Aerosol hygroscopicity and visibility estimates in the Great Smoky Mountains National Park

National Park Service.Includes bibliographical references (pages 79-82).Summertime visibility in the National Parks in the Eastern United States is often very poor, due to high particulate mass concentrations and high relative humidities. As a part of the Southeastern Aerosol and Visibility Study (SEAVS) in the Great Smoky Mountains National Park during the summer of 1995, aerosol size distributions (Dp = 0.1-3 µm) were measured with an Active Scattering Aerosol Spectrometer (ASASP-X). A relative humidity (RH) controlled inlet allowed for both dry and humidified measurements. The objective of this experiment was to examine the aerosol size distribution and its variation with RH to characterize its effect on visibility in the region. The ASASP-X was calibrated with polystyrene latex spheres (PSL) (m = 1.588), however, the instrument response was sensitive to the refractive index of the measured particles, which was typically much lower than that of PSL. An inversion technique accounting for varying particle real refractive index was developed to invert ASASP-X data to particle size. Dry (RH < 15%) particle refractive indices were calculated using the partial molar refractive index method and 12-hour fine aerosol (<2.5 µm) chemical compositions from the National Park Service Interagency Monitoring of Protected Visual Environments (IMPROVE) filter samples. A study average dry refractive index of m = 1.49 ± 0.02 was determined. The dry aerosol number distributions inverted using the scaling method were fit with single mode lognormal curves, resulting in dry accumulation mode size parameters. A study average total volume concentration of 7 ± 5 µm3 cm-3 was determined, with a maximum value of 26 µm3 cm-3. The large variability was due to extremes in meteorological situations occurring during the study. The study average volume median diameter was 0.18 ± 0.03 µm, with an average geometric standard deviation of 1.45 ± 0.06. A newly-developed iteration method was used to determine wet refractive indices, wet accumulation mode volume concentrations and water mass concentrations as a function of relative humidity. Theoretical predictions of water mass concentrations were determined using a chemical equilibrium model assuming only ammonium and sulfate were hygroscopic. Comparisons of predicted and experimental water mass showed agreement within experimental uncertainties. To examine the effects of particles on visibility, particle light scattering coefficients, bsp, were calculated with derived size parameters, refractive index and Mie theory. Dry scattering agreed well with nephelometer measurements made at SEAVS, with an average bsp of 0.0406-km-1. Estimates of particle light scattering growth (b/b0) were determined from ratios of wet and dry light scattering coefficients, and also agreed with nephelometer results. The new inversion techniques were compared to earlier, simpler methods which ignored variations in aerosol chemical composition. The simpler method yielded smaller mean diameters, however, hygroscopicity estimates were comparable to those derived using daily varying chemical composition. This suggests that although the aerosol chemical composition is needed to determine aerosol size parameters, it may not be critical for deriving hygroscopicity (or other ratios of size parameters). This result may be specific to this study, as the variation in refractive index with RH assumed by previous models appears to be a good estimate for that observed during SEAVS.Funding agency: National Park Service # 1443-CA0001-920006, AMD#5/SUB#3

Impacts of increasing aridity and wildfires on aerosol loading in the intermountain Western US

Feedbacks between climate warming, land surface aridity, and wildfire-derived aerosols represent a large source of uncertainty in future climate predictions. Here, long-term observations of aerosol optical depth, surface level aerosol loading, fire-area burned, and hydrologic simulations are used to show that regional-scale increases in aridity and resulting wildfires have significantly increased summertime aerosol loading in remote high elevation regions of the Intermountain West of the United States. Surface summertime organic aerosol loading and total aerosol optical depth were both strongly correlated (p < 0.05) with aridity and fire area burned at high elevation sites across major western US mountain ranges. These results demonstrate that surface-level organic aerosol loading is dominated by summertime wildfires at many high elevation sites. This analysis provides new constraints for climate projections on the influence of drought and resulting wildfires on aerosol loading. These empirical observations will help better constrain projected increases in organic aerosol loading with increased fire activity under climate change

Enhancing wind erosion monitoring and assessment for U.S. rangelands

Wind erosion is a major resource concern for rangeland managers because it can impact soil health, ecosystem structure and function, hydrologic processes, agricultural production, and air quality. Despite its significance, little is known about which landscapes are eroding, by how much, and when. The National Wind Erosion Research Network was established in 2014 to develop tools for monitoring and assessing wind erosion and dust emissions across the United States. The Network, currently consisting of 13 sites, creates opportunities to enhance existing rangeland soil, vegetation, and air quality monitoring programs. Decision-support tools developed by the Network will improve the prediction and management of wind erosion across rangeland ecosystems. © 2017 The Author(s)The Rangelands archives are made available by the Society for Range Management and the University of Arizona Libraries. Contact [email protected] for further information

Cold comfort? Reconceiving the practices of bathing in British self-build eco-homes

Living sustainably involves a broad spectrum of practices, from relying on a technological fix to a deep green vision. The latter is often articulated by advocates and critics alike as involving shifting to a simpler lifestyle that dispenses with some of the (perceived) frivolous or environmentally damaging attachments to luxury or convenience. This article explores practices of reconceiving comfort in the context of the social and material architectures of eco-housing. Comfort is defined as an ongoing process, a negotiation between different elements (e.g., climate, materials and bodies) in a particular place. This article uses three case studies of self-built eco-communities in Britain (Green Hills, Landmatters, and Tinkers Bubble) and analyzes their bathrooms and bathing practices. In the eco-communities' bathing practices, comfort was reconceived as not being reliant on particular facilities, furniture, or temperature, as not private but as collective and shared, and as an embodied relation. This article demonstrates the relationality of comfort, how it is therefore possible to reconceive comfort, and how comfort can be understood as a practice. This focus on practices also challenges social practice theories to more purposefully engage with those already living a highly ecological lifestyle to understand how radical change is navigated

Identification of a BRCA2-Specific modifier locus at 6p24 related to breast cancer risk

Common genetic variants contribute to the observed variation in breast cancer risk for BRCA2 mutation carriers; those known to date have all been found through population-based genome-wide association studies (GWAS). To comprehensively identify breast cancer risk modifying loci for BRCA2 mutation carriers, we conducted a deep replication of an ongoing GWAS discovery study. Using the ranked P-values of the breast cancer associations with the imputed genotype of 1.4 M SNPs, 19,029 SNPs were selected and designed for inclusion on a custom Illumina array that included a total of 211,155 SNPs as part of a multi-consortial project. DNA samples from 3,881 breast cancer affected and 4,330 unaffected BRCA2 mutation carriers from 47 studies belonging to the Consortium of Investigators of Modifiers of BRCA1/2 were genotyped and available for analysis. We replicated previously reported breast cancer susceptibility alleles in these BRCA2 mutation carriers and for several regions (including FGFR2, MAP3K1, CDKN2A/B, and PTHLH) identified SNPs that have stronger evidence of association than those previously published. We also identified a novel susceptibility allele at 6p24 that was inversely associated with risk in BRCA2 mutation carriers (rs9348512; per allele HR = 0.85, 95% CI 0.80-0.90, P = 3.9×10−8). This SNP was not associated with breast cancer risk either in the general population or in BRCA1 mutation carriers. The locus lies within a region containing TFAP2A, which encodes a transcriptional activation protein that interacts with several tumor suppressor genes. This report identifies the first breast cancer risk locus specific to a BRCA2 mutation background. This comprehensive update of novel and previously reported breast cancer susceptibility loci contributes to the establishment of a panel of SNPs that modify breast cancer risk in BRCA2 mutation carriers. This panel may have clinical utility for women with BRCA2 mutations weighing options for medical prevention of breast cancer

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570