SETBP1 Mutations as a Biomarker for Myelodysplasia /Myeloproliferative Neoplasm Overlap Syndrome

Myelodysplasia (MDS) /myeloproliferative neoplasm (MPN) overlap syndrome has been described since the 2001 WHO classification as disorders that have both proliferative and dysplastic changes simultaneously. Specific disorders include chronic myelomonocytic leukemia (CMML), juvenile myelomonocytic leukemia (JMML), BCR-ABL negative atypical chronic myeloid leukemia (aCML) and unclassifiable MDS/MPN (MPN/MDS-U). Recurrent gene mutations in these conditions have been described. Among them, SETBP1 mutations have been identified in up to 32% of aCML, 24% of JMML, 18% of CMML and 10% of MDS/MPN-U patients. The mutation hotspot lies in the amino acid residues 858-871 in the SETBP1 protein. SETBP1 mutations in MDS/MPN overlap syndrome is associated with accelerated transformation to leukemia and poor prognosis. In this review, we summarized the latest data on the role of SETBP1 mutations in the overlap syndrome. SETBP1 mutations may serve as a biomarker for the diagnosis and poor prognosis of the overlap syndrome

The Multiplicity of M-Dwarfs in Young Moving Groups

We image 104 newly identified low-mass (mostly M-dwarf) pre-main sequence members of nearby young moving groups with Magellan Adaptive Optics (MagAO) and identify 27 binaries with instantaneous projected separation as small as 40 mas. 15 were previously unknown. The total number of multiple systems in this sample including spectroscopic and visual binaries from the literature is 36, giving a raw multiplicity rate of at least $35^{+5}_{-4}\%$ for this population. In the separation range of roughly 1 - 300 AU in which infrared AO imaging is most sensitive, the raw multiplicity rate is at least $24^{+5}_{-4}\%$ for binaries resolved by the MagAO infrared camera (Clio). The M-star sub-sample of 87 stars yields a raw multiplicity of at least $30^{+5}_{-4}\%$ over all separations, $21^{+5}_{-4}\%$ for secondary companions resolved by Clio from 1 to 300 AU ($23^{+5}_{-4}\%$ for all known binaries in this separation range). A combined analysis with binaries discovered by the Search for Associations Containing Young stars shows that multiplicity fraction as a function of mass and age over the range of 0.2 to 1.2 $M_\odot$ and 10 - 200 Myr appears to be linearly flat in both parameters and across YMGs. This suggests that multiplicity rates are largely set by 100 Myr without appreciable evolution thereafter. After bias corrections are applied, the multiplicity fraction of low-mass YMG members ($< 0.6 M_\odot$) is in excess of the field.Comment: 25 page

Work stress and alcohol consumption among adolescents: moderation by family and peer influences

Excessive alcohol use in adolescence can be detrimental to health and academic performance. Few studies consider the moderating effects of parental and peer influence within the context of adolescent work outside of the school environment. This study aims to examine work stress among adolescents and the association with alcohol use and drunkenness, in the context of parental and peer influences. Grade 12 students who participated in Monitoring the Future surveys between 2005 and 2009 (n = 12,341) were included in this study. Independent variables included work stress (job satisfaction, perceived safety, and perceived safety of possessions), self-reported perceptions towards academics and influence from parents and peers. Frequency of alcohol use and drunkenness were measured for lifetime, last 30 days and 12 months. The moderating effects of academic aspiration, parental, and peer influence were assessed on the relationship between work stress and alcohol use. Any work stress was positively associated with alcohol use over the past 12 months (odds ratio = 1.12, 95% confidence interval (CI) 1.02-1.23). Stratified analysis found that peer influence significantly moderated the relationship between work stress and alcohol use over the lifetime and past 12 months. Among adolescents with work stress, odds ratios of alcohol use over the lifetime was 0.83 (95% CI 0.71-0.97) for those with low negative peer influence and 1.09 (95% CI 0.97-1.22) for those with high negative peer influence. Problematic drinking patterns were more apparent among high school students who experienced stress at work. Positive peer influence, however, may buffer the adverse effect of work stress on alcohol use

Two Transiting Earth-size Planets Near Resonance Orbiting a Nearby Cool Star

Discoveries from the prime Kepler mission demonstrated that small planets (< 3 Earth-radii) are common outcomes of planet formation. While Kepler detected many such planets, all but a handful orbit faint, distant stars and are not amenable to precise follow up measurements. Here, we report the discovery of two small planets transiting K2-21, a bright (K = 9.4) M0 dwarf located 65$\pm$6 pc from Earth. We detected the transiting planets in photometry collected during Campaign 3 of NASA's K2 mission. Analysis of transit light curves reveals that the planets have small radii compared to their host star, 2.60 $\pm$ 0.14% and 3.15 $\pm$ 0.20%, respectively. We obtained follow up NIR spectroscopy of K2-21 to constrain host star properties, which imply planet sizes of 1.59 $\pm$ 0.43 Earth-radii and 1.92 $\pm$ 0.53 Earth-radii, respectively, straddling the boundary between high-density, rocky planets and low-density planets with thick gaseous envelopes. The planets have orbital periods of 9.32414 days and 15.50120 days, respectively, and have a period ratio of 1.6624, very near to the 5:3 mean motion resonance, which may be a record of the system's formation history. Transit timing variations (TTVs) due to gravitational interactions between the planets may be detectable using ground-based telescopes. Finally, this system offers a convenient laboratory for studying the bulk composition and atmospheric properties of small planets with low equilibrium temperatures.Comment: Updated to ApJ accepted version; photometry available alongside LaTeX source; 10 pages, 7 figure

Validation and Utilization of a Clinical Next-Generation Sequencing Panel for Selected Cardiovascular Disorders

The development of high-throughput technologies such as next-generation sequencing (NGS) has allowed for thousands of DNA loci to be interrogated simultaneously in a fast and economical method for the detection of clinically deleterious variants. Whenever a clinical diagnosis is known, a targeted NGS approach involving the use of disease-specific gene panels can be employed. This approach is often valuable as it allows for a more specific and clinically relevant interpretation of results. Here, we describe the customization, validation, and utilization of a commercially available targeted enrichment platform for the scalability of clinical diagnostic cardiovascular genetic tests, including the design of the gene panels, the technical parameters for the quality assurance and quality control, the customization of the bioinformatics pipeline, and the post-bioinformatics analysis procedures. Regions of poor base coverage were detected and targeted by Sanger sequencing as needed. All panels were successfully validated using genotype-known DNA samples either commercially available or from research subjects previously tested in outside clinical laboratories. In our experience, utilizing several of the sub-panels in a clinical setting with 33 real-life cardiovascular patients, we found that 20% of tests requested were reported to have at least one pathogenic or likely pathogenic variant that could explain the patient phenotype. For each of these patients, the positive results may aid the clinical team and the patients in best developing a disease management plan and in identifying relatives at risk

Dietary Patterns, Abdominal Visceral Adipose Tissue and Cardiometabolic Risk Factors in African Americans: the Jackson Heart Study

Dietary behavior is an important lifestyle factor to impact an individual’s risk of developing cardiovascular disease (CVD). However, the influence of specific dietary factors on CVD risk for African Americans remains unclear. We conducted a cross-sectional study of 1775 participants from Jackson Heart Study (JHS) Exam 2 (between 2006 and 2009) who were free of hypertension, diabetes and CVD at the baseline (between 2001 and 2004). Dietary intakes were documented using a validated food-frequency questionnaire (FFQ) and dietary patterns were generated by factor analysis. Three major dietary patterns were identified: a “southern”, a “fast food” and a “prudent” pattern. After adjustment for age, sex, smoking and alcohol status, education level and physical activity, high “southern” pattern score was associated with an increased odds ratio (OR) for high abdominal visceral adipose tissue (VAT) (OR:1.80, 95%CI:1.1–3.0, p=0.02), hypertension (OR:1.42, 95%CI:1.1–1.9, p=0.02), diabetes (OR:2.03, 95%CI:1.1–3.9, p=0.03) and metabolic syndrome (OR:2.16, 95%CI:1.3–3.6, p=0.004). Similar associations were also observed in the “fast food” pattern (p ranges 0.03–0.0001). The “prudent” pattern was significantly associated, in a protective direction, with hypertension (OR 0.69, 95%CI 0.5–0.9, p=0.02). In conclusion, dietary patterns, especially the “southern” pattern, identified from a regional specific FFQ in this Deep South African Americans, are correlated with abdominal VAT and cardiometabolic risk factors

A Population‐Based Twin Study on Sleep Duration and Body Composition

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/93648/1/oby.2011.274.pd

Dynamical Masses of Young M Dwarfs: Masses and Orbital Parameters of GJ 3305 AB, the Wide Binary Companion to the Imaged Exoplanet Host 51 Eri

We combine new high resolution imaging and spectroscopy from Keck/NIRC2, Discovery Channel Telescope/DSSI, and Keck/HIRES with published astrometry and radial velocities to measure individual masses and orbital elements of the GJ 3305 AB system, a young (~20 Myr) M+M binary (unresolved spectral type M0) member of the β Pictoris moving group comoving with the imaged exoplanet host 51 Eri. We measure a total system mass of 1.11 ± 0.04 M_⊙, a period of 29.03 ± 0.50 year, a semimajor axis of 9.78 ± 0.14 AU, and an eccentricity of 0.19 ± 0.02. The primary component has a dynamical mass of 0.67 ± 0.05 M_⊙ and the secondary has a mass of 0.44 ± 0.05 M_⊙. The recently updated BHAC15 models are consistent with the masses of both stars to within 1.5σ. Given the observed masses the models predict an age of the GJ 3305 AB system of 37 ± 9 Myr. Based on the observed system architecture and our dynamical mass measurement, it is unlikely that the orbit of 51 Eri b has been significantly altered by the Kozai–Lidov mechanism