Basic Atomic Physics

Contains reports on seven research projects.National Science Foundation (Grant PHY 87-06560)Joint Services Electronics Program (Contract DAAL03-86-K-0001)Joint Services Electronics Program (Contract DAAL03-89-C-0002)National Science Foundation (Grant PHY 86-05893)U.S. Navy - Office of Naval Research (Contract N00014-83-K-0695)U.S. Navy - Office of Naval Research (Contract N00014-89-J-1207

Basic Atomic Physics

Contains reports on five research projects.Joint Services Electronics Program Contract DAAL03-89-C-0001National Science Foundation Grant PHY 87-06560National Science Foundation Contract PHY 86-05893U.S. Army Research Office Contract DAAL03-89-K-0082U.S. Navy - Office of Naval Research Contract N00014-89-J-1207U.S. Navy - Office of Naval Research Contract N00014-83-K-069

Common Genetic Polymorphisms Influence Blood Biomarker Measurements in COPD

Implementing precision medicine for complex diseases such as chronic obstructive lung disease (COPD) will require extensive use of biomarkers and an in-depth understanding of how genetic, epigenetic, and environmental variations contribute to phenotypic diversity and disease progression. A meta-analysis from two large cohorts of current and former smokers with and without COPD [SPIROMICS (N = 750); COPDGene (N = 590)] was used to identify single nucleotide polymorphisms (SNPs) associated with measurement of 88 blood proteins (protein quantitative trait loci; pQTLs). PQTLs consistently replicated between the two cohorts. Features of pQTLs were compared to previously reported expression QTLs (eQTLs). Inference of causal relations of pQTL genotypes, biomarker measurements, and four clinical COPD phenotypes (airflow obstruction, emphysema, exacerbation history, and chronic bronchitis) were explored using conditional independence tests. We identified 527 highly significant (p 10% of measured variation in 13 protein biomarkers, with a single SNP (rs7041; p = 10−392) explaining 71%-75% of the measured variation in vitamin D binding protein (gene = GC). Some of these pQTLs [e.g., pQTLs for VDBP, sRAGE (gene = AGER), surfactant protein D (gene = SFTPD), and TNFRSF10C] have been previously associated with COPD phenotypes. Most pQTLs were local (cis), but distant (trans) pQTL SNPs in the ABO blood group locus were the top pQTL SNPs for five proteins. The inclusion of pQTL SNPs improved the clinical predictive value for the established association of sRAGE and emphysema, and the explanation of variance (R2) for emphysema improved from 0.3 to 0.4 when the pQTL SNP was included in the model along with clinical covariates. Causal modeling provided insight into specific pQTL-disease relationships for airflow obstruction and emphysema. In conclusion, given the frequency of highly significant local pQTLs, the large amount of variance potentially explained by pQTL, and the differences observed between pQTLs and eQTLs SNPs, we recommend that protein biomarker-disease association studies take into account the potential effect of common local SNPs and that pQTLs be integrated along with eQTLs to uncover disease mechanisms. Large-scale blood biomarker studies would also benefit from close attention to the ABO blood group

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Middle School to Professional Development: Interdisciplinary STEM for Multiple Stakeholders

The STEMITL project is an interdisciplinary collaboration between a Southeastern University\u27s middle grades education department and local PDS partner school districts incorporating six full-day immersive projects for seventh-grade students. During the 2016-2017 academic year, seventh-grade students were brought to the university\u27s newly constructed STEAM Center where middle grades practicum students implemented day-long interdisciplinary lessons co-designed by faculty and teacher candidates. Lessons incorporated social studies, science, mathematics, and literacy around a central theme of water pollution in China

Advancing the science of patient safety and quality improvement to the next level

This paper describes our journey to advance the science and practice of patient safety and quality improvement. The journey began with efforts to identify hazards through an incident reporting system called the Intensive Care Unit Safety Reporting System. We quickly found that identifying hazards was merely a first step. We also needed to investigate and learn from these hazards to prevent patient harm. Therefore, we developed the Comprehensive Unit-based Safety Program (CUSP) to identify and learn from local defects and improve teamwork and safety culture. Teams across many units faced common problems, such as healthcare-acquired infections, for which there is empiric evidence on prevention practices, but the evidence is unreliably applied. This discovery led us to develop a model to translate research into practice (TRIP). We combined TRIP with CUSP for the Keystone ICU Project design, with the goal of improving care for adult patients in Michigan intensive care units (ICUs). The resulting dramatic and sustained reductions in central line-associated bloodstream infections (CLABSIs) in Michigan led to a national initiative to reduce CLABSIs across the United States. Applying the perspectives from different academic disciplines helped us learn how this national effort succeeded, an approach we also used to study cardiac surgery-related errors. Still, the CLABSI effort addressed one type of harm, while patients are at risk for over a dozen and care systems relying more on the heroism of clinicians than on safe design. Current efforts include building a quality management infrastructure to support improvement work and defining the skills, resources, and accountability needed at every level of a health system. We are also partnering with patients, their loved ones, and others to eliminate all harms, optimize patient experience and outcomes, and reduce waste. In this trans-disciplinary systems approach, we hope to reduce all harms, improve productivity, and enhance joy for clinicians

Genome-wide association study of lung function and clinical implication in heavy smokers.

BackgroundThe aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD.MethodsGenome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers.ResultsA functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10- 8) and FEV1 (p = 2.1 × 10- 9). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10- 4) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P <  2.2 × 10- 16).ConclusionsThis study is the first to show genome-wide significant association of rs28929474 in SERPINA1 with lung function. Of clinical importance, heterozygotes of rs28929474 (4.7% of subjects) have significantly reduced pulmonary function, demonstrating a major impact in smokers. The multi-gene model is significantly associated with CT-based emphysema and clinical outcome measures of severity. Combining genetic information with demographic and environmental factors will further increase the predictive power for assessing reduced lung function and COPD severity

Genome-wide association study of lung function and clinical implication in heavy smokers

Abstract Background The aim of this study is to identify genetic loci associated with post-bronchodilator FEV1/FVC and FEV1, and develop a multi-gene predictive model for lung function in COPD. Methods Genome-wide association study (GWAS) of post-bronchodilator FEV1/FVC and FEV1 was performed in 1645 non-Hispanic White European descent smokers. Results A functional rare variant in SERPINA1 (rs28929474: Glu342Lys) was significantly associated with post-bronchodilator FEV1/FVC (p = 1.2 × 10− 8) and FEV1 (p = 2.1 × 10− 9). In addition, this variant was associated with COPD (OR = 2.3; p = 7.8 × 10− 4) and severity (OR = 4.1; p = 0.0036). Heterozygous subjects (CT genotype) had significantly lower lung function and higher percentage of COPD and more severe COPD than subjects with the CC genotype. 8.6% of the variance of post-bronchodilator FEV1/FVC can be explained by SNPs in 10 genes with age, sex, and pack-years of cigarette smoking (P <  2.2 × 10− 16). Conclusions This study is the first to show genome-wide significant association of rs28929474 in SERPINA1 with lung function. Of clinical importance, heterozygotes of rs28929474 (4.7% of subjects) have significantly reduced pulmonary function, demonstrating a major impact in smokers. The multi-gene model is significantly associated with CT-based emphysema and clinical outcome measures of severity. Combining genetic information with demographic and environmental factors will further increase the predictive power for assessing reduced lung function and COPD severity