Selecting additional tag SNPs for tolerating missing data in genotyping

BACKGROUND: Recent studies have shown that the patterns of linkage disequilibrium observed in human populations have a block-like structure, and a small subset of SNPs (called tag SNPs) is sufficient to distinguish each pair of haplotype patterns in the block. In reality, some tag SNPs may be missing, and we may fail to distinguish two distinct haplotypes due to the ambiguity caused by missing data. RESULTS: We show there exists a subset of SNPs (referred to as robust tag SNPs) which can still distinguish all distinct haplotypes even when some SNPs are missing. The problem of finding minimum robust tag SNPs is shown to be NP-hard. To find robust tag SNPs efficiently, we propose two greedy algorithms and one linear programming relaxation algorithm. The experimental results indicate that (1) the solutions found by these algorithms are quite close to the optimal solution; (2) the genotyping cost saved by using tag SNPs can be as high as 80%; and (3) genotyping additional tag SNPs for tolerating missing data is still cost-effective. CONCLUSION: Genotyping robust tag SNPs is more practical than just genotyping the minimum tag SNPs if we can not avoid the occurrence of missing data. Our theoretical analysis and experimental results show that the performance of our algorithms is not only efficient but the solution found is also close to the optimal solution

Approximation algorithms for the shortest total path length spanning tree problem

AbstractGiven an undirected graph with a nonnegative weight on each edge, the shortest total path length spanning tree problem is to find a spanning tree of the graph such that the total path length summed over all pairs of the vertices is minimized. In this paper, we present several approximation algorithms for this problem. Our algorithms achieve approximation ratios of 2, 15/8, and 3/2 in time O(n2+f(G)),O(n3), and O(n4) respectively, in which f(G) is the time complexity for computing all-pairs shortest paths of the input graph G and n is the number of vertices of G. Furthermore, we show that the approximation ratio of (4/3+ε) can be achieved in polynomial time for any constant ε>0

Risk factors for pulmonary tuberculosis in patients with chronic obstructive airway disease in Taiwan: a nationwide cohort study

BACKGROUND: An association between chronic obstructive pulmonary disease (COPD) and tuberculosis (TB) has been described, mainly due to smoking and corticosteroid use. Whether inhaled corticosteroid (ICS) therapy is associated with an increased risk of TB remains unclear. METHODS: We selected COPD cases by using six diagnostic scenarios and control subjects from a nationwide health insurance database, and applied time-dependent Cox regression analysis to identify the risk factors for TB. RESULTS: Among 1,000,000 beneficiaries, 23,594 COPD cases and 47,188 non-COPD control subjects were selected. Cox regression analysis revealed that age, male gender, diabetes mellitus, end-stage renal disease, and cirrhosis, as well as COPD (hazard ratio = 2.468 [2.205–2.762]) were independent risk factors for TB. Among the COPD cases, those who developed TB received more oral corticosteroids and oral β-agonists. Time-dependent Cox regression analysis revealed that age, male gender, diabetes mellitus, low income, oral corticosteroid dose, and oral β-agonist dose, but not ICS dose, were independent risk factors for TB. The identified risk factors and their hazard ratios were similar among the COPD cases selected using different scenarios. CONCLUSION: Keeping a high suspicion and regularly monitoring for the development of pulmonary TB in COPD patients are necessary, especially for those receiving higher doses of oral corticosteroids and other COPD medications. Although ICS therapy has been shown to predispose COPD patients to pneumonia in large randomized clinical trials, it does not increase the risk of TB in real world practice

Risk Factors in Predicting Prognosis of Neonatal Bacterial Meningitis—A Systematic Review

Background: Neonatal bacterial meningitis is a severe infection with high mortality and morbidity. It is necessary to identify factors associated with a high risk of a poor prognosis so that we can prevent them with more appropriate treatments. This study was performed to summarize the prognostic factors known to predict adverse outcomes in neonatal bacterial meningitis.Methods: The Medline/PubMed, Cochrane Library and Embase databases were searched for studies of prognostic risk factors in neonates with bacterial meningitis. Studies published from the initiation of the database to April 30th, 2017 were included. The quality of cohort studies was assessed by the Newcastle-Ottawa Scale (NOS). The quality of cross-section studies was assessed by the Agency for Healthcare Research and Quality (AHRQ) scale. Each prognostic factor known to cause adverse outcomes is summarized.Results: Sixteen studies were identified, including 7 cohort studies and 9 cross section studies. Seizure and high protein levels in the cerebrospinal fluid (CSF) predict a poor prognosis in this disease. Coma, the need for ventilation support, and leukopenia also had some value for predicting poor prognoses. A bulging anterior fontanelle was valuable for predicting mortality. Low CSF glucose levels, thrombocytopenia, gestational age (GA) < 37 weeks and an altered sensorium were correlated with a poor prognosis. A birth weight < 2500 g, early onset meningitis and positive CSF cultures were correlated with mortality.Conclusions: This study provides a preliminary exploration of prognostic factors in neonatal bacterial meningitis and thereby fills some of the gaps in the study of prognoses in this disease. These prognostic factors can be used to predict and estimate outcomes in neonatal bacterial meningitis. Without a meta-analysis, the reliability of these factors cannot be assured. In addition, these results emphasize that there is an urgent need for a standardized protocol for follow-up and well-designed prognostic studies in neonatal bacterial meningitis

Design and Research of Electron Cyclotron Resonance Heating and Current Dive System on HL-2M Tokamak

A research has been conducted to develop an 8MW electron cyclotron resonance heating and current drive (ECRH/ECCD) system on HL-2M tokamak. The ECRH system compromise eight 1MW gyrotrons, eight evacuated transmission lines and three launchers. The main purpose of the ECRH system was to suppress the neo-classical tearing modes and control the plasma profile. This paper presents an overview of the design and studies performed in this framework. Some primary test results of the critical components have been released in this paper, e.g. polarizers, power monitor and fast steering launchers

Pulmonary Tuberculosis and Delay in Anti-Tuberculous Treatment Are Important Risk Factors for Chronic Obstructive Pulmonary Disease

OBJECTIVE: Tuberculosis (TB) remains the leading cause of death among infectious diseases worldwide. It has been suggested as an important risk factor of chronic obstructive pulmonary disease (COPD), which is also a major cause of morbidity and mortality. This study investigated the impact of pulmonary TB and anti-TB treatment on the risk of developing COPD. DESIGN, SETTING, AND PARTICIPANTS: This cohort study used the National Health Insurance Database of Taiwan, particularly the Longitudinal Health Insurance Database 2005 to obtain 3,176 pulmonary TB cases and 15,880 control subjects matched in age, sex, and timing of entering the database. MAIN OUTCOME MEASURES: Hazard ratios of potential risk factors of COPD, especially pulmonary TB and anti-TB treatment. RESULTS: The mean age of pulmonary TB cases was 51.9±19.2. The interval between the initial study date and commencement of anti-TB treatment (delay in anti-TB treatment) was 75.8±65.4 days. Independent risk factors for developing COPD were age, male, low income, and history of pulmonary TB (hazard ratio 2.054 [1.768-2.387]), while diabetes mellitus was protective. The impact of TB persisted for six years after TB diagnosis and was significant in women and subjects aged >70 years. Among TB patients, delay in anti-TB treatment had a dose-response relationship with the risk of developing COPD. CONCLUSIONS: Some cases of COPD may be preventable by controlling the TB epidemic, early TB diagnosis, and prompt initiation of appropriate anti-TB treatment. Follow-up care and early intervention for COPD may be necessary for treated TB patients