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Abstract Graduate students across disciplines are eager for experiential training that enables them to address real-world environmental challenges. Simultaneously, communities across the world face numerous environmental challenges, including increased frequency of extreme heat in summer and poor air quality, and could benefit from the expertise and engagement of graduate students with the requisite skills and interests to address these challenges. In this paper we bring together lessons learned from three interdisciplinary graduate training programs focused on preparing graduate students to contribute to urban environmental solutions by working in partnerships with non-academic organizations. We discuss the multiple elements required for partnerships to be mutually beneficial, including using a T-shaped approach to training that incorporates both depth and breadth while making strong efforts to broaden participation. We share lessons with the goal of enhancing graduate programs to improve training of students to address urban environmental challenges globally. This training aligns with the United Nations Sustainable Development Goal 17, “Partnership for the Goals,” which aims to achieve sustainable development goals through partnerships among entities.

Objective: Aircraft noise exposure is linked to cardiovascular disease risk. One understudied candidate pathway is obesity. This study investigates the association between aircraft noise and obesity among female participants in two prospective Nurses’ Health Study (NHS and NHSII) cohorts. Methods: Aircraft day-night average sound levels (DNL) were estimated at participant residential addresses from modeled 1 dB (dB) noise contours above 44 dB for 90 United States (U.S.) airports in 5-year intervals 1995–2010. Biennial surveys (1994–2017) provided information on body mass index (BMI; dichotomized, categorical) and other individual characteristics. Change in BMI from age 18 (BMI18; tertiles) was also calculated. Aircraft noise exposures were dichotomized (45, 55 dB), categorized (

Abstract The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance has been critical for pandemic control, however not all countries can currently sustain community pathogen surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but less is known about the utility of water surveillance of pathogens in low-income countries. Here we show how wastewater surveillance of SAR-CoV-2 can be used to identify temporal changes and help determine circulating variants quickly. In Malawi, a country with limited community-based COVID-19 testing capacity, we explore the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020–May 2022, we collect water from up to 112 river or defunct wastewater treatment plant sites, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predate peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights how wastewater can be used to detect emerging waves, identify variants of concern, and provide an early warning system in settings with no formal sewage systems.

Abstract Neurons that participate in sensory processing often display “ON” responses, i.e., fire transiently at the onset of a stimulus. ON transients are widespread, perhaps universal to sensory coding, yet their function is not always well-understood. Here, we show that ON responses in the Drosophila thermosensory system extrapolate the trajectory of temperature change, priming escape behavior if unsafe thermal conditions are imminent. First, we show that second-order thermosensory projection neurons (TPN-IIIs) and their Lateral Horn targets (TLHONs), display ON responses to thermal stimuli, independent of direction of change (heating or cooling) and of absolute temperature. Instead, they track the rate of temperature change, with TLHONs firing exclusively to rapid changes (>0.2 °C/s). Next, we use connectomics to track TLHONs’ output to descending neurons that control walking and escape, and modeling and genetic silencing to demonstrate how ON transients can flexibly amplify aversive responses to small thermal change. Our results suggest that, across sensory systems, ON transients may represent a general mechanism to systematically anticipate and respond to salient or dangerous conditions.

Abstract As global SARS-CoV-2 burden and testing frequency have decreased, wastewater surveillance has emerged as a key tool to support clinical surveillance efforts. The aims of this study were to identify and characterize SARS-CoV-2 variants in wastewater samples collected from urban centers across South Africa. Here we show that wastewater sequencing analyses are temporally concordant with clinical genomic surveillance and reveal the presence of multiple lineages not detected by clinical surveillance. We show that wastewater genomics can support SARS-CoV-2 epidemiological investigations by reliably recovering the prevalence of local circulating variants, even when clinical samples are not available. Further, we find that analysis of mutations observed in wastewater can provide a signal of upcoming lineage transitions. Our study demonstrates the utility of wastewater genomics to monitor evolution and spread of endemic viruses.

The immunological signatures driving the severity of coronavirus disease 19 (COVID-19) in Ghanaians remain poorly understood. We performed bulk transcriptome sequencing of nasopharyngeal samples from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected Ghanaians with mild and severe COVID-19, as well as healthy controls to characterize immune signatures at the primary SARS-CoV-2 infection site and identify drivers of disease severity. Generally, a heightened antiviral response was observed in SARS-CoV-2-infected Ghanaians compared with uninfected controls. COVID-19 severity was associated with immune suppression, overexpression of proinflammatory cytokines, including CRNN, IL1A, S100A7, and IL23A, and activation of pathways involved in keratinocyte proliferation. SAMD9L was among the differentially regulated interferon-stimulated genes in our mild and severe disease cohorts, suggesting that it may play a critical role in SARS-CoV-2 pathogenesis. By comparing our data with a publicly available dataset from a non-African (Indians) (GSE166530), an elevated expression of antiviral response-related genes was noted in COVID-19-infected Ghanaians. Overall, the study describes immune signatures driving COVID-19 severity in Ghanaians and identifies immune drivers that could serve as potential prognostic markers for future outbreaks or pandemics. It further provides important preliminary evidence suggesting differences in antiviral response at the upper respiratory interface in sub-Saharan Africans (Ghanaians) and non-Africans, which could be contributing to the differences in disease outcomes. Further studies using larger datasets from different populations will expand on these findings.

Introduction Vertebral artery stenting represents a viable option in treating symptomatic vertebral artery atherosclerotic stenosis. However, its safety and efficacy in improving neurological status and reducing recurrent strokes remain to be established. Methods We systematically searched PubMed, Embase, and Cochrane databases using keywords with Boolean operators to increase search sensitivity and specificity (‘extracranial’; ‘stenting’; ‘vertebral artery’; ‘stenosis’). We included articles reporting patients > 18 years old with symptomatic extracranial vertebral artery stenoses due to atherosclerosis treated with stenting (with or without angioplasty). Those reporting patients with vertebral dissections were excluded. Patients’ characteristics, procedural details, complications, and outcomes were extracted. Estimated rates weighted for sample size were generated for each variable using fixed and random effects models. Results From 89 unique studies identified, 21 met our inclusion criteria and were included in the analysis, comprising 1499 patients with 1570 lesions. The mean age was 65 years, and 74.4% were men. The mean baseline NIHSS was 4.6. The most frequent stenosis location was the V1 segment of the vertebral artery (88.4%). Device‐related issues occurred in 1.8%. Periprocedural ischemic and hemorrhagic complications occurred in 2.1% and 1.7%, respectively. Neurological improvement post‐procedure was observed in 84.2%, and the in‐hospital mortality rate was 2.1%. During follow‐up, in‐stent stenosis >50% was observed in 12.8%, and retreatment with either re‐stenting or angioplasty was performed in 10.8%. Ischemic complications during follow‐up occurred in 5%, and the overall mortality rate was 5%. Conclusion Stenting for the treatment of atherosclerotic vertebral artery stenosis is technically feasible, associated with a high rate of neurological improvement and low short and long‐term complication rates.

Background: Animal and epidemiologic studies indicate that air pollution may adversely affect fertility. However, the level of evidence is limited and specific pollutants driving the association are inconsistent across studies. Methods: We used data from a web-based preconception cohort study of pregnancy planners enrolled during 2013–2019 (Pregnancy Study Online; PRESTO). Eligible participants self-identified as female, were aged 21–45 years, resided in the United States (U.S.) or Canada, and were trying to conceive without fertility treatments. Participants completed a baseline questionnaire and bi-monthly follow-up questionnaires until conception or 12 months. We analyzed data from 8,747 participants (U.S.: 7,304; Canada: 1,443) who had been trying to conceive for

Abstract The manufacture and production of industrial chemicals continues to increase, with hundreds of thousands of chemicals and chemical mixtures used worldwide, leading to widespread population exposures and resultant health impacts. Low-wealth communities and communities of color often bear disproportionate burdens of exposure and impact; all compounded by regulatory delays to the detriment of public health. Multiple authoritative bodies and scientific consensus groups have called for actions to prevent harmful exposures via improved policy approaches. We worked across multiple disciplines to develop consensus recommendations for health-protective, scientific approaches to reduce harmful chemical exposures, which can be applied to current US policies governing industrial chemicals and environmental pollutants. This consensus identifies five principles and scientific recommendations for improving how agencies like the US Environmental Protection Agency (EPA) approach and conduct hazard and risk assessment and risk management analyses: (1) the financial burden of data generation for any given chemical on (or to be introduced to) the market should be on the chemical producers that benefit from their production and use; (2) lack of data does not equate to lack of hazard, exposure, or risk; (3) populations at greater risk, including those that are more susceptible or more highly exposed, must be better identified and protected to account for their real-world risks; (4) hazard and risk assessments should not assume existence of a “safe” or “no-risk” level of chemical exposure in the diverse general population; and (5) hazard and risk assessments must evaluate and account for financial conflicts of interest in the body of evidence. While many of these recommendations focus specifically on the EPA, they are general principles for environmental health that could be adopted by any agency or entity engaged in exposure, hazard, and risk assessment. We also detail recommendations for four priority areas in companion papers (exposure assessment methods, human variability assessment, methods for quantifying non-cancer health outcomes, and a framework for defining chemical classes). These recommendations constitute key steps for improved evidence-based environmental health decision-making and public health protection.

Abstract Human health risk assessment currently uses the reference dose or reference concentration (RfD, RfC) approach to describe the level of exposure to chemical hazards without appreciable risk for non-cancer health effects in people. However, this “bright line” approach assumes that there is minimal risk below the RfD/RfC with some undefined level of increased risk at exposures above the RfD/RfC and has limited utility for decision-making. Rather than this dichotomous approach, non-cancer risk assessment can benefit from incorporating probabilistic methods to estimate the amount of risk across a wide range of exposures and define a risk-specific dose. We identify and review existing approaches for conducting probabilistic non-cancer risk assessments. Using perchloroethylene (PCE), a priority chemical for the U.S. Environmental Protection Agency under the Toxic Substances Control Act, we calculate risk-specific doses for the effects on cognitive deficits using probabilistic risk assessment approaches. Our probabilistic risk assessment shows that chronic exposure to 0.004 ppm PCE is associated with approximately 1-in-1,000 risk for a 5% reduced performance on the Wechsler Memory Scale Visual Reproduction subtest with 95% confidence. This exposure level associated with a 1-in-1000 risk for non-cancer neurocognitive deficits is lower than the current RfC for PCE of 0.0059 ppm, which is based on standard point of departure and uncertainty factor approaches for the same neurotoxic effects in occupationally exposed adults. We found that the population-level risk of cognitive deficit (indicating central nervous system dysfunction) is estimated to be greater than the cancer risk level of 1-in-100,000 at a similar chronic exposure level. The extension of toxicological endpoints to more clinically relevant endpoints, along with consideration of magnitude and severity of effect, will help in the selection of acceptable risk targets for non-cancer effects. We find that probabilistic approaches can 1) provide greater context to existing RfDs and RfCs by describing the probability of effect across a range of exposure levels including the RfD/RfC in a diverse population for a given magnitude of effect and confidence level, 2) relate effects of chemical exposures to clinical disease risk so that the resulting risk assessments can better inform decision-makers and benefit-cost analysis, and 3) better reflect the underlying biology and uncertainties of population risks.

Abstract The growing frequency, intensity, and duration of extreme heat events necessitates interventions to reduce heat exposures. Local opportunities for heat adaptation may be optimally identified through collection of both quantitative exposure metrics and qualitative data on perceptions of heat. In this study, we used mixed methods to characterize heat exposure among urban residents in the area of Boston, Massachusetts, US, in summer 2020. Repeated interviews of N = 24 study participants ascertained heat vulnerability and adaptation strategies. Participants also used low-cost sensors to collect temperature, location, sleep, and physical activity data. We saw significant differences across temperature metrics: median personal temperature exposures were 3.9 °C higher than median ambient weather station temperatures. Existing air conditioning (AC) units did not adequately control indoor temperatures to desired thermostat levels: even with AC use, indoor maximum temperatures increased by 0.24 °C per °C of maximum outdoor temperature. Sleep duration was not associated with indoor or outdoor temperature. On warmer days, we observed a range of changes in time-at-home, expected given our small study size. Interview results further indicated opportunities for heat adaptation interventions including AC upgrades, hydration education campaigns, and amelioration of energy costs during high heat periods. Our mixed methods design informs heat adaptation interventions tailored to the challenges faced by residents in the study area. The strength of our community-academic partnership was a large part of the success of the mixed methods approach.

Health impact assessments have estimated substantial health co-benefits of climate change mitigation strategies due to reductions in air pollution in the US; however, few studies have considered children’s health impacts and related equity implications. We estimated the potential health co-benefits to children related to improved air quality associated with various emissions cap and investment scenarios for the transportation sector in the Northeastern and Mid-Atlantic US proposed under the Transportation and Climate Initiative (TCI). We modeled changes in ambient fine particulate matter and nitrogen dioxide between 2022 and 2032 associated with on-road transportation sector emissions under nine hypothetical carbon dioxide (CO _2 ) emissions cap and investment scenarios proposed under TCI using the Community Multiscale Air Quality (CMAQ) model version 5.2. We estimated potential health co-benefits for adverse birth and pediatric respiratory and neurodevelopmental outcomes using an expanded version of the Environmental Benefits Mapping and Analysis Program, known as BenMAPR. We also examined impacts on pediatric asthma exacerbations across racial/ethnic groups. We found that health benefits to children increased as the CO _2 emission caps became more ambitious. The combination of the highest emissions cap (25%) and the investment scenario which prioritized public transit improvement (Diversified strategy) conferred the greatest children’s health benefits for the majority of health outcomes considered, resulting in approximately $82 million per year in economic savings. Assessment of the distribution of avoided pediatric asthma exacerbations showed benefits across all racial and ethnic groups, with a slightly greater reduction in cases for non-White populations. Decarbonization policies in the transportation sector in the Eastern US have the potential to provide important air quality and pediatric health co-benefits.

Introduction Post-traumatic stress disorder (PTSD) is a debilitating disorder affecting approximately 6% of the population. Current treatments have been shown to efficaciously reduce symptom burden between 30%-50%. However, due to the high intensity of treatment over a long period of time. drop-out rates are as high as 50%. Objectives Assess the effect of one-time ketamine infusion in subanasthetic dosage on PTSD psychotherapy Assess feasibility and effect of massed, four days, esposure focused psychotherapy for PTSd Methods Here, we tested the efficacy of a four-day exposure and processing-focused psychotherapy at reducing PTSD severity. Twenty-seven participants with chronic PTSD were randomized to two groups, one receiving a one-time infusion of ketamine in a subanesthetic dose (0.5mg/kg for 40 minutes), the other receiving midazolam. Both groups underwent four 90-120 minutes of daily psychotherapy sessions a day after infusion, followed by in-vivo exposure practice. The severity of PTSD was assessed with the PCL-5 before and at the end of treatment, and at 30 and 90 days follow-up. Brain reactivation to the trauma reminders was measured using fMRI Results PTSD severity in both treatment groups decreased by 13, 16, and 15 points on the PCL-5 at the end of treatment, 30 days follow-up, and 90 days respectively, surpassing the minimum clinical difference of 7.9 points. There was no significant difference in symptom reductions between the treatment groups. However, brain reactivation to trauma stories differed between the groups, with the ketamine group showing a decline in the amygdala and hippocampus reactivation compared to the midazolam group, at the end of treatment. Image: Conclusions Our results imply comparable efficacy of this short-term intervention to standard trauma-focused psychotherapies, emphasizing its clinical usefulness as a short and effective intervention. Disclosure of Interest None Declared

Introduction EXCELLENT (NCT03685578; Cerenovus) is a large, prospective, international, real‐world registry of endovascular clot removal in acute ischemic stroke (AIS) with EmboTrap as the first line mechanical thrombectomy (MT) device, which included collection and analysis of the retrieved thrombus material. Methods Between September 2018 and March 2021, 1000 “all‐comer” patients were enrolled at 34 global sites (27 US, 5 EU, 1 UK, 1 Israel) and treated according to standard of care at each center (with Embrotrap as first line). The study employed blind endpoint evaluation, including a core imaging lab and an independent 90‐day mRS assessment. Retrieved clot was collected per each MT maneuver from 538 subjects across 26 sites and clot analysis was performed by independent central labs blinded to clinical data. Results mITT population included 998 subjects. Mean age was 69.9±14.18 years (range 18–102), 51.8% (517/998) subjects were female and 9.9% (97/997) had a pre‐stroke mRS 3–5. Baseline NIHSS was 15.6±6.87 (range 0–36); 10.1% (82/815) subjects had a large core (ASPECTS 0–5); 5.8% (57/990) had posterior stroke; 56.3% (523/929) underwent MT ≤ 6hrs of onset and 38.1% (380/998) received IV‐tPA prior to MT. First pass eTICI 2c‐3 was achieved in 38.3% (377/984) and final 2b‐3 in 94.5 % (930/984; median number of passes = 1) of subjects. 90‐day mRS≤2 or ≤pre‐stroke was 46.9% (429/915) and 90‐day all‐cause mortality was 19.0% (175/921). The univariate analysis of clot components showed high red blood cell and low platelet content were significant predictors of good mRS outcome (p

Background Toward development of diagnostics for cryptogenic stroke, we hypothesize that histomic features of stroke blood clots retrieved by mechanical thrombectomy could be used to delineate stroke etiology. Methods Clots were retrieved from patients undergoing thrombectomy, and etiology was determined by the trial of TOAST (Trial of Org 10172 in Acute Stroke Treatment) score. After sectioning and hematoxylin and eosin staining, clot components (red blood cells [RBCs], fibrin–platelet aggregates [FPs], and white blood cells [WBCs]) were segmented on whole slide images. Histomic features were engineered to capture structural distribution of RBC/FP regions, including radiomics, radial composition, and RBC/FP object features. To locally characterize WBCs, textural features derived from nuclear and extranuclear regions were computed from each WBC to define classes, which we summarized into class frequency distributions. Univariate and multivariate statistics were used to identify significant differences in engineered features between large artery atherosclerosis (LAA) and cardioembolic cases. The top 3 significant RBC/FP and WBC features were used to train a complement Naïve Bayes model, which was then used to predict the etiology of cryptogenic cases. Results In our data (n=53), 31 clots were cardioembolic, 8 were LAA, 4 were of strokes of other determined etiology, and 10 were cryptogenic. We identified 17 significant RBC/FP features and 3 significant WBC class frequency distributions that were different between cardioembolic and LAA. A complement Naïve Bayes model accurately classified cardioembolic versus LAA with a validation area under the receiver operating characteristic curve of 0.87±0.03, a performance substantially higher to using clot component percent composition (area under the receiver operating characteristic curve=0.69±0.16) that is the current state‐of‐the‐art. Further, cryptogenic cases were reliably classified as cardioembolic or LAA in cross‐validation analysis. Conclusion We present a first‐of‐its‐kind histomics pipeline to robustly quantify the complex structure and WBC heterogeneity in acute ischemic stroke clots and classify cryptogenic cases. We hope this work begins to pave the way for histopathology biomarkers for stroke etiology diagnosis.

Background Vascular geometry plays an important role in stroke thrombectomy outcomes, but few studies have examined complex characteristics of vessel morphology. The authors hypothesized that engineered vessel cross‐section features could be used to predict thrombectomy first‐pass effect (FPE). Methods The authors analyzed computed tomography angiography and noncontrast computed tomagraphy from 50 patients with anterior circulation stroke thrombectomy. After segmentation, traditional metrics (vessel tortuosity and angulation) were calculated from vessel centerlines that were transformed into the same coordinate system and same region of interest. Univariate statistical analysis and geometric morphometrics were used to interrogate differences in geometry between cases that did and did not achieve FPE, which classical angulation and tortuosity did not quantify. To describe these differences, complex cross‐section features were engineered and quantified using a semiautomatic pipeline. Machine learning was used to train predictive models of FPE based on significant cross‐section features. Results Only one local tortuosity metric was significantly different (q=0.019) between FPE and first‐pass failure cases. The most significant principal component score (q=0.012) from geometric morphometrics highlighted the M1 segment of the middle cerebral artery and upper cavernous internal carotid artery variation as morphological indicators of first‐pass outcome. Fifteen cross‐section features, corresponding to internal carotid artery and middle cerebral artery regions, were significantly different between cases that did and did not achieve FPE. Predictive models exhibited a strong prediction of FPE (area under the curve=0.98±0.05) and outperformed models using traditional tortuosity and angulation features. Conclusion Cross‐section features are a novel class of powerful and interpretable predictors of FPE, which could assist in treatment decision‐making.

BackgroundInequities in Coronavirus Disease 2019 (COVID-19) vaccine and booster coverage may contribute to future disparities in morbidity and mortality within and between Massachusetts (MA) communities.Methods and findingsWe conducted a population-based cross-sectional study of primary series vaccination and booster coverage 18 months into the general population vaccine rollout. We obtained public-use data on residents vaccinated and boosted by ZIP code (and by age group: 5 to 19, 20 to 39, 40 to 64, 65+) from MA Department of Public Health, as of October 10, 2022. We constructed population denominators for postal ZIP codes by aggregating census tract population estimates from the 2015-2019 American Community Survey. We excluded nonresidential ZIP codes and the smallest ZIP codes containing 1% of the state's population. We mapped variation in ZIP code-level primary series vaccine and booster coverage and used regression models to evaluate the association of these measures with ZIP code-level socioeconomic and demographic characteristics. Because age is strongly associated with COVID-19 severity and vaccine access/uptake, we assessed whether observed socioeconomic and racial/ethnic inequities persisted after adjusting for age composition and plotted age-specific vaccine and booster coverage by deciles of ZIP code characteristics. We analyzed data on 418 ZIP codes. We observed wide geographic variation in primary series vaccination and booster rates, with marked inequities by ZIP code-level education, median household income, essential worker share, and racial/ethnic composition. In age-stratified analyses, primary series vaccine coverage was very high among the elderly. However, we found large inequities in vaccination rates among younger adults and children, and very large inequities in booster rates for all age groups. In multivariable regression models, each 10 percentage point increase in "percent college educated" was associated with a 5.1 (95% confidence interval (CI) 3.9 to 6.3, p < 0.001) percentage point increase in primary series vaccine coverage and a 5.4 (95% CI 4.5 to 6.4, p < 0.001) percentage point increase in booster coverage. Although ZIP codes with higher "percent Black/Latino/Indigenous" and higher "percent essential workers" had lower vaccine coverage (-0.8, 95% CI -1.3 to -0.3, p < 0.01; -5.5, 95% CI -7.3 to -3.8, p < 0.001), these associations became strongly positive after adjusting for age and education (1.9, 95% CI 1.0 to 2.8, p < 0.001; 4.8, 95% CI 2.6 to 7.1, p < 0.001), consistent with high demand for vaccines among Black/Latino/Indigenous and essential worker populations within age and education groups. Strong positive associations between "median household income" and vaccination were attenuated after adjusting for age. Limitations of the study include imprecision of the estimated population denominators, lack of individual-level sociodemographic data, and potential for residential ZIP code misreporting in vaccination data.ConclusionsEighteen months into MA's general population vaccine rollout, there remained large inequities in COVID-19 primary series vaccine and booster coverage across MA ZIP codes, particularly among younger age groups. Disparities in vaccination coverage by racial/ethnic composition were statistically explained by differences in age and education levels, which may mediate the effects of structural racism on vaccine uptake. Efforts to increase booster coverage are needed to limit future socioeconomic and racial/ethnic disparities in COVID-19 morbidity and mortality.

Background Recent widespread adoption of a transradial approach in adults has encouraged its use and expansion in children; however, the safety and feasibility of the transradial approach in the latter has not been established. We evaluated these characteristics in our pediatric case series and compared our results with those in the literature. Methods Our prospectively maintained database was retrospectively searched for consecutive patients ≤18 years of age who underwent diagnostic and interventional neuroangiography through the transradial approach. Patient demographics, indications for the procedure, use of ultrasound guidance, arterial size at the access site, intra‐ and postprocedure complications, and outcomes were recorded. For the literature review, systematic searches of PubMed, MEDLINE, and Embase databases were conducted using keywords with Boolean operators (“radial artery” AND “pediatric”) for studies published in English between January 2000 and September 2021. Continuous variables were reported as means or medians and respective standard deviations and interquartile ranges according to data normality. Categorical variables were reported as frequencies. Results Twenty‐one patients were included in our series (mean age, 16.6±2.23 years, range 9–17 years; male sex, 11 [52.4%]). The transradial approach was used for diagnostic angiography in 15 cases (71.4%) and intervention in 6 (28.6%). Ultrasound guidance was used and a “radial cocktail” (verapamil‐heparin‐nitroglycerin) was given in all cases. Mean radial artery access‐site diameter was 2.2±0.46 mm. Two cases (9.5%) required conversion to femoral access. Two patients (9.5%) suffered reversible vasospasm. No radial artery occlusion or permanent neurologic deficits were recorded. The systematic review showed results similar to ours for vasospasm rates (6.3% and 9.5%, respectively) and procedural outcomes (92% and 91%, respectively). [Correction added on November 8, 2022, after first online publication: In the preceding sentence, the value 7% was changed to 6.3%, and the value 93% was changed to 92%.] Conclusion Our results and the literature review demonstrate that the transradial approach is a safe and feasible option for pediatric patients. Routine use of ultrasound guidance, selection of appropriately sized catheters, and prophylactic use of vasodilators and antispasmodics can help ensure the success of the procedure and limit common access‐site complications.

Abstract Background Associations between community-level risk factors and COVID-19 incidence have been used to identify vulnerable subpopulations and target interventions, but the variability of these associations over time remains largely unknown. We evaluated variability in the associations between community-level predictors and COVID-19 case incidence in 351 cities and towns in Massachusetts from March to October 2020. Methods Using publicly available sociodemographic, occupational, environmental, and mobility datasets, we developed mixed-effect, adjusted Poisson regression models to depict associations between these variables and town-level COVID-19 case incidence data across five distinct time periods from March to October 2020. We examined town-level demographic variables, including population proportions by race, ethnicity, and age, as well as factors related to occupation, housing density, economic vulnerability, air pollution (PM2.5), and institutional facilities. We calculated incidence rate ratios (IRR) associated with these predictors and compared these values across the multiple time periods to assess variability in the observed associations over time. Results Associations between key predictor variables and town-level incidence varied across the five time periods. We observed reductions over time in the association with percentage of Black residents (IRR = 1.12 [95%CI: 1.12–1.13]) in early spring, IRR = 1.01 [95%CI: 1.00–1.01] in early fall) and COVID-19 incidence. The association with number of long-term care facility beds per capita also decreased over time (IRR = 1.28 [95%CI: 1.26–1.31] in spring, IRR = 1.07 [95%CI: 1.05–1.09] in fall). Controlling for other factors, towns with higher percentages of essential workers experienced elevated incidences of COVID-19 throughout the pandemic (e.g., IRR = 1.30 [95%CI: 1.27–1.33] in spring, IRR = 1.20 [95%CI: 1.17–1.22] in fall). Towns with higher proportions of Latinx residents also had sustained elevated incidence over time (IRR = 1.19 [95%CI: 1.18–1.21] in spring, IRR = 1.14 [95%CI: 1.13–1.15] in fall). Conclusions Town-level COVID-19 risk factors varied with time in this study. In Massachusetts, racial (but not ethnic) disparities in COVID-19 incidence may have decreased across the first 8 months of the pandemic, perhaps indicating greater success in risk mitigation in selected communities. Our approach can be used to evaluate effectiveness of public health interventions and target specific mitigation efforts on the community level.

Introduction: Focal segmental glomerulosclerosis (FSGS) is characterized by proteinuria and a histologic pattern of glomerular lesions of diverse etiology that share features including glomerular scarring and podocyte foot process effacement. Roundabout guidance receptor 2 (ROBO2)/slit guidance ligand 2 (SLIT2) signaling destabilizes the slit diaphragm and reduces podocyte adhesion to the glomerular basement membrane (GBM). Preclinical studies suggest that inhibition of glomerular ROBO2/SLIT2 signaling can stabilize podocyte adhesion and reduce proteinuria. This clinical trial evaluates the preliminary efficacy and safety of ROBO2/SLIT2 inhibition with the ROBO2 fusion protein PF-06730512 in patients with FSGS. Methods: The Study to Evaluate PF-06730512 in Adults With FSGS (PODO; ClinicalTrials.gov identifier NCT03448692), an open-label, phase 2a, multicenter trial in adults with FSGS, will enroll patients into 2 cohorts (n = 22 per cohort) to receive either high- or low-dose PF-06730512 (intravenous) every 2 weeks for 12 weeks. Key inclusion criteria include a confirmed biopsy diagnosis of FSGS, an estimated glomerular filtration rate (eGFR) ≥45 ml/min/1.73 m2 based on the Chronic Kidney Disease Epidemiology Collaboration formula (30–45 with a recent biopsy), and urinary protein-to-creatinine ratio (UPCR) >1.5 g/g. Key exclusion criteria include collapsing FSGS, serious/active infection, ≥50% tubulointerstitial fibrosis on biopsy, and organ transplantation. The primary endpoint is change from baseline to week 13 in UPCR; secondary endpoints include safety, changes in eGFR, and PF-06730512 serum concentration. Results: This ongoing trial will report the efficacy, safety, pharmacokinetics, and biomarker results of PF-06730512 for patients with FSGS. Conclusion: Findings from this proof-of-concept study may support further development and evaluation of PF-06730512 to treat FSGS and warrant assessment in phase 3 clinical trials.

Simões, Levy et al. use a combination of experiments and models to study how Drosophila flies steer away from dangerous heat. They discover that flies use small temperature differences between the antennae to turn clear of thermal danger; they also demonstrate that heat avoidance, a simple innate behavior, contains unexpected plasticity.

Abstract Background Pediatric asthma is currently the most prevalent chronic disease in the United States, with children in lower income families disproportionately affected. This increased health burden is partly due to lower-quality and insufficient maintenance of affordable housing. A movement towards ‘green’ retrofits that improve energy efficiency and increase ventilation in existing affordable housing offers an opportunity to provide cost-effective interventions that can address these health disparities. Methods We combine indoor air quality modeling with a previously developed discrete event model for pediatric asthma exacerbation to simulate the effects of different types of energy retrofits implemented at an affordable housing site in Boston, MA. Results Simulation results show that retrofits lead to overall better health outcomes and healthcare cost savings if reduced air exchange due to energy-saving air tightening is compensated by mechanical ventilation. Especially when exposed to indoor tobacco smoke and intensive gas-stove cooking such retrofit would lead to an average annual cost saving of over USD 200, while without mechanical ventilation the same children would have experienced an increase of almost USD 200/year in health care utilization cost. Conclusion The combination of indoor air quality modeling and discrete event modeling applied in this paper can allow for the inclusion of health impacts in cost-benefit analyses of proposed affordable housing energy retrofits.

A Caucasian man in his 60s with a history of Cognard Type IIB dural arteriovenous fistula presented to the emergency room with right eye proptosis, chemosis, hyperemia, epiphora, diplopia, and blurred vision. Magnetic resonance imaging and magnetic resonance angiography revealed spontaneous, bilateral Barrow Type D carotid-cavernous fistulas (CCFs) that were later confirmed through cerebral angiography. The patient had no history of head or ocular trauma. Given the acute nature of presentation and worsening diplopia, the patient was scheduled for transvenous embolization. However, during the preprocedure angiogram, spontaneous resolution of the bilateral CCFs was observed. Complete resolution of all symptoms was noticed during follow-up. Given the rare nature of bilateral, indirect CCFs, our case stands out as the only reported instance whereby resolution of bilateral, indirect CCFs occurred spontaneously without any intervention.

Abstract Background Intracranial aneurysms (IAs) are dangerous because of their potential to rupture. We previously found significant RNA expression differences in circulating neutrophils between patients with and without unruptured IAs and trained machine learning models to predict presence of IA using 40 neutrophil transcriptomes. Here, we aim to develop a predictive model for unruptured IA using neutrophil transcriptomes from a larger population and more robust machine learning methods. Methods Neutrophil RNA extracted from the blood of 134 patients (55 with IA, 79 IA-free controls) was subjected to next-generation RNA sequencing. In a randomly-selected training cohort (n = 94), the Least Absolute Shrinkage and Selection Operator (LASSO) selected transcripts, from which we constructed prediction models via 4 well-established supervised machine-learning algorithms (K-Nearest Neighbors, Random Forest, and Support Vector Machines with Gaussian and cubic kernels). We tested the models in the remaining samples (n = 40) and assessed model performance by receiver-operating-characteristic (ROC) curves. Real-time quantitative polymerase chain reaction (RT-qPCR) of 9 IA-associated genes was used to verify gene expression in a subset of 49 neutrophil RNA samples. We also examined the potential influence of demographics and comorbidities on model prediction. Results Feature selection using LASSO in the training cohort identified 37 IA-associated transcripts. Models trained using these transcripts had a maximum accuracy of 90% in the testing cohort. The testing performance across all methods had an average area under ROC curve (AUC) = 0.97, an improvement over our previous models. The Random Forest model performed best across both training and testing cohorts. RT-qPCR confirmed expression differences in 7 of 9 genes tested. Gene ontology and IPA network analyses performed on the 37 model genes reflected dysregulated inflammation, cell signaling, and apoptosis processes. In our data, demographics and comorbidities did not affect model performance. Conclusions We improved upon our previous IA prediction models based on circulating neutrophil transcriptomes by increasing sample size and by implementing LASSO and more robust machine learning methods. Future studies are needed to validate these models in larger cohorts and further investigate effect of covariates.

Intraprocedural rupture (IPR) of an intracranial aneurysm is the most feared complication of primary and stent-assisted coiling because it carries a high risk of morbidity and mortality. The endovascular strategy applied to control IPR depends on the cause of the rupture and stage of the procedure. Rupture during primary or stent-assisted coiling is traditionally managed with the use of continued packing, balloon microcatheter placement, or in rare cases, with parent artery sacrifice. In this technical note, we describe the use of temporary coiling of the parent artery to control IPR in three cases. Temporary parent artery coiling creates a subocclusive state, resulting in aneurysmal blood flow reduction without interruption of blood flow to the distal territory. Flow reduction combined with the thrombogenicity of the previously deployed coils results in hemostasis. In the cases presented here, IPR occurred during the late stage of coiling. In each case, parent artery coiling was performed along with heparin reversal. After confirmation of hemostasis, the coils were retrieved to restore normal blood flow. We demonstrate that the technique of temporary parent artery coiling may be a safe and effective option for the management of IPR during primary or stent-assisted coiling.

Abstract The Compact Linear Collider (CLIC) is a proposed future high-luminosity linear electron-positron collider operating at three energy stages, with nominal centre-of-mass energies s $$ \sqrt{s} $$ = 380 GeV, 1.5 TeV, and 3 TeV. Its aim is to explore the energy frontier, providing sensitivity to physics beyond the Standard Model (BSM) and precision measurements of Standard Model processes with an emphasis on Higgs boson and top-quark physics. The opportunities for top-quark physics at CLIC are discussed in this paper. The initial stage of operation focuses on top-quark pair production measurements, as well as the search for rare flavour-changing neutral current (FCNC) top-quark decays. It also includes a top-quark pair production threshold scan around 350 GeV which provides a precise measurement of the top-quark mass in a well-defined theoretical framework. At the higher-energy stages, studies are made of top-quark pairs produced in association with other particles. A study of t̄tH production including the extraction of the top Yukawa coupling is presented as well as a study of vector boson fusion (VBF) production, which gives direct access to high-energy electroweak interactions. Operation above 1 TeV leads to more highly collimated jet environments where dedicated methods are used to analyse the jet constituents. These techniques enable studies of the top-quark pair production, and hence the sensitivity to BSM physics, to be extended to higher energies. This paper also includes phenomenological interpretations that may be performed using the results from the extensive top-quark physics programme at CLIC.

Abstract A new design of a detector plane of sub-millimetre thickness for an electromagnetic sampling calorimeter is presented. It is intended to be used in the luminometers LumiCal and BeamCal in future linear e$$^{+}$$ + e$$^{-}$$ - collider experiments. The detector planes were produced utilising novel connectivity scheme technologies. They were installed in a compact prototype of the calorimeter and tested at DESY with an electron beam of energy 1–5 GeV. The performance of a prototype of a compact LumiCal comprising eight detector planes was studied. The effective Molière radius at 5 GeV was determined to be (8.1 ± 0.1 (stat) ± 0.3 (syst)) mm, a value well reproduced by the Monte Carlo (MC) simulation (8.4 ± 0.1) mm. The dependence of the effective Molière radius on the electron energy in the range 1–5 GeV was also studied. Good agreement was obtained between data and MC simulation.

Antecedentes: Los tolchés son franjas de árboles dentro del paisaje agrícola yucateco; proporcionan varios servicios ecosistémicos, incluyendo el suministro de material leñoso. Preguntas e hipótesis: ¿Existen diferencias en la estructura de la vegetación leñosa de los tolchés a lo largo de la distancia al pueblo y la intensidad de uso? La hipótesis es que los atributos estructurales de la vegetación de los tolchés son afectados negativamente por la intensidad del uso del bosque, que disminuye de los márgenes del poblado, al área agrícola, hasta llegar a la vegetación madura. Descripción de datos: Se evaluaron los atributos estructurales de tolchés y vegetación madura (VM), se realizó una rarefacción para estandarizar el esfuerzo de muestreo, un modelo lineal univariante seguido de pruebas a posteriori. Sitio y años de estudio: El estudio se realizó en tolchés y VM de Yaxcabá, Yucatán, de febrero a julio de 2019. Métodos: Se establecieron 44 unidades de muestreo (UM): 36 UM se ubicaron en tolchés, de 3 grupos diferenciados por su distancia al poblado y 8 UM se ubicaron en VM. Se registraron los individuos leñosos > 2.5 cm de DAP y se evaluaron las diferencias de los valores estructurales de ambas condiciones. Resultados: La diversidad de los tolchés fueron significativamente superiores a la alcanzada por la VM, relacionada a la distancia al poblado. Conclusiones: Se determinó la influencia de un patrón de aprovechamiento basado en la distancia al poblado. Niveles intermedios de aprovechamiento favorecen la riqueza y diversidad de los tolchés.

Since December 2019, the coronavirus 2019 (COVID-19) pandemic has rapidly spread and overwhelmed healthcare systems worldwide, urging physicians to understand how to manage this novel infection. Early in the pandemic, more severe forms of COVID-19 have been observed in patients with cardiovascular comorbidities, who are often treated with renin-angiotensin aldosterone system (RAAS)-blockers, such as angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), but whether these are indeed independent risk factors is unknown. The cellular receptor for the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the membrane-bound angiotensin converting enzyme 2 (ACE2), as for SARS-CoV(-1). Experimental data suggest that expression of ACE2 may be increased by RAAS-blockers, raising concerns that these drugs may facilitate viral cell entry. On the other hand, ACE2 is a key counter-regulator of the RAAS, by degrading angiotensin II into angiotensin (1-7), and may thereby mediate beneficial effects in COVID-19. These considerations have raised concerns about the management of these drugs, and early comments shed vivid controversy among physicians. This review will describe the homeostatic balance between ACE-angiotensin II and ACE2-angiotensin (1-7) and summarize the pathophysiological rationale underlying the debated role of the RAAS and its modulators in the context of the pandemic. In addition, we will review available evidence investigating the impact of RAAS blockers on the course and prognosis of COVID-19 and discuss why retrospective observational studies should be interpreted with caution. These considerations highlight the importance of solid evidence-based data in order to guide physicians in the management of RAAS-interfering drugs in the general population as well as in patients with more or less severe forms of SARS-CoV-2 infection.

Background: Early life exposure to neurotoxicants and non-chemical psychosocial stressors can impede development of prefrontal cortical functions that promote behavioral regulation and thereby may predispose to adolescent risk-taking related behaviors (e.g., substance use or high-risk sexual activity). This is particularly concerning for communities exposed to multiple stressors. Methods: This study examined the relation of exposure to mixtures of chemical stressors, non-chemical psychosocial stressors, and other risk factors with neuropsychological correlates of risk-taking. Specifically, we assessed psychometric measures of both adverse behavioral regulation and adaptive attributes among adolescents (age ∼ 15 years) in the New Bedford Cohort (NBC), a sociodemographically diverse cohort of 788 children born 1993–1998 to mothers residing near the New Bedford Harbor Superfund site. The NBC includes biomarkers of prenatal exposure to organochlorines and metals; sociodemographic, parental and home characteristics; and periodic neurodevelopmental assessments. We modelled exposure mixtures using multi-dimensional smooths within generalized additive models. Results: Children of younger mothers with lower IQ who were exposed prenatally to higher polychlorinated biphenyls and lead had poorer anger control. This pattern was not apparent for children of older mothers with higher IQs. Direction of associations between increased hyperactivity and prenatal levels of organochlorine mixtures differed by maternal age and depression symptoms. Higher cord blood Pb levels, in conjunction with poorer HOME scores, were associated with poorer self-esteem when mothers had fewer depression symptoms. Conclusions: Analyses suggest that prenatal chemical exposures and non-chemical factors interact to contribute to neuropsychological correlates of risk-taking behaviors in adolescence. By simultaneously considering multiple factors associated with adverse behavioral regulation, we identified potential high-risk combinations that reflect both chemical and psychosocial stressors amenable to intervention.

BackgroundThe rupture of an intracranial aneurysm (IA) causes devastating subarachnoid hemorrhages, yet most IAs remain undiscovered until they rupture. Recently, we found an IA RNA expression signature of circulating neutrophils, and used transcriptome data to build predictive models for unruptured IAs. In this study, we evaluate the feasibility of using whole blood transcriptomes to predict the presence of unruptured IAs.MethodsWe subjected RNA from peripheral whole blood of 67 patients (34 with unruptured IA, 33 without IA) to next-generation RNA sequencing. Model genes were identified using the least absolute shrinkage and selection operator (LASSO) in a random training cohort (n = 47). These genes were used to train a Gaussian Support Vector Machine (gSVM) model to distinguish patients with IA. The model was applied to an independent testing cohort (n = 20) to evaluate performance by receiver operating characteristic (ROC) curve. Gene ontology and pathway analyses investigated the underlying biology of the model genes.ResultsWe identified 18 genes that could distinguish IA patients in a training cohort with 85% accuracy. This SVM model also had 85% accuracy in the testing cohort, with an area under the ROC curve of 0.91. Bioinformatics reflected activation and recruitment of leukocytes, activation of macrophages, and inflammatory response, suggesting that the biomarker captures important processes in IA pathogenesis.ConclusionsCirculating whole blood transcriptomes can detect the presence of unruptured IAs. Pending additional testing in larger cohorts, this could serve as a foundation to develop a simple blood-based test to facilitate screening and early detection of IAs.

Abstract Background Intracranial aneurysms (IAs) are dangerous because of their potential to rupture and cause deadly subarachnoid hemorrhages. Previously, we found significant RNA expression differences in circulating neutrophils between patients with unruptured IAs and aneurysm-free controls. Searching for circulating biomarkers for unruptured IAs, we tested the feasibility of developing classification algorithms that use neutrophil RNA expression levels from blood samples to predict the presence of an IA. Methods Neutrophil RNA extracted from blood samples from 40 patients (20 with angiography-confirmed unruptured IA, 20 angiography-confirmed IA-free controls) was subjected to next-generation RNA sequencing to obtain neutrophil transcriptomes. In a randomly-selected training cohort of 30 of the 40 samples (15 with IA, 15 controls), we performed differential expression analysis. Significantly differentially expressed transcripts (false discovery rate

Abstract Background Communities with large minority populations often are located near sources of pollution and have higher crime rates, which may work in combination with other factors to influence health. Poor self-rated health is related to chronic health conditions and premature mortality, with minority populations most likely to report poor health. To address how both resident perception of neighborhood environments and chronic health conditions individually and collectively influence health, we examined self-rated health and its association with multiple types of perceived environmental hazards in a majority-Hispanic urban population. Methods We conducted interviews with 354 residents of Chelsea, Massachusetts, US and asked about self-rated health, perceptions of their neighborhood, including participant-reported environmental hazards (e.g., air quality, odors and noise), aspects of the social environment (e.g., feeling safe, neighborhood crime, social cohesion), and culture-related stressors (e.g., immigration status, language stress, ethnic identity). Log-linear models examined the independent and multivariable associations between these factors and fair/poor self-rated health, controlling for socio-demographic characteristics and preexisting health conditions. Results Forty-one percent of participants reported fair/poor self-rated health. Participants frequently perceived environmental hazards such as problems with pests and regular noise disturbance as well as feeling unsafe. In a multivariable model, a greater number of reported noise disturbances (≥ 2 noise sources = 1.53 [1.04–2.26]) and reported insecurity with immigration status (1.66 [1.01–2.73]) were positively associated with fair/poor self-rated health. High social cohesion was inversely associated (0.74 [0.48–1.14]) with fair/poor self-rated health in the multivariable model. Conclusions Negative perceptions of environmental hazards and reported cultural stressors were significantly associated with fair/poor self-rated health among residents in a low-income majority-minority community, with social cohesion having a beneficial association with self-rated health. Efforts to improve health should recognize the importance of public perceptions of social and environmental hazards found in neighborhood environments, and benefits of strengthening community connections.

Abstract A prototype of a luminometer, designed for a future $$e^+e^-$$ e+e- collider detector, and consisting at present of a four-plane module, was tested in the CERN PS accelerator T9 beam. The objective of this beam test was to demonstrate a multi-plane tungsten/silicon operation, to study the development of the electromagnetic shower and to compare it with MC simulations. The Molière radius has been determined to be 24.0 ± 0.6 (stat.) ± 1.5 (syst.) mm using a parametrization of the shower shape. Very good agreement was found between data and a detailed Geant4 simulation.