Shared and unique common genetic determinants between pediatric and adult celiac disease

Table S1. Functional profiles of the top non-HLA association signals identified in Paediatric CD and Adult CD among north Indians. Table S2. Test of heterogeneity (Breslow-Day test) for associated SNPs in PaediatricCD and AdultCD groups. Table S3. cis-eQTL evaluation of associated SNPs. Table S4. GRAIL analysis revealed seven genes with significant (p <0.05) interaction with 39 known non-HLA coeliac disease loci. These seven genes are from four loci identified in this study. (DOCX 26 kb

Birth outcomes following self-inflicted poisoning during pregnancy, California, 2000 to 2004.

OBJECTIVE: To describe birth outcomes following intentional acute poisoning during pregnancy. SETTING: California Linked Vital Statistics-Patient Discharge Database, 2000 to 2004. PARTICIPANTS: Pregnant women age 15 to 44, who had a singleton live birth or fetal death that occurred between gestational ages 20 and 42 weeks who were discharged from the hospital for an intentional poisoning were compared to pregnant women discharged from the hospital for any nonpoisoning diagnosis. Intentional acute poisoning hospital discharges were identifed by the presence of an ICD-9-CM E-Codes E950-E952 (suicide, attempted suicide and self-inflicted injuries specified as intentional.) METHODS: Through a retrospective cohort design, birth outcomes including low birth weight; preterm birth; fetal, neonatal, and infant death; and congenital anomalies were identified by the presence of ICD-9-CM diagnosis codes or by notation in the dataset. RESULTS: There were 430 hospital discharges for an intentional poisoning during pregnancy documented in the dataset (rate=25.87/100,000 person years). The rate of intentional poisoning was greatest in the first weeks of gestation and declined with increasing gestational age. Analgesics, antipyretics, and antirheumatics were most commonly implicated. Adverse birth outcomes associated with intentional poisoning included preterm birth (odds ratio [OR]=1.34; 95% Confidence Interval [CI] [1.01, 1.77]), low birth weight (OR=1.49; 95% CI [1.04, 2.12]), and circulatory system congenital anomalies (OR=2.17; 95% CI [1.02, 4.59]). CONCLUSION: Intentional acute poisoning during pregnancy was associated with several adverse birth outcomes; however, these relationships may be confounded by concomitant maternal substance abuse

Life After Sport: Athletic Career Transition and Transferable Skills

Permission to include this article granted by Journal of ExcellenceAthletes transitioning out of sport are faced with many obstacles. Well-trained counselors have the appropriate skills to assist athletes through athletic career transition. An examination of the literature focused on career retirement and transferable skills lead to the development of intervention recommendations for athletes transitioning out of sport. Treatment recommendations include psycho-educational and cognitive behavioural interventions that focus on the emotions associated with transitioning from sport as well as an emphasis on transferable skills.Ye

Chronic renal insufficiency among Asian Indians with type 2 diabetes: I. Role of RAAS gene polymorphisms

BACKGROUND: Renal failure in diabetes is mediated by multiple pathways. Experimental and clinical evidences suggest that renin-angiotensin-aldosterone system (RAAS) has a crucial role in diabetic kidney disease. A relationship between the RAAS genotypes and chronic renal insufficiency (CRI) among type 2 diabetes subjects has therefore been speculated. We investigated the contribution of selected RAAS gene polymorphisms to CRI among type 2 diabetic Asian Indian subjects. METHODS: Twelve single nucleotide polymorphisms (SNPs) from six genes namely-renin (REN), angiotensinogen (ATG), angiotensin converting enzyme I (ACE), angiotensin II type 1 receptor (AT1) and aldosterone synthase (CYP11B2) gene from the RAAS pathway and one from chymase pathway were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method and tested for their association with diabetic CRI using a case-control approach. Successive cases presenting to study centres with type 2 diabetes of ≥2 years duration and moderate CRI diagnosed by serum creatinine ≥3 mg/dl after exclusion of non-diabetic causes of CRI (n = 196) were compared with diabetes subjects with no evidence of renal disease (n = 225). Logistic regression analysis was carried out to correlate various clinical parameters with genotypes, and to study pair wise interactions between SNPs of different genes. RESULTS: Of the 12 SNPs genotyped, Glu53Stop in AGT and A>T (-777) in AT1 genes, were monomorphic and not included for further analysis. We observed a highly significant association of Met235Thr SNP in angiotensinogen gene with CRI (O.R. 2.68, 95%CI: 2.01–3.57 for Thr allele, O.R. 2.94, 95%CI: 1.88–4.59 for Thr/Thr genotype and O.R. 2.68, 95%CI: 1.97–3.64 for ACC haplotype). A significant allelic and genotypic association of T>C (-344) SNP in aldosterone synthase gene (O.R. 1.57, 95%CI: 1.16–2.14 and O.R. 1.81, 95%CI: 1.21–2.71 respectively), and genotypic association of GA genotype of G>A (-1903) in chymase gene (O.R. 2.06, 95%CI: 1.34–3.17) were also observed. CONCLUSION: SNPs Met235Thr in angiotensinogen, T>C (-344) in aldosterone synthase, and G>A (-1903) in chymase genes are significantly associated with diabetic chronic renal insufficiency in Indian patients and warrant replication in larger sample sets. Use of such markers for prediction of susceptibility to diabetes specific renal disease in the ethnically Indian population appears promising

Caucasian and Asian Specific Rheumatoid Arthritis Risk Loci Reveal Limited Replication and Apparent Allelic Heterogeneity in North Indians

Genome-wide association studies and meta-analysis indicate that several genes/loci are consistently associated with rheumatoid arthritis (RA) in European and Asian populations. To evaluate the transferability status of these findings to an ethnically diverse north Indian population, we performed a replication analysis. We investigated the association of 47 single-nucleotide polymorphisms (SNPs) at 43 of these genes/loci with RA in a north Indian cohort comprising 983 RA cases and 1007 age and gender matched controls. Genotyping was done using Infinium human 660w-quad. Association analysis by chi-square test implemented in plink was carried out in two steps. Firstly, association of the index or surrogate SNP (r2>0.8, calculated from reference GIH Hap-Map population) was tested. In the second step, evidence for allelic/locus heterogeneity at aforementioned genes/loci was assessed for by testing additional flanking SNPs in linkage equilibrium with index/surrogate marker

Association of TGFβ1, TNFα, CCR2 and CCR5 gene polymorphisms in type-2 diabetes and renal insufficiency among Asian Indians

BACKGROUND: Cytokines play an important role in the development of diabetic chronic renal insufficiency (CRI). Transforming growth factor β1 (TGF β1) induces renal hypertrophy and fibrosis, and cytokines like tumor necrosis factor-alpha (TNFα), chemoattractant protein-1 (MCP-1), and regulated upon activation and normal T cell expressed and secreted (RANTES) mediate macrophage infiltration into kidney. Over expression of these chemokines leads to glomerulosclerosis and interstitial fibrosis. The effect of MCP-1 and RANTES on kidney is conferred by their receptors i.e., chemokine receptor (CCR)-2 and CCR-5 respectively. We tested association of nine single nucleotide polymorphisms (SNPs) from TGFβ1, TNFα, CCR2 and CCR5 genes among individuals with type-2 diabetes with and without renal insufficiency. METHODS: Type-2 diabetes subjects with chronic renal insufficiency (serum creatinine ≥ 3.0 mg/dl) constituted the cases, and matched individuals with diabetes of duration ≥ 10 years and normoalbuminuria were evaluated as controls from four centres in India. Allelic and genotypic contributions of nine SNPs from TGFβ1, TNFα, CCR2 and CCR5 genes to diabetic CRI were tested by computing odds ratio (OR) and 95% confidence intervals (CI). Sub-analysis of CRI cases diabetic retinopathy status as dependent variable and SNP genotypes as independent variable in a univariate logistic regression was also performed. RESULTS: SNPs Tyr81His and Thr263Ile in TGF β1 gene were monomorphic, and Arg25Pro in TGF β1 gene and Δ32 polymorphism in CCR5 gene were minor variants (minor allele frequency <0.05) and therefore were not considered for case-control analysis. A significant allelic association of 59029G>A SNP of CCR5 gene has been observed and the allele 59029A seems to confer predisposition to development of diabetic CRI (OR 1.39; CI 1.04–1.84). In CRI subjects a compound group of genotypes "GA and AA" of SNP G>A -800 was found to confer predisposition for proliferative retinopathy (OR 3.03; CI 1.08–8.50, p = 0.035). CONCLUSION: Of the various cytokine gene polymorphisms tested, allele 59029A of CCR5 gene is significantly associated with diabetic renal insufficiency among Asian Indians. Result obtained for 59029G>A SNP of CCR5 gene is in conformity with reports from a Japanese population but due to sub-optimal power of the sample, replication in larger sample set is warranted

Applying design patterns in the search-based optimization of software product line architectures

The design of the product line architecture (PLA) is a difficult activity that can benefit from the application of design patterns and from the use of a search-based optimization approach, which is generally guided by different objectives related, for instance, to cohesion, coupling and PLA extensibility. The use of design patterns for PLAs is a recent research field, not completely explored yet. Some works apply the patterns manually and for a specific domain. Approaches to search-based PLA design do not consider the usage of these patterns. To allow such use, this paper introduces a mutation operator named “Pattern-Driven Mutation Operator” that includes methods to automatically identify suitable scopes and apply the patterns Strategy, Bridge and Mediator with the search-based approach multi-objective optimization approach for PLA. A metamodel is proposed to represent and identify suitable scopes to receive each one of the patterns, avoiding the introduction of architectural anomalies. Empirical results are also presented, showing evidences that the use of the proposed operator produces a greater diversity of solutions and improves the quality of the PLAs obtained in the search-based optimization process, regarding the values of software metrics

Reconstructing Native American Population History

The peopling of the Americas has been the subject of extensive genetic, archaeological and linguistic research; however, central questions remain unresolved1–5. One contentious issue is whether the settlement occurred via a single6–8 or multiple streams of migration from Siberia9–15. The pattern of dispersals within the Americas is also poorly understood. To address these questions at higher resolution than was previously possible, we assembled data from 52 Native American and 17 Siberian groups genotyped at 364,470 single nucleotide polymorphisms. We show that Native Americans descend from at least three streams of Asian gene flow. Most descend entirely from a single ancestral population that we call “First American”. However, speakers of Eskimo-Aleut languages from the Arctic inherit almost half their ancestry from a second stream of Asian gene flow, and the Na-Dene-speaking Chipewyan from Canada inherit roughly one-tenth of their ancestry from a third stream. We show that the initial peopling followed a southward expansion facilitated by the coast, with sequential population splits and little gene flow after divergence, especially in South America. A major exception is in Chibchan-speakers on both sides of the Panama Isthmus, who have ancestry from both North and South America