Search

BACKGROUND. Most GWAS of plasma proteomics have focused on White individuals of European ancestry, limiting biological insight from other ancestry-enriched protein quantitative loci (pQTL). METHODS. We conducted a discovery GWAS of approximately 3,000 plasma proteins measured by the antibody-based Olink platform in 1,054 Black adults from the Jackson Heart Study (JHS) and validated our findings in the Multi-Ethnic Study of Atherosclerosis (MESA). The genetic architecture of identified pQTLs was further explored through fine mapping and admixture association analysis. Finally, using our pQTL findings, we performed a phenome-wide association study (PheWAS) across 2 large multiethnic electronic health record (EHR) systems in All of Us and BioMe. RESULTS. We identified 1,002 pQTLs for 925 protein assays. Fine mapping and admixture analyses suggested allelic heterogeneity of the plasma proteome across diverse populations. We identified associations for variants enriched in African ancestry, many in diseases that lack precise biomarkers, including c/s-pQTLs for cathepsin L (CTSL) and Siglec-9, which were linked with sarcoidosis and non-Hodgkin's lymphoma, respectively. We found concordant associations across clinical diagnoses and laboratory measurements, elucidating disease pathways, including a cis-pQTL associated with circulating CD58, WBC count, and multiple sclerosis. CONCLUSIONS. Our findings emphasize the value of leveraging diverse populations to enhance biological insights from proteomics GWAS, and we have made this resource readily available as an interactive web portal. FUNDING. NIH K08 HL161445-01A1; 5T32HL160522-03; HHSN268201600034I; HL133870., Introduction Large-scale GWAS have uncovered thousands of loci implicated in human disease. However, genotype is often far removed from phenotype, limiting insight into the pathological processes that result in disease. [...]

Clonal hematopoiesis of indeterminate potential (CHIP) is associated with an increased risk of cardiovascular diseases (CVDs), putatively via inflammasome activation. We pursued an inflammatory gene modifier scan for CHIP-associated CVD risk among 424,651 UK Biobank participants. We identified CHIP using whole-exome sequencing data of blood DNA and modeled as a composite, considering all driver genes together, as well as separately for common drivers (DNMT3A, TET2, ASXL1, and JAK2). We developed predicted gene expression scores for 26 inflammasome-related genes and assessed how they modify CHIP-associated CVD risk. We identified IL1RAP as a potential key molecule for CHIP-associated CVD risk across genes and increased AIM2 gene expression leading to heightened JAK2- and ASXLI-associated CVD risk. We show that CRISPR-induced Asx/1-mutated murine macrophages had a particularly heightened inflammatory response to AIM2 agonism, associated with an increased DNA damage response, as well as increased IL-10 secretion, mirroring a CVDprotective effect of IL10 expression in ASXL1 CHIP. Our study supports the role of inflammasomes in CHIP-associated CVD and provides evidence to support gene-specific strategies to address CHIP-associated CVD risk., Introduction Clonal hematopoiesis (CH) of indeterminate potential (CHIP) is the age-related acquisition and expansion of somatic mutations of genes frequently mutated in hematologic malignancies (e.g., DNMT3A, TET2, ASXL1, or JAK2) [...]

PURPOSE Over 95% of patients who screen positive on the Patient Health Questionnaire-9 (PHQ-9) suicide risk item do not attempt or die by suicide, which could lead to unnecessary treatment and/or misallocation of limited resources. The present study seeks to determine if suicide risk screening can be meaningfully improved to identify the highest-risk patients. METHODS Patients eligible to receive medical treatment from the US Department of Defense medical system were recruited from 6 military primary care clinics located at 5 military installations around the United States. Patients completed self-report measures including the PHQ-9 and 16 items from the Suicide Cognitions Scale (SCS) during routine primary care clinic visits. Postbaseline suicidal behaviors (suicide attempts, interrupted attempts, and aborted attempts) were assessed by evaluators who were blind to screening results using the Self-Injurious Thoughts and Behaviors Interview. RESULTS Among 2,744 patients, 13 (0.5%) engaged in suicidal behavior in the 30 days after screening and 28 (1.0%) displayed suicidal behavior in the 90 days after screening. Multiple SCS items differentiated patients with suicidal behavior less than 30 days after screening positive for suicide risk. Augmenting the PHQ-9 suicide risk item with SCS items improved the identification of patients who were most likely to have suicidal behavior within a month of screening positive without sacrificing sensitivity. CONCLUSION Among primary care patients who screen positive for suicide risk on the PHQ-9, SCS items improved screening efficiency by identifying those patients who are most likely to engage in suicidal behavior within the next 30 days. Key words: primary health care; mass screening, suicide, INTRODUCTION From 1999 to 2017, the US suicide rate increased by more than 33%. (1) Suicides have increased at an even faster rate among military personnel and veterans. (2) Nearly [...]

African Americans and other minorities (AAOM) are under-represented in careers in medicine, public health, and research. Furthermore, African Americans suffer more disproportionately from racial health disparities across most health indicators. Scholars suggest that the underrepresentation of AAOM public health and medical professionals contributes to the racial and ethnic health disparity trends in the USA. Thus, an increase in African American public health professionals may lead to a decrease in health disparities in African American communities. This manuscript will share a qualitative research study designed to explore motivators to engage African American students into careers in public health. Grounded theory and the feedforward model were used to explore critical career motivators, career decisions, career trajectories, barriers, and methods to overcome barriers among 20 African American public health graduate students and professionals. Eight motivators and six recommendations were identified to engage African Americans into careers in Public Health., Author(s): Kent D. Key [sup.1] [sup.2] Author Affiliations: (1) grid.17088.36, 0000 0001 2150 1785, College of Human Medicine, Division of Public Health, Michigan State University, , 200 East 1st Street, [...]

Veterans who have experienced traumatic events may develop posttraumatic stress disorder (PTSD) and depression. These traumatic experiences and their sequelae can lead Veterans to question their religious and spiritual faith. [...]

The adipose-derived hormone leptin maintains energy balance in part through central nervous system-mediated increases in sympathetic outflow that enhance fat burning. Triggering of β-adrenergic receptors in adipocytes stimulates energy expenditure by cyclic AMP (cAMP)-dependent increases in lipolysis and fatty-acid oxidation. Although the mechanism is unclear, catecholamine signalling is thought to be disrupted in obesity, leading to the development of insulin resistance. Here we show that the cAMP response element binding (CREB) coactivator Crtc3 promotes obesity by attenuating β-adrenergic receptor signalling in adipose tissue. Crtc3 was activated in response to catecholamine signals, when it reduced adenyl cyclase activity by upregulating the expression of Rgs2, a GTPase-activating protein that also inhibits adenyl cyclase activity. As a common human CRTC3 variant with increased transcriptional activity is associated with adiposity in two distinct Mexican-American cohorts, these results suggest that adipocyte CRTC3 may play a role in the development of obesity in humans., Obesity is a major risk factor in the development of insulin resistance, which is characterized by decreased glucose uptake into muscle and increased glucose production by the liver. Obesity affects [...]

CGI-58 is the defective gene in the human neutral lipid storage disease called Chanarin-Dorfman syndrome. This disorder causes intracellular lipid droplets to accumulate in nonadipose tissues, such as skin and blood cells. Here, disruption of the homologous CGI-58 gene in Arabidopsis thaliana resulted in the accumulation of neutral lipid droplets in mature leaves. Mass spectroscopy of isolated lipid droplets from cgi-58 loss-of-function mutants showed they contain triacylglycerols with common leaf-specific fatty acids. Leaves of mature cgi-58 plants exhibited a marked increase in absolute triacylglycarol levels, more than 10-fold higher than in wild-type plants. Lipid levels in the oil-storing seeds of cgi-58 loss-of-function plants were unchanged, and unlike mutations in [beta]-oxidation, the cgi-58 seeds germinated and grew normally, requiring no rescue with sucrose. We conclude that the participation of CGI-58 in neutral lipid homeostasis of nonfat-storing tissues is similar, although not identical, between plant and animal species. This unique insight may have implications for designing a new generation of technologies that enhance the neutral lipid content and composition of crop plants. compartmentation | plant lipid metabolism doi/ 10.1073/pnas.0911359107

The hematopoietic system produces a large number of highly specialized cell types that are derived through a hierarchical differentiation process from a common stem cell population, miRNAs are critical players in orchestrating this differentiation. Here, we report the development and application of a high-throughput microfluidic real-time quantitative PCR (RT-qPCR) approach for generating global miRNA profiles for 27 phenotypically distinct cell populations isolated from normal adult mouse hematopoietic tissues. A total of 80,000 RT-qPCR assays were used to map the landscape of miRNA expression across the hematopoietic hierarchy, including rare progenitor and stem cell populations. We show that miRNA profiles allow for the direct inference of cell lineage relations and functional similarity. Our analysis reveals a close relatedness of the miRNA expression patterns in multipotent progenitors and stem cells, followed by a major reprogramming upon restriction of differentiation potential to a single lineage. The analysis of miRNA expression in single hematopoietic cells further demonstrates that miRNA expression is very tightly regulated within highly purified populations, underscoring the potential of single-cell miRNA profiling for assessing compartment heterogeneity. RT-qPCR | stem cell | hematopoiesis | microfluidic | single cell doi/ 10.1073/pnas.1009320107

Background. Genome-wide association studies (GWAS) may yield insights into longevity. Methods. We performed a meta-analysis of GWAS in Caucasians from four prospective cohort studies: the Age, Gene/ Environment Susceptibility-Reykjavik Study, the Cardiovascular Health Study, the Framingham Heart Study, and the Rotterdam Study participating in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) Consortium. Longevity was defined as survival to age 90 years or older (n = 1,836); the comparison group comprised cohort members who died between the ages of 55 and 80 years (n = 1,955). In a second discovery stage, additional genotyping was conducted in the Leiden Longevity Study cohort and the Danish 1905 cohort. Results. There were 273 single-nucleotide polymorphism (SNP) associations with p < .0001, but none reached the prespecified significance level of 5 x [10.sup.-8]. Of the most significant SNPs, 24 were independent signals, and 16 of these SNPs were successfully genotyped in the second discovery stage, with one association for rs9664222, reaching 6.77 x [10.sup.-7] for the combined meta-analysis of CHARGE and the stage 2 cohorts. The SNP lies in a region near MINPP1 (chromosome 10), a well-conserved gene involved in regulation of cellular proliferation. The minor allele was associated with lower odds of survival past age 90 (odds ratio = 0.82). Associations of interest in a homologue of the longevity assurance gene (LASS3) and PAPPA2 were not strengthened in the second stage. Conclusion. Survival studies of larger size or more extreme or specific phenotypes may support or refine these initial findings. Key Words: Longevity--Genome-wide association study--Meta-analysis. doi: 10.1093/gerona/glq028

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jpubeco.2009.12.004 Byline: Kent D. Messer (a), Gregory L. Poe (b), Daniel Rondeau (c), William D. Schulze (b), Christian A. Vossler (d) Keywords: Voting; Social preferences; Random price voting mechanism Abstract: Public referenda are frequently used to determine the provision of public goods. As public programs have distributional consequences, a compelling question is what impact, if any, do social preferences have on voting behavior. This paper explores this issue using laboratory experiments wherein voting outcomes lead to a known distribution of net benefits across participants. Preferences are elicited using a novel Random Price Voting Mechanism (RPVM), which is more efficient in eliciting preferences than a dichotomous choice referendum but gives consistent results. Results suggest that social preferences, in particular a social efficiency motive, lead to economically meaningful deviations from selfish voting choices and increase the likelihood that welfare-enhancing programs are implemented. Author Affiliation: (a) University of Delaware, United States (b) Cornell University, United States (c) University of Victoria, Canada (d) University of Tennessee, United States Article History: Received 11 March 2008; Revised 18 December 2009; Accepted 21 December 2009

Models of organizational learning typically assume that organizations rely upon performance feedback and that an exogenous (uncontrollable) environment presents the problems that organizations seek to solve. By contrast, we consider [...]

Transmissible spongiform encephalopathies (TSEs), or prion diseases, are neurodegenerative diseases that affect many mammalian species. Some examples include bovine spongiform encephalopathy (BSE) in cattle, scrapie in sheep and goats, Creutzfeldt-Jakob [...]

Anti-Semitism is resurgent throughout much of the world. A new theoretical model of anti-Semitism is presented and tested in 3 experiments. The model proposes that mortality salience increases anti-Semitism and that anti-Semitism often manifests as hostility toward Israel. Study 1 showed that mortality salience led to greater levels of anti-Semitism and lowered support for Israel. This effect occurred only in a bogus pipeline condition, indicating that social desirability masks hostility toward Jews and Israel. Study 2 showed that mortality salience caused Israel, but no other country, to perceptually loom large. Study 3 showed that mortality salience increased punitiveness toward Israel's human rights violations more than it increased hostility toward the identical human rights violations committed by Russia or India. Collectively, results suggest that Jews constitute a unique cultural threat to many people's worldviews, that anti-Semitism causes hostility to Israel, and that hostility to Israel may feed back to increase anti-Semitism. Keywords: anti-Semitism, Israel, subtle prejudice, terror management theory, human rights

The loss introduced by an etched photonic crystal in a vertical-cavity surface-emitting laser (VCSEL) has contributed to the transverse optical confinement and supported modes. The effect of modal loss on the slope efficiency and modal behavior is examined and the model is consistent with experimental measurements and has provided a means of accurate design of single-mode photonic crystal VCSELs.

A study was carried out to determine the role of human genes in the incidence and risk of a cardiac stroke. Results revealed that patients with the presence of genetic locus on chromosome 12p13 are at a higher risk of experiencing a cardiac stroke.

The modernist perceptions in organizational risk research, and their limitations and origin are investigated. From a modernist view, risk research centers mainly on individuals, treating risk preferences as provided exogenously and omitting ethical factors. A contradicting post-modern approach in organizational risk is proposed.

Three groups of pigeons were trained in a same/different task with 32, 64, or 1,024 color-picture stimuli. They were tested with novel transfer pictures. The training-testing cycle was repeated with training-set doublings. The 32-item group learned the same/different task as rapidly as a previous 8-item group and transferred better than the 8-item group at the 32-item training set. The 64- and 1,024-item groups learned the task only somewhat slower than other groups, but their transfer was better and equivalent to baseline performances. These results show that pigeons trained with small sets (e.g., 8 items) have carryover effects that hamper transfer when the training set is expanded. Without carryover effects (i.e., initial transfer from the 32- and 64-item groups), pigeons show the same degree of transfer as rhesus and capuchin monkeys at these same set sizes. This finding has implications for the general ability of abstract-concept learning across species with different neural architectures. Keywords: same-different learning, abstract-concept learning, item-specific learning, relational learning, restricted domain learning

Transmissible spongiform encephalopathy (TSE) diseases are known to cross species barriers, but the pathologic and biochemical changes that occur during transmission are not well understood. To better understand these changes, [...]

Numerous writers have argued that our nation's ecological problems stem in large part from the traditional values, attitudes and beliefs prevalent within our society (e.g., Disch, 1970). For example, it [...]

Noncontact long-range position sensing is desirable for a number of applications. We have designed and fabricated a monolithically integrated vertical-cavity surface-emitting laser (VCSEL) and p-type/ intrinsic/n-type (PIN) photodetectors for optical position sensing. Calculations using the reflection from a periodic metallic corrugation as a position gauge indicate resolution in the submicron regime. High device uniformity is obtained using novel fabrication techniques. We observe a threshold current of 0.52 mA for the VCSELs and a detector responsivity of 0.38 A/W at 840 nm. The optical cross talk between VCSELs and detectors is also quantified. OCIS codes: 130.5990, 250.7260.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1744-7976.2008.00130.x Byline: Maurice Doyon (1), Virginie Simard (2), Kent D. Messer (3), Lota D. Tamini (4), Harry M. Kaiser (5) Abstract: Using experimental economics, this paper tests the potential impacts of modifying the centralized quota exchange system in Quebec with the intent of decreasing the quota price while minimizing negative impacts on auction effectiveness. Two separate treatments are applied to a uniform price auction similar to that employed in Quebec. The first treatment is an exclusion (5% or 15%) of the highest buyer bids and seller offers. The second is a tax (2% or 10%) on all units offered for sale that remain unsold. Various combinations of the two treatments are also tested. The results suggest that exclusion of the highest bids and offers can decrease the price of the quota and that a 15% exclusion rate is more effective than a 5% rate. The tax alone has little impact on quota price. The combination of the two treatments generates a more marked reduction in both the number of exchanges and the price of the quota than when the tax or the exclusion is applied individually. However, the combination of treatments results in a greater loss of economic efficiency. In all cases, relatively small market price reductions are realized at the expense of substantial losses in economic efficiency. La presente etude teste de maniere experimentale la capacite d'une modification au systeme centralise de vente du quota a faire diminuer le prix du quota laitier au Quebec tout en minimisant les impacts negatifs des changements sur l'efficacite de l'enchere. Cette modification consiste a appliquer deux traitements sur l'enchere de prix uniforme ou s'echange le quota. Le premier traitement consiste en une exclusion (5% ou 15%) des mises les plus elevees des acheteurs et des vendeurs. Le second traitement est une taxe (2% ou 10%) appliquee aux unites que les vendeurs mettent en marche et ne reussissent pas a vendre. Differentes combinaisons de ces deux traitements sont egalement testees. Les donnees generees permettent de conclure que le mecanisme d'exclusion des mises les plus elevees permet de faire diminuer le prix du quota, l'exclusion de 15%etant plus efficace que celle de 5%. Pour sa part, la taxe seule a peu d'impact sur le prix du quota tandis que la combinaison des deux traitements entraine une diminution du nombre de transactions et du prix du quota plus marquee que lorsque les traitements de taxe et d'exclusion sont appliques individuellement. Cela a comme corollaire d'entrainer une perte d'efficaciteeconomique plus importante. Dans tous les cas, des baisses de prix de marche relativement modestes sont realisees au cout d'importantes pertes d'efficaciteeconomique. Author Affiliation: (1)Professor, Department of Agricultural Economics and Consumer Science, 4310-F, Pavillon Paul-Comtois, Laval University, Quebec, Quebec G1K 7P4 (corresponding author: phone: 418-656-2131, ext: 4546; fax: 418-656-7821; e-mail:Maurice.doyon@eac.ulaval.ca). (2)Analyst at La Financiere Agricole, 1026 chemin St-Joseph, St-Nicolas, Quebec G7A 2A3 (phone: 418-831-8445; e-mail:simardvirginie@hotmail.com). (3)Assistant Professor, Food & Resource Economics, 266 Townsead Hall, University of Delaware, Newark, DE 19716 (phone: 302-831-1316; e-mail:messer@udel.edu). (4)Senior Researcher, Institut de Recherche et de Developpement en Agroenvironnement (IRDA), 2700, rue Einstein Quebec, Quebec, G1P 3W8 (phone: 418-646-7826; e-mail:lota-d.tamini@irda.qc.ca). (5)Professor, Cornell University, Department of Applied Economics and Management, 350 Warren Hall, Ithaca, NY 14850 (phone: 607-255-1598; e-mail:hmk2@Cornell.edu).

The study attempts to test a firm-level behavioral explanation for differences in firm's propensities to engage in acquisitions. The results indicate that firm-level behavioral characteristics played a significant role in explaining which firms engaged in acquisition activity.

A study was conducted to explain the views of Herbert A. Simon and Michael Polanyi on rationality and knowledge. Their disparities to differing underlying philosophical perspectives are traced. Simon's work emphasized cognition over action, knowledge over tacit knowledge, and means over ends. Polanyi, on the other hand, provides counterbalancing emphases for these orientations.

In an effort to better understand the mechanisms that regulate oil accumulation and packaging in seeds, transgenic cotton lines were generated using a Brassica napus nonfunctional delta-12 fatty acid desaturase (FAD2) gene under control of the phaseolin promoter. Seeds of numerous transgenic plant lines had reduced oil content compared with null-segregating siblings or nontransformed seeds. Seed oil content was quantified by [sup.1]H-NMR, and was reduced to 12% or less of seed weight in transgenics from 20% by weight in nontransformed controls. Light- and electron-microscopic analyses of severely Iowered lines, showed a reduction in overall cotyledon thickness and a disruption in cellular and subcellular organization. Lipid bodies and protein bodies were fewer in transgenics, and their size and distribution in cells was different than that in nontransformed seeds. Coincident with reduced storage reserves, sucrose levels were elevated in transgenic seeds. The overall effect of oil suppression was to selectively reduce the size of the embryo, but the seed coat and fiber properties remained unaffected in seeds. In fact there was a significant increase in lint percentage in all oil-suppressed lines examined. Overall we propose that expression of the nonfunctional Bnfad2 allele in cottonseeds disrupts normal oil biosynthesis and provides for redirection of carbon reserves.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1559-1816.2008.00356.x Byline: Kent D. Harber (a2), Lee Jussim (b), Kathleen A. Kennedy (c), Robin Freyberg (d), Lisa Baum (b) Abstract: This research introduces the Social Support Opinion Survey (SSOS), the first measure of social support from the provider's perspective. Studies 1-3 developed the SSOS and confirmed that support opinions can be reliably characterized as directive (attempting to govern how others cope) and nondirective (facilitating without governing how others cope). Studies 4-6 showed that social support opinions relate to more basic cognitive, emotional, and interpersonal styles. Directive opinions were related to cognitive rigidity (need for structure, need for certainty, and just-world beliefs) and to an exchange orientation. Nondirective opinions, in contrast, were related to emotional differentiation, use of emotions as information, empathy, and a communal orientation. Thus, people may reveal who they are by how they help. Author Affiliation: (a)Rutgers University at Newark (b)Rutgers University (c)Princeton University (d)Stern College for WomenYeshiva University Article note: (2) Kent D. Harber, Department of Psychology, Rutgers University at Newark, Smith Hall, 101 Warren Street, Newark, NJ 07102. E-mail: kharber@psychology.rutgers.edu

Concepts--rules that transcend training stimuli--have been argued to be unique to some species. Pigeons, a focus of much concept-learning research, were tested for learning a matching-to-sample abstract concept. Five pigeons were trained with three cartoon stimuli. Pigeons pecked a sample 10 times and then chose which of two simultaneously presented comparison stimuli matched the sample. After acquisition, abstract-concept learning was tested by presenting novel cartoons on 12 out of 96 trials for 4 consecutive sessions. A cycle of doubling the training set followed by retraining and novel-testing was repeated eight times, increasing the set size from 3 to 768 items. Transfer performance improved from chance (i.e., no abstract-concept learning) to a level equivalent to baseline performance (>80%) and was similar to an equivalent function for same/different abstract-concept learning. Analyses assessed the possibility that item-specific choice strategies accounted for acquisition and transfer performance. These analyses converged to rule out item-specific strategies at all but the smallest set-sizes (3-24 items). Ruling out these possibilities adds to the evidence that pigeons learned the relational abstract concept of matching-to-sample. Keywords: matching-to-sample, same/different, abstract-concept learning, generalized matching, pigeon

Background Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods & findings Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10.sup.-29 ); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses., Author(s): Eleanor Wheeler 1, Aaron Leong 2,3, Ching-Ti Liu 4, Marie-France Hivert 5,6, Rona J. Strawbridge 7,8, Clara Podmore 9,10, Man Li 11,12,13, Jie Yao 14, Xueling Sim 15, Jaeyoung [...]

Height is a highly heritable, classic polygenic trait with approximately 700 common associated variants identified through genome-wide association studies so far. Here, we report 83 height-associated coding variants with lower minor-allele frequencies (in the range of 0.14.8%) and effects of up to 2centimetres per allele (such as those in IHH, STC2, AR and CRISPLD2), greater than ten times the average effect of common variants. In functional follow-up studies, rare height-increasing alleles of STC2 (giving an increase of 12centimetres per allele) compromised proteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4 in vitro, resulting in higher bioavailability of insulin-like growth factors. These 83 height-associated variants overlap genes that are mutated in monogenic growth disorders and highlight new biological candidates (such as ADAMTS3, IL11RA and NOX4) and pathways (such as proteoglycan and glycosaminoglycan synthesis) involved in growth. Our results demonstrate that sufficiently large sample sizes can uncover rare and low-frequency variants of moderate-to-large effect associated with polygenic human phenotypes, and that these variants implicate relevant genes and pathways., Author(s): Eirini Marouli [1]; Mariaelisa Graff [2]; Carolina Medina-Gomez [3, 4]; Ken Sin Lo [5]; Andrew R. Wood [6]; Troels R. Kjaer [7]; Rebecca S. Fine [8, 9, 10]; Yingchang [...]

Chronic granulomatous disease (CGD) is an inherited immune deficiency characterized by increased susceptibility to infection with Staphylococcus, certain gram-negative bacteria, and fungi. Granulibacter bethesdensis, a newly described genus and species within the family Acetobacteraceae, was recently isolated from four CGD patients residing in geographically distinct locales who presented with fever and lymphadenitis. We sequenced the genome of the reference strain of Granulibacter bethesdensis, which was isolated from lymph nodes of the original patient. The genome contains 2,708,355 base pairs in a single circular chromosome, in which 2,437 putative open reading frames (ORFs) were identified, 1,470 of which share sequence similarity with ORFs in the nonpathogenic but related Gluconobacter oxydans genome. Included in the 967 ORFs that are unique to G. bethesdensis are ORFs potentially important for virulence, adherence, DNA uptake, and methanol utilization. GC% values and best BLAST analysis suggested that some of these unique ORFs were recently acquired. Comparison of G. bethesdensis to other known CGD pathogens demonstrated conservation of some putative virulence factors, suggesting possible common mechanisms involved in pathogenesis in CGD. Genotyping of the four patient isolates by use of a custom microarray demonstrated genome-wide variations in regions encoding DNA uptake systems and transcriptional regulators and in hypothetical ORFs. G. bethesdensis is a genetically diverse emerging human pathogen that may have recently acquired virulence factors new to this family of organisms.

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.jpubeco.2007.08.001 Byline: Kent D. Messer (a), Homa Zarghamee (b), Harry M. Kaiser (c), William D. Schulze (c) Keywords: Voluntary contribution mechanism; Cheap talk; Voting; Status quo bias; Social norms; Context; Charitable contributions Abstract: This research examines how three common contextual factors can affect contributions in the linear voluntary contributions mechanism (VCM). Using business student subjects and a low marginal per capita rate of return, the results show that contributions in the last of ten rounds range from 18% for the traditional VCM with no initial cheap talk, no voting, and a status quo of not giving to 94% in a VCM with initial cheap talk, voting, and a status quo of giving. The results demonstrate that context can make the VCM produce sustained efficiencies similar to incentive-compatible public-good mechanisms. Author Affiliation: (a) University of Delaware, United States (b) Santa Clara University, United States (c) Cornell University, United States Article History: Received 15 August 2006; Revised 26 July 2007; Accepted 6 August 2007 Article Note: (footnote) [star] The authors would like to acknowledge support from the Decision, Risk, and Management Science Program at the National Science Foundation. In addition, we would like to thank James Andreoni, Ravi Kanbur, and two anonymous referees for helpful comments. All conclusions, opinions, and errors are the sole responsibility of the authors.

To purchase or authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1559-1816.2007.00240.x Byline: Kent D. Fairfield (a2), Keith G. Allred (b) Abstract: People typically regard mixed-motive negotiations as competitive situations requiring assertive strategies, which often preclude achieving integrative gains. However, much of Argyris' (1976, 1982, 1993) work suggests that questions, rather than just statements, are necessary to create clear understanding of other people's interests and goals, which has been shown (Allred, Mallozzi, Matsui, & Raia, 1997) to be linked to integrative gains. Experimental evidence indicated that the more positive regard negotiators felt for each other, the more they would inquire into the other's needs and interests. The evidence also suggested that more inquiry produced more accurate understanding of the other side's interests, which led to greater integrative gains. These findings are congruent with theory of successful dialogue derived in less contentious settings. Author Affiliation: (a)Silberman College of BusinessFairleigh Dickinson University (b)Kennedy School of GovernmentHarvard University Article note: (2) Correspondence concerning this article should be addressed to Kent D. Fairfield, Silberman College of Business, Fairleigh Dickinson University, 1000 River Road, H-DH2-06, Teaneck, NJ 07666. E-mail: kent@fdu.edu

In April 2005, 4 transplant recipients became ill after receiving organs infected with lymphocytic choriomeningitis virus (LCMV); 3 subsequently died. All organs came from a donor who had been exposed [...]

A study was conducted to measure and compare the coherence properties of 2 * 1 arrays of photonic crystal vertical-cavity surface-emitting lasers. The results show that the amplitude and phase of the complex degree of coherence are correlated, such that coherence is maximized near in-phase and out-of-phase coupling conditions, and controllable by independent current injection to each array element.

The small-signal modulation characteristics of a monolithic dual resonator vertical cavity surface emitting laser are discussed. It is seen that the relaxation oscillation frequency depends solely on the total photon density rather than the individual currents in the two cavities.

Dropout from outpatient mental health treatment may contribute to high rates of relapse and rehospitalization among veterans with chronic posttraumatic stress disorder (PTSD). In a quasi-experimental cohort study, 87 male and 17 female veterans discharging from residential PTSD treatment received either standard referral to outpatient care (N = 77) or standard referrals supplemented by biweekly telephone calls (N = 27). Telephone monitoring and support was feasible and acceptable to 85% of clients. Compared to prior patient cohorts, clients receiving telephone support were twice as likely (88% vs. 43%) to complete an outpatient visit within 1 month of discharge and reported higher satisfaction with care. KEY WORDS: posttraumatic stress disorder; veterans.

Wedge-shaped holes are designed, fabricated, and characterized in proton-implanted holey vertical-cavity surface-emitting lasers (VCSELs). Continuous-wave and pulsed measurements indicate that this holey structure can decrease threshold current, increase maximum single-mode output power, and increase the efficiency of the VCSELs.

The temperature dependence of threshold current in vertical-cavity surface-emitting lasers(VCSELs) can be approximated by Tth (T) = [alpha] [beta]{T - [T.sub.min]}[.sup.2]. This expression provides a useful tool to analyze VCSEL temperature characteristics.

In vertebrates, the endocannabinoid signaling pathway is an important lipid regulatory pathway that modulates a variety of physiological and behavioral processes. N-Acylethanolamines (NAEs) comprise a group of fatty acid derivatives that function within this pathway, and their signaling activity is terminated by an enzyme called fatty acid amide hydrolase (FAAH), which hydrolyzes NAEs to ethanolamine and their corresponding free fatty acids. Bioinformatic approaches led to the identification of plant homologues of FAAH that are capable of hydrolyzing NAEs in vitro. To better understand the role of NAEs in plants, we identified T-DNA knockouts to Arabidopsis FAAH (AtFAAH; At5g64440) and generated plants overexpressing AtFAAH. Here we show that seeds of AtFAAH knockouts had elevated levels of endogenous NAEs, and seedling growth was hypersensitive to exogenously applied NAE. On the other hand, seeds and seedlings of AtFAAH overexpressors had lower endogenous NAE content, and seedlings were less sensitive to exogenous NAE. Moreover, AtFAAH overexpressors displayed enhanced seedling growth and increased cell size. AtFAAH expression and FAAH catalytic activity increased during seed germination and seedling growth, consistent with the timing of NAE depletion during seedling establishment. Collectively, our results show that AtFAAH is one, but not the only, modulator of endogenous NAE levels in plants, and that NAE depletion likely participates in the regulation of plant growth. endocannabinoids | lipids | seedling growth | signaling