A system for phenotype harmonization in the National Heart, Lung, and Blood Institute Trans-Omics for Precision Medicine (TOPMed) program

Genotype-phenotype association studies often combine phenotype data from multiple studies to increase statistical power. Harmonization of the data usually requires substantial effort due to heterogeneity in phenotype definitions, study design, data collection procedures, and data-set organization. Here we describe a centralized system for phenotype harmonization that includes input from phenotype domain and study experts, quality control, documentation, reproducible results, and data-sharing mechanisms. This system was developed for the National Heart, Lung, and Blood Institute’s Trans-Omics for Precision Medicine (TOPMed) program, which is generating genomic and other -omics data for more than 80 studies with extensive phenotype data. To date, 63 phenotypes have been harmonized across thousands of participants (recruited in 1948–2012) from up to 17 studies per phenotype. Here we discuss challenges in this undertaking and how they were addressed. The harmonized phenotype data and associated documentation have been submitted to National Institutes of Health data repositories for controlled access by the scientific community. We also provide materials to facilitate future harmonization efforts by the community, which include 1) the software code used to generate the 63 harmonized phenotypes, enabling others to reproduce, modify, or extend these harmonizations to additional studies, and 2) the results of labeling thousands of phenotype variables with controlled vocabulary terms

Central Asia and Kashmir, an appraisal of post and present links

The author intends to show the floral relationships between the Kashmir Valley and Central Asia. Two points in particular are emphasized : 1) The archeobotanic relationship between these 2 regions (several archaeological Indian findings in Kashmir are analyzed). 2) The affinities between present flora of Himalayan Kashmir and those of Central Asia.L'auteur entend montrer les liens floristiques entre la vallée du Cachemire et l'Asie centrale. Deux points sont particulièrement soulignés : 1) Les liens archéobotaniques entre ces deux régions (nombreuses trouvailles archéologiques indiennes au Cachemire analysées) ; 2) Les affinités entre la présente flore du Cachemire himalayen et celle de l'Asie centrale.Buth G.M., Navchoo Irshad A., Asti Navayan. Central Asia and Kashmir, an appraisal of post and present links. In: Journal d'agriculture traditionnelle et de botanique appliquée, 34ᵉ année,1987. pp. 57-64

Composite arterial grafts versus conventional grafting for coronary artery bypass grafting

AbstractObjectivesComposite arterial grafts for coronary artery bypass grafting surgery allow complete arterial revascularization but are limited by the inflow of a single internal thoracic artery supplying all the grafted vessels. We reviewed the safety of composite arterial grafts using either bilateral internal thoracic arteries or a single internal thoracic artery and radial artery.MethodsFrom January 1999 to July 2002, 402 consecutive patients receiving composite grafts only were compared to a control group of patients (n = 542) undergoing coronary artery bypass grafting with internal thoracic artery and saphenous veins operated upon by the same surgeons. Two different statistical approaches were used to compare groups in this retrospective analysis. First, propensity score analysis with greedy matching technique was used to match patients from each group. Second, a multivariate analysis was performed looking at a combined patient outcome of death, intra-aortic balloon counterpulsation utilization, myocardial infarction, stroke, and prolonged ventilation on all patients in both groups.ResultsAfter matching by propensity score, the major clinical outcomes in composite arterial (n = 249) and control (n = 249) groups were found to be similar. The in-hospital mortality in the composite group was 1.2% as compared with 0.4% in matched patients (P = .62). However, patients in the composite group were found to have a significantly longer pump time (P < .0001), longer clamp time (P < .0001), increased incidence of prolonged mechanical ventilation (12.8% vs 4.8%; P = .002), and higher incidence of combined morbidity outcome (13.6% vs 6.4%; P = .007) as compared with matched patients. Multivariable analysis showed that composite arterial grafting was an independent predictor of the combined morbidity outcome with an odds ratio of 2.1 (1.2-3.7).ConclusionsThese findings suggest that composite arterial grafting may be associated with an increase in risk-adjusted patient morbidity when compared with a conventional coronary artery bypass grafting group, although a mortality difference was not demonstrable

Static Detection of Livelocks in Ada Multitasking Programs

Abstract. In this paper we present algorithms to statically detect livelocks in Ada multitasking programs. Although the algorithms ’ worst-case execution time is exponential, they can be expected to run in polynomial time. Since the problem is strongly connected to finding infinite loops, which is undecidable in general, our algorithms compute only an approximation to the real solution of the problem. As a consequence our algorithms may compute false positives.

A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee

Many clinical trials have evaluated the benefit of long-term use of antiplatelet drugs in reducing the risk of clinical thrombotic events. Aspirin and ticlopidine have been shown to be effective, but both have potentially serious adverse effects. Clopidogrel, a new thienopyridine derivative similar to ticlopidine, is an inhibitor of platelet aggregation induced by adenosine diphosphate. METHODS: CAPRIE was a randomised, blinded, international trial designed to assess the relative efficacy of clopidogrel (75 mg once daily) and aspirin (325 mg once daily) in reducing the risk of a composite outcome cluster of ischaemic stroke, myocardial infarction, or vascular death; their relative safety was also assessed. The population studied comprised subgroups of patients with atherosclerotic vascular disease manifested as either recent ischaemic stroke, recent myocardial infarction, or symptomatic peripheral arterial disease. Patients were followed for 1 to 3 years. FINDINGS: 19,185 patients, with more than 6300 in each of the clinical subgroups, were recruited over 3 years, with a mean follow-up of 1.91 years. There were 1960 first events included in the outcome cluster on which an intention-to-treat analysis showed that patients treated with clopidogrel had an annual 5.32% risk of ischaemic stroke, myocardial infarction, or vascular death compared with 5.83% with aspirin. These rates reflect a statistically significant (p = 0.043) relative-risk reduction of 8.7% in favour of clopidogrel (95% Cl 0.3-16.5). Corresponding on-treatment analysis yielded a relative-risk reduction of 9.4%. There were no major differences in terms of safety. Reported adverse experiences in the clopidogrel and aspirin groups judged to be severe included rash (0.26% vs 0.10%), diarrhoea (0.23% vs 0.11%), upper gastrointestinal discomfort (0.97% vs 1.22%), intracranial haemorrhage (0.33% vs 0.47%), and gastrointestinal haemorrhage (0.52% vs 0.72%), respectively. There were ten (0.10%) patients in the clopidogrel group with significant reductions in neutrophils (< 1.2 x 10(9)/L) and 16 (0.17%) in the aspirin group. INTERPRETATION: Long-term administration of clopidogrel to patients with atherosclerotic vascular disease is more effective than aspirin in reducing the combined risk of ischaemic stroke, myocardial infarction, or vascular death. The overall safety profile of clopidogrel is at least as good as that of medium-dose aspirin