The Human Anatomic Gene Expression Library (H-ANGEL), the H-Inv integrative display of human gene expression across disparate technologies and platforms

The Human Anatomic Gene Expression Library (H-ANGEL) is a resource for information concerning the anatomical distribution and expression of human gene transcripts. The tool contains protein expression data from multiple platforms that has been associated with both manually annotated full-length cDNAs from H-InvDB and RefSeq sequences. Of the H-Inv predicted genes, 18 897 have associated expression data generated by at least one platform. H-ANGEL utilizes categorized mRNA expression data from both publicly available and proprietary sources. It incorporates data generated by three types of methods from seven different platforms. The data are provided to the user in the form of a web-based viewer with numerous query options. H-ANGEL is updated with each new release of cDNA and genome sequence build. In future editions, we will incorporate the capability for expression data updates from existing and new platforms. H-ANGEL is accessible at http://www.jbirc.aist.go.jp/hinv/h-angel/

Menthol Cigarette Smoking and Obesity in Young Adult Daily Smokers in Hawaii

This study investigates 1) the relationship between menthol cigarette smoking and obesity and 2) the association of body mass index with the nicotine metabolite ratio among menthol and non-menthol daily smokers aged 18–35 (n = 175). A brief survey on smoking and measures of height and weight, carbon monoxide, and saliva samples were collected from participants from May to December 2013 in Honolulu, Hawaii. Multiple regression was used to estimate differences in body mass index among menthol and non-menthol smokers and the association of menthol smoking with obesity. We calculated the log of the nicotine metabolite ratio to examine differences in the nicotine metabolite ratio among normal, overweight, and obese smokers. Sixty-eight percent of smokers used menthol cigarettes. Results showed that 62% of normal, 54% of overweight, and 91% of obese smokers used menthol cigarettes (p = .000). The mean body mass index was significantly higher among menthol compared with non-menthol smokers (29.4 versus 24.5, p = .000). After controlling for gender, marital status, educational attainment, employment status, and race/ethnicity, menthol smokers were more than 3 times as likely as non-menthol smokers to be obese (p = .04). The nicotine metabolite ratio was significantly lower for overweight menthol smokers compared with non-menthol smokers (.16 versus .26, p = .02) in the unadjusted model, but was not significant after adjusting for the covariates. Consistent with prior studies, our data show that menthol smokers are more likely to be obese compared with non-menthol smokers. Future studies are needed to determine how flavored tobacco products influence obesity among smokers

Effects of automated alerts on unnecessarily repeated serology tests in a cardiovascular surgery department: a time series analysis

<p>Abstract</p> <p>Background</p> <p>Laboratory testing is frequently unnecessary, particularly repetitive testing. Among the interventions proposed to reduce unnecessary testing, Computerized Decision Support Systems (CDSS) have been shown to be effective, but their impact depends on their technical characteristics. The objective of the study was to evaluate the impact of a Serology-CDSS providing point of care reminders of previous existing serology results, embedded in a Computerized Physician Order Entry at a university teaching hospital in Paris, France.</p> <p>Methods</p> <p>A CDSS was implemented in the Cardiovascular Surgery department of the hospital in order to decrease inappropriate repetitions of viral serology tests (HBV).</p> <p>A time series analysis was performed to assess the impact of the alert on physicians' practices. The study took place between January 2004 and December 2007. The primary outcome was the proportion of unnecessarily repeated HBs antigen tests over the periods of the study. A test was considered unnecessary when it was ordered within 90 days after a previous test for the same patient. A secondary outcome was the proportion of potentially unnecessary HBs antigen test orders cancelled after an alert display.</p> <p>Results</p> <p>In the pre-intervention period, 3,480 viral serology tests were ordered, of which 538 (15.5%) were unnecessarily repeated. During the intervention period, of the 2,095 HBs antigen tests performed, 330 unnecessary repetitions (15.8%) were observed. Before the intervention, the mean proportion of unnecessarily repeated HBs antigen tests increased by 0.4% per month (absolute increase, 95% CI 0.2% to 0.6%, <it>p </it>< 0.001). After the intervention, a significant trend change occurred, with a monthly difference estimated at -0.4% (95% CI -0.7% to -0.1%, <it>p </it>= 0.02) resulting in a stable proportion of unnecessarily repeated HBs antigen tests. A total of 380 unnecessary tests were ordered among 500 alerts displayed (compliance rate 24%).</p> <p>Conclusions</p> <p>The proportion of unnecessarily repeated tests immediately dropped after CDSS implementation and remained stable, contrasting with the significant continuous increase observed before. The compliance rate confirmed the effect of the alerts. It is necessary to continue experimentation with dedicated systems in order to improve understanding of the diversity of CDSS and their impact on clinical practice.</p

Experimental study on boron distribution and transport at plasma-facing components during impurity powder dropping in the Large Helical Device

Toward real-time wall conditioning, impurity powder dropping experiments with boron powder were performed in the 22nd experimental campaign of the Large Helical Device. To examine the deposition and desorption process of boron, we focus on boron hydride (BH) molecules which presumably populate near plasma-facing components. We performed spatially-resolved spectroscopic measurements of emission by boron ions and BH molecules. From the measurement, we found that BH and B+ were concentrated on the divertor viewing chord, which suggest boron deposition in the divertor region. By comparing Hγ emissions with and without boron injection, neutral hydrogen shows uniform reduction in the SOL region, whereas less reduction of neutral hydrogen is confirmed in the divertor region. Although emissions from BH and B+ increased linearly, emissions by B0 and B4+ became constant after the middle of the discharge. Continuous reduction of carbon density in the core plasma was confirmed even after B0 and B4+ became constant. The results may show reduction of hydrogen recycling and facilitation of impurity gettering by boron in the divertor region and thus effective real-time wall conditioning

A research agenda to support the development and implementation of genomics-based clinical informatics tools and resources.

OBJECTIVE: The Genomic Medicine Working Group of the National Advisory Council for Human Genome Research virtually hosted its 13th genomic medicine meeting titled Developing a Clinical Genomic Informatics Research Agenda . The meeting\u27s goal was to articulate a research strategy to develop Genomics-based Clinical Informatics Tools and Resources (GCIT) to improve the detection, treatment, and reporting of genetic disorders in clinical settings. MATERIALS AND METHODS: Experts from government agencies, the private sector, and academia in genomic medicine and clinical informatics were invited to address the meeting\u27s goals. Invitees were also asked to complete a survey to assess important considerations needed to develop a genomic-based clinical informatics research strategy. RESULTS: Outcomes from the meeting included identifying short-term research needs, such as designing and implementing standards-based interfaces between laboratory information systems and electronic health records, as well as long-term projects, such as identifying and addressing barriers related to the establishment and implementation of genomic data exchange systems that, in turn, the research community could help address. DISCUSSION: Discussions centered on identifying gaps and barriers that impede the use of GCIT in genomic medicine. Emergent themes from the meeting included developing an implementation science framework, defining a value proposition for all stakeholders, fostering engagement with patients and partners to develop applications under patient control, promoting the use of relevant clinical workflows in research, and lowering related barriers to regulatory processes. Another key theme was recognizing pervasive biases in data and information systems, algorithms, access, value, and knowledge repositories and identifying ways to resolve them

Macrophage-Specific Chemokines Induced via Innate Immunity by Amino Acid Copolymers and Their Role in EAE

The random amino acid copolymer poly(Y,E,A,K)n (Copaxone®) is widely used in multiple sclerosis treatment and a second generation copolymer poly(Y,F,A,K)n with enhanced efficacy in experimental autoimmune encephalomyelitis in mice has been described. A major mechanism through which copolymers function to ameliorate disease is the generation of immunosuppressive IL-10-secreting regulatory T cells entering the CNS. In addition, the antigen presenting cell to which these copolymers bind through MHC Class II proteins may have an important role. Here, both CCL22 (a Th2 cell chemoattractant) in large amounts and CXCL13 in much smaller amounts are shown to be secreted after administration of YFAK to mice and to a smaller extent by YEAK parallel to their serum concentrations. Moreover, bone marrow-derived macrophages secrete CCL22 in vitro in response to YFAK and to higher concentrations of YEAK. Strikingly, these chemokines are also secreted into serum of MHC Class II −/− mice, indicating that an innate immune receptor on these cells also has an important role. Thus, both the innate and the adaptive immune systems are involved in the mechanism of EAE amelioration by YFAK. The enhanced ability of YFAK to stimulate the innate immune system may account for its enhanced efficacy in EAE treatment

Inflammation-dependent cerebrospinal fluid hypersecretion by the choroid plexus epithelium in posthemorrhagic hydrocephalus

This is the author accepted manuscript. The final version is available from Springer Nature via the DOI in this recordThere is another record in ORE for this publication: http://hdl.handle.net/10871/33419The choroid plexus epithelium (CPE) secretes higher volumes of fluid (cerebrospinal fluid, CSF) than any other epithelium and simultaneously functions as the blood-CSF barrier to gate immune cell entry into the central nervous system. Posthemorrhagic hydrocephalus (PHH), an expansion of the cerebral ventricles due to CSF accumulation following intraventricular hemorrhage (IVH), is a common disease usually treated by suboptimal CSF shunting techniques. PHH is classically attributed to primary impairments in CSF reabsorption, but little experimental evidence supports this concept. In contrast, the potential contribution of CSF secretion to PHH has received little attention. In a rat model of PHH, we demonstrate that IVH causes a Toll-like receptor 4 (TLR4)- and NF-κB-dependent inflammatory response in the CPE that is associated with a ∼3-fold increase in bumetanide-sensitive CSF secretion. IVH-induced hypersecretion of CSF is mediated by TLR4-dependent activation of the Ste20-type stress kinase SPAK, which binds, phosphorylates, and stimulates the NKCC1 co-transporter at the CPE apical membrane. Genetic depletion of TLR4 or SPAK normalizes hyperactive CSF secretion rates and reduces PHH symptoms, as does treatment with drugs that antagonize TLR4-NF-κB signaling or the SPAK-NKCC1 co-transporter complex. These data uncover a previously unrecognized contribution of CSF hypersecretion to the pathogenesis of PHH, demonstrate a new role for TLRs in regulation of the internal brain milieu, and identify a kinase-regulated mechanism of CSF secretion that could be targeted by repurposed US Food and Drug Administration (FDA)-approved drugs to treat hydrocephalus.We thank D.R. Alessi (Dundee) and R.P. Lifton (Rockefeller) for their support. K.T.K. is supported by the March of Dimes Basil O'Connor Award, a Simons Foundation SFARI Grant, the Hydrocephalus Association Innovator Award, and the NIH (4K12NS080223-05). J.M.S. is supported by the National Institute of Neurological Disorders and Stroke (NINDS) (NS060801; NS061808) and the US Department of Veterans Affairs (1BX002889); R.M. is supported by the Howard Hughes Medical Institute

Happiness around the world: A combined etic-emic approach across 63 countries.

What does it mean to be happy? The vast majority of cross-cultural studies on happiness have employed a Western-origin, or "WEIRD" measure of happiness that conceptualizes it as a self-centered (or "independent"), high-arousal emotion. However, research from Eastern cultures, particularly Japan, conceptualizes happiness as including an interpersonal aspect emphasizing harmony and connectedness to others. Following a combined emic-etic approach (Cheung, van de Vijver & Leong, 2011), we assessed the cross-cultural applicability of a measure of independent happiness developed in the US (Subjective Happiness Scale; Lyubomirsky & Lepper, 1999) and a measure of interdependent happiness developed in Japan (Interdependent Happiness Scale; Hitokoto & Uchida, 2015), with data from 63 countries representing 7 sociocultural regions. Results indicate that the schema of independent happiness was more coherent in more WEIRD countries. In contrast, the coherence of interdependent happiness was unrelated to a country's "WEIRD-ness." Reliabilities of both happiness measures were lowest in African and Middle Eastern countries, suggesting these two conceptualizations of happiness may not be globally comprehensive. Overall, while the two measures had many similar correlates and properties, the self-focused concept of independent happiness is "WEIRD-er" than interdependent happiness, suggesting cross-cultural researchers should attend to both conceptualizations

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements