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Abstract Agricultural practices affect soil microbes which are critical to soil health and sustainable agriculture. To understand prokaryotic and fungal assembly under agricultural practices, we use machine learning-based methods. We show that fertility source is the most pronounced factor for microbial assembly especially for fungi, and its effect decreases with soil depths. Fertility source also shapes microbial co-occurrence patterns revealed by machine learning, leading to fungi-dominated modules sensitive to fertility down to 30 cm depth. Tillage affects soil microbiomes at 0-20 cm depth, enhancing dispersal and stochastic processes but potentially jeopardizing microbial interactions. Cover crop effects are less pronounced and lack depth-dependent patterns. Machine learning reveals that the impact of agricultural practices on microbial communities is multifaceted and highlights the role of fertility source over the soil depth. Machine learning overcomes the linear limitations of traditional methods and offers enhanced insights into the mechanisms underlying microbial assembly and distributions in agriculture soils.

Abstract DNA methylation (DNAm) is one of the most reliable biomarkers of aging across mammalian tissues. While the age-dependent global loss of DNAm has been well characterized, DNAm gain is less characterized. Studies have demonstrated that CpGs which gain methylation with age are enriched in Polycomb Repressive Complex 2 (PRC2) targets. However, whole-genome examination of all PRC2 targets as well as determination of the pan-tissue or tissue-specific nature of these associations is lacking. Here, we show that low-methylated regions (LMRs) which are highly bound by PRC2 in embryonic stem cells (PRC2 LMRs) gain methylation with age in all examined somatic mitotic cells. We estimated that this epigenetic change represents around 90% of the age-dependent DNAm gain genome-wide. Therefore, we propose the “PRC2-AgeIndex,” defined as the average DNAm in PRC2 LMRs, as a universal biomarker of cellular aging in somatic cells which can distinguish the effect of different anti-aging interventions.

Objective: The study objective was to determine if intraoperative peritoneal catheter placement is associated with improved outcomes in neonates undergoing high-risk cardiac surgery with cardiopulmonary bypass. Methods: This propensity score–matched retrospective study used data from 22 academic pediatric cardiac intensive care units. Consecutive neonates undergoing Society of Thoracic Surgeons–European Association for Cardio-Thoracic Surgery category 3 to 5 cardiac surgery with cardiopulmonary bypass at centers participating in the NEonatal and Pediatric Heart Renal Outcomes Network collaborative were studied to determine the association of the use of an intraoperative placed peritoneal catheter for dialysis or passive drainage with clinical outcomes, including the duration of mechanical ventilation. Results: Among 1490 eligible neonates in the NEonatal and Pediatric Heart Renal Outcomes Network dataset, a propensity-matched analysis was used to compare 395 patients with peritoneal catheter placement with 628 patients without peritoneal catheter placement. Time to extubation and most clinical outcomes were similar. Postoperative length of stay was 5 days longer in the peritoneal catheter placement cohort (17 vs 22 days, P = .001). There was a 50% higher incidence of moderate to severe acute kidney injury in the no-peritoneal catheter cohort (12% vs 18%, P = .02). Subgroup analyses between specific treatments and in highest risk patients yielded similar associations. Conclusions: This study does not demonstrate improved outcomes among neonates with placement of a peritoneal catheter during cardiac surgery. Outcomes were similar apart from longer hospital stay in the peritoneal catheter cohort. The no-peritoneal catheter cohort had a 50% higher incidence of moderate to severe acute kidney injury (12% vs 18%). This analysis does not support indiscriminate peritoneal catheter use, although it may support the utility for postoperative fluid removal among neonates at risk for acute kidney injury. A multicenter controlled trial may better elucidate peritoneal catheter effects.

Abstract This is the protocol for a Campbell systematic review. The objectives are as follows. The proposed systematic review is an update to, and extension of, Lipsey et al. (2007). As such we build on their previous aims to: (i) Assess and synthesise the overall impact of cognitive behavioural therapy (CBT) on offender recidivism; (ii) Examine possible sources of variability in the effectiveness of CBT. Data permitting, we will examine if the effectiveness of CBT varies by: (a) Characteristics of the CBT intervention (e.g., cognitive restructuring vs. cognitive skills training, group v. individual implementation; and/or custodial v. community setting, and/or), (b) Characteristics of the population (e.g., juveniles vs. adult offenders), (c) Implementation factors (e.g., implementing practitioner, use of structured/manualised approaches, delivery mode, and/or programme duration or intensity), (d) Evaluation methods (e.g., randomised vs. non‐randomised research designs); (iv) Determine whether there is a decline in the effect of CBT on recidivism over time; and (v) Investigate whether there is an interaction between implementation factors and time in terms of the effect on recidivism.

Job burnout is a stress-related phenomenon that is a significant threat to the health and performance of organizations and employees. Interventions to ameliorate potentials for burnout have been limited by the lack of a comprehensive tool that considers work system stressors. Thus, the aim of this study was to develop a questionnaire for predicting job burnout based on the macroergonomics work system approach. The setting was a petrochemical company in South Iran. In the qualitative phase of this sequential exploratory mixed methods research, 971 meaning codes were extracted from fourteen one-to-one and seven focus group interviews (n = 59). The codes were subject to Directed Content Analysis, which yielded three themes and 15 dimensions, which were used to inform the development of reliable and valid questionnaire. Items for each of the dimensions were sourced from exiting scales. To test the developed Work System Stress Questionnaire (WSSQ) in terms of its ability to predict burnout, a survey which included demographic items, the WSSQ, and the Maslach Burnout Inventory was completed by 359 employees. Hierarchical linear regression modelling of the data indicated that Task Significance, Job Demands, Work-Life Conflict, and Work Schedule predicted Emotional Exhaustion, and altogether explained 58 % variance. Task Significance, Violence and Harassment, Work-Life Conflict, and Job Insecurity predicted the Depersonalization and explained 29 % variance. Decision Latitude, Welfare and Financial Facilities, Task Significance, and Structural Problems predicted Personal Accomplishment and explained 26 % variance. All 15 dimensions were valid (CVI range .73–.90) and reliable (Cronbach's alpha range .71–.93). The results confirm the ability of the WSSQ to explain more variance regarding job burnout than previous studies. In turn, the WSSQ will enable remedial actions to be put into place. It may also be useful for understanding the consequences associated with other organizational ergonomic variables that are related to job stress.

Background Chronic pain is a complex disease that requires interprofessional care for effective management. Despite the need for multidisciplinary care, disease and health care inequities can prevent individuals from attaining adequate treatment. Factors such as mental health, cost, and distance to a health care center can contribute to health care accessibility inequality. The aim of this study is to examine declined referrals at the Toronto Academic Pain Medicine Institute (TAPMI) to determine the reason for declining care and number of declined referrals.Methods A retrospective chart review of all declined referrals at TAPMI in 2018 and 2022 was conducted. Referral documentation and the intake decision were extracted from the electronic medical charts by the research team and verified by the clinical intake team. Chi-square tests were conducted to determine whether the proportion of declined referrals changed between the years reviewed.Results The number of declined referrals due to mental health complexities increased significantly from 51 (11%) in 2018 to 180 (18%) in 2022 (χ2 = 10.9, P = 0.0009). A significant rise in the number of declines due to mental health service requests was also observed (χ2 = 24.53, P

ABSTRACTBackground Despite the established efficacy of multidisciplinary chronic pain care, barriers such as inflated referral wait times and uncoordinated care further hinder patient health care access.Aims Here we describe the evolution of a single-entry model (SEM) for coordinating access to chronic pain care across seven hospitals in Toronto and explore the impact on patient care 6 years after implementation.Methods In 2017, an innovative SEM was implemented for chronic pain referrals in Toronto and surrounding areas. Referrals are received centrally, triaged by a clinical team, and assigned an appointment according to the level of urgency and the most appropriate care setting/provider. To evaluate the impact of the SEM, a retrospective analysis was undertaken to determine referral patterns, patient characteristics, and referral wait times over the past 6 years.Results Implementation of an SEM streamlined the number of steps in the referral process and led to a standardized referral form with common inclusion and exclusion criteria across sites. Over the 6-year period, referrals increased by 93% and the number of unique providers increased by 91%. Chronic pain service wait times were reduced from 299 (±158) days to 176 (±103) days. However, certain pain diagnoses such as chronic pelvic pain and fibromyalgia far exceed the average.Conclusions The results indicate that the SEM helped reduce wait times for pain conditions and standardized the referral pathway. Continued data capture efforts can help identify gaps in care to enable further health care refinement and improvement.

The National Academies of Sciences, Engineering, and Medicine recommends per- and polyfluoroalkyl substance (PFAS) blood testing for patients with risk of elevated exposure, and the Agency for Toxic Substances and Disease Registry (ATSDR) suggests PFAS blood testing based on exposure. Barriers to PFAS blood testing include cost, access to labs, and evolving laboratory methods. We quantify water and serum PFAS levels among a highly-exposed cohort in an area with groundwater contaminated by historical agricultural biosolid application. We compare the gold standard PFAS serum test with a commercial test and results from a one-compartment toxicokinetic model. Participants were adults (n = 30) whose household (n = 19) water had levels of the sum of six PFAS > 500 ng/L. Serum PFAS were measured using liquid chromatography-tandem mass spectrometry. Demographic and water consumption data were collected via telephone. Serum PFAS results from the commercial test were accessed via medical record. Statistical analysis included descriptive statistics and bivariate plots of serum levels. Perfluorohexanoic acid, perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorobutanesulfonic acid, perfluorohexanesulfonic acid (PFHxS), and perfluorooctanesulfonic acid (PFOS) were detected in 19 wells, and PFHpA, PFOA, PFNA, perfluorodecanoic acid, perfluoroundecanoic acid, PFHxS, and PFOS were detected in at least 19 participants’ serum. In well water, PFOA and PFOS levels had geometric means (GMs) of 1749 ng/L (geometric standard deviation [GSD] 2.4) and 887 ng/L (GSD 19.7), respectively. In serum, PFOA and PFOS had GMs of 116.2 µg/L (GSD 13.5) and 58.3 µg/L (GSD 13.8), respectively. Our results are comparable with and had a wider mix of PFAS than other high-exposure cohorts. There was good agreement between the commercial and gold standard tests for PFOA, PFNA, and PFHxS, and mixed agreement between the gold standard test and modeled predictions, suggesting water-based toxicokinetic models of serum PFAS may be inadequate for assessing exposure in this population.

Abstract Background Homelessness is a traumatic experience, and can have a devastating effect on those experiencing it. People who are homeless often face significant barriers when accessing public services, and have often experienced adverse childhood events, extreme social disadvantage, physical, emotional and sexual abuse, neglect, low self‐esteem, poor physical and mental health, and much lower life expectancy compared to the general population. Rates of problematic substance use are disproportionately high, with many using drugs and alcohol to deal with the stress of living on the street, to keep warm, or to block out memories of previous abuse or trauma. Substance dependency can also create barriers to successful transition to stable housing. Objectives To understand the effectiveness of different substance use interventions for adults experiencing homelessness. Search Methods The primary source of studies for was the 4th edition of the Homelessness Effectiveness Studies Evidence and Gaps Maps (EGM). Searches for the EGM were completed in September 2021. Other potential studies were identified through a call for grey evidence, hand‐searching key journals, and unpacking relevant systematic reviews. Selection Criteria Eligible studies were impact evaluations that involved some comparison group. We included studies that tested the effectiveness of substance use interventions, and measured substance use outcomes, for adults experiencing homelessness in high income countries. Data Collection and Analysis Descriptive characteristics and statistical information in included studies were coded and checked by at least two members of the review team. Studies selected for the review were assessed for confidence in the findings. Standardised effect sizes were calculated and, if a study did not provide sufficient raw data for the calculation of an effect size, author(s) were contacted to obtain these data. We used random‐effects meta‐analysis and robust‐variance estimation procedures to synthesise effect sizes. If a study included multiple effects, we carried out a critical assessment to determine (even if only theoretically) whether the effects are likely to be dependent. Where dependent effects were identified, we used robust variance estimation to determine whether we can account for these. Where effect sizes were converted from a binary to continuous measure (or vice versa), we undertook a sensitivity analysis by running an additional analysis with these studies omitted. We also assessed the sensitivity of results to inclusion of non‐randomised studies and studies classified as low confidence in findings. All included an assessment of statistical heterogeneity. Finally, we undertook analysis to assess whether publication bias was likely to be a factor in our findings. For those studies that we were unable to include in meta‐analysis, we have provided a narrative synthesis of the study and its findings. Main Results We included 48 individual papers covering 34 unique studies. The studies covered 15, 255 participants, with all but one of the studies being from the United States and Canada. Most papers were rated as low confidence (n = 25, or 52%). By far the most common reason for studies being rated as low confidence was high rates of attrition and/or differential attrition of study participants, that fell below the What Works Clearinghouse liberal attrition standard. Eleven of the included studies were rated as medium confidence and 12 studies as high confidence. The interventions included in our analysis were more effective in reducing substance use than treatment as usual, with an overall effect size of –0.11 SD (95% confidence interval [CI], −0.27, 0.05). There was substantial heterogeneity across studies, and the results were sensitive to the removal of low confidence studies (−0.21 SD, 95% CI [−0.59, 0.17] − 6 studies, 17 effect sizes), the removal of quasi‐experimental studies (−0.14 SD, 95% CI [−0.30, 0.02] − 14 studies, 41 effect sizes) and the removal of studies where an effect size had been converted from a binary to a continuous outcome (−0.08 SD, 95% CI [−0.31, 0.15] − 10 studies, 31 effect sizes). This suggests that the findings are sensitive to the inclusion of lower quality studies, although unusually the average effect increases when we removed low confidence studies. The average effect for abstinence‐based interventions compared to treatment‐as‐usual (TAU) service provision was –0.28 SD (95% CI, −0.65, 0.09) (6 studies, 15 effect sizes), and for harm reduction interventions compared to a TAU service provision is close to 0 at 0.03 SD (95% CI, −0.08, 0.14) (9 studies, 30 effect sizes). The confidence intervals for both estimates are wide and crossing zero. For both, the comparison groups are primarily abstinence‐based, with the exception of two studies where the comparison group condition was unclear. We found that both Assertative Community Treatment and Intensive Case Management were no better than treatment as usual, with average effect on substance use of 0.03 SD, 95% CI [−0.07, 0.13] and –0.47 SD, 95% CI [−0.72, −0.21] 0.05 SD, 95% CI [−0.28, 0.39] respectively. These findings are consistent with wider research, and it is important to note that we only examined the effect on substance use outcomes (these interventions can be effective in terms of other outcomes). We found that CM interventions can be effective in reducing substance use compared to treatment as usual, with an average effect of –0.47 SD, 95% CI (−0.72, −0.21). All of these results need to be considered in light of the quality of the underlying evidence. There were six further interventions where we undertook narrative synthesis. These syntheses suggest that Group Work, Harm Reduction Psychotherapy, and Therapeutic Communities are effective in reducing substance use, with mixed results found for Motivational Interviewing and Talking Therapies (including Cognitive Behavioural Therapy). The narrative synthesis suggested that Residential Rehabilitation was no better than treatment as usual in terms of reducing substance use for our population of interest. Authors' Conclusions Although our analysis of harm reduction versus treatment as usual, abstinence versus treatment as usual, and harm reduction versus abstinence suggests that these different approaches make little real difference to the outcomes achieved in comparison to treatment as usual. The findings suggest that some individual interventions are more effective than others. The overall low quality of the primary studies suggests that further primary impact research could be beneficial.

Introduction & Background The level of food insecurity in England is widening, with low-income families requiring more support to reduce income inequalities. The government have introduced policies to address these issues with targeted subsidies on healthy food on programs such as the Healthy Start Scheme. Despite this, national uptake of the Healthy Start Scheme remains lower than the government target. Objectives & Approach Our study aims to predict uptake and take up discrepancies at a local authority level and understand the measures contributing to the prediction using anonymised supermarket loyalty card data records for over 4 million customers, deprivation and food insecurity measures. We used a machine-learning approach utilising transactional data, ONS Index of Deprivation datasets, neighbourhood statistics, and NHS Healthy Start Scheme uptake data. Regression prediction models were used to evaluate and predict the outcomes, whilst feature importance tools were used to evaluate the variables weighing within the model. Relevance to Digital Footprints This study leverages transaction data from a UK retailer to understand lifestyle factors at a local authority level and assesses their usefulness in predicting the scheme’s uptake. Loyalty card transactional data can provide valuable insight into purchase behaviour linked to health and nutrition. Results The Linear and Ridge Regression models performed better than other prediction models. Analysis of measures revealed that whilst deprivation and population-related measures had a high contribution to the prediction model, findings from transactional data measures provided valuable insight into shopping behavioural characteristics that contribute to the model performance. Results suggested that areas with higher spending on fruits and vegetables and high-calorie food were associated with higher uptake prediction in test data but the converse for high spend on fish. Conclusions & Implications Our study indicates that shopping data measures such as spend on fruits and vegetables, high-calorie food, fish and products bought can be utilised for prediction models for uptake and take-up discrepancy of the Healthy Start Scheme. This study highlights the complexity of understanding factors influencing public policy effectiveness and the need for tailored approaches in diverse urban contexts.

Abstract Plant-based product replacements are gaining popularity. However, the long-term health implications remain poorly understood, and available methods, though accurate, are expensive and burdensome, impeding the study of sufficiently large cohorts. To identify dietary transitions over time, we examine anonymised loyalty-card shopping records from Co-op Food, UK. We focus on 10,626 frequent customers who directly replaced milk with alternative milk. We then use product nutritional information to estimate weekly nutrient intake before and after the transition. 83% who converted to alternative milk saw a fall in iodine (44%), calcium (30%) and vitamin B12 (39%) consumption, with 57% reducing iodine purchase by more than 50%. The decline is even higher for those switching dairy and meat products. Our findings suggest that dietary transitions - such as replacing milk with alternative milk - could lead to nutritional deficiencies, notably iodine, which, if not addressed, may represent a significant public health concern, particularly in countries which do not mandate salt iodisation.

Abstract Background and Aim Esophageal squamous papilloma (ESP) is a benign growth in the esophagus with unknown malignant potential. The mechanism underlying ESP formation is unknown, but human papillomavirus (HPV) infection has been proposed as a potential etiology. We sought to investigate the clinical characteristic of ESP in our population, review the current literature, and highlight the role of HPV. Methods This is a retrospective case–control study conducted at two referral centers. We selected the ESP population by free‐text search in the pathology department database and selected controls randomly from the general endoscopy population. Immunostains were used to evaluate ESP tissue for HPV. Results Between January 2016 and December 2021, we identified 66 patients with ESP, with a prevalence of 0.72%. ESP patients were younger, with a median age of 52 years (P = 0.021), and more likely African American (34.4 vs 7.5%, P

Abstract The evolution of the hominin hand has been widely linked to the use and production of flaked stone tool technologies. After the earliest handheld flake tools emerged, shifts in hominin hand anatomy allowing for greater force during precision gripping and ease when manipulating objects in-hand are observed in the fossil record. Previous research has demonstrated how biometric traits, such as hand and digit lengths and precision grip strength, impact functional performance and ergonomic relationships when using flake and core technologies. These studies are consistent with the idea that evolutionary selective pressures would have favoured individuals better able to efficiently and effectively produce and use flaked stone tools. After the advent of composite technologies during the Middle Stone Age and Middle Palaeolithic, fossil evidence reveals differences in hand anatomy between populations, but there is minimal evidence for an increase in precision gripping capabilities. Furthermore, there is little research investigating the selective pressures, if any, impacting manual anatomy after the introduction of hafted composite stone technologies (‘handles’). Here we investigated the possible influence of tool-user biometric variation on the functional performance of 420 hafted Clovis knife replicas. Our results suggest there to be no statistical relationships between biometric variables and cutting performance. Therefore, we argue that the advent of hafted stone technologies may have acted as a ‘performance equaliser’ within populations and removed (or reduced) selective pressures favouring forceful precision gripping capabilities, which in turn could have increased the relative importance of cultural evolutionary selective pressures in the determination of a stone tool’s performance.

The characterization of human behavior in real-world contexts is critical for developing a comprehensive model of human health. Recent technological advancements have enabled wearables and sensors to passively and unobtrusively record and presumably quantify human behavior. Better understanding human activities in unobtrusive and passive ways is an indispensable tool in understanding the relationship between behavioral determinants of health and diseases. Adult individuals (N = 60) emulated the behaviors of smoking, exercising, eating, and medication (pill) taking in a laboratory setting while equipped with smartwatches that captured accelerometer data. The collected data underwent expert annotation and was used to train a deep neural network integrating convolutional and long short-term memory architectures to effectively segment time series into discrete activities. An average macro-F1 score of at least 85.1 resulted from a rigorous leave-one-subject-out cross-validation procedure conducted across participants. The score indicates the method’s high performance and potential for real-world applications, such as identifying health behaviors and informing strategies to influence health. Collectively, we demonstrated the potential of AI and its contributing role to healthcare during the early phases of diagnosis, prognosis, and/or intervention. From predictive analytics to personalized treatment plans, AI has the potential to assist healthcare professionals in making informed decisions, leading to more efficient and tailored patient care.

Individual animals in managed populations are subject to controlled social and physical environmental conditions that impact their behaviour patterns, choice of social associates, ability to experience positive welfare states, and ultimately their overall health status and quality of life [...]

We characterized the epidemiology, host–pathogen characteristics, and outcomes of severe adult pulmonary Streptococcus pyogenes infections that coincided with a high community caseload in central Scotland, UK. The pulmonary infections had high illness and death rates and were associated with socioeconomic deprivation, influenza A co-infection, and the M1UK lineage of S. pyogenes.

Following the waning severity of COVID-19 due to vaccination and the development of immunity, the current variants of SARS-CoV-2 often lead to mild upper respiratory tract infections (MURTIs), suggesting it is an appropriate time to review the pathogenesis and treatment of such illnesses. The present article reviews the diverse causes of MURTIs and the mechanisms leading to symptomatic illness. Different symptoms of MURTIs develop in a staggered manner and require targeted symptomatic treatment. A wide variety of remedies for home treatment is available, including over-the-counter drugs and plant-derived substances. Recent pharmacological research has increased the understanding of molecular effects, and clinical studies have shown the efficacy of certain herbal remedies. However, the use of subjective endpoints in these clinical studies may suggest limited validity of the results. In this position paper, the importance of patient-centric outcomes, including a subjective perception of improved well-being, is emphasized. A best practice approach for the management of MURTIs, in which pharmacists and physicians create an improved multi-professional healthcare setting and provide healthcare education to patients, is proposed. Pharmacists act as first-line consultants and provide patients with remedies, considering the individual patient’s preferences towards chemical or plant-derived drugs and providing advice for self-monitoring. Physicians act as second-line consultants if symptoms worsen and subsequently initiate appropriate therapies. In conclusion, general awareness of MURTIs should be increased amongst medical professionals and patients, thus improving their management.

Abstract Spin Hall oscillators (SHOs) based on bilayers of a ferromagnet (FM) and a non-magnetic heavy metal (HM) are electrically tunable nanoscale microwave signal generators. Achieving high output power in SHOs requires driving large-amplitude magnetization dynamics by a direct spin Hall current. Here we present an SHO engineered to have easy-plane magnetic anisotropy oriented normal to the bilayer plane, enabling large-amplitude easy-plane dynamics driven by spin Hall current. Our experiments and micromagnetic simulations demonstrate that the easy-plane anisotropy can be achieved by tuning the magnetic shape anisotropy and perpendicular magnetic anisotropy in a nanowire SHO, leading to a significant enhancement of the generated microwave power. The easy-plane SHO experimentally demonstrated here is an ideal candidate for realization of a spintronic spiking neuron. Our results provide an approach to design of high-power SHOs for wireless communications, neuromorphic computing, and microwave assisted magnetic recording.

Abstract Background Helicopter Emergency Medical Services (HEMS) are a limited and expensive resource, and should be intelligently tasked. HEMS dispatch was identified as a key research priority in 2011, with a call to identify a ‘general set of criteria with the highest discriminating potential’. However, there have been no published data analyses in the past decade that specifically address this priority, and this priority has been reaffirmed in 2023. The objective of this study was to define the dispatch criteria available at the time of the initial emergency call with the greatest HEMS utility using a large, regional, multi-organizational dataset in the UK. Methods This retrospective observational study utilized dispatch data from a regional emergency medical service (EMS) and three HEMS organisations in the East of England, 2016–2019. In a logistic regression model, Advanced Medical Priority Dispatch System (AMPDS) codes with ≥ 50 HEMS dispatches in the study period were compared with the remainder to identify codes with high-levels of HEMS patient contact and HEMS-level intervention/drug/diagnostic (HLIDD). The primary outcome was to identify AMPDS codes with a > 10% HEMS dispatch rate of all EMS taskings that would result in 10–20 high-utility HEMS dispatches per 24-h period in the East of England. Data were analysed in R, and are reported as number (percentage); significance was p 10% HEMS dispatch of all EMS taskings) resulted in 17 taskings per 24-h period. This definition derived nine AMPDS codes with high HEMS utility. Conclusion We have identified nine ‘golden’ AMPDS codes, available at the time of initial emergency call, that are associated with high-levels of whole-system and HEMS utility in the East of England. We propose that UK EMS should consider immediate HEMS dispatch to these codes.

Abstract Keratins are an integral part of cell structure and function. Here, it is shown that ectopic expression of a truncated isoform of keratin 81 (tKRT81) in breast cancer is upregulated in metastatic lesions compared to primary tumors and patient‐derived circulating tumor cells, and is associated with more aggressive subtypes. tKRT81 physically interacts with keratin 18 (KRT18) and leads to changes in the cytosolic keratin intermediate filament network and desmosomal plaque formation. These structural changes are associated with a softer, more elastically deformable cancer cell with enhanced adhesion and clustering ability leading to greater in vivo lung metastatic burden. This work describes a novel biomechanical mechanism by which tKRT81 promotes metastasis, highlighting the importance of the biophysical characteristics of tumor cells.

BACKGROUND: In October 2015, the Massachusetts Medicaid program temporarily stopped reimbursement for procedures in which the International Classification of Diseases, Tenth Edition, code for serum aneuploidy screening used by certain communities was stipulated. This change led to a substantial number of patients who went without aneuploidy screening for approximately 3 years. OBJECTIVE: This study aimed to determine the change in use and cost-effectiveness of prenatal aneuploidy serum screening in a low-risk Hispanic Medicaid population in Massachusetts. STUDY DESIGN: We conducted a retrospective chart review of Spanish-speaking pregnant patients younger than 35 years of age who underwent aneuploidy serum screening at a Massachusetts community health center. The study compared the aneuploidy serum screening rates for the periods before and after May 2016 when the Massachusetts Medicaid program, MassHealth, temporarily discontinued reimbursement for the screening. Based on these rates, we developed a Markov cohort simulation model to assess the economic value of reimbursed aneuploidy screening vs nonreimbursed or limited screening. Clinical outcomes included trisomy 21, live births, and therapeutic abortions for a trisomy 21 diagnosis. Economic outcomes included discounted quality-adjusted life years and lifetime medical costs, net health benefit, and incremental cost-effectiveness ratios. RESULTS: Before the MassHealth policy change, 69% (55/80) of pregnant individuals selected quad or sequential screens in comparison with only 9% (10/112) who selected screens after the policy change. Traditional aneuploidy serum screening in a low-risk (aged

Background: Prior research has established a link between thalamic pathology and cognitive impairment (CI) in people with multiple sclerosis (pwMS). However, the translation of these findings to pwMS in everyday clinical settings has been insufficient. Objective: To assess which global and/or thalamic imaging biomarkers can be used to identify pwMS at risk for CI and cognitive worsening (CW) in a real-world setting. Methods: This was an international, multi-center (11 centers), longitudinal, retrospective, real-word study of people with relapsing-remitting MS (pwRRMS). Brain MRI exams acquired at baseline and follow-up were collected. Cognitive status was evaluated using the Symbol Digit Modalities Test (SDMT). Thalamic volume (TV) measurement was performed on T2-FLAIR, as well as on T1-WI, when available. Thalamic dysconnectivity, T2-lesion volume (T2-LV), and volumes of gray matter (GM), whole brain (WB) and lateral ventricles (LVV) were also assessed. Results: 332 pwMS were followed for an average of 2.8 years. At baseline, T2-LV, LVV, TV and thalamic dysconnectivity on T2-FLAIR (p

Mechanical property prediction plays a crucial role in the steel industry, enabling better materials selection and enhancing production efficiency. In this study, we propose a novel framework that facilitates optimal materials selection for steel’s alloying elements, based on accurate predictions of the Jominy hardness curve. Leveraging Gaussian Process (GP) regression, we provide probabilistic predictions of steel hardenability characteristics from alloy element composition. Taking it a step further, our framework incorporates these accurate predictions into a constrained optimization process, yielding optimal compositions that reduce overall spending while meeting performance specifications. Through data obtained from 1080 steel samples, our GP regression model exhibits high accuracy, achieving an RMSE of 1.37 and showcasing significant improvements in the field. Moreover, our constrained optimization utilizing the GP model and historical market data reveals an average cost reduction of 18% on alloying element expenses, highlighting the tangible cost-saving potential of this approach. By leveraging Gaussian Process (GP) regression, we not only achieve accurate predictions of the Jominy hardness curve based on alloy element composition, but we also introduce a crucial element of uncertainty quantification. This empowers us to place trust in the results of our optimization process, ensuring robust and reliable materials selection. The integration of GP regression and optimization provides a powerful tool for achieving cost-effective materials selection and marks a significant advancement compared to existing studies. This research underscores the promise of machine learning in the steel industry, demonstrating its ability to yield substantial cost savings and enhance decision-making in materials selection.

Introduction & Background Netflix now has a consumer base of over 230 million worldwide. During the pandemic, its customers watched 203.8 million hours of content daily, with their activity, content choices and preferences being continually logged. The digital footprint data amassed in this process underpins a symbiotic relationship between supplier and consumer. Black-box algorithms convert these logs into personalised functionality and recommendations, producing improved customer experiences while generating revenue for the business. Whether the consumer willingly accepts this trade-off or not, it’s now almost impossible to use online services without leaving digital traces. But how representative of an individual’s actual preferences and behaviours are these? What biases exist in such datasets? And to what degree are consumers cognisant of how these datasets are being used? Objectives & Approach This study surveyed participants to interrogate their understanding of the data Netflix makes available to its subscribers. The objectives were to explore their perceptions relating to the data collected about them and encourage them to think critically about their digital footprint. It was also the intention of the research group that participants feel a sense of empowerment / control over the data made available to them. UK-based participants were provided with instructions on how to access their viewing history (programme titles, dates of access) and invited to inspect it. 61 participants opted to donate their data to the study, along with responses to a survey reflecting their understanding of what they had retrieved. Relevance to Digital Footprints While it may have been possible to work with Netflix to retrieve viewer data, by accessing via the participants instead, the researchers were enabling them to review and make informed choices about what they shared. One of the potential issues with this approach is that it provides an opportunity for participants to curate their data, should there be content that they would be uncomfortable sharing. Alternately, they may choose to withdraw from the study altogether based on what they see. While this has its drawbacks in terms of data inaccuracies and self-selection effect, it was felt important to the research team to prioritise the participants autonomy, encouraging them to be candid and share. If nothing else, it is hoped that by taking part in the study, there is the potential for participants to be inspired to think about the footprints they leave every time they go online so that they might be more mindful of them in future. Results In terms of bias, using only the Netflix data meant that the researchers were only accessing participants who pay for that service. Further, the researchers would only be accessing what would be a proportion of the participants’ viewing. If only using one service however, Netflix is arguably the service to use as according to statistica©, In 2021 it was the most subscribed (paid) supplier in the UK. 76% of respondents view more streamed content than terrestrial broadcast content and utilise an average of 3.5 streaming services. 36% of respondents also stated that they share their Netflix user profiles with at least one other person. Despite these limitations, 84% of respondents nonetheless considered that the captured content was representative of their ‘personal tastes and viewing habits.’ 76% were not aware until participating in the study that it was possible to extract their viewing data from Netflix, and 34% said they’d likely review it again. 33% indicated surprise as to the extent of information captured about them; but 91% believed that the streaming platform collected more information than was made available. Conclusions & Implications This study shows the potential of data donation to understand viewing habits, binge watching and related well-being indicators, with 43% of surveyed individuals offering their data for research. What has not been established in this study is why 57% of the group declined to share their data. It can be speculated that it may have been a reluctance to share once the data was inspected or that the process to access and then upload it may have been too much of a hurdle. An implication for this type of study may include a requirement to over-recruit in anticipation of a high drop-out rate or that data extraction and sharing needs to be made as simple and convenient as practicable for the participant. Given that one of the objectives of the research was to encourage participants to have more curiosity in and awareness / control of their digital footprints, consideration should be given to seeing if participant interest in further exploration of their data could be increased from the 24% seen here. This might be driven by the data type, any perceived utility it might have for the participant or any perceived ways in which it might be used to impact / influence them in some way by a 3rd party.

Introduction & Background The shift towards plant-based diets remains on the rise. Several observational studies have suggested that adopting these diets can result in some fundamental nutrient deficiencies, such as iodine deficiency. This can be especially harmful to a developing fetus, leading to growth impairment and, in extreme cases, cretinism. Nonetheless, understanding of long-term health consequences of this shift remains a challenge, particularly regarding nutritional impact at broader population scales. Objectives & Approach Our study focuses on the effects of transitioning to plant-based diets on the purchasing and assumed intake of essential nutrients like iodine, calcium, and vitamin B12. We analysed anonymized shopping records of 10,626 loyal customers who switched from regular milk to alternative milk products. By matching the transaction data with nutritional information, we estimated the weekly nutrient purchases before and after the transition. Our data was collected from a national food retailer across the UK. Relevance to Digital Footprints Loyalty-card transactional logs held by retailers reflect a valuable lens into nutritional intake data. This data can provide insight into the potential impact of purchasing behaviours, such as the potential health effects of dietary changes at scale. Our approach leverages AI modelling accompanied by rigorous variable importance methods to uncover potentially hidden insights on the impact of nutritional shifts to plant-based goods. Results Results indicate that 83% of individuals deemed regular customers, who switched to plant-based milk, experienced a decrease in their purchases of iodine (44%), calcium (30%), and vitamin B12 (39%) from their normal purchase patterns at the retailer. Additionally, 57% of these individuals decreased their iodine purchases by more than 50%. The reduction in these nutrients is even more significant for those who switch to plant-based dairy and meat products. Conclusions & Implications Our research indicates that dietary changes, such as switching from purchasing regular milk to alternative milks, may lead to insufficient intake of essential dietary nutrients such as iodine. This represents a significant potential health concern for the public if not remediated, especially in countries that do not require salt to be fortified with iodine.

ABSTRACT: Clostridial cellulitis or dermatitis affects commercial turkey flocks, primarily as they approach market age. In the field, this disease has been effectively controlled with antibiotics, but alternatives to antibiotics are needed. Bacterin-toxoid vaccination programs have been shown to prevent clostridial diseases in other species, including humans. Results from previous field studies indicate that vaccination with an experimental whole-cell Clostridium septicum (CS) bacterin-toxoid oil emulsion vaccine reduced clostridial dermatitis-associated mortality and antibiotic usage for some commercial turkey flocks, but vaccination was not always efficacious. To improve vaccine efficacy, studies were conducted to optimize the antigenic component of the experimental vaccine and to determine the appropriate antigen to adjuvant ratio, route, and volume for vaccine administration. It was determined that the phase of culture at time of formalin inactivation played a key role in serum antibody titer and larger volume vaccine doses produced higher serum antibody immune response regardless of antigen:adjuvant formulation ratio or route of injection. No significant differences (P > 0.05) were found between formulation ratios or between the subcutaneous and tail head injection sites. Based on these results, we propose to look further into the relationship between culture phase and antigenic components produced by CS under different culture conditions.

Objective Features of multisystem inflammatory syndrome in children (MIS‐C) overlap with other syndromes, making the diagnosis difficult for clinicians. We aimed to compare clinical differences between patients with and without clinical MIS‐C diagnosis and develop a diagnostic prediction model to assist clinicians in identification of patients with MIS‐C within the first 24 hours of hospital presentation. Methods A cohort of 127 patients (

Background: Upper respiratory tract infections occur with an annual incidence of 17.2 billion cases globally. The negative impact that symptoms have on sleep is thought to slow the recovery process. Plant-derived aromatics have been used since ancient times to treat respiratory illnesses. In this narrative review, we summarize the use of aromatics for the symptomatic relief of upper respiratory tract infections and how this affects sleep quality. Methods: Literature searches were conducted using a series of search terms and results were screened for relevance. Additional references were included according to the expert knowledge of the authors. Discussion: Multiple studies have observed that essential oil mixtures of aromatics enhance symptom relief for upper respiratory tract infections and their inhalation has been reported to have antitussive effects. Clinical trials assessing the efficacy of an ointment containing menthol, eucalyptus and camphor found patients to experience faster nasal cooling and decongestion times. Treatment with the same ointment also resulted in significant improvements in reported sleep quality. Aromatic treatment did not improve objective nasal airway measures in any of the studies. Conclusion: Whilst not affecting objective measures of nasal airway resistance, the use of aromatics leads to improvements in a number of subjective sensations associated with the common cold. Such benefits result in better sleep, which likely aids recovery. Therefore, aromatics remain a well tolerated and effective option for the symptomatic relief of upper respiratory tract infections.

Abstract Acquisition of resistance to targeted therapies remains a major clinical obstacle for the HER2+ subtype of breast cancer. Using an isogeneic progression series of HER2+ breast cancer metastasis we demonstrate that metastatic cells have an increased capacity to acquire resistance to the covalent, pan-ErbB inhibitor, neratinib. RNA sequencing analyses comparing parental and metastatic cells identified upregulation of transglutaminase 2 (TG2). Genetic depletion and overexpression approaches established that TG2 is both necessary and sufficient for acquisition of neratinib resistance. Mechanistically, we describe a pathway in which TG2-mediates activation of NF-κB signaling leading to upregulation of IL-6 in metastatic cells. This autocrine expression of IL-6 functions to maintain enhanced levels of TG2 via JAK:STAT3 signaling. This drug persistence feedback loop can be interrupted through the use of the JAK1/2 inhibitor ruxolitinib. In vivo application of ruxolitinib had no effect on tumor growth under non-treated conditions, but effectively prevented acquisition of resistance, leading to tumor regression upon coadministration with neratinib. Overall, our studies reveal a mechanism in metastatic breast cancer cells that predisposes them to acquisition of resistance to ErbB-targeted therapeutics. Clinically, immediate application of ruxolitinib could prevent acquisition of resistance and improve patient responses to HER2-targeted therapies.

BackgroundThere is a paucity of research examining the effects of the COVID-19 pandemic on the healthy lifestyle behaviors of hematological cancer patients. We examined changes in healthy lifestyle behaviors since the pandemic and identified factors associated with these changes among members of this high-risk population.MethodsHematological cancer patients (n = 394) completed a self-report online survey from July to August 2020. The survey assessed pandemic-related changes in exercise, alcohol consumption, and consumption of fruit, vegetables, and wholegrains. Information relating to several demographic, clinical, and psychological factors was also collected. Factors associated with changes in healthy lifestyle behaviors were analyzed using logistic regression.ResultsJust 14% of patients surveyed reported exercising more during the pandemic (39% exercised less). Only a quarter (24%) improved their diet, while nearly half (45%) reported eating less fruit, vegetables, and wholegrains. Just over a quarter (28%) consumed less alcohol (17% consumed more alcohol). Fear of contracting COVID-19 and psychological distress were significantly associated with reduced exercise. Younger age was significantly associated with both increased alcohol consumption and increased exercise. Being a woman was significantly associated with unfavorable changes in diet and being married was significantly associated with decreased alcohol consumption.ConclusionA substantial proportion of hematological cancer patients reported unfavorable changes in healthy lifestyle behaviors during the pandemic. Results highlight the importance of supporting healthy lifestyle practices among this particularly vulnerable group to ensure health is optimized while undergoing treatment and when in remission, particularly during crisis times like the COVID-19 pandemic.

Healthy indoor environments influence the comfort, health and wellbeing of the occupants. Monitoring the indoor temperature, relative humidity and CO2 levels in primary schools during the COVID-19 pandemic was mandated by a local authority in Scotland. The aim was to investigate the comfort and safety of the teachers and their pupils. This paper presents the measurements of indoor climate in 20 classrooms in four different primary schools in Scotland. The schools were of different architypes. The classrooms were of different sizes, orientations and occupancy, and had different ventilation systems. Ventilation was achieved either by manually opening the windows, or by a mechanical ventilation system. Indoor air temperature, relative humidity and carbon dioxide (CO2) concentrations were continuously monitored for one week during the heating season 2020/21. Occupancy and opening of the windows were logged in by the teachers. The ventilation rates in the classrooms were estimated by measuring the CO2 concentrations. On the 20 classrooms of the study, data of 19 were analysed. The results show that four of the five mechanically ventilated classrooms performed better than natural ventilation, which indicates that opening the windows depended on the customs and habits. Classrooms in naturally ventilated Victorian buildings have the worst average ventilation rate (4.38 L/s per person) compared to the other classrooms (5.8 L/s per person for the more recent naturally ventilated ones, and 6.08 L/s per person for the mechanically ventilated ones). The results of this preliminary study will be used as the basis to find ways to ensure adequate ventilation in natural ventilated classrooms.

Abstract Background There are increasing concerns about mental health consequences of the COVID-19 pandemic among seafarers. This study aims to assess the effects of the current global health pandemic on life satisfaction and adverse psychological outcomes among seafarers. Methods In this cross-sectional study, 470 multinational seafarers working on board ships of two international shipping companies were assessed. Mental health outcomes were assessed by the general anxiety disorder (GAD-7) questionnaire, post-traumatic stress disorder (PTSD-8) questionnaire, and patient health questionnaire (PHQ-9) depressive severity score. Multivariate logistic regression was used to determine the association of demographic and work-related variables with mental health outcomes. Results Overall, 439 out of 470 invited seafarers with a mean age of 34.5 (SD: 8.05) years participated in this study (participation rate: 93.4%). The prevalence of anxiety, depressive, and post-traumatic stress symptoms was 12.4, 14.1, and 37.3%, respectively. In the multivariate model, the current vessel’s signing duration was directly associated with the odds of depressive and intrusion symptoms. Moreover, the duration of work per week was inversely associated with hyper-vigilance and avoidance. Also, non-officers, compared to officers, experienced significantly lower anxiety and depressive symptoms, hyper-vigilance, and avoidance. Conclusion The present study revealed a high prevalence of mental health problems among seafarers during the COVID-19 pandemic. We recommend that more evidence is generated regarding psychosocial health issues for this vulnerable occupation.

Reducing tillage and supporting continuous living cover (CLC) can improve agroecosystem sustainability under both organic and conventional field crop production. What is less clear, however, is how reducing tillage affects the economic sustainability of organic field crop systems with CLC as compared to conventional field crop systems. To address this knowledge gap, we conducted a comprehensive economic analysis based on field records and crop yields from the long-term Farming Systems Trial (FST) at Rodale Institute in Kutztown, Pennsylvania. The FST (established in 1981) comprises three farming systems (conventional, low-input organic, and manure-based organic) which were split into tilled and reduced-till treatments in 2008. FST field activities, inputs, and crop yields from 2008 to 2020 were used to construct enterprise budgets to assess cumulative labor, costs, returns, and economic risk of six replicated theoretical farms. Reducing tillage on the conventional farms led to lower gross revenues (−10%), but lower annual costs (−5%) helped maintain similar net returns but increased economic risk as compared to tilled conventional farms. Reducing tillage on the low-input organic farms also led to lower gross revenues (−13%) and lower annual costs (−6%), which maintained net returns and increased risk relative to the tilled, low-input organic farms. For the more diverse manure-based organic farms that include periods of mixed perennial cover, reducing tillage had a smaller effect on overall costs (−2%) and no effect on gross revenues, net returns, or economic risk. Overall, reducing tillage did not affect the long-term profitability of any of the three FST farming systems. Regardless of tillage practices or organic price premiums, the manure-based organic system supported higher net returns than the conventional system. This finding suggests that continuous living cover and manure inputs may have a greater influence on system profitability than tillage practices.

The Varaždin aquifer is the only source of drinking water for inhabitants of the Varaždin County. In the last decades, groundwater contamination with nitrate has become an increasing problem. Therefore, there is a need to define the origin of nitrate as the first step in groundwater remediation. The data in this article consist of δ18O and δ15N values in nitrate in groundwater, and δ15N in solid matter. Groundwater was sampled in the period from April 2018 to December 2019 at 10 different sites by pumping the wells, and directly in the gravel pit in Šijanec. Representative solid samples of plants, soil, manure, and synthetic fertilizers were collected from arable land in two field campaigns (July and October 2019). The presented dataset can be used as a baseline for identification of nitrate sources in groundwater and possible nitrate attenuation processes. The data is related to the research article “Tracking the nitrogen cycle in a vulnerable alluvial system using a multi proxy approach: case study Varaždin alluvial aquifer, Croatia.” [1].

BackgroundA variety of factors influence seafarers' health. Such factors might affect their satisfaction with life.AimsTo examine the relationships between seafarers' mental health status and satisfaction with life by using a structural equation method.MethodsIn this survey, 470 seafarers were selected via convenience sampling method from two shipping companies. Validated questionnaires including Satisfaction with Life Scale (SWLS), generalized anxiety disorder-7 (GAD-7), Post-traumatic Stress Disorder-8 (PTSD-8), Patient Health Questionnaire-9 (PHQ-9), General Health Questionnaire-12 (GHQ-12), Perceived Health status and Depression-Anxiety-Stress scale-21 (DASS-21) were used to assess different aspects of well-being and life satisfaction. The stratified path analysis method was applied to analyze the data.Results439 seafarers (200 officers and 237 non-officers) with a mean age of 34.5 (SD: 8.05) participated in the current study. The GHQ score directly affected satisfaction with life in both officers (β = 0.35) and non-officers (β = 0.40). Also, perceived health status directly and indirectly affected satisfaction with life among officers (β = 0.19) and non-officers (β = 0.06). While officers working days per month indirectly impacted satisfaction with life through the general anxiety disorder, perceived health status, depression, anxiety, stress and current mental health. In non-officers, generalized anxiety disorder had the most potent indirect effects on satisfaction with life through perceived health status and current mental health.ConclusionPerceived health status, directly and indirectly, affected seafarers' satisfaction with life. Measures should be taken in order to improve seafarers' perceived health status and its effects on satisfaction with life.

Objective:. Whether a Blumgart anastomosis (BA) is superior to Cattell-Warren anastomosis (CWA) in terms of postoperative pancreatic fistula (POPF) following pancreatoduodenectomy. Importance:. Complications driven by POPF following pancreatic cancer resection may hinder adjuvant therapy, shortening survival. BA may reduce complications compared to CWA, improving the use of adjuvant therapy and prolonging survival. Methods:. A multicenter double-blind, controlled trial of patients undergoing resection for suspected pancreatic head cancer, randomized during surgery to a BA or CWA, stratified by pancreatic consistency and duct diameter. The primary end point was POPF, and secondary outcome measures were adjuvant therapy use, specified surgical complications, quality of life, and survival from the date of randomization. For a 10% POPF reduction, 416 patients were required, 208 per arm (two-sided α = 0·05; power = 80%). Results:. Z-score at planned interim analysis was 0.474 so recruitment was held to 238 patients; 236 patients were analyzed (112 BA and 124 CWA). No significant differences in POPF were observed between BA and CWA, odds ratio (95% confidence interval [CI]) 1·04 (0.58–1.88), P = 0.887, nor in serious adverse events. Adjuvant therapy was delivered to 98 (62%) of 159 eligible patients with any malignancy; statistically unrelated to arm or postoperative complications. Twelve-month overall survival, hazard ratio (95% CI), did not differ between anastomoses; BA 0.787 (0.713–0.868) and CWA 0.854 (0.792–0.921), P = 0.266, nor for the 58 patients with complications, median (IQR), 0.83 (0.74–0.91) compared to 101 patients without complications 0.82 (0.76–0.89) (P = 0.977). Conclusions:. PANasta represents the most robust analysis of BA versus CWA to date.

Introduction Kidney cancer (renal cell cancer (RCC)) is the seventh most common cancer in the UK. As RCC is largely curable if detected at an early stage and most patients have no symptoms, there is international interest in evaluating a screening programme for RCC. The Yorkshire Kidney Screening Trial (YKST) will assess the feasibility of adding non-contrast abdominal CT scanning to screen for RCC and other abdominal pathology within the Yorkshire Lung Screening Trial (YLST), a randomised trial of community-based CT screening for lung cancer.Methods and analysis In YLST, ever-smokers aged 55–80 years registered with a general practice in Leeds have been randomised to a Lung Health Check assessment, including a thoracic low-dose CT (LDCT) for those at high risk of lung cancer, or routine care. YLST participants randomised to the Lung Health Check arm who attend for the second round of screening at 2 years without a history of RCC or abdominal CT scan within the previous 6 months will be invited to take part in YKST. We anticipate inviting 4700 participants. Those who consent will have an abdominal CT immediately following their YLST thoracic LDCT. A subset of participants and the healthcare workers involved will be invited to take part in a qualitative interview. Primary objectives are to quantify the uptake of the abdominal CT, assess the acceptability of the combined screening approach and pilot the majority of procedures for a subsequent randomised controlled trial of RCC screening within lung cancer screening.Ethics and dissemination YKST was approved by the North West-Preston Research Ethics Committee (21/NW/0021), and the Health Research Authority on 3 February 2021. Trial results will be disseminated at clinical meetings, in peer-reviewed journals and to policy-makers. Findings will be made available to participants via the study website (www.YKST.org).Trial registration numbers NCT05005195 and ISRCTN18055040.

Abstract Background Homelessness is a major social and public health concern. It is a traumatic experience, and can have a devastating effect on those experiencing it. People who are homeless often face significant barriers when accessing public services, and those experiencing more visible and extreme forms of homelessness have often faced adverse childhood events, extreme social disadvantage, physical, emotional and sexual abuse, neglect, low self‐esteem, poor physical and mental health, and much lower life expectancy compared to the general population. Problematic substance use is disproportionately high amongst people experiencing homelessness, with many using drugs and alcohol to deal with the stress of living on the street, to keep warm, or to block out memories of previous abuse or trauma. Drug overdose is a major cause of death for people experiencing street homelessness. Substance dependency can also create barriers to successful transition to stable housing. There is ongoing policy interest in the effectiveness of different interventions that aim to stop, reduce or prevent problematic substance use, and there is specific interest in the relative effectiveness of interventions that adopt harm reduction or abstinence‐based approaches. Objectives The objective of this review is to understand the effectiveness of different substance use interventions. The review will consider the effectiveness of harm reduction‐based interventions, and abstinence‐based interventions, for adults experiencing homelessness. The focus of the review is on high‐income countries. Search Methods The primary source of studies for potential inclusion in this review is the Homelessness Effectiveness Studies Evidence and Gaps Maps (EGM). The first of these was published in 2018, with updates published in 2019 and 2020. A further update is due to be published in the summer of 2022. It is this update that provides the final list of studies from which this review will draw. The search for this update (EGM 4th edition) was completed in September 2021. Other potential studies will be identified through a call for grey evidence and hand‐searching key journals. Selection Criteria Eligible studies will be impact evaluations with designs at levels, 3, 4 and 5 of the Maryland Scientific Methods scale. This therefore includes all studies categorised as either ‘Randomised Controlled Trials’ or ‘nonexperimental designs with a comparison group’ from the studies which form the basis of the Homelessness Effectiveness Studies Evidence and Gap Maps (EGM) created by CHI and the Campbell Collaboration. We are interested in studies that examine the effect of interventions on substance use outcomes. Studies to be excluded are those with designs at levels 1 and 2 of the Maryland Scientific Methods scale, for example, studies without a control or comparison group, ‘before vs. after’ designs (without an untreated comparison group), and cross‐sectional regressions. Data Collection and Analysis Descriptive characteristics and statistical information in included studies will be coded and checked by at least two members of the review team. Studies selected for the review will be assessed for confidence in the findings using a critical appraisal tool for determining confidence in primary studies. Standardised effect sizes will be calculated and, if a study does not provide sufficient raw data for the calculation of an effect size, we will attempt to contact the author(s) to obtain this data. We will aim to use random‐effects meta‐analysis and robust‐variance estimation procedures to synthesise effect sizes. If a study includes multiple effects, we will carry out a critical assessment to determine (even if only theoretically) whether the effects are likely to be dependent. Where we suspect dependent effects, we will determine whether we can account for these by robust variance estimation. We will explore the moderating influence of participant and study characteristics, such as gender, race, substances targeted and length of follow‐up. Where effect sizes are converted from a binary to continuous measure (or vice versa), we will undertake a sensitivity analysis to investigate the effect of the inclusion of studies with a converted effect size in the meta‐analysis by running an additional analysis with these studies omitted. We will also assess the sensitivity of results to inclusion of non‐randomised studies and studies classified as low confidence in findings. All analyses will include an assessment of statistical heterogeneity. Finally, we will undertake analysis to assess whether publication bias is likely to be a factor in our findings.

Abstract Sustained adrenergic stimulation by norepinephrine (NE) contributes to ovarian carcinoma metastasis and impairment of chemotherapy response. Although the effect of sustained NE stimulation in cancer progression is well established, less is known about its role in cancer initiation. To determine the extent to which stress hormones influence ovarian cancer initiation, we conducted a long-term (> 3 months; > 40 population doublings) experiment in which normal immortalized fallopian tube secretory (iFTSEC283) and ovarian surface epithelial (iOSE11) cell lines and their isogenic pairs containing a p53 mutation (iFTSEC283p53R175H; iOSE11p53R175H), were continuously exposed to NE (100 nM, 1 μM, 10 μM). Fallopian tube cells displayed a p53-independent increase in proliferation and colony-forming ability in response to NE, while ovarian surface epithelial cells displayed a p53-independent decrease in both assays. Fallopian tube cells with mutant p53 showed a mild loss of chromosomes and TP53 status was also a defining factor in transcriptional response of fallopian tube cells to long-term NE treatment.

Abstract Background The trial will study the effects of the Whole School SEND Review on secondary school pupils in English mainstream education, to understand the impact of the intervention on academic attainment, wellbeing, and school attendance. The Review is designed to facilitate whole-school change through providing enhanced, intensive and sustained support and training in inclusive education for school special educational needs coordinators and leadership teams. The trial will have a specific focus on pupils designated as having special educational needs or disabilities. Methods We recruited 160 English secondary schools (approx. 58,000 pupils across two cohorts) to a two-arm pragmatic parallel cluster randomised controlled trial, with allocation at the school level. Randomisation will be stratified by school region. The primary outcome is attainment in English language (using standardised national test results at 16 years) for pupils designated as having a special educational need (approx. 4000 pupils). Secondary outcomes will be measured for pupils both with and without a special educational need designation and include pupil wellbeing (measured using the Strengths and Difficulties Questionnaire), absences and exclusions, and attainment in Mathematics and English language at 16 years. The intervention will be implemented from July 2021 and analysis of outcomes (for the year 9 cohort) will take place in September 2023, with further analysis (for the year 8 cohort) in September 2024 if the evaluation shows that acceptable implementation fidelity has been achieved. Discussion Pupils with special educational needs represent a significant and often vulnerable part of the secondary school population, are disproportionately likely to be excluded from school, eligible for free school meals, or supported by children’s social care. Despite these multiple important areas of need, school leaders report substantial challenges in making additional provision for this group. Previous research has highlighted the development of inclusive school cultures (rather focusing primarily on targeted individualised approaches) as being important. This trial will investigate how an intervention designed to drive whole school change may lead to outcomes for pupils with and without a special educational needs designation. As such, this trial is expected to make an important contribution to research evidence and to UK educational policy. Trial registration ISRCTN registry ISRCTN11339306 . Registered on 12 March 2020 (retrospectively registered).

The blended online digital (BOLD) approach to teaching is popular within many universities. Despite this popularity, our understanding of the experiences of students making the transition to online learning is limited, specifically an examination of those elements associated with success. The aim of this study is to explore the experiences of students transitioning from a traditional mode of delivery to a more online approach in an inaugural BOLD Bachelor of Nursing program at a regional multi-campus institution in Victoria, Australia. Fifteen students across two regional campuses participated in one of four focus groups. This qualitative exploration of students’ experience contributes to contemporary insights into how we might begin to develop programs of study that help students develop self-regulation. A modified method of thematic analysis of phenomenological data was employed to analyse the focus group interview data to identify themes that represent the meaning of the transition experience for students. This qualitative exploration of students’ experience contributes to contemporary insights into how we might begin to develop programs of study that help students develop self-regulation.

Limited research has examined inspiratory muscle performance (IMP) and functional performance (FP) of patients after valve replacement surgery (VRS). The purpose of this study was to examine IMP as well as several measures of FP in patients post-VRS. The study results of 27 patients revealed that patients undergoing transcatheter VRS were significantly (p = 0.01) older than patients undergoing minimally invasive or median sternotomy VRS with the median sternotomy VRS group performing significantly (p < 0.05) better than the transcatheter VRS group in the 6-min walk test, 5x sit-to-stand test, and sustained maximal inspiratory pressure. The 6-min walk test and IMP measures in all groups were significantly (p < 0.001) lower than predicted values. Significant (p < 0.05) relationships were found between IMP and FP with greater IMP being associated with greater FP. Pre-operative and early post-operative rehabilitation may improve IMP and FP post-VRS.

Background: The COVID-19 pandemic presents one of the greatest threats to pediatric pain care seen in generations. Due to public health restrictions, many pediatric pain clinics halted in-person appointments, delaying and disrupting access to care. There is no existing research on the impacts of COVID-19 on pediatric chronic pain care in Canada or the challenges experienced by health care professionals and pain clinics. Aims: The aim of this study was to evaluate the impact of COVID-19 on Canadian pediatric chronic pain care by documenting how health care professionals provided care during the first six months of the pandemic. Methods: Two Canadian online cross-sectional surveys were conducted: one among Canadian pediatric pain clinic directors (Study 1) and another among multidisciplinary pediatric pain health care professionals (Study 2). Results: Responses from 13/13 Canadian pediatric pain clinics/rehabilitation programs indicated that all clinics provided virtual care during the pandemic. No significant changes were reported on the frequency of appointment requests. Most clinics reported no perceived change in patient pain levels (n = 9/13, 69%) or occurrence of pain flares (n = 10/13, 77%). Results from 151 individual health care professionals indicated that the majority (90%) of non–emergency department respondents were providing virtual care. The main challenges of virtual care included technological barriers, financial concerns, infrastructure and logistics, privacy, and clinical challenges. Conclusions: This study documented the impact of the COVID-19 pandemic on pediatric chronic pain care in Canada and highlighted the rapid shift to using virtual solutions. Simultaneously, respondents outlined current challenges and potential solutions to consider in the development of virtual care guidelines and policy in Canada.

OBJECTIVES:. Patients admitted to intensive care often require treatment with invasive mechanical ventilation and high concentrations of oxygen. Mechanical ventilation can cause acute lung injury that may be exacerbated by oxygen therapy. Uncertainty remains about which oxygen therapy targets result in the best clinical outcomes for these patients. This review aims to determine whether higher or lower oxygenation targets are beneficial for mechanically ventilated adult patients. DATA SOURCES:. Excerpta Medica dataBASE, Medical Literature Analysis and Retrieval System Online, and Cochrane medical databases were searched from inception through to February 28, 2021. STUDY SELECTION:. Randomized controlled trials comparing higher and lower oxygen targets in adult patients receiving invasive mechanical ventilation via an endotracheal tube or tracheostomy in an intensive care setting. DATA EXTRACTION:. Study setting, participant type, participant numbers, and intervention targets were captured. Outcome measures included “mortality at longest follow-up” (primary), mechanical ventilator duration and free days, vasopressor-free days, patients on renal replacement therapy, renal replacement free days, cost benefit, and quality of life scores. Evidence certainty and risk of bias were evaluated using Grading of Recommendations Assessment, Development and Evaluation and the Cochrane Risk of Bias tool. A random-effects models was used. Post hoc subgroup analysis looked separately at studies comparing hypoxemia versus normoxemia and normoxemia versus hyperoxemia. DATA SYNTHESIS:. Data from eight trials (4,415 participants) were analyzed. Comparing higher and lower oxygen targets, there was no difference in mortality (odds ratio, 0.95; 95% CI, 0.74–1.22), but heterogeneous and overlapping target ranges limit the validity and clinical relevance of this finding. Data from seven studies (n = 4,245) demonstrated targeting normoxemia compared with hyperoxemia may reduce mortality at longest follow-up (0.73 [0.57–0.95]) but this estimate had very low certainty. There was no difference in mortality between targeting relative hypoxemia or normoxemia (1.20 [0.83–1.73]). CONCLUSIONS:. This systematic review and meta-analysis identified possible increased mortality with liberal oxygen targeting strategies and no difference in morbidity between high or low oxygen targets in mechanically ventilated adults. Findings were limited by substantial heterogeneity in study methodology and further research is urgently required to define optimal oxygen therapy targets.

Nursing has seen a dominance of women within the profession, and today, the presence of men in the role remains less understood and appreciated. Males considering or entering nursing face challenges concerning role misconception, marginalization, and gender bias. With a looming shortage of nurses on the horizon, it is more important now than ever before to find better ways of engaging males into nursing. The aim of the study was to examine the psychological constructs that influence male perceptions of nursing as they seek to navigate the profession, and what aspects influence men to consider nursing as a career. To achieve this, a systematic review and mixed research synthesis (integrated design) was conducted. English language research published between 1999 and 2019 was eligible. The methodological rigor of qualitative articles followed the Critical Appraisal Skills Program, while the Best Evidence Medical Education guided the quantitative review. Among the 24 publications identified, three sub-themes emerged from the overarching theme of the funambulist or tightrope walker. Sub-themes included societal, inner and collective voices that inform men’s place in nursing or their decision making about entering the profession. There is a need to re-visit what it means to be a nurse in order to address the gendered stereotypes that impact men entering the nursing profession.

Abstract Background Prescribing in dental practice has a relatively small but important contribution to the quantity of antibiotics prescribed in primary care. This study aimed to analyse antibiotic prescribing in dentistry over time (2010–2016) in 4 different Northern European countries and their relative contribution to national outpatients consumption. Methods This retrospective study evaluated the frequency and number of national antibiotic prescriptions written by dentists in England, Scotland, Norway and Sweden. The consumption of such antibiotics was measured using WHO defined daily doses (DDDs), DDDs per 100,000 inhabitants per day (DIDs100,000). Results A total of more than 27 million prescriptions (27,026,599) archived between 2010 and 2016 from the four countries were analysed. The national contribution of Norwegian dentists to the total primary care prescription during this period was 8%. The corresponding figures for Sweden, Scotland and England were 7, 6, and 8%. Dental contribution to National antibiotic use in all four countries has decreased over the study time period for commonly prescribed antibiotics in dentistry, i.e., the beta-lactams (Phenoxymethyl penicillin/Amoxicillin) and metronidazole. There were less numbers of prescriptions by dentists in Norway and Sweden compared to England and Scotland. Marked differences in some classes of antibiotics were noted with Phenoxymethyl penicillin dominating in Sweden/Norway compared to Amoxicillin and Metronidazole in England/Scotland. In England and Scotland, dentists were the largest prescribers of metronidazole in primary care. Clindamycin prescriptions was higher in Norway and Sweden. Conclusion Noticeable differences exist in prescribing patterns for the management of oral infections. High levels of metronidazole use in England and Scotland also require further analysis. All countries over the study period showed a decrease in total numbers of antibiotics prescribed.

This study was conducted to understand the relationship between various critical temperatures and the stability of the secondary phases inside the heat-affected-zone (HAZ) of welded Grade 91 (Gr.91) steel parts. Type IV cracking has been observed in the HAZ, and it is widely accepted that the stabilities of the secondary phases in Gr.91 steel are critical to the creep resistance, which is related to the crack failure of this steel. In this work, the stabilities of the secondary phases, including those of the M23C6, MX, and Z phases, were simulated by computational thermodynamics. Equilibrium cooling and Scheil simulations were carried out in order to understand the phase stability in welded Gr.91 steel. The effect of four critical temperatures—that is, Ac1 (the threshold temperature at which austenite begins to form), Ac3 (the threshold temperature at which ferrite is fully transformed into austenite), and the M23C6 and Z phase threshold temperatures—on the thickness of the HAZ and phase stability in the HAZ is discussed. Overall, the simulations presented in this paper explain the mechanisms that can affect the creep resistance of Gr.91 steel, and can offer a possible solution to the problem of how to increase creep resistance at elevated temperatures by optimizing the steel composition, welding, and heat treatment process parameters. The simulation results from this work provide guidance for future alloy development to improve creep resistance in order to prevent type IV cracking.