Use of cystatin C to inform metformin eligibility among adult veterans with diabetes.

AimsRecommendations for metformin use are dependent on eGFR category: eGFR >45 ml/min/1.73 m2 - "first-line agent"; eGFR 30-44 - "use with caution"; eGFR<30 - "do not use". Misclassification of metformin eligibility by creatinine-based MDRD GFR estimates (eGFRcr) may contribute to its misuse. We investigated the impact of cystatin c estimates of GFR (eGFRcys) on metformin eligibility.MethodsIn a consecutive cohort of 550 Veterans with diabetes, metformin use and eligibility were assessed by eGFR category, using eGFRcr and eGFRcys. Discrepancy in eligibility was defined as cases where eGFRcr and eGFRcys categories (<30, 30-44, 45-60, and >60 ml/min/1.73 m2) differed with an absolute difference in eGFR of >5 ml/min/1.73 m2. We modeled predictors of metformin use and eGFR category discrepancy with multivariable relative risk regression and multinomial logistic regression.ResultsSubjects were 95% male, median age 68, and racially diverse (45% White, 22% Black, 11% Asian, 22% unknown). Metformin use decreased with severity of eGFRcr category, from 63% in eGFRcr >60 to 3% in eGFRcr <30. eGFRcys reclassified 20% of Veterans into different eGFR categories. Factors associated with a more severe eGFRcys category compared to eGFRcr were older age (aOR = 2.21 per decade, 1.44-1.82), higher BMI (aOR = 1.04 per kg/m2, 1.01-1.08) and albuminuria >30 mg/g (aOR = 1.81, 1.20-2.73).ConclusionsMetformin use is low among Veterans with CKD. eGFRcys may serve as a confirmatory estimate of kidney function to allow safe use of metformin among patients with CKD, particularly among older individuals and those with albuminuria

Robo-AO Kepler Survey IV: the effect of nearby stars on 3857 planetary candidate systems

We present the overall statistical results from the Robo-AO Kepler planetary candidate survey, comprising of 3857 high-angular resolution observations of planetary candidate systems with Robo-AO, an automated laser adaptive optics system. These observations reveal previously unknown nearby stars blended with the planetary candidate host star which alter the derived planetary radii or may be the source of an astrophysical false positive transit signal. In the first three papers in the survey, we detected 440 nearby stars around 3313 planetary candidate host stars. In this paper, we present observations of 532 planetary candidate host stars, detecting 94 companions around 88 stars; 84 of these companions have not previously been observed in high-resolution. We also report 50 more-widely-separated companions near 715 targets previously observed by Robo-AO. We derive corrected planetary radius estimates for the 814 planetary candidates in systems with a detected nearby star. If planetary candidates are equally likely to orbit the primary or secondary star, the radius estimates for planetary candidates in systems with likely bound nearby stars increase by a factor of 1.54, on average. We find that 35 previously-believed rocky planet candidates are likely not rocky due to the presence of nearby stars. From the combined data sets from the complete Robo-AO KOI survey, we find that 14.5\pm0.5% of planetary candidate hosts have a nearby star with 4", while 1.2% have two nearby stars and 0.08% have three. We find that 16% of Earth-sized, 13% of Neptune-sized, 14% of Saturn-sized, and 19% of Jupiter-sized planet candidates have detected nearby stars.Comment: Accepted to the Astronomical Journa

Structural Insight into KCNQ (Kv7) Channel Assembly and Channelopathy

SummaryKv7.x (KCNQ) voltage-gated potassium channels form the cardiac and auditory IKs current and the neuronal M-current. The five Kv7 subtypes have distinct assembly preferences encoded by a C-terminal cytoplasmic assembly domain, the A-domain Tail. Here, we present the high-resolution structure of the Kv7.4 A-domain Tail together with biochemical experiments that show that the domain is a self-assembling, parallel, four-stranded coiled coil. Structural analysis and biochemical studies indicate conservation of the coiled coil in all Kv7 subtypes and that a limited set of interactions encode assembly specificity determinants. Kv7 mutations have prominent roles in arrhythmias, deafness, and epilepsy. The structure together with biochemical data indicate that A-domain Tail arrhythmia mutations cluster on the solvent-accessible surface of the subunit interface at a likely site of action for modulatory proteins. Together, the data provide a framework for understanding Kv7 assembly specificity and the molecular basis of a distinct set of Kv7 channelopathies

Robo-AO Kepler Survey V: The effect of physically associated stellar companions on planetary systems

The Kepler light curves used to detect thousands of planetary candidates are susceptible to dilution due to blending with previously unknown nearby stars. With the automated laser adaptive optics instrument, Robo-AO, we have observed 620 nearby stars around 3857 planetary candidates host stars. Many of the nearby stars, however, are not bound to the KOI. In this paper, we quantify the association probability between each KOI and detected nearby stars through several methods. Galactic stellar models and the observed stellar density are used to estimate the number and properties of unbound stars. We estimate the spectral type and distance to 145 KOIs with nearby stars using multi-band observations from Robo-AO and Keck-AO. We find most nearby stars within 1" of a Kepler planetary candidate are likely bound, in agreement with past studies. We use likely bound stars as well as the precise stellar parameters from the California Kepler Survey to search for correlations between stellar binarity and planetary properties. No significant difference between the binarity fraction of single and multiple planet systems is found, and planet hosting stars follow similar binarity trends as field stars, many of which likely host their own non-aligned planets. We find that hot Jupiters are ~4x more likely than other planets to reside in a binary star system. We correct the radius estimates of the planet candidates in characterized systems and find that for likely bound systems, the estimated planetary candidate radii will increase on average by a factor of 1.77, if either star is equally likely to host the planet. We find that the planetary radius gap is robust to the impact of dilution, and find an intriguing 95%-confidence discrepancy between the radius distribution of small planets in single and binary systems.Comment: 19 pages, 12 figures, submitted to AAS Journal

Child educational progress in Born in Bradford pregnancies affected by gestational diabetes and also exposed to maternal common mental disorders

Abstract Gestational diabetes and the maternal mental disorders of anxiety and depression have been implicated in adverse offspring neuro-behavioural outcomes but these exposures have only been studied in isolation. 1051 children whose mothers were diagnosed with gestational diabetes in UK’s Born in Bradford cohort had linkage to maternal primary care records, providing diagnostic and treatment codes for depression and anxiety. Education record linkage provided results of the Early Years Foundation Stage Profile from the first year of school, aged five. Risk of not attaining a ‘Good level of development’ was analysed using multivariable Poisson regression within a generalised estimating equation framework. Multiple imputation was implemented for missing data. There was limited evidence of increased risk of failure to attain a ‘good level of development’ in those additionally exposed to maternal mental disorders (adjusted RR 1.21; 95% CI 0.94, 1.55). However, there was more evidence in children of Pakistani maternal ethnicity (adjusted RR 1.36; 95% CI 1.04, 1.77) than White British; this may have been driven by English not being the primary language spoken in the home. Therefore there may be groups with GDM in whom it is particularly important to optimise both maternal physical and mental health to improve child outcomes

Crossover of Organizational Commitment

Spousal commitment toward an employee\u27s organization is a little-studied construct that deserves attention because his or her spouse may influence the employee\u27s assessments of organizational commitment and turnover intentions. Using 186 couples, this study investigated spousal influence on U.S. military members’ organizational commitment and their decisions to reenlist. Results of a structural equation model analysis indicate that indirect mechanisms of crossover (e.g., positive emotions displayed by the spouse during discussions of reenlistment) facilitated the positive relationships between the organizational commitment of military spouses and members. Findings and discussion contribute to the fields of organizational commitment and crossover, and we conclude our analysis by offering practical implications for nonmilitary occupations

The Physical Activity Resource Assessment (PARA) instrument: Evaluating features, amenities and incivilities of physical activity resources in urban neighborhoods

Background: Neighborhood environment factors may influence physical activity (PA). The purpose of this study was to develop and test a brief instrument to systematically document and describe the type, features, amenities, quality and incivilities of a variety of PA resources. Method: The one-page Physical Activity Resource Assessment (PARA) instrument was developed to assess all publicly available PA resources in thirteen urban lower income, high ethnic minority concentration neighborhoods that surrounded public housing developments (HDs) and four higher income, low ethnic minority concentration comparison neighborhoods. Neighborhoods had similar population density and connectivity. Trained field coders rated 97 PA resources (including parks, churches, schools, sports facilities, fitness centers, community centers, and trails) on location, type, cost, features, amenities, quality and incivilities. Assessments typically took about 10 minutes to complete. Results: HD neighborhoods had a mean of 4.9 PA resources (n = 73) with considerable variability in the type of resources available for each neighborhood. Comparison neighborhoods had a mean of 6 resources (n = 24). Most resources were accessible at no cost (82%). Resources in both types of neighborhoods typically had about 2 to 3 PA features and amenities, and the quality was usually mediocre to good in both types of neighborhoods. Incivilities at PA resources in HD neighborhoods were significantly more common than in comparison neighborhoods. Conclusion: Although PA resources were similar in number, features and amenities, the overall appearance of the resources in HD neighborhoods was much worse as indicated by substantially worse incivilities ratings in HD neighborhoods. The more comprehensive assessment, including features, amenities and incivilities, provided by the PARA may be important to distinguish between PA resources in lower and higher deprivation areas

The Physical Activity Resource Assessment (PARA) instrument: Evaluating features, amenities and incivilities of physical activity resources in urban neighborhoods

BACKGROUND: Neighborhood environment factors may influence physical activity (PA). The purpose of this study was to develop and test a brief instrument to systematically document and describe the type, features, amenities, quality and incivilities of a variety of PA resources. METHOD: The one-page Physical Activity Resource Assessment (PARA) instrument was developed to assess all publicly available PA resources in thirteen urban lower income, high ethnic minority concentration neighborhoods that surrounded public housing developments (HDs) and four higher income, low ethnic minority concentration comparison neighborhoods. Neighborhoods had similar population density and connectivity. Trained field coders rated 97 PA resources (including parks, churches, schools, sports facilities, fitness centers, community centers, and trails) on location, type, cost, features, amenities, quality and incivilities. Assessments typically took about 10 minutes to complete. RESULTS: HD neighborhoods had a mean of 4.9 PA resources (n = 73) with considerable variability in the type of resources available for each neighborhood. Comparison neighborhoods had a mean of 6 resources (n = 24). Most resources were accessible at no cost (82%). Resources in both types of neighborhoods typically had about 2 to 3 PA features and amenities, and the quality was usually mediocre to good in both types of neighborhoods. Incivilities at PA resources in HD neighborhoods were significantly more common than in comparison neighborhoods. CONCLUSION: Although PA resources were similar in number, features and amenities, the overall appearance of the resources in HD neighborhoods was much worse as indicated by substantially worse incivilities ratings in HD neighborhoods. The more comprehensive assessment, including features, amenities and incivilities, provided by the PARA may be important to distinguish between PA resources in lower and higher deprivation areas