Direct and Legacy Effects of Varying Cool-Season Precipitation Totals on Ecosystem Carbon Flux in a Semi-Arid Mixed Grassland.

In the semi-arid grasslands of the southwest United States, annual precipitation is divided between warm-season (July-September) convective precipitation and cool-season (December-March) frontal storms. While evidence suggests shifts in precipitation seasonal distribution, there is a poor understanding of the ecosystem carbon flux responses to cool-season precipitation and the potential legacy effects on subsequent warm-season carbon fluxes. Results from a two-year experiment with three cool-season precipitation treatments (dry, received 5th percentile cool-season total precipitation; normal, 50th; wet, 95th) and constant warm-season precipitation illustrate the direct and legacy effects on carbon fluxes, but in opposing ways. In wet cool-season plots, gross primary productivity (GPP) and ecosystem respiration (ER) were 103% and 127% higher than in normal cool-season plots. In dry cool-season plots, GPP and ER were 47% and 85% lower compared to normal cool-season plots. Unexpectedly, we found a positive legacy effect of the dry cool-season treatment on warm-season carbon flux, resulting in a significant increase in both GPP and ER in the subsequent warm season, compared to normal cool-season plots. Our results reveal positive legacy effects of cool-season drought on warm-season carbon fluxes and highlight the importance of the relatively under-studied cool-growing season and its direct/indirect impact on the ecosystem carbon budget.

The OBS UK Dashboard: an interactive tool for representative trial site selection to facilitate equality and diversity in maternity research.

BACKGROUND: Obstetric Bleeding Study UK (OBS UK) (award ID: 152057) is a National Institute for Health and Care Research (NIHR)-funded stepped wedge cluster randomised controlled trial of a complex intervention for postpartum haemorrhage. This was developed in Wales and evaluated in a feasibility study, with improvements in maternal outcomes observed. Generalisability of the findings is limited by lack of control data and limited ethnic diversity in the Welsh obstetric patient population compared to the United Kingdom (UK): 94% of the Welsh population identifies as White, versus 82% in the UK. Non-White ethnicity and socioeconomic deprivation are linked to increased risk of adverse maternal outcomes. Traditionally, decisions regarding site selection are based on desire to complete trials on target in 'tried and tested' research active institutions. To ensure widespread applicability of the results and investigate the impact of ethnicity and social deprivation on trial outcomes, maternity units were recruited that represent the ethnic diversity and social deprivation profiles of the UK. METHOD: Using routinely collected, publicly available data, an interactive dashboard was developed that demonstrates the demographics of the population served by each maternity unit in the UK, to inform site recruitment. Data on births per year, ethnic and socioeconomic group of the population for each maternity unit, across the UK, were integrated into the dashboard. RESULTS: The dashboard demonstrates that OBS UK trial sites reflect the ethnic and socioeconomic diversity of the UK (study vs UK population ethnicity: White 79.2% vs 81.7%, Asian 10.5% vs 9.3%, Black 4.7% vs 4.0%, Mixed 2.5% vs 2.9%, Other 3.0% vs 2.1%) with variation in site demography, size and location. Missing data varied across sites and nations and is presented. CONCLUSION: The NIHR equality, diversity and inclusion strategy states studies must widen participation, facilitating individuals from all backgrounds to engage. The development of this novel interactive dashboard demonstrates an innovative way of achieving this. National Health Service (NHS) maternity researchers should consider using this tool to enhance diversity in research, address health disparities and improve generalisability of findings. This approach could be applied to healthcare settings beyond maternity care and across different global populations. TRIAL REGISTRATION: ISRCTN 17679951. Registered on August 30, 2023.

Whole Nervous System Expression of Glutamate Receptors Reveals Distinct Receptor Roles in Sensorimotor Circuits.

The goal of connectomics is to reveal the links between neural circuits and behavior. Larvae of the primitive chordate Ciona are well-suited to make contributions in this area. In addition to having a described connectome, Ciona larvae have a range of readily quantified behaviors. Moreover, the small number of neurons in the larval CNS (∼180) holds the promise of a comprehensive characterization of individual neurons. We present single-neuron predictions for glutamate receptor (GlutR) expression based on in situ hybridization. Included are both ionotropic receptors (AMPA, NMDA, and kainate) and metabotropic receptors. The predicted glutamate receptor expression dataset is discussed in the context of known circuits driving behaviors such as phototaxis, mechanosensation, and looming shadow response. The predicted expression of AMPA and NMDA receptors may help resolve issues regarding the co-production of GABA and glutamate by a subset of photoreceptors. The targets of these photoreceptors in the midbrain appear to express NMDA receptors, but not AMPA receptors. This is in agreement with previous results indicating that GABA is the primary neurotransmitter from the photoreceptors evoking a swimming response through a disinhibition mechanism and that glutamate may, therefore, have only a modulatory action in this circuit. Other findings reported here are more unexpected. For example, many of the targets of glutamatergic epidermal sensory neurons (ESNs) do not express any of the ionotropic receptors, yet the ESNs themselves express metabotropic receptors. Thus, we speculate that their production of glutamate may be for communication with neighboring ESNs, rather than to their interneuron targets.

Racial Attitudes and Perceptions of Government Response during the COVID-19 Pandemic: Implications for Public Health Strategies.

BACKGROUND: This study explored whether opinions about the government's role in addressing the COVID-19 pandemic vary based on demographic characteristics and racial beliefs. We hypothesized that opinions about the United States (U.S.) government's response to COVID-19 would differ based on an individual's characteristics such as age, race, and racial beliefs. METHODS: We utilized an Inter-University Consortium for Political and Social Research dataset to examine differences in opinion regarding the government's pandemic response, considering personal characteristics and racial beliefs. Descriptive statistics depicted respondents' characteristics, and a Chi-square test for independence assessed whether differences emerged based on racial attitude, self-reported racial identity, sex, income, education, and age. Logistic regression analyses were conducted to independently determine which characteristics were associated with differences in evaluating the government's pandemic response. RESULTS: The sample consisted of 1028 respondents: 47.5% male and 52.5% female. Overall, the group viewed the government unfavorably, with only 40% reporting that the government responded correctly and 54% believing the government is almost always wasteful and inefficient. Hispanics or Latinos were more likely to view the government as wasteful or inefficient, while more Whites rated the government's pandemic response as appropriate. Individuals who believed that racial discrimination is the main reason why many Black people cannot get ahead generally regarded the government's pandemic response more favorably. Only 5% deemed the government's response excessive. Being Black, younger, and female was associated with the view that racial discrimination is the main reason why many Black people cannot get ahead. Individuals who felt this way viewed the government unfavorably by almost a 2:1 ratio. CONCLUSIONS: A majority of U.S. residents do not believe the government responded correctly to the pandemic and more than half viewed the government as wasteful and inefficient. Differences emerged by ethnicity and racial attitudes, with individuals of color holding more negative views of the government's response. Understanding this perspective can help develop messaging and strategies that resonate with communities where racial and minority groups live.

AI implementation: Radiologists' perspectives on AI-enabled opportunistic CT screening.

OBJECTIVE: AI adoption requires perceived value by end-users. AI-enabled opportunistic CT screening (OS) detects incidental clinically meaningful imaging risk markers on CT for potential preventative health benefit. This investigation assesses radiologists' perspectives on AI and OS. METHODS: An online survey was distributed to 7500 practicing radiologists among ACR membership of which 4619 opened the emails. Familiarity with and views of AI applications were queried and tabulated, as well as knowledge of OS and inducements and impediments to use. RESULTS: Respondent (n = 211) demographics: mean age 55 years, 73 % male, 91 % diagnostic radiologists, 46 % in private practice. 68 % reported using AI in practice, while 52 % were only somewhat familiar with AI. 70 % viewed AI positively though only 46 % reported AI's overall accuracy met expectations. 57 % were unfamiliar with OS, with 52 % of those familiar having a positive opinion. Patient perceptions were the most commonly reported (25 %) inducement for OS use. Provider (44 %) and patient (40 %) costs were the most common impediments. Respondents reported that osteoporosis/osteopenia (81 %), fatty liver (78 %), and atherosclerotic cardiovascular disease risk (76 %) could be well assessed by OS. Most indicated OS output requires radiologist oversight/signoff and should be included in a separate "screening" section in the Radiology report. 28 % indicated willingness to spend 1-3 min reviewing AI-generated output while 18 % would not spend any time. Society guidelines/recommendations were most likely to impact OS implementation. DISCUSSION: Radiologists' perspectives on AI and OS provide practical insights on AI implementation. Increasing end-user familiarity with AI-enabled applications and development of society guidelines/recommendations are likely essential prerequisites for Radiology AI adoption.

Manufacture, characterization, and elucidation of drug release mechanisms of etonogestrel implants based on ethylene vinyl acetate.

In this work, etonogestrel implants were manufactured using coextrusion. The purpose of the study was to correlate changes in microstructure and transport properties that occurred in etonogestrel implants to drug release mechanisms. The implants consisted of an EVA 28 (28 % vinyl acetate) core containing dispersed and dissolved etonogestrel, and an EVA 15 (15 % vinyl acetate) skin. The drug release was determined to be via diffusion at a controlled rate and governed by implant dimensions. In-vitro release revealed evidence of supersaturation in the implant core and skin, likely from the intense mechanical energy input during the twin-screw manufacturing process. Subsequently during storage under ambient conditions, supersaturation resulted in recrystallization of drug crystals, preferentially in the implant core. Etonogestrel solubility and diffusivity in EVA were determined by permeation experiments and used for release modeling. Drug release from the EVA skin layer deviated from the predicted values due to 1) formation of a drug depletion zone in the core and 2) presence of a stagnant media layer adjacent to the skin. Drug release from implant ends was significantly faster than predicted. Air-filled pores were observed in the implant core using microCT which likely contributed to the faster release from implant ends.

Ion Correlations Decrease Particle Aggregation Rate by Increasing Hydration Forces at Interfaces.

The connection between solution structure, particle forces, and emergent phenomena at solid-liquid interfaces remains ambiguous. In this case study on boehmite aggregation, we established a connection between interfacial solution structure, emerging hydration forces between two approaching particles, and the resulting structure and kinetics of particle aggregation. In contrast to expectations from continuum-based theories, we observed a nonmonotonic dependence of the aggregation rate on the concentration of sodium chloride, nitrate, or nitrite, decreasing by 15-fold in 4 molal compared to 1 molal solutions. These results are accompanied by an increase in repulsive hydration forces and interfacial oscillatory features from 0.27-0.31 nm in 0.01 molal to 0.38-0.52 nm in 2 molal. Moreover, molecular dynamics (MD) simulations indicated that these changes correspond to enhanced ion correlations near the interface and produced loosely bound aggregates that retain electrolyte between the particles. We anticipate that these results will enable the prediction of particle aggregation, attachment, and assembly, with broad relevance to interfacial phenomena.

Cervical squamous cell carcinoma outcomes across continents: A retrospective study.

OBJECTIVE: To assess the influence of geographies and race on the survival outcomes in patients diagnosed with cervical squamous cell carcinoma (CSCC) across three continents. METHODS: This multicontinental retrospective study was conducted in 8 hospitals across Asia, Europe, and North America (NA). Clinicopathologic data of 595 patients with presumed early stages of CSCC, treated surgically, with curative intent was collected. Descriptive analysis and Cox regression models were produced. RESULTS: A total of 595 patients, consisting of 445 (74.8 %) white, 75 (12.6 %) Blacks, and 75 (12.6 %) Asian patients were included. Geographical distribution comprised 69 % of patients from NA, 22 % from Europe, and 9 % from Asia. The median age at diagnosis was 46 years. The median overall survival (OS) and relapse-free survival (RFS) were 22.09 years and 21.19 years, respectively. Patient characteristics varied significantly across geographical regions, except for consensus tumor grade. Patients in Europe from middle-income countries with limited CC screening had a substantially higher risk of death than those in NA (HR, 1.79; 95 % CI, 1.13 to 2.79; p = 0.015). Patients from single center in Japan had higher risk of relapse than those from the four heterogeneous NA centers (sub-distribution hazard ratio, 2.19; 95 % CI, 1.22 to 3.95; p = 0.009), although OS did not differ significantly. Race remained statistically insignificant for survival outcomes across the three continents but seemed to influence survival outcomes in NA centers. CONCLUSION: Our study highlights impact of geographies and races on CSCC survival outcomes, emphasizing the need of considering these factors when developing targeted interventions against CSCC.

Suicidality among clients in a network of coordinated specialty care (CSC) programs for first-episode psychosis: Rates, changes in rates, and their predictors.

BACKGROUND: People experiencing their first episode of psychosis have high risk of suicide, and programs specializing in early psychosis have not always achieved reduced risk. The present study analyzes patterns of suicide ideation, self-harm, and suicide attempts within the Connection Learning Healthcare System of 23 early psychosis programs in Pennsylvania and Maryland that follow the Coordinated Specialty Care treatment model. METHOD: People with first episode psychosis (n = 1101) were assessed at admission and every six months using a standardized battery that included self-reported past-month ideation and clinician-reported past-six-month ideation, self-harm, and suicide attempts. RESULTS: At admission, there were 28 % rates of self-reported past-month suicide ideation and 52 % rates clinician-reported past-six-month suicide ideation, 23 % rate of clinician-reported self-harm, and 15 % rate of attempts. After the first six months of treatment there were significantly lower rates of clinician-reported suicidality (with reductions of at least 77 %), and after the first year of treatment there was significantly lower self-reported ideation (with approximately 54 % reporting lower past-month ideation). Changes were not accounted for by differential early discharge. A range of psychosocial variables predicted within- and between-subject variability in suicidality. Social and role functioning, depressive symptom severity, and a sense of recovery were significant within-subject predictors of all four measures of suicidality. CONCLUSIONS: Compared to admission, we observed substantially lower rates of suicidality within the first year of treatment for clients with first episode psychosis in Coordinated Specialty Care. Reductions were predicted by some of the variables targeted by the treatment model.

Clinical decision support systems for maternity care: a systematic review and meta-analysis.

Background: The use of Clinical Decision Support Systems (CDSS) is increasing throughout healthcare and may be able to improve safety and outcomes in maternity care, but maternity care has key differences to other disciplines that complicate the use of CDSS. We aimed to identify evaluated CDSS and synthesise evidence of their impact on maternity care. Methods: We conducted a systematic review for articles published before 24th May 2024 that described i) CDSS that ii) investigated the impact of their use iii) in maternity settings. Medline, CINAHL, CENTRAL and HMIC were searched for articles relating to evaluations of CDSS in maternity settings, with forward- and backward-citation tracing conducted for included articles. Risk of bias was assessed using the Mixed Methods Assessment Tool, and CDSS were described according to the clinical problem, purpose, design, and technical environment. Quantitative results from articles reporting appropriate data were meta-analysed to estimate odds of a CDSS achieving its desired outcome using a multi-level random effects model, first by individual CDSS and then across all CDSS. PROSPERO ID: CRD42022348157. Findings: We screened 12,039 papers and included 87 articles describing 47 unique CDSS. 24 articles (28%) described randomised controlled trials, 30 (34%) described non-randomised interventional studies, 10 (11%) described mixed methods studies, 10 (11%) described qualitative studies, 7 (8%) described quantitative descriptive studies, and 7 (8%) described economic evaluations. 49 (56%) were in High-Income Countries and 38 (44%) in Low- and Middle-Income countries, with no CDSS trialled in both income categories. Meta-analysis of 35 included studies found an odds ratio for improved outcomes of 1.69 (95% confidence interval 1.24-2.30). There was substantial variation in effects, aims, CDSS types, context, study designs, and outcomes. Interpretation: Most CDSS evaluations showed improvements in outcomes, but there was heterogeneity in all aspects of design and evaluation of systems. CDSS are increasingly important in delivering healthcare, and Electronic Health Records and mHealth will increase their availability, but traditional epidemiological methods may be limited in guiding design and demonstrating effectiveness due to rapid CDSS development lifecycles and the complex systems in which they are embedded. Development methods that are attentive to context, such as Human Centred Design, will help to meet this need. Funding: None.

Agaricus bisporus mushroom anaphylaxis: A case report and review of the literature.

Background: Anaphylaxis in response to edible mushrooms is uncommon, and sensitization may be independent of occupational exposure. Globally, A garicus bisporus is one the most cultivated mushroom species, comprising the button, portobello, and Swiss brown varietals. Objective: Our aim was to describe a case of anaphylaxis in an older nonatopic patient following ingestion of A bisporus and undertake a review of the literature. Methods: A 77-year-old female was referred to the allergy clinic with a history of grade 3 hypotensive anaphylaxis following ingestion of a mushroom omelette. Her tryptase level 4 hours following acute symptoms was elevated. She continued to consume all other omelette ingredients with the exception of mushroom. Additional investigations included specific IgE testing as well as comprehensive skin prick testing (SPT) to raw and boiled mushrooms. Results: One month after her index reaction, the result of SPT to boiled button mushroom was positive. The patient's baseline tryptase level was normal. The results of further SPT with other commonly available boiled mushrooms (the A bisporus mushrooms portobello and Swiss brown, as well as enoki, oyster, and shiitake mushrooms) were also positive.A review of the literature revealed 27 other cases, with an average patient age of 28.8 years (range 8-68 years) and no gender predisposition. Cases from Europe (n = 14, 51.8%) and Asia (n = 12, 44.4%) comprised the majority of the reports. A bisporus was reported in more than one-third of the cases (n = 10, 37.1%) from Australia, India, Portugal, Spain, and the United Kingdom. Cross-sensitization among the edible mushroom species was evident for those individuals who were tested, but no clear and consistent pattern was identified. In some cases, further diagnostics identified α-mannosidase, α-trehalose, mannitol, and ribosomal protein as specific mushroom allergens. Conclusion: Clinicians should be aware of mushroom as a cause for anaphylaxis, especially in nonatopic and de novo presentations.

The Australasian Registry for Severe Cutaneous Adverse Reactions (AUS-SCAR) - Providing a roadmap for closing the diagnostic, patient, and healthcare gaps for a group of rare drug eruptions.

Background: Severe cutaneous adverse reactions (SCAR) are a group of delayed presumed T-cell mediated hypersensitivities associated with significant morbidity and mortality. Despite their shared global healthcare burden and impact, the clinical phenotypes, genomic predisposition, drug causality, and treatment outcomes may vary. We describe the establishment and results from the first Australasian registry for SCAR (AUS-SCAR), that via a collaborative network advances strategies for the prevention, diagnosis and treatment of SCAR. Methods: Prospective multi-center registry of SCAR in Australian adult and adolescents, with planned regional expansion. The registry collects externally verified phenotypic data drug causality, therapeutics and long-term patient outcomes. In addition, biorepository specimens and DNA are collected at participating sites. Results: we report on the first 100 patients enrolled in the AUS-SCAR database. DRESS (50%) is the most predominant phenotype followed by SJS/TEN (39%) and AGEP (10%), with median age of 52 years old (IQR 37.5, 66) with 1:1 male-to-female ratio. The median latency for all implicated drugs is highly variable but similar for DRESS (median 15 days IQR 5,25) and SJS/TEN (median 21 days, IQR 7,27), while lowest for AGEP (median 2.5 days, IQR 1,8). Antibiotics (54.5%) are more commonly listed as primary implicated drug compare with non-antibiotics agent (45.5%). Mortality rate at 90 days was highest in SJS/TEN at 23.1%, followed by DRESS (4%) and AGEP (0%). Conclusion: In the first prospective national phenotypic and biorepository of SCAR in the southern hemisphere we demonstrate notable differences to other reported registries; including DRESS-predominant phenotype, varied antibiotic causality and low overall mortality rate. This study also highlights the lack of standardised preventative pharmacogenomic measures and in vitro/in vivo diagnostic strategies to ascertain drug causality. Trial registration: ANZCTR ACTRN12619000241134. Registered 19 February 2019.

Prehospital central venous catheters.

The use of whole blood in the prehospital setting is increasing. Currently available intraosseous and peripheral venous catheters limit the flow of blood products and fluid during resuscitation. Central venous catheters can be effectively placed in the prehospital environment. Rapid, high-volume infusion of blood products can be lifesaving.

A growth-differentiation factor 15 receptor agonist in randomized placebo-controlled trials in healthy or obese persons.

BACKGROUND: Growth Differentiation Factor 15 (GDF15), a divergent member of the TGF-ß superfamily, signals via the hindbrain glial-derived neurotrophic factor receptor alpha-like and rearranged during transfection receptor co-receptor (GFRAL-RET) complex. In nonclinical species, GDF15 is a potent anorexigen leading to substantial weight loss. MBL949 is a half-life extended recombinant human GDF15 dimer. METHODS: MBL949 was evaluated in multiple nonclinical species and then in humans in two randomized and placebo-controlled clinical trials. In the Phase 1 first-in-human, single ascending dose trial MBL949 or placebo was injected subcutaneously to overweight and obese healthy volunteers (n=65) at doses ranging from 0.03 to 20 mg. In Phase 2, MBL949 or placebo was administered subcutaneously every other week for a total of 8 doses to obese participants (n=126) in five different dose regimens predicted to be efficacious based on data from the Phase 1 trial. RESULTS: In nonclinical species, MBL949 was generally safe and effective with reduced food intake and body weight in mice, rats, dogs, and monkeys. Weight loss was primarily from reduced fat, and metabolic endpoints improved. A single ascending dose study in overweight or obese healthy adults demonstrated mean terminal half-life of 18-22 days, and evidence of weight loss at the higher doses. In the Phase 2, weight loss was minimal following biweekly dosing of MBL949 for 14 weeks. MBL949 was safe and generally tolerated in humans over the dose range tested, adverse events of the gastrointestinal system were the most frequent observed. CONCLUSION: The prolonged half-life of MBL949 supports biweekly dosing in patients. MBL949 had an acceptable safety profile. The robust weight loss observed in nonclinical species did not translate to weight loss efficacy in humans. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199090.

Impact of racial microaggressions in psychotherapy vignettes with african american clients: An experimental analogue design.

Mental health researchers have focused on promoting culturally sensitive clinical care (Herman et al., 2007; Whaley & Davis, 2007), emphasizing the need to understand how biases may impact client well-being. Clients report that their therapists commit racial microaggressions-subtle, sometimes unintentional, racial slights-during treatment (Owen et al., 2014). Yet, existing studies often rely on retrospective evaluations of clients and cannot establish the causal impact of varying ambiguity of microaggressions on clients. This study uses an experimental analogue design to examine offensiveness, emotional reactions, and evaluations of the interaction across three distinct levels of microaggression statements: subtle, moderate, and overt. We recruited 158 adult African American participants and randomly assigned them to watch a brief counseling vignette. We found significant differences between the control and three microaggression statements on all outcome variables. We did not find significant differences between the microaggression conditions. This study, in conjunction with previous correlational research, highlights the detrimental impact of microaggressions within psychotherapy, regardless of racially explicit content. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

A 73-Year-Old Female Diagnosed With Dermatofibrosarcoma Protuberans in the Primary Care Setting: A Case Report and Literature Review of Misdiagnosed Cases.

Dermatofibrosarcoma protuberans (DFSP) is a rare, slow-growing, malignant tumor in the dermis and subcutaneous fat diagnosed by pathological and immunohistochemical examinations. This case report provides the dermatological findings of a 73-year-old woman with DFSP who presented to a primary care clinic with a longstanding nodular lesion on her left upper thigh. Dermatological examination showed a solitary, skin-colored violaceous/hyperpigmented nodule on the superior anteromedial portion of the left thigh. A punch biopsy revealed spindle cell proliferation, and diffuse CD34 positivity, confirming the diagnosis of DFSP. A dermatology referral was placed for further management and complete surgical excision. Patient underwent wide local excision (WLE) and has no recurrence to date. Unfortunately, DFSP is commonly misdiagnosed before skin biopsy which delays treatment. This case is significant because DFSP is not often diagnosed accurately outside the dermatology specialty and serves as a reminder to practitioners to use biopsies during the diagnostic process of skin findings to prevent the delay in management.

Negative Lifestyle Factors Specific to Aging Persons Living with HIV and Multimorbidity.

The primary goal of medical care during the pre-antiretroviral therapy (ART) era was to keep persons living with human immunodeficiency virus (HIV) alive, whereas since the advent of ART, the treatment objective has shifted to decreasing viral loads and infectiousness while increasing CD4+ T-cell counts and longevity. The health crisis, however, is in preventing and managing multimorbidity (ie, type 2 diabetes), which develops at a more accelerated or accentuated pace among aging persons living with HIV. Relative to the general population and age-matched uninfected adults, it may be more difficult for aging HIV-positive persons who also suffer from multimorbidity to improve negative lifestyle factors to the extent that their behaviors could support the prevention and management of diseases. With recommendations and a viable solution, this article explores the impact of negative lifestyle factors (ie, poor mental health, suboptimal nutrition, physical inactivity, alcohol use) on the health of aging individuals living with HIV.

How Negative Lifestyle Factors Impact Aging Persons Living with HIVThis literature review highlights negative lifestyle factors experienced by aging persons living with HIV, including poor mental health (i.e., depression, cognitive decline), poor nutrition, physical inactivity, alcohol use, sexually transmitted infection, poor sleep quality, and treatment noncompliance as promoting diseases (e.g., type 2 diabetes, hypertension, obesity, cardiovascular disease) and early death. A possible solution to decreasing or eliminating negative lifestyle factors in the aging HIV-positive population is to develop disease prevention-focused teams in clinical and community settings. However, if team development is impractical, primary healthcare providers should routinely assess and monitor lifestyle factors (i.e., cognitive decline) and, if needed, provide appropriate referrals to licensed or certified specialists (e.g., psychologist, clinical dietitian, medical exercise specialist, or health coach).

Reasons for Discharge in a National Network of Early Psychosis Intervention Programs.

BACKGROUND: Discharge from early psychosis intervention is a critical stage of treatment that may occur for a variety of reasons. This study characterizes reasons for discharge among participants in early psychosis intervention programs participating in the Early Psychosis Intervention Network (EPINET) which comprises >100 programs in the United States organized under 8 academic hubs. STUDY DESIGN: We analyzed 1787 discharges, focusing on program completion, unilateral termination by the client/family, and lost contact with the client/family. We performed exploratory analyses of demographic, clinical, and functional predictors of discharge reason. Variables predictive of discharge type were included in multilevel logistic regressions, allowing for the estimation of predictors of discharge reason and variability in rates by program and hub. STUDY RESULTS: An estimated 20%-30% of enrolled patients completed the program. Program completion rates were higher among participants who were older on admission, had lower negative symptoms severity, spent more time in education, employment, or training, and who were covered by private insurance (a close proxy for socioeconomic status). Programs were more likely to lose contact with male participants, Black participants, and participants who were never covered by private insurance. After accounting for patient-level factors, there was substantial program-level variation in all 3 discharge outcomes, and hub-level variability in the proportion of participants who completed the program. The impact of race on program completion varied substantially by program. CONCLUSIONS: Participants were discharged from early psychosis intervention services for diverse reasons, some of which were associated with sociocultural factors. Disengagement is a widespread problem affecting all hubs.

Automating incidence and prevalence analysis in open cohorts.

MOTIVATION: Data is increasingly used for improvement and research in public health, especially administrative data such as that collected in electronic health records. Patients enter and exit these typically open-cohort datasets non-uniformly; this can render simple questions about incidence and prevalence time-consuming and with unnecessary variation between analyses. We therefore developed methods to automate analysis of incidence and prevalence in open cohort datasets, to improve transparency, productivity and reproducibility of analyses. IMPLEMENTATION: We provide both a code-free set of rules for incidence and prevalence that can be applied to any open cohort, and a python Command Line Interface implementation of these rules requiring python 3.9 or later. GENERAL FEATURES: The Command Line Interface is used to calculate incidence and point prevalence time series from open cohort data. The ruleset can be used in developing other implementations or can be rearranged to form other analytical questions such as period prevalence. AVAILABILITY: The command line interface is freely available from https://github.com/THINKINGGroup/analogy_publication .

Human cancer genomes harbor the mutational signature of tobacco-specific nitrosamines NNN and NNK.

Tobacco usage is linked to multiple cancer types and accounts for a quarter of all cancer-related deaths. Tobacco smoke contains various carcinogenic compounds, including polycyclic aromatic hydrocarbons (PAH), though the mutagenic potential of many tobacco-related chemicals remains largely unexplored. In particular, the highly carcinogenic tobacco-specific nitrosamines NNN and NNK form pre-mutagenic pyridyloxobutyl (POB) DNA adducts. In the study presented here, we identified genome-scale POB-induced mutational signatures in cell lines and rat tumors, while also investigating their role in human cancer. These signatures are characterized by T>N and C>T mutations forming from specific POB adducts damaging dT and dC residues. Analysis of 2,780 cancer genomes uncovered POB signatures in ∼180 tumors; from cancer types distinct from the ones linked to smoking-related signatures SBS4 and SBS92. This suggests that, unlike PAH compounds, the POB pathway may contribute uniquely to the mutational landscapes of certain hematological malignancies and cancers of the kidney, breast, prostate and pancreas.