Pediatric Transplantation in the United States, 1996–2005

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73448/1/j.1600-6143.2007.01780.x.pd

Sibling comparisons elucidate the associations between educational attainment polygenic scores and alcohol, nicotine and cannabis.

Background and aimsThe associations between low educational attainment and substance use disorders (SUDs) may be related to a common genetic vulnerability. We aimed to elucidate the associations between polygenic scores for educational attainment and clinical criterion counts for three SUDs (alcohol, nicotine and cannabis).DesignPolygenic association and sibling comparison methods. The latter strengthens inferences in observational research by controlling for confounding factors that differ between families.SettingSix sites in the United States.ParticipantsEuropean ancestry participants aged 25 years and older from the Collaborative Study on the Genetics of Alcoholism (COGA). Polygenic association analyses included 5582 (54% female) participants. Sibling comparisons included 3098 (52% female) participants from 1226 sibling groups nested within the overall sample.MeasurementsOutcomes included criterion counts for DSM-5 alcohol use disorder (AUDSX), Fagerström nicotine dependence (NDSX) and DSM-5 cannabis use disorder (CUDSX). We derived polygenic scores for educational attainment (EduYears-GPS) using summary statistics from a large (> 1 million) genome-wide association study of educational attainment.FindingsIn polygenic association analyses, higher EduYears-GPS predicted lower AUDSX, NDSX and CUDSX [P < 0.01, effect sizes (R2 ) ranging from 0.30 to 1.84%]. These effects were robust in sibling comparisons, where sibling differences in EduYears-GPS predicted all three SUDs (P < 0.05, R2 0.13-0.20%).ConclusionsIndividuals who carry more alleles associated with educational attainment tend to meet fewer clinical criteria for alcohol, nicotine and cannabis use disorders, and these effects are robust to rigorous controls for potentially confounding factors that differ between families (e.g. socio-economic status, urban-rural residency and parental education)

Weak Reprocessed Features in the Broad Line Radio Galaxy 3C382

We present a detailed X-ray study of the Broad Line Radio Galaxy 3C382, observed with the BeppoSAX satellite in a very bright state. The continuum emission is well modeled with a power law that steepens at high energies, with an e-folding energy of about 120 keV. At soft energies a clear excess of emission is detected, which can not be explained solely by the extended thermal halo seen in a ROSAT HRI image. A second, more intense soft X-ray component, possibly related to an accretion disk, is required by the data. Both a reflection component (R=0.3) and an iron line (EW \sim 50) are detected, at levels much weaker than in Seyfert galaxies, suggesting a common origin. Combining our measurements with results from the literature we find that the iron line has remained approximately constant over 9 years while the continuum varied by a factor of 5. Thus the fluorescent gas does not respond promptly to the variations of the X-ray primary source, suggesting that the reprocessing site is located away, likely at parsec distances. While the continuum shape indicates that X-rays derive from a thermal Comptonization process, the weakness of other spectral features implies that either the upper layers of the optically thick accretion disk are completely ionized or the corona above the disk is outflowing with mildly relativistic velocity.Comment: 11 pages, 4 figures. Accepted for publication in the Astrophysical Journa

Functional characterisation of human pulmonary monocyte-like cells in lipopolysaccharide-mediated acute lung inflammation.

BACKGROUND: We have previously reported the presence of novel subpopulations of pulmonary monocyte-like cells (PMLC) in the human lung; resident PMLC (rPMLC, HLA-DR(+)CD14(++)CD16(+)cells) and inducible PMLC (iPMLC, HLA-DR(+)CD14(++)CD16(-) cells). iPMLC are significantly increased in bronchoalveolar lavage (BAL) fluid following inhalation of lipopolysaccharide (LPS). We have carried out the first functional evaluation of PMLC subpopulations in the inflamed lung, following the isolation of these cells, and other lineages, from BAL fluid using novel and complex protocols. METHODS: iPMLC, rPMLC, alveolar macrophages (AM), neutrophils, and regulatory T cells were quantified in BAL fluid of healthy subjects at 9 hours post-LPS inhalation (n = 15). Cell surface antigen expression by iPMLC, rPMLC and AM and the ability of each lineage to proliferate and to undergo phagocytosis were investigated using flow cytometry. Basal cytokine production by iPMLC compared to AM following their isolation from BAL fluid and the responsiveness of both cell types following in vitro treatment with the synthetic corticosteroid dexamethasone were assessed. RESULTS: rPMLC have a significantly increased expression of mature macrophage markers and of the proliferation antigen Ki67, compared to iPMLC. Our cytokine data revealed a pro-inflammatory, corticosteroid-resistant phenotype of iPMLC in this model. CONCLUSIONS: These data emphasise the presence of functionally distinct subpopulations of the monocyte/macrophage lineage in the human lung in experimental acute lung inflammation

Lung function decline over 25 years of follow-up among black and white adults in the ARIC study cohort

Interpretation of longitudinal information about lung function decline from middle to older age has been limited by loss to follow-up that may be correlated with baseline lung function or the rate of decline. We conducted these analyses to estimate age-related decline in lung function across groups of race, sex, and smoking status while accounting for dropout from the Atherosclerosis Risk in Communities Study

Classifying Chronic Lower Respiratory Disease Events in Epidemiologic Cohort Studies

Rationale: One in 12 adults has chronic obstructive pulmonary disease or asthma. Acute exacerbations of these chronic lower respiratory diseases (CLRDs) are a major cause of morbidity and mortality. Valid approaches to classifying cases and exacerbations in the general population are needed to facilitate prevention research

The Future of Indiana’s Water Resources: A Report from the Indiana Climate Change Impacts Assessment

This report from the Indiana Climate Change Impacts Assessment (IN CCIA) applies climate change projections for the state to explore how continued changes in Indiana’s climate are going to affect all aspects of water resources, including soil water, evaporation, runoff, snow cover, streamflow, drought, and flooding. As local temperatures continue to rise and rainfall patterns shift, managing the multiple water needs of communities, natural systems, recreation, industry, and agriculture will become increasingly difficult. Ensuring that enough water is available in the right places and at the right times will require awareness of Indiana’s changing water resources and planning at regional and state levels

The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands. Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry. Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell. Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus

Reorganization of surviving mammal communities after the end-Pleistocene megafaunal extinction

Large mammals are at high risk of extinction globally. To understand the consequences of their demise for community assembly, we tracked community structure through the end- Pleistocene megafaunal extinction in North America.We decomposed the effects of biotic and abiotic factors by analyzing co-occurrence within the mutual ranges of species pairs. Although shifting climate drove an increase in niche overlap, co-occurrence decreased, signaling shifts in biotic interactions. Furthermore, the effect of abiotic factors on cooccurrence remained constant over time while the effect of biotic factors decreased. Biotic factors apparently played a key role in continental-scale community assembly before the extinctions. Specifically, large mammals likely promoted co-occurrence in the Pleistocene, and their loss contributed to the modern assembly pattern in which co-occurrence frequently falls below random expectations. Includes supplementary materials

Reorganization of surviving mammal communities after the end-Pleistocene megafaunal extinction

Large mammals are at high risk of extinction globally. To understand the consequences of their demise for community assembly, we tracked community structure through the end-Pleistocene megafaunal extinction in North America. We decomposed the effects of biotic and abiotic factors by analyzing co-occurrence within the mutual ranges of species pairs. Although shifting climate drove an increase in niche overlap, co-occurrence decreased, signaling shifts in biotic interactions. Furthermore, the effect of abiotic factors on co-occurrence remained constant over time while the effect of biotic factors decreased. Biotic factors apparently played a key role in continental-scale community assembly before the extinctions. Specifically, large mammals likely promoted co-occurrence in the Pleistocene, and their loss contributed to the modern assembly pattern in which co-occurrence frequently falls below random expectations.Peer reviewe