Ground-based remote sensing of an elevated forest fire aerosol layer at Whistler, BC: implications for interpretation of mountaintop chemistry

On 30 August 2009, intense forest fires in interior British Columbia (BC) coupled with winds from the east and northeast resulted in transport of a broad forest fire plume across southwestern BC. The physico-chemical and optical characteristics of the plume as observed from Saturna Island (AERONET), CORALNet-UBC and the Whistler Mountain air chemistry facility were consistent with forest fire plumes that have been observed elsewhere in continental North America. However, the importance of three-dimensional transport in relation to the interpretation of mountaintop chemistry observations is highlighted on the basis of deployment of both a <i>CL31</i> ceilometer and a single particle mass spectrometer (SPMS) in a mountainous setting. The SPMS is used to identify the biomass plume based on levoglucosan and potassium markers. Data from the SPMS are also used to show that the biomass plume was correlated with nitrate, but not correlated with sulphate or sodium. This study not only provides baseline measurements of biomass burning plume physico-chemical characteristics in western Canada, but also highlights the importance of lidar remote sensing methods in the interpretation of mountaintop chemistry measurements

An electronic family health history tool to identify and manage patients at increased risk for colorectal cancer: protocol for a randomized controlled trial.

BackgroundColorectal cancer is the fourth most commonly diagnosed cancer in the United States. Approximately 3-10% of the population has an increased risk for colorectal cancer due to family history and warrants more frequent or intensive screening. Yet, &lt; 50% of that high-risk population receives guideline-concordant care. Systematic collection of family health history and decision support may improve guideline-concordant screening for patients at increased risk of colorectal cancer. We seek to test the effectiveness of a web-based, systematic family health history collection tool and decision support platform (MeTree) to improve risk assessment and appropriate management of colorectal cancer risk among patients in the Department of Veterans Affairs primary care practices.MethodsIn this ongoing randomized controlled trial, primary care providers at the Durham Veterans Affairs Health Care System and the Madison VA Medical Center are randomized to immediate intervention or wait-list control. Veterans are eligible if assigned to enrolled providers, have an upcoming primary care appointment, and have no conditions that would place them at increased risk for colorectal cancer (such as personal history, adenomatous polyps, or inflammatory bowel disease). Those with a recent lower endoscopy (e.g. colonoscopy, sigmoidoscopy) are excluded. Immediate intervention patients put their family health history information into a web-based platform, MeTree, which provides both patient- and provider-facing decision support reports. Wait-list control patients access MeTree 12 months post-consent. The primary outcome is the risk-concordant colorectal cancer screening referral rate obtained via chart review. Secondary outcomes include patient completion of risk management recommendations (e.g. colonoscopy) and referral for genetic consultation. We will also conduct an economic analysis and an assessment of providers' experience with MeTree clinical decision support recommendations to inform future implementation efforts if the intervention is found to be effective.DiscussionThis trial will assess the feasibility and effectiveness of patient-collected family health history linked to decision support to promote risk-appropriate screening in a large healthcare system such as the Department of Veterans Affairs.Trial registrationClinicalTrials.gov, NCT02247336 . Registered on 25 September 2014

Genome-wide association study of multisite chronic pain in UK Biobank

Chronic pain is highly prevalent worldwide and represents a significant socioeconomic and public health burden. Several aspects of chronic pain, for example back pain and a severity-related phenotype ‘chronic pain grade’, have been shown previously to be complex heritable traits with a polygenic component. Additional pain-related phenotypes capturing aspects of an individual’s overall sensitivity to experiencing and reporting chronic pain have also been suggested as a focus for investigation. We made use of a measure of the number of sites of chronic pain in individuals within the UK general population. This measure, termed Multisite Chronic Pain (MCP), is a complex trait and its genetic architecture has not previously been investigated. To address this, we carried out a large-scale genome-wide association study (GWAS) of MCP in ~380,000 UK Biobank participants. Our findings were consistent with MCP having a significant polygenic component, with a Single Nucleotide Polymorphism (SNP) heritability of 10.2%. In total 76 independent lead SNPs at 39 risk loci were associated with MCP. Additional gene-level association analyses identified neurogenesis, synaptic plasticity, nervous system development, cell-cycle progression and apoptosis genes as enriched for genetic association with MCP. Genetic correlations were observed between MCP and a range of psychiatric, autoimmune and anthropometric traits, including major depressive disorder (MDD), asthma and Body Mass Index (BMI). Furthermore, in Mendelian randomisation (MR) analyses a causal effect of MCP on MDD was observed. Additionally, a polygenic risk score (PRS) for MCP was found to significantly predict chronic widespread pain (pain all over the body), indicating the existence of genetic variants contributing to both of these pain phenotypes. Overall, our findings support the proposition that chronic pain involves a strong nervous system component with implications for our understanding of the physiology of chronic pain. These discoveries may also inform the future development of novel treatment approaches

Static Scaling Behavior of High-Molecular-Weight Polymers in Dilute Solution: A Reexamination

Previous theories of dilute polymer solutions have failed to distinguish clearly between two very different ways of taking the long-chain limit: (I) $N \to\infty$ at fixed temperature $T$, and (II) $N \to\infty$, $T \to T_\theta$ with $x \equiv N^\phi (T-T_\theta)$ fixed. I argue that the modern two-parameter theory (continuum Edwards model) applies to case II --- not case I --- and in fact gives exactly the crossover scaling functions for $x \ge 0$ modulo two nonuniversal scale factors. A Wilson-type renormalization group clarifies the connection between crossover scaling functions and continuum field theories. [Also contains a general discussion of the connection between the Wilson and field-theoretic renormalization groups. Comments solicited.]Comment: 10 pages including 1 figure, 181159 bytes Postscript (NYU-TH-93/05/01

Causal relevance of blood lipid fractions in the development of carotid atherosclerosis: Mendelian randomization analysis.

BACKGROUND: Carotid intima-media thickness (CIMT), a subclinical measure of atherosclerosis, is associated with risk of coronary heart disease events. Statins reduce progression of CIMT and coronary heart disease risk in proportion to the reduction in low-density lipoprotein cholesterol. However, interventions targeting triglycerides (TGs) or high-density lipoprotein cholesterol (HDL-C) have produced inconsistent effects on CIMT and coronary heart disease risk, making it uncertain whether such agents are ineffective for coronary heart disease prevention or whether CIMT is an inadequate marker of HDL-C or TG-mediated effects. We aimed to determine the causal association among the 3 major blood lipid fractions and common CIMT using mendelian randomization analysis. METHODS AND RESULTS: Genetic scores specific for low-density lipoprotein cholesterol, HDL-C, and TGs were derived based on single nucleotide polymorphisms from a gene-centric array in ≈5000 individuals (Cardiochip scores) and from a genome-wide association meta-analysis in >100 000 individuals (Global Lipids Genetic Consortium scores). These were used as instruments in a mendelian randomization analysis in 2 prospective cohort studies. A genetically predicted 1 mmol/L higher low-density lipoprotein cholesterol concentration was associated with a higher common CIMT by 0.03 mm (95% confidence interval, 0.01-0.04) and 0.04 mm (95% confidence interval, 0.02-0.06) based on the Cardiochip and Global Lipids Genetic Consortium scores, respectively. HDL-C and TGs were not causally associated with CIMT. CONCLUSIONS: Our findings confirm a causal relationship between low-density lipoprotein cholesterol and CIMT but not with HDL-C and TGs. At present, the suitability of CIMT as a surrogate marker in trials of cardiovascular therapies targeting HDL-C and TGs is questionable and requires further study

Impacts of an intense wildfire smoke episode on surface radiation, energy and carbon fluxes in southwestern British Columbia, Canada

A short, but severe, wildfire smoke episode in July 2015, with an aerosol optical depth (AOD) approaching 9, is shown to strongly impact radiation budgets across four distinct land-use types (forest, field, urban and wetland). At three of the sites, impacts on the energy balance are also apparent, while the event also appears to elicit an ecosystem response with respect to carbon fluxes at the wetland and a forested site. Greatest impacts on radiation and energy budgets were observed at the forested site where the role of canopy architecture and the complex physiological responses to an increase in diffuse radiation were most important. At the forest site, the arrival of smoke reduced both sensible and latent heat flux substantially but also lowered sensible heat flux more than the latent heat flux. With widespread standing water, and little physiological control on evapotranspiration, the impacts on the partitioning of turbulent fluxes were modest at the wetland compared to the physiologically dominated fluxes at the forested site. Despite the short duration and singular nature of the event, there was some evidence of a diffuse radiation fertilization effect when AOD was near or below 2. With lighter smoke, both the wetland and forested site appeared to show enhanced photosynthetic activity (a greater sink for carbon dioxide). However, with dense smoke, the forested site was a strong carbon source. Given the extensive forest cover in the Pacific Northwest and the growing importance of forest fires in the region, these results suggest that wildfire aerosol during the growing season potentially plays an important role in the regional ecosystem response to smoke and ultimately the carbon budget of the region.</p

Sex-Stratified Genome-Wide Association Study of Multisite Chronic Pain in UK Biobank

Chronic pain is highly prevalent worldwide and imparts a significant socioeconomic and public health burden. Factors influencing susceptibility to, and mechanisms of, chronic pain development, are not fully understood, but sex is thought to play a significant role, and chronic pain is more prevalent in women than in men. To investigate sex differences in chronic pain, we carried out a sex-stratified genome-wide association study of Multisite Chronic Pain (MCP), a derived chronic pain phenotype, in UK Biobank on 178,556 men and 209,093 women, as well as investigating sex-specific genetic correlations with a range of psychiatric, autoimmune and anthropometric phenotypes and the relationship between sex-specific polygenic risk scores for MCP and chronic widespread pain. We also assessed whether MCP-associated genes showed expression pattern enrichment across tissues. A total of 123 SNPs at five independent loci were significantly associated with MCP in men. In women, a total of 286 genome-wide significant SNPs at ten independent loci were discovered. Meta-analysis of sex-stratified GWAS outputs revealed a further 87 independent associated SNPs. Gene-level analyses revealed sex-specific MCP associations, with 31 genes significantly associated in females, 37 genes associated in males, and a single gene, DCC, associated in both sexes. We found evidence for sex-specific pleiotropy and risk for MCP was found to be associated with chronic widespread pain in a sex-differential manner. Male and female MCP were highly genetically correlated, but at an rg of significantly less than 1 (0.92). All 37 male MCP-associated genes and all but one of 31 female MCP-associated genes were found to be expressed in the dorsal root ganglion, and there was a degree of enrichment for expression in sex-specific tissues. Overall, the findings indicate that sex differences in chronic pain exist at the SNP, gene and transcript abundance level, and highlight possible sex-specific pleiotropy for MCP. Results support the proposition of a strong central nervous-system component to chronic pain in both sexes, additionally highlighting a potential role for the DRG and nociception

Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites (BORTAS) experiment: design, execution and science overview

We describe the design and execution of the BORTAS (Quantifying the impact of BOReal forest fires on Tropospheric oxidants over the Atlantic using Aircraft and Satellites) experiment, which has the overarching objective of understanding the chemical aging of air masses that contain the emission products from seasonal boreal wildfires and how these air masses subsequently impact downwind atmospheric composition. The central focus of the experiment was a two-week deployment of the UK BAe-146-301 Atmospheric Research Aircraft (ARA) over eastern Canada, based out of Halifax, Nova Scotia. Atmospheric ground-based and sonde measurements over Canada and the Azores associated with the planned July 2010 deployment of the ARA, which was postponed by 12 months due to UK-based flights related to the dispersal of material emitted by the Eyjafjallajökull volcano, went ahead and constituted phase A of the experiment. Phase B of BORTAS in July 2011 involved the same atmospheric measurements, but included the ARA, special satellite observations and a more comprehensive ground-based measurement suite. The high-frequency aircraft data provided a comprehensive chemical snapshot of pyrogenic plumes from wildfires, corresponding to photochemical (and physical) ages ranging from 45 sr 10 days, largely by virtue of widespread fires over Northwestern Ontario. Airborne measurements reported a large number of emitted gases including semi-volatile species, some of which have not been been previously reported in pyrogenic plumes, with the corresponding emission ratios agreeing with previous work for common gases. Analysis of the NOy data shows evidence of net ozone production in pyrogenic plumes, controlled by aerosol abundance, which increases as a function of photochemical age. The coordinated ground-based and sonde data provided detailed but spatially limited information that put the aircraft data into context of the longer burning season in the boundary layer. Ground-based measurements of particulate matter smaller than 2.5 μm (PM2.5) over Halifax show that forest fires can on an episodic basis represent a substantial contribution to total surface PM2.5

UK and Ireland survey of MPharm student and staff experiences of mental health curricula, with a focus on Mental Health First Aid

Background: One in four people experience a mental health problem every year and improving mental health care is an international priority. In the course of their work, pharmacists frequently encounter people with mental health problems. The experience of mental health teaching, including Mental Health First Aid (MHFA) training, in undergraduate pharmacy (MPharm) students in the UK and Ireland is not well documented. Students’ viewpoints, contextualised with curricular overviews provided by staff, were analysed to understand their experience. Methods: An anonymous, online questionnaire was distributed to MPharm students and staff in the UK and Ireland. Students were asked closed questions regarding their course and exposure to MHFA, which were analysed using descriptive statistics. Open questions were included to enable explanations and these data were used to contextualise the quantitative findings. One member of staff from each university was invited to answer a modified staff version of the questionnaire, to provide a curriculum overview and staff perspective. Results: 232 students and 13 staff, from 22 universities, responded. Three-quarters of students did not agree with the statement that ‘mental health was embedded throughout the MPharm’. Most students (80.6%) stated that they were taught neuropharmacology whilst 44.8% stated that their course included communicating with people about their mental health. One-third (33.2%) of students stated that their degree ‘adequately prepared them to help people with their mental health’. Twenty-six students (11.6%) had completed MHFA training of which 89% would endorse inclusion of this within the MPharm. Of those who had not completed the training, 81% expressed a desire to do so. Those who completed MHFA training self-reported greater preparedness than those who did not, but student numbers were small. Conclusions: Mental health teaching for pharmacy undergraduates is more focussed on theoretical aspects rather than applied skills. MHFA was viewed by students as one way to enhance skill application. The association of the increased self-reported preparedness of those who completed MHFA could be confounded by a positive environmental cultural. MPharm programmes need sufficient focus on real-world skills such as communication and crisis response, to complement the fundamental science

Common Variants at 10 Genomic Loci Influence Hemoglobin A(1C) Levels via Glycemic and Nonglycemic Pathways

OBJECTIVE-Glycated hemoglobin (HbA(1c)), used to monitor and diagnose diabetes, is influenced by average glycemia over a 2- to 3-month period. Genetic factors affecting expression, turnover, and abnormal glycation of hemoglobin could also be associated with increased levels of HbA(1c). We aimed to identify such genetic factors and investigate the extent to which they influence diabetes classification based on HbA(1c) levels.RESEARCH DESIGN AND METHODS-We studied associations with HbA(1c) in up to 46,368 nondiabetic adults of European descent from 23 genome-wide association studies (GWAS) and 8 cohorts with de novo genotyped single nucleotide polymorphisms (SNPs). We combined studies using inverse-variance meta-analysis and tested mediation by glycemia using conditional analyses. We estimated the global effect of HbA(1c) loci using a multilocus risk score, and used net reclassification to estimate genetic effects on diabetes screening.RESULTS-Ten loci reached genome-wide significant association with HbA(1c), including six new loci near FN3K (lead SNP/P value, rs1046896/P = 1.6 x 10(-26)), HFE (rs1800562/P = 2.6 x 10(-20)), TMPRSS6 (rs855791/P = 2.7 x 10(-14)), ANK1 (rs4737009/P = 6.1 x 10(-12)), SPTA1 (rs2779116/P = 2.8 x 10(-9)) and ATP11A/TUBGCP3 (rs7998202/P = 5.2 x 10(-9)), and four known HbA(1c) loci: HK1 (rs16926246/P = 3.1 x 10(-54)), MTNR1B (rs1387153/P = 4.0 X 10(-11)), GCK (rs1799884/P = 1.5 x 10(-20)) and G6PC2/ABCB11 (rs552976/P = 8.2 x 10(-18)). We show that associations with HbA(1c) are partly a function of hyperglycemia associated with 3 of the 10 loci (GCK, G6PC2 and MTNR1B). The seven nonglycemic loci accounted for a 0.19 (%HbA(1c)) difference between the extreme 10% tails of the risk score, and would reclassify similar to 2% of a general white population screened for diabetes with HbA(1c).CONCLUSIONS-GWAS identified 10 genetic loci reproducibly associated with HbA(1c). Six are novel and seven map to loci where rarer variants cause hereditary anemias and iron storage disorders. Common variants at these loci likely influence HbA(1c) levels via erythrocyte biology, and confer a small but detectable reclassification of diabetes diagnosis by HbA(1c) Diabetes 59: 3229-3239, 201