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Abstract The seafloor plays a vital role in Earth's climate by storing carbon. However, human activities that disturb the seafloor undermine this function and receive little regulatory attention. This oversight is often due to a lack of empirical data linked to low sampling resolution of the heterogeneous seafloor, highlighting the need for a simple, fast, reproducible quantification approach. We address this gap by presenting a simple sediment resuspension assay that allows highly replicated sampling of heterogeneous sediments, quantifying the immediate impact on organic carbon mineralization. It is based on biochemical oxygen demand and compares sediment oxygen demand between undisturbed sediment cores and those subjected to resuspension, estimating resuspension‐induced CO₂ production. Oxygen demand in the resuspension treatment was 2.4–13.4 times higher than in the undisturbed cores, resulting in resuspension‐induced CO₂ production of 210–2064 μmol CO₂ m−2 h−1. This immediate resuspension effect on organic carbon mineralization suggests a substantial impact on organic C stocks that could otherwise contribute to carbon sequestration. Our assay is notable for its simplicity and accessibility. It offers a critical step towards a more accurate large‐scale assessment of sediment resuspension impacts across the heterogeneous seafloor, evaluating its vulnerability to disturbance and the role of demersal fishing in exacerbating climate change.

Abstract Introduction This study sought to describe treatment patterns, persistence, and effectiveness of upadacitinib (UPA) alone and compared to other Janus kinase inhibitors (JAKis) or tumor necrosis factor inhibitors (TNFis) in patients with rheumatoid arthritis (RA). Methods This retrospective, non-interventional study used the OPAL dataset, derived from electronic medical records. Patients initiated UPA (N = 2624), other JAKis (baricitinib and tofacitinib [N = 925]), or TNFis (adalimumab, etanercept, certolizumab, golimumab, infliximab [N = 3540]) between May 2020 and March 2023. Median persistence (Kaplan–Meier) and effectiveness (Disease Activity Score 28-joint C-reactive protein, three variables [DAS28CRP{3}]) were evaluated for UPA-treated patients and in three propensity score-matched cohorts: UPA monotherapy versus combination therapy, UPA versus other JAKis, and UPA versus TNFis. Results In patients prescribed UPA, 41.3% were ≥ 65 years old, 33.8% were prescribed as first-line advanced therapy, and 27.2% were prescribed monotherapy. Persistence on UPA was 26.6 months (95% confidence intervals: 24.4, 29.9) and longest in earlier lines of therapy. The DAS28CRP(3) remission rate was 73% at 3 months, with improvements observed across lines of therapy. UPA monotherapy and combination therapy had similar persistence (27.8 [23.5, 33.4] versus 30.4 months [22.1, 35.3], p = 0.84) and effectiveness. UPA showed longer persistence than other JAKis (28.8 [25.6, 32.4] versus 17.2 months [14.9, 19.8], p

Abstract Background We evaluated the feasibility, safety, and efficacy of a 2D-planar robot for minimally supervised home-based upper-limb therapy for post-stroke hemiparesis. Methods The H-Man, end effector robot, combined with web-based software application for remote tele-monitoring were evaluated at homes of participants. Inclusion criteria were: strokes > 28 days, Fugl-Meyer Motor Assessment (FMA) > 10-60/66, presence of a carer and absence of medical contraindications. Participants performed self-directed, minimally supervised robotics-assisted therapy (RAT) at home for 30 consecutive days, after 2 therapist-supervised clinic on-boarding sessions. Web-based compliance measures were: accessed sessions of > 20 min/day, training minutes/day and active training hours/30 days. Clinical outcomes at weeks 0, 5 (post-training), 12 and 24 (follow-up) consisted of FMA, Action Research Arm Test (ARAT) and WHO-Stroke Specific Quality of Life (SSQOL). To estimate immediate economic benefits of the home-based robotic therapy, we performed cost-effectiveness analysis (CEA), followed by budget impact analysis (BIA). Results Altogether, all 12 participants completed Home-RAT without adverse events; 9 (75.0%) were males, mean (SD) age, 59.4 years (9.5), median (IQR) stroke duration 38.6 weeks (25.4, 79.6) baseline FMA (0–66) 42.1 ± 13.2, ARAT (0–57) 25.4 ± 19.5, SSQOL (0–245) 185.3 ± 32.8. At week 5 follow-up, mean (SD) accessed days were 26.3 days ± 6.4, active training hours of 35.3 h ± 14.7/30 days, or ~ 6 days/week and 77 training minutes ± 20.9/day were observed. Significant gains were observed from baseline across time; ΔFMA 2.4 at week 5 (FMA 44.5, CI 95% 39.7–49.3, p

Abstract Background To explore perspectives of work readiness, including readiness to work rurally, among health students trained in Australia during the COVID-19 pandemic. Methods Participants were allied health, medicine, and nursing students in the later years of their degree (third, fourth or final year of an undergraduate entry to practice degree, or second year of postgraduate entry to practice degree), where training is clinically immersive. These students had completed a University Department of Rural Health facilitated rural and remote placement between January 2021 and October 2022. They participated in a cross-sectional online survey (n = 426), comprising Likert-scale questions. Interested survey respondents participated in a semi-structured interview (n = 34). Multiple logistic regression was conducted to examine the predictors of work readiness within the survey, and interview data was analysed via reflexive thematic analysis. Results Among survey respondents, 69.7% felt they would be ready to be a health practitioner when the time came to graduate and 71.8% felt clinically prepared to work in a rural location. Concerns about having developed enough clinical skills on placements to competently practice on graduation and being able to continue studying their course during the pandemic were both predictive of work readiness and feeling clinically prepared to work rurally. Four themes reflecting factors impacting work readiness were developed from interview data: (1) ‘I’d estimate probably a 20–30% reduction in face-to-face handling practice over the course of all of my placements’ encompassed student concerns regarding the collective impact of cancelled placements and lower patient attendance at healthcare facilities on clinical skill development; (2) ‘Two and a half years of sitting behind a computer’ related to student experiences of superficial learning and cohort disconnectedness due to online course delivery and loss of on campus simulations; (3) ‘I’ll still need like a lot of support in my grad year’ related to students recognising the need for support and supervision post-qualifying to bridge the gaps in their learning; and (4) ‘We are the COVID nurses’ encompassed student recognition of skills gained including communication skills, competence with technology and telehealth, knowledge of infection control, and work readiness skills (e.g. adaptability and resilience) as a result of training during the global pandemic. Conclusions Universities can support work readiness during pandemic circumstances by fostering clinical skills development through continuation of quality placement experiences and face-to-face curriculum delivery. Although health graduates trained during the pandemic are likely to have a range of additional work ready skills, health services will need to proactively support their transition into the workforce in the coming years.

Abstract Background Anaemia during pregnancy is common worldwide. In Australia, approximately 17% of non-pregnant women of reproductive age have anaemia, increasing to a rate of 25% in pregnant women. This study sought to determine the rate of screening for anaemia in pregnancy in regional New South Wales, and to determine whether screening and treatment protocols followed the recommended guidelines. Methods This retrospective study reviewed antenatal and postnatal (48 h) data of women (n = 150) who had a live birth at Bathurst Hospital between 01/01/2020 and 30/04/2020. Demographic data, risk factors for anaemia in pregnancy, antenatal bloods, treatments provided in trimesters one (T1), two (T2) and three (T3), and postpartum complications were recorded. These were compared to the Australian Red Cross Guidelines (ARCG) using descriptive statistics. Results Of the women with screening data available (n = 103), they were mostly aged 20-35yrs (79.6%), 23.3% were obese, 97.1% were iron deficient, 17% were anaemic and only a few (5.3%) completed the full pregnancy screening as recommended by the ARCG while a majority completed only partial screenings specifically Hb levels in T1 (56.7%), T2 (44.7%) and T3 (36.6%). Compliance to oral iron was largely undocumented, but constipation was a common side effect among the women. IV iron was administered in 14.0% of women, approximately 1.75x higher than the recommended rate. Conclusions This study provided useful information about compliance to screening and treatment guidelines for anaemia in pregnancy. We identified the need for improved documentation and communication between various health providers to ensure adequate antenatal care to prevent maternal complications during pregnancy. This will improve patient care and encourage further developments in maternal care, bridging the rural health gap.

Abstract This study addresses the effect of using animal excreta on the nutritional content of forages, focusing on macro- and micro-element concentrations (nitrogen; N, phosphorus; P, sulphur; S, copper; Cu, zinc; Zn, manganese; Mn, selenium; Se) from animal feed to excreta, soil, and plants. Data were collected from pot and field trials using separate applications of sheep or cattle urine and faeces. Key findings indicate that soil organic carbon (SOC) and the type of excreta significantly influences nutrient uptake by forages, with varied responses among the seven elements defined above. Although urine contributes fewer micronutrients compared to faeces (as applied at a natural volume/mass basis, respectively), it notably improves forage yield and micronutrient accumulation, thus potentially delivering positive consequences at the farm level regarding economic performance and soil fertility when swards upon clayey soil types receive said urine in temperate agro-climatic regions (i.e., South West England in the current context). In contrast, faeces application in isolation hinders Se and Mn uptake, once again potentially delivering unintended consequences such as micronutrient deficiencies in areas of high faeces deposition. As it is unlikely that (b)ovine grazing fields will receive either urine or faeces in isolation, we also explored combined applications of both excreta types which demonstrates synergistic effects on N, Cu, and Zn uptake, with either synergistic or dilution effects being observed for P and S, depending largely on SOC levels. Additionally, interactions between excreta types can result in dilution or antagonistic effects on Mn and Se uptake. Notably, high SOC combined with faeces reduces Mn and Se in forages, raising concerns for grazed ruminant systems under certain biotic situations, e.g., due to insufficient soil Se levels typically observed in UK pastures for livestock growth. These findings underscore the importance of considering SOC and excreta nutritional composition when designing forage management to optimize nutrient uptake. It should be noted that these findings have potential ramifications for broader studies of sustainable agriculture through system-scale analyses, as the granularity of results reported herein elucidate gaps in knowledge which could affect, both positively and negatively, the interpretation of model-based environmental impact assessments of cattle and sheep production (e.g., in the case of increased yields [beneficial] or the requirement of additional synthetic supplementation [detrimental]).

The purpose of this scoping review was to map the literature on the relationship between cultural continuity and health among Métis people as well as how this knowledge could be translated into cancer prevention initiatives. We included any Métis-specific literature evaluating connections between culture, health, and well-being. We conducted electronic searches of Medline, PubMed, Embase, PsychInfo, I-Portal, and hand-searched journals, and reviewed the grey literature. Based on our inclusion criteria, articles were screened and assessed for eligibility, resulting in a sample of 22 publications. Qualitative, quantitative, and mixed methods designs were considered. The 22 publications included in this review were diverse, ranging from population-based studies to reports and news articles. There were no limitations to publication year, and most of the data presented in this review were published more than five years ago. Nevertheless, the results demonstrate the potential role of Métis cultural continuity in cancer prevention. The scoping review revealed the current lack of Métis-specific data regarding health and its intersectionality with culture. However, the existing literature indicates that cultural continuity for Métis appears to influence health and well-being positively. As such, there may be benefits to incorporating cultural continuity in cancer prevention efforts.

Objectives Research to develop early screening tools to determine an individual’s risk of developing adult-onset disease is a growing field. Expectant parents may find themselves with an option in the future to undergo screening to determine not only genetic abnormalities in their child but also their risk of developing adult-onset non-communicable diseases (NCD) such as hypertension, obesity or hypercholesterolaemia. To ensure acceptability and feasibility of new screening tools researchers must work in partnership with healthcare consumers to discern consumers’ current understanding and acceptance of these technologies in research and the potential for clinical applications. We sought to engage with healthcare consumers to develop a consensus, using a modified Delphi study design, for the acceptability of (1) screening tools for use within pregnancy that would indicate a child’s risk for developing NCD, and (2) targeted early interventions for those identified at a higher risk of developing NCD using precision medicine approaches. The acceptability of future research design and conduct as well as the implications for implementation into routine healthcare were discussed. In addition, participants were asked to rank the non-communicable diseases they believed were of most importance for precision medicine research focus, in line with recent calls for better involvement of healthcare consumers in setting research questions and defining priority areas.Design A modified two-stage Delphi study design including an in-person consumer workshop (stage 1) and online follow-up survey (stage 2), was used to evaluate consumer consensus for research to develop precision medicine tools for early detection and potential intervention to reduce onset of NCDs. The acceptability of research design and conduct and future implications for the implementation of newly developed tools into routine healthcare was also addressed.Setting and participants We engaged 76 healthcare consumers in 2020, in the Hunter New England Region, New South Wales, Australia. Participants were recruited from existing healthcare consumer organisations, research programmes and healthcare networks through purposeful selection, with a focus on participants having a broad range of experiences and backgrounds to ensure adequate representativeness.Results and conclusions Our findings indicate the majority (98%) of participants in our study believe early screening for risk of NCD in their children was acceptable, provided it was equitable and clear pathways for referral and support were available.

BackgroundPostpartum anxiety and depression are common in new parents. While effective interventions exist, they are often delivered in person, which can be a barrier for some parents seeking help. One approach to overcoming these barriers is the delivery of evidence-based self-help interventions via websites, smartphone apps, and other digital media. ObjectiveThis study aims to evaluate the effectiveness of technology-based distal interventions in reducing or preventing symptoms of postpartum depression or anxiety in male and female birth and adoptive parents, explore the effectiveness of technology-based distal interventions in increasing social ties, and determine the level of adherence to and satisfaction with technology-based distal interventions. MethodsA systematic review and series of meta-analyses were conducted. Three electronic bibliographic databases (PsycINFO, PubMed, and Cochrane Library) were searched for randomized controlled trials evaluating technology-based distal interventions for postpartum depression or anxiety in birth and adoptive parents. Searches were updated on August 1, 2023, before conducting the final meta-analyses. Data on trial characteristics, effectiveness, adherence, satisfaction, and quality were extracted. Screening and data extraction were conducted by 2 reviewers. Risk of bias was assessed using the Joanna Briggs Institute quality rating scale for randomized controlled trials. Studies were initially synthesized qualitatively. Where possible, studies were also quantitatively synthesized through 5 meta-analyses. ResultsOverall, 18 articles met the inclusion criteria for the systematic review, with 14 (78%) providing sufficient data for a meta-analysis. A small significant between-group effect on depression favored the intervention conditions at the postintervention (Cohen d=–0.28, 95% CI –0.41 to –0.15; P

BackgroundResearch in the developmental origins of health and disease provides compelling evidence that adverse events during the first 1000 days of life from conception can impact life course health. Despite many decades of research, we still lack a complete understanding of the mechanisms underlying some of these associations. The Newcastle 1000 Study (NEW1000) is a comprehensive, prospective population-based pregnancy cohort study based in Newcastle, New South Wales, Australia, that will recruit pregnant women and their partners at 11-14 weeks’ gestation, with assessments at 20, 28, and 36 weeks; birth; 6 weeks; and 6 months, in order to provide detailed data about the first 1000 days of life to investigate the developmental origins of noncommunicable diseases. ObjectiveThe study aims to provide a longitudinal multisystem approach to phenotyping, supported by robust clinical data and collection of biological samples in NEW1000. MethodsThis manuscript describes in detail the large variety of samples collected in the study and the method of collection, storage, and utility of the samples in the biobank, with a particular focus on incorporation of the samples into emerging and novel large-scale “-omics” platforms, including the genome, microbiome, epigenome, transcriptome, fragmentome, metabolome, proteome, exposome, and cell-free DNA and RNA. Specifically, this manuscript details the methods used to collect, process, and store biological samples, including maternal, paternal, and fetal blood, microbiome (stool, skin, vaginal, oral), urine, saliva, hair, toenail, placenta, colostrum, and breastmilk. ResultsRecruitment for the study began in March 2021. As of July 2024, 1040 women and 684 partners were enrolled, with 922 infants born. The NEW1000 biobank contains 24,357 plasma aliquots from ethylenediaminetetraacetic acid (EDTA) tubes, 5284 buffy coat aliquots, 4000 plasma aliquots from lithium heparin tubes, 15,884 blood serum aliquots, 2977 PAX RNA tubes, 26,595 urine sample aliquots, 2280 fecal swabs, 17,687 microbiome swabs, 2356 saliva sample aliquots, 1195 breastmilk sample aliquots, 4007 placental tissue aliquots, 2680 hair samples, and 2193 nail samples. ConclusionsNEW1000 will generate a multigenerational, deeply phenotyped cohort with a comprehensive biobank of samples relevant to a large variety of analyses, including multiple -omics platforms. International Registered Report Identifier (IRRID)DERR1-10.2196/63562

Summary: Transport through the nuclear pore complex (NPC) relies on intrinsically disordered FG-nucleoporins (FG-Nups) forming a selective barrier. Away from the NPC, FG-Nups readily form condensates and aggregates, and we address how this behavior is surveilled in cells. FG-Nups, including Nsp1, together with the nuclear transport receptor Kap95, form a native daughter cell-specific cytosolic condensate in yeast. In aged cells, this condensate disappears as cytosolic Nsp1 levels decline. Biochemical assays and modeling show that Nsp1 is a modulator of FG-Nup condensates, promoting a liquid-like state. Nsp1’s presence in the cytosol and condensates is critical, as a reduction of cytosolic levels in young cells induces NPC defects and a general decline in protein quality control that quantitatively mimics aging phenotypes. These phenotypes can be rescued by a cytosolic form of Nsp1. We conclude that Nsp1 is a phase state regulator that surveils FG-Nups and impacts general protein homeostasis.

IntroductionWe report the partial regression of metastatic squamous cell carcinoma (SCC) after reduction of long-term azathioprine therapy while awaiting surgery. The patient was a 69-year-old man with a history of kidney transplantation. Moderately differentiated SCC arising in the anterior neck was initially diagnosed, followed later by poorly differentiated SCC metastases to cervical lymph nodes. Lymph node clearance was performed 28 days after a reduction in azathioprine dosage. The palpable lymph node lesion had noticeably decreased in size at the time of surgery, and subsequent histology only detected 7mm and 0.2mm deposits of poorly differentiated SCC in 2 of 5 level I nodes, and a further 10 reactive nodes from levels II and III. One positive level I and another benign level II/III node, demonstrated necrosis, histiocytic infiltration and fibrosis, interpreted as features of regression. Hence, we investigated the role of immune cells in the partial regression of metastatic SCC after reduction of long-term azathioprine therapy while awaiting surgery.MethodsMultispectral immunohistochemistry using custom markers was performed on regions of interest of excised cervical lymph nodes, encompassing the entire SCC deposit and the surrounding adjacent stroma to quantify to number and types of immune cells present.ResultsMultispectral immunohistochemistry revealed the heavy infiltration of activated T cells in the tumour, as well as PD-L1+ antigen-presenting cells in the surrounding adjacent stroma, suggesting an immunologically mediated partial regression.DiscussionWe hypothesize that this reaction was triggered by azathioprine dose reduction. Dose modification of long-term immunosuppressive medications in patients with a transplantation history who later develop SCCs warrants further investigation.

Abstract Microtransactions provide optional, virtual, video game goods that, for an additional cost to the player, provide additional game content and alter the gameplay experience. Loot boxes—a specific form of microtransaction—offer randomised rewards in exchange for payment, and are argued to be structurally and psychologically similar to gambling. Nascent research suggests that a link exists between autism and both problematic gaming and problematic gambling. Here, we investigated the relationships between autistic characteristics and experiences, and excessive video gaming and microtransaction expenditure. A sample of 1178 adults from Australia, Aotearoa, and The United States were recruited from Prolific Academic, and completed a survey measuring in-game expenditure, autistic characteristics and experiences, problematic gaming, problematic gambling, and risky loot box use. Analyses showed positive associations between autistic characteristics and experiences with problematic gaming and problem gambling symptomatology. However, results also showed a small, negative association between autistic characteristics and experiences and spending on loot boxes when problem gambling symptoms, problematic gaming, and risky loot box use were statistically controlled for. These results suggest that autistic gamers may be vulnerable to problematic gaming and gambling, but that this effect does not extend to the purchasing of microtransactions.

Abstract Globe-LFMC 2.0, an updated version of Globe-LFMC, is a comprehensive dataset of over 280,000 Live Fuel Moisture Content (LFMC) measurements. These measurements were gathered through field campaigns conducted in 15 countries spanning 47 years. In contrast to its prior version, Globe-LFMC 2.0 incorporates over 120,000 additional data entries, introduces more than 800 new sampling sites, and comprises LFMC values obtained from samples collected until the calendar year 2023. Each entry within the dataset provides essential information, including date, geographical coordinates, plant species, functional type, and, where available, topographical details. Moreover, the dataset encompasses insights into the sampling and weighing procedures, as well as information about land cover type and meteorological conditions at the time and location of each sampling event. Globe-LFMC 2.0 can facilitate advanced LFMC research, supporting studies on wildfire behaviour, physiological traits, ecological dynamics, and land surface modelling, whether remote sensing-based or otherwise. This dataset represents a valuable resource for researchers exploring the diverse LFMC aspects, contributing to the broader field of environmental and ecological research.

Abstract Tor is widely used for staying anonymous online and accessing onion websites; unfortunately, Tor is popular for distributing and viewing illicit child sexual abuse material (CSAM). From 2018 to 2023, we analyse 176,683 onion domains and find that one-fifth share CSAM. We find that CSAM is easily available using 21 out of the 26 most-used Tor search engines. We analyse 110,133,715 search sessions from the Ahmia.fi search engine and discover that 11.1% seek CSAM. When searching CSAM by age, 40.5% search for 11-year-olds and younger; 11.0% for 12-year-olds; 8.2% for 13-year-olds; 11.6% for 14-year-olds; 10.9% for 15-year-olds; and 12.7% for 16-year-olds. We demonstrate accurate filtering for search engines, introduce intervention, show a questionnaire for CSAM users, and analyse 11,470 responses. 65.3% of CSAM users first saw the material when they were children themselves, and half of the respondents first saw the material accidentally, demonstrating the availability of CSAM. 48.1% want to stop using CSAM. Some seek help through Tor, and self-help websites are popular. Our survey finds commonalities between CSAM use and addiction. Help-seeking correlates with increasing viewing duration and frequency, depression, anxiety, self-harming thoughts, guilt, and shame. Yet, 73.9% of help seekers have not been able to receive it.

Abstract Background Halting and reversing the upward trend in obesity requires sustained implementation of comprehensive, evidence-based strategies at the population-level. The LiveLighter® program targets adults using a range of public education strategies, including mass media campaigns, to support healthy lifestyle changes to attain or maintain a healthy weight and reduce the risk of chronic disease. LiveLighter® has been implemented in Western Australia (WA) since 2012 and, to our knowledge, includes the longest running adult-targeted mass media campaign for healthy weight and lifestyle promotion and education globally. This evaluation assessed the impact of LiveLighter® on WA adults’ knowledge, intentions and behaviours as they relate to healthy eating and body weight from 2012 to 2019. Methods LiveLighter® mass media campaigns, which are TV-led and aired statewide, depict genuine, graphic imagery of visceral fat around internal organs to raise awareness about the link between excess body weight and chronic diseases; demonstrate how unhealthy food and drink consumption can contribute to unhealthy weight gain; and recommend healthy alternatives. Cross-sectional telephone surveys were conducted at baseline and following each campaign phase with an independent, randomly selected sample of WA adults aged 25 to 49 years (n = 501 to n = 1504 per survey) to assess their knowledge of the link between excess body weight and chronic diseases, and their intentions and behaviours related to healthy eating and weight. Multivariable logistic regression models were undertaken to assess differences in responses between baseline and each post-campaign survey. Results Compared to baseline, there were significant increases in the proportion of respondents reporting knowledge of excess body weight as a risk factor for certain cancers and type 2 diabetes, intentions to eat more fruit and vegetables and drink less sugar sweetened beverages (SSBs) in the next seven days, and the proportion of respondents who reported meeting guidelines for daily vegetable intake. Reported consumption of SSBs significantly decreased. Conclusions LiveLighter® is associated with improvements in knowledge of the health risks associated with excess body mass, increased vegetable intake and reduced SSB consumption in WA adults. These findings support the use of sustained, well-designed healthy lifestyle promotion and education programs as part of a comprehensive obesity prevention strategy.

The Seychelles blue bond is an innovative finance mechanism that has played a pivotal role in shaping the global landscape of blue bonds. Seychelles leadership in the blue economy sets a significant precedent. However, this precedent has also raised concerns among various stakeholders. This study evaluates of Seychelles’ sovereign blue bond, which was co-developed by the government of Seychelles and the World Bank. Three themes are explored, how the blue bond relates to other actors and donors in the blue economy space of Seychelles; how the blue bond contributes to advancing the national agenda and blue economy of Seychelles; and the key strengths, enablers and weaknesses of the blue bond. A series of considerations for future blue financing and blue bond mechanisms are presented, based on the findings of this study, to ensure that financing extends beyond blue washing and contributes meaningfully to the holistic transition to a sustainable blue economy. Our findings imply significant considerations for stakeholders in sustainable finance, suggesting ways to enhance the efficacy of blue bonds and emphasising the need for further research on their long-term impact and integration with other financial instruments.

IntroductionThe process of co-creation can enable more effective, agile and integrated healthcare solutions achieving outcomes that effectively translate to healthcare delivery. Collaborative knowledge generation is particularly important in fields such as pediatric chronic pain where there is a complex interplay between biological, social, environmental, emotional, familial and school factors. The co-creation initiative described here was designed to amplify the voices of youth with chronic pain and their families and a variety of key stakeholders and generate novel approaches to the management of chronic pediatric pain in the setting of the South Australian Pediatric Chronic Pain Service.MethodsStakeholders who were identified as influential in this ecosystem were allocated to 6 groups. A skilled facilitator co-prepared and delivered the workshop, engaging participants in three structured activities. Firstly, the challenges to service delivery were outlined, followed by the groups discussing what is currently working. The second activity involved lateral thinking without restrictions on time, resources or system to generate solutions to the key challenges presented. Finally, stakeholders were asked to agree on a generated solution from Activity 2 and build a case for actionable implementation of this solution. Data were summarised by the workshop facilitator and reflexive thematic analysis was used for coding and generating themes.ResultsFrom Activity 1, six themes collectively demonstrated that stakeholders valued many of the existing strengths of the service delivery, but some areas such as pain education was undervalued. Activity 2 generated solutions from high-level ideas to more day-to- day management strategies. Each of six groups generated unique solutions to an identified challenge for Activity 3.DiscussionEngaging a wide variety of stakeholders in collaborative knowledge generation successfully provided the South Australian Pediatric Chronic Pain Service with a variety of novel, scalable solution across the healthcare continuum. Equally important is that this initiative helped to raise awareness about the complex issues faced in pediatric chronic pain care and helped to establish new partnerships that have led to enhanced service delivery.

Abstract Background Traditional plaster‐cast fabrication of an ankle‐foot orthosis (AFO), although robust, is time‐consuming and cumbersome. 3D scanning is quickly gaining attention as an alternative to plaster casting the foot and ankle region for AFO fabrication. The aim of this study was to assess the accuracy and speed of two high‐performing 3D scanners compared with plaster casting in pediatric patients requiring an AFO. Methods Ten participants (mean age 10.0 ± 3.9 years) prescribed AFOs for a movement disorder were 3D scanned with the high‐cost Artec Eva (Eva) and low‐cost Structure Sensor II (SSII) using one‐person (1p) and two‐person (2p) protocols. Accuracy and speed for both 3D scanners were compared with corresponding plaster cast measures (≤5% acceptable difference). Bland and Altman plots were generated to show mean bias and limits of agreement. Results Overall, Eva and SSII were accurate for foot, ankle, and lower leg key clinical landmarks (Eva‐1p: 4.4 ± 7.3%; Eva‐2p: 3.2 ± 7.5%; SSII‐1p: 0.6 ± 7.4%; SSII‐2p: 0.7 ± 8.2%). Bland and Altman plots for the SSII demonstrated lower biases for 1p (bias 0.5 mm, LoA: −12.4–13.5 mm) and 2p (0.4 mm, LoA: −11.4–12.2 mm) protocols compared with Eva for 1p (bias 2.3 mm, LoA: −8.0–12.7 mm) and 2p (1.8 mm, LoA: −10.7–14.3 mm) protocols. The SSII 2p protocol was the fastest 3D scanning method (26.4 ± 11.1 s). Conclusions The high‐cost Eva and low‐cost SSII 3D scanners using the 1p and 2p protocols produced comparable accuracy and faster capture of key clinical landmarks compared with plaster cast measures for the fabrication of AFOs in pediatric patients.

Introduction Small for gestational age (SGA) infants are at increased risk of fetal distress in labour requiring emergency operative birth (by caesarean section (CS), vacuum or forceps). We have previously shown that maternal oral sildenafil citrate (SC) in labour halves the need for operative birth for suspected fetal distress in women with appropriately grown term infants.Methods and analysis RidStress 2 is a phase III randomised, double-blinded, placebo-controlled trial of 660 women with an SGA or suboptimally grown fetus (estimated fetal weight or abdominal circumference90% power to detect a similar reduction for the secondary outcome of any operative birth (CS or instrumental vaginal birth) for fetal distress.Ethics and dissemination Ethics approval was granted by the Mater Misericordiae Limited Human Research Ethics Committee (EC00332) on 11 September 2020. We plan to disseminate the results of this randomised controlled trial through presentations at scientific meetings and peer-reviewed journals, adhering to all relevant reporting guidelines.Trial registration number RidStress 2 is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12621000354886, 29/03/2021) and the Therapeutic Goods Association of Australia (date registered: 16 March 2021).

This article argues that public contestability is a critical attribute of governance arrangements designed to align AI deployment with the public interest. Mechanisms to collectively contest decisions which do not track public interests are an important guardrail against erroneous, exclusionary, and arbitrary decision-making. On that basis, we suggest that efforts to align AI to the public interest through democratic participation will benefit substantially from strengthening capabilities for public contestation outside aggregative and deliberative processes. We draw on insights from democratic and regulatory theory to explore three underlying requirements for public contestability in AI governance: (1) capabilities to organise; (2) separation of powers; and (3) access to alternative and independent information. While recognising that suitable mechanisms for contestability will vary by system and context, we sketch out some possibilities for embedding public contestability in AI governance frameworks with a view to provoking further discussion on institutional design.

Summary:. Pediatric hand burns are difficult to treat, with thin tissue with critical structures close to the skin and the small scale of the anatomy of children’s hands. Additionally, pediatric burns can be challenging due to the concern for donor-site morbidity and the paucity of donor sites when reconstructing these wounds. In this report, we discuss the successful application of a piscine-derived acellular dermal matrix in a 13-month-old child with deep partial thickness and full-thickness burns to the right upper extremity. She had excellent long term cosmetic results and function by 3 years postoperatively, including full extension and flexion of all digits in her right hand.

Background: Factors that influence quality of life (QoL) are used to determine the burden of disease, risk factors, and monitor management. Objectives: This study investigated the Australian inflammatory bowel disease (IBD) population and factors that affect QoL. Design: A national online survey was available to Australian IBD patients. Respondents were required to have a medical diagnosis of Crohn’s disease or ulcerative colitis, over 18 years of age, and receive healthcare in Australia. Methods: A mixture of validated questionnaires and additional questions were utilized to assess disease activity, QoL, and depression, anxiety and stress levels as well as demographic information. A variety of nonparametric statistical tests were used to explore relationships and compare groups. Results: A total of 825 participated in the survey across Australia with a 75% completion rate. The median Crohn’s and Ulcerative Colitis Questionnaire-8 (CUCQ-8) score was 37 with higher scores indicating worse QoL; those who have access to local support networks ( Md = 36) had significantly lower CUCQ-8 scores compared to those who do not ( Md = 44), U = 38,178, p = 0.014, r = 0.1. Similarly, those who feel adequately supported by local networks ( Md = 35) had significantly lower CUCU-8 compared to those who do not ( Md = 48), U = 30,772, p

Abstract Background An increasing number of studies have described new and persistent symptoms and conditions as potential post-acute sequelae of SARS-CoV-2 infection (PASC). However, it remains unclear whether certain symptoms or conditions occur more frequently among persons with SARS-CoV-2 infection compared with those never infected with SARS-CoV-2. We compared the occurrence of specific COVID-associated symptoms and conditions as potential PASC 31- to 150-day following a SARS-CoV-2 test among adults and children with positive and negative test results. Methods We conducted a retrospective cohort study using electronic health record (EHR) data from 43 PCORnet sites participating in a national COVID-19 surveillance program. This study included 3,091,580 adults (316,249 SARS-CoV-2 positive; 2,775,331 negative) and 675,643 children (62,131 positive; 613,512 negative) who had a SARS-CoV-2 laboratory test during March 1, 2020–May 31, 2021 documented in their EHR. We used logistic regression to calculate the odds of having a symptom and Cox models to calculate the risk of having a newly diagnosed condition associated with a SARS-CoV-2 positive test. Results After adjustment for baseline covariates, hospitalized adults and children with a positive test had increased odds of being diagnosed with ≥ 1 symptom (adults: adjusted odds ratio[aOR], 1.17[95% CI, 1.11–1.23]; children: aOR, 1.18[95% CI, 1.08–1.28]) or shortness of breath (adults: aOR, 1.50[95% CI, 1.38–1.63]; children: aOR, 1.40[95% CI, 1.15–1.70]) 31–150 days following a SARS-CoV-2 test compared with hospitalized individuals with a negative test. Hospitalized adults with a positive test also had increased odds of being diagnosed with ≥ 3 symptoms or fatigue compared with those testing negative. The risks of being newly diagnosed with type 1 or type 2 diabetes (adjusted hazard ratio[aHR], 1.25[95% CI, 1.17–1.33]), hematologic disorders (aHR, 1.19[95% CI, 1.11–1.28]), or respiratory disease (aHR, 1.44[95% CI, 1.30–1.60]) were higher among hospitalized adults with a positive test compared with those with a negative test. Non-hospitalized adults with a positive test also had higher odds or increased risk of being diagnosed with certain symptoms or conditions. Conclusions Patients with SARS-CoV-2 infection, especially those who were hospitalized, were at higher risk of being diagnosed with certain symptoms and conditions after acute infection.

Abstract Background Cumulative malaria parasite exposure in endemic regions often results in the acquisition of partial immunity and asymptomatic infections. There is limited information on how host-parasite interactions mediate the maintenance of chronic symptomless infections that sustain malaria transmission. Methods Here, we determined the gene expression profiles of the parasite population and the corresponding host peripheral blood mononuclear cells (PBMCs) from 21 children (

The parallel evolution of lateral plates and body shape in the threespine stickleback (Gasterosteus aculeatus) is an iconic example of adaptation. We test a case of contemporary evolutionary transition in a recently isolated population of marine G. aculeatus in British Columbia, Canada. We investigate Ectodysplasin (Eda) genotypes, plate counts, neutral genetic divergence, and whole-body phenotypes to determine the genetic and phenotypic distance between this population and nearby comparative populations. Our focal population is in the process of adapting both genetically and phenotypically to a freshwater environment, and we provide an example of the genetic basis for parallel evolution on a contemporary timescale. The frequency of Eda genotypes and lateral plate phenotypes in our focal population is not consistent with those of marine or fully freshwater populations. Although our focal population is genetically distinct from nearby marine populations, these fish still more closely resemble marine populations in overall body shape while demonstrating an intriguing intermediate phenotype. Eda frequency and lateral plate phenotype change faster than body shape in response to freshwater conditions, suggesting that the pace of adaptation differs across traits in response to the same environmental conditions. Our results further bolster the case for G. aculeatus as a key model of contemporary evolution.

Abstract Background Responding to international research showing that early introduction of common food allergens can reduce the chance of developing allergies, in 2016 the Australasian Society of Clinical Immunology and Allergy (ASCIA) revised allergen introduction guidelines, recommending earlier introduction of allergens to infants in their first year. Australia has high food allergy rates, and limited understanding of adherence to allergen introduction guidelines, especially in rural areas. This project explored rural parent adherence to ASCIA guidelines. Methods This was a mixed method cross sectional study using an online survey including multiple-choice and qualitative short answer responses. The sample were 336 women from two rural health districts in New South Wales. All were aged 18 or over, and either pregnant or had delivered a baby since July 2018. Descriptive statistics were used to measure behavioural alignment with the recommended guidelines, thematic analysis was used to analyse attitudes and explanations. Results In 84.3% of children, feeding adhered to all four guidelines studied, including no elimination of allergens during pregnancy (98%), age of introduction of solids (97.7%), continuation of breast milk/cow’s milk formula during introduction of solids (95%), and age of introduction of allergens (92.9%). Adherence was not significantly correlated with the education (X2 = 17.9, P = .056), prior history of allergy [neither mother (X2 = 0.945,P = .623) nor previous children (X2 = 0.401,P = .818)], or primary care received during pregnancy. More than 90% of participants agreed or strongly agreed that the guidelines are realistic, trustworthy, and important for the health of their child. However, thematic analysis revealed that parents’ perceptions of a child’s individual progress, and medical conditions or other circumstances, such as challenges with breastfeeding, will often take precedence over adherence to specific guideline recommendations. Conclusions High rates of adherence with ASCIA guidelines found here are comparable with findings from metropolitan studies and encouraging for future population health. Participant comments on the guidelines imply to rural policymakers that there are multiple influences on parent decisions about infant feeding, often including parents’ own intuition and experiences. Further studies to improve understanding of the role of information, carers, and other influences on parent decision-making concerning feeding attitudes and behaviours will be necessary to optimise adherence in rural areas.

Abstract Background People with a mental health condition experience a high prevalence of chronic disease risk behaviours e.g., tobacco smoking and physical inactivity. Recommended ‘preventive care’ to address these risks is infrequently provided by community mental health services. This study aimed to elucidate, among community mental health managers and clinicians, suggestions for strategies to support provision of preventive care. Methods Three qualitative focus groups (n = 14 clinicians) were undertaken in one regional community mental health service to gather perspectives of barriers to preventive care provision, deductively coded against the domains of the Theoretical Domains Framework (TDF). Drawing on the learnings from the focus groups, individual interviews (n = 15 managers and clinicians) were conducted in two services to identify suggestions for strategies to increase preventive care. Strategies were inductively coded and mapped into TDF domains. Results Barriers were identified across a wide range of TDF domains, most notably knowledge and environmental context and resources. Nine strategies were identified across three themes: training, resources and systems changes; mapping to all 14 TDF domains. Conclusion Future research seeking to increase implementation of preventive care may be guided by these findings. There is need for greater recognition and resourcing of preventive care as a priority and integral component of mental health treatment.

Abstract Background Over the last decades, many strategies to procure and improve xylose consumption in Saccharomyces cerevisiae have been reported. This includes the introduction of efficient xylose-assimilating enzymes, the improvement of xylose transport, or the alteration of the sugar signaling response. However, different strain backgrounds are often used, making it difficult to determine if the findings are transferrable both to other xylose-consuming strains and to other xylose-assimilation pathways. For example, the influence of anomerization rates between α- and β-xylopyranose in pathway optimization and sugar sensing is relatively unexplored. Results In this study, we tested the effect of expressing a xylose epimerase in S. cerevisiae strains carrying different xylose-consuming routes. First, XIs originating from three different species in isogenic S. cerevisiae strains were tested and the XI from Lachnoclostridium phytofermentans was found to give the best performance. The benefit of increasing the anomerization rate of xylose by adding a xylose epimerase to the XI strains was confirmed, as higher biomass formation and faster xylose consumption were obtained. However, the impact of xylose epimerase was XI-dependent, indicating that anomer preference may differ from enzyme to enzyme. The addition of the xylose epimerase in xylose reductase/xylitol dehydrogenase (XR/XDH)-carrying strains gave no improvement in xylose assimilation, suggesting that the XR from Spathaspora passalidarum had no anomer preference, in contrast to other reported XRs. The reduction in accumulated xylitol that was observed when the xylose epimerase was added may be associated with the upregulation of genes encoding endogenous aldose reductases which could be affected by the anomerization rate. Finally, xylose epimerase addition did not affect the sugar signaling, whereas the type of xylose pathway (XI vs. XR/XDH) did. Conclusions Although xylose anomer specificity is often overlooked, the addition of xylose epimerase should be considered as a key engineering step, especially when using the best-performing XI enzyme from L. phytofermentans. Additional research into the binding mechanism of xylose is needed to elucidate the enzyme-specific effect and decrease in xylitol accumulation. Finally, the differences in sugar signaling responses between XI and XR/XDH strains indicate that either the redox balance or the growth rate impacts the SNF1/Mig1p sensing pathway.

Abstract Background Cervical epidural hematoma (CEH) is defined as a collection of blood in the suprameningeal space. Mechanisms of this rare pathology include spontaneous, postsurgical, and traumatic as the main subtypes. This unique case of traumatic CEH represents an even smaller subset of these cases. Management varies by symptom presentation, mechanism of injury, and other contraindications. Case presentation This case presents a 32 year old African American female on an oral anticoagulant sustaining traumatic cervical hematoma after a motor vehicle collision. Patient complained of neck, abdominal, and back pain. Imaging revealed a cervical spinal hematoma at the level of C3–C6. This case discusses the management of CEH for the general population and in the setting of anticoagulation. Conclusion Management of each case of CEH must be carefully considered and tailored based on their symptom presentation and progression of disease. As the use of anticoagulation including factor Xa inhibitors becomes more prevalent, there is greater need to understand the detailed pathophysiological aspect of the injuries. Targeted reversal agents such as Prothrombin Concentrate can be used for conservative treatment. Adjunct testing such as thromboelastogram can be used to help guide management.

The challenges northern remote communities in Canada face acquiring regular access to affordable and healthy food have been well documented. Our Indigenous Health Research Group, made up of an informal network of researchers from universities across Canada, has partnered with northern communities, Tribal Councils, and Political organizations (Assembly of First Nations, Nishnawbe Aski Nation) in Yukon, Northwest Territories, British Columbia, and Ontario since 2004 to document and support local land-based food strategies to increase local food capacity. While much of this work has focused on supporting traditional food harvesting efforts, many community partners are seeking to develop small-scale gardening to increase access to fresh fruit and vegetables. As part of a five-year project supporting local food initiatives in four communities in northern Canada (Northwest Territories and northern Ontario), we worked with the Moose Cree First Nation in Moose Factory, Ontario and their local Food Developer to support food sustainability planning. The research presented in this article describes collaborative efforts between Moose Cree First Nation Band Council leadership, community members, and our research group in support of local garden development as part of their local food sustainability strategy. With the guidance and engagement of community, we worked with families in Moose Factory to build and plant family-centered gardens. The article focuses on start-up engagement strategies, garden uptake, garden construction and planting activities, garden yields, and individual feedback from gardeners describing their experiences with the project.

Diffuse large B-cell lymphoma (DLBCL) is the most common malignancy that develops in patients with ataxia-telangiectasia, a cancer-predisposing inherited syndrome characterized by inactivating germline ATM mutations. ATM is also frequently mutated in sporadic DLBCL. To investigate lymphomagenic mechanisms and lymphoma-specific dependencies underlying defective ATM, we applied ribonucleic acid (RNA)-seq and genome-scale loss-offunction clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 screens to systematically interrogate B-cell lymphomas arising in a novel murine model (Atm-/-nu-/-) with constitutional Atm loss, thymic aplasia but residual T-cell populations. Atm-/-nu-/-lymphomas, which phenotypically resemble either activated B-cell-like or germinal center Bcell-like DLBCL, harbor a complex karyotype, and are characterized by MYC pathway activation. In Atm-/-nu-/-lymphomas, we discovered nucleotide biosynthesis as a MYCdependent cellular vulnerability that can be targeted through the synergistic nucleotidedepleting actions of mycophenolate mofetil (MMF) and the WEE1 inhibitor, adavosertib (AZD1775). The latter is mediated through a synthetically lethal interaction between RRM2 suppression and MYC dysregulation that results in replication stress overload in Atm-/-nu-/-lymphoma cells. Validation in cell line models of human DLBCL confirmed the broad applicability of nucleotide depletion as a therapeutic strategy for MYC-driven DLBCL independent of ATM mutation status. Our findings extend current understanding of lymphomagenic mechanisms underpinning ATM loss and highlight nucleotide metabolism as a targetable therapeutic vulnerability in MYC-driven DLBCL.

While much of the studies within the Uses and Gratifications (U&G) tradition were set to predict facets of media use, the current study examines how use motivations, nature of platform use, and privacy-related perceptions predict users’ use continuance intentions for Facebook, Instagram, Twitter, and TikTok and their problematic use (i.e., addiction), simultaneously. The study uses a cross-sectional survey of undergraduate students at a large Midwestern University ( N = 685), where participants expressed their motivations to use each of the four platforms (depending on their active use of the platform), platform affinity and other usage factors, their intentions to continue using the platform, and their problematic use of the platform. Findings showed superiority of Instagram in terms of U&G. Regression models highlighted differences in the four platforms’ problematic use and continuance intentions. Findings are discussed within the framework of reconceptualizing U&G outcomes within the evolving social media environment.

Summary:. Calcinosis cutis is a disease process characterized by calcified lesions in the skin. Although there are five subtypes of calcinosis, idiopathic calcinosis cutis is a rare disease process with no clear etiology. It has been described in many parts of the body; however, there are only five reported cases specifically involving the hands. We describe the presentation and successful treatment of a case of idiopathic calcinosis cutis in a 65-year-old man with lesions on his bilateral hands. We believe that surgical excision of symptomatic lesions is a safe and effective treatment for idiopathic calcinosis cutis of the hands.

Summary: Background: The aim of this study was to detail incidence rates and relative risks for severe adverse perinatal outcomes by birthweight centile categories in a large Australian cohort of late preterm and term infants. Methods: This was a retrospective cohort study of singleton infants (≥34+0 weeks gestation) between 2000 and 2018 in Queensland, Australia. Study outcomes were perinatal mortality, severe neurological morbidity, and other severe morbidity. Categorical outcomes were compared using Chi-squared tests. Continuous outcomes were compared using t-tests. Multinomial logistic regression investigated the effect of birthweight centile on study outcomes. Findings: The final cohort comprised 991,042 infants. Perinatal mortality occurred in 1944 infants (0.19%). The incidence and risk of perinatal mortality increased as birthweight decreased, peaking for infants

IntroductionThere have been few controlled evaluations of Social Prescribing (SP), in which link workers support lonely individuals to engage with community-based social activities. This study reports early outcomes of a trial comparing General Practitioner treatment-as-usual (TAU) with TAU combined with Social Prescribing (SP) in adults experiencing loneliness in Queensland.MethodsParticipants were 114 individuals who were non-randomly assigned to one of two conditions (SP, n = 63; TAU, n = 51) and assessed at baseline and 8 weeks, on primary outcomes (loneliness, well-being, health service use in past 2 months) and secondary outcomes (social anxiety, psychological distress, social trust).ResultsRetention was high (79.4%) in the SP condition. Time × condition interaction effects were found for loneliness and social trust, with improvement observed only in SP participants over the 8-week period. SP participants reported significant improvement on all other outcomes with small-to-moderate effect sizes (ULS-8 loneliness, wellbeing, psychological distress, social anxiety). However, interaction effects did not reach significance.DiscussionSocial prescribing effects were small to moderate at the 8-week follow up. Group-based activities are available in communities across Australia, however, further research using well-matched control samples and longer-term follow ups are required to provide robust evidence to support a wider roll out.

Abstract Chlamydia trachomatis (Ct) remains the most common bacterial sexually transmitted pathogen worldwide, causing significant morbidity particularly among women, including pelvic inflammatory disease, ectopic pregnancy, and infertility. Several vaccines are advancing through pre-clinical and clinical development, and it is likely that one or more vaccines will progress into human efficacy trials soon. In this Perspective, we present a case for considering the challenges of Ct vaccine development through a lens of equity and justice. These challenges include the need to protect against multiple serovars, in both females and males, at multiple anatomic sites, and in resource poor areas of the world. We propose that early consideration of vaccine implementation by conducting community-engaged research will ensure that a scientifically sound chlamydia vaccine promotes equity, justice, and shared-gendered responsibility for STI prevention.

Objective To analyze comparative treatment persistence for first‐line baricitinib (BARI) versus first‐line tumor necrosis factor inhibitor (TNFi) in patients with rheumatoid arthritis (RA) and for first‐line BARI initiated as monotherapy versus first‐line BARI initiated with at least one conventional synthetic disease‐modifying antirheumatic drug (csDMARD). Methods Patients with RA who initiated BARI or TNFi as first‐line biologic or targeted synthetic DMARD from October 1, 2015, to September 30, 2021, were identified in the OPAL data set. Drug survival times to 6, 12, and 24 months were analyzed using restricted mean survival time (RMST). Multiple imputation and inverse probability of treatment weighting were used to address missing data and nonrandom treatment assignment. Results A total of 545 patients initiated first‐line BARI, including 118 as monotherapy and 427 as csDMARD combination therapy. Three thousand five hundred patients initiated first‐line TNFi. There was no difference in drug survival to 6 or 12 months for BARI compared with TNFi; differences in RMST were 0.02 months (95% CI: −0.08 to 0.013; P = 0.65) and 0.31 months (95% CI: −0.02 to 0.63; P = 0.06), respectively. Patients in the BARI group had 1.00 month (95% CI: 0.14 to 1.86; P = 0.02) longer drug survival to 24 months. There was no difference in drug survival for BARI monotherapy compared with combination therapy, with differences in RMST to 6, 12, and 24 months of −0.19 months (95% CI: −0.50 to 0.12; P = 0.12), −0.35 months (95% CI: −1.17 to 0.42; P = 0.41), and −0.56 months (95% CI: −2.66 to 1.54; P = 0.60), respectively. Conclusion In this comparative analysis, treatment persistence up to 24 months was significantly longer for first‐line BARI compared with TNFi, but the effect size of 1.00 month is not clinically meaningful. There was no difference in persistence for BARI monotherapy versus combination therapy.

Summary: Background: The aim of this study was to ascertain risks of neonatal mortality, severe neurological morbidity and severe non-neurological morbidity related to the 5-min Apgar score in early term (37+0–38+6 weeks), full term (39+0–40+6 weeks), late term (41+0–41+6 weeks), and post term (≥42+0 weeks) infants. Methods: This was a retrospective cohort study of 941,221 term singleton births between 2000 and 2018 in Queensland, Australia. Apgar scores at 5-min were categorized into five groups: Apgar 0 or 1, 2 or 3, 4–6, 7 or 8 and 9 or 10. Gestational age was stratified into 4 groups: Early term, full term, late term and post term. Three specific neonatal study outcomes were considered: 1) Neonatal mortality 2) Severe neurological morbidity and 3) Severe non-neurological morbidity. Poisson multivariable regression models were used to determine relative risk ratios for the effect of gestational age and Apgar scores on these severe neonatal outcomes. We hypothesized that a low Apgar score of 37 weeks’ gestation with the risk greatest in the early term cohort. Funding: National Health and Medical Research Council and Mater Foundation.

IntroductionFetal growth restriction (FGR) is a common pregnancy complication, caused by placental insufficiency, with serious adverse consequences for development in utero and postnatal wellbeing. There are no antenatal treatments to improve growth or organ development in FGR, and animal models are essential to mimic the physiological adaptations in FGR and to assess potential interventions. This study aimed to identify the temporal nature of reduced developmental trajectory in fetuses with FGR, and to examine the effects of common factors that may mediate differential growth such as glucocorticoid treatment. We hypothesised that the trajectory of growth would be adversely impacted by FGR.MethodsFGR was induced via surgical placental insufficiency in fetal sheep (89 days gestation/0.6 gestation; n=135) and compared to age-matched controls over the last third of gestation and into neonatal life (n=153).ResultsBody weight of FGR fetuses/lambs was significantly reduced compared to controls (p

Meiotic recombination between homologous chromosomes is initiated by the formation of hundreds of programmed double-strand breaks (DSBs). Approximately 10% of these DSBs result in crossovers (COs), sites of physical DNA exchange between homologs that are critical to correct chromosome segregation. Virtually all COs are formed by coordinated efforts of the MSH4/MSH5 and MLH1/MLH3 heterodimers, the latter representing the defining marks of CO sites. The regulation of CO number and position is poorly understood, but undoubtedly requires the coordinated action of multiple repair pathways. In a previous report, we found gene-trap disruption of the DNA helicase, FANCJ (BRIP1/BACH1), elicited elevated numbers of MLH1 foci and chiasmata. In somatic cells, FANCJ interacts with numerous DNA repair proteins including MLH1, and we hypothesized that FANCJ functions with MLH1 to regulate the major CO pathway. To further elucidate the meiotic function of FANCJ, we produced three new Fancj mutant mouse lines via CRISPR/Cas9 gene editing: a full-gene deletion, truncation of the N-terminal Helicase domain, and a C-terminal dual-tagged allele. We also generated an antibody against the C-terminus of the mouse FANCJ protein. Surprisingly, none of our Fancj mutants show any change in either MLH1 focus counts during pachynema or total CO number at diakinesis of prophase I. We find evidence that FANCJ and MLH1 do not interact in meiosis; further, FANCJ does not co-localize with MSH4, MLH1, or MLH3 in meiosis. Instead, FANCJ co-localizes with BRCA1 and TOPBP1, forming discrete foci along the chromosome cores beginning in early meiotic prophase I and densely localized to unsynapsed chromosome axes in late zygonema and to the XY chromosomes in early pachynema. Fancj mutants also exhibit a subtle persistence of DSBs in pachynema. Collectively, these data indicate a role for FANCJ in early DSB repair, but they rule out a role for FANCJ in MLH1-mediated CO events.

Summary: Perlecan (HSPG2), a heparan sulfate proteoglycan similar to agrin, is key for extracellular matrix (ECM) maturation and stabilization. Although crucial for cardiac development, its role remains elusive. We show that perlecan expression increases as cardiomyocytes mature in vivo and during human pluripotent stem cell differentiation to cardiomyocytes (hPSC-CMs). Perlecan-haploinsuffient hPSCs (HSPG2+/−) differentiate efficiently, but late-stage CMs have structural, contractile, metabolic, and ECM gene dysregulation. In keeping with this, late-stage HSPG2+/− hPSC-CMs have immature features, including reduced ⍺-actinin expression and increased glycolytic metabolism and proliferation. Moreover, perlecan-haploinsuffient engineered heart tissues have reduced tissue thickness and force generation. Conversely, hPSC-CMs grown on a perlecan-peptide substrate are enlarged and display increased nucleation, typical of hypertrophic growth. Together, perlecan appears to play the opposite role of agrin, promoting cellular maturation rather than hyperplasia and proliferation. Perlecan signaling is likely mediated via its binding to the dystroglycan complex. Targeting perlecan-dependent signaling may help reverse the phenotypic switch common to heart failure.

Abstract Aim To investigate the relationship between social media use and loneliness and psychological wellbeing of youth in rural New South Wales. Design This was a web-based cross-sectional survey. Methods The survey consisted of 33 items including demography (12 items), participants’ social media use (9 items), mood and anxiety (6 items), perceived loneliness (6 items), the impact of COVID-19 on social media usage or perceived loneliness (2 items). The participants’ mood and anxiety were evaluated using the psychological distress tool (K6), while loneliness was measured using the De Jong Gierveld 6-item scale. Total loneliness and psychological distress scores were compared between demographic variables. Results A total of 47 participants, aged 16–24 years took part in the study. The majority were women (68%) and many had K6 score that was indicative of psychological distress (68%). About half of the participants indicated that Facebook (FB) was their most used social media platform and two in five participants were on social media within 10 min of waking up each day, about 30% spent more than 20 h per week on social media, and more than two-third sent private messages, images, or videos, multiple times a day. The mean loneliness score was 2.89 (range, 0 to 6), with 0 being ‘not lonely’ and 6 being ‘intense social loneliness’. One-way ANOVA and χ2 test results showed that those who used FB most frequently had significantly higher mean scores for loneliness compared to those that used other social media platforms (p = 0.015). Linear regression analysis revealed that those who commonly used FB were more likely to report higher loneliness scores (coefficient = –1.45, 95%CI –2.63, –0.28, p = 0.017), while gender (p = 0.039), age (p = 0.048), household composition (p = 0.023), and education level (p = 0.014) were associated with severe psychological distress. Conclusions The study found that social media usage, particularly FB, as measured by time used and active or passive engagement with the medium, was significantly linked to loneliness, with some impact on psychological distress. Social media use within ten minutes of waking increased the likelihood of psychological distress. However, neither loneliness nor psychological distress were associated with rurality among the rural youth in this study.

Abstract Background In high‐income countries, hope facilitates parental coping and builds the clinical relationship between families of children with cancer and their clinicians. However, the manifestation of hope in low‐ and middle‐income countries (LMICs) remains poorly understood. Our study explores Guatemalan parents' experiences with hope during the pediatric oncology diagnostic process and aims to identify discrete actions clinicians take to support hope. Methods This qualitative study utilized audio‐recordings of the diagnostic process and an additional semi‐structured interview for 20 families of children with cancer at Unidad Nacional de Oncología Pediátrica in Guatemala. Spanish audio‐recordings were translated into English, transcribed, and coded using a priori and novel codes. Thematic content analysis using constant comparative methods explored parents' hopes and concerns. Results At diagnosis, Guatemalan parents expressed both hopes and concerns related to the entire cancer continuum. Throughout the diagnostic process, hope grew as concerns were alleviated. Clinicians supported hope by creating a supportive environment, providing information, affirming religious beliefs, and empowering parents. These strategies helped parents shift their focus from fear and uncertainty toward hope for their child's future. Parents expressed that establishing hope improved mood, promoted acceptance, and enabled them to care for themselves and their children. Conclusion These results confirm the relevance of supporting hope in pediatric oncology settings in LMICs and suggest that culture informs hope‐related needs. Supporting hope is critical across cultures and can be integrated into clinical conversation using the four processes identified by our results.

ABSTRACT Importance In remote communities of the Northern Territory, Australia, children experience high rates of otitis media (OM), commonly caused by non‐typeable Haemophilus influenzae (NTHi). Few data exist on antibiotic susceptibility of NTHi from OM. Objective To determine whether population‐level nasopharyngeal NTHi antibiotic susceptibility data could inform antibiotic treatment for OM. Methods NTHi isolates (n = 92) collected from ear discharge between 2003 and 2013 were selected to time‐ and age‐match NTHi isolates from the nasopharyngeal carriage (n = 95). Antimicrobial susceptibility were tested. Phylogenomic trees and a genome‐wide association study (GWAS) were performed to determine the similarity of nasopharyngeal and ear isolates at a population level. Results Among 174 NTHi isolates available for antimicrobial susceptibility testing, 10.3% (18/174) were resistant to ampicillin and 9.2% (16/174) were resistant to trimethoprim‐sulfamethoxazole. Small numbers of isolates (≤3) were resistant to tetracycline, chloramphenicol, or amoxicillin‐clavulanic acid. There was no statistical difference in the proportion of ampicillin‐resistant (P = 0.11) or trimethoprim‐sulfamethoxazole‐resistant isolates (P = 0.70) between ear discharge and nasopharynx‐derived NTHi isolates. Three multi‐drug resistant NTHi isolates were identified. Phylogenomic trees showed no clustering of 187 Haemophilus influenzae isolates based on anatomical niche (nasopharynx or ear discharge), and no genetic variations that distinguished NTHi derived from ear discharge and nasopharyngeal carriage were evident in the GWAS. Interpretation In this population‐level study, nasopharyngeal and ear discharge isolates did not represent distinct microbial populations. These results support tracking of population‐level nasopharyngeal NTHi antibiotic resistance patterns to inform clinical management of OM in this population.

Understanding the impacts of herbicides on soil microbial communities is important, as these organisms mediate a wide range of ecosystem services. Here, we investigated whether the diversity and function of soil microbial communities were significantly influenced by one-off applications of atrazine, diuron, fluazifop-P-butyl, haloxyfop-P-methyl and pendimethalin as pure compounds at their recommended doses over multiple time points (1, 3, 7, 14, 30 and 60 days). Phylogenetic marker gene sequencing revealed that none of the herbicides influenced the numbers of bacterial and archaeal taxa or the evenness of their abundances. Similarly, none of the herbicides influenced the composition of bacterial and archaeal communities, except for diuron, fluazifop-P-methyl and pendimethalin, which were associated with larger relative abundances of a small number of OTUs on day 30 only. Functionally, none of the herbicides significantly influenced fluorescein diacetate hydrolysis (FDA) and beta-glucosidase activities or the induced respiratory responses of soil microbial communities to a range of substrates. These data indicate that the active herbicide ingredients tested may have minimal non-target effects when applied once at their recommended dose. Given their frequent use, it is important to next consider whether these herbicides have more pronounced effects at higher doses and application frequencies.

ABSTRACTAboveground biomass (AGB) can serve as an indicator when estimating various biogeochemical processes in peatlands, an ecosystem which provides countless ecosystem services and plays a key role in climate regulation. While remote sensing has been extensively employed to assess AGB across vast areas in forested peatlands its application to small and treeless peatlands, which are typical of the alpine regions, has been limited. Due to the characteristics of peatlands, innovative approaches capable of capturing their fine-scale, highly heterogeneous and short-stature vegetation cover are needed. Likewise, other key requirements include an ability to overcome site accessibility barriers, cost-effective acquisition of datasets and minimizing damage of these protected habitats. Hence, the utilization of Unmanned Aerial Vehicles (UAVs) offers a viable means for mapping AGB in alpine peatlands. In this study, the AGB of the Val di Ciampo alpine peatland (Veneto Region, Italy) was estimated by combining datasets derived from in situ vegetation samples as well as UAV-based LiDAR, hyperspectral and RGB sensors. A limited number of vegetation samples were used to reduce the impact of the study on the ecosystem. The results indicate that a linear regression can model the relationship between AGB and Leaf Area Index (LAI) with a significant explanatory ability (R2 = 0.72; p

Background: Hopelessness is an important risk factor for depression and suicide. However, few suitable measures exist for use in the general population, limiting research testing aetiological models. The present study aimed to develop and validate a new measure of hopelessness using a community-based sample. Method: Twenty-nine candidate items underwent refinement via three sequential stages– (1) feedback from 15 experts, (2) scale development (N = 218), and (3) scale validation (N = 218)—resulting in the final 5-item scale, the Hopelessness Inventory-5 (HI-5). Results: EFA and CFA supported the unidimensionality of the new HI-5 scale, with excellent fit indices (SRMR=0.02, RMSEA=0.06, CFI=0.99, TLI=0.97). High Cronbach's alpha (0.92) indicated that the scale was internally consistent. Bivariate correlations with related constructs supported both convergent and divergent validity. Comparing information curves of the HI-5 and a shortened BHS indicated that the HI-5 provided more information across a wider range of the latent trait. Limitations: The HI-5 was not validated against the original BHS. The sampling method may have led to limited hopelessness scores in the very high range and overrepresentation of females. Conclusions: The HI-5 is a brief, succinctly-worded, and freely available scale, developed using expert feedback and validated in a community sample. It is intended to facilitate the advancement of research and theory that include hopelessness as a key risk factor for mental ill health in the general population.

ABSTRACTSelective transport through the nuclear pore complex (NPC) depends on the dynamic binding of FG-repeat containing nucleoporins, the FG-nups, with each other and with Karyopherins (Kaps). Here, we assessed the specificity and mechanism by which the aliphatic alcohol 1,6-hexanediol (1,6HD) disrupts the permeability barrier of NPCs in live baker’s yeast cells. After a 10-minute exposure to 5% 1,6HD, no notable changes were observed in cell growth, cytosolic pH and ATP levels, or the appearance of organelles. However, effects on the cytoskeleton and Hsp104 were noted. 1,6HD clearly affected the NPC permeability barrier, allowing passive nuclear entry of a 177kDa reporter protein that is normally confined to the cytosol. Moreover, multiple Kaps were displaced from NPCs, and the displacement of Kap122-GFP correlated with the observed passive permeability changes. 1,6HD thus temporarily permeates NPCs, and in line with Kap-centric models, the mechanism includes the release of numerous Kaps from the NPCs.

Background Hypertension and diabetes are associated with increased COVID‐19 severity. The association between level of control of these conditions and COVID‐19 severity is less well understood. Methods and Results This retrospective cohort study identified adults with COVID‐19, March 2020 to February 2022, in 43 US health systems in the National Patient‐Centered Clinical Research Network. Hypertension control was categorized as blood pressure (BP)