Ebola disease outbreak caused by the Sudan virus in Uganda, 2022: a descriptive epidemiological study.

BACKGROUND: Uganda has had seven Ebola disease outbreaks, between 2000 and 2022. On Sept 20, 2022, the Ministry of Health declared a Sudan virus disease outbreak in Mubende District, Central Uganda. We describe the epidemiological characteristics and transmission dynamics. METHODS: For this descriptive study, cases were classified as suspected, probable, or confirmed using Ministry of Health case definitions. We investigated all reported cases to obtain data on case-patient demographics, exposures, and signs and symptoms, and identified transmission chains. We conducted a descriptive epidemiological study and also calculated basic reproduction number (Ro) estimates. FINDINGS: Between Aug 8 and Nov 27, 2022, 164 cases (142 confirmed, 22 probable) were identified from nine (6%) of 146 districts. The median age was 29 years (IQR 20-38), 95 (58%) of 164 patients were male, and 77 (47%) patients died. Symptom onsets ranged from Aug 8 to Nov 27, 2022. The case fatality rate was highest in children younger than 10 years (17 [74%] of 23 patients). Fever (135 [84%] of 160 patients), vomiting (93 [58%] patients), weakness (89 [56%] patients), and diarrhoea (81 [51%] patients) were the most common symptoms; bleeding was uncommon (21 [13%] patients). Before outbreak identification, most case-patients (26 [60%] of 43 patients) sought care at private health facilities. The median incubation was 6 days (IQR 5-8), and median time from onset to death was 10 days (7-23). Most early cases represented health-care-associated transmission (43 [26%] of 164 patients); most later cases represented household transmission (109 [66%]). Overall Ro was 1·25. INTERPRETATION: Despite delayed detection, the 2022 Sudan virus disease outbreak was rapidly controlled, possibly thanks to a low Ro. Children (aged <10 years) were at the highest risk of death, highlighting the need for targeted interventions to improve their outcomes during Ebola disease outbreaks. Initial care-seeking occurred at facilities outside the government system, showing a need to ensure that private and public facilities receive training to identify possible Ebola disease cases during an outbreak. Health-care-associated transmission in private health facilities drove the early outbreak, suggesting gaps in infection prevention and control. FUNDING: None.

When can we trust structural models derived from pair distribution function measurements?

The pair distribution function (PDF) is an important metric for characterising structure in complex materials, but it is well known that meaningfully different structural models can sometimes give rise to equivalent PDFs. In this paper, we discuss the use of model likelihoods as a general approach for discriminating between such homometric structure solutions. Drawing on two main case studies-one concerning the structure of a small peptide and the other amorphous calcium carbonate-we show how consideration of model likelihood can help drive robust structure solution, even in cases where the PDF is particularly information-poor. The obvious thread of these individual case studies is the potential role for machine-learning approaches to help guide structure determination from the PDF, and our paper finishes with some forward-looking discussion along these lines.

Vaginitis and risk of sexually transmitted infections: results of a multi-center U.S. clinical study using STI nucleic acid amplification testing.

Significant increases in rates of sexually transmitted infections (STIs) caused by Trichomonas vaginalis (TV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Mycoplasma genitalium (MG) are occurring in the United States. We present results of a U.S. study examining the intersection of STIs and vaginitis. Among 1,051 women with diagnoses for the presence or absence of bacterial vaginosis (BV) and/or symptomatic vulvovaginal candidiasis (VVC), 195 (18.5%) had one or more STIs, including 101 (9.6%) with TV, 24 (2.3%) with CT, 9 (0.8%) with NG, and 93 (8.8%) with MG. STI prevalence in BV-positive women was 26.3% (136/518), significantly higher than STI prevalence of 12.5% (59/474) in BV-negative women (P < 0.0002). Unlike infections with CT or NG, solo infections of MG or TV were each significantly associated with a diagnosis of BV-positive/VVC-negative (OR 3.0751; 95% CI 1.5797-5.9858, P = 0.0113, and OR 2.873; 95% CI 1.5687-5.2619, P = 0.0017, respectively) and with mixed infections containing MG and TV (OR 3.4886; 95% CI 1.8901-6.439, P = 0.0042, and OR 3.1858; 95% CI 1.809-5.6103, P = 0.0014, respectively). TV and MG infection rates were higher in all Nugent score (NS) categories than CT and NG infection rates; however, both STIs had similar comparative prevalence ratios to CT in NS 6-10 vs NS 0-5 (CT: 3.06% vs 1.4%, 2.2-fold; MG: 10.7% vs 6.1%, 1.8-fold; TV: 14.5% vs 7.0%, 2.1-fold). NG prevalence was relatively invariant by the NS category. These results highlight the complexity of associations of STIs with two major causes of vaginitis and underscore the importance of STI testing in women seeking care for abnormal vaginal discharge and inflammation. IMPORTANCE: This study reports high rates for sexually transmitted infections (STIs) in women seeking care for symptoms of vaginitis and bacterial vaginosis, revealing highly complex associations of STIs with two of the major causes of vaginal dysbiosis. These results underscore the importance of STI testing in women seeking care for abnormal vaginal discharge and inflammation.

Estimates of the excess cost burden of Ehlers-Danlos syndromes: a United States MarketScan® claims database analysis.

Introduction: Patients with Ehlers-Danlos syndromes (EDS) and hypermobility spectrum disorders (HSD) have significant health challenges that are well-documented, however their impact in terms of cost is not known. Our research objective was to examine the cost burden of EDS and HSD in the United States. We focused this analysis on those with commercial insurance plans. Methods: We queried the MarketScan® database for year 2021 for claims that contained an ICD-10 diagnosis code for EDS or hypermobility. Excess costs for patients in the EDS and HSD cohorts were determined by matching each patient to one patient in the database that did not have a claim for EDS or HSD and comparing total costs for the calendar year. We determined whether patients had claims for selected comorbid conditions likely to impact costs during the calendar year. Results: Sample sizes were 5,113 for adult (age ≥ 18) patients with EDS, 4,880 for adult patients with HSD, 1,059 for child (age 5-17) patients with EDS, and 2,427 for child patients with HSD. The mean excess costs were $21,100 for adult EDS patients, $11,600 for adult HSD patients, $17,000 for child EDS patients, and $11,000 for child HSD patients. EDS and HSD cohorts, both adults and children, with any of the comorbidities had greater healthcare costs. The largest difference was found in the EDS cohort with gastrointestinal comorbid conditions, with more than double the costs for adults. Discussion: We found that patients in the MarketScan database, adults and children, who had EDS or HSD had substantially higher associated excess healthcare costs than patients without EDS or HSD when considering age, sex, geographic location, and comorbidities. These disproportionate healthcare costs in this population have health policy and economic implications, including the need for rapid diagnosis, access to treatment, and accelerated research to advance treatments.

Multi-omic analysis of SDHB-deficient pheochromocytomas and paragangliomas identifies metastasis and treatment-related molecular profiles.

Hereditary SDHB-mutant pheochromocytomas (PC) and paragangliomas (PG) are rare tumours with a high propensity to metastasize although their clinical behaviour is unpredictable. To characterize the genomic landscape of these tumours and identify metastasis biomarkers, we performed multi-omic analysis on 94 tumours from 79 patients using seven molecular methods. Sympathetic (chromaffin cell) and parasympathetic (non-chromaffin cell) PCPG had distinct molecular profiles reflecting their cell-of-origin and biochemical profile. TERT and ATRX-alterations were associated with metastatic PCPG and these tumours had an increased mutation load, and distinct transcriptional and telomeric features. Most PCPG had quiet genomes with some rare co-operative driver events observed, including EPAS1/HIF-2α mutations. Two mechanisms of acquired resistance to DNA alkylating chemotherapies were also detected - MGMT overexpression and mismatch repair-deficiency causing hypermutation. Our comprehensive multi-omic analysis of SDHB-mutant PCPG therefore identified features of metastatic disease and treatment response, expanding our understanding of these rare neuroendocrine tumours.

Using Geospatial Analysis to Identify Priority Communities for Cervical Cancer Prevention in Texas.

Introduction: Despite being almost entirely preventable, cervical cancer is the fourth most frequently diagnosed cancer among women worldwide. Cervical cancer incidence suggests missed opportunities for prevention. Geospatial analysis could strategically guide public health interventions. This study aimed to identify geographic clusters of cervical cancer incidence in Texas, a state with higher than national rates of cervical cancer incidence and mortality. Methods: In this population-based cross-sectional study, the authors analyzed incident cervical cancer data among Texas women aged 30-64 years, from 2014 to 2018. The authors conducted a purely spatial Poisson-based analysis function in SaTScan to examine geographic clusters of higher-than-expected proportions of cervical cancer incidence (i.e., hot spots) and adjusted for age. Results: A total of 5,060 women aged 30-64 years with incident cervical cancer diagnosis (mean age: 45.7 years, SD=9.6), including 1,840 (36.4%) Hispanic, 591 (11.7%) non-Hispanic Black, 2,397 (47.4%) non-Hispanic White, and 232 (4.6%) other races, were analyzed. Spatial scan analysis detected 7 significant hot spots of cervical cancer incidence. Hot spots were identified in the South Texas Plains (near Mexico border), Gulf Coast (Houston), Prairies and Lakes (North Texas), Panhandle Plains (Northwest Texas), and Piney Woods (Southeast Texas) regions of Texas. Hot spots, compared with the rest of Texas, had higher proportions of Hispanic population and individuals with socioeconomic disadvantages. Conclusions: This study found spatial variation in cervical cancer incidence in Texas. The hot spot areas can benefit from targeted, novel, scalable, and cost-effective interventions to increase human papillomavirus vaccination and screening and early detection and treatment of precancerous cervical lesions.

Cervical Pap screening among women living with HIV in Puerto Rico and the United States - Medical Monitoring Project, 2018-2021.

Our objective was to determine the prevalence of cervical Pap screening among women living with HIV (WLWH) in Puerto Rico (P.R.) and other selected United States (U.S.) jurisdictions. Additionally, we sought to compare selected characteristics of WLWH who underwent cervical Pap screening between P.R. and the other U.S. jurisdictions. We analyzed data from the 2018-2021 cycles of CDC's Medical Monitoring Project (MMP), a national surveillance system among adults with HIV residing in P.R. (n = 218) and 22 other MMP jurisdictions (n = 3,653). Weighted percentages and 95 % confidence intervals (CIs) for selected characteristics were estimated. Prevalence ratios with predicted marginal means were calculated. An estimated 91.6 % and 84.6 % of WLWH underwent cervical Pap screening in P.R. and the other 22 MMP jurisdictions, respectively (Prevalence Ratio = 1.08, 95% CI = 1.03-1.13). Among WLWH who underwent cervical Pap screening, those in P.R. were more likely to be 50+ years of age, have a household annual income below $20,000, engage in binge drinking, never smoke, and have Medicaid/other public insurance than those in the other 22 MMP jurisdictions (p < 0.05). No differences were found between P.R. and the other 22 MMP jurisdictions in the percentage reporting higher than the median HIV-stigma score, experiencing HIV health care discrimination, and having ≥ 1 sexual partner in the past 12 months. Although cervical Pap screening rates among WLWH were higher in P.R. than in the other 22 MMP jurisdictions, both surpass the Healthy People 2030 target. Future research should assess adherence and compliance with updated cervical cancer screening guidelines.

Effect of Childcare Influenza Vaccine Requirement on Vaccination Rates, New York City, 2012-2020.

OBJECTIVES: In 2014, New York City initiated a childcare influenza vaccine requirement to increase influenza vaccination rates among children aged 6-59 months attending city-regulated childcare, including prekindergarten. We evaluated the requirement's effect on vaccination rates in childcare-aged children in New York City. METHODS: We examined influenza vaccination rates in children aged 6-59 months and by age groups of 1, 2, 3, and 4 years for 8 influenza seasons (2012-2013 through 2019-2020), representing 2 seasons before the requirement, 2 seasons during the requirement, 2 seasons after its suspension, and 2 seasons after its reinstatement. We also assessed rates in a comparison group of children aged 5-8 years. We performed a difference-in-differences analysis to compare rate differences in age groups when the requirement was and was not in effect. We considered P < .05 as significant based on the Wald χ2 test. RESULTS: Influenza vaccination rates among children aged 6-59 months increased 3.7 percentage points (from 47.7% to 51.4%) by the requirement's second year and declined 6.7 percentage points to 44.7% after suspension. After reinstatement, rates increased 10.7 percentage points to 55.4%. Rate changes were most pronounced among 4-year-olds, increasing 12.7 percentage points (from 45.3% to 58.0%) by the requirement's second year, declining 14.1 percentage points to 43.9% after suspension, and increasing 22.2 percentage points to 66.1% after reinstatement. In the comparison group, rates increased 4.9 percentage points (from 36.5% to 41.4%) after reinstatement. Rates increased significantly among 4-year-olds before versus at the initial requirement and decreased significantly after suspension. After reinstatement, rates increased significantly among all groups except 1-year-olds. CONCLUSION: The New York City influenza vaccine requirement improved influenza vaccination rates among preschool-aged children, adding to the evidence base showing that vaccine requirements raise vaccination rates.

Clinical Implementation of DIGEST as an Evidence-Based Practice Tool for Videofluoroscopy in Oncology: A Six-Year Single Institution Implementation Evaluation.

Clinical implementation of evidence-based practice (EBP) tools is a healthcare priority. The Dynamic Grade of Swallowing Toxicity (DIGEST) is an EBP tool developed in 2016 for videofluoroscopy in head and neck (H&N) oncology with clinical implementation as a goal. We sought to examine: (1) feasibility of clinical implementation of DIGEST in a national comprehensive cancer center, and (2) fidelity of DIGEST adoption in real-world practice. A retrospective implementation evaluation was conducted in accordance with the STARI framework. Electronic health record (EHR) databases were queried for all consecutive modified barium swallow (MBS) studies conducted at MD Anderson Cancer Center from 2016 to 2021. Implementation outcomes included: feasibility as measured by DIGEST reporting in EHR (as a marker of clinical use) and fidelity as measured by accuracy of DIGEST reporting relative to the decision-tree logic (penetration-aspiration scale [PAS], residue, and Safety [S] and Efficiency [E] grades). Contextual factors examined included year, setting, cancer type, MBS indication, and provider. 13,055 MBS were conducted by 29 providers in 7,842 unique patients across the lifespan in diverse oncology populations (69% M; age 1-96 years; 58% H&N cancer; 10% inpatient, 90% outpatient). DIGEST was reported in 12,137/13,088 exams over the 6-year implementation period representing 93% (95% CI: 93-94%) adoption in all exams and 99% (95% CI: 98-99%) of exams excluding the total laryngectomy population (n = 730). DIGEST reporting varied modestly by year, cancer type, and setting/provider (> 91% in all subgroups, p < 0.001). Accuracy of DIGEST reporting was high for overall DIGEST (incorrect SE profile 1.6%, 200/12,137), DIGEST-safety (incorrect PAS 0.4% 51/12,137) and DIGEST-efficiency (incorrect residue 1.2%, 148/12,137). Clinical implementation of DIGEST was feasible with high fidelity in a busy oncology practice across a large number of providers. Adoption of the tool across the lifespan in diverse cancer diagnoses may motivate validation beyond H&N oncology.

Lesions to the mediodorsal thalamus, but not orbitofrontal cortex, enhance volatility beliefs linked to paranoia.

Beliefs-attitudes toward some state of the environment-guide action selection and should be robust to variability but sensitive to meaningful change. Beliefs about volatility (expectation of change) are associated with paranoia in humans, but the brain regions responsible for volatility beliefs remain unknown. The orbitofrontal cortex (OFC) is central to adaptive behavior, whereas the magnocellular mediodorsal thalamus (MDmc) is essential for arbitrating between perceptions and action policies. We assessed belief updating in a three-choice probabilistic reversal learning task following excitotoxic lesions of the MDmc (n = 3) or OFC (n = 3) and compared performance with that of unoperated monkeys (n = 14). Computational analyses indicated a double dissociation: MDmc, but not OFC, lesions were associated with erratic switching behavior and heightened volatility belief (as in paranoia in humans), whereas OFC, but not MDmc, lesions were associated with increased lose-stay behavior and reward learning rates. Given the consilience across species and models, these results have implications for understanding paranoia.

Bound star clusters observed in a lensed galaxy 460 Myr after the Big Bang.

The Cosmic Gems arc is among the brightest and highly magnified galaxies observed at redshift z ≈ 10.2 (ref. 1). However, it is an intrinsically ultraviolet faint galaxy, in the range of those now thought to drive the reionization of the Universe2-4. Hitherto the smallest features resolved in a galaxy at a comparable redshift are between a few hundreds and a few tens of parsecs (pc)5,6. Here we report JWST observations of the Cosmic Gems. The light of the galaxy is resolved into five star clusters located in a region smaller than 70 pc. They exhibit minimal dust attenuation and low metallicity, ages younger than 50 Myr and intrinsic masses of about 106M⊙. Their lensing-corrected sizes are approximately 1 pc, resulting in stellar surface densities near 105M⊙ pc-2, three orders of magnitude higher than typical young star clusters in the local Universe7. Despite the uncertainties inherent to the lensing model, they are consistent with being gravitationally bound stellar systems, that is, proto-globular clusters. We conclude that star cluster formation and feedback likely contributed to shaping the properties of galaxies during the epoch of reionization.

Role of pharmacists in the care of adult asthma patients: A scoping review.

BACKGROUND: Asthma is a common long-term condition that affects people of all ages. Evidence suggests that a significant proportion of asthma patients in the Gulf Cooperation Council (GCC) do not receive appropriate diagnosis, monitoring and/or treatment. When inadequately treated, asthma can negatively affect quality of life and may lead to hospitalisation and death. Although pharmacists play a role in asthma care globally, there appears to be no defined role for pharmacists in providing care to patients with asthma in the GCC countries. AIM: This scoping review aims to review and summarise studies conducted in the GCC countries involving pharmacists in the management of adults with asthma or evaluating pharmacists' asthma care knowledge and/or skills. METHOD: A systematic scoping review was undertaken. Seven databases were searched using relevant search terms for articles published up to May 2023. Studies that evaluated pharmacists roles, knowledge and skills in providing asthma care to adults in the United Arab Emirates (UAE), Qatar, Kuwait, Oman, Saudi Arabia, and Bahrain were considered eligible for inclusion. Extracted data were collated using tables and used to produce narrative descriptive summaries. RESULTS: Out of the 1588 search results, only seven studies met the inclusion criteria. Of those, only one developed and tested a pharmacist-led inhaler technique educational intervention in the UAE within community pharmacy setting for asthma patients. The remaining six studies assessed community pharmacists knowledge in providing asthma management and patient education in UAE, Saudi Arabia and Qatar. The quality of the included studies varied with four relying on simulated patients to assess pharmacists knowledge. The study that tested the intervention suggested improvement in inhaler technique and asthma symptoms control after receiving the intervention. The findings suggest a need to improve pharmacists knowledge of inhaler technique demonstration (mainly Metered Dose Inhalers), asthma management advice and assessment of asthma control and medication use. CONCLUSION: This review highlights a lack of research on pharmacist-led asthma interventions and identifies training needs to enable pharmacists to be involved in asthma care in the GCC countries. Future research could develop approaches involving pharmacists to improve asthma care and outcomes in the region.

Allenamides as a Powerful Tool to Incorporate Diversity: Thia-Michael Lipidation of Semisynthetic Peptides and Access to ß-Keto Amides.

Lipopeptides are an important class of biomolecules for drug development. Compared with conventional acylation, a chemoselective lipidation strategy offers a more efficient strategy for late-stage structural derivatisation of a peptide scaffold. It provides access to chemically diverse compounds possessing intriguing and non-native moieties. Utilising an allenamide, we report the first semisynthesis of antimicrobial lipopeptides leveraging a highly efficient thia-Michael addition of chemically diverse lipophilic thiols. Using chemoenzymatically prepared polymyxin B nonapeptide (PMBN) as a model scaffold, an optimised allenamide-mediated thia-Michael addition effected rapid and near quantitative lipidation, affording vinyl sulfide-linked lipopeptide derivatives. Harnessing the utility of this new methodology, 22 lipophilic thiols of unprecedented chemical diversity were introduced to the PMBN framework. These included alkyl thiols, substituted aromatic thiols, heterocyclic thiols and those bearing additional functional groups (e.g., amines), ultimately yielding analogues with potent Gram-negative antimicrobial activity and substantially attenuated nephrotoxicity. Furthermore, we report facile routes to transform the allenamide into a ß-keto amide on unprotected peptides, offering a powerful "jack-of-all-trades" synthetic intermediate to enable further peptide modification.

Nativity Disparities in Colorectal Cancer Screening Among Hispanics in the United States.

Hispanics in the United States (U.S.) have previously exhibited lower guideline-concordant colorectal cancer (CRC) screening uptake than non-Hispanic (NH) Whites, with disparities accentuated in foreign-born Hispanics, however it is unclear whether nativity-related CRC screening disparities have changed in the last two decades and whether these disparities are attenuated after adjusting for socioeconomic and demographic characteristics. We evaluated CRC screening adherence in foreign- and U.S.-born Hispanics compared to U.S.-born NH Whites. We used 2019 National Health Interview Survey data to compare the prevalence of up-to-date CRC screening per the 2019 U.S. Preventive Services Task Force recommendations among Hispanic nativity subgroups (i.e., foreign- and U.S.-born) and U.S.-born NH Whites using unadjusted and adjusted weighted log-linked binomial regression. Foreign- and U.S.-born Hispanics had a significantly lower unadjusted prevalence of up-to-date screening than U.S.-born NH Whites (47.18% and 64.18% versus 70.70%; p < 0.0001 and p = 0.0109, respectively). After adjusting for socioeconomic and demographic differences, the prevalence of up-to-date screening was lower in foreign-born Hispanics compared to U.S.-born NH Whites [adjusted prevalence ratio 0.80 (95% confidence interval 0.70-0.91)]; however, no statistically significant difference was observed between U.S.-born Hispanics and NH Whites. Our results suggest a low screening uptake in foreign-born Hispanics independent of socioeconomic and demographic differences. Future interventions should target foreign-born Hispanics to address disparities and promote early detection and prevention of CRC regardless of socioeconomic factors.

Using the Dynamic Well-Stirred Model to Extrapolate Hepatic Clearance of Organic Anion-Transporting Polypeptide Transporter Substrates without Assuming Albumin-Mediated Hepatic Drug Uptake.

Extrapolating in vivo hepatic clearance from in vitro uptake data is a known challenge, especially for organic anion-transporting polypeptide transporter (OATP) substrates, and the well-stirred model (WSM) commonly yields systematic underpredictions for those anionic drugs, hypothetically due to "albumin-mediated hepatic drug uptake". In the present study, we demonstrate that the WSM incorporating the dynamic free fraction (f D), a measure of drug protein binding affinity, performs reasonably well in predicting hepatic clearance of OATP substrates. For a selection of anionic drugs, including atorvastatin, fluvastatin, pravastatin, rosuvastatin, pitavastatin, cerivastatin, and repaglinide, this dynamic well-stirred model (dWSM) correctly predicts hepatic plasma clearance within 2-fold error for six out of seven OATP substrates examined. The geometric mean of clearance ratios between the predicted and the observed values falls in the range of 1.21-1.38. As expected, the WSM with unbound fraction (f u) systematically underpredicts hepatic clearance with greater than 2-fold error for five out of seven drugs, and the geometric mean of clearance ratios between the predicted and the observed values is in the range of 0.20-0.29. The results suggest that, despite its simplicity, the dWSM operates well for transporter-mediated uptake clearance, and that clearance under-prediction of OATP substrates may not necessarily be associated with the chemical class of the anionic drugs, nor is it a result of albumin-mediated hepatic drug uptake as currently hypothesized. Instead, the superior prediction power of the dWSM confirms the utility of the dynamic free fraction in clearance prediction and the importance of drug plasma binding kinetics in hepatic uptake clearance. SIGNIFICANCE STATEMENT: The traditional well-stirred model (WSM) consistently underpredicts organin anion-transporting polypeptide transporter (OATP)-mediated hepatic uptake clearance, hypothetically due to the albumin-mediated hepatic drug uptake. In this manuscript, we apply the dynamic WSM to extrapolate hepatic clearance of the OATP substrates, and our results show significant improvements in clearance prediction without assuming albumin-mediated hepatic drug uptake.

Risk factors for Cryptosporidium contamination in Minnesota public supply wells.

In a recent monitoring study of Minnesota's public supply wells, Cryptosporidium was commonly detected with 40% of the wells having at least one detection. Risk factors for Cryptosporidium occurrence in drinking water supply wells, beyond surface water influence, remain poorly understood. To address this gap, physical and chemical factors were assessed as potential predictors of Cryptosporidium occurrence in 135 public supply wells in Minnesota. Univariable analysis, regression techniques, and classification trees were used to analyze the data. Many variables were identified as significant risk factors in univariable analysis and several remained significant throughout the succeeding analysis techniques. These factors fell into general categories of well use and construction, aquifer characteristics, and connectedness to the land surface, well capture zones, and land use therein, existence of potential contaminant sources within 200-feet of the well, and variability in the chemical and isotopic parameters measured during the study. These risk categories, and the specific variables and threshold values we have identified, can help guide future research on factors influencing Cryptosporidium contamination of wells and can be used by environmental health programs to develop risk-based sampling plans and design interventions that reduce associated health risks.

Frequent and strong cold-air pooling drives temperate forest composition.

Cold-air pooling is an important topoclimatic process that creates temperature inversions with the coldest air at the lowest elevations. Incomplete understanding of sub-canopy spatiotemporal cold-air pooling dynamics and associated ecological impacts hinders predictions and conservation actions related to climate change and cold-dependent species and functions. To determine if and how cold-air pooling influences forest composition, we characterized the frequency, strength, and temporal dynamics of cold-air pooling in the sub-canopy at local to regional scales in New England, USA. We established a network of 48 plots along elevational transects and continuously measured sub-canopy air temperatures for 6-10 months (depending on site). We then estimated overstory and understory community temperature preferences by surveying tree composition in each plot and combining these data with known species temperature preferences. We found that cold-air pooling was frequent (19-43% seasonal occurrences) and that sites with the most frequent inversions displayed inverted forest composition patterns across slopes with more cold-adapted species, namely conifers, at low instead of high elevations. We also observed both local and regional variability in cold-air pooling dynamics, revealing that while cold-air pooling is common, it is also spatially complex. Our study, which uniquely focused on broad spatial and temporal scales, has revealed some rarely reported cold-air pooling dynamics. For instance, we discovered frequent and strong temperature inversions that occurred across seasons and in some locations were most frequent during the daytime, likely affecting forest composition. Together, our results show that cold-air pooling is a fundamental ecological process that requires integration into modeling efforts predicting future forest vegetation patterns under climate change, as well as greater consideration for conservation strategies identifying potential climate refugia for cold-adapted species.

A programmatic update on COVID-19 vaccination in rural communities in the United States.

When public health experts think of rural barriers to vaccines, they often initially focus on access, which makes sense with a new vaccine during a pandemic. This commentary highlights that there can be more complexity to vaccine uptake in rural communities. What follows are some examples of CDC's efforts to better understand rural health and learnings to inform ongoing vaccination efforts in rural communities.

Support for primary care prescribing for adult ADHD in England: national survey.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is a common neurodevelopmental disorder, for which there are effective pharmacological treatments that improve symptoms and reduce complications. Guidelines published by the National Institute for Health and Care Excellence recommend that primary care practitioners prescribe medication for adult ADHD under shared-care agreements with Adult Mental Health Services (AMHS). However, provision remains uneven, with some practitioners reporting a lack of support. AIM: This study aimed to describe elements of support, and their availability/use, in primary care prescribing for adult ADHD medication in England to improve access for this underserved population and inform service improvement. DESIGN AND SETTING: Cross-sectional surveys were used to elicit data from commissioners, health professionals (HPs), and people with lived experience of ADHD (LE) across England about elements supporting pharmacological treatment of ADHD in primary care. METHOD: Three interlinked cross-sectional surveys were used to ask every integrated care board in England (commissioners), along with convenience samples of HPs and LEs, about prescribing rates, AMHS availability, wait times, and shared-care agreement protocols/policies for the pharmacological treatment of ADHD in primary care. Descriptive analyses, percentages, and confidence intervals were used to summarise responses by stakeholder group. Variations in reported provision and practice were explored and displayed visually using mapping software. RESULTS: Data from 782 responders (42 commissioners, 331 HPs, 409 LEs) revealed differences in reported provision by stakeholder group, including for prescribing (95% of HPs versus 64% of LEs). In all, >40% of responders reported extended AMHS wait times of ≥2 years. There was some variability by NHS region - for example, London had the lowest reported extended wait time (25%), while East of England had the highest (55%). CONCLUSION: Elements supporting appropriate shared-care prescribing of ADHD medication via primary care are not universally available in England. Coordinated approaches are needed to address these gaps.