP were assessed throughout. Tissues were collected 3 h, 24 h, or 21 days later. Both electrical stimulation and capsaicin undermined locomotor function and increased the area of hemorrhage. Changes in BP/flow varied depending on type of noxious input, with only shock producing changes in BP. Providing behavioral control over the termination of noxious stimulation attenuated the rise in BP and hemorrhage. Pretreatment with the α-1 adrenergic receptor inverse agonist, prazosin, reduced the stimulation-induced rise in BP and hemorrhage. Prazosin also attenuated the adverse effect that noxious stimulation has on long-term recovery. Administration of the adrenergic agonist, norepinephrine 1 day after injury induced an increase in BP and disrupted locomotor function, but had little effect on hemorrhage. Further, inducing a rise in BP/flow using norepinephrine undermined long-term recovery and increased tissue loss. Mediational analyses suggest that the pain-induced rise in blood flow may foster hemorrhage after SCI. Increased BP appears to act through an independent process to adversely affect locomotor performance, tissue sparing, and long-term recovery.

Responding to emergencies requires many different individuals and organisations to work well together under extraordinary circumstances. Unfortunately, the management of animal welfare in emergencies remains largely disconnected from emergency management overall. This is due predominately to professional silos and a failure to understand the importance of human-animal-environment (h-a-e) interdependencies. One Welfare (OW) is a concept with these interrelationships at its core. This paper argues that by adopting an OW framework it will be possible to achieve a transdisciplinary approach to emergency management in which all stakeholders acknowledge the importance of the h-a-e interdependencies and work to implement a framework to support this. Acknowledging that such a transformational change will not be easy, this paper proposes several strategies to overcome the challenges and optimise the outcomes for animal welfare emergency management (AWEM). These include legislation and policy changes including h-a-e interface interactions as business as usual, improving knowledge through interprofessional education and training, incorporating One Welfare champions, and recognising the role of animals as vital conduits into communities.

SrMn 2 P 2 and CaMn 2 P 2 are insulators that adopt the trigonal CaAl 2 Si 2 -type structure containing corrugated Mn honeycomb layers. Magnetic susceptibility χ and heat capacity versus temperature T data reveal a weak first-order antiferromagnetic (AFM) transition at the Néel temperature [Formula: see text] K for SrMn 2 P 2 and a strong first-order AFM transition at [Formula: see text] K for CaMn 2 P 2 Both compounds exhibit isotropic and nearly T -independent [Formula: see text], suggesting magnetic structures in which nearest-neighbor moments are aligned at [Formula: see text] to each other. The 31 P NMR measurements confirm the strong first-order transition in CaMn 2 P 2 but show critical slowing down above [Formula: see text] for SrMn 2 P 2 , thus also evidencing second-order character. The 31 P NMR measurements indicate that the AFM structure of CaMn 2 P 2 is commensurate with the lattice whereas that of SrMn 2 P 2 is incommensurate. These first-order AFM transitions are unique among the class of (Ca, Sr, Ba)Mn 2 (P, As, Sb, Bi) 2 compounds that otherwise exhibit second-order AFM transitions. This result challenges our understanding of the circumstances under which first-order AFM transitions occur., Competing Interests: The authors declare no competing interest.

Baleen whales influence their ecosystems through immense prey consumption and nutrient recycling 1-3 . It is difficult to accurately gauge the magnitude of their current or historic ecosystem role without measuring feeding rates and prey consumed. To date, prey consumption of the largest species has been estimated using metabolic models 3-9 based on extrapolations that lack empirical validation. Here, we used tags deployed on seven baleen whale (Mysticeti) species (n = 321 tag deployments) in conjunction with acoustic measurements of prey density to calculate prey consumption at daily to annual scales from the Atlantic, Pacific, and Southern Oceans. Our results suggest that previous studies 3-9 have underestimated baleen whale prey consumption by threefold or more in some ecosystems. In the Southern Ocean alone, we calculate that pre-whaling populations of mysticetes annually consumed 430 million tonnes of Antarctic krill (Euphausia superba), twice the current estimated total biomass of E. superba 10 , and more than twice the global catch of marine fisheries today 11 . Larger whale populations may have supported higher productivity in large marine regions through enhanced nutrient recycling: our findings suggest mysticetes recycled 1.2 × 10 4  tonnes iron yr -1 in the Southern Ocean before whaling compared to 1.2 × 10 3  tonnes iron yr -1 recycled by whales today. The recovery of baleen whales and their nutrient recycling services 2,3,7 could augment productivity and restore ecosystem function lost during 20th century whaling 12,13 ., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: The intense interactions between people, animals and environmental systems in urban informal settlements compromise human and environmental health. Inadequate water and sanitation services, compounded by exposure to flooding and climate change risks, expose inhabitants to environmental contamination causing poor health and wellbeing and degrading ecosystems. However, the exact nature and full scope of risks and exposure pathways between human health and the environment in informal settlements are uncertain. Existing models are limited to microbiological linkages related to faecal-oral exposures at the individual level, and do not account for a broader range of human-environmental variables and interactions that affect population health and wellbeing., Methods: We undertook a 12-month health and environmental assessment in 12 flood-prone informal settlements in Makassar, Indonesia. We obtained caregiver-reported health data, anthropometric measurements, stool and blood samples from children < 5 years, and health and wellbeing data for children 5-14 years and adult respondents. We collected environmental data including temperature, mosquito and rat species abundance, and water and sediment samples. Demographic, built environment and household asset data were also collected. We combined our data with existing literature to generate a novel planetary health model of health and environment in informal settlements., Results: Across the 12 settlements, 593 households and 2764 participants were enrolled. Two-thirds (64·1%) of all houses (26·3-82·7% per settlement) had formal land tenure documentation. Cough, fever and diarrhoea in the week prior to the survey were reported among an average of 34.3%, 26.9% and 9.7% of children aged < 5 years, respectively; although proportions varied over time, prevalence among these youngest children was consistently higher than among children 5-14 years or adult respondents. Among children < 5 years, 44·3% experienced stunting, 41·1% underweight, 12.4% wasting, and 26.5% were anaemic. There was self- or carer-reported poor mental health among 16.6% of children aged 5-14 years and 13.9% of adult respondents. Rates of potential risky exposures from swimming in waterways, eating uncooked produce, and eating soil or dirt were high, as were exposures to flooding and livestock. Just over one third of households (35.3%) had access to municipal water, and contamination of well water with E. coli and nitrogen species was common. Most (79·5%) houses had an in-house toilet, but no houses were connected to a piped sewer network or safe, properly constructed septic tank. Median monthly settlement outdoor temperatures ranged from 26·2 °C to 29.3 °C, and were on average, 1·1 °C warmer inside houses than outside. Mosquito density varied over time, with Culex quinquefasciatus accounting for 94·7% of species. Framed by a planetary health lens, our model includes four thematic domains: (1) the physical/built environment; (2) the ecological environment; (3) human health; and (4) socio-economic wellbeing, and is structured at individual, household, settlement, and city/beyond spatial scales., Conclusions: Our planetary health model includes key risk factors and faecal-oral exposure pathways but extends beyond conventional microbiological faecal-oral enteropathogen exposure pathways to comprehensively account for a wider range of variables affecting health in urban informal settlements. It includes broader ecological interconnections and planetary health-related variables at the household, settlement and city levels. It proposes a composite framework of markers to assess water and sanitation challenges and flood risks in urban informal settlements for optimal design and monitoring of interventions., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The mouse preimplantation embryo is sensitive to its environment, including maternal dietary protein restriction, which can alter the developmental programme and affect lifetime health. Previously, we have shown maternal low-protein diet (LPD) causes a reduction in blastocyst mTORC1 signalling coinciding with reduced availability of branched-chain amino acids (BCAAs) in surrounding uterine fluid. BCAA deficiency leads to increased endocytosis and lysosome biogenesis in blastocyst trophectoderm (TE), a response to promote compensatory histotrophic nutrition. Here, we first investigated the induction mechanism by individual variation in BCAA deficiency in an in vitro quantitative model of TE responsiveness. We found isoleucine (ILE) deficiency as the most effective activator of TE endocytosis and lysosome biogenesis, with less potent roles for other BCAAs and insulin; cell volume was also influential. TE response to low ILE included upregulation of vesicles comprising megalin receptor and cathepsin-B, and the response was activated from blastocyst formation. Secondly, we identified the transcription factor TFEB as mediating the histotrophic response by translocation from cytoplasm to nucleus during ILE deficiency and in response to mTORC1 inhibition. Lastly, we investigated whether a similar mechanism responsive to maternal nutritional status was found in human blastocysts. Blastocysts from women with high body-mass index, but not the method of fertilisation, revealed stimulated lysosome biogenesis and TFEB nuclear migration. We propose TE lysosomal phenotype as an early biomarker of environmental nutrient stress that may associate with long-term health outcomes.

Microglia are the brain immune cells and their function is highly dependent on cell motility. It was hypothesised that morphological variability leads to differences in motility, ultimately impacting on the microglial function. Here, we assessed microglial morphology in 32 controls, 44 Alzheimer's disease (AD) cases and 16 AD cases from patients immunised against Aβ42 (iAD) using 2D and 3D approaches. Our 2D assessment showed an increased number of microglia in iAD vs. AD (P = 0.032) and controls (P = 0.018). Ramified microglia were fewer in AD vs. controls (P = 0.041) but increased in iAD compared to AD (P < 0.001) and controls (P = 0.006). 3D reconstructions highlighted larger cell bodies in AD vs. controls (P = 0.049) and increased total process length in iAD vs. AD (P = 0.032), with negative correlations detected for pan-Aβ load with total process length (P < 0.001) in AD and number of primary processes (P = 0.043) in iAD. In summary, reactive/amoeboid microglia are the most represented population in the aged human brain. AD does not affect the number of microglia, but the ramified population is decreased adopting a more reactive morphology. Aβ removal by immunotherapy leads to increased ramified microglia, implying that the cells retain plasticity in an aged disease brain meriting further investigation., (© 2021. The Author(s).)

Background: The extent of intergenerational transmission of child maltreatment is unclear due to methodological limitations in previous studies. In this study, we aimed to examine factors associated with intergenerational transmission of child maltreatment and quantify its extent in a population sample over a 30-year period in South Australia., Methods: In this retrospective cohort study, we used linked administrative data from the South Australian Birth Registry to identify dyads of mothers and their children both born in South Australia between July 1, 1986, and June 30, 2017. Three child protection system (CPS) outcomes (any CPS involvement, substantiated maltreatment, and time spent in out-of-home care) were computed from data obtained from the South Australian Department for Child Protection. Multivariable Cox regression models were used to estimate hazard ratios (HRs) for child CPS outcomes according to their mother's CPS exposure., Findings: 38 556 unique mother-child dyads were included. 458 (2·0%) of 23 437 children whose mothers had no CPS involvement in childhood had a substantiated report of maltreatment and 127 (0·5%) spent time in out-of-home care. By comparison, 970 (22·1%) of 4382 children whose mothers experienced substantiated maltreatment in childhood had substantiated maltreatment and 469 (10·7%) spent time in out-of-home care. After adjusting for potential confounders, children of mothers with any CPS involvement in childhood had an increased risk of CPS contact compared with children whose mothers had no CPS involvement; this risk was greatest for children of mothers who had both substantiated maltreatment and spent time in out-of-home care (HR 6·25 [95% CI 5·59-6·98] for any CPS involvement, 13·69 [10·08-16·92] for substantiated maltreatment, and 25·78 [18·23-36·45] for any time in out-of-home care). Risks of child CPS outcomes were substantially increased for children of mothers who had a first CPS notification under the age of 1 year or who had any CPS notification at age 13-17 years., Interpretation: Children are at high risk of maltreatment if their mother experienced maltreatment as a child. Assisting survivors of childhood maltreatment, particularly female survivors, provides a crucial intervention opportunity to help prevent further child abuse and neglect., Funding: Australian National Health and Medical Research Council; Channel 7 Children's Research Foundation., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Monoclonal antibodies (mAb) and natural ligands targeting costimulatory tumor necrosis factor receptors (TNFR) exhibit a wide range of agonistic activities and antitumor responses. The mechanisms underlying these differential agonistic activities remain poorly understood. Here, we employ a panel of experimental and clinically-relevant molecules targeting human CD40, 4-1BB and OX40 to examine this issue. Confocal and STORM microscopy reveal that strongly agonistic reagents induce clusters characterized by small area and high receptor density. Using antibody pairs differing only in isotype we show that hIgG2 confers significantly more receptor clustering than hIgG1 across all three receptors, explaining its greater agonistic activity, with receptor clustering shielding the receptor-agonist complex from further molecular access. Nevertheless, discrete receptor clustering patterns are observed with different hIgG2 mAb, with a unique rod-shaped assembly observed with the most agonistic mAb. These findings dispel the notion that larger receptor clusters elicit greater agonism, and instead point to receptor density and subsequent super-structure as key determinants.