Investigation of three-dimensional shock wave/turbulent-boundary-layer interaction initiated by a single fin

Three-dimensional shock wave/turbulent-boundary-layer interaction of a hypersonic flow passing a single fin mounted on a flat plate at a Mach number of five and unit Reynolds number 3.7×10^7 was conducted by a large-eddy simulation approach. The performed large-eddy simulation has demonstrated good agreement with experimental data in terms of mean flowfield structures, surface pressure distribution, and surface flow pattern. Furthermore, the shock wave system, flow separation structure, and turbulence characteristics were all investigated by analyzing the obtained large-eddy simulation dataset. It was found that, for this kind of three-dimensional shock wave/turbulent-boundary-layer interaction problem, the flow characteristics in different regions have been dominated by respective wall turbulence, free shear layer turbulence, and corner vortex motions in different regions. In the reverse flow region, near-wall quasi-streamwise streaky structures were observed just beneath the main separation vortex, indicating that the transition of the pathway of the separation flow to turbulence may occur within a short distance from the reattachment location. The obtained large-eddy simulation results have provided a clear and direct evidence of the primary reverse flow and the secondary separation flow being essentially turbulent

Water Formation Reaction under Interfacial Confinement: Al0.25Si0.75O2 on O-Ru(0001)

Confined nanosized spaces at the interface between a metal and a seemingly inert material, such as a silicate, have recently been shown to influence the chemistry at the metal surface. In prior work, we observed that a bilayer (BL) silica on Ru(0001) can change the reaction pathway of the water formation reaction (WFR) near room temperature when compared to the bare metal. In this work, we looked at the effect of doping the silicate with Al, resulting in a stoichiometry of AlSiO . We investigated the kinetics of WFR at elevated H pressures and various temperatures under interfacial confinement using ambient pressure X-ray photoelectron spectroscopy. The apparent activation energy was lower than that on bare Ru(0001) but higher than that on the BL-silica/Ru(0001). The apparent reaction order with respect to H was also determined. The increased residence time of water at the surface, resulting from the presence of the BL-aluminosilicate (and its subsequent electrostatic stabilization), favors the so-called disproportionation reaction pathway (*HO + *O ↔ 2 *OH), but with a higher energy barrier than for pure BL-silica.Research was carried out in part at the 23-ID-2 (IOS) beamline of the National Synchrotron Light Source II and the Center for Functional Nanomaterials, which are U.S. DOE Office of Science Facilities, and the Scientific Data and Computing Center, a component of the Computational Science Initiative, at Brookhaven National Laboratory under Contract No. DE-SC0012704. This research used resources of the National Energy Research Scientific Computing Center, a DOE Office of Science User Facility supported by the Office of Science of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. J.C. thanks the Spanish Ministry of Science, Innovation and Universities for a “Severo Ochoa” grant (BES-2015-075748) through “Severo Ochoa” Excellence Programme (SEV-2016-0683). Z.D. is supported by ACS PRF grant #61059-ND5

A detailed clinical and molecular survey of subjects with nonsyndromic USH2A retinopathy reveals an allelic hierarchy of disease-causing variants.

Defects in USH2A cause both isolated retinal disease and Usher syndrome (ie, retinal disease and deafness). To gain insights into isolated/nonsyndromic USH2A retinopathy, we screened USH2A in 186 probands with recessive retinal disease and no hearing complaint in childhood (discovery cohort) and in 84 probands with recessive retinal disease (replication cohort). Detailed phenotyping, including retinal imaging and audiological assessment, was performed in individuals with two likely disease-causing USH2A variants. Further genetic testing, including screening for a deep-intronic disease-causing variant and large deletions/duplications, was performed in those with one likely disease-causing change. Overall, 23 of 186 probands (discovery cohort) were found to harbour two likely disease-causing variants in USH2A. Some of these variants were predominantly associated with nonsyndromic retinal degeneration ('retinal disease-specific'); these included the common c.2276 G>T, p.(Cys759Phe) mutation and five additional variants: c.2802 T>G, p.(Cys934Trp); c.10073 G>A, p.(Cys3358Tyr); c.11156 G>A, p.(Arg3719His); c.12295-3 T>A; and c.12575 G>A, p.(Arg4192His). An allelic hierarchy was observed in the discovery cohort and confirmed in the replication cohort. In nonsyndromic USH2A disease, retinopathy was consistent with retinitis pigmentosa and the audiological phenotype was variable. USH2A retinopathy is a common cause of nonsyndromic recessive retinal degeneration and has a different mutational spectrum to that observed in Usher syndrome. The following model is proposed: the presence of at least one 'retinal disease-specific' USH2A allele in a patient with USH2A-related disease results in the preservation of normal hearing. Careful genotype-phenotype studies such as this will become increasingly important, especially now that high-throughput sequencing is widely used in the clinical setting.European Journal of Human Genetics advance online publication, 4 February 2015; doi:10.1038/ejhg.2014.283

Screening and Treatment Outcomes in Adults and Children With Type 1 Diabetes and Asymptomatic Celiac Disease: The CD-DIET Study.

OBJECTIVE: To describe celiac disease (CD) screening rates and glycemic outcomes of a gluten-free diet (GFD) in patients with type 1 diabetes who are asymptomatic for CD. RESEARCH DESIGN AND METHODS: Asymptomatic patients (8-45 years) were screened for CD. Biopsy-confirmed CD participants were randomized to GFD or gluten-containing diet (GCD) to assess changes in HbA RESULTS: Adults had higher CD-seropositivity rates than children (6.8% [95% CI 4.9-8.2%, CONCLUSIONS: CD is frequently observed in asymptomatic patients with type 1 diabetes, and clinical vigilance is warranted with initiation of a GFD

Consumers of natural health products: natural-born pharmacovigilantes?

<p>Abstract</p> <p>Background</p> <p>Natural health products (NHPs), such as herbal medicines and vitamins, are widely available over-the-counter and are often purchased by consumers without advice from a healthcare provider. This study examined how consumers respond when they believe they have experienced NHP-related adverse drug reactions (ADRs) in order to determine how to improve current safety monitoring strategies.</p> <p>Methods</p> <p>Qualitative semi-structured interviews were conducted with twelve consumers who had experienced a self-identified NHP-related ADR. Key emergent themes were identified and coded using content analysis techniques.</p> <p>Results</p> <p>Consumers were generally not comfortable enough with their conventional health care providers to discuss their NHP-related ADRs. Consumers reported being more comfortable discussing NHP-related ADRs with personnel from health food stores, friends or family with whom they had developed trusted relationships. No one reported their suspected ADR to Health Canada and most did not know this was possible.</p> <p>Conclusion</p> <p>Consumers generally did not report their suspected NHP-related ADRs to healthcare providers or to Health Canada. Passive reporting systems for collecting information on NHP-related ADRs cannot be effective if consumers who experience NHP-related ADRs do not report their experiences. Healthcare providers, health food store personnel, manufacturers and other stakeholders also need to take responsibility for reporting ADRs in order to improve current pharmacovigilance of NHPs.</p

The Gender Congruency Effect across languages in bilinguals: A meta-analysis

In the study of gender representation and processing in bilinguals, two contrasting perspectives exist: integrated vs. the autonomous (Costa, Kovacic, Fedorenko, & Caramazza, 2003). In the former, cross-linguistic interactions during the selection of grammatical gender values are expected; in the latter, they are not. To address this issue, authors have typically explored the cross-linguistic Gender Congruency Effect (GCE: a facilitation on the naming or translation of second language [L2] nouns when their first language [L1] translations are of the same gender, in comparison to those of a different gender). However, the literature suggests that this effect is sometimes difficult to observe and might vary as a function of variables such as the syntactic structure produced to translate or name the target (bare nouns vs. noun phrases), the phonological gender transparency of both languages (whether or not they have phonological gender cues associated with the ending letter [e.g., “–a” for feminine words and “–o” for masculine words in Romance languages]), the degree of L2 proficiency, and task requirements (naming vs. translation). The aim of the present quantitative meta-analysis is to examine the robustness of the cross-linguistic GCE obtained during language production. It involves 25 experiments from 11 studies. The results support a bilingual gender-integrated view, in that they show a small but significant GC effect regardless of the variables mentioned above.This paper was funded through the state budget with reference IF / 00784/2013 / CP1158 / CT0013. The study has also been partially supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653). Government of Spain—Ministry of Education, Culture and Sports—through the Training program for Academic Staff (Ayudas para la Formación del Profesorado Universitario, FPU grant BOE-B-2017-2646), the research project (reference PSI2015-65116-P) granted by the Spanish Ministry of Economy and Competitiveness, and the grant for research groups (reference ED431B 2019/2020) from the Galician Government, as well as by the FCT (Foundation for Science and Technology, Portugal) through the state budget (reference IF / 00784/2013 / CP1158 / CT0013). Finally, the study has also been partially supported by the FCT and the Portuguese Ministry of Science, Technology and Higher Education through national funds and co-financed by FEDER through COMPETE2020 under the PT2020 Partnership Agreement (POCI-01-0145-FEDER-007653

Lupus risk variants in the PXK locus alter B-cell receptor internalization

Genome wide association studies have identified variants in PXK that confer risk for humoral autoimmune diseases, including systemic lupus erythematosus (SLE or lupus), rheumatoid arthritis and more recently systemic sclerosis. While PXK is involved in trafficking of epidermal growth factor Receptor (EGFR) in COS-7 cells, mechanisms linking PXK to lupus pathophysiology have remained undefined. In an effort to uncover the mechanism at this locus that increases lupus-risk, we undertook a fine-mapping analysis in a large multi-ancestral study of lupus patients and controls. We define a large (257kb) common haplotype marking a single causal variant that confers lupus risk detected only in European ancestral populations and spans the promoter through the 3' UTR of PXK. The strongest association was found at rs6445972 with P &lt; 4.62 × 10-10, OR 0.81 (0.75 - 0.86). Using stepwise logistic regression analysis, we demonstrate that one signal drives the genetic association in the region. Bayesian analysis confirms our results, identifying a 95% credible set consisting of 172 variants spanning 202 kb. Functionally, we found that PXK operates on the B-cell antigen receptor (BCR); we confirmed that PXK influenced the rate of BCR internalization. Furthermore, we demonstrate that individuals carrying the risk haplotype exhibited a decreased rate of BCR internalization, a process known to impact B cell survival and cell fate. Taken together, these data define a new candidate mechanism for the genetic association of variants around PXK with lupus risk and highlight the regulation of intracellular trafficking as a genetically regulated pathway mediating human autoimmunity

Temporal Trends in Care and Outcomes of Patients Receiving Fibrinolytic Therapy Compared to Primary Percutaneous Coronary Intervention: Insights From the Get With The Guidelines Coronary Artery Disease (GWTG‐CAD) Registry

Background: Timely reperfusion after ST‐elevation myocardial infarction (STEMI) improves survival. Guidelines recommend primary percutaneous coronary intervention (PPCI) within 90 minutes of arrival at a PCI‐capable hospital. The alternative is fibrinolysis within 30 minutes for those in those for whom timely transfer to a PCI‐capable hospital is not feasible. Methods and Results: We identified STEMI patients receiving reperfusion therapy at 229 hospitals participating in the Get With the Guidelines—Coronary Artery Disease (GWTG‐CAD) database (January 1, 2003 through December 31, 2008). Temporal trends in the use of fibrinolysis and PPCI, its timeliness, and in‐hospital mortality outcomes were assessed. We also assessed predictors of fibrinolysis versus PPCI and compliance with performance measures. Defect‐free care was defined as 100% compliance with all performance measures. We identified 29 190 STEMI patients, of whom 2441 (8.4%) received fibrinolysis; 38.2% of these patients achieved door‐to‐needle times ≤30 minutes. Median door‐to‐needle times increased from 36 to 60 minutes (P=0.005) over the study period. Among PPCI patients, median door‐to‐balloon times decreased from 94 to 64 minutes (P<0.0001) over the same period. In‐hospital mortality was higher with fibrinolysis than with PPCI (4.6% vs 3.3%, P=0.001) and did not change significantly over time. Patients receiving fibrinolysis were less likely to receive defect‐free care compared with their PPCI counterparts. Conclusions: Use of fibrinolysis for STEMI has decreased over time with concomitant worsening of door‐to‐needle times. Over the same time period, use of PPCI increased with improvement in door‐to‐balloon times. In‐hospital mortality was higher with fibrinolysis than with PPCI. As reperfusion for STEMI continues to shift from fibrinolysis to PPCI, it will be critical to ensure that door‐to‐needle times and outcomes do not worsen