Search

We analyzed the floral morphology and nectar production of several cultivars and species of Monarda representing five cultivars and four species grown in Georgia Piedmont and Montane regions. Over the course of two seasons, we detected significant differences among the samples in terms of inflorescence size, petal lobe and corolla widths and lengths, and total sugar content. M. didyma had larger glomerules, longer corollas and petal lobes, and higher nectar volume and total sugar content per flower. M. fistulosa and M. punctata had smaller glomerules, corolla and petal lobe lengths, and total sugar content per flower. Petal lobe and corolla length strongly correlated with sucrose and nectar production. Combined with data on horticultural performance, these results could be valuable in informing breeding goals for conservation-oriented landscape plants.

BackgroundAttention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders among children. Pharmacotherapy has been the primary treatment for ADHD, supplemented by behavioral interventions. Digital and exercise interventions are promising nonpharmacologic approaches for enhancing the physical and psychological health of children with ADHD. However, the combined impact of digital and exercise therapies remains unclear. ObjectiveThe aim of this study was to determine whether BrainFit, a novel digital intervention combining gamified cognitive and exercise training, is efficacious in reducing ADHD symptoms and executive function (EF) among school-aged children with ADHD. MethodsThis 4-week prospective randomized controlled trial included 90 children (6-12 years old) who visited the ADHD outpatient clinic and met the diagnostic criteria for ADHD. The participants were randomized (1:1) to the BrainFit intervention (n=44) or a waitlist control (n=46) between March and August 2022. The intervention consisted of 12 30-minute sessions delivered on an iPad over 4 weeks with 3 sessions per week (Monday, Wednesday, and Friday after school) under the supervision of trained staff. The primary outcomes were parent-rated symptoms of attention and hyperactivity assessed according to the Swanson, Nolan, and Pelham questionnaire (SNAP-IV) rating scale and EF skills assessed by the Behavior Rating Inventory of Executive Function (BRIEF) scale, evaluated pre and post intervention. Intention-to-treat analysis was performed on 80 children after attrition. A nonparametric resampling-based permutation test was used for hypothesis testing of intervention effects. ResultsAmong the 145 children who met the inclusion criteria, 90 consented and were randomized; ultimately, 80 (88.9%) children completed the study and were included in the analysis. The participants’ average age was 8.4 (SD 1.3) years, including 63 (78.8%) male participants. The most common ADHD subtype was hyperactive/impulsive (54/80, 68%) and 23 (29%) children had severe symptoms. At the endpoint of the study, the BrainFit intervention group had a significantly larger improvement in total ADHD symptoms (SNAP-IV total score) as compared to those in the control group (β=–12.203, 95% CI –17.882 to –6.523; P

The durability of thick solar glass mirrors has been evaluated in this study by exposing samples at two potential exposure sites. Samples have been exposed for a period of 18 months at different orientations (North, South, East, and West) to evaluate the impact of orientation on the durability. The samples performance has been evaluated by measuring the specular reflectance of the glass samples before and after an appropriate cleaning process. In addition, the contact angle and the surface energy have been analysed. Obtained results show that mirror durability is very specific to the environmental conditions of the exposure site.

Abstract Text‐to‐image artificial intelligence (AI) programs are popular public‐facing tools that generate novel images based on user prompts. Given that they are trained from Internet data, they may reflect societal biases, as has been shown for text‐to‐text large language model programs. We sought to investigate whether 3 common text‐to‐image AI systems recapitulated stereotypes held about surgeons and other health care professionals. All platforms queried were able to reproduce common aspects of the profession including attire, equipment, and background settings, but there were differences between programs most notably regarding visible race and gender diversity. Thus, historical stereotypes of surgeons may be reinforced by the public's use of text‐to‐image AI systems, particularly those without procedures to regulate generated output. As AI systems become more ubiquitous, understanding the implications of their use in health care and for health care‐adjacent purposes is critical to advocate for and preserve the core values and goals of our profession.

BackgroundA substantial percentage of the US population is not up to date on guideline-recommended cancer screenings. Identifying interventions that effectively improve screening rates would enhance the delivery of such screening. Interventions involving health IT (HIT) show promise, but much remains unknown about how HIT is optimized to support cancer screening in primary care. ObjectiveThis scoping review aims to identify (1) HIT-based interventions that effectively support guideline concordance in breast, cervical, and colorectal cancer screening provision and follow-up in the primary care setting and (2) barriers or facilitators to the implementation of effective HIT in this setting. MethodsFollowing scoping review guidelines, we searched MEDLINE, CINAHL Plus, Web of Science, and IEEE Xplore databases for US-based studies from 2015 to 2021 that featured HIT targeting breast, colorectal, and cervical cancer screening in primary care. Studies were dual screened using a review criteria checklist. Data extraction was guided by the following implementation science frameworks: the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework; the Expert Recommendations for Implementing Change taxonomy; and implementation strategy reporting domains. It was also guided by the Integrated Technology Implementation Model that incorporates theories of both implementation science and technology adoption. Reporting was guided by PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews). ResultsA total of 101 studies met the inclusion criteria. Most studies (85/101, 84.2%) involved electronic health record–based HIT interventions. The most common HIT function was clinical decision support, primarily used for panel management or at the point of care. Most studies related to HIT targeting colorectal cancer screening (83/101, 82.2%), followed by studies related to breast cancer screening (28/101, 27.7%), and cervical cancer screening (19/101, 18.8%). Improvements in cancer screening were associated with HIT-based interventions in most studies (36/54, 67% of colorectal cancer–relevant studies; 9/14, 64% of breast cancer–relevant studies; and 7/10, 70% of cervical cancer–relevant studies). Most studies (79/101, 78.2%) reported on the reach of certain interventions, while 17.8% (18/101) of the included studies reported on the adoption or maintenance. Reported barriers and facilitators to HIT adoption primarily related to inner context factors of primary care settings (eg, staffing and organizational policies that support or hinder HIT adoption). Implementation strategies for HIT adoption were reported in 23.8% (24/101) of the included studies. ConclusionsThere are substantial evidence gaps regarding the effectiveness of HIT-based interventions, especially those targeting guideline-concordant breast and colorectal cancer screening in primary care. Even less is known about how to enhance the adoption of technologies that have been proven effective in supporting breast, colorectal, or cervical cancer screening. Research is needed to ensure that the potential benefits of effective HIT-based interventions equitably reach diverse primary care populations.

We evaluated several horticultural cultivars and species of Monarda, a genus native to North America with a center of diversity in the Southeast and advertised as beneficial to wildlife, to assess landscape performance with respect to vegetative habit, flower production, and disease tolerance in Georgia Piedmont and montane habitats. We established two experimental sites: the State Botanical Garden of Georgia in Athens (USDA Zone 8b) and the Georgia Mountain Education and Research Center in Blairsville (USDA Zone 7b). We then tracked plant performance over 2 years after establishment. Our study included 10 samples of Monarda, representing five cultivars and four species. Estimated height and width at flowering showed M. bradburiana, M. Sugar Buzz® Grape Gumball, and the M. punctata ecotypes were smaller than other tested taxa. M. fistulosa had the most flowers at the Blairsville site and equal flowering with M. punctata at the Athens location, but most taxa flowered for 2 to 3 months with ∼100 flowering stems per stand. All samples were susceptible to powdery mildew, but M. bradburiana displayed the highest level of tolerance. Otherwise, cultivars tended to be more tolerant to powdery mildew than species. The observed variations in horticultural characteristics and performance highlight the high value of this genus for Georgia landscapes.

Abstract Background and aims Despite that 93% of people indicate that a mattress plays a pivotal role in achieving high‐quality sleep, there is a scarcity of research investigating the influence of mattresses on sleep quality, pain, and mood in nonclinical poor sleepers. The purpose was to examine the effectiveness of a pressure‐releasing medium‐firm grid mattress on sleep and health outcomes (e.g., mood, pain, daytime fatigue) of adults with nonclinical insomnia symptoms using a quasi‐experimental design. Methods Participants were 39 adults (mean age = 45.29) with nonclinical insomnia (i.e., occasional sleeplessness). Following 1 week of baseline assessments on their current mattress, they slept on a pressure‐relieving grid mattress for 8 weeks. Participants completed self‐report assessments of the Pittsburgh Sleep Quality Index, Berlin Questionnaire, Insomnia Severity Index, Restorative Sleep Questionnaire, Perceived Stress Scale, Profile of Mood States, Daytime Fatigue Scale, Pain and Sleep Questionnaire, and Brief Pain Inventory at Baseline and Weeks 1, 2, 3, 4, and 8. Participants continually wore an Oura Ring to objectively assess sleep and daytime activity. The data were collected from January 2022 to April 2022 and were stored electronically. Repeated‐measures analyses of variance were used to analyze mean time differences. Results Self‐reported sleep quality, perceived pain, perceived stress, mood, and daytime fatigue improved significantly from Baseline to Week 8, p's

Catheter-associated right atrial thrombus (CRAT) is a potential complication of central venous catheter placement and is associated with an increase in morbidity and mortality. The precise incidence of CRAT is unknown, and there is a lack of clear screening and management guidelines for this condition. Additionally, the diagnosis is often missed when using transthoracic echocardiography (TTE) alone. Here, we present a case of a 64-year-old female admitted to the medical intensive care unit with multiorgan dysfunction who was diagnosed with hemodialysis catheter-associated right atrial thrombus (HDCRAT) via intensivist-performed point of care transesophageal echocardiography (TEE) after an initial TTE was negative. This patient was successfully treated with systemic anticoagulation, local thrombolysis, and delayed removal of the temporary hemodialysis catheter. Our experience serves to highlight the improved visualization of the right atrium and the diagnostic superiority of HDCRAT with TEE. We suspect that with greater utilization of TEE among intensivists, CRAT and HDCRAT will have increased recognition. It is imperative that intensivists are aware of this complication and various management strategies. Still, more studies are needed to establish clear management guidelines for CRAT and the associated complications.

Introduction In over 50 years since the genetic counseling (GC) profession began, a systematic study of GC communication skills and patient-reported outcomes in actual sessions across multiple clinical specialties has never been conducted. To optimize GC quality and improve efficiency of care, the field must first be able to comprehensively measure GC skills and determine which skills are most critical to achieving positive patient experiences and outcomes. This study aims to characterise GC communication skills using a novel and pragmatic measure and link variations in communication skills to patient-reported outcomes, across clinical specialties and with patients from diverse backgrounds in the USA. Our community-engagement and provider-engagement approach is crucial to develop recommendations for quality, culturally informed GC care, which are greatly needed to improve GC practice.Methods and analysis A mixed methods, sequential explanatory design will be used to collect and analyze: audio-recorded GC sessions in cancer, cardiac, and prenatal/reproductive genetic indications; pre-visit and post-visit quantitative surveys capturing patient experiences and outcomes and post-visit qualitative interview data. A novel, practical checklist will measure GC communication skills. Coincidence analysis will identify patterns of GC skills that are consistent with high scores on patient-reported measures. Two-level, multilevel models will be used to evaluate how GC communication skills and other session/patient characteristics predict patient-reported outcomes. Four community advisory boards (CABs) and a genetic counselor advisory board will inform the study design and analysis.Ethics and dissemination This study has been approved by the single Institutional Review Board of the University of Minnesota. This research poses no greater than minimal risk to participants. Results from this study will be shared through national and international conferences and through community-based dissemination as guided by the study’s CABs. A lay summary will also be disseminated to all participants.

Background: Human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC) remains a treatment-resistance disease with limited response to immunotherapy. While T cells in HNSCC are known to display phenotypic dysfunction, whether they retain rescuable functional capacity and tumor-killing capability remains unclear. Methods: To investigate the functionality and tumor-specificity of tumor-infiltrating lymphocytes (TILs) across HNSCCs, malignant cell lines and TILs were derived from 31 HPV-negative HNSCCs at the time of standard surgical resection. T cell functional capacity was evaluated through ex vivo expansion, immunophenotyping, and IsoLight single-cell proteomics. Tumor-specificity was investigated through both bulk and single-cell tumor-TIL co-culture. Results: TILs could be successfully generated from 24 patients (77%), including both previously untreated and radiation recurrent HNSCCs. We demonstrate that across HNSCCs, TILs express multiple exhaustion markers but maintain a predominantly effector memory phenotype. After ex vivo expansion, TILs retain immunogenic functionality even from radiation-resistant, exhausted, and T cell-depleted disease. We further demonstrate tumor-specificity of T cells across HNSCC patients through patient-matched malignant cell-T cell co-culture. Finally, we use optofluidic technology to establish an autologous single tumor cell-single T cell co-culture platform for HNSCC. Cells derived from three HNSCC patients underwent single-cell co-culture which enabled identification and visualization of individual tumor-killing TILs in real-time in all patients. Conclusions: These studies show that cancer-specific T cells exist across HNSCC patients with rescuable immunogenicity and can be identified on a single-cell level. These data lay the foundation for development of patient-specific T cell immunotherapies in HNSCC.

Abstract Background Memory CD8+ T cells expand with age. We previously demonstrated an age-associated expansion of effector memory (EM) CD8+ T cells expressing low levels of IL-7 receptor alpha (IL-7Rαlow) and the presence of its gene signature (i.e., IL-7Rαlow aging genes) in peripheral blood of older adults without Alzheimer’s disease (AD). Considering age as the strongest risk factor for AD and the recent finding of EM CD8+ T cell expansion, mostly IL-7Rαlow cells, in AD, we investigated whether subjects with AD have alterations in IL-7Rαlow aging gene signature, especially in relation to genes possibly associated with AD and disease severity. Results We identified a set of 29 candidate genes (i.e., putative AD genes) which could be differentially expressed in peripheral blood of patients with AD through the systematic search of publicly available datasets. Of the 29 putative AD genes, 9 genes (31%) were IL-7Rαlow aging genes (P

Nirmatrelvir/ritonavir (PAXLOVIDTM, Pfizer) is an anti-infective inhibiting CYP3A4 indicated for the treatment of COVID-19 in adults at increased risk of severe COVID-19. As a newly approved product, PAXLOVID has limited safety information regarding rare events and serious adverse events (SAEs). This review describes the characterization of the real-world safety profile of products with similar pharmacological properties to PAXLOVID and aims to understand the impact of any drug interaction on the concomitantly prescribed products. A literature search of articles in PubMed published between 2018 and 2023 was conducted to assess the real-world frequency of safety outcomes of interest, specifically those meeting the criteria of serious adverse reaction. The review was restricted to observational, noninterventional studies and included CYP3A4 inhibitors prescribed for short-term treatment of infections in the outpatient setting. Twenty-one articles were included in the review. Most focused on a small, predefined list of safety outcomes and did not provide insight into the broader range of safety outcomes that might occur for the evaluated products with similar pharmacological properties to PAXLOVID or the impact of any interaction on the concomitant product. The findings highlight the challenges in obtaining proxy safety outcomes characteristics via a review of products with comparable pharmacological properties and underscore the need to have large, rapidly accessible data sources that can contribute to the safety profile of newly authorized products in the real world.

Abstract Background Maternal obesity and advanced age have been associated with an increased risk of structural congenital heart defects in the offspring. Whether these factors may also cause abnormalities in infant cardiac dimension and function is unknown. This study investigates whether maternal body mass index (BMI) and maternal age are associated with changes in left ventricular (LV) dimensions and function in the newborn. Methods Infants enrolled in the Copenhagen Baby Heart Study (CBHS), who were born at term, and contributed with a transthoracic echocardiography (TTE) within 60 days of birth were included. The exposure variables were prepregnancy maternal BMI (kg/m2)

ABSTRACT: In the United States, lactation milk yields are not measured directly but are calculated from the test-day milk yields. Still, test-day milk yields are estimated from partial yields obtained from single milkings. Various methods have been proposed to estimate test-day milk yields, primarily to deal with unequal milking intervals dating back to the 1970s and 1980s. The Wiggans model is a de facto method for estimating test-day milk yields in the United States, which was initially proposed for cows milked 3 times daily, assuming a linear relationship between a proportional test-day milk yield and milking interval. However, the linearity assumption did not hold precisely in Holstein cows milked twice daily because of prolonged and uneven milking intervals. The present study reviewed and evaluated the nonlinear models that extended the Wiggans model for estimating daily or test-day milk yields. These nonlinear models, except step functions, demonstrated smaller errors and greater accuracies for estimated test-day milk yields compared with the conventional methods. The nonlinear models offered additional benefits. For example, the locally weighted regression model (e.g., locally estimated scatterplot smoothing) could utilize data information in scalable neighborhoods and weigh observations according to their distance in milking interval time. General additive models provide a flexible, unified framework to model nonlinear predictor variables additively. Another drawback of the conventional methods is a loss of accuracy caused by discretizing milking interval time into large bins while deriving multiplicative correction factors for estimating test-day milk yields. To overcome this problem, we proposed a general approach that allows milk yield correction factors to be derived for every possible milking interval time, resulting in more accurately estimated test-day milk yields. This approach can be applied to any model, including nonparametric models.

Abstract Broadly neutralizing monoclonal antibodies (mAbs) are being developed for HIV-1 prevention. Hence, these mAbs and licensed oral pre-exposure prophylaxis (PrEP) (tenofovir-emtricitabine) can be concomitantly administered in clinical trials. In 48 US participants (men and transgender persons who have sex with men) who received the HIV-1 mAb VRC01 and remained HIV-free in an antibody-mediated-prevention trial (ClinicalTrials.gov #NCT02716675), we conduct a post-hoc analysis and find that VRC01 clearance is 0.08 L/day faster (p = 0.005), and dose-normalized area-under-the-curve of VRC01 serum concentration over-time is 0.29 day/mL lower (p

Abstract Background The objective of the Heartland Study is to address major knowledge gaps concerning the health effects of herbicides on maternal and infant health. To achieve this goal, a two-phased, prospective longitudinal cohort study is being conducted. Phase 1 is designed to evaluate associations between biomarkers of herbicide concentration and pregnancy/childbirth outcomes. Phase 2 is designed to evaluate potential associations between herbicide biomarkers and early childhood neurological development. Methods People (target enrollment of 2,000) who are seeking prenatal care, are ages 18 or older, and are ≤ 20 + 6 weeks gestation will be eligible for recruitment. The Heartland Study will utilize a combination of questionnaire data and biospecimen collections to meet the study objectives. One prenatal urine and buccal sample will be collected per trimester to assess the impact of herbicide concentration levels on pregnancy outcomes. Infant buccal specimens will be collected post-delivery. All questionnaires will be collected by trained study staff and clinic staff will remain blinded to all individual level research data. All data will be stored in a secure REDCap database. Hospitals in the agriculturally intensive states in the Midwestern region will be recruited as study sites. Currently participating clinical sites include Indiana University School of Medicine- affiliated Hospitals in Indianapolis, Indiana; Franciscan Health Center in Indianapolis, Indiana; Gundersen Lutheran Medical Center in La Crosse, Wisconsin, and University of Iowa in Iowa City, Iowa. An anticipated 30% of the total enrollment will be recruited from rural areas to evaluate herbicide concentrations among those pregnant people residing in the rural Midwest. Perinatal outcomes (e.g. birth outcomes, preterm birth, preeclampsia, etc.) will be extracted by trained study teams and analyzed for their relationship to herbicide concentration levels using appropriate multivariable models. Discussion Though decades of study have shown that environmental chemicals may have important impacts on the health of parents and infants, there is a paucity of prospective longitudinal data on reproductive impacts of herbicides. The recent, rapid increases in herbicide use across agricultural regions of the United States necessitate further research into the human health effects of these chemicals, particularly in pregnant people. The Heartland Study provides an invaluable opportunity to evaluate health impacts of herbicides during pregnancy and beyond. Trial registration The study is registered at clinicaltrials.gov, NCT05492708 with initial registration and release 05 August, 2022.

Abstract Background Teledermatology (TD) is an evidence-based practice that may increase access to dermatologic care. We sought to use the Exploration, Preparation, Implementation, and Sustainment (EPIS) and the Reach, Efficacy, Adoption, Implementation, and Maintenance (RE-AIM) frameworks to evaluate implementation of TD at Duke. Methods The EPIS and RE-AIM frameworks were deployed to design and implement a TD program that leveraged the strengths of the Duke University Health System and addressed previously reported barriers to implementation of store-and-forward and synchronous TD models. In the resultant hybrid TD model, trained primary care providers (PCPs) sent e-comm referrals with clinical and dermatoscopic images to dermatology. These e-consults were reviewed asynchronously and patients were scheduled for a synchronous video visit with dermatology within days. Dermatologists managed the patient plan. This hybrid TD model was piloted at four primary care clinics. Pertinent outcomes from a TD-adapted RE-AIM framework were tracked using electronic health record data. Patient satisfaction was assessed using a post-video visit survey (n = 18). Implementation barriers and facilitators were also collected through provider surveys (n = 24 PCPs, n = 10 dermatologists, n = 10 dermatology residents). Results At four PCP clinics throughout 9/1/2021–4/30/2022, there were 218 TD referrals. Video visits occurred on average 7.5 ± 0.5 days after referral and 18/18 patients completing the post-visit survey were satisfied. Adoption varied between clinics, with one placing 22% of all dermatology referrals as TD and another placing 2%. The primary PCP barriers to TD were time burdens, lack of fit in clinic flow, and discomfort with image taking. Top-endorsed potential facilitating interventions included allowing for rash referrals without dermoscopy and assurance for clinical evaluation within 3 days. Conclusions The use of implementation science frameworks allowed for identification of system and contextual strengths which informed the hybrid TD pilot. Barriers and facilitating interventions will provide guidance for expansion and ongoing maintenance of TD.

Nilotinib, a tyrosine kinase inhibitor that targets the Abelson tyrosine kinase (c-Abl) signaling pathway, is FDA-approved to treat chronic myeloid leukemia. Nilotinib has properties indicative of a possible utility in neuroprotection that have prompted exploration of repurposing the drug for the treatment of Alzheimer’s disease (AD) and Parkinson’s disease (PD). AD is a progressive age-related neurodegenerative disorder characterized by the deposition of extracellular amyloid-β plaques and intracellular neurofibrillary tangles. It is incurable and affects approximately 50 million patients worldwide. Nilotinib reduces c-Abl phosphorylation, amyloid-β levels, and dopaminergic neuron degeneration in preclinical AD models. This study explores the effects of nilotinib on amyloid processing and mitochondrial functioning in the SH-SY5Y human neuroblastoma cell line. SH-SY5Y cells were exposed to nilotinib (1, 5, and 10 µM). Real-time PCR and immunoblot analysis were performed to quantify the expression of genes pertaining to amyloid-β processing and neuronal health. Nilotinib did not significantly change APP, BACE1, or ADAM10 mRNA levels. However, BACE1 protein was significantly increased at 1 µM, and ADAM10 was increased at 10 µM nilotinib without affecting APP protein expression. Further, nilotinib treatment did not affect the expression of genes associated with neuronal health and mitochondrial functioning. Taken together, our findings do not support the efficacy of nilotinib treatment for neuroprotection.

In many financial markets across the globe, full historical position disclosure is not required of mutual funds, or it is subject to prolonged delays, often due to regulatory restrictions. This makes measuring fund manager performance based upon the stock-picking and market-timing skills from past literatures impossible. This study introduces a new methodology utilizing sector weight analysis to estimate the stock-picking and market timing skills of 198 Chinese equity mutual fund managers. Within-sample predictions confirm that the new measures are robust and reliably identify fund managers who outperform their peers, suggesting that this method may be useful in other institutional settings where the full historical position of funds is unavailable. Fund managers with lower stock picking or market timing skills are more likely to improve their skills in the following period, which suggests that manager skills develop and change over time. Finally, our analysis reveals that fund managers with higher stock picking skills are significantly less likely to be replaced, thereby enjoying greater job security.

Whole genome sequencing is replacing traditional laboratory surveillance methods as the primary tool to track and characterize clusters and outbreaks of the foodborne and zoonotic pathogen Salmonella enterica (S. enterica). In this study, 438 S. enterica isolates representing 35 serovars and 13 broad vehicle categories from one hundred epidemiologically confirmed outbreaks were evaluated for genetic variation to develop epidemiologically relevant interpretation guidelines for Salmonella disease cluster detection. The Illumina sequences were analyzed by core genome multi-locus sequence typing (cgMLST) and screened for antimicrobial resistance (AR) determinants and plasmids. Ninety-three of the one hundred outbreaks exhibited a close allele range (less than 10 allele differences with a subset closer than 5). The remaining seven outbreaks showed increased variation, of which three were considered polyclonal. A total of 16 and 28 outbreaks, respectively, showed variations in the AR and plasmid profiles. The serovars Newport and I 4,[5],12:i:-, as well as the zoonotic and poultry product vehicles, were overrepresented among the outbreaks, showing increased variation. A close allele range in cgMLST profiles can be considered a reliable proxy for epidemiological relatedness for the vast majority of S. enterica outbreak investigations. Variations associated with mobile elements happen relatively frequently during outbreaks and could be reflective of changing selective pressures.

Abstract Urbanization is homogenizing residential developments and soils across a wide climate gradient of the United States. Land development practices commonly install landscapes on low-quality compacted fill material. While previous research shows that soil quality beneath urban lawns improves over time, studies used golf courses to represent lawns or sampled across variable development and management styles. Limited data on sandy soil quality within residential landscapes in subtropical climate warranted investigation. To evaluate the effect of age on residential soil characteristics, two residential developments from Central and Southwest Florida were selected based on known lot ages up to 31 years. Soil samples (0 to 30 cm) were collected from landscape beds and lawns, along with lawn of common areas, to evaluate bulk density and organic matter over time. Though landscape beds typically require less management, soil characteristics were similar between lawns and landscape beds, suggesting similar processes. Bulk densities decreased by 22–34% and 9–20% within the upper (0–15 cm) and lower (15–30 cm) soil depths, respectively. Upper layer soil carbon accumulation rates ranged from 0.060 to 0.156 kg C m−2 yr−1, comparable to previous studies but did not exceed 0.021 kg C m−2 yr−1 or were not significant for greater depths. The results of this study are representative of past chronosequence studies conducted in cooler climates with fine soil texture. Sandy soil texture and warm climate do not govern carbon sequestration rates, but instead vegetation type and landscape management practices overcome these conditions.

Genomic characterization of an Escherichia coli O157:H7 strain linked to leafy greens–associated outbreaks dates its emergence to late 2015. One clade has notable accessory genomic content and a previously described mutation putatively associated with increased arsenic tolerance. This strain is a reoccurring, emerging, or persistent strain causing illness over an extended period.

Abstract We analyzed 5 years (2016–2020) of nested Canadian data from the Study for Monitoring Antimicrobial Resistance Trends (SMART) to identify pathogen predominance and antimicrobial resistance (AMR) patterns of adult Gram-negative infections in Canadian health care and to complement other public surveillance programs and studies in Canada. A total of 6853 isolates were analyzed from medical (44%), surgical (18%), intensive care (22%) and emergency units (15%) and from respiratory tract (36%), intra-abdominal (25%), urinary tract (24%) and bloodstream (15%) infections. Overall, E. coli (36%), P. aeruginosa (18%) and K. pneumoniae (12%) were the most frequent isolates and P. aeruginosa was the most common respiratory pathogen. 18% of Enterobacterales species were ESBL positive. Collective susceptibility profiles showed that P. aeruginosa isolates were highly susceptible (> 95%) to ceftolozane/tazobactam and colistin, though markedly less susceptible (58–74%) to other antimicrobials tested. Multi-drug resistance (MDR) was present in 10% of P. aeruginosa isolates and was more frequent in those from respiratory infections and from ICU than non-ICU locations. Of P. aeruginosa isolates that were resistant to combinations of ceftazidime, piperacillin/tazobactam and meropenem, 73–96% were susceptible to ceftolozane/tazobactam over the period of the study. These national data can now be combined with clinical prediction rules and genomic data to enable expert antimicrobial stewardship applications and guide treatment policies to optimize adult patient care.

Abstract Background Logic models map the short-term and long-term outcomes that are expected to occur with a program, and thus are an essential tool for evaluation. Funding agencies, especially in the United States (US), have encouraged the use of logic models among their grantees. They also use logic models to clarify expectations for their own funding initiatives. It is increasingly recognized that logic models should be developed through a participatory approach which allows input from those who carry out the program being evaluated. While there are many positive examples of participatory logic modeling, funders have generally not engaged grantees in developing the logic model associated with their own initiatives. This article describes an instance where a US funder of a multi-site initiative fully engaged the funded organizations in developing the initiative logic model. The focus of the case study is Implementation Science Centers in Cancer Control (ISC3), a multi-year initiative funded by the National Cancer Institute. Methods The reflective case study was collectively constructed by representatives of the seven centers funded under ISC3. Members of the Cross-Center Evaluation (CCE) Work Group jointly articulated the process through which the logic model was developed and refined. Individual Work Group members contributed descriptions of how their respective centers reviewed and used the logic model. Cross-cutting themes and lessons emerged through CCE Work Group meetings and the writing process. Results The initial logic model for ISC3 changed in significant ways as a result of the input of the funded groups. Authentic participation in the development of the logic model led to strong buy-in among the centers, as evidenced by their utilization. The centers shifted both their evaluation design and their programmatic strategy to better accommodate the expectations reflected in the initiative logic model. Conclusions The ISC3 case study demonstrates how participatory logic modeling can be mutually beneficial to funders, grantees and evaluators of multi-site initiatives. Funded groups have important insights about what is feasible and what will be required to achieve the initiative’s stated objectives. They can also help identify the contextual factors that either inhibit or facilitate success, which can then be incorporated into both the logic model and the evaluation design. In addition, when grantees co-develop the logic model, they have a better understanding and appreciation of the funder’s expectations and thus are better positioned to meet those expectations.

Abstract While historically viewed as an insulin insensitive organ, it is now accepted that insulin has a role in brain physiology. Changes in brain insulin and IGF1 signaling have been associated with neurological diseases, however the molecular factors regulating brain insulin sensitivity remain uncertain. In this study, we proposed that a recently described protein, termed Inceptor, may play a role in brain insulin and IGF1 resistance. We studied Inceptor in healthy and diseased nervous tissue to understand the distribution of the protein and examine how it may change in states of insulin resistance. We found that Inceptor is in fact present in cerebellum, hippocampus, hypothalamus, and cortex of the brain in neurons, with higher levels in cortex of female compared to male mice. We also confirmed that Inceptor colocalized with IR and IGF1R in brain. We saw little difference in insulin receptor signaling following Inceptor knockdown in neuron cultures, or in Inceptor levels with high-fat diet in mouse or Alzheimer’s disease in mouse or human tissue. These results all provide significant advancements to our understanding of Inceptor in the brain. Protocol registration The Stage 1 registered report manuscript was accepted-in-principle on 9 August 2022. This manuscript was registered through Open Science Forum (OSF) on 24 August 2022 and is available here: https://osf.io/9q8sw .

Pacific Island countries have experienced periodic dengue, chikungunya and Zika outbreaks for decades. The prevention and control of these mosquito-borne diseases rely heavily on control of Aedes aegypti mosquitoes, which in most settings are the primary vector. Introgression of the intracellular bacterium Wolbachia pipientis (wMel strain) into Ae. aegypti populations reduces their vector competence and consequently lowers dengue incidence in the human population. Here we describe successful area-wide deployments of wMel-infected Ae. aegypti in Suva, Lautoka, Nadi (Fiji), Port Vila (Vanuatu) and South Tarawa (Kiribati). With community support, weekly releases of wMel-infected Ae. aegypti mosquitoes for between 2 to 5 months resulted in wMel introgression in nearly all locations. Long term monitoring confirmed a high, self-sustaining prevalence of wMel infecting mosquitoes in almost all deployment areas. Measurement of public health outcomes were disrupted by the Covid19 pandemic but are expected to emerge in the coming years.

Abstract Species distribution models (SDMs) are used to map and predict the geographic distributions of animals based on environmental covariates. Typically, SDMs require high‐resolution habitat data and time series information on animal locations. For data‐limited regions, defined as having scarce habitat or animal survey data, modeling is more challenging, often failing to incorporate important environmental attributes. For example, for sea otters (Enhydra lutris), a federally protected keystone species with variable population trends across the species' range, predictive modeling of distributions has been successfully conducted in areas with robust sea otter population and habitat data. We used open‐access data and employed a presence‐only model, maximum entropy (MaxEnt), to investigate subtidal habitat associations (substrate and algal cover, bathymetry, and rugosity) of northern sea otters (E. lutris kenyoni) for a data‐limited ecosystem, represented by Kachemak Bay, Alaska. Habitat association results corroborated previous findings regarding the importance of bathymetry and understory kelp as predictors of sea otter presence. Novel associations were detected as filamentous algae and shell litter were positively and negatively associated with northern sea otter presence, respectively, advancing existing knowledge of sea otter benthic habitat associations useful for predicting habitat suitability. This study provides a quantitative framework for conducting species distribution modeling with limited temporal and spatial animal distribution and abundance data. Utilizing drop camera information, our novel approach allowed for a better understanding of habitat requirements for a stable northern sea otter population, including bathymetry, understory kelp, and filamentous algae as positive predictors of sea otter presence in Kachemak Bay, Alaska.

Identifying motivation for enrollment in MOOCs has been an important way to predict participant success rates. But themes for motivation have largely centered around themes for enrolling in any MOOC, and not ones specific to the course being studied. In this study, qualitatively coding discussion forums was combined with topic modeling to identify participants’ motivation for enrolling in two successive statistics education professional development online courses. Computational text mining, such as topic modeling, is a learning analytics field that has proven effective in analyzing large volumes of text to automatically identify topics or themes. This contrasts with traditional qualitative approaches, in which researchers manually apply labels (or codes) to parts of text to identify common themes. Combining topic modeling and qualitative research may prove useful to education researchers and practitioners in better understanding and improving online learning contexts that feature asynchronous discussion. Three topic modeling approaches were used in this study, including both unsupervised and semi-supervised modeling techniques. The three topic modeling approaches were validated and compared to determine which participants were assigned motivation themes that most closely aligned to their posts made in an introductory discussion forum. A discussion of how each technique can be useful for identifying topical themes within discussion forum data is included. Though the three techniques have varying success rates in identifying motivation for enrolling in the MOOCs, they do all identify similar themes for motivation that are specific to statistics education.

Aim of the study: Survival to hospital discharge from out-of-hospital cardiac arrest (OHCA) after receiving treatment from emergency medical services (EMS) is less than 10% in the United States. Community-focused interventions improve survival rates, but there is limited information on how to gain support for new interventions or program activities within these populations. Using data from the RAndomized Cluster Evaluation of Cardiac ARrest Systems (RACE-CARS) trial, we aimed to identify the factors influencing emergency response agencies’ support in implementing an OHCA intervention. Methods: North Carolina counties were stratified into high-performing or low-performing counties based on the county’s cardiac arrest volume, percent of bystander-cardiopulmonary resuscitation (CPR) performed, patient survival to hospital discharge, cerebral performance in patients after cardiac arrest, and perceived engagement in the RACE-CARS project. We randomly selected 4 high-performing and 3 low-performing counties and conducted semi-structured qualitative interviews with emergency response stakeholders in each county. Results: From 10/2021 to 02/2022, we completed 29 interviews across the 7 counties (EMS (n = 9), telecommunications (n = 7), fire/first responders (n = 7), and hospital representatives (n = 6)). We identified three themes salient to community support for OHCA intervention: (1) initiating support at emergency response agencies; (2) obtaining support from emergency response agency staff (senior leadership and emergency response teams); and (3) and maintaining support. For each theme, we described similarities and differences by high- and low-performing county. Conclusions: We identified techniques for supporting effective engagement of emergency response agencies in community-based interventions for OHCA improving survival rates. This work may inform future programs and initiatives around implementation of community-based interventions for OHCA.

Abstract The crustal evolution of the southernmost ∼2000–1800 Ma Trans‐Hudson orogen (THO) is enigmatic due to burial by Phanerozoic sediments. We provide new insights through petrochronologic analysis of a paragneiss drill core sample. Detrital zircon age peaks at 2625, 2340, and 1880 Ma and Hf isotopes suggest Paleoproterozoic arc development proximal to Archean source(s). Phase equilibria modeling and ternary feldspar thermometry suggest peak conditions of ≥1 GPa, ≥900°C, the first recognition of extreme, ultra‐high temperature metamorphism in the THO. The largely isobaric P‐T path, rapid heating rate, and ∼20 Myr duration (1872–1850 Ma) of peak conditions suggest that this metamorphism occurred in a back‐arc tectonic setting. The sample records post‐peak (1850–1815 Ma) mid‐crustal residence, slow cooling, and exhumation. Further retrogression occurred during Proterozoic regional exhumation (1630–1470 Ma) and Phanerozoic (360–220 Ma) reheating and/or fluid influx. Evidence for Paleoproterozoic arc(s) supports geophysical data for Archean cratonic and Paleoproterozoic arc crust in this region.

Objectives A national survey aimed to measure how men with prostate cancer perceived their involvement in and decisions around their care immediately after diagnosis. This study aimed to describe any differences found by socio-demographic groups.Design Cross-sectional study of men who were diagnosed with and treated for prostate cancer.Setting The National Prostate Cancer Audit patient-reported experience measures (PREMs) survey in England.Participants Men diagnosed in 2014–2016, with non-metastatic prostate cancer, were surveyed. Responses from 32 796 men were individually linked to records from a national clinical audit and to administrative hospital data. Age, ethnicity, deprivation and disease risk classification were used to explore variation in responses to selected questions.Primary and secondary outcome measures Responses to five questions from the PREMs survey: the proportion responding to the highest positive category was compared across the socio-demographic characteristics above.Results When adjusted for other factors, older men were less likely than men under the age of 60 to feel side effects had been explained in a way they could understand (men 80+: relative risk (RR)=0.92, 95% CI 0.84 to 1.00), that their views were considered (RR=0.79, 95% CI 0.73 to 0.87) or that they were involved in decisions (RR=0.92, 95% CI 0.85 to 1.00). The latter was also apparent for men who were not white (black men: RR=0.89, 95% CI 0.82 to 0.98; Asian men: RR=0.85, 95% CI 0.75 to 0.96) and, to a lesser extent, for more deprived men.Conclusions The observed discrepancies highlight the need for more focus on initiatives to improve the experience of ethnic minority patients and those older than 60 years. The findings also argue for further validation of discriminatory instruments to help cancer care providers fully understand the variation in the experience of their patients.

Rapid conversion of force into a biological signal enables living cells to respond to mechanical forces in their environment. The force is believed to initially affect the plasma membrane and then alter the behavior of membrane proteins. Phospholipase D2 (PLD2) is a mechanosensitive enzyme that is regulated by a structured membrane-lipid site comprised of cholesterol and saturated ganglioside (GM1). Here we show stretch activation of TWIK-related K+ channel (TREK-1) is mechanically evoked by PLD2 and spatial patterning involving ordered GM1 and 4,5-bisphosphate (PIP2) clusters in mammalian cells. First, mechanical force deforms the ordered lipids, which disrupts the interaction of PLD2 with the GM1 lipids and allows a complex of TREK-1 and PLD2 to associate with PIP2 clusters. The association with PIP2 activates the enzyme, which produces the second messenger phosphatidic acid (PA) that gates the channel. Co-expression of catalytically inactive PLD2 inhibits TREK-1 stretch currents in a biological membrane. Cellular uptake of cholesterol inhibits TREK-1 currents in culture and depletion of cholesterol from astrocytes releases TREK-1 from GM1 lipids in mouse brain. Depletion of the PLD2 ortholog in flies results in hypersensitivity to mechanical force. We conclude PLD2 mechanosensitivity combines with TREK-1 ion permeability to elicit a mechanically evoked response.

ABSTRACT Wolbachia are a genus of insect endosymbiotic bacteria which includes strains wMel and wAlbB that are being utilized as a biocontrol tool to reduce the incidence of Aedes aegypti-transmitted viral diseases like dengue. However, the precise mechanisms underpinning the antiviral activity of these Wolbachia strains are not well defined. Here, we generated a panel of Ae. aegypti-derived cell lines infected with antiviral strains wMel and wAlbB or the non-antiviral Wolbachia strain wPip to understand host cell morphological changes specifically induced by antiviral strains. Antiviral strains were frequently found to be entirely wrapped by the host endoplasmic reticulum (ER) membrane, while wPip bacteria clustered separately in the host cell cytoplasm. ER-derived lipid droplets (LDs) increased in volume in wMel- and wAlbB-infected cell lines and mosquito tissues compared to cells infected with wPip or Wolbachia-free controls. Inhibition of fatty acid synthase (required for triacylglycerol biosynthesis) reduced LD formation and significantly restored ER-associated dengue virus replication in cells occupied by wMel. Together, this suggests that antiviral Wolbachia strains may specifically alter the lipid composition of the ER to preclude the establishment of dengue virus (DENV) replication complexes. Defining Wolbachia’s antiviral mechanisms will support the application and longevity of this effective biocontrol tool that is already being used at scale.IMPORTANCEAedes aegypti transmits a range of important human pathogenic viruses like dengue. However, infection of Ae. aegypti with the insect endosymbiotic bacterium, Wolbachia, reduces the risk of mosquito to human viral transmission. Wolbachia is being utilized at field sites across more than 13 countries to reduce the incidence of viruses like dengue, but it is not well understood how Wolbachia induces its antiviral effects. To examine this at the subcellular level, we compared how different strains of Wolbachia with varying antiviral strengths associate with and modify host cell structures. Strongly antiviral strains were found to specifically associate with the host endoplasmic reticulum and induce striking impacts on host cell lipid droplets. Inhibiting Wolbachia-induced lipid redistribution partially restored dengue virus replication demonstrating this is a contributing role for Wolbachia's antiviral activity. These findings provide new insights into how antiviral Wolbachia strains associate with and modify Ae. aegypti host cells.

IntroductionThe Veterans Health Administration (VHA) Diffusion of Excellence (DoE) program provides a system to identify, replicate, and spread promising practices across the largest integrated healthcare system in the United States. DoE identifies innovations that have been successfully implemented in the VHA through a Shark Tank style competition. VHA facility and regional directors bid resources needed to replicate promising practices. Winning facilities/regions receive external facilitation to aid in replication/implementation over the course of a year. DoE staff then support diffusion of successful practices across the nationwide VHA.MethodsOrganized around the Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) Framework, we summarize results of an ongoing long-term mixed-methods implementation evaluation of DoE. Data sources include: Shark Tank application and bid details, tracking practice adoptions through a Diffusion Marketplace, characteristics of VHA facilities, focus groups with Shark Tank bidders, structured observations of DoE events, surveys of DoE program participants, and semi-structured interviews of national VHA program office leaders, VHA healthcare system/facility executives, practice developers, implementation teams and facilitators.ResultsIn the first eight Shark Tanks (2016–2022), 3,280 Shark Tank applications were submitted; 88 were designated DoE Promising Practices (i.e., practices receive facilitated replication). DoE has effectively spread practices across the VHA, with 1,440 documented instances of adoption/replication of practices across the VHA. This includes 180 adoptions/replications in facilities located in rural areas. Leadership decisions to adopt innovations are often based on big picture considerations such as constituency support and linkage to organizational goals. DoE Promising Practices that have the greatest national spread have been successfully replicated at new sites during the facilitated replication process, have close partnerships with VHA national program offices, and tend to be less expensive to implement. Two indicators of sustainment indicate that 56 of the 88 Promising Practices are still being diffused across the VHA; 56% of facilities originally replicating the practices have sustained them, even up to 6 years after the first Shark Tank.ConclusionDoE has developed a sustainable process for the identification, replication, and spread of promising practices as part of a learning health system committed to providing equitable access to high quality care.

Context: Governments made emergency declarations to restrict the presence of family carers in long-term care homes (LTCHs) as part of infection control measures during the pandemic. Within Canada, two visitor statuses were created: ‘essential’ to the health of the resident and ‘non-essential’ or ‘social visitor’, who were subject to additional restrictions. Objective: This study explored family carers’ experiences navigating in-person access to their relatives in LTCH during the pandemic. Methods: Using interpretive description, a sample of 14 family carers (nine daughters, five spouses) living in British Columbia, Canada, participated in in-depth interviews via video call about their experiences between March 2020 and June 2021. Findings: Analyses illustrated variability in carers’ visitor status across families and over time. Two key themes were identified: 1) “Fighting a Losing Battle” describes how reductionist attitudes and policies minimized the role of caregiving and resulted in traumatic disruptions in familial relationships; 2) “Who’s In and Who’s Out” captures inequities in how visitor status policies were applied. Limitations: Restrictions on conducting research during the pandemic resulted in a smaller sample of family carer participants. Implications: Findings highlight the patchwork implementation of visitor policies over the initial 17 months of the pandemic and the precarious space family carers continue to occupy within the LTC sector. Future research should focus on formalising support for family presence during public health emergencies.

Aims: Children of parents with substance use and/or other mental health (SU/MH) diagnoses are at increased risk for health problems. It is unknown whether these children benefit from receiving primary care at the same clinic as their parents. Thus, among children of parents with >1 SU/MH diagnosis, we examined the association of parent-child clinic concordance with rates of well-child checks (WCCs) and childhood vaccinations. Design: Retrospective cohort study using electronic health record (EHR) data from the OCHIN network of community health organizations (CHOs), 2010-2018. Setting: 280 CHOs across 17 states. Participants/Cases: 41,413 parents with >1 SU/MH diagnosis, linked to 65,417 children aged 0 to 17 years, each with >1 visit to an OCHIN clinic during the study period. Measurements: Dependent variables: rates of WCCs during (1) the first 15 months of life, and (2) ages 3 to 17 years; vaccine completeness (3) by the age of 2, and (4) before the age of 18. Estimates were attained using generalized estimating equations Poisson or logistic regression. Findings: Among children utilizing the same clinic as their parent versus children using a different clinic (reference group), we observed greater WCC rates in the first 15 months of life [adjusted rate ratio (aRR) = 1.06; 95% confidence interval (CI) = 1.02-1.10]; no difference in WCC rates in ages 3 to 17; higher odds for vaccine completion before age 2 [adjusted odds ratio (aOR) = 1.12; 95% CI = 1.03-1.21]; and lower odds for vaccine completion before age 18 (aOR = 0.88; 95% CI = 0.81-0.95). Conclusion: Among children whose parents have at least one SU/MH diagnosis, parent-child clinic concordance was associated with greater rates of WCCs and higher odds of completed vaccinations for children in the youngest age groups, but not the older children. This suggests the need for greater emphasis on family-oriented healthcare for young children of parents with SU/MH diagnoses; this may be less important for older children.

Mapping the connectivity of diverse neuronal types provides the foundation for understanding the structure and function of neural circuits. High-throughput and low-cost neuroanatomical techniques based on RNA barcode sequencing have the potential to map circuits at cellular resolution and a brain-wide scale, but existing Sindbis virus-based techniques can only map long-range projections using anterograde tracing approaches. Rabies virus can complement anterograde tracing approaches by enabling either retrograde labeling of projection neurons or monosynaptic tracing of direct inputs to genetically targeted postsynaptic neurons. However, barcoded rabies virus has so far been only used to map non-neuronal cellular interactions in vivo and synaptic connectivity of cultured neurons. Here we combine barcoded rabies virus with single-cell and in situ sequencing to perform retrograde labeling and transsynaptic labeling in the mouse brain. We sequenced 96 retrogradely labeled cells and 295 transsynaptically labeled cells using single-cell RNA-seq, and 4130 retrogradely labeled cells and 2914 transsynaptically labeled cells in situ. We found that the transcriptomic identities of rabies virus-infected cells can be robustly identified using both single-cell RNA-seq and in situ sequencing. By associating gene expression with connectivity inferred from barcode sequencing, we distinguished long-range projecting cortical cell types from multiple cortical areas and identified cell types with converging or diverging synaptic connectivity. Combining in situ sequencing with barcoded rabies virus complements existing sequencing-based neuroanatomical techniques and provides a potential path for mapping synaptic connectivity of neuronal types at scale.

Sex as a biological variable has been recognized for decades to be a critical aspect of the drug development process, as differences in drug pharmacology and toxicity in female versus male subjects can drive the success or failure of new therapeutics. These concepts in development of traditional drug systems have only recently begun to be applied for advancing nanomedicine systems that are designed for drug delivery or imaging in the central nervous system (CNS). This review provides a comprehensive overview of the current state of two fields of research - nanomedicine and acute brain injury—centering on sex as a biological variable. We highlight areas of each field that provide foundational understanding of sex as a biological variable in nanomedicine, brain development, immune response, and pathophysiology of traumatic brain injury and stroke. We describe current knowledge on female versus male physiology as well as a growing number of empirical reports that directly address sex as a biological variable in these contexts. In sum, the data make clear two key observations. First, the manner in which sex affects nanomedicine distribution, toxicity, or efficacy is important, complex, and depends on the specific nanoparticle system under considerations; second, although field knowledge is accumulating to enable us to understand sex as a biological variable in the fields of nanomedicine and acute brain injury, there are critical gaps in knowledge that will need to be addressed. We anticipate that understanding sex as a biological variable in the development of nanomedicine systems to treat acute CNS injury will be an important determinant of their success.

We present JWST/Mid Infrared Instrument (MIRI) low-resolution spectroscopy (4.75–14 μ m) of the first known substellar companion, Gliese 229Bab, which was recently resolved into a tight binary brown dwarf. Previous atmospheric retrieval studies modeling Gliese 229B as a single brown dwarf have reported anomalously high carbon-to-oxygen ratios (C/O) of ≈1.1 using 1–5 μ m ground-based spectra. Here, we fit the MIRI spectrum of Gliese 229Bab with a two-component binary model using the Sonora Elf Owl grid and additionally account for the observed K -band flux ratio of the binary brown dwarf. Assuming the two brown dwarfs share the same abundances, we obtain C/O = 0.65 ± 0.05 and ${\rm{[M/H]}}=0.0{0}_{-0.03}^{+0.04}$ as their abundances (2 σ statistical errors), which are fully consistent with the host star abundances. We also recover the same abundances if we fit the MIRI spectrum with a single brown dwarf model, indicating that binarity does not strongly affect inferred abundances from mid-infrared data when the T _eff are similar between components of the binary. In addition, we measure ${T}_{\mathrm{eff}}=90{0}_{-29}^{+78}$ K and ${T}_{\mathrm{eff}}=77{5}_{-33}^{+20}$ K for the two brown dwarfs. We find that the vertical diffusion coefficients of $\mathrm{log}{K}_{zz}\approx 4.0$ are identical between the two brown dwarfs and in line with $\mathrm{log}{K}_{zz}$ values inferred for isolated brown dwarfs of similar T _eff . Our results demonstrate the power of mid-infrared spectroscopy in providing robust atmospheric abundance measurements for brown dwarf companions and, by extension, giant planets.

BackgroundVeterans who identify as lesbian, gay, bisexual, transgender, queer, questioning, and related identities (LGBTQ+) have faced discrimination that puts them at increased risk for depression, anxiety, and suicide. Upstream interventions like the PRIDE in All Who Served program can improve internalized prejudice, suicidality, symptoms of depression, and symptoms of anxiety by addressing minority stress, facilitating social connection, and promoting engagement with the healthcare system. Yet, little is known about who benefits most from these types of services.Methods and materialsSixty-six US military veterans (Mean age = 47.06, SD = 13.74) provided outcome surveys before and after a 10-week health promotion group for LGBTQ+ individuals at one of 10 Veterans Health Administration (VA) Medical Centers. Subscales of a coping self-efficacy measure (e.g., problem-solving, social support, thought-stopping), and demographic factors were examined as moderators of treatment outcomes.ResultsCoping self-efficacy moderated effects across treatment outcomes with those lower in coping self-efficacy beliefs reporting the greatest benefit of the intervention. Reduction in anxiety symptoms was moderated only by problem-solving coping self-efficacy, while suicidality was moderated only by social support. Reduction of internalized prejudice and depression symptoms were moderated by both problem-solving and social support coping self-efficacy, while thought-stopping (a frequent target of traditional cognitive therapies) only moderated internalized prejudice, but not clinical symptom indicators. Most demographic factors (e.g., age, race, gender) did not impact treatment outcomes; however, sexual orientation was significant such that those who identified as bisexual, queer, or something else (e.g., pansexual) had greater reductions in internalized prejudice than their single gender-attracted peers.Discussion and conclusionIndividual differences like coping self-efficacy and sexual orientation are rarely considered in clinical care settings when shaping policy or implementing tailored programs. Understanding implications for who is most likely to improve could inform program refinement and implementation of affirming interventions for minoritized people.

Background: As many as 95% of individuals across the lifespan with autism spectrum disorder (ASD) have at least one comorbidity. While research focused only on the health of autistic adolescents is limited, we do know that fewer than 14% of these youth receive appropriate transition services to self-manage their health. These limitations have resulted in poor outcomes and premature mortality. Little is known about how parents and their adolescent children address this health burden. Objective: The objective of this study is twofold. First to compare the perceptions of adolescents with ASD and their parents regarding adolescents’ contextual and process variables (depressive symptoms, health knowledge, health communication/planning, self-efficacy, self-determination) and health self-management (HSM) behavior. The second is to examine social facilitation for HSM behaviors in adolescents with ASD and their parents. Methods: In this community-based study, an online survey was used to compare the perspectives of 40 adolescents with ASD aged 12 to 22 years and their parents on the adolescents’ HSM behaviors. Contextual and process variable measures (PROMISE, Starx, General Self-efficacy Scale, AIR Self-determination Scale, Social Facilitation Questionnaire) were completed by both adolescents (adolescent/pediatric version) and parents (parent version). Results: Descriptive analysis indicated that parents were teaching self-management to adolescents for monitoring and preventing illness, including medication knowledge and how to talk to their doctor. The largest differences were found between parents’ and adolescents’ perceptions regarding teaching and learning about independent management of existing health conditions. Additionally, adolescents rated their self-efficacy (t (38) = 3.62, p

Immune literacy garnered significant attention in recent years due to the threat posed by emerging infectious diseases. The pace of immunological discoveries and their relevance to society are substantial yet coordinated educational efforts have been rare. This motivated us to create a task force of educators to reflect on pedagogical approaches to teaching immunology and to draft, develop, and evaluate key competencies for undergraduate immunology education. The research questions addressed include: 1) Which competencies are considered important by educators? 2) Are the illustrative skills clear, accurate and well aligned with the core competencies listed in the Vision and Change report?; 3) What are the concerns of immunology educators about competencies and skills? We collected data on the draft competencies using surveys, focus groups, and interviews. The iterative revision phase followed the community review phase before finalizing the framework. Here, we report a hierarchical learning framework, with six core competencies, twenty illustrative skills, and companion immunology-specific example learning outcomes. Predominant themes from interviews and focus groups, which informed revisions of this framework are shared. With the growing need for immunology education across the sciences, the ImmunoSkills Guide and accompanying discussion can be used as a resource for educators, administrators and policymakers.

With sizable volatile envelopes but smaller radii than the solar system ice giants, sub-Neptunes have been revealed as one of the most common types of planet in the galaxy. While the spectroscopic characterization of larger sub-Neptunes (2.5–4 R _⊕ ) has revealed hydrogen-dominated atmospheres, smaller sub-Neptunes (1.6–2.5 R _⊕ ) could either host thin, rapidly evaporating, hydrogen-rich atmospheres or be stable, metal-rich “water worlds” with high mean molecular weight atmospheres and a fundamentally different formation and evolutionary history. Here, we present the 0.6–2.8 μ m JWST/NIRISS/SOSS transmission spectrum of GJ 9827 d, the smallest (1.98 R _⊕ ) warm ( T _eq,A=0.3 ∼ 620 K) sub-Neptune where atmospheric absorbers have been detected to date. Our two transit observations with NIRISS/SOSS, combined with the existing HST/WFC3 spectrum, enable us to break the clouds–metallicity degeneracy. We detect water in a highly metal-enriched “steam world” atmosphere (O/H of ∼4 by mass and H _2 O found to be the background gas with a volume mixing ratio of >31%). We further show that these results are robust to stellar contamination through the transit light source effect. We do not detect escaping metastable He, which, combined with previous nondetections of escaping He and H, supports the steam atmosphere scenario. In water-rich atmospheres, hydrogen loss driven by water photolysis happens predominantly in the ionized form, which eludes observational constraints. We also detect several flares in the NIRISS/SOSS light curves with far-UV energies of the order of 10 ^30 erg, highlighting the active nature of the star. Further atmospheric characterization of GJ 9827 d probing carbon or sulfur species could reveal the origin of its high metal enrichment.

Recent mid-infrared observations with JWST's Mid-Infrared Instrument Low Resolution Spectrometer (MIRI LRS) have resulted in the first direct detections of absorption features from silicate clouds in the transmission spectra of two transiting exoplanets, WASP-17 b and WASP-107 b. In this Letter, we measure the mid-infrared (5–12 μ m) dayside emission spectrum of the benchmark hot Jupiter HD 189733 b with MIRI LRS by combining data from two secondary-eclipse observations. We confirm the previous detection of H _2 O absorption at 6.5 μ m from Spitzer's Infrared Spectrograph (IRS) and additionally detect H _2 S as well as an absorption feature at 8.7 μ m in both secondary-eclipse observations. The excess absorption at 8.7 μ m can be explained by the presence of small (∼0.01 μ m) grains of SiO _2 [s] in the uppermost layers of HD 189733 b’s dayside atmosphere. This is the first direct detection of silicate clouds in HD 189733 b’s atmosphere, and the first detection of a distinct absorption feature from silicate clouds on the dayside of any hot Jupiter. We find that models including SiO _2 [s] are preferred by 6–7 σ over clear models and those with other potential cloud species. The high-altitude location of these silicate particles is best explained by formation in the hottest regions of HD 189733 b’s dayside atmosphere near the substellar point. We additionally find that HD 189733 b’s emission spectrum longward of 9 μ m displays residual features not well captured by our current atmospheric models. When combined with other JWST observations of HD 189733 b’s transmission and emission spectra at shorter wavelengths, these observations will provide us with the most detailed picture to date of the atmospheric composition and cloud properties of this benchmark hot Jupiter.

Heart failure (HF) with reduced ejection fraction (HFrEF) is a risk factor for drug-induced QT interval prolongation. It is unknown if HF with preserved ejection fraction (HFpEF) is also associated with an increased risk. Dofetilide and sotalol are potent QT interval-prolonging agents that are frequently used in patients with HFpEF, in whom atrial fibrillation is a common comorbidity. We tested the hypothesis that the risk of QT interval prolongation associated with dofetilide and sotalol is increased in patients with HFpEF. We conducted a retrospective cohort study conducted using electronic health records from the Indiana Network for Patient Care (January 31, 2010 -May 3, 2021). After removing patients with overlapping diagnoses of HFpEF and HFrEF, no diagnosis code, and absence of QT interval records, we identified patients taking dofetilide or sotalol among three groups: HFrEF (n = 138), HFpEF (n = 109), and no HF (n = 729). QT prolongation was defined as heart rate-corrected QT (QTc) > 500 ms during dofetilide/sotalol therapy. Unadjusted odds ratios (OR) for QT prolongation were determined by univariate analysis. Adjusted ORs were determined by generalized estimating equations (GEE) with logit link to account for an individual cluster with different times of hospitalization and covariates. QTc prolongation associated with dofetilide or sotalol occurred in 53.2%, 71.7% and 30.0% of patients with HFpEF, HFrEF, and patients with no HF, respectively. After adjusting for age, sex, race, serum potassium and magnesium concentrations, kidney function, concomitant drug therapy, and comorbid conditions, the adjusted odds of QTc prolongation were significantly higher in patients with HFpEF [OR = 1.98 (95% CI 1.17-3.33)], and in those with HFrEF [OR = 5.23, (3.15-8.67)], compared to those with no evidence of HF. The odds of QT prolongation among inpatients receiving dofetilide or sotalol were increased in patients with HFpEF and HFrEF compared to those who did not have HF.

We report the discovery and characterization of a small planet, TOI-1408 c, on a 2.2 day orbit located interior to a previously known hot Jupiter, TOI-1408 b ( P = 4.42 days, M = 1.86 ± 0.02 M _Jup , R = 2.4 ± 0.5 R _Jup ) that exhibits grazing transits. The two planets are near 2:1 period commensurability, resulting in significant transit timing variations (TTVs) for both planets and transit duration variations for the inner planet. The TTV amplitude for TOI-1408 c is 15% of the planet’s orbital period, marking the largest TTV amplitude relative to the orbital period measured to date. Photodynamical modeling of ground-based radial velocity (RV) observations and transit light curves obtained with the Transiting Exoplanet Survey Satellite and ground-based facilities leads to an inner planet radius of 2.22 ± 0.06 R _⊕ and mass of 7.6 ± 0.2 M _⊕ that locates the planet into the sub-Neptune regime. The proximity to the 2:1 period commensurability leads to the libration of the resonant argument of the inner planet. The RV measurements support the existence of a third body with an orbital period of several thousand days. This discovery places the system among the rare systems featuring a hot Jupiter accompanied by an inner low-mass planet.

The early period of the COVID-19 pandemic limited access to HIV services for children and adolescents living with HIV (C/ALHIV). To determine progress in providing care and treatment services, we describe viral load coverage (VLC) and suppression (VLS) (