Prospective relationships between body weight and physical activity: an observational analysis from the NAVIGATOR study

Objectives: While bidirectional relationships exist between body weight and physical activity, direction of causality remains uncertain and previous studies have been limited by self-reported activity or weight and small sample size. We investigated the prospective relationships between weight and physical activity. Design: Observational analysis of data from the Nateglinide And Valsartan in Impaired Glucose Tolerance Outcomes Research (NAVIGATOR) study, a double-blinded randomised clinical trial of nateglinide and valsartan, respectively. Setting Multinational study of 9306 participants. Participants: Participants with biochemically confirmed impaired glucose tolerance had annual measurements of both weight and step count using research grade pedometers, worn for 7 days consecutively. Along with randomisation to valsartan or placebo plus nateglinide or placebo, participants took part in a lifestyle modification programme. Outcome measures: Longitudinal regression using weight as response value and physical activity as predictor value was conducted, adjusted for baseline covariates. Analysis was then repeated with physical activity as response value and weight as predictor value. Only participants with a response value preceded by at least three annual response values were included. Results: Adequate data were available for 2811 (30%) of NAVIGATOR participants. Previous weight (χ2=16.8; p<0.0001), but not change in weight (χ2=0.1; p=0.71) was inversely associated with subsequent step count, indicating lower subsequent levels of physical activity in heavier individuals. Change in step count (χ2=5.9; p=0.02) but not previous step count (χ2=0.9; p=0.34) was inversely associated with subsequent weight. However, in the context of trajectories already established for weight (χ2 for previous weight measurements 747.3; p<0.0001) and physical activity (χ2 for previous step count 432.6; p<0.0001), these effects were of limited clinical importance. Conclusions: While a prospective bidirectional relationship was observed between weight and physical activity, the magnitude of any effect was very small in the context of natural trajectories already established for these variables

Do MODIS-defined dust sources have a geomorphological signature?

The preferential dust source (PDS) scheme enables large-scale mapping of geomorphology in terms of importance for dust emissions but has not been independently tested other than at local scales. We examine the PDS qualitative conceptual model of surface emissivity alongside a quantitative measurement of dust loading from Moderate Resolution Imaging Spectroradiometer (MODIS) Deep Blue Collection 6 for the Chihuahuan Desert. The predicted ranked importance of each geomorphic type for dust emissions is compared with the actual ranked importance as determined from the satellite-derived dust loading. For this region, the predicted variability and magnitude of dust emissions from most surface types present coincides with the observed characteristics demonstrating the significance of geomorphological controls on emission. The exception is for areas of low magnitude but persistent emissions such as alluvial surfaces where PDS overpredicts dustiness. As PDS is a good predictor of emissions and incorporates surface dynamics it could improve models of future dust emissions

Trends in Drug Utilization, Glycemic Control, and Rates of Severe Hypoglycemia, 2006-2013.

ObjectiveTo examine temporal trends in utilization of glucose-lowering medications, glycemic control, and rate of severe hypoglycemia among patients with type 2 diabetes (T2DM).Research design and methodsUsing claims data from 1.66 million privately insured and Medicare Advantage patients with T2DM from 2006 to 2013, we estimated the annual 1) age- and sex-standardized proportion of patients who filled each class of agents; 2) age-, sex-, race-, and region-standardized proportion with hemoglobin A1c (HbA1c) <6%, 6 to <7%, 7 to <8%, 8 to <9%, ≥9%; and 3) age- and sex-standardized rate of severe hypoglycemia among those using medications. Proportions were calculated overall and stratified by age-group (18-44, 45-64, 65-74, and ≥75 years) and number of chronic comorbidities (zero, one, and two or more).ResultsFrom 2006 to 2013, use increased for metformin (from 47.6 to 53.5%), dipeptidyl peptidase 4 inhibitors (0.5 to 14.9%), and insulin (17.1 to 23.0%) but declined for sulfonylureas (38.8 to 30.8%) and thiazolidinediones (28.5 to 5.6%; all P < 0.001). The proportion of patients with HbA1c <7% declined (from 56.4 to 54.2%; P < 0.001) and with HbA1c ≥9% increased (9.9 to 12.2%; P < 0.001). Glycemic control varied by age and was poor among 23.3% of the youngest and 6.3% of the oldest patients in 2013. The overall rate of severe hypoglycemia remained the same (1.3 per 100 person-years; P = 0.72), declined modestly among the oldest patients (from 2.9 to 2.3; P < 0.001), and remained high among those with two or more comorbidities (3.2 to 3.5; P = 0.36).ConclusionsDuring the recent 8-year period, the use of glucose-lowering drugs has changed dramatically among patients with T2DM. Overall glycemic control has not improved and remains poor among nearly a quarter of the youngest patients. The overall rate of severe hypoglycemia remains largely unchanged

Symptom profiles and illness course among Anabaptist and Non-Anabaptist adults with major mood disorders

Background: Anabaptists comprise large and growing Amish and Mennonite populations with a unique genetic heritage and cultural background. Little is known about the symptoms and course of major mood disorders in Anabaptists. Even less is known about the impact of potential moderators on symptom severity and course. Methods: A sample of Amish and Mennonite participants with bipolar, recurrent unipolar, or schizoaffective bipolar disorder (n = 155) were systematically evaluated with a well-validated instrument. Cases were compared with non-Anabaptist participants (n = 155) matched for age, sex, and psychiatric diagnosis and evaluated by the same methods. Results: Despite substantial cultural differences, the profile of manic and depressive symptoms during illness episodes did not significantly differ between the two groups. Alcohol use disorder (AUD) was significantly less frequent among Anabaptists, and was associated with more major depressive episodes and more hospitalizations for major depression in Anabaptist, but not non-Anabaptist participants. Lifetime history of head injury showed a trend toward association with more episodes of major depression in both Anabaptist and non-Anabaptist groups that did not withstand multiple test correction. Conclusions: The presentation of a highly heritable psychiatric illness such as bipolar disorder does not differ in cases drawn from genetically unique Anabaptist populations. However, alcohol comorbidity, head injury, and their effects on illness course suggest some differences that deserve further investigation

Evolutionary biology for the 21st century

New theoretical and conceptual frameworks are required for evolutionary biology to capitalize on the wealth of data now becoming available from the study of genomes, phenotypes, and organisms - including humans - in their natural environments.Molecular and Cellular BiologyOrganismic and Evolutionary Biolog

Individual and joint trajectories of change in bone, lean mass and physical performance in older men.

BackgroundDeclines in bone, muscle and physical performance are associated with adverse health outcomes in older adults. However, few studies have described concurrent age-related patterns of change in these factors. The purpose of this study was to characterize change in four properties of muscle, physical performance, and bone in a prospective cohort study of older men.MethodsUsing repeated longitudinal data from up to four visits across 6.9 years from up to 4681 men (mean age at baseline 72.7 yrs. ±5.3) participating in the Osteoporotic Fractures in Men (MrOS) Study, we used group-based trajectory models (PROC TRAJ in SAS) to identify age-related patterns of change in four properties of muscle, physical performance, and bone: total hip bone mineral (BMD) density (g/m2) and appendicular lean mass/ht2 (kg/m2), by DXA; grip strength (kg), by hand dynamometry; and walking speed (m/s), by usual walking pace over 6 m. We also described joint trajectories in all pair-wise combinations of these measures. Mean posterior probabilities of placement in each trajectory (or joint membership in latent groups) were used to assess internal reliability of the model. The number of trajectories for each individual factor was limited to three, to ensure that the pair-wise determination of joint trajectories would yield a tractable number of groups as well as model fit considerations.ResultsThe patterns of change identified were generally similar for all measures, with three district groups declining over time at roughly similar rates; joint trajectories revealed similar patterns with no cross-over or convergence between groups. Mean posterior probabilities for all trajectories were similar and consistently above 0.8 indicating reasonable model fit to the data.ConclusionsOur description of trajectories of change with age in bone mineral density, grip strength, walking speed and appendicular lean mass found that groups identified by these methods appeared to have little crossover or convergence of change with age, even when considering joint trajectories of change in these factors

NAA10 p.(N101K) disrupts N-terminal acetyltransferase complex NatA and is associated with developmental delay and hemihypertrophy

Nearly half of all human proteins are acetylated at their N-termini by the NatA N-terminal acetyltransferase complex. NAA10 is evolutionarily conserved as the catalytic subunit of NatA in complex with NAA15, but may also have NatA-independent functions. Several NAA10 variants are associated with genetic disorders. The phenotypic spectrum includes developmental delay, intellectual disability, and cardiac abnormalities. Here, we have identified the previously undescribed NAA10 c.303C>A and c.303C>G p.(N101K) variants in two unrelated girls. These girls have developmental delay, but they both also display hemihypertrophy a feature normally not observed or registered among these cases. Functional studies revealed that NAA10 p.(N101K) is completely impaired in its ability to bind NAA15 and to form an enzymatically active NatA complex. In contrast, the integrity of NAA10 p.(N101K) as a monomeric acetyltransferase is intact. Thus, this NAA10 variant may represent the best example of the impact of NatA mediated N-terminal acetylation, isolated from other potential NAA10-mediated cellular functions and may provide important insights into the phenotypes observed in individuals expressing pathogenic NAA10 variants.publishedVersio

The social functioning in dementia scale (SF-DEM): exploratory factor analysis and psychometric properties in mild, moderate, and severe dementia

Introduction: The psychometric properties of the social functioning in dementia scale over different dementia severities are unknown. Methods: We interviewed 299 family carers of people with mild, moderate, or severe dementia from two UK research sites; examined acceptability (completion rates); conducted exploratory factor analysis; and tested each factor's internal consistency and construct validity. Results: Of 299, 285 (95.3%) carers completed questionnaires. Factor analysis indicated three distinct factors with acceptable internal consistency: spending time with other people, correlating with overall social function (r = 0.56, P <.001) and activities of daily living (r = −0.48, P <.001); communicating with other people correlating with activities of daily living (r = −0.66, P <.001); and sensitivity to other people correlating with quality of life (r = 0.35, P <.001) and inversely with neuropsychiatric symptoms (r = −0.45, P <.001). The three factors' correlations with other domains were similar across all dementia severities. Discussion: The social functioning in dementia scale carer version measures three social functioning domains and has satisfactory psychometric properties in all severities of dementia