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Background: Pellagra is caused by niacin (vitamin B3) deficiency and manifested by a distinctive dermatitis. Isoniazid is critical for treating tuberculosis globally and is a component of most regimens to prevent tuberculosis. Isoniazid may contribute to pellagra by disrupting intracellular niacin synthesis. In 2017, Malawian clinicians recognized a high incidence of pellagra-like rashes after scale-up of isoniazid preventive treatment (IPT) to people living with HIV (PLHIV). This increase in pellagra incidence among PLHIV coincided with a seasonal period of sustained food insecurity in the region, which obscured epidemiological interpretations. Although isoniazid has been implicated as a secondary cause of pellagra for decades, no hypothesis-driven epidemiological study has assessed this relationship in a population exposed to isoniazid. We developed this case-control protocol to assess the association between large-scale isoniazid distribution and pellagra in Malawi.Methods: We measure the relative odds of having pellagra among isoniazid-exposed people compared to those without exposure while controlling for other pellagra risk factors. Secondary aims include measuring time from isoniazid initiation to onset of dermatitis, comparing niacin metabolites 1-methylnicotinamide (1-MN), and l-methyl-2-pyridone-5-carboxamide (2-PYR) in urine as a proxy for total body niacin status among subpopulations, and describing clinical outcomes after 30-days multi-B vitamin (containing 300 mg nicotinamide daily) therapy and isoniazid cessation (if exposed). We aim to enroll 197 participants with pellagra and 788 age- and sex-matched controls (1:4 ratio) presenting at three dermatology clinics. Four randomly selected community clinics within 3–25 km of designated dermatology clinics will refer persons with pellagra-like symptoms to one of the study enrollment sites for diagnosis. Trained study dermatologists will conduct a detailed exposure questionnaire and perform anthropometric measurements. A subset of enrollees will provide a casual urine specimen for niacin metabolites quantification and/or point-of-care isoniazid detection to confirm whether participants recently ingested isoniazid. We will use conditional logistic regression, matching age and sex, to estimate odds ratios for the primary study aim.Discussion: The results of this study will inform the programmatic scale-up of isoniazid-containing regimens to prevent tuberculosis.

Premenstrual dysphoric disorder (PMDD), a more severe manifestation of premenstrual syndrome (PMS), is characterized by emotional, behavioral, and physical symptoms that begin in the mid-to-late luteal phase of the menstrual cycle, when estradiol and progesterone levels precipitously decline, and remit after the onset of menses. Remotely monitoring physiologic variables associated with PMDD depression symptoms, such as heart rate variability (HRV), sleep, and physical activity, holds promise for developing an affective state prediction model. Switching into and out of depressive states is associated with an increased risk of suicide, and therefore, monitoring periods of affective switching may help mitigate risk. Management of other chronic health conditions, including cardiovascular disease and diabetes, has benefited from remote digital monitoring paradigms that enable patients and physicians to monitor symptoms in real-time and make behavioral and medication adjustments. PMDD is a chronic condition that may benefit from real-time, remote monitoring. However, clinical practice has not advanced to monitoring affective states in real-time. Identifying remote monitoring paradigms that can detect within-person affective state change may help facilitate later research on timely and efficacious interventions for individuals with PMDD. This narrative review synthesizes the current literature on behavioral and physiological correlates of PMDD suitable for remote monitoring during the menstrual cycle. The reliable measurement of heart rate variability (HRV), sleep, and physical activity, with existing wearable technology, suggests the potential of a remote monitoring paradigm in PMDD and other depressive disorders.

Introduction: Mental illness is a clinically significant disturbance in an individual's cognition, emotion regulation, or behavior. Stigma toward mental health comes in two primary forms: Self-stigma and perceived public stigma. Purpose: The objective of this study is to quantify the amount of stigma toward mental illness in rural adults and analyze differences in stigma across demographic groups. Methods: Adults were offered a 14-item questionnaire at five different sites from January 2023 to April 2023. Rural distinctions were made based on participants' reported county of residence following the Indiana Office of Community and Rural Affairs (OCRA) definition of rurality. Demographic information such as age, gender, marital status, total household income, and highest level of education were also obtained. Results: Rural adults experience mild amounts of self-stigma (14.52 +/- 5.0) and moderate amounts of perceived public stigma (18.4 +/- 4.3). Adults aged 46-65 experience more significant levels of perceived public stigma when compared to those of younger participants. An inverse relationship exists between the highest level of education and self-stigma towards mental illness. Seventy two percent of respondents agreed or strongly agreed with the statement, “In general, others believe that having a mental illness is a sign of personal weakness or inadequacy.” Conclusions: This study demonstrates that perceived public stigma toward mental illness presents a significant barrier to care for mental illness. Adults aged 46-65 are especially vulnerable to the perceived public stigma toward mental illness. To provide the largest benefit to rural populations, anti-stigma campaigns should focus on perceived public stigma among adults aged 46-65.

IntroductionPeople with HIV (PWH), particularly those at the intersection of sexual and gender identities, face enduring obstacles to accessing HIV care, including structural stigma, structural racism and discrimination, housing instability, and limited access to health insurance. To address these challenges, Medical-Legal Partnerships (MLPs) in HIV care offer an innovative approach that integrates medical and legal services. By targeting health-harming legal needs (HHLN), MLPs aim to enhance the HIV care continuum outcomes for PWH.MethodsThis study examines the benefits and challenges of MLPs within organizations serving PWH through the social-ecological model. MLP providers (n=111) identified organizational-level challenges such as funding limitations, resource integration issues, and staffing constraints.ResultsMLPs demonstrated numerous benefits, including patient impact and benefits, comprehensive service provision, enhanced staff support and capacity, and potential for policy influence.DiscussionThese results underscore the feasibility of MLPs while offering valuable insights into their efficacy and challenges, guiding the implementation of MLPs to address health-harming legal needs, including discrimination, and thereby improving HIV care outcomes.

Laser wire-feed metal additive manufacturing (LWAM) is an innovative technology that shows many advantages compared with traditional manufacturing approaches. Despite these advantages, its industrial adoption is limited by complex parameter management and inconsistent process quality. To address these issues and improve geometric accuracy, this study explores how process parameters influence bead geometry. We conducted a parameter study varying laser power, wire feed rate, traverse speed, and welding angle. Using a full factorial design with a central composite design methodology, we assessed bead height and width. This allowed us to develop a model to estimate ideal process parameters. The findings offer a detailed analysis of parameter interactions and their effects on bead geometry, aiming to enhance geometric accuracy and process stability in LWAM. Moreover, we have evaluated the proposed process parameters from our developed model, which showed a significant enhancement to the overall quality. This was validated via printing a single layer and multi-layer structures. The quality of the final predicted sample using the proposed method was improved by 40% compared to the best sample produced for the Design of Experiment trials.

Plasma-facing components (PFC) in nuclear fusion reactors are exposed to demanding conditions during operation. The combination of thermal loads, plasma exposure as well as neutron induced damage and activation limits the number of materials suitable for this application. Due to its properties, tungsten (W) is foreseen as plasma-facing material (PFM) for the future DEMOnstration power plant. It is considered suitable due to its exceptionally high melting point, excellent thermal conductivity, low tritium retention and low erosion resistance during plasma exposure. But even tungsten armored PFCs have a limited lifetime due to, among other factors, surface erosion and the resulting thickness reduction of the armor material.In-situ local deposition of tungsten by means of additive manufacturing (AM) could counteract surface erosion and thus increase the service life span of PFCs. After evaluation of the potential AM processes qualified for this task, the wire-based laser metal deposition (LMD-w) process was selected as the most suitable process. First trials were conducted to examine if it is possible to reliably deposit tungsten onto tungsten substrate using the LMD-w process. In these first studies, single welding beads were generated, and in later experiments, entire layers were created from several welding beads which are arranged next to each other. To ensure reproducibility of the results, the substrate temperature was kept constant. Further experiments aimed at the elimination or minimization of problems such as oxidation, occurrence of balling defects, porosity, cracking, surface waviness and insufficient connection to the substrate. To increase the welding bead quality, the input parameters like laser power, deposition velocity, wire feed rate, inert gas flow, as well as the wire position were optimized. Furthermore, stacking of several layers, as well as the remelting of an already created layer, were carried out and investigated. This study represents the first steps in testing the feasibility of an in-situ surface regeneration concept for PFCs.

Abstract The COVID‐19 pandemic has affected nearly everyone, however experiences and perceptions of COVID have been different across rural and urban areas in the United States, including effects on mental health. The purpose of the current study is to examine changes in levels of reported anxiety and depression within rural and urban populations before and during the COVID‐19 pandemic in the United States. Using the National Health Interview Survey (NHIS), we used a repeated cross‐sectional study design including adults (age 18 or older) who were sampled in 2019 and 2020. We examined the relationship between worsening mental health outcomes (depression and anxiety) and rurality, controlling for individual's demographic and health‐related measures. Individuals living in an urban area were more likely to report worsening anxiety (28.8% vs. 23.0% p

Structural extracellular polymeric substances (EPS) contribute to the bioflocculation performance of activated sludge systems. This research investigates the potential of bioaugmentation of a structural EPS producer, Azoarcus communis, as a bioflocculation improvement or remediation approach. An antibiotic-resistant and fluorescent protein-producing mutant was constructed to monitor the survival, persistence, and location of the augmented strain in the membrane bioreactor. Preliminary batch tests against a kaolin clay model system and deflocculated sludge revealed the flocculation potential of this strain. Morphological image analysis and fluorescence microscopy suggest that most of the bacteria augmented in suspension were initially attached to the sludge flocs with, however, only a limited fraction getting incorporated within the activated sludge floc biomass. This limited bioaugmentation prevented assessing its impact on bioflocculation and might be explained by metazoan and protozoan grazing, together with competition with indigenous organisms and sub-optimal growth conditions in the reactor for the engineered strain. HIGHLIGHTS The structural EPS producer Azoarcus is bioaugmented to enhance sludge bioflocculation.; Augmentation with an antibiotic-resistant and fluorescent mutant strain ensures proper enumeration and localization.; Azoarcus initially attached to sludge flocs but long-term persistence was limited.; An MBR setup avoids initial washout but grazing by metazoa and protozoa remains a problem.;

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) is associated with liver and cardiovascular morbidity and mortality. Recently published NAFLD Quality Standards include 11 key performance indicators (KPIs) of good clinical care. This national study, endorsed by British Association for the Study of the Liver (BASL) and British Society of Gastroenterology (BSG), aimed to benchmark NAFLD care in UK hospitals against these KPIs. Methods: This study included all new patients with NAFLD reviewed in the outpatient clinic in the months of March 2019 and March 2022. Participating UK hospitals self-registered for the study through BASL/BSG. KPI outcomes were compared using Fisher’s exact or Chi-square tests. Results: Data from 776 patients with NAFLD attending 34 hospitals (England [25], Scotland [four], Wales [three], Northern Ireland [two]) were collected. A total of 85.3% of hospitals reported established local liver disease assessment pathways, yet only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment documented at the point of referral to secondary care. In secondary care, 79.1% of patients had fibrosis assessment. Assessment of cardiometabolic risk factors including obesity, type 2 diabetes, hypertension, and smoking were conducted in 73.2%, 33.0%, 19.3%, and 54.9% of all patients, respectively. There was limited documentation of diet (35.7%) and exercise advice (55.1%). Excluding those on statins, only 9.1% of patients with NAFLD at increased cardiovascular risk (T2DM and/or QRISK-3 >10%) had documented discussion of statin treatment. Significant KPI improvements from 2019 to 2022 were evident in use of non-invasive fibrosis assessment before secondary care referral, statin recommendations, and diet and exercise recommendations. Conclusions: This national study identified substantial variation in NAFLD management in the UK with clear areas for improvement, particularly fibrosis risk assessment before secondary care referral and management of associated cardiometabolic risk factors. Impact and implications: This study identified significant variation in the management of NAFLD in the UK. Only 27.9% of patients with suspected NAFLD had non-invasive fibrosis assessment performed to identify those at greater risk of advanced liver disease before specialist referral. Greater emphasis is needed on the management of associated cardiometabolic risk factors in individuals with NAFLD. Hospitals with multidisciplinary NAFLD service provision had higher rates of fibrosis evaluation and assessment and management of cardiometabolic risk than hospitals without multidisciplinary services. Further work is needed to align guideline recommendations and real-world practice in NAFLD care.

Managing agricultural landscapes to simultaneously provide multiple ecosystem services is crucial to meet both environmental and societal demands. This not only requires surveying and modeling many ecosystem services at the same time, but also quantifying the impact of agricultural management and the surrounding landscape on agroecosystem multifunctionality. In this study, we assessed the agroecosystem multifunctionality of 12 organic apple orchards and 12 orchards with integrated pest management (IPM) using field data on 23 indicators for agronomical, ecological and economic performance. Furthermore, the ecological performance indicators were also quantified in 12 semi-natural grasslands to obtain a benchmark for the overall impact of agricultural management on biodiversity and biodiversity-based ecosystem services. We found that organic farming at the field scale had relatively limited beneficial effects on ecological performance, yet it provided farmers with a similar income relative to IPM, despite lower yield levels. Overall orchard multifunctionality did not differ between organic and IPM orchards, regardless of hypothetical stakeholder interests, and a clear trade-off between biodiversity and yield was found within both orchard systems. Structural equation models revealed that in addition to orchard management, also within-orchard location, local biodiversity and characteristics of the surrounding landscape were directly and/or indirectly driving ecosystem service indicator levels. Surrounding semi-natural habitat and landscape complexity enhanced biodiversity and biodiversity-based ecosystem services, and the higher provisioning of several services in the semi-natural benchmark further emphasizes the importance of preserving semi-natural habitats within the agricultural landscape. Overall, our results indicate that reconciling ecological, agronomical and economic goals requires a vision that goes beyond the field-level agricultural management. Therefore, we argue that policy measures should not only address local farm management, but should also target actions towards other stakeholders such as land managers and agricultural markets.

An intuitive and generalisable approach to spatial-temporal feature extraction for high-density (HD) functional Near-Infrared Spectroscopy (fNIRS) brain-computer interface (BCI) is proposed, demonstrated here using Frequency-Domain (FD) fNIRS for motor-task classification. Enabled by the HD probe design, layered topographical maps of Oxy/deOxy Haemoglobin changes are used to train a 3D convolutional neural network (CNN), enabling simultaneous extraction of spatial and temporal features. The proposed spatial-temporal CNN is shown to effectively exploit the spatial relationships in HD fNIRS measurements to improve the classification of the functional haemodynamic response, achieving an average F1 score of 0.69 across seven subjects in a mixed subjects training scheme, and improving subject-independent classification as compared to a standard temporal CNN.

Background and Aims: This study aimed to evaluate adherence to subcutaneous biologic therapy and impact of nonadherence including risk factors and outcomes in academic centers with integrated specialty pharmacies for patients with inflammatory bowel disease (IBD). Methods: This was a multicenter, retrospective cohort analysis of patients aged ≥18 years receiving care in 3 tertiary care outpatient IBD clinics with integrated specialty pharmacies. Subjects were prescribed injectable anti-TNF therapy (adalimumab, certolizumab, golimumab) or anti-IL 12/23 therapy (ustekinumab) with at least 3 consecutive prescription claims. The primary outcomes were medication possession ratio (MPR), percent achieving optimal adherence (MPR > 0.86); in addition, we sought to verify a prior risk factor model including smoking status, narcotic use, psychiatric history, and prior biologic use. Secondary outcomes included emergency department visits (ED) and IBD-related hospitalizations. Statistical analysis was performed using Wilcox rank sum test, Pearson’s Chi-squared test, and logistic regression model as an unordered, factor variable to flexibly estimate the probabilities of adherence. Results: Six hundred eight subjects were included. Overall median MPR was 0.95 (interquartile range 0.47, 1) and adherence was 68%–70%. When the number of risk factors for nonadherence increased, the likelihood of nonadherence increased (P < .05). In unadjusted and adjusted analysis, nonadherence increased the likelihood of ED visits [rate ratio 1.45 (95% confidence interval 1.05, 1.97)] and hospitalizations [rate ratio 1.60 (95% confidence interval 1.16, 2.10)]. Conclusion: Academic centers with integrated pharmacies had high adherence. Prior risk factors for nonadherence remained significant in this multicenter model. Nonadherence was associated with higher likelihood of hospitalizations and ED visits.

Abstract Purpose This study is a scoping review of the different methods used to measure rurality in the health services research (HSR) literature. Methods We identified peer-reviewed empirical studies from 2010–2020 from seven leading HSR journals, including the Journal of Rural Health, that used any definition to measure rurality as a part of their analysis. From each study, we identified the geographic unit (e.g., county, zip code) and definition (e.g., Rural Urban Continuum Codes, Rural Urban Commuting Areas) used to classify categories of rurality. We analyzed whether geographic units and definitions used to classify rurality differed by focus area of studies, including costs, quality, and access to care. Lastly, we examined the number of rural categories used by authors to assess rural areas. Findings In 103 included studies, five different geographic units and 11 definitions were used to measure rurality. The most common geographic units used to measure rurality were county (n = 59, 57%), which was used most frequently in studies examining cost (n = 12, 75%) and access (n = 33, 57.9%). Rural Urban Commuting Area codes were the most common definition used to measure rurality for studies examining access (n = 13, 22.8%) and quality (n = 10, 44%). The majority of included studies made rural versus urban comparisons (n = 82, 80%) as opposed to focusing on rural populations only (n = 21, 20%). Among studies that compared rural and urban populations, most studies used only one category to identify rural locations (n = 49 of 82 studies, 60%). Conclusion Geographic units and definitions to determine rurality were used inconsistently within and across studies with an HSR focus. This finding may affect how health disparities by rural location are determined and thus how resources and federal funds are allocated. Future research should focus on developing a standardized system to determine under what circumstances researchers should use different geographic units and methods to determine rurality by HSR focus area.