State-level income inequality and mortality among infants born in the United States 2007-2010: A Cohort Study

BACKGROUND: United States state-level income inequality is positively associated with infant mortality in ecological studies. We exploit spatiotemporal variations in a large dataset containing individual-level data to conduct a cohort study and to investigate whether current income inequality and increases in income inequality are associated with infant and neonatal mortality risk over the period of the 2007-2010 Great Recession in the United States. METHODS: We used data on 16,145,716 infants and their mothers from the 2007-2010 United States Statistics Linked Infant Birth and Death Records. Multilevel logistic regression was used to determine whether 1) US state-level income inequality, as measured by Z-transformed Gini coefficients in the year of birth and 2) change in Gini coefficient between 1990 and year of birth (2007-2010), predicted infant or neonatal mortality. Our analyses adjusted for both individual and state-level covariates. RESULTS: From 2007 to 2010 there were 98,002 infant deaths: an infant mortality rate of 6.07 infant deaths per 1000 live births. When controlling for state and individual level characteristics, there was no significant relationship between Gini Z-score and infant mortality risk. However, the observed increase in the Gini Z-score was associated with a small but significant increase likelihood of infant mortality (AOR = 1.03 to 1.06 from 2007 to 2010). Similar findings were observed when the neonatal mortality was the outcome (AOR = 1.05 to 1.13 from 2007 to 2010). CONCLUSIONS: Infants born in states with greater changes in income inequality between 1990 and 2007 to 2010 experienced a greater likelihood of infant and neonatal mortality

Understanding Hydrologic Variation Through Time-Series Analysis

2010 S.C. Water Resources Conference - Science and Policy Challenges for a Sustainable Futur

Exome sequencing followed by large-scale genotyping suggests a limited role for moderately rare risk factors of strong effect in schizophrenia.

Schizophrenia is a severe psychiatric disorder with strong heritability and marked heterogeneity in symptoms, course, and treatment response. There is strong interest in identifying genetic risk factors that can help to elucidate the pathophysiology and that might result in the development of improved treatments. Linkage and genome-wide association studies (GWASs) suggest that the genetic basis of schizophrenia is heterogeneous. However, it remains unclear whether the underlying genetic variants are mostly moderately rare and can be identified by the genotyping of variants observed in sequenced cases in large follow-up cohorts or whether they will typically be much rarer and therefore more effectively identified by gene-based methods that seek to combine candidate variants. Here, we consider 166 persons who have schizophrenia or schizoaffective disorder and who have had either their genomes or their exomes sequenced to high coverage. From these data, we selected 5,155 variants that were further evaluated in an independent cohort of 2,617 cases and 1,800 controls. No single variant showed a study-wide significant association in the initial or follow-up cohorts. However, we identified a number of case-specific variants, some of which might be real risk factors for schizophrenia, and these can be readily interrogated in other data sets. Our results indicate that schizophrenia risk is unlikely to be predominantly influenced by variants just outside the range detectable by GWASs. Rather, multiple rarer genetic variants must contribute substantially to the predisposition to schizophrenia, suggesting that both very large sample sizes and gene-based association tests will be required for securely identifying genetic risk factors. © 2012 The American Society of Human Genetics

Clinical impact of recurrently mutated genes on lymphoma diagnostics

Similar to the inherent clinical heterogeneity of most, if not all, lymphoma entities, the genetic landscape of these tumors is markedly complex in the majority of cases, with a rapidly growing list of recurrently mutated genes discovered in recent years by next-generation sequencing technology. Whilst a few genes have been implied to have diagnostic, prognostic and even predictive impact, most gene mutations still require rigorous validation in larger, preferably prospective patient series, to scrutinize their potential role in lymphoma diagnostics and patient management. In selected entities, a predominantly mutated gene is identified in almost all cases (e.g. Waldenström's macroglobulinemia/lymphoplasmacytic lymphoma and hairy-cell leukemia), while for the vast majority of lymphomas a quite diverse mutation pattern is observed, with a limited number of frequently mutated genes followed by a seemingly endless tail of genes with mutations at a low frequency. Herein, the European Expert Group on NGS-based Diagnostics in Lymphomas (EGNL) summarizes the current status of this ever-evolving field, and, based on the present evidence level, segregates mutations into the following categories: i) immediate impact on treatment decisions, ii) diagnostic impact, iii) prognostic impact, iv) potential clinical impact in the near future, or v) should only be considered for research purposes. In the coming years, coordinated efforts aiming to apply targeted next-generation sequencing in large patient series will be needed in order to elucidate if a particular gene mutation will have an immediate impact on the lymphoma classification, and ultimately aid clinical decision making

Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations

Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal prior to treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared to wildtype RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology

Suicide ideation of individuals in online social networks

Suicide explains the largest number of death tolls among Japanese adolescents in their twenties and thirties. Suicide is also a major cause of death for adolescents in many other countries. Although social isolation has been implicated to influence the tendency to suicidal behavior, the impact of social isolation on suicide in the context of explicit social networks of individuals is scarcely explored. To address this question, we examined a large data set obtained from a social networking service dominant in Japan. The social network is composed of a set of friendship ties between pairs of users created by mutual endorsement. We carried out the logistic regression to identify users' characteristics, both related and unrelated to social networks, which contribute to suicide ideation. We defined suicide ideation of a user as the membership to at least one active user-defined community related to suicide. We found that the number of communities to which a user belongs to, the intransitivity (i.e., paucity of triangles including the user), and the fraction of suicidal neighbors in the social network, contributed the most to suicide ideation in this order. Other characteristics including the age and gender contributed little to suicide ideation. We also found qualitatively the same results for depressive symptoms.Comment: 4 figures, 9 table

Vertebral anti-fracture efficacy of strontium ranelate according to pre-treatment bone turnover

Osteoporotic post-menopausal women patients in two randomised trials comparing the anti-fracture efficacy of strontium ranelate with placebo were separated into tertiles according to their baseline levels of biochemical markers of bone formation and resorption. The vertebral anti-fracture efficacy of strontium ranelate was shown to be independent of baseline bone turnover levels. INTRODUCTION: Bone turnover (BTO) levels vary among women at risk of osteoporotic fracture. Strontium ranelate is an anti-osteoporotic treatment increasing bone formation and reducing bone resorption. It was hypothesised that its anti-fracture efficacy would be independent of baseline BTO levels. METHODS: Post-menopausal women with osteoporosis from two pooled studies were stratified in tertiles according to baseline levels of two BTO markers: bone-specific alkaline phosphatase (b-ALP, n = 4995) and serum C-telopeptide cross-links (sCTX, n = 4891). Vertebral fracture risk was assessed over 3 years with strontium ranelate 2 g/day or placebo. RESULTS: In the placebo group, relative risk of vertebral fractures increased with BTO tertiles by 32% and 24% for patients in the highest tertile for b-ALP and CTX, respectively, compared to those in the lowest tertile. In the strontium ranelate group, incidences of vertebral fracture did not differ significantly across BTO tertiles. Significant reductions in vertebral fractures with strontium ranelate were seen in all tertiles of both markers, with relative risk reductions of 31% to 47% relative to placebo. Risk reduction did not differ among tertiles (b-ALP: p = 0.513; sCTX: p = 0.290). CONCLUSION: The vertebral anti-fracture efficacy of strontium ranelate was independent of baseline BTO levels. Strontium ranelate offers clinical benefits to women across a wide range of metabolic states