Recent Advances in X-Ray Microanalysis in Dermatology

Electron microprobe and proton microprobe X-ray analysis can be used in several areas of dermatological research. With a proton probe, the distribution of trace elements in human hair can be determined. In contrast to sulfur, which is homogeneously distributed, calcium, iron, and zinc appear to be non-homogeneously distributed over the hair cross-section. Electron microprobe analysis on freeze-dried cryosections of guinea-pig and human epidermis shows a marked gradient of Na, P and K over the stratum granulosum. In sections of freeze-substituted human skin this gradient is less steep. This difference is likely to be due to a decrease in water content of the epidermis towards the stratum corneum. Electron microprobe analysis of the epidermis can, for analysis of trace elements, be complemented by the proton microprobe. Quantitative agreement between the two techniques can be obtained by the use of a standard. Proton micro probe analysis was used to determine the distribution of Ni or Cr in human epidermis exposed to nickel or chromate ions. Possible differences in water content between the stratum corneum of patients with atopic eczema and normal stratum corneum was investigated in skin freeze- substituted with Br-doped resin. No significant differences were observed. Proliferative reactions in the epidermis appear to be associated with increased levels of the elements P and K. Such changes were found in guinea-pig skin after exposure to sodium lauryl sulfate, and in plaques of skin from patients with psoriasis

Up-to-date on mortality in COPD - report from the OLIN COPD study

<p>Abstract</p> <p>Background</p> <p>The poor recognition and related underdiagnosis of COPD contributes to an underestimation of mortality in subjects with COPD. Data derived from population studies can advance our understanding of the true burden of COPD. The objective of this report was to evaluate the impact of COPD on mortality and its predictors in a cohort of subjects with and without COPD recruited during the twenty first century.</p> <p>Methods</p> <p>All subjects with COPD (n = 993) defined according to the GOLD spirometric criteria, FEV₁/FVC < 0.70, and gender- and age-matched subjects without airway obstruction, non-COPD (n = 993), were identified in a clinical follow-up survey of the Obstructive Lung Disease in Northern Sweden (OLIN) Studies cohorts in 2002-2004. Mortality was observed until the end of year 2007. Baseline data from examination at recruitment were used in the risk factor analyses; age, smoking status, lung function (FEV₁% predicted) and reported heart disease.</p> <p>Results</p> <p>The mortality was significantly higher among subjects with COPD, 10.9%, compared to subjects without COPD, 5.8% (p < 0.001). Mortality was associated with higher age, being a current smoker, male gender, and COPD. Replacing COPD with FEV₁% predicted in the multivariate model resulted in the decreasing level of FEV₁being a significant risk factor for death, while heart disease was not a significant risk factor for death in any of the models.</p> <p>Conclusions</p> <p>In this cohort COPD and decreased FEV₁were significant risk factors for death when adjusted for age, gender, smoking habits and reported heart disease.</p

Genome-Wide Association Analysis of Autoantibody Positivity in Type 1 Diabetes Cases

The genetic basis of autoantibody production is largely unknown outside of associations located in the major histocompatibility complex (MHC) human leukocyte antigen (HLA) region. The aim of this study is the discovery of new genetic associations with autoantibody positivity using genome-wide association scan single nucleotide polymorphism (SNP) data in type 1 diabetes (T1D) patients with autoantibody measurements. We measured two anti-islet autoantibodies, glutamate decarboxylase (GADA, n = 2,506), insulinoma-associated antigen 2 (IA-2A, n = 2,498), antibodies to the autoimmune thyroid (Graves') disease (AITD) autoantigen thyroid peroxidase (TPOA, n = 8,300), and antibodies against gastric parietal cells (PCA, n = 4,328) that are associated with autoimmune gastritis. Two loci passed a stringent genome-wide significance level (p<10(-10)): 1q23/FCRL3 with IA-2A and 9q34/ABO with PCA. Eleven of 52 non-MHC T1D loci showed evidence of association with at least one autoantibody at a false discovery rate of 16%: 16p11/IL27-IA-2A, 2q24/IFIH1-IA-2A and PCA, 2q32/STAT4-TPOA, 10p15/IL2RA-GADA, 6q15/BACH2-TPOA, 21q22/UBASH3A-TPOA, 1p13/PTPN22-TPOA, 2q33/CTLA4-TPOA, 4q27/IL2/TPOA, 15q14/RASGRP1/TPOA, and 12q24/SH2B3-GADA and TPOA. Analysis of the TPOA-associated loci in 2,477 cases with Graves' disease identified two new AITD loci (BACH2 and UBASH3A)

Seasonal climatic effects and feedbacks of anthropogenic heat release due to global energy consumption with CAM5

Anthropogenic heat release (AHR) is the heat generated in global energy consumption, which has not been considered in global climate models generally. The global high-resolution AHR from 1992 to 2013, which is estimated by using the Defense Meteorological Satellite Program (DMSP)/Operational Linescan System (OLS) satellite data, is implemented into the Community Atmosphere Model version 5 (CAM5). The seasonal climatic effects and possible feedbacks of AHR are examined in this study. The modeling results show that AHR increases the global annual mean surface temperature and land surface temperature by 0.02 ± 0.01 K (1σ uncertainty) and 0.05 ± 0.02 K (1σ uncertainty), respectively. The global climatic effect of AHR varies with season: with a stronger climatic effect in the boreal winter leading to global mean land surface temperature increases by 0.10 ± 0.01 K (1σ uncertainty). In the selected regions (40°N–60°N, 0°E–45°E) of Central and Western Europe the average surface temperature increases by 0.46 K in the boreal summer, and in the selected regions (45°N–75°N, 30°E–140°E) of northern Eurasia the average surface temperature increases by 0.83 K in the boreal winter. AHR changes the height and thermodynamic structure of the global planetary boundary layer, as well as the stability of the lower troposphere, which affects the global atmospheric circulation and low cloud fraction. In addition, at the surface both the shortwave radiation flux in the boreal summer and the down-welling longwave flux in the boreal winter change signifi- cantly, as a result of the change in low clouds caused by the effect of AHR. This study suggests a possible new mechanism of AHR effect on global climate through changing the global low-cloud fraction, which is crucial for global energy balance, by modifying the thermodynamic structure and stability of the lower troposphere. Thus this study improves our understanding of the global climate change caused by human activities

Coulomb dissociation of N 20,21

Neutron-rich light nuclei and their reactions play an important role in the creation of chemical elements. Here, data from a Coulomb dissociation experiment on N20,21 are reported. Relativistic N20,21 ions impinged on a lead target and the Coulomb dissociation cross section was determined in a kinematically complete experiment. Using the detailed balance theorem, the N19(n,γ)N20 and N20(n,γ)N21 excitation functions and thermonuclear reaction rates have been determined. The N19(n,γ)N20 rate is up to a factor of 5 higher at

SmokeHaz: systematic reviews and meta-analyses of the effects of smoking on respiratory health

Background: Smoking tobacco increases the risk of respiratory disease in adults and children, but communicating the magnitude of these effects in a scientific manner that is accessible and usable by public and policymakers presents a challenge. We have therefore summarised scientific data on the impact of smoking on respiratory diseases to provide the content for a unique resource, SmokeHaz. Methods: We conducted systematic reviews and meta-analyses of longitudinal studies (published to 2013) identified from electronic databases, grey literature, and experts. Random effect meta-analyses were used to pool the findings. Results: We included 216 papers. Among adult smokers, we confirmed substantially increased risks of lung cancer (Risk Ratio (RR) 10.92, 95% CI 8.28-14.40; 34 studies), COPD (RR 4.01, 95% CI 3.18-5.05; 22 studies) and asthma (RR 1.61, 95% CI 1.07-2.42; 8 studies). Exposure to passive smoke significantly increased the risk of lung cancer in adult non-smokers; and increased the risks of asthma, wheeze, lower respiratory infections, and reduced lung function in children. Smoking significantly increased the risk of sleep apnoea, and asthma exacerbations in adult and pregnant populations; and active and passive smoking increased the risk of tuberculosis. Conclusions: These findings have been translated into easily digestible content and published on the SmokeHaz website (www.smokehaz.eu)

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe