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This review aimed to identify measurement tools to assess dietary intake and physical activity (PA) among individuals with autism spectrum disorder (ASD) and describe the evidence of validity and availability of each tool. Searches were conducted in PubMed, Embase, CINAHL, and PsycINFO using keywords for ASD, PA, diet, and assessment/measurement (n = 2364 articles). After removing duplicates and title/abstract screening, 212 full-text articles were reviewed, and 113 articles were included for data extraction. The most common dietary and PA assessment tools were identified, and each reviewer independently extracted the data on target population of the assessment tool, type of instrument, evidence on psychometrics validation, constructs measured, and instrument availability. Our findings highlight the need for instruments developed for and/or validated in this population.

Abstract Background In recognition of the burden of Perinatal Mental Health problems, NHS England invested £365 million to transform women’s access to mental health care, including investment in Community Perinatal Mental Health Services. This study examined how elements of provider care affected women’s engagement with these services. Methods Semi-structured interviews were conducted with 139 women and explored their experiences of care from 10 different Community Perinatal Mental Health Teams; including which service components participants believed made a difference to their initial and continued engagement. Realist analysis was used to create context-mechanism-outcome configurations (CMOCs) across interviews, since not all parts of the configurations were always articulated within singular interviews. Results Four key pillars for engagement were identified: perinatal competence, relationship building, accurate reassurance, and reliability. The way perinatal competencies were relayed to women mattered; compassion, understanding and consistency were critical interactional styles. The extent to which these factors affected women’s engagement varied by their context and personal characteristics. Conclusions As mental health problems increase, disproportionately affecting vulnerable populations, it is critical to continue to ensure support is not only available, but appropriately meets the needs of those individuals. Our findings suggest that key staff behaviours applied at the right time can support women’s engagement and potentially contribute to better treatment outcomes.

Abstract Background We initially reported on the cost-effectiveness of a 6-month randomized controlled implementation trial which evaluated Health TAPESTRY, a primary care program for older adults, at the McMaster Family Health Team (FHT) site and 5 other FHT sites in Ontario, Canada. While there were no statistically significant between-group differences in outcomes at month 6 post randomization, positive outcomes were observed at the McMaster FHT site, which recruited 40% (204/512) of the participants. The objective of this post-hoc study was to determine the cost-effectiveness of Health TAPESTRY based on data from the McMaster FHT site. Methods Costs included the cost to implement Health TAPESTRY at McMaster as well as healthcare resource consumed, which were costed using publicly available sources. Health-related-quality-of-life was evaluated with the EQ-5L-5L at baseline and at month 6 post randomization. Quality-adjusted-life-years (QALYs) were calculated under an-area-under the curve approach. Unadjusted and adjusted regression analyses (two independent regression analyses on costs and QALYs, seemingly unrelated regression [SUR], net benefit regression) as well as difference-in-difference and propensity score matching (PSM) methods, were used to deal with the non-randomized nature of the trial. Sampling uncertainty inherent to the trial data was estimated using non-parametric bootstrapping. The return on investment (ROI) associated with Health TAPESTRY was calculated. All costs were reported in 2021 Canadian dollars. Results With an intervention cost of $293/patient, Health TAPESTRY was the preferred strategy in the unadjusted and adjusted analyses. The results of our bootstrap analyses indicated that Health TAPESTRY was cost-effective compared to usual care at commonly accepted WTP thresholds. For example, if decision makers were willing to pay $50,000 per QALY gained, the probability of Health TAPESTRY to be cost effective compared to usual care varied from 0.72 (unadjusted analysis) to 0.96 (SUR) when using a WTP of $50,000/QALY gained. The DID and ROI analyses indicated that Health Tapestry generated a positive ROI. Conclusion Health TAPESTRY was the preferred strategy when implemented at the McMaster FHT. We caution care in interpreting the results because of the post-hoc nature of the analyses and limited sample size based on one site.

The relationship between the inverse Langevin function and the proposed r0-r1-Lambert W function is defined. The derived relationship leads to new approximations for the inverse Langevin function with lower relative error bounds than comparable published approximations. High accuracy approximations, based on Schröder’s root approximations of the first kind, are detailed. Several applications are detailed.

Abstract Mental disorders are leading causes of disability and premature death worldwide, partly due to high comorbidity with cardiometabolic disorders. Reasons for this comorbidity are still poorly understood. We leverage nation-wide health records and near-complete genealogies of Denmark and Sweden (n = 17 million) to reveal the genetic and environmental contributions underlying the observed comorbidity between six mental disorders and 15 cardiometabolic disorders. Genetic factors contributed about 50% to the comorbidity of schizophrenia, affective disorders, and autism spectrum disorder with cardiometabolic disorders, whereas the comorbidity of attention-deficit/hyperactivity disorder and anorexia with cardiometabolic disorders was mainly or fully driven by environmental factors. In this work we provide causal insight to guide clinical and scientific initiatives directed at achieving mechanistic understanding as well as preventing and alleviating the consequences of these disorders.

Abstract Given high costs of Oncotype DX (ODX) testing, widely used in recurrence risk assessment for early-stage breast cancer, studies have predicted ODX using quantitative clinicopathologic variables. However, such models have incorporated only small cohorts. Using a cohort of patients from the National Cancer Database (NCDB, n = 53,346), we trained machine learning models to predict low-risk (0-25) or high-risk (26-100) ODX using quantitative estrogen receptor (ER)/progesterone receptor (PR)/Ki-67 status, quantitative ER/PR status alone, and no quantitative features. Models were externally validated on a diverse cohort of 970 patients (median follow-up 55 months) for accuracy in ODX prediction and recurrence. Comparing the area under the receiver operating characteristic curve (AUROC) in a held-out set from NCDB, models incorporating quantitative ER/PR (AUROC 0.78, 95% CI 0.77–0.80) and ER/PR/Ki-67 (AUROC 0.81, 95% CI 0.80–0.83) outperformed the non-quantitative model (AUROC 0.70, 95% CI 0.68–0.72). These results were preserved in the validation cohort, where the ER/PR/Ki-67 model (AUROC 0.87, 95% CI 0.81–0.93, p = 0.009) and the ER/PR model (AUROC 0.86, 95% CI 0.80–0.92, p = 0.031) significantly outperformed the non-quantitative model (AUROC 0.80, 95% CI 0.73–0.87). Using a high-sensitivity rule-out threshold, the non-quantitative, quantitative ER/PR and ER/PR/Ki-67 models identified 35%, 30% and 43% of patients as low-risk in the validation cohort. Of these low-risk patients, fewer than 3% had a recurrence at 5 years. These models may help identify patients who can forgo genomic testing and initiate endocrine therapy alone. An online calculator is provided for further study.

Introduction: Atrophy of the nucleus basalis of Meynert (NBM) is an early indicator of Alzheimer's disease (AD). However, reduced integrity of the NBM white matter tracts may be more relevant for cognitive impairment and progression to dementia than NBM volume. Research is needed to compare differences in NBM volume and integrity of the lateral and medial NBM tracts across early and later stages of AD progression. Methods: 187 participants were included in this study who were either healthy controls (HC; n = 50) or had early mild cognitive impairment (EMCI; n = 50), late MCI (LMCI; n = 37), or AD (n = 50). NBM volume was calculated using voxel-based morphometry and mean diffusivity (MD) of the lateral and medial NBM tracts were extracted using probabilistic tractography. Between group differences in NBM volume and tract MD were compared using linear mixed models controlling for age, sex, and either total intracranial volume or MD of a control mask, respectively. Associations between NBM volume and tract MD with executive function, memory, language, and visuospatial function were also analysed. Results: NBM volume was smallest in AD followed by LMCI (p

Summary: Background: Deployment and access to state-of-the-art precision medicine technologies remains a fundamental challenge in providing equitable global cancer care in low-resource settings. The expansion of digital pathology in recent years and its potential interface with diagnostic artificial intelligence algorithms provides an opportunity to democratize access to personalized medicine. Current digital pathology workstations, however, cost thousands to hundreds of thousands of dollars. As cancer incidence rises in many low- and middle-income countries, the validation and implementation of low-cost automated diagnostic tools will be crucial to helping healthcare providers manage the growing burden of cancer. Methods: Here we describe a low-cost ($230) workstation for digital slide capture and computational analysis composed of open-source components. We analyze the predictive performance of deep learning models when they are used to evaluate pathology images captured using this open-source workstation versus images captured using common, significantly more expensive hardware. Validation studies assessed model performance on three distinct datasets and predictive models: head and neck squamous cell carcinoma (HPV positive versus HPV negative), lung cancer (adenocarcinoma versus squamous cell carcinoma), and breast cancer (invasive ductal carcinoma versus invasive lobular carcinoma). Findings: When compared to traditional pathology image capture methods, low-cost digital slide capture and analysis with the open-source workstation, including the low-cost microscope device, was associated with model performance of comparable accuracy for breast, lung, and HNSCC classification. At the patient level of analysis, AUROC was 0.84 for HNSCC HPV status prediction, 1.0 for lung cancer subtype prediction, and 0.80 for breast cancer classification. Interpretation: Our ability to maintain model performance despite decreased image quality and low-power computational hardware demonstrates that it is feasible to massively reduce costs associated with deploying deep learning models for digital pathology applications. Improving access to cutting-edge diagnostic tools may provide an avenue for reducing disparities in cancer care between high- and low-income regions. Funding: Funding for this project including personnel support was provided via grants from NIH/NCI R25-CA240134, NIH/NCI U01-CA243075, NIH/NIDCR R56-DE030958, NIH/NCI R01-CA276652, NIH/NCI K08-CA283261, NIH/NCI-SOAR 25CA240134, SU2C (Stand Up to Cancer) Fanconi Anemia Research Fund – Farrah Fawcett Foundation Head and Neck Cancer Research Team Grant, and the European Union Horizon Program (I3LUNG).

Movement patterns of bearded capuchin monkeys (Cebus (Sapajus) libidinosus) in northeastern Brazil are likely impacted by environmental features such as elevation, vegetation density, or vegetation type. Habitat preferences of these monkeys provide insights regarding the impact of environmental features on species ecology and the degree to which they incorporate these features in movement decisions. In order to evaluate environmental features influencing movement patterns and predict areas suitable for movement, we employed a maximum entropy modelling approach, using observation points along capuchin monkey daily routes as species presence points. We combined these presence points with spatial data on important environmental features from remotely sensed data on land cover and topography. A spectral mixing analysis procedure was used to generate fraction images that represent green vegetation, shade and soil of the study area. A Landsat Thematic Mapper scene of the area of study was geometrically and atmospherically corrected and used as input in a Minimum Noise Fraction (MNF) procedure and a linear spectral unmixing approach was used to generate the fraction images. These fraction images and elevation were the environmental layer inputs for our logistic MaxEnt model of capuchin movement. Our models' predictive power (test AUC) was 0.775. Areas of high elevation (>450 m) showed low probabilities of presence, and percent green vegetation was the greatest overall contributor to model AUC. This work has implications for predicting daily movement patterns of capuchins in our field site, as suitability values from our model may relate to habitat preference and facility of movement.

Abstract Background Suicide is a leading cause of maternal death during pregnancy and the year after birth (the perinatal period). While maternal suicide is a relatively rare event with a prevalence of 3.84 per 100,000 live births in the UK [1], the impact of maternal suicide is profound and long-lasting. Many more women will attempt suicide during the perinatal period, with a worldwide estimated prevalence of 680 per 100,000 in pregnancy and 210 per 100,000 in the year after birth [2]. Qualitative research into perinatal suicide attempts is crucial to understand the experiences, motives and the circumstances surrounding these events, but this has largely been unexplored. Aim Our study aimed to explore the experiences of women and birthing people who had a perinatal suicide attempt and to understand the context and contributing factors surrounding their perinatal suicide attempt. Methods Through iterative feedback from a group of women with lived experience of perinatal mental illness and relevant stakeholders, a qualitative study design was developed. We recruited women and birthing people (N = 11) in the UK who self-reported as having undertaken a suicide attempt. Interviews were conducted virtually, recorded and transcribed. Using NVivo software, a critical realist approach to Thematic Analysis was followed, and themes were developed. Results Three key themes were identified that contributed to the perinatal suicide attempt. The first theme ‘Trauma and Adversities’ captures the traumatic events and life adversities with which participants started their pregnancy journeys. The second theme, ‘Disillusionment with Motherhood’ brings together a range of sub-themes highlighting various challenges related to pregnancy, birth and motherhood resulting in a decline in women’s mental health. The third theme, ‘Entrapment and Despair’, presents a range of factors that leads to a significant deterioration of women’s mental health, marked by feelings of failure, hopelessness and losing control. Conclusions Feelings of entrapment and despair in women who are struggling with motherhood, alongside a background of traumatic events and life adversities may indicate warning signs of a perinatal suicide. Meaningful enquiry around these factors could lead to timely detection, thus improving care and potentially prevent future maternal suicides.

Abstract Background The National Health Service in England pledged >£365 million to improve access to mental healthcare services via Community Perinatal Mental Health Teams (CPMHTs) and reduce the rate of perinatal relapse in women with severe mental illness. This study aimed to explore changes in service use patterns following the implementation of CPMHTs in pregnant women with a history of specialist mental healthcare in England, and conduct a cost-analysis on these changes. Methods This study used a longitudinal cohort design based on existing routine administrative data. The study population was all women residing in England with an onset of pregnancy on or after 1st April 2016 and who gave birth on or before 31st March 2018 with pre-existing mental illness (N = 70,323). Resource use and costs were compared before and after the implementation of CPMHTs. The economic perspective was limited to secondary mental health services, and the time horizon was the perinatal period (from the start of pregnancy to 1-year post-birth, ~ 21 months). Results The percentage of women using community mental healthcare services over the perinatal period was higher for areas with CPMHTs (30.96%, n=9,653) compared to areas without CPMHTs (24.72%, n=9,615). The overall percentage of women using acute care services (inpatient and crisis resolution teams) over the perinatal period was lower for areas with CPMHTs (4.94%, n=1,540 vs. 5.58%, n=2,171), comprising reduced crisis resolution team contacts (4.41%, n=1,375 vs. 5.23%, n=2,035) but increased psychiatric admissions (1.43%, n=445 vs. 1.13%, n=441). Total mental healthcare costs over the perinatal period were significantly higher for areas with CPMHTs (fully adjusted incremental cost £111, 95% CI £29 to £192, p-value 0.008). Conclusions Following implementation of CPMHTs, the percentage of women using acute care decreased while the percentage of women using community care increased. However, the greater use of inpatient admissions alongside greater use of community care resulted in a significantly higher mean cost of secondary mental health service use for women in the CPMHT group compared with no CPMHT. Increased costs must be considered with caution as no data was available on relevant outcomes such as quality of life or satisfaction with services.

Abstract Deep learning methods have emerged as powerful tools for analyzing histopathological images, but current methods are often specialized for specific domains and software environments, and few open-source options exist for deploying models in an interactive interface. Experimenting with different deep learning approaches typically requires switching software libraries and reprocessing data, reducing the feasibility and practicality of experimenting with new architectures. We developed a flexible deep learning library for histopathology called Slideflow, a package which supports a broad array of deep learning methods for digital pathology and includes a fast whole-slide interface for deploying trained models. Slideflow includes unique tools for whole-slide image data processing, efficient stain normalization and augmentation, weakly-supervised whole-slide classification, uncertainty quantification, feature generation, feature space analysis, and explainability. Whole-slide image processing is highly optimized, enabling whole-slide tile extraction at 40x magnification in 2.5 s per slide. The framework-agnostic data processing pipeline enables rapid experimentation with new methods built with either Tensorflow or PyTorch, and the graphical user interface supports real-time visualization of slides, predictions, heatmaps, and feature space characteristics on a variety of hardware devices, including ARM-based devices such as the Raspberry Pi.

Abstract Background After ivermectin became available, diethylcarbamazine (DEC) use was discontinued because of severe adverse reactions, including ocular reactions, in individuals with high Onchocerca volvulus microfilaridermia (microfilariae/mg skin, SmfD). Assuming long-term ivermectin use led to 40) mfAC and three pre-treatment ( 0–5, > 5) SmfD categories. A linear mixed model evaluated factors and covariates impacting mfAC levels. Ocular AEs were summarized by type and start post-treatment. Logistic models evaluated factors and covariates impacting the risk for ocular AEs. Results Moxidectin and ivermectin had the same effect on mfAC levels. These increased from pre-treatment to Day 4 and Month 1 in 20% and 16% of participants, respectively. Six and 12 months post-treatment, mfAC were detected in ≈5% and ≈3% of participants, respectively. Ocular Mazzotti reactions occurred in 12.4% of moxidectin- and 10.2% of ivermectin-treated participants without difference in type or severity. The risk for ≥ 1 ocular Mazzotti reaction increased for women (OR 1.537, 95% CI 1.096–2.157) and with mfAC levels pre- and 4 days post-treatment (OR 0: > 10 mfAC 2.704, 95% CI 1.27–5.749 and 1.619, 95% CI 0.80–3.280, respectively). Conclusions The impact of SmfD and mfAC levels before and early after treatment on ocular AEs needs to be better understood before making decisions on the risk-benefit of strategies including DEC. Such decisions should take into account interindividual variability in SmfD, mfAC levels and treatment response and risks to even a small percentage of individuals. Graphical Abstract

ObjectivesTo characterize factors associated with parental willingness for their children participation in a COVID-19 vaccine trial, use of different COVID-19 vaccines and acceptance of a third vaccine dose.MethodsParents of children aged 12–17 years in Lima, Perú were asked to complete an online questionnaire via social networks, from November 9, 2021, to April 23, 2022. We calculated crude and adjusted prevalence ratios with 95% confidence intervals to compare factors with the mentioned outcomes.ResultsFrom 523 parents responding, 374 completed the survey. 90.4% would give their children a third vaccine dose, 36.6% would allow their children participation in a COVID-19 vaccine clinical trial, and 33.2% would accept different vaccine brands between doses. Parental belief that COVID-19 vaccine studies met quality standards was associated with acceptance of a third booster dose (adjusted PR 3.25; 95% CI1.57–6.74; p = 0.002), enrolment in a COVID-19 clinical trial (adjusted PR 4.49; 95% CI1.25–16.06; p = 0.02), and acceptance of different COVID-19 vaccine brands between doses (adjusted PR 10.02; 95% CI1.40–71.95; p = 0.02).ConclusionMost parents would accept a third vaccine booster dose, approximately a third would participate in COVID-19 vaccine trials. Believing COVID-19 vaccines studies fulfilled quality standards was associated with the study outcomes. It is necessary to inform about the rigorous processes for the development of COVID-19 vaccines to generate confidence in parents to accept these vaccine-related outcomes.

Abstract Miscanthus is a perennial grass that can yield substantial amounts of biomass in land areas considered marginal. In the Coastal Plain region of North Carolina, marginal lands are typically located in coarse‐textured soils with low nutrient retention and water‐holding capacity, and high erosivity potential. Little is known about miscanthus water use under these conditions. We conducted a study to better understand the efficiency with which miscanthus uses natural resources such as water and radiant energy to produce harvestable dry biomass in comparison to corn, a typical commodity crop grown in the region. We hypothesized that under non‐limiting soil water conditions, miscanthus would have greater available energy and water use rates owing to its greater leaf area, thus leading to greater agronomic yields. Conversely, these effects would be negated under drought conditions. Our measurements showed that miscanthus intercepted more radiant energy than corn, which led to greater albedo (by 0.05), lower net radiation (by 4% or 0.4 MJ m−2 day−1), and lower soil heat flux (by 69% or 1.0 MJ m−2 day−1) than corn on average. Consequently, miscanthus had greater available energy (by 7% or 0.6 MJ m−2 day−1) and water use rates (by 14% or 0.5 mm day−1) than corn throughout the growing season on average, which partially confirmed our hypothesis. Greater water use rates and radiation interception by miscanthus did not translate to greater water‐use (1.5 g kg−1 vs. 1.6 g kg−1) and radiation‐use (0.9 g MJ−1 vs. 1.1 g MJ−1) efficiencies than corn. Compared to literature values, our data indicated that water and radiation availability were not limiting at our study site. Thus, it is likely that marginal land features present at the Coastal Plain region such as low soil fertility and high air temperatures throughout the growing season may constrain agronomic yields even if soil water and radiant energy are non‐limiting.

Chronic pain syndromes affect over one-third of the US adult population and often lead to significant disability and a reduced quality of life. Despite their high prevalence, causal links between chronic pain syndromes and anatomic abnormalities are often not apparent. Most current chronic pain treatments provide modest, if any, relief. Thus, there is a pressing need to understand the causal mechanisms implicated in chronic pain as a means to develop more targeted interventions for improvement in clinical outcomes and reduction in morbidity and financial burden. In the present manuscript, we summarize the current literature on treatment for chronic pain, and hypothesize that non-specific chronic back pain (without a clear organic etiology, such as tumors, infections or fractures) is of psychophysiologic origin. Based on this hypothesis, we developed Psychophysiologic Symptom Relief Therapy (PSRT), a novel pain reduction intervention for understanding and treating chronic pain. In this manuscript, we provide the rationale for PSRT, which we have tested in a pilot trial with a subsequent larger randomized trial underway. In the proposed trial, we will evaluate whether non-specific chronic back pain can be treated by addressing the underlying stressors and psychological underpinnings without specific physical interventions.

BackgroundSince the COVID-19 pandemic began, we have seen rapid growth in telemedicine use. However, telehealth care and services are not equally distributed, and not all patients with breast cancer have equal access across US regions. There are notable gaps in existing literature regarding the influence of neighborhood-level socioeconomic status on telemedicine use in patients with breast cancer and oncology services offered through telehealth versus in-person visits. ObjectiveWe assessed the relationship between neighborhood socioeconomic disadvantage and telemedicine use among patients with breast cancer and examined differential provisions of oncology services between telehealth and in-person visits. MethodsNeighborhood socioeconomic disadvantage was measured using the Area Deprivation Index (ADI), with higher scores indicating greater disadvantages. Telemedicine and in-person visits were defined as having had a telehealth and in-person visit with a provider, respectively, in the past 12 months. Multivariable logistic regression was performed to examine the association between ADI and telemedicine use. The McNemar test was used to assess match-paired data on types of oncology services comparing telehealth and in-person visits. ResultsThe mean age of the patients with breast cancer (n=1163) was 61.8 (SD 12.0) years; 4.58% (52/1161) identified as Asian, 19.72% (229/1161) as Black, 3.01% (35/1161) as Hispanic, and 72.78% (845/1161) as White. Overall, 35.96% (416/1157) had a telemedicine visit in the past 12 months. Of these patients, 65% (266/409) had a videoconference visit only, 22.7% (93/409) had a telephone visit only, and 12.2% (50/409) had visits by both videoconference and telephone. Higher ADI scores were associated with a lower likelihood of telemedicine use (adjusted odds ratio [AOR] 0.89, 95% CI 0.82-0.97). Black (AOR 2.38, 95% CI 1.41-4.00) and Hispanic (AOR 2.65, 95% CI 1.07-6.58) patients had greater odds of telemedicine use than White patients. Compared to patients with high school or less education, those with an associate’s degree (AOR 2.67, 95% CI 1.33-5.35), a bachelor’s degree (AOR 2.75, 95% CI 1.38-5.48), or a graduate or professional degree (AOR 2.57, 95% CI 1.31-5.04) had higher odds of telemedicine use in the past 12 months. There were no significant differences in providing treatment consultation (45/405, 11.1% vs 55/405, 13.6%; P=.32) or cancer genetic counseling (11/405, 2.7% vs 19/405, 4.7%; P=.14) between telehealth and in-person visits. Of the telemedicine users, 95.8% (390/407) reported being somewhat to extremely satisfied, and 61.8% (254/411) were likely or very likely to continue using telemedicine. ConclusionsIn this study of a multiethnic cohort of patients with breast cancer, our findings suggest that neighborhood-level socioeconomic disparities exist in telemedicine use and that telehealth visits could be used to provide treatment consultation and cancer genetic counseling. Oncology programs should address these disparities and needs to improve care delivery and achieve telehealth equity for their patient populations.

BackgroundThe use of large language models (LLM) has recently gained popularity in diverse areas, including answering questions posted by patients as well as medical professionals.ObjectiveTo evaluate the performance and limitations of LLMs in providing the correct diagnosis for a complex clinical case.DesignSeventy-five consecutive clinical cases were selected from the Massachusetts General Hospital Case Records, and differential diagnoses were generated by OpenAI’s GPT3.5 and 4 models.ResultsThe mean number of diagnoses provided by the Massachusetts General Hospital case discussants was 16.77, by GPT3.5 30 and by GPT4 15.45 (p

Abstract Low temperature ionic conducting materials such as OH− and H+ ionic conductors are important electrolytes for electrochemical devices. Here we show the discovery of mixed OH−/H+ conduction in ceramic materials. SrZr0.8Y0.2O3-δ exhibits a high ionic conductivity of approximately 0.01 S cm−1 at 90 °C in both water and wet air, which has been demonstrated by direct ammonia fuel cells. Neutron diffraction confirms the presence of OD bonds in the lattice of deuterated SrZr0.8Y0.2O3-δ . The OH− ionic conduction of CaZr0.8Y0.2O3-δ in water was demonstrated by electrolysis of both H2 18O and D2O. The ionic conductivity of CaZr0.8Y0.2O3-δ in 6 M KOH solution is around 0.1 S cm−1 at 90 °C, 100 times higher than that in pure water, indicating increased OH− ionic conductivity with a higher concentration of feed OH− ions. Density functional theory calculations suggest the diffusion of OH− ions relies on oxygen vacancies and temporarily formed hydrogen bonds. This opens a window to discovering new ceramic ionic conducting materials for near ambient temperature fuel cells, electrolysers and other electrochemical devices.

Abstract Miscanthus is a productive perennial grass that is suitable as a bioenergy crop in “marginal” lands (e.g., eroded soils) with low water holding capacity. However, little is known about the impact of miscanthus residues on vapor transport and soil water budgets. Laboratory experiments were conducted to measure the vapor conductance through miscanthus residues and its effect on soil water evaporation. The ranges for the length, width, and thickness of residue elements were 0.5–9.0, 0.1–0.5, and 0.1–0.5 cm, respectively. Average residue areal, bulk, and skeletal densities were 0.88 kg m−2, 24 kg m−3, and 1006 kg m−3, respectively, giving a porosity of 0.98 m3 m−3. A power function described the decrease in conductance with increasing residue load. The corresponding conductance for a residue load of 0.88 kg m−2 was 1.6 mm s−1. During the first days of a 60‐day drying experiment, cumulative evaporation showed logarithmic decay with increasing residue load. Conversely, cumulative evaporation during the last days of the study showed little difference between treatments. Measurements indicated that there is a “critical” residue load (∼1.0 kg m−2) beyond which evaporation no longer decreases appreciably when the soil is under the stage 1 evaporation regime. Results suggest that soil water conservation in marginal lands may be accomplished by maintaining moderate amounts of bioenergy grass residue covering the soil. Determining “critical” loads for different residue types is a knowledge gap that merits further research.

Introduction: Duchenne muscular dystrophy (DMD) is a fatal striated muscle degenerative disease. DMD is caused by loss of dystrophin protein, which results in sarcolemmal instability and cycles of myofiber degeneration and regeneration. Pathology is exacerbated by overactivation of infiltrating immune cells and fibroblasts, which leads to chronic inflammation and fibrosis. Mineralocorticoid receptors (MR), a type of nuclear steroid hormone receptors, are potential therapeutic targets for DMD. MR antagonists show clinical efficacy on DMD cardiomyopathy and preclinical efficacy on skeletal muscle in DMD models.Methods: We have previously generated myofiber and myeloid MR knockout mouse models to dissect cell-specific functions of MR within dystrophic muscles. Here, we compared skeletal muscle gene expression from both knockouts to further define cell-type specific signaling downstream from MR.Results: Myeloid MR knockout increased proinflammatory and profibrotic signaling, including numerous myofibroblast signature genes. Tenascin C was the most highly upregulated fibrotic gene in myeloid MR-knockout skeletal muscle and is a component of fibrosis in dystrophic skeletal muscle. Surprisingly, lysyl oxidase (Lox), canonically a collagen crosslinker, was increased in both MR knockouts, but did not localize to fibrotic regions of skeletal muscle. Lox localized within myofibers, including only a region of quadriceps muscles. Lysyl oxidase like 1 (Loxl1), another Lox family member, was increased only in myeloid MR knockout muscle and localized specifically to fibrotic regions.Discussion: This study suggests that MR signaling in the dystrophic muscle microenvironment involves communication between contributing cell types and modulates inflammatory and fibrotic pathways in muscle disease.

Abstract Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK’s Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a ‘Good level of development’ was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a ‘good level of development’ in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes.

Abstract Background Lower respiratory tract infections are the leading cause of mortality in young children globally. In many resource-limited settings clinicians rely on guidelines such as IMCI or ETAT + that promote empiric antibiotic utilization for management of acute respiratory illness (ARI). Numerous evaluations of both guidelines have shown an overall positive response however, several challenges have also been reported, including the potential for over-prescribing of unnecessary antibiotics. The aims of this study were to describe the antibiotic prescribing practices for children less than 24 months of age with symptoms of ARI, that were admitted to Kenema Government Hospital (KGH) in the Eastern Province of Sierra Leone, and to identify the number of children empirically prescribed antibiotics who were admitted to hospital with ARI, as well as their clinical signs, symptoms, and outcomes. Methods We conducted a prospective study of children

Objectives: We examined the association of nasopharyngeal (NP) pneumococcal co-colonization (>1 pneumococcal serotype) and pneumococcal density in young Peruvian children enrolled in a prospective cohort study. Methods: NP swabs collected monthly from children aged

Telemedicine emerged as an alternative care delivery system used to offer effective long-term management to patients with chronic, inflammatory conditions such as psoriatic disease. Teledermatology can provide reliable clinical information through thorough history-taking and virtual evaluations that include patient-provided images and disease activity assessment tools that may help accurately diagnose and manage patients with psoriasis. The integration of validated screening tools for psoriatic arthritis and effective teledermatology practices may improve access to specialists, thus avoiding preventable delays in the diagnosis and treatment of patients with psoriatic arthritis. Although the provision of telehealthcare should not completely replace high quality, in-person dermatologic or rheumatologic visits, the convenience and collaborative nature of teledermatology may lead to expanded access and expedited care in the appropriate setting, whether it be in a virtual or in-person visit.

The oral microbial flora may be significantly altered by orthodontic therapy and the use of fixed orthodontic brackets. Most orthodontic research has focused on cariogenic pathogens, while some evidence has demonstrated an increase in many known periodontal pathogens. However, little is known about the prevalence of the Gram-negative periodontal pathogen Selenomonas noxia (SN) among these patients. Using an existing saliva biorepository, n = 208 samples from adult and pediatric orthodontic and non-orthodontic patients were identified and screened for the presence of SN using qPCR and validated primers. In the pediatric study sample (n = 89), 36% tested positive for the presence of SN, with orthodontic patients comprising more SN-positive samples (87.5%) than SN-negative samples (78.9%), p = 0.0271. In the adult study sample (n = 119), SN was found in 28.6%, with orthodontic patients comprising 58.8% of positive samples and only 28.2% of negative samples (p < 0.0001). These data demonstrated that both pediatric and adult orthodontic patients exhibited higher prevalence of SN compared with age-matched non-orthodontic controls. As this microorganism is associated not only with periodontal disease but also long-term health issues such as obesity, more research is needed regarding the factors that increase the prevalence of this microbe.

In his On the Art of Building, Renaissance humanist Leon Battista Alberti wrote that the ancient Egyptians believed that alphabetical languages would one day all be lost, but the pictorial method of writing they used could be understood easily by intellectuals everywhere and far into the future. Amidst a renewed appreciation of ancient Egyptian hieroglyphics found on obelisks in Italy and the discovery of Horapollo’s Hieroglyphica, which purported to translate the language, Renaissance humanists like Alberti developed an obsession with this ancient form of non-alphabetical writing. Additionally, a growing awareness of the lost language of their Etruscan ancestors further ignited an anxiety among Italian humanists that their own ideas might one day become unintelligible. As Egyptomania spread through the Italian peninsula, some saw an answer to their fears in the pictorial hieroglyphics of the ancient Egyptians, for they perceived, in Egyptian writing, the potential for a universal language. Thus, many created Renaissance hieroglyphs based on those of the Egyptians. This essay examines the successes and failures of these neo-hieroglyphs, which early modern humanists and artists created hoping that a language divorced from alphabetical text might better convey the memory of their names and contributions to posterity.

Expression of microRNAs, such as miR-365, is known to be dysregulated in many tumors, including oral cancers, although little is known about their role or functions. The objective of this project is to evaluate the downstream targets of miR-365 to determine any potential pathways or effects. Downstream targets for miR-365 (miRdatabase target scores > 90) were used for qPCR screening of oral cancer cell lines (SCC4, SCC9, SCC15, SCC25, CAL27). Each oral cancer cell line expressed miR-365 downstream targets molybdenum cofactor synthesis-2 (MOCS2), erythropoietin receptor (EPOR), IQ motif containing-K (IQCK), carboxypeptidase A3 (CPA3), solute carrier family 24 member-3 (SLC24A3), and coiled-coil domain containing 47 (CCDC47)—although the expression levels varied somewhat. However, differential results were observed with ubiquitin protein ligase E3 component n-recognin-3 (UBR3), nudix hydrolase-12 (NUDT12), zinc finger CCHC-type containing-14 (ZCCHC14), and homeobox and leucine zipper encoding (HOMEZ). These data suggest that many of the miR-365 targets are expressed in the oral cancers screened, with the differential expression of UBR3, ZCCHC14, HOMEZ, and NUDT12, which may be correlated with chemoresistance among two specific oral cancer cell lines (SCC25, SCC9). These results suggest this differential expression may signal potential targets for patient treatment with tumors exhibiting miR-365 and chemotherapeutic resistance.

Dental office protocols to combat the SARS-CoV-2 (COVID-19) pandemic include mouth washing for an extended 60 s, thereby reducing detectable oral virus. However, it is unclear whether this protocol has any effects on the newly identified periodontal pathogen and obesity-related bacterium often found among pediatric patients, Selenomonas noxia. To determine if the mouthwash protocol has any measurable effect on S. noxia amongst pediatric patients, clinical pediatric saliva samples were obtained from pediatric patients during routine visits for clinical care and treatment. Using an approved protocol, two saliva samples were collected on the same visit before and after chlorhexidine mouthwash (Sample A, Sample B). The third sample (Sample C) was taken at the recall appointment—usually between two and eight weeks later. A total of n = 97 pre-mouthwash samples, and an equal number of matching post-mouthwash samples (n = 97) were collected, with a small number of matching recall samples (n = 36) that were subsequently collected and identified. The demographic composition of the study sample was analyzed using Chi square statistics. Sample DNA from the matching pre-, post-, and recall collections (Sample A, Sample B, and Sample C) was isolated and screened using qPCR and validated primers, which revealed that 11.1% (n = 4/36) from Sample A tested positive for S. noxia with 0% (n = 0/36) of Sample B testing positive and 13.9% (n = 5/36) of the recall (Sample C) testing positive. In addition, comparative analysis of the qPCR cycle threshold data revealed relatively lower expression (quantity) of S. noxia DNA among the recall samples, as determined by two-tailed t-tests (p=0.004). These data and results provide new evidence for the oral prevalence of S. noxia among pediatric patients, while also demonstrating that the COVID-19 protocol of mouth washing prior to clinical treatment for periods extending up to 60 s may be sufficient to reduce the levels of detectable S. noxia—at least temporarily. More research will be needed to determine whether these effects may be limited to the short- or may exhibit more lasting effects in the long-term.

Abstract Circulating miR-371a-3p has excellent performance in the detection of viable (non-teratoma) germ cell tumor (GCT) pre-orchiectomy; however, its ability to detect occult disease is understudied. To refine the serum miR-371a-3p assay in the minimal residual disease setting we compared performance of raw (Cq) and normalized (∆Cq, RQ) values from prior assays, and validated interlaboratory concordance by aliquot swapping. Revised assay performance was determined in a cohort of 32 patients suspected of occult retroperitoneal disease. Assay superiority was determined by comparing resulting receiver-operator characteristic (ROC) curves using the Delong method. Pairwise t-tests were used to test for interlaboratory concordance. Performance was comparable when thresholding based on raw Cq vs. normalized values. Interlaboratory concordance of miR-371a-3p was high, but reference genes miR-30b-5p and cel-miR-39-3p were discordant. Introduction of an indeterminate range of Cq 28–35 with a repeat run for any indeterminate improved assay accuracy from 0.84 to 0.92 in a group of patients suspected of occult GCT. We recommend that serum miR-371a-3p test protocols are updated to (a) utilize threshold-based approaches using raw Cq values, (b) continue to include an endogenous (e.g., miR-30b-5p) and exogenous non-human spike-in (e.g., cel-miR-39-3p) microRNA for quality control, and (c) to re-run any sample with an indeterminate result.

Abstract Background Healthcare-based Independent Domestic Violence Advisors (hIDVA) are evidence-based programmes that provide emotional and practical support to service users experiencing domestic abuse. hIDVA programmes are found to improve health outcomes for service users and are increasingly delivered across a range of healthcare settings. However, it is unclear how hIDVA programmes are implemented across maternity services and the key facilitators and barriers to their implementation. The aim of this study was to identify; how many English National Health Service (NHS) Trusts with maternity services have a hIDVA programme; which departments within the Trust they operate in; what format, content, and variation in hIDVA programmes exist; and key facilitators and barriers of implementation in maternity services. Methods A national survey of safeguarding midwives (Midwives whose role specifically tasks them to protect pregnant women from harm including physical, emotional, sexual and financial harm and neglect) within all maternity services across England; descriptive statistics were used to summarise responses. A World Café event (a participatory method, which aims to create a café atmosphere to facilitate informal conversation) with 38 national key stakeholders to examine barriers and facilitators to hIDVA programme implementation. Results 86/124 Trusts (69%) with a maternity service responded to the survey; 59(69%) of respondents reported that they had a hIDVA programme, and 47(55%) of the hIDVA programmes operated within maternity services. Key facilitators to implementation of hIDVA programmes included training of NHS staff about the hIDVA role and regular communication between Trust staff and hIDVA staff; hIDVA staff working directly from the Trust; co-creation of hIDVA programmes with experts by experience; governance and middle- and senior-management support. Key barriers included hIDVA staff having a lack of access to a private space for their work, insecure funding for hIDVA programmes and issues with recruitment and retention of hIDVA staff. Conclusions Despite hIDVA programmes role in improving the health outcomes of service users experiencing domestic abuse, increased funding and staff training is needed to successfully implement hIDVA staff in maternity services. Integrated Care Board commissioning of acute and mental health trust services would benefit from ensuring hIDVA programmes and clinician DVA training are prioritised.

IntroductionThe COVID-19 pandemic posed a significant lifecourse rupture, not least to those who had specific physical vulnerabilities to the virus, but also to those who were suffering with mental ill health. Women and birthing people who were pregnant, experienced a perinatal bereavement, or were in the first post-partum year (i.e., perinatal) were exposed to a number of risk factors for mental ill health, including alterations to the way in which their perinatal care was delivered.MethodsA consensus statement was derived from a cross-disciplinary collaboration of experts, whereby evidence from collaborative work on perinatal mental health during the COVID-19 pandemic was synthesised, and priorities were established as recommendations for research, healthcare practice, and policy.ResultsThe synthesis of research focused on the effect of the COVID-19 pandemic on perinatal health outcomes and care practices led to three immediate recommendations: what to retain, what to reinstate, and what to remove from perinatal mental healthcare provision. Longer-term recommendations for action were also made, categorised as follows: Equity and Relational Healthcare; Parity of Esteem in Mental and Physical Healthcare with an Emphasis on Specialist Perinatal Services; and Horizon Scanning for Perinatal Mental Health Research, Policy, & Practice.DiscussionThe evidence base on the effect of the pandemic on perinatal mental health is growing. This consensus statement synthesises said evidence and makes recommendations for a post-pandemic recovery and re-build of perinatal mental health services and care provision.

Environmental exposures during the perinatal period are known to have a long-term effect on adult physical and mental health. One such influential environmental exposure is the time of year of birth which affects the amount of daylight, nutrients, and viral load that an individual is exposed to within this key developmental period. Here, we investigate associations between season of birth (seasonality), four mental health traits (n = 137,588) and multi-modal neuroimaging measures (n = 33,212) within the UK Biobank. Summer births were associated with probable recurrent Major Depressive Disorder (β = 0.026, pcorr = 0.028) and greater mean cortical thickness in temporal and occipital lobes (β = 0.013 to 0.014, pcorr

Background Pulse wave velocity (PWV) is a noninvasive measure of arterial stiffness and predictor of cardiovascular disease. However, the association between PWV and vascular calcification across different vascular beds has not been fully investigated. This study aimed to quantify the association between PWV and multiterritory calcification and to explore whether PWV can identify individuals with vascular calcification beyond traditional risk factors. Methods and Results Among 1351 older adults (mean age, 79.2 years [SD, 4.1]) from the ARIC (Atherosclerosis Risk in Communities) study, we measured segment‐specific PWVs: heart–carotid, heart–femoral, carotid–femoral, heart–ankle, brachial–ankle, and femoral–ankle. Dependent variables were high calcium score (≥75th percentile of Agatston score) across different vascular beds: coronary arteries, aortic valve ring, aortic valve, mitral valve, ascending aorta, and descending aorta. Quartiles of carotid–femoral, heart–femoral, heart–ankle, and brachial–ankle PWV were significantly associated with coronary artery calcium (eg, adjusted odds ratio [OR] for the highest versus lowest quartile of carotid–femoral PWV, 1.84 [95% CI, 1.24–2.74]). Overall, PWVs were most strongly associated with descending aorta calcification, with significant results for carotid–femoral, heart–femoral, heart–ankle, and brachial–ankle PWV (eg, adjusted OR for the highest versus lowest quartile of carotid–femoral PWV, 3.99 [95% CI, 2.61–6.17]). In contrast, femoral–ankle PWV was inversely associated with descending aorta calcification. Some PWVs improved the discrimination of coronary artery calcium and descending aorta calcification beyond traditional risk factors. Conclusions The associations of PWV with vascular calcification varied substantially across segments, with descending aorta calcification most closely linked to PWVs. Our study suggests that some PWVs, especially carotid–femoral PWV, are helpful to identify individuals with coronary artery calcium and descending aorta calcification.

Abstract Artificial intelligence methods including deep neural networks (DNN) can provide rapid molecular classification of tumors from routine histology with accuracy that matches or exceeds human pathologists. Discerning how neural networks make their predictions remains a significant challenge, but explainability tools help provide insights into what models have learned when corresponding histologic features are poorly defined. Here, we present a method for improving explainability of DNN models using synthetic histology generated by a conditional generative adversarial network (cGAN). We show that cGANs generate high-quality synthetic histology images that can be leveraged for explaining DNN models trained to classify molecularly-subtyped tumors, exposing histologic features associated with molecular state. Fine-tuning synthetic histology through class and layer blending illustrates nuanced morphologic differences between tumor subtypes. Finally, we demonstrate the use of synthetic histology for augmenting pathologist-in-training education, showing that these intuitive visualizations can reinforce and improve understanding of histologic manifestations of tumor biology.

Abstract Background Endocrine-resistant HR+/HER2- breast cancer (BC) and triple-negative BC (TNBC) are of interest for molecularly informed treatment due to their aggressive natures and limited treatment profiles. Patients of African Ancestry (AA) experience higher rates of TNBC and mortality than European Ancestry (EA) patients, despite lower overall BC incidence. Here, we compare the molecular landscapes of AA and EA patients with HR+/HER2- BC and TNBC in a real-world cohort to promote equity in precision oncology by illuminating the heterogeneity of potentially druggable genomic and transcriptomic pathways. Methods De-identified records from patients with TNBC or HR+/HER2- BC in the Tempus Database were randomly selected (N = 5000), with most having stage IV disease. Mutations, gene expression, and transcriptional signatures were evaluated from next-generation sequencing data. Genetic ancestry was estimated from DNA-seq. Differences in mutational prevalence, gene expression, and transcriptional signatures between AA and EA were compared. EA patients were used as the reference population for log fold-changes (logFC) in expression. Results After applying inclusion criteria, 3433 samples were evaluated (n = 623 AA and n = 2810 EA). Observed patterns of dysregulated pathways demonstrated significant heterogeneity among the two groups. Notably, PIK3CA mutations were significantly lower in AA HR+/HER2- tumors (AA = 34% vs. EA = 42%, P

Abstract OncotypeDX and MammaPrint assays have not been validated to predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NACT) in early-stage breast cancer patients. We analyzed the 2010–2019 National Cancer Database and found that high OncotypeDX recurrence scores or high MammaPrint scores were associated with greater odds of pCR. Our findings suggest that OncotypeDX and MammaPrint testing predict pCR after NACT and could facilitate clinical decision-making between clinicians and patients.

Based on the geometry of a radial function, a sequence of approximations for arcsine, arccosine and arctangent are detailed. The approximations for arcsine and arccosine are sharp at the points zero and one. Convergence of the approximations is proved and the convergence is significantly better than Taylor series approximations for arguments approaching one. The established approximations can be utilized as the basis for Newton-Raphson iteration and analytical approximations, of modest complexity, and with relative error bounds of the order of 10−16, and lower, can be defined. Applications of the approximations include: first, upper and lower bounded functions, of arbitrary accuracy, for arcsine, arccosine and arctangent. Second, approximations with significantly higher accuracy based on the upper or lower bounded approximations. Third, approximations for the square of arcsine with better convergence than well established series for this function. Fourth, approximations to arccosine and arcsine, to even order powers, with relative errors that are significantly lower than published approximations. Fifth, approximations for the inverse tangent integral function and several unknown integrals.

Abstract Large language models such as ChatGPT can produce increasingly realistic text, with unknown information on the accuracy and integrity of using these models in scientific writing. We gathered fifth research abstracts from five high-impact factor medical journals and asked ChatGPT to generate research abstracts based on their titles and journals. Most generated abstracts were detected using an AI output detector, ‘GPT-2 Output Detector’, with % ‘fake’ scores (higher meaning more likely to be generated) of median [interquartile range] of 99.98% ‘fake’ [12.73%, 99.98%] compared with median 0.02% [IQR 0.02%, 0.09%] for the original abstracts. The AUROC of the AI output detector was 0.94. Generated abstracts scored lower than original abstracts when run through a plagiarism detector website and iThenticate (higher scores meaning more matching text found). When given a mixture of original and general abstracts, blinded human reviewers correctly identified 68% of generated abstracts as being generated by ChatGPT, but incorrectly identified 14% of original abstracts as being generated. Reviewers indicated that it was surprisingly difficult to differentiate between the two, though abstracts they suspected were generated were vaguer and more formulaic. ChatGPT writes believable scientific abstracts, though with completely generated data. Depending on publisher-specific guidelines, AI output detectors may serve as an editorial tool to help maintain scientific standards. The boundaries of ethical and acceptable use of large language models to help scientific writing are still being discussed, and different journals and conferences are adopting varying policies.

Abstract Gene expression-based recurrence assays are strongly recommended to guide the use of chemotherapy in hormone receptor-positive, HER2-negative breast cancer, but such testing is expensive, can contribute to delays in care, and may not be available in low-resource settings. Here, we describe the training and independent validation of a deep learning model that predicts recurrence assay result and risk of recurrence using both digital histology and clinical risk factors. We demonstrate that this approach outperforms an established clinical nomogram (area under the receiver operating characteristic curve of 0.83 versus 0.76 in an external validation cohort, p = 0.0005) and can identify a subset of patients with excellent prognoses who may not need further genomic testing.

New evidence has suggested that oral and gut microflora may have significant impacts on the predisposition, development, and stability of obesity in adults over time—although less is known about this phenomenon in children. Compared with healthy-weight controls, overweight and obese adult patients are now known to harbor specific pathogens, such as Selenomonas noxia (S. noxia), that are capable of digesting normally non-digestible cellulose and fibers that significantly increase caloric extraction from normal dietary intake. To evaluate this phenomenon, clinical saliva samples (N = 122) from subjects with a normal BMI (18–25) and a BMI over 25 (overweight, obese) from an existing biorepository were screened using qPCR. The prevalence of S. noxia in samples from normal-BMI participants were lower (21.4%) than in overweight-BMI (25–29; 46.1%) and obese-BMI (30 and above; 36.8%) samples—a strong, positive correlation that was not significantly affected by age or race and ethnicity. These data strongly suggest that S. noxia may be intricately associated with overweight and obesity among patients, and more research will be needed to determine the positive and negative feedback mechanisms that may be responsible for these observations as well as the interventions needed to remove or reduce the potential effects of this oral pathogen.

Abstract There are many benefits of breastfeeding to women and their infants but meeting the recommended 6 months of exclusive breastfeeding is likely to be more challenging for women with severe mental illness (SMI). This is the first systematic review that aims to examine evidence of (a) infant feeding outcomes in women with SMI and the factors associated with this, (b) the experiences of infant feeding and infant feeding support for women with SMI, (c) interventions for supporting infant feeding among these women and (d) health care professionals' attitudes toward supporting infant feeding in women with SMI. Mixed methods systematic review was carried out using the principles of Joanna Briggs Institute's (JBI) 'convergent integrated' methodology. CINAHL, PsycINFO, Medline and MIDIRS were used to search literature between 1994 and 2022. The quality of selected articles was assessed using JBI critical appraisal tools and thematic synthesis was undertaken to obtain findings. Eighteen papers were included in the final review. Women with SMI were less likely to initiate and continue breastfeeding than women without SMI. Several challenges with breastfeeding were highlighted, and while these were often linked to women's mental health difficulties, inconsistent advice from health care professionals and poor support with breastfeeding further compounded these challenges. This review highlights that policy and practice need to take into account the individual challenges women with SMI face when planning, initiating and maintaining breastfeeding. Education and training for health care professionals are needed to enable them to provide tailored infant feeding support to women with SMI, which reflects their individual needs.

Abstract Genetic studies in psychiatry have primarily focused on the effects of common genetic variants, but few have investigated the role of rare genetic variants, particularly for major depression. In order to explore the role of rare variants in the gap between estimates of single nucleotide polymorphism (SNP) heritability and twin study heritability, we examined the contribution of common and rare genetic variants to latent traits underlying psychiatric disorders using high-quality imputed genotype data from the UK Biobank. Using a pre-registered analysis, we used items from the UK Biobank Mental Health Questionnaire relevant to three psychiatric disorders: major depression (N = 134,463), bipolar disorder (N = 117,376) and schizophrenia (N = 130,013) and identified a general hierarchical factor for each that described participants’ responses. We calculated participants’ scores on these latent traits and conducted single-variant genetic association testing (MAF > 0.05%), gene-based burden testing and pathway association testing associations with these latent traits. We tested for enrichment of rare variants (MAF 0.05–1%) in genes that had been previously identified by common variant genome-wide association studies, and genes previously associated with Mendelian disorders having relevant symptoms. We found moderate genetic correlations between the latent traits in our study and case–control phenotypes in previous genome-wide association studies, and identified one common genetic variant (rs72657988, minor allele frequency = 8.23%, p = 1.01 × 10−9) associated with the general factor of schizophrenia, but no other single variants, genes or pathways passed significance thresholds in this analysis, and we did not find enrichment in previously identified genes.

Abstract Background Mental health conditions are common during the perinatal period and associated with maternal, foetal, and neonatal morbidity and mortality. There is an established bidirectional relationship between mental health conditions and intimate partner violence (IPV), including during and after pregnancy. Mean lifetime prevalence of physical, sexual or emotional IPV exposure among women in rural Ethiopia is estimated to be 61% and may be even higher during the perinatal period. We aimed to explore the perspectives of women and antenatal care (ANC) health workers on the relationship between all types of IPV and perinatal mental health, to inform the adaptation of a psychological intervention for pregnant women experiencing IPV in rural Ethiopia. Methods We conducted in-depth qualitative interviews with 16 pregnant women and 12 health workers in the Gurage zone of the Southern Nations, Nationalities and People’s Region of Ethiopia, between December 2018 and December 2019. We conducted thematic analysis of English-translated transcripts of audio-recorded Amharic-language interviews. Results Participants contextualised IPV as the primary form of abusive treatment women experienced, connected by multiple pathways to emotional and bodily distress. Patriarchal norms explained how the actions of neighbours, family, community leaders, law enforcement, and government agents in response to IPV often reinforced women’s experiences of abuse. This created a sense of powerlessness, exacerbated by the tension between high cultural expectations of reciprocal generosity and severe deprivation. Women and health workers advocated a psychological intervention to address women’s powerlessness over the range of difficulties they faced in their daily lives. Conclusions Women and health workers in rural Ethiopia perceive multiple, interconnected pathways between IPV and perinatal emotional difficulties. Contrary to expectations of sensitivity, women and health workers were comfortable discussing the impact of IPV on perinatal mental health, and supported the need for brief mental health interventions integrated into ANC.

Abstract Schizophrenia (SCZ) and major depressive disorder (MDD) are complex psychiatric disorders which contribute substantially to the global burden of disease. Both psychopathologies are heritable with some genetic overlap between them. Importantly, SCZ and MDD have also been found to be associated with environmental risk factors. However, rather than being independent of genetic influences, exposure to environmental risk factors may be under genetic control, known as gene-environment correlation (rGE). In this study we investigated rGE in relation to polygenic risk scores for SCZ and MDD in adults, derived from large genome-wide association studies, across two different British community samples: Understanding Society (USoc) and the National Child Development Study (NCDS). We tested whether established environmental risk factors for SCZ and/or MDD are correlated with polygenic scores in adults and whether these associations differ between the two disorders and cohorts. Findings partially overlapped between disorders and cohorts. In NCDS, we identified a significant correlation between the genetic risk for MDD and an indicator of low socio-economic status, but no significant findings emerged for SCZ. In USoc, we replicated associations between indicators of low socio-economic status and the genetic propensity for MDD. In addition, we identified associations between the genetic susceptibility for SCZ and being single or divorced. Results across both studies provide further evidence that the genetic risk for SCZ and MDD were associated with common environmental risk factors, specifically MDD’s association with lower socio-economic status.

Abstract Background DNA methylation is an epigenetic mark associated with the repression of gene promoters. Its pattern in the genome is disrupted with age and these changes can be used to statistically predict age with epigenetic clocks. Altered rates of aging inferred from these clocks are observed in human disease. However, the molecular mechanisms underpinning age-associated DNA methylation changes remain unknown. Local DNA sequence can program steady-state DNA methylation levels, but how it influences age-associated methylation changes is unknown. Results We analyze longitudinal human DNA methylation trajectories at 345,895 CpGs from 600 individuals aged between 67 and 80 to understand the factors responsible for age-associated epigenetic changes at individual CpGs. We show that changes in methylation with age occur at 182,760 loci largely independently of variation in cell type proportions. These changes are especially apparent at 8322 low CpG density loci. Using SNP data from the same individuals, we demonstrate that methylation trajectories are affected by local sequence polymorphisms at 1487 low CpG density loci. More generally, we find that low CpG density regions are particularly prone to change and do so variably between individuals in people aged over 65. This differs from the behavior of these regions in younger individuals where they predominantly lose methylation. Conclusions Our results, which we reproduce in two independent groups of individuals, demonstrate that local DNA sequence influences age-associated DNA methylation changes in humans in vivo. We suggest that this occurs because interactions between CpGs reinforce maintenance of methylation patterns in CpG dense regions.

Background: Aspiration of intervertebral disc space is often done to confirm the diagnosis of native vertebral osteomyelitis. A study has not been done examining the utility of cell counts and differentials of the aspirated fluid in diagnosing native vertebral osteomyelitis (NVO). Methods: In this feasibility study, we prospectively enrolled patients with a suspected diagnosis of NVO referred to the Division of Neuroradiology for image-guided needle aspiration of the intervertebral disc. In this study, manual cell count was done on the aspirated fluid, followed by a differential cytospin technique and touch prep. We obtained demographic, lab, and microbiologic data and used the receiver operating curve (ROC) for statistical analysis. Results: Over 12 months, we performed 17 aspirates on 14 patients. The median age was 70.5 years (range: 45–77). The median manual cell count on the aspirated fluid was 52 cells µL−1 (range: 0–6656), the median neutrophil percentage on the touch prep slide was 73 % (range: 5 %–100 %), and the median neutrophil percentage on the cytospin slide was 82 % (range: 0 %–100 %). Routine bacterial cultures were positive in five cases, and the 16S ribosomal RNA gene polymerase chain reaction was positive in two cases. The optimal cutoff for a cell count of 104 total nucleated cells offered a sensitivity and specificity of 86 %, and a neutrophil cutoff of 83 % was associated with a 71 % sensitivity and specificity. Conclusion: An image-guided aspirated specimen leukocyte differential of ≥83 % neutrophils or a leukocyte count of ≥104 µL−1 was a sensitive and specific test for diagnosing patients with suspected NVO. Additionally, more extensive studies are warranted to confirm the findings.

Background: The continuous evolution of the SARS-CoV-2 pandemic has led to a high demand for diagnostic testing and major shortages in testing materials, especially in low- and middle-income countries. As an alternative to testing individual samples, pooling of respiratory samples has been suggested. Previous studies have assessed performance of pooling, mainly using nasopharyngeal samples for the detection of SARS-CoV-2, but few studies have examined the performance of pooling the more practical nasal swabs or saliva samples. Objective: To evaluate the sensitivity, specificity, and potential cost reduction of pooling of nasal swab (NS) and saliva (SL) samples for detection of SARS-CoV-2 in a community-based cohort study in Lima, Peru. Study design: A prospective cohort study was conducted in a community setting in San Juan de Lurigancho, Lima-Peru. NS and SL samples were collected from 132 participants twice-a-week for a 2-month period. Pools of 2 to 12 samples of the same type, from participants of the same household, were tested by RT-PCR. After pooled testing, all individual samples from positive pools and all individual samples from randomly chosen negative pools were evaluated. For assessment of diagnostic performance, pool testing results were compared with results from individual testing, which served as reference, and concordance in pooled and individual test detections was evaluated. Laboratory costs for both types of samples and testing were compared. Results: A total of 2008 NS and 2002 SL samples were collected from 132 study participants. We tested 329 NS and 333 SL pools. The mean pool size for NS and SL pools was 6.22 (SD = 0.92) and 6.39 (SD = 1.71), respectively. Using individual testing as reference, NS pooling of 6 had a sensitivity and specificity of 94% and 100%, respectively, with kappa of 0.97 (CI 95%: 0.93–1.00). The corresponding values for SL pooling of 6 were 83%, 100%, and 0.90 (CI 95%: 0.83–0.97). Compared with individual testing, pooling resulted in a cost reduction of 74.8% for NS and 72.4% for SL samples. Conclusions: Pooling easy-to-collect respiratory samples, especially NS, demonstrated very high diagnostic performance for detection of SARS-CoV-2 with substantial cost savings. This approach could be considered in large population screening programs, especially in LMIC.

The Veterans Health Administration (VHA) has served as a leader in the implementation of telerehabilitation technologies and continues to expand utilization of non-traditional patient encounters to better serve a geographically and demographically diverse population. Amyotrophic Lateral Sclerosis (ALS) is a progressive neurodegenerative disease impacting Veterans at a higher rate than the civilian population and associated with high levels of disability and limited access to subspecialized care. There is growing evidence supporting exercise-based interventions as an independent or adjunctive treatment to maintain or restore function for this patient population; many of these interventions can be delivered remotely by telehealth. The recent advancements in disease-modifying therapies for neuromuscular disorders will likely increase the importance of rehabilitation interventions to maximize functional outcomes. Here, we review the evidence for specific exercise interventions in ALS and the evidence for telehealth-based exercise in neuromuscular disorders. We then use this existing literature to propose a framework for telehealth delivery of these treatments, including feasible exercise interventions and remote outcome measures, recommended peripheral devices, and an example of a current remote group exercise program offered through VHA.

Previous research has demonstrated that the human papillomavirus (HPV) can infect a wide range of human tissues, including those within the oral cavity. High-risk oral HPV strains have been associated with the development and progression of oral cancers, including oral squamous cell carcinomas. Although many studies have examined the prevalence of the high-risk strains HPV16 and HPV18, far fewer have assessed the prevalence of other high-risk HPV strains. An approved study protocol was used to identify HPV52 and HPV58 among clinical samples (n = 87) from a saliva biorepository. Quantitative polymerase chain reaction (qPCR) and validated primers for HPV52 and HPV58 were used to facilitate this screening. This screening demonstrated that a total of n = 4/45 or 8.9% of adult saliva samples harbored high-risk HPV52, and n = 2/45 or 4.4% tested positive for high-risk HPV58. In addition, a total of n = 6/42 or 14.3% of the pediatric saliva samples tested positive for high-risk HPV, including n = 5/42 or 11.9% with HPV52 and n = 3/42 or 7.1% for HPV58. These data demonstrate the presence of the high-risk oncogenic HPV52 and HPV58 strains among both adult and pediatric clinical patient samples. More detailed longitudinal research must be conducted to determine whether this prevalence may be increasing or decreasing over time. In addition, these data strongly support public health prevention efforts, such as knowledge and awareness of the nine-valent HPV vaccine covering additional high-risk strains, including HPV52 and HPV58.