Exposure to Household Air Pollution from Biomass Cookstoves and Blood Pressure Among Women in Rural Honduras: A Cross‐Sectional Study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed cross‐sectional associations of 24‐hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleaner‐burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24‐hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove users’ exposures were 66 μg/m3 (38) and 137 μg/m3(194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7‐4.3) per unit increase in natural log‐transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3‐8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0‐2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups

An Evaluation of Non-Uniform Grade Distribution with the Emergency Medicine Off-Service Standardized Letters of Evaluation

Introduction: Standardized Letters of Evaluation (SLOEs) are designed to objectively compare medical students to their peers for completed emergency medicine (EM) rotations to be used in the EM residency match. In an attempt to adapt quickly to the lack of availability of in-person EM rotations due to COVID restrictions, “off-service” SLOEs (OSLOEs) were allowed in place of traditional SLOEs. The purpose of this study was to assess the utility of OSLOEs for candidate selection during the 2020-21 application cycle at a single EM residency.Methods: A retrospective cohort review of all OSLOEs submitted during the 2020-21 academic year to an EM residency program was performed. A total of 270 OSLOES were eligible for review. Summary statistics were calculated for the study variables recorded, including global rank, grade, categorical details, and rank.Results: Of the 270 OSLOEs reviewed, 61.9% ranked candidates in the top 10% of their class, with 95% being ranked in the top two categories. Over 90% of students were graded as honors or high pass and over 75% of students were ranked in the top 1/3 for each specific OSLOE category.Conclusion: Our findings reveal questionable utility of the objective measures in the OSLOE as there are signs it may suffer from non-uniform grade distribution, leading to low utility for candidate selection. Our data shows marked over-ranking within the highest 2 categories. EM program directors and faculty should use caution as the OSLOE may not carry the same weight as a traditional SLOE when objectively evaluating prospectivestudents for a match into EM

Exposure to Household Air Pollution from Biomass Cookstoves and Levels of Fractional Exhaled Nitric Oxide (FeNO) among Honduran Women

Household air pollution is estimated to be responsible for nearly three million premature deaths annually. Measuring fractional exhaled nitric oxide (FeNO) may improve the limited understanding of the association of household air pollution and airway inflammation. We evaluated the cross-sectional association of FeNO with exposure to household air pollution (24-h average kitchen and personal fine particulate matter and black carbon; stove type) among 139 women in rural Honduras using traditional stoves or cleaner-burning Justastoves. We additionally evaluated interaction by age. Results were generally consistent with a null association; we did not observe a consistent pattern for interaction by age. Evidence from ambient and household air pollution regarding FeNO is inconsistent, and may be attributable to differing study populations, exposures, and FeNO measurement procedures (e.g., the flow rate used to measure FeNO)

Staying warm or moist? Operative temperature and thermal preferences of common frogs (Rana temporaria), and effects on locomotion

Ambient temperature largely determines the body temperature of amphibians, and thus their hydration state and physiological performance. Microhabitat conditions chosen by terrestrial amphibians may represent a trade-off between high ambient temperatures, which maximize performance but cause high rates of water loss, and low temperatures, which, in turn, slow desiccation, but potentially hinder performance. We determined the operative temperature of common frogs (Rana temporaria) by placing 3% agar models in different microhabitats and measuring their temperature and water loss. Temperature measurements derived from the models accurately matched the body temperature of live frogs placed in the same microhabitat. Operative temperatures were lower than ambient temperatures on a warm day, probably because of evaporative water loss, but they were similar to or even slightly higher than ambient temperatures on a cool day, possibly because of warmth from the substrate. Frogs in the field selected moist and cool habitats, and their body temperatures ranged from 15 to 21 °C. In a temperature gradient in the laboratory, captive frogs chose significantly higher temperatures (19.4±1.7 °C) when the gradient floor was covered entirely with wet sand than when sand was wet in the cool end, but dry in the warm end (17.6±2.5 °C). The relevance of the preferred temperature was assessed through jumping performance experiments, using frogs with different body temperatures. Jump length was lower at low body temperature (6 °C) than at higher body temperatures, and peaked at 15 °C. Our results suggest that the frogs select favourable microhabitats of intermediate temperature, which could result in reduced water loss and peak physiological and behavioural performance.Prof. Sue W. Nicolson and the National Research Foundation, South Africa, are thanked for funding A.K.’s journey to Poland. C.R.T. was supported by a grant from the Australian Research Council (DP0879851).http://www.thebhs.org/pubs_journal.htmlab201

Mechanical Thrombectomy for Acute Stroke: Early versus Late Time Window Outcomes

BACKGROUND AND PURPOSERecent trials have shown benefit of thrombectomy in patients selected by penumbral imaging in the late (>6 hours) window. However, the role penumbral imaging is not clear in the early (0‐6 hours) window. We sought to evaluate if time to treatment modifies the effect of endovascular reperfusion in stroke patients with evidence of salvageable tissue on CT perfusion (CTP).METHODSWe retrospectively analyzed consecutive patients who underwent thrombectomy in a single center. Demographics, comorbidities, National Institute of Health Stroke Scale (NIHSS), rtPA administration, ASPECTS, core infarct volume, onset to skin puncture time, recanalization (mTICI IIb/III), final infarct volume were compared between patients with good and poor 90‐day outcomes (mRS 0‐2 vs. 3‐6). Multivariable logistic regression analyses were used to identify independent predictors of a good (mRS 0‐2) 90‐day outcome.RESULTSA total of 235 patients were studied, out of which 52.3% were female. Univariate analysis showed that the groups (early vs. late) were balanced for age (P = .23), NIHSS (P = .63), vessel occlusion location (P = .78), initial core infarct volume (P = .15), and recanalization (mTICI IIb/III) rates (P = .22). Favorable outcome (mRS 0‐2) at 90 days (P = .30) were similar. There was a significant difference in final infarct volume (P = .04). Shift analysis did not reveal any significant difference in 90‐day outcome (P = .14). After adjustment; age (P < .001), NIHSS (P = .01), recanalization (P = .008), and final infarct volume (P < .001) were predictive of favorable outcome.CONCLUSIONSPenumbral imaging‐based selection of patients for thrombectomy is effective regardless of onset time and yields similar functional outcomes in early and late window patients.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/155458/1/jon12698_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/155458/2/jon12698.pd

Exposure to household air pollution from biomass cookstoves and blood pressure among women in rural Honduras: A crossâ sectional study

Growing evidence links household air pollution exposure from biomass cookstoves with elevated blood pressure. We assessed crossâ sectional associations of 24â hour mean concentrations of personal and kitchen fine particulate matter (PM2.5), black carbon (BC), and stove type with blood pressure, adjusting for confounders, among 147 women using traditional or cleanerâ burning Justa stoves in Honduras. We investigated effect modification by age and body mass index. Traditional stove users had mean (standard deviation) personal and kitchen 24â hour PM2.5 concentrations of 126 μg/m3 (77) and 360 μg/m3 (374), while Justa stove usersâ exposures were 66 μg/m3 (38) and 137 μg/m3 (194), respectively. BC concentrations were similarly lower among Justa stove users. Adjusted mean systolic blood pressure was 2.5 mm Hg higher (95% CI, 0.7â 4.3) per unit increase in natural logâ transformed kitchen PM2.5 concentration; results were stronger among women of 40 years or older (5.2 mm Hg increase, 95% CI, 2.3â 8.1). Adjusted odds of borderline high and high blood pressure (categorized) were also elevated (odds ratio = 1.5, 95% CI, 1.0â 2.3). Some results included null values and are suggestive. Results suggest that reduced household air pollution, even when concentrations exceed air quality guidelines, may help lower cardiovascular disease risk, particularly among older subgroups.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146816/1/ina12507.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146816/2/ina12507_am.pd

Development and validation of a targeted gene sequencing panel for application to disparate cancers

Next generation sequencing has revolutionised genomic studies of cancer, having facilitated the development of precision oncology treatments based on a tumour’s molecular profile. We aimed to develop a targeted gene sequencing panel for application to disparate cancer types with particular focus on tumours of the head and neck, plus test for utility in liquid biopsy. The final panel designed through Roche/Nimblegen combined 451 cancer-associated genes (2.01 Mb target region). 136 patient DNA samples were collected for performance and application testing. Panel sensitivity and precision were measured using well-characterised DNA controls (n = 47), and specificity by Sanger sequencing of the Aryl Hydrocarbon Receptor Interacting Protein (AIP) gene in 89 patients. Assessment of liquid biopsy application employed a pool of synthetic circulating tumour DNA (ctDNA). Library preparation and sequencing were conducted on Illumina-based platforms prior to analysis with our accredited (ISO15189) bioinformatics pipeline. We achieved a mean coverage of 395x, with sensitivity and specificity of >99% and precision of >97%. Liquid biopsy revealed detection to 1.25% variant allele frequency. Application to head and neck tumours/cancers resulted in detection of mutations aligned to published databases. In conclusion, we have developed an analytically-validated panel for application to cancers of disparate types with utility in liquid biopsy

The Science Performance of JWST as Characterized in Commissioning

This paper characterizes the actual science performance of the James Webb Space Telescope (JWST), as determined from the six month commissioning period. We summarize the performance of the spacecraft, telescope, science instruments, and ground system, with an emphasis on differences from pre-launch expectations. Commissioning has made clear that JWST is fully capable of achieving the discoveries for which it was built. Moreover, almost across the board, the science performance of JWST is better than expected; in most cases, JWST will go deeper faster than expected. The telescope and instrument suite have demonstrated the sensitivity, stability, image quality, and spectral range that are necessary to transform our understanding of the cosmos through observations spanning from near-earth asteroids to the most distant galaxies.Comment: 5th version as accepted to PASP; 31 pages, 18 figures; https://iopscience.iop.org/article/10.1088/1538-3873/acb29

The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer

Abstract: Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors