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Abstract Accurate diagnosis and monitoring of neurodegenerative diseases require reliable biomarkers. Cerebrospinal fluid (CSF) proteins are promising candidates for reflecting brain pathology; however, their diagnostic utility may be compromised by natural variability between individuals, weakening their association with disease. Here, we measured the levels of 69 pre-selected proteins in cerebrospinal fluid using antibody-based suspension bead array technology in a multi-disease cohort of 499 individuals with neurodegenerative disorders including Alzheimer’s disease (AD), behavioral variant frontotemporal dementia, primary progressive aphasias, amyotrophic lateral sclerosis (ALS), corticobasal syndrome, primary supranuclear palsy, along with healthy controls. We identify significant inter-individual variability in overall CSF levels of brain-derived proteins, which could not be attributed to specific disease associations. Using linear modelling, we show that adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF in the context of neurodegenerative disorders. We further demonstrate a simplified approach for the adjustment using pairs of correlated proteins with opposite alteration in the diseases. With this approach, the proteins adjust for each other and further increase the biomarker performance through additive effect. When comparing the diseases, two proteins—neurofilament medium and myelin basic protein—showed increased levels in ALS compared to other diseases, and neurogranin showed a specific increase in AD. Several other proteins showed similar trends across the studied diseases, indicating that these proteins likely reflect shared processes related to neurodegeneration. Overall, our findings suggest that accounting for inter-individual variability is crucial in future studies to improve the identification and performance of relevant biomarkers. Importantly, we highlight the need for multi-disease studies to identify disease-specific biomarkers.

Abstract Cheek swabs, heterogeneous samples consisting primarily of buccal epithelial cells, are widely used in pediatric DNA methylation studies and biomarker creation. However, the decrease in buccal proportion with age in adults remains unexamined in childhood. We analyzed cheek swabs from 4626 typically developing children 2-months to 20-years-old. Estimated buccal proportion declined throughout childhood with both increasing chronological and predicted epigenetic age. However, buccal proportion did not associate with age throughout adolescence. Variability in buccal proportion increased with age through the entire developmental range. These trends held inversely true for neutrophil proportions. Correcting for buccal proportion attenuated the weak association with PedBE age acceleration to non-significance during initial estimation. Notably, correcting for buccal proportion attenuated the association of PedBE age acceleration with obsessive-compulsive disorder and strengthened the association with diurnal cortisol slope. Thus, the age-related change in children’s oral cells is a crucial consideration for cell type-sensitive research.

Alzheimer’s disease is a prominent chronic neurodegenerative condition characterized by a gradual decline in memory leading to dementia. Growing evidence suggests that Alzheimer’s disease is associated with accumulating various amyloid-β oligomers in the brain, influenced by complex genetic and environmental factors. The memory and cognitive deficits observed during the prodromal and mild cognitive impairment phases of Alzheimer’s disease are believed to primarily result from synaptic dysfunction. Throughout life, environmental factors can lead to enduring changes in gene expression and the emergence of brain disorders. These changes, known as epigenetic modifications, also play a crucial role in regulating the formation of synapses and their adaptability in response to neuronal activity. In this context, we highlight recent advances in understanding the roles played by key components of the epigenetic machinery, specifically DNA methylation, histone modification, and microRNAs, in the development of Alzheimer’s disease, synaptic function, and activity-dependent synaptic plasticity. Moreover, we explore various strategies, including enriched environments, exposure to non-invasive brain stimulation, and the use of pharmacological agents, aimed at improving synaptic function and enhancing long-term potentiation, a process integral to epigenetic mechanisms. Lastly, we deliberate on the development of effective epigenetic agents and safe therapeutic approaches for managing Alzheimer’s disease. We suggest that addressing Alzheimer’s disease may require distinct tailored epigenetic drugs targeting different disease stages or pathways rather than relying on a single drug.

Sesame (Sesamum indicum) is a specialty crop with increasing interest as an alternative, rotational crop for U.S. agricultural systems. This crop is susceptible to several pathogens, including Pseudomonas and Xanthomonas species. Two bacterial isolates were recently cultured from sesame in North Carolina symptomatic of bacterial spot and identified as Pseudomonas amygdali pv. sesami (Pas) and Xanthomonas sp. These isolates were used for hybrid whole-genome sequencing and assembly using Illumina and PacBio to develop robust genomic resources for these disease-causing strains. The results provide the most complete Pas genome available and placed the Xanthomonas sp. isolate into the X. arboricola species designation. Improved genomic resources for pathogens of sesame are needed to accurately detect, characterize, and employ timely management of the disease. [Figure: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Abstract Background Understanding site-related factors that influence enrolment within multicenter randomized controlled trials (RCT) may help reduce trial delays and cost over-runs and prevent early trial discontinuation. In this analysis of PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial), we describe patient enrolment patterns and examine factors influencing site-based monthly enrolment. Design Retrospective analysis of a multicenter RCT. Methods The PROSPECT multicenter RCT enrolled patients in the main trial from July 2015 to March 2019. We documented site characteristics and trial metrics including data from the methods center tracking documents, site-level data at trial initiation, screening logs submitted by research coordinators, and prospectively collected case report forms. In this retrospective analysis of trial data, we analyzed enrolment patterns across sites using negative binomial regression to explore the association between monthly enrolment rate accounting for number of ICU beds, site characteristics, and trial metrics. Results Overall, 41 sites enrolling 2365 patients in the PROSPECT main trial were analyzed. After accounting for number of beds in each ICU, site launch early in the trial was associated with higher monthly enrolment rates, but time to first enrolment and research coordinator experience was not. We observed considerable variability in the number of active screening months and enrolment rates across sites. Conclusion These findings highlight the complexity of recruitment dynamics in critical care RCTs and emphasize the need for tailored approaches to trial planning and execution. Trial registration PROSPECT (Probiotics: Prevention of Severe Pneumonia and Endotracheal Colonization Trial): NCT02462590 (registered June 2, 2015).

Abstract Developmental delays have been associated with metabolic disturbances in children. Previous research in the childhood autism risk from genetics and the environment (CHARGE) case–control study identified neurodevelopment-related plasma metabolites in children, suggesting disturbances in the energy-related tricarboxylic acid (TCA) cycle and 1-carbon metabolism (1CM). Here, we investigated associations between children’s neurodevelopmental outcomes and their mothers’ plasma metabolite profiles in a subset of mother–child dyads from CHARGE, including those with autism spectrum disorder (ASD, n = 209), Down syndrome (DS, n = 76), idiopathic developmental delay (iDD, n = 64), and typically developed (TD, n = 185) controls. Multiple linear regression revealed associations between child neurodevelopmental outcomes and maternal plasma metabolites related to the TCA cycle, 1CM, and lipid metabolism. Despite profound metabolic disturbances in children with DS reported previously, few of these differences were observed in the mothers, which might reflect differences in gene dosage between children with DS and their euploid mothers. Notably differences in maternal metabolism related to ASD and iDD followed similar patterns of disturbance in previously reported metabolic signatures in children but were generally smaller in magnitude. Similar patterns of metabolic disturbances observed in mothers and their children with ASD or iDD could reflect shared genetic, mitochondrial, and/or environmental risk factors.

Abstract Based on the success of cancer immunotherapy, personalized cancer vaccines have emerged as a leading oncology treatment. Antigen presentation on MHC class I (MHC-I) is crucial for the adaptive immune response to cancer cells, necessitating highly predictive computational methods to model this phenomenon. Here, we introduce HLApollo, a transformer-based model for peptide-MHC-I (pMHC-I) presentation prediction, leveraging the language of peptides, MHC, and source proteins. HLApollo provides end-to-end treatment of MHC-I sequences and deconvolution of multi-allelic data, using a negative-set switching strategy to mitigate misassigned negatives in unlabelled ligandome data. HLApollo shows a 12.65% increase in average precision (AP) on ligandome data and a 4.1% AP increase on immunogenicity test data compared to next-best models. Incorporating protein features from protein language models yields further gains and reduces the need for gene expression measurements. Guided by clinical use, we demonstrate pan-allelic generalization which effectively captures rare alleles in underrepresented ancestries.

Objective: Racial disparities in organ allocation may result in differential survival for marginalized groups. This study aims to examine the impact of the November 2017 lung allocation policy change (LAPC) on trends and outcomes of Hispanic lung transplant (LT) recipients. Methods: The United Network for Organ Sharing database was used to identify adult (older than age 18 years) LT recipients between January 2010 and March 2023. Recipients were categorized into 3 self-identified racial groups (Hispanic, non-Hispanic White, and non-Hispanic other). The Mann-Kendall trend test was used to assess the trend in rates of Hispanic LT over 5 years pre- and 5 years post-LAPC. The primary outcome was 1-year mortality. Results: A total of 28,495 recipients from 80 centers were included, with 15,343 (53.8%) prepolicy change and 13,152 (46.2%) postpolicy change. The racial distribution of LT recipients was pre-LAPC: Hispanic: 1013 (6.6%), White: 12,601 (82.1%), Other: 1729 (11.3%) and post-LAPC: Hispanic: 1522 (11.6%), White: 9873 (75.0%), Other: 1757 (13.4%) (P

Abstract Background Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well‐established long‐term intervention recognized for its universal anti‐ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair‐deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity. Methods Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1Δ/− progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney. Results Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P

Abstract Background Positive outcomes of simulation programmes to prepare students for placement are widely noted. However, few studies adequately describe considerations for designing allied health placement simulations. There exists a conceptual framework to guide such simulation design, which draws on theory and educational expertise but to date lacks varied stakeholder perspectives. This study aimed to identify implications for the design of allied health placement simulation from participants’ experiences of a simulation-based, interprofessional, novice placement preparation programme. Methods Occupational therapy, physiotherapy and podiatry students finishing their first year of study were offered a 1-week intensive interprofessional simulation immediately before their first placement. Focus groups in the following weeks allowed participants to discuss their experiences of the programme, preparation for student placements, and recommendations. These were transcribed and interpreted using reflexive thematic analysis and then abductively related to the conceptual framework. Results In total, 22 participants broadly representative of the simulation programme participants contributed to separate focus groups with domestic-enrolled students (n = 7), international students (n = 5), external practice educators (n = 6), and simulated participants (n = 4). Inductive reflexive thematic analysis generated six themes: (i) engaging learning environment, (ii) realism and relevance, (iii) student confidence and communication, (iv) international students’ needs, (v) recommendations to facilitate further preparation for placement, and (vi) importance of preparation to engage in simulation. All participant groups were invested in the programme and highlighted learning opportunities. An immersive and relatable experience with active participation contributed to confidence and communication skill development. International students noted needs pertaining to cultural and language expectations. Other participant recommendations related to the equity of opportunities and specific preparation for placement student-educator interactions. Finally, every participant group noted features of effective preparation for simulation-based education. Conclusions Relating these findings abductively to the literature and conceptual frameworks, this study highlights simulation design considerations for learner needs assessment, engagement, realism, psychological safety, and challenge to prepare learners for their first clinical placement. Specific implications for adequately preparing all participant groups, design considerations for the needs of culturally diverse students, and balancing interprofessional and discipline-specific learning are highlighted from a lived experience viewpoint. Future research may engage greater stakeholder co-design in simulation-based education.

Abstract Background Paracetamol is the most consumed medicine globally. Its accessibility contributes to common overdose. Paracetamol overdose is responsible for > 50% of acute liver failure cases, making it the second most common reason for a liver transplant. Rapid quantitation of paracetamol is crucial to guide treatment of paracetamol overdose. Current tests require invasive sampling and relatively long turnaround times. Paper arrow-mass spectrometry (PA-MS) combines sample collection, extraction, separation, enrichment and ionisation onto a single paper strip, achieving rapid, accurate, cost-effective and eco-friendly analysis direct from raw human saliva. Methods To validate PA-MS against an established test, 17 healthy adults were recruited. Samples were collected before and at 15, 30, 60, 120 and 240 min after ingesting 1 g of paracetamol. Plasma measured with an established clinical test served as the reference standard to validate PA-MS with three biofluids—plasma, resting saliva (RS) and stimulated saliva (SS). Participants’ views of blood, RS and SS sampling procedures were assessed qualitatively. Cross-validation was assessed using Lin’s concordance correlation coefficients (CCC), Bland–Altman difference plots, and ratios of PA-MS to the reference standard test. Results PA-MS using stimulated saliva offers a reliable alternative to intravenous blood sampling. The CCC is 0.93, the mean difference with the reference test is − 0.14 mg/L, and the ratios compared to the reference test are 0.84–1.27 from correlated samples collected at 5 intervals over 4 h for each participant. Conclusions Paracetamol detection from SS with PA-MS provides a reliable result that can aid timely treatment decisions. Differences between paracetamol concentration in resting and stimulated saliva were also identified for the first time, highlighting the importance of standardising saliva collection methods in general. This study marks a major milestone towards rapid and convenient saliva analysis.

Abstract Circulating tumor DNA (ctDNA) has shown potential as a non-invasive tumor biomarker in neuroblastoma. Previous studies used generic assays for detection of selected predefined oncogenic variants as markers of ctDNA, which limits the sensitivity and excludes a subset of patients from analysis. Here we assessed patient-specific ctDNA analysis for treatment evaluation and detection of relapse in neuroblastoma. We generated personalized sequencing panels targeting 10 tumor-specific single nucleotide variants (SNVs) for each patient and performed ctDNA analysis of 136 plasma samples collected longitudinally in 13 children with neuroblastoma. ctDNA was detected using ultra-deep next generation sequencing with unique molecular identifiers to eliminate polymerase-induced errors. We found that the levels of ctDNA at diagnosis correlated with risk group and decreased gradually during effective treatment. All samples collected during follow-up in patients without disease relapse were ctDNA-negative. All four relapses were associated with elevated ctDNA levels, and a majority of the analyzed SNVs were detected at time of relapse. In one case, ctDNA became positive 78 days before the relapse was diagnosed with routine assessment and increased by over a thousandfold before the start of additional treatment. Overall, ctDNA was more uniformly elevated at diagnosis, showed less putative false positive results, and was more sensitive for detection of relapse compared to five serum or urine tumor markers used in clinical routine. In conclusion, personalized ctDNA analysis is suitable for clinical monitoring of tumor burden and may be used in all neuroblastoma patients regardless of risk group or tumor genetics.

Abstract Background The Universal Infant Free School Meal (UIFSM) policy was introduced in 2014/15 in England and Scotland for schoolchildren aged 4–7 years, leading to an increase in school meal uptake. UK school meals are known to be healthier and less industrially processed than food brought from home (packed lunches). However, the impact of the UIFSM policy on the quantity of ultra-processed food (UPF) consumed at school during lunchtime is unknown. This study aimed to evaluate the impact of the UIFSM policy on lunchtime intakes of UPF in English and Scottish schoolchildren. Methods Data from the UK National Diet and Nutrition Survey (2008–2019) were used to conduct a difference-in-difference (DID) natural experiment. Outcomes included school meal uptake and the average intake of UPF (% of total lunch in grams (%g) and % total lunch in Kcal (%Kcal)) during school lunchtime. The change in the outcomes before and after the introduction of UIFSM (September 2014 in England, January 2015 in Scotland) in the intervention group (4–7 years, n = 835) was compared to the change in an unexposed control group (8–11 years, n = 783), using linear regression. Inverse probability weights were used to balance characteristics between intervention and control groups. Results Before UIFSM, school meal uptake and consumption of UPFs were similar in the intervention and control groups. The DID model showed that after UIFSM, school meal uptake rose by 25%-points (pp) (95% CI 14.2, 35.9) and consumption of UPFs (%g) decreased by 6.8pp (95% CI -12.5,-1.0). Analyses indicated this was driven by increases in minimally processed dairy and eggs, and starchy foods, and decreases in ultra-processed salty snacks, bread and drinks. The differences were larger in the lowest-income children (-19.3 UPF(%g); 95% CI -30.4,-8.2) compared to middle- and high-income children. Analyses using UPF %Kcal had similar conclusions. Conclusions This study builds on previous evidence suggesting that UIFSM had a positive impact on dietary patterns, showing that it reduced consumption of UPFs at school lunchtime, with the greatest impact for children from the lowest-income households. Universal free school meals could be an important policy for long term equitable improvements in children’s diet.

Abstract Background Poverty is a key social determinant of mental health among forcibly displaced persons. This study aimed to design and pilot test a strategy to integrate existing mental health and economic inclusion interventions for displaced families in Ecuador. Methods We conducted a series of qualitative interviews (n = 30), focus groups (n = 6), and workshops (n = 3) to develop a set of strategies for integrating cross-cutting and focused mental health and psychosocial support (MHPSS) strategies into an existing economic inclusion program for displaced families in Quito. We non-randomly assigned two field offices in Quito to (1) integrate cross-cutting strategies focused on improving economic outcomes or (2) integrate both those cross-cutting strategies plus focused MHPSS strategies into an economic inclusion program. We measured site-level implementation outcomes (adoption, appropriateness, acceptability, feasibility, fidelity, reach, retention, usability) and participant-level psychosocial (wellbeing, depressive symptoms, anxiety symptoms, functioning) and economic inclusion outcomes (financial resources, diet diversity, social capital/networks, self-reliance) over six months. We conducted a mixed-methods analysis to explore the acceptability and feasibility of the integration strategies and the ability to evaluate their effects in a future cluster randomized trial. Results We developed a toolkit that included 10 strategies for integrating MHPSS into economic inclusion interventions. Fifty displaced persons participating in an existing economic inclusion program (25 per study condition) were enrolled and 88% remained in the study through the six-month follow-up. Participants and implementers reported that the integration strategy was appropriate, acceptable, feasible, and usable. Implementers, including people without prior experience in delivering mental health services, were able to deliver the intervention with high fidelity. Integration of focused MHPSS intervention components into an economic inclusion program appeared to improve MHPSS outcomes, the strength of social capital and networks, and engagement in economic and other programs. Conclusions This study provides preliminary evidence of the acceptability and feasibility of integrating MHPSS into economic inclusion programs for displaced people. We found evidence supporting evaluation methods that can be employed in a future study to definitively test the added value of integrated approaches to mental health and economic wellbeing for displaced persons.

Abstract Objective Memory is one of the most sensitive markers of cognitive compromise in people with new‐onset epilepsy. Nonetheless, around half of these cases score within the normal range on standard memory testing. Here we explore whether memory retention at a 1‐week delay reveals otherwise undetected memory compromise in such individuals, and how it relates to subjective memory complaints and mood. Methods Using a prospective design, 38 adults with new‐onset epilepsy underwent baseline memory screening via telephone using an abbreviated Rey Auditory Verbal Learning Test (RAVLT). Psychological screening occurred via online questionnaires. One week later, without forewarning, participants completed three follow‐up memory tasks. Of particular focus, we explored longer‐term memory performances and forgetting trajectories in those individuals (n = 23) who demonstrated normal memory performances (scores >10th percentile) at baseline (30‐min delay). Outcomes were compared to 32 healthy controls, matched for age, sex, and education. Results As a group, people with epilepsy performed worse than controls on all memory measures, with 44 percent impaired at baseline testing. Of those unimpaired at baseline, the rate and volume of information loss over 1 week was significantly greater than for controls. Contextual memory performance at 1 week was also significantly poorer for people with epilepsy. At the individual level, the prevalence of impaired forgetting was not significantly different between patients and controls. Subjective memory complaints were not related to any objective tests but were strongly related to self‐reported mood and anxiety symptoms. Significance People with new‐onset epilepsy show reduced memory at short and extended intervals. For those showing normal memory at baseline, information does appear to be forgotten more quickly than in healthy controls, though the effect is not large. The findings indicate that while extended delay memory testing is not essential in all new epilepsy cases, it could provide useful information for particular individuals. Plain Language Statement Memory problems are common in people with epilepsy shortly after seizure onset, however, many individuals still show normal memory performances on standard neuropsychological testing. Through testing memory at an extended timepoint (1 week), our study found that on average, these individuals showed a slightly quicker rate of forgetting over a 1‐week period than people without a brain condition. Self‐reported memory complaints in people with new epilepsy were unrelated to their actual memory skills on testing at short and long timepoints but were rather linked to lower mood and quality of life.

Abstract Objective We evaluated huperzine A treatment in the Genetic Absence Epilepsy Rat from Strasbourg (GAERS) model of genetic generalized epilepsy (GGE) with absence seizures. Methods Adult male GAERS (N = 15) were implanted with EEG recording electrodes 10 days before receiving study drug. Each animal received the following six treatments as a single, intraperitoneal dose, 7 days apart (in random order): huperzine A (0.3, 1.0, or 3.0 mg/kg), two periods of vehicle (0.9% NaCl), or ethosuximide (100 mg/kg) as a positive control. Electroencephalograms (EEGs) were acquired for 24 h before and after each treatment and analyzed for seizure activity during the 90‐min period immediately post‐treatment, including 30‐min intervals at 30, 60, and 90 min. Additional analyses evaluated seizure activity over the 24‐h post‐treatment period using 60‐min intervals at 6, 12, and 24 h. The cumulative 24‐h periods before and after each administered treatment were also compared. Results Two‐way ANOVA showed a treatment difference [F(91,182) = 3.592, p

In Scotland, the policy landscape around rent controls is rapidly evolving and full of uncertainty. At this critical moment, an international symposium in Edinburgh brought together activists and academics in similar contexts living with or fighting for rent controls from across Europe and North America. This contribution is organised around reflections from the participants on (1) the history of rent controls in their area; (2) the current rent regulations in operation and their effectiveness; (3) the role of tenants’ organisations and (4) landlord and other pro-real estate lobbies in shaping the discourse around rent controls; and (5) reflections on what a satisfactory resolution on the rent control issue might look like and how it relates to other dimensions of the housing system. Our collective hope is that these reflections contribute to sharpening and clarifying the re-emergence of demands for rent control in Europe and North America as a powerful tool––if insufficient by itself––for shaping a decommodified housing system.

Abstract Background Social inequalities in child mental health are an important public health concern. Whilst previous studies have examined inequalities at a single time point, very few have used repeated measures outcome data to describe how these inequalities emerge. Our aims were to describe social inequalities in child internalising and externalising problems across multiple countries and to explore how these inequalities change as children age. Methods We used longitudinal data from eight birth cohorts containing participants from twelve countries (Australia, Belgium, Denmark, France, Germany, Greece, Italy, Netherlands, Poland, Norway, Spain and the United Kingdom). The number of included children in each cohort ranged from N = 584 (Greece) to N = 73,042 (Norway), with a total sample of N = 149,604. Child socio‐economic circumstances (SEC) were measured using self‐reported maternal education at birth. Child mental health outcomes were internalising and externalising problems measured using either the Strengths and Difficulties Questionnaire or the Child Behavior Checklist. The number of data collection waves in each cohort ranged from two to seven, with the mean child age ranging from two to eighteen years old. We modelled the slope index of inequality (SII) using sex‐stratified multi‐level models. Results For almost all cohorts, at the earliest age of measurement children born into more deprived SECs had higher internalising and externalising scores than children born to less deprived SECs. For example, in Norway at age 2 years, boys born to mothers of lower education had an estimated 0.3 (95% CI 0.3, 0.4) standard deviation higher levels of internalising problems (SII) compared to children born to mothers with high education. The exceptions were for boys in Australia (age 2) and both sexes in Greece (age 6), where we observed minimal social inequalities. In UK, Denmark and Netherlands inequalities decreased as children aged, however for other countries (France, Norway, Australia and Crete) inequalities were heterogeneous depending on child sex and outcome. For all countries except France inequalities remained at the oldest point of measurement. Conclusions Social inequalities in internalising and externalising problems were evident across a range of EU countries, with inequalities emerging early and generally persisting throughout childhood.

Abstract The demand for electric power has consistently been on the rise, owing to urbanisation and technological improvements. On the generation side, renewable sources have been favoured over their polluting, exhaustible, non‐renewable counterparts. These changes in the power system have necessitated a system for maintaining the supply‐demand balance, to maintain system stability. A complex power system is also more prone to blackouts and grid failure. Islanding helps in provision of supply to consumers in a microgrid, reducing the possibility of a blackout. Depending on the power demand and generation, loads need to be shed or restored to mitigate power imbalances. A wide area distribution management system (WADMS) is proposed to dynamically shed and restore loads in the islanded mode, with the aid of micro phasor measurement units (µPMUs). A priority and consumer‐based load shedding and restoration (PCLS) algorithm is proposed in the WADMS that preferentially sheds or restores loads based on their assigned load priority indices and number of consumers. The algorithm has been tested on a modified IEEE 13 bus system, incorporated with a solar photovoltaic (PV) system, diesel generators (DGs) and an energy storage system (ESS) in MATLAB Simulink.

Abstract Two cystic fibrosis (CF) rat models, one carrying the common Phe508del mutation and the other a nonsense cystic fibrosis transmembrane conductance regulator (CFTR) mutation (knockout) were previously characterised. Although relevant CFTR mRNA reductions were present in the lung, no overt CF lung disease was observed. This study used flexiVent lung mechanic assessment and regional ventilation assessment via X-ray velocimetry (XV) functional imaging to assess the lung phenotype in both models. To determine the sensitivity of XV regional ventilation imaging, the effect of a localised physical obstruction (delivery of agar beads to part of the lungs) on lung ventilation was examined. At baseline, Phe508del and knockout CF rats had a lower inspiratory capacity, total respiratory system compliance, and static compliance than wildtype rats. Following agar bead delivery all XV ventilation parameters were altered, with substantial increases in poorly ventilated regions and ventilation heterogeneity. XV ventilation maps accurately identified locations of bead-induced airflow changes. Despite unremarkable lung histopathology, this study indicated that CF rats display altered respiratory mechanics, with CF rats needing to exert additional effort to expand and deflate their lungs due to increased stiffness. This study demonstrated the utility of XV imaging providing spatial lung ventilation information.

Abstract Background Traumatic injuries, defined as physical injuries with sudden onset, are a major cause of distress and disability, with far-reaching societal consequences. A significant proportion of trauma survivors report persistent symptoms and difficulties after the injury, and studies show unmet health care needs. Self-management programs delivered in the sub-acute phase after traumatic injuries are scarcely evaluated. The aim of the present study is to evaluate the effectiveness of a self-management program (SEMPO), delivered 3–4 months after moderate-to-severe traumatic injury. Methods This study protocol describes a pragmatic randomized controlled trial (RCT) with two classical RCT arms (intervention and control) and an explorative self-selection arm. 220 patients will be recruited from Oslo University Hospital, the largest Trauma Referral Centre in Norway. Patients aged 18–72 years residing in the south-east region of Norway, admitted to the Trauma Centre directly or within 72 h after having sustained a moderate to severe traumatic injury, defined as a New Injury Severity Score > 9, having at least 2 days hospital stay, and reporting injury-related symptoms and impairment at discharge from the acute hospital will be included. Patients will be randomly assigned to either a classical RCT randomization arm (intervention or control arm) or to a self-selection arm. In the randomization arm, participants are further randomized into intervention or control group. Participants allocated to the self-selection arm will choose to partake either in the intervention or control arm. The primary outcome is the level of self-efficacy in trauma coping assessed 6 months after completion of the intervention, with a similar time point for the control group. Secondary outcomes include symptom burden, physical functioning and disability, return to work and health care utilization, health-related quality of life, and communication competency. In addition, patients will be asked to nominate one domain-related measurement as their preferred outcome measure. Discussion This RCT will determine the effect of a self-management program tailored to patients with moderate to severe physical trauma, and the self-selection arm incorporates the potential influence of patient treatment preferences on intervention results. If the intervention proves effective, cost-effectiveness and cost-utility analyses will be performed and thereby provide important information for clinicians and policy makers. Trial registration The study is registered in Clinical Trials with the identifier: NCT06305819. Registered on March 05, 2004.

Abstract Background N6-methyladenosine (m6A) is the most common internal RNA modification and is involved in regulation of RNA and protein expression. AlkB family member 5 (ALKBH5) is a m6A demethylase. Given the important role of m6A in biological mechanisms, m6A and its regulators, have been implicated in many disease processes, including cancer. However, the contribution of ALKBH5 to invasive breast cancer (BC) remains poorly understood. The aim of this study was to evaluate the clinicopathological value of ALKBH5 in BC. Methods Publicly available data were used to investigate ALKBH5 mRNA alterations, prognostic significance, and association with clinical parameters at the genomic and transcriptomic level. Differentially expressed genes (DEGs) and enriched pathways with low or high ALKBH5 expression were investigated. Immunohistochemistry (IHC) was used to assess ALKBH5 protein expression in a large well-characterised BC series (n = 1327) to determine the clinical significance and association of ALKBH5 expression. Results Reduced ALKBH5 mRNA expression was significantly associated with poor prognosis and unfavourable clinical parameters. ALKBH5 gene harboured few mutations and/or copy number alternations, but low ALKBH5 mRNA expression was seen. Patients with low ALKBH5 mRNA expression had a number of differentially expressed genes and enriched pathways, including the cytokine-cytokine receptor interaction pathway. Low ALKBH5 protein expression was significantly associated with unfavourable clinical parameters associated with tumour progression including larger tumour size and worse Nottingham Prognostic Index group. Conclusion This study implicates ALKBH5 in BC and highlights the need for further functional studies to decipher the role of ALKBH5 and RNA m6A methylation in BC progression.

Abstract A significant warming effect on arctic tundra is greening. Although this increase in predominantly woody vegetation has been linked to increases in gross primary productivity, increasing temperatures also stimulate ecosystem respiration. We present a novel analysis from small-scale plot measurements showing that the shape of the temperature- and light-dependent sink-to-source threshold (where net ecosystem exchange (NEE) equals zero) differs between two tussock tundra ecosystems differing in leaf area index (LAI). At the higher LAI site, the threshold is exceeded (i.e the ecosystem becomes a source) at relatively higher temperatures under low light but at lower temperatures under high light. At the lower LAI site, the threshold is exceeded at relatively lower temperatures under low light but at higher temperatures under high light. We confirmed this response at a single site where LAI was experimentally increased. This suggests the carbon balance of the tundra may be sensitive to small increases in temperature under low light, but that this effect may be significantly offset by increases in LAI. Importantly, we found that this LAI effect is reversed under high light, and so in a warming tundra, greater vegetation cover could have a progressively negative effect on net carbon uptake.

Abstract Background Forestry and land-use change are leading causes of habitat loss, degradation, and fragmentation worldwide. The boreal forest biome is no exception, and only a small proportion of this forest type remains intact. Since forestry will remain a major land-use in this region, measures must be taken to ensure forest dependent biodiversity. Stand level features and structures promoting conservation relevant species have received much attention, but the landscape level perspective is often missing. Hence, we review the literature that has related fragmentation in the surrounding landscape to occurrence of threatened, declining, red-listed, rare, or deadwood dependent species as well as those considered to be indicator, flagship, umbrella, and/or keystone species in a given boreal forest stand. Methods A comprehensive search string was developed, benchmarked, and adapted for four bibliographic databases, two search engines, and 37 specialist websites. The online evidence synthesis tool Cadima was used for screening of both abstracts and full texts. All articles meeting the inclusion criteria were subject to study validity assessment and included in a narrative table. Studies reporting means and variance were included in quantitative meta-analysis when more than 3 comparable studies were available. Results The searches resulted in 20 890 unique articles that were reduced to 172 studies from 153 articles. These studies related stand level presence, abundance, species richness, and/or composition of conservation relevant species to landscape factors such as: categorical fragmentation intensity (higher vs. lower), amount of habitat or non-habitat, distance to habitat, and/or habitat configuration, on scales ranging from tens to tens of thousands of ha. Forty-three studies were suitable for meta-analysis. These showed a significant negative effect of fragmentation on both presence and abundance of conservation relevant species, as well as a near significant trend for species richness. This was particularly clear when fragmentation was measured as distance to surrounding habitat for presence, and as habitat amount for abundance. The organism groups with the strongest support for a negative effect of fragmentation were wood fungi and birds. Conclusion As hypothesised, there is strong support for negative effects of fragmentation in boreal forest. These results emphasize the negative consequences of the intensive forestry and associated landscape transformation that has been the norm for the last century. We argue that this should have direct implications for policy makers to shift towards including a landscape perspective in all planning of harvesting, preserving, and restoring forest. In addition, we found that research effort has been very uneven between organism groups, that studies on landscape change over time were rare, and that many studies have not quantified the difference in fragmentation intensity among landscapes making it difficult to quantify the extent of the negative effect. One way forward would be to revisit the studies included here in to incorporate change over time, as well as a true quantification of landscape fragmentation. By doing so, the scale of the negative effects would be much better analysed, which would greatly assist conservation practitioners all throughout the boreal forest biome.

Abstract Introduction Since the beginning of the COVID-19 pandemic, COVID-19 risk mitigation measures have expanded to include increased rules and surveillance in supportive housing. Yet, in the context of the dual public health emergencies of COVID-19 and the unregulated drug toxicity crisis, we have not evaluated the unintended health and social consequences of such measures, especially on criminalized women. In order to address this dearth of evidence, our aim was to assess the association between increased housing rules and surveillance during COVID-19 and (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal among women sex workers who use drugs in Vancouver, BC. Methods This study is nested within An Evaluation of Sex Workers Health Access (AESHA), a community-based prospective cohort of women sex workers in Metro Vancouver (2010–present). Using cross-sectional data collected during the first year of COVID-19 (April 2020–2021), we developed separate multivariable logistic regression confounder models to examine the independent associations between experiencing increased housing rules and surveillance during COVID-19 on (a) nonfatal overdose, and (b) administration of naloxone for overdose reversal in the last 6 months. Results Amongst 166 participants, 10.8% reported experiencing a recent non-fatal overdose and 31.3% recently administered naloxone for overdose reversal. 56.6% reported experiencing increased rules and surveillance within their housing during COVID-19. The prevalence of non-fatal overdose and administering naloxone was significantly elevated among those exposed to increased housing rules and surveillance during COVID-19 versus those who were unexposed (83.3% vs. 52.1%; 75.0% vs. 48.2%, respectively). In separate multivariate confounder models, exposure to increased housing rules and surveillance during COVID-19 was independently associated with increased odds of administering naloxone [AOR: 3.66, CI: 1.63–8.21], and marginally associated with non-fatal overdose [AOR: 3.49, CI: 0.92–13.27]. Conclusion Efforts to prioritize the right to safe, adequate and affordable housing must avoid reinforcing an overly coercive reliance on surveillance measures which, while often well-intended, can negatively shape residents’ well-being. Furthermore, public health responses to pandemics must include criminalized populations so that measures do not exacerbate overdose risk. Implementation of a regulated drug supply is recommended, alongside housing policies that promote residents' rights, safety, and health.

Abstract Introduction This study sought to evaluate the cost-effectiveness of baloxavir marboxil compared with oseltamivir or no antiviral treatment from a US payer perspective using data from a real-world US administrative claims study. Given baloxavir’s ability to rapidly stop viral shedding, the potential health economic implications of a baloxavir-induced population-level reduction in viral transmission was also explored. Methods A decision tree cost-effectiveness model was developed for seasonal influenza (2018–2020) using a lifetime time horizon with 3.0% discounting for costs and quality-adjusted life-years (QALYs). Patients aged ≥ 12 years could receive baloxavir, oseltamivir or no antiviral treatment. Patient characteristics, complications, and costs were derived from the Merative™ MarketScan® Research Databases including US commercial claims and Medicare and Medicaid Supplemental databases. A scenario analysis explored the impact of reduced viral transmission with baloxavir. Results In the base case analysis, baloxavir was cost-effective within a willingness-to-pay threshold of US$100,000/QALY compared with oseltamivir [incremental cost-effectiveness ratio (ICER), $6813/QALY gained] or no antiviral treatment (ICER, $669/QALY gained). The net monetary benefit (NMB) of baloxavir was $1180 and $6208 compared with oseltamivir and no treatment, respectively. The NMB of baloxavir increased linearly with reductions in viral transmission, where a 5% transmission reduction yielded an NMB of $2592 versus oseltamivir and $7621 versus no treatment. Baloxavir became dominant (more effective and less costly, with ICERs

Abstract Background Work-integrated learning (WIL) is a core aspect of allied health education. WIL placements typically focus on developing clinical skills, with broader conceptions of work readiness a secondary consideration. Near-peer mentoring (NPM), where senior students mentor junior students, is one WIL placement model that holds promise for developing students’ work readiness, along with additional benefits for educators and service users. While there is emerging evidence of the benefits of NPM in allied health, a more comprehensive understanding of the design and outcomes of NPM WIL placements for allied health students, their educators and service users is needed. Methods A systematic search of seven electronic databases (CINAHL, ERIC, ProQuest Education, Medline, PsychInfo, EMBASE and Scopus) from 2003 to 2022 was conducted with 4195 records reviewed. Included studies reported on near-peer mentoring between at least one of the identified 11 allied health professionals providing services to real people (i.e. not simulation). Data extracted included pedagogical approaches, type of service model and relationship of peers to each other and educator, objectives for implementing the NPM, and effects for students. Quality appraisal was undertaken using the Standards for Reporting of Qualitative Research (SRQR). Results Fourteen studies met the inclusion criteria. The majority were North American in origin, from the disciplines of pharmacy, physiotherapy, psychology and occupational therapy, and used a range of research designs. Four types of placement design were observed from incidental co-location of students and observing outcomes through to deliberate preparation of students and/or educators for their roles in a NPM placement. Outcomes for junior students included lowered anxiety leading to increased confidence and motivation to learn and thus enhanced clinical skills. Senior student outcomes included development of educator skills, increased confidence, and enhanced professional reasoning. Service users and educators also benefited from NPM; however, evidence was sparse in these areas. Conclusion The evidence supports near-peer mentoring as a valuable WIL model to support work readiness, and several general pedagogical designs are evident. Future research should design NPM WIL with a greater integration of educational theory and evaluate outcomes beyond satisfaction and self-reported experiences.

Objective: Evaluate efficacy of cognitive behavioural therapy for sleep and fatigue adapted for brain injury relative to health education control in alleviating sleep disturbance and fatigue after acquired brain injury. Design: Parallel groups randomized controlled trial. Subjects: 126 community dwelling adults with stroke or traumatic brain injury. Methods: Participants were randomized 2:1 to receive 8-weeks of cognitive behavioural therapy for sleep and fatigue (n = 86) or health education (n = 40). The Pittsburgh Sleep Quality Index was assessed pre- and post-treatment, and 2 and 4-months post-treatment, with secondary measures of insomnia, fatigue, sleepiness, mood, quality of life, activity levels, self-efficacy, and actigraphy. Results: Both groups showed improved sleep by 4-month follow-up. However, cognitive behavioural therapy for sleep and fatigue had significantly larger and more rapid improvements than health education immediately post-treatment (β = –1.50, p

Molecular characterization of tumors is essential to identify predictive biomarkers that inform treatment decisions and improve precision immunotherapy development and administration. However, challenges such as the heterogeneity of tumors and patient responses, limited efficacy of current biomarkers, and the predominant reliance on single-omics data, have hindered advances in accurately predicting treatment outcomes. Standard therapy generally applies a “one size fits all” approach, which not only provides ineffective or limited responses, but also an increased risk of off-target toxicities and acceleration of resistance mechanisms or adverse effects. As the development of emerging multi- and spatial-omics platforms continues to evolve, an effective tumor assessment platform providing utility in a clinical setting should i) enable high-throughput and robust screening in a variety of biological matrices, ii) provide in-depth information resolved with single to subcellular precision, and iii) improve accessibility in economical point-of-care settings. In this perspective, we explore the application of label-free Raman spectroscopy as a tumor profiling tool for precision immunotherapy. We examine how Raman spectroscopy’s non-invasive, label-free approach can deepen our understanding of intricate inter- and intra-cellular interactions within the tumor-immune microenvironment. Furthermore, we discuss the analytical advances in Raman spectroscopy, highlighting its evolution to be utilized as a single “Raman-omics” approach. Lastly, we highlight the translational potential of Raman for its integration in clinical practice for safe and precise patient-centric immunotherapy.

Conclusions: The SHA2PE score demonstrates potential in predicting cases of low-risk LGIB, offering a high NPV for hospitalization, the need for intrahospital intervention, and return visits to the ED. However, these findings should be interpreted cautiously given the low prevalence of interventions and limitations in the study’s population and design.

Category: Ankle; Trauma Introduction/Purpose: High energy trauma to the ankle joint can cause soft tissue damage and bone disruption of the tibial plafond. Currently, the most widely accepted treatment options are the External Fixation and the Open Reduction and Internal Fixation (ORIF) surgical procedures. The goal of this study was to determine if the quality of these procedures in patients with a Type-C Tibial Plafond Fracture has a relationship with a patient’s chances of developing a post-surgical complication. Methods: This retrospective study included a population of 131 patients with a Type-C Tibial Plafond Fracture who were operated on at Grady Memorial Hospital from 2012 to 2023. No exclusions based on past medical history were applied. Grady Sectra Fluoroscopy videos as well as AP and Lateral x-rays were evaluated and the AP translation, Lateral Translation, Anatomic Lateral Distal Tibia Angle (aLDTA), and Anterior Distal Tibia Angle (ADTA) measurements of the tibial plafond fracture post External Fixation and ORIF procedures were recorded, and any differences were assessed. Binary Logistic Regression was used to determine if there was a significant difference in any of the External Fixation measurements and post-operative complications. Pearson Correlation was used to determine if the alignment in the External Fixation was a predictor of the alignment after ORIF. Results: The initial population sample of 131 patients was reduced to 99 patients due to patients being excluded from the study because their imaging files were incomplete. The data showed that neither the translational nor angular alignments post External Fixation nor ORIF had any statistically significant correlation to a patient’s chances of developing a post-surgical complication. Using the Pearson Efficient, the External Fixation AP and Lateral translation measurements were 0.16 (p-value 0.12) and 0.171 (p-value 0.095) respectively, so there was no significant correlation to the final AP and Lateral measurements of the ORIF procedure. The External Fixation aLDTA and ADTA values of 0.289 (p-value 0.004) and 0.336 (p-value < 0.001) respectively, were significantly related to the final aLDTA and ADTA angles of the ORIF procedure. Conclusion: The results from this study will have a positive implication on clinical practice as it encourages trauma orthopedic surgeons to achieve tibial plafond alignment angles during the External Fixation procedure that are as anatomically correct as possible in order to improve the efficacy and accuracy of the ORIF procedure.

Studying primary biological aerosol particles in the Arctic is crucial to understanding their role in cloud formation and climate regulation at high latitudes. During the Arctic Ocean 2018 expedition, fluorescent primary biological aerosol particles (fPBAPs) were observed, using a multiparameter bioaerosol spectrometer, near the North Pole during the transition from summer to early fall. The fPBAPs showed a strong correlation with the occurrence of ice nucleating particles (INPs) and had similar concentration levels during the first half of the expedition. This relationship highlights the potential importance of biological sources of INPs in the formation of mixed-phase clouds during the central Arctic’s summer and early fall seasons. Our analysis shows that the observed fPBAPs were independent of local wind speed and the co-occurrence of other coarse mode particles, suggesting sources other than local sea spray from leads, melt ponds, re-suspension of particles from the surface, or other wind-driven processes within the pack ice. In contrast, other fluorescent particles were correlated with wind speed and coarse mode particle concentration. A multi-day event of high concentrations of fPBAPs was observed at the North Pole, during which the contribution of fPBAPs to the total concentration of coarse mode aerosol increased dramatically from less than 0.1% up to 55%. Analysis of chemical composition and particle size suggested a marine origin for these fPBAPs, a hypothesis further supported by additional evidence. Air parcel trajectory analysis coupled with ocean productivity reanalysis data, as well as analysis of large-scale meteorological conditions, all linked the high concentrations of fPBAPs to biologically active, ice-free areas of the Arctic Ocean.

Abstract Convective cloud processes are sensitive to environmental conditions that vary on scales smaller than reanalysis data sets (sub‐reanalysis scales). Convective environment variability within areas representative of reanalysis data sets is quantified using large‐domain, high‐resolution (∆x = 100 m) simulations of convective cloud systems throughout the tropics and subtropics. Even after removing locations of resolved clouds and precipitation, convective environment parameters vary significantly on these scales. For example, for half of the simulated data, 500 hPa relative humidity varies by ∼30% within a typical reanalysis area. Surface winds, convective available potential energy, and middle‐tropospheric moisture are the most variable convective environment parameters for both continental and maritime regimes, while above‐surface temperature and winds are the least variable. While high‐resolution, sub‐reanalysis‐scale extrema are well‐correlated with the reanalysis‐area mean values, some of the most extreme convective environments can occur within regions with moderate reanalysis‐area mean values, particularly for continental regions.

Aquaculture farms represent a complex 3D environment and face regular seasonal challenges such as acute and chronically elevated temperatures during summer. Further, fish are exposed to the interaction between their environment and farm operations, which can cause challenging conditions. In the context of modern net-pen aquaculture and ocean warming, there is therefore a need to understand the welfare of these commercially important species under the realistic conditions they encounter. Fish were tagged with two types of biologgers measuring temperature, heart rate, external acceleration, and depth of fish as they experienced standard aquaculture operations over two periods of thermal stress, one short-term and one long-term. The fish response during the thermal stress events was compared with the periods preceding and following both events, and an additional analysis was carried out to further explore the effects of feeding and farm operations. Fish displayed signs of both secondary and potentially tertiary stress in response to the short- and long-term heat event and both heart rate and acceleration increased in response to feeding but displayed a more nuanced response to operations. As part of the broader concept of precision fish farming, this research, based on data from 7 individual fish, represents a case study that presents the potential use of biologgers as tools for recognising early signs of stress by observing the secondary stress response, thereby demonstrating the potential for informed and timely stress identification to guide farm management decisions to enhance fish welfare and production efficiency in commercial aquaculture.

ABSTRACTOver the last 20 years, the larva of the greater waxmoth, Galleria mellonella, has rapidly increased in popularity as an in vivo mammalian replacement model organism for the study of human pathogens. Experimental readouts of response to infection are most often limited to observing the melanization cascade and quantifying larval death and, whilst transcriptomic and proteomic approaches, and methods to determine microbial load are also used, a more comprehensive toolkit of profiling infection over time could transform the applicability of this model. As an invertebrate, Galleria harbour an innate immune system comprised of both humoral components and a repertoire of innate immune cells – termed haemocytes. Although information on subtypes of haemocytes exists, there are conflicting reports on their exact number and function. Flow cytometry has previously been used to assay Galleria haemocytes, but protocols include both centrifugation and fixation – physical methods which have the potential to affect haemocyte morphology prior to analysis. Here, we present a method for live haemocyte analysis by flow cytometry, revealing that Galleria haemocytes constitute only a single resolvable population, based on relative size or internal complexity. Using fluorescent zymosan particles, we extend our method to show that up to 80% of the Galleria haemocyte population display phagocytic capability. Finally, we demonstrate that the developed assay reliably replicates in vitro data, showing that cell wall β-1,3-glucan masking by Candida albicans subverts phagocytic responses. As such, our method provides a new tool with which to rapidly assess phagocytosis and understand live infection dynamics in Galleria.

Chocolate beverages made from cocoa powder contain phenolic compounds, especially flavonoids, as antioxidants, but these compounds are easily degraded. Incorporating clove bud extract is recommended to improve the quality of these beverages. However, encapsulation is necessary to protect bioactive compounds and reduce bitterness. This study investigated the total phenolic and flavonoid content, antioxidant activity, and characteristics of chocolate beverages formulated with encapsulated clove bud extract. Six formulations ranging from 0% to 10% encapsulated extract were evaluated. The results show that the incorporation of the encapsulated extract significantly improved several attributes as the percentage of clove extract increased. Phenolic and flavonoid content, antioxidant activity, hygroscopicity, lightness (L*), total color difference (∆E), viscosity, solubility, and soluble solids increased. In contrast, moisture content, red/green (a*) and blue/yellow (b*) values, sedimentation, pH, and dissolution time decreased. Panelists preferred beverages with up to 4% encapsulated clove extract, suggesting the potential for healthier ready-to-drink chocolates.

Purpose This study focuses on higher education as a pathway to establishment in a new society for female immigrants and its role in well-being. Building on previous research that highlights social capital and empowerment as significant factors for successful establishment in a new society, and experiencing well-being, this study aims to explore if higher education can promote female immigrants’ establishment in Swedish society. Methods Interviews were used to explore female immigrants’ experiences of higher education and establishment in Swedish society. Thematic analysis was used to analyse the empirical material, generating a nuanced understanding of the studied topic. Results Higher education was found to promote establishment in Swedish society, ultimately leading to an experience of well-being. Pursuing higher education was perceived as a means of achieving personal fulfilment and success while fostering new social connections. Important factors in pursuing higher education included favourable living conditions, personal motivation, and a positive educational attitude. Conclusion The study provides insights into female immigrants’ higher education experiences in a context that promotes establishment in Swedish society and well-being. However, more research is needed to fully investigate the driving factors for female immigrants pursuing higher education, considering their migrant background and living conditions.

Background The importance of nutrition in optimizing the health and performance of professional soccer players has been well established. Despite published practical recommendations for the dietary requirements for professional soccer players, many players fail to meet these guidelines. Thus, the primary purpose of this study was to assess the impact of targeted nutritional education and behavior change interventions on dietary intake in professional football players. Additionally, previous research within this population has reported elevations in resting metabolic rate (RMR) following match-play. Therefore, a further aim of this study was to examine whether any changes in dietary intake would influence RMR following match-play.Methods Twenty players from the professional development phase in an English Premier League club (age: 18.4 ± 1.0 years; body mass: 76.1 ± 6.0 kg; stature: 1.80 ± 0.07 m) were randomly assigned to an “Intervention” (INT) group (n = 10), who received numerous nutritional education and behavior change interventions, or a “Control” (CON) group (n = 10), who received no nutrition support. Dietary intake was assessed daily throughout the match-week (Match Day (MD)-2, MD-1, MD, MD + 1, and MD + 2), whilst RMR was assessed on MD-1, MD + 1, and MD + 2. Statistical analyses on the intervention effects on dietary intake and RMR were carried out using a two factor (group and day) analysis of variance (ANOVA) with a subsequent Bonferroni post-hoc test.Results Mean energy (3393 ± 852 vs. 2572 ± 577 kcal · day−1) and CHO (5.36 ± 1.9 vs. 3.47 ± 1.1 g · kg−1 BW · day−1) intake was significantly higher (p

Background: Limited data are available on vitamin A kinetics and total body stores (TBS) in women. Such information can be obtained using compartmental modeling and retinol isotope dilution (RID). Objectives: Objectives were to apply population-based (“super-subject”) modeling to determine retinol kinetics in nonpregnant Ghanaian women of reproductive age and to use RID to predict TBS in the group and its individuals. Methods: Women (n = 89) ingested a dose of [2H6]retinyl acetate and blood samples (3/woman) were collected from 6 h to 91 d, with all participants sampled at 14 d, about half at either 21 or 28 d, and each at one other time. Composite data (plasma retinol fraction of dose; FDp) were analyzed using Simulation, Analysis and Modeling software to obtain kinetic parameters, TBS, and other state variables as well as model-derived values for the RID composite coefficient FaS. The latter were used in the RID equation TBS (μmol) = FaS × 1/SAp (where SAp is plasma retinol specific activity) to predict TBS at various times. Results: Model-predicted TBS was 973 μmol (n = 87). Geometric mean RID-predicted TBS was 965, 926, and 1006 μmol at 14, 21, and 28 d, respectively, with wide ranges [for example, 252–3848 μmol on day 14 (n = 86)]; TBS predictions were similar at later times. Participants had a mean 2 y of vitamin A in stores and estimated liver vitamin A concentrations in the normal range. Model-predicted vitamin A disposal rate was 1.3 μmol/d and plasma recycling number was 37. Conclusions: Super-subject modeling provides an estimate of group mean TBS as well as group-specific values for the RID coefficient FaS; the latter can be used to confidently predict TBS by RID for individual participants in the group under study or in similar individuals at 14 d or more after isotope ingestion. Trial registration number: Trial is registered (NCT04632771) at https://clinicaltrials.gov.

ABSTRACT: Salmonella enteretidis (SE) has a great propensity to translocate from the cecum into internal organs such as the spleen and liver. However, a major concern is the ability of SE to colonize the ovaries. This study aimed to evaluate the efficacy of cell walls from Saccharomyces cerevisiae to control the Salmonella load in the ceca and ovaries of commercial layer pullets. Ten-week-old layer pullets were divided into 2 groups: one group was fed a control diet with commercial feed without additives, and another group was fed the same diet supplemented with 0.5 kg/metric ton of yeast cell walls (YCWs). At 16 wk of age, the birds in both groups were challenged with 3.0 × 109 CFU/mL SE by oral gavage. The birds were euthanized on d 7 and 14 postchallenge to collect the ceca and ovaries for Salmonella load determination. The results demonstrated that there were no statistical differences in ovary SE infection rates. The trend in the prevalence of SE positivity in the ovaries was similar at 14 d, with 2.1% (YCW pullets) to 4.2% positive for the ovaries of the nontreated pullets. There was also no significant difference in the SE log10 MPN/gram between the YCW and the control groups. In the ceca, the high level of SE (3.0 × 109 cfu/pullet), which results in ovarian transmission, causes high intestinal tract inflammation. There was a significant difference in the prevalence of SE in the ceca at 7 d postchallenge but not at 14 d postchallenge. In conclusion, the reduction in Salmonella load observed in the ceca on d 7 in this study shows the potential of YCW supplementation for reducing Salmonella colonization in poultry.

Single-use plastics (SUPs) in life science laboratories account for approximately 5.5 million tonnes of waste per year globally. Of SUPs used in life science laboratories, Petri dishes, centrifuge tubes, and inoculation loops are some of the most common. In order to reduce the reliance on petrochemical-based SUPs in the life science research laboratory and minimize the negative environmental impacts associated with SUPs, this research investigates the applicability of polylactic acid (PLA) in single-use labware as a replacement for petrochemical-based plastics. PLA is one of the most well-studied biodegradable plastics that can be produced from sustainable resources. Commercially available PLA was used to 3D print a select range of labware to test the suitability of PLA-based material for routine microbiology work. An injection moulded PLA-based Petri dish was also designed and produced, for increased optical clarity. The biocompatibility was tested against Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus epidermidis) strains of bacteria. The PLA-based labware did not negatively impact the cell growth, viability, and metabolic activity of the bacterial cultures. The injection moulded PLA Petri dish showed a reduced colony forming unit count for the Gram-negative E. coli strain compared to the polystyrene Petri dish, ∼1.5 × 109 CFU/mL and ∼3.0 × 109 CFU/mL respectively, during late-exponential growth. The colony counts were, however, in the same order of magnitude. This observed difference may be due to the internal environment inside the Petri dish, hence the internal O2 concentration, humidity, and temperature during bacterial growth were investigated. This work demonstrates, for the first time, a full successful workflow of bacterial growth using a sustainable bioplastic, providing a pathway to reducing the environmental impacts of SUPs in life science laboratories.

Outcomes in patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) are poor. Loncastuximab-teserine (Lonca) is an antibody drug conjugate (ADC) which was FDA approved for R/R DLBCL patients who have received at least 2 prior lines of therapy based on the LOTIS-2 trial. However, there are limited data regarding its efficacy in the real-world setting (RWS). This retrospective study included 21 US centers and evaluated outcomes of patients with R/R DLBCL treated with Lonca. Our analysis includes 187 patients with notably higher risk baseline features compared to LOTIS-2 including a higher proportion of patients with bulky disease (17% vs 0%), high-grade B-cell histology (HGBL) (22% vs 8%), and increased number of prior lines of therapy (median 4 vs 3). The complete response (CR) rate was 14% and overall response rate (ORR) was 32%. Median event free (EFS) and overall survival (OS) were 2.1 and 4.6 months, respectively. Those with bulky disease and HGBL had significantly worse outcomes, and those with non-germinal center cell of origin and CR to most recent line of therapy demonstrated superior outcomes. In summary, in this largest retrospective cohort study of Lonca in the RWS, the response rates, EFS, and OS were lower than those reported in LOTIS-2, which is likely reflective of its use in higher risk and more heavily pre-treated patients within the real world compared to those enrolled on clinical study.

Summary: Over 75% of patients with ovarian cancer present with late-stage disease, often accompanied by extensive metastasis. The metastatic cascade is driven by a sub-population of transcriptionally plastic cells known as ''leader cells'' (LCs), which play a critical role in collective invasion yet remain poorly understood. LCs are marked by the expression of keratin-14 (KRT14), which determines their migratory and invasive capacity in ovarian cancer. This study demonstrates that KRT14+ LCs promote tumor progression through immunosuppression and immune privilege in vivo. In the ID8 syngeneic epithelial ovarian cancer mouse model, tumor-specific loss of KRT14+ LCs impairs tumor progression and metastatic spread without affecting cellular proliferation. Immune profiling shows reduced immunosuppressive regulatory T cells (Tregs) and M2 macrophages and improved CD8+ T cell/Treg ratios in LC knockout (LCKO) mice. Conversely, forced LC overexpression accelerates metastasis and increases the secretion of immunosuppressive chemokines, such as CCL22 and CCL5, highlighting the role of KRT14+ LCs in immune suppression and metastatic progression.

Abstract Background Overdose deaths continue to rise within the United States, despite effective treatments such as buprenorphine and methadone for opioid use disorder (OUD). Mobile medical units with the ability to dispense buprenorphine have been developed to engage patients and eliminate barriers to accessing OUD treatment. This study reports survey responses of patients of a mobile medical unit dispensing buprenorphine in areas of Chicago, IL with high overdose rates. Methods All patients who were dispensed buprenorphine via the mobile medical unit were invited to participate in a 7-item anonymous survey between May 24, 2023, and August 25, 2023. The survey included 5-point satisfaction scale, multiple-choice, and open-ended questions. Outcomes included satisfaction with buprenorphine dispensing from the mobile medical unit, satisfaction with filling buprenorphine at a pharmacy in the past, barriers experienced at pharmacies when filling buprenorphine, and whether the client would have started treatment that day if the mobile medical unit had not been present. Satisfaction scale and multiple-choice question responses were assessed using descriptive statistics. Wilcoxon signed-rank test was used to compare median satisfaction levels between receiving buprenorphine from the mobile medical unit versus filling a buprenorphine prescription at a community pharmacy. Open-ended questions were analyzed qualitatively using inductive thematic analysis. Results 106 unique patients were dispensed buprenorphine from the mobile unit during the study period. Of these patients, 54 (51%) completed the survey. Respondents reported high satisfaction with the buprenorphine dispensing process as a part of a mobile medical unit. Of those who had previously filled buprenorphine at a pharmacy, 83% reported at least one barrier, with delays in prescription dispensing from a community pharmacy, lack of transportation to/from the pharmacy, and opioid withdrawal symptoms being the most common barriers. 87% reported they would not have started buprenorphine that same day if the mobile medical unit had not been present. Nearly half of survey participants reported having taken buprenorphine that was not prescribed to them. Qualitative analysis of open-ended survey responses noted the importance of convenient accessibility, comprehensive care, and a non-judgmental environment. Conclusions Mobile medical units that dispense buprenorphine are an innovative model to reach patients with OUD who have significant treatment access barriers. This study found that patients who experienced barriers to accessing buprenorphine from a pharmacy were highly satisfied with the mobile medical unit’s buprenorphine dispensing process. Programs seeking to develop mobile buprenorphine dispensing programs should consider patient priorities of accessibility, comprehensive care, and welcoming, non-judgmental environments.

Higher education here is taken to be education beyond school level: often at an institution (a university) that has degree-awarding powers, though some programmes may lead to a diploma, certificate or other award or qualification. Nomenclature around “research” in the associated teaching and learning is contested: professional enquiry, scholarship of teaching and learning, pedagogical research… are some of the terms used. Authors discuss and distinguish such terms. An ethical issue is a circumstance in which a moral conflict arises or is implicit and should be resolved in a morally acceptable way. These include privacy, informed consent, insider research and power relationships within higher education research; there are also fluid challenges around the use of digital contributions. Authors present a narrative exegesis of work in the associated areas, which authors argue will be of use to universities promoting such research, and of particular interest to two groups of academics wishing to systematically develop their practice in ways that contribute to the field: those on teaching-only contracts, who would also demonstrate their research credentials; and researchers from non-education-cognate fields. Authors identify directions for further work.

Abstract Background Female fertility is an important trait in dairy cattle. Identifying putative causal variants associated with fertility may help to improve the accuracy of genomic prediction of fertility. Combining expression data (eQTL) of genes, exons, gene splicing and allele specific expression is a promising approach to fine map QTL to get closer to the causal mutations. Another approach is to identify genomic differences between cows selected for high and low fertility and a selection experiment in New Zealand has created exactly this resource. Our objective was to combine multiple types of expression data, fertility traits and allele frequency in high- (POS) and low-fertility (NEG) cows with a genome-wide association study (GWAS) on calving interval in Australian cows to fine-map QTL associated with fertility in both Australia and New Zealand dairy cattle populations. Results Variants that were significantly associated with calving interval (CI) were strongly enriched for variants associated with gene, exon, gene splicing and allele-specific expression, indicating that there is substantial overlap between QTL associated with CI and eQTL. We identified 671 genes with significant differential expression between POS and NEG cows, with the largest fold change detected for the CCDC196 gene on chromosome 10. Our results provide numerous candidate genes associated with female fertility in dairy cattle, including GYS2 and TIGAR on chromosome 5 and SYT3 and HSD17B14 on chromosome 18. Multiple QTL regions were located in regions with large numbers of copy number variants (CNV). To identify the causal mutations for these variants, long read sequencing may be useful. Conclusions Variants that were significantly associated with CI were highly enriched for eQTL. We detected 671 genes that were differentially expressed between POS and NEG cows. Several QTL detected for CI overlapped with eQTL, providing candidate genes for fertility in dairy cattle.

Abstract Introduction Globally, the COVID-19 pandemic upended healthcare services and created economic vulnerability for many. Criminalization of sex work meant sex workers were largely ineligible for Canada’s government-based financial pandemic relief, the Canadian Emergency Response Benefit. Sex workers’ loss of income and inability to access financial support services during the pandemic resulted in many unable to pay rent or mortgage, and in need of assistance with basic needs items including food. Little is known about the unique experiences of sex workers who faced challenges in accessing food during the pandemic and its impact on healthcare access. Thus, we aimed to identify the association between pandemic-related challenges accessing food and primary healthcare among sex workers. Methods Prospective data were drawn from a cohort of women sex workers in Vancouver, Canada (An Evaluation of Sex Workers’ Health Access, AESHA; 2010-present). Data were collected via questionnaires administered bi-annually from October 2020-August 2021. We used univariate and multivariable logistic regression with generalized estimating equations to assess the association between pandemic-related challenges accessing food and challenges accessing primary healthcare over the study period. Results Of 170 participants, 41% experienced pandemic-related challenges in accessing food and 26% reported challenges accessing healthcare. Median age was 45 years (IQR:36–53), 56% were of Indigenous ancestry, 86% experienced intimate partner violence in the last six months, and 62% reported non-injection substance use in the last six months. Experiencing pandemic-related challenges accessing food was positively associated with challenges accessing primary healthcare (Adjusted Odds Ratio: 1.99, 95% Confidence Interval: 1.02–3.88) after adjustment for confounders. Conclusions Findings provide insight about the potential role community-based healthcare delivery settings (e.g., community clinics) can play in ameliorating access to basic needs such as food among those who are highly marginalized. Future pandemic response efforts should also take the most marginalized populations’ needs into consideration by establishing strategies to ensure continuity of essential services providing food and other basic needs. Lastly, policies are needed establishing basic income support and improve access to food resources for marginalized women in times of crisis.