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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.