Quality control of phenotypic forms data in the Type 1 Diabetes Genetics Consortium

Background When collecting phenotypic data in clinics across the globe, the Type 1 Diabetes Genetics Consortium (T1DGC) used several techniques that ensured consistency, completeness, and accuracy of the data

Direct Optimal Mapping Image Power Spectrum and its Window Functions

The key to detecting neutral hydrogen during the epoch of reionization (EoR) is to separate the cosmological signal from the dominating foreground radiation. We developed direct optimal mapping (Xu et al. 2022) to map interferometric visibilities; it contains only linear operations, with full knowledge of point spread functions from visibilities to images. Here we present an FFT-based image power spectrum and its window functions based on direct optimal mapping. We use noiseless simulation, based on the Hydrogen Epoch of Reionization Array (HERA) Phase I configuration, to study the image power spectrum properties. The window functions show $<10^{-11}$ power leakage from the foreground-dominated region into the EoR window; the 2D and 1D power spectra also verify the separation between the foregrounds and the EoR. Furthermore, we simulated visibilities from a $uv$-complete array and calculated its image power spectrum. The result shows that the foreground--EoR leakage is further suppressed below $10^{-12}$, dominated by the tapering function sidelobes; the 2D power spectrum does not show signs of the horizon wedge. The $uv$-complete result provides a reference case for future 21cm cosmology array designs.Comment: Submitted to Ap

Lowering Homocysteine in Patients with Ischemic Stroke to Prevent Recurrent Stroke, Myocardial Infarction, and Death: The Vitamin Intervention for Stroke Prevention (VISP) Randomized Controlled Trial

Context: In observational studies, elevated plasma total homocysteine levels have been positively associated with ischemic stroke risk. However the utility of homocysteine-lowering therapy to reduce that risk has not been confirmed by randomized trials. Objective: To determine whether high doses of folic acid, pyridoxine (vitamin B6), and cobalamin (vitamin B 12), given to lower total homocysteine levels, reduce the risk of recurrent stroke over a 2-year period compared with low doses of these vitamins. Design: Double-blind randomized controlled trial (September 1996-May 2003). Setting and Participants: 3680 adults with nondisabling cerebral infarction at 56 university-affiliated hospitals, community hospitals, private neurology practices, and Veterans Affairs medical centers across the United States, Canada, and Scotland. Interventions: All participants received best medical and surgical care plus a daily multivitamin containing the US Food and Drug Administration\u27s reference daily intakes of other vitamins; patients were randomly assigned to receive once-daily doses of the high-dose formulation (n = 1827), containing 25 mg of pyridoxine, 0.4 mg of cobalamin, and 2.5 mg of folic acid; or the low-dose formulation (n = 1853), containing 200 pg of pyridoxine, 6 pg of cobalamin, and 20 pg of folic acid. Main Outcome Measures: Recurrent cerebral infarction (primary outcome); coronary heart disease (CHD) events and death (secondary outcomes). Results: Mean reduction of total homocysteine was 2 μmol/L greater in the high-dose group than in the low-dose group, but there was no treatment effect on any end point. The unadjusted risk ratio for any stroke, CHD event, or death was 1.0 (95% confidence interval [CI], 0.8-1.1), with chances of an event within 2 years of 18.0% in the high-dose group and 18.6% in the low-dose group. The risk of ischemic stroke within 2 years was 9. 2% for the high-dose and 8.8% for the low-dose groups (risk ratio, 1.0; 95% CI, 0.8-1.3) (P=.80 by log-rank test of the primary hypothesis of difference in ischemic stroke between treatment groups). There was a persistent and graded association between baseline total homocysteine level and outcomes. A 3 μmol/L lower total homocysteine level was associated with a 10% lower risk of stroke (P=.05), a 26% lower risk of CHD events (P\u3c.001), and a 16% lower risk of death (P=.001) in the low-dose group and a nonsignificantly lower risk in the high-dose group by 2% for stroke, 7% for CHD events, and 7% for death. Conclusions: In this trial, moderate reduction of total homocysteine after nondisabling cerebral infarction had no effect on vascular outcomes during the 2 years of follow-up. However, the consistent findings of an association of total homocysteine with vascular risk suggests that further exploration of the hypothesis is warranted and longer trials in different populations with elevated total homocysteine may be necessary

Designing and implementing sample and data collection for an international genetics study: the Type 1 Diabetes Genetics Consortium

Background and Purpose The Type 1 Diabetes Genetics Consortium (T1DGC) is an international project whose primary aims are to: (a) discover genes that modify type 1 diabetes risk; and (b) expand upon the existing genetic resources for type 1 diabetes research. The initial goal was to collect 2500 affected sibling pair (ASP) families worldwide. Methods T1DGC was organized into four regional networks (Asia-Pacific, Europe, North America, and the United Kingdom) and a Coordinating Center. A Steering Committee, with representatives from each network, the Coordinating Center, and the funding organizations, was responsible for T1DGC operations. The Coordinating Center, with regional network representatives, developed study documents and data systems. Each network established laboratories for: DNA extraction and cell line production; human leukocyte antigen genotyping; and autoantibody measurement. Samples were tracked from the point of collection, processed at network laboratories and stored for deposit at National Institute for Diabetes and Digestive and Kidney Diseases (NIDDK) Central Repositories. Phenotypic data were collected and entered into the study database maintained by the Coordinating Center. Results T1DGC achieved its original ASP recruitment goal. In response to research design changes, the T1DGC infrastructure also recruited trios, cases, and controls. Results of genetic analyses have identified many novel regions that affect susceptibility to type 1 diabetes. T1DGC created a resource of data and samples that is accessible to the research community. Limitations Participation in T1DGC was declined by some countries due to study requirements for the processing of samples at network laboratories and/or final deposition of samples in NIDDK Central Repositories. Re-contact of participants was not included in informed consent templates, preventing collection of additional samples for functional studies. Conclusions T1DGC implemented a distributed, regional network structure to reach ASP recruitment targets. The infrastructure proved robust and flexible enough to accommodate additional recruitment. T1DGC has established significant resources that provide a basis for future discovery in the study of type 1 diabetes genetics.Joan E Hilner, Letitia H Perdue, Elizabeth G Sides, June J Pierce, Ana M Wägner, Alan Aldrich, Amanda Loth, Lotte Albret, Lynne E Wagenknecht, Concepcion Nierras, Beena Akolkar and the T1DG

Medication coaching program for patients with minor stroke or TIA: A pilot study

<p>Abstract</p> <p>Background</p> <p>Patients who are hospitalized with a first or recurrent stroke often are discharged with new medications or adjustment to the doses of pre-admission medications, which can be confusing and pose safety issues if misunderstood. The purpose of this pilot study was to assess the feasibility of medication coaching via telephone after discharge in patients with stroke.</p> <p>Methods</p> <p>Two-arm pilot study of a medication coaching program with 30 patients (20 intervention, 10 control). Consecutive patients admitted with stroke or TIA with at least 2 medications changed between admission and discharge were included. The medication coach contacted intervention arm patients post-discharge via phone call to discuss risk factors, review medications and triage patients’ questions to a stroke nurse and/or pharmacist. Intervention and control participants were contacted at 3 months for outcomes. The main outcomes were feasibility (appropriateness of script, ability to reach participants, and provide requested information) and participant evaluation of medication coaching.</p> <p>Results</p> <p>The median lengths of the coaching and follow-up calls with requested answers to these questions were 27 minutes and 12 minutes, respectively, and participant evaluations of the coaching were positive. The intervention participants were more likely to have seen their primary care provider than were control participants by 3 months post discharge.</p> <p>Conclusions</p> <p>This medication coaching study executed early after discharge demonstrated feasibility of coaching and educating stroke patients with a trained coach. Results from our small pilot showed a possible trend towards improved appointment-keeping with primary care providers in those who received coaching.</p