Deborah H. Glueck

Lineage-specific gene duplication and loss in human and great ape evolution.

Given that gene duplication is a major driving force of evolutionary change and the key mechanism underlying the emergence of new genes and biological processes, this study sought to use a novel genome-wide approach to identify genes that have undergone lineage-specific duplications or contractions among several hominoid lineages. Interspecies cDNA array-based comparative genomic hybridization was used to individually compare copy number variation for 39,711 cDNAs, representing 29,619 human genes, across five hominoid species, including human. We identified 1,005 genes, either as isolated genes or in clusters positionally biased toward rearrangement-prone genomic regions, that produced relative hybridization signals unique to one or more of the hominoid lineages. Measured as a function of the evolutionary age of each lineage, genes showing copy number expansions were most pronounced in human (134) and include a number of genes thought to be involved in the structure and function of the brain. This work represents, to our knowledge, the first genome-wide gene-based survey of gene duplication across hominoid species. The genes identified here likely represent a significant majority of the major gene copy number changes that have occurred over the past 15 million years of human and great ape evolution and are likely to underlie some of the key phenotypic characteristics that distinguish these species.

Fat distribution and metabolic changes are strongly correlated and energy expenditure is increased in the HIV lipodystrophy syndrome

ObjectiveTo examine the relationships between protease inhibitor (PI) therapy, body fat distribution and metabolic disturbances in the HIV lipodystrophy syndrome. DesignCross-sectional study. SettingHIV primary care practices. PatientsPI-treated patients with lipodystrophy (n = 14) and PI-treated (n = 13) and PI-naive (n = 5) patients without lipodystrophy. Main outcome measuresBody composition was assessed by physical examination, dual-energy X-ray absorptiometry and computed tomography. Insulin sensitivity (SI) was measured using the insulin-modified frequently sampled intravenous glucose tolerance test. Lipid profiles, other metabolic parameters, duration of HIV infection, CD4 lymphocyte counts, HIV-1 RNA load and resting energy expenditure (REE) were also assessed. ResultsPI-treated patients with lipodystrophy were significantly less insulin sensitive than PI-treated patients and PI-naive patients without any changes in fat distribution (SI(22) × 10−4 (min−1/μU/ml) versus 3.2 × 10−4 and 4.6 × 10−4 (min−1/μU/ml), respectively;P < 0.001). Visceral adipose tissue area and other measures of central adiposity correlated strongly with metabolic disturbances as did the percent of total body fat present in the extremities; visceral adipose tissue was an independent predictor of insulin sensitivity and high density lipoprotein cholesterol levels. REE per kg lean body mass was significantly higher in the group with lipodystrophy compared to the groups without lipodystrophy (36.9 versus 31.5 and 29.4 kcal/kg lean body mass;P < 0.001), and SI was strongly correlated with and was an independent predictor of REE in this population. ConclusionsBody fat distribution and metabolic disturbances are strongly correlated in the HIV lipodystrophy syndrome and REE is increased.

Associations of maternal BMI and gestational weight gain with neonatal adiposity in the Healthy Start study

BACKGROUND Maternal obesity and weight gain during pregnancy are risk factors for child obesity. Associations may be attributable to causal effects of the intrauterine environment or genetic and postnatal environmental factors. OBJECTIVE We estimated associations of maternal prepregnancy body mass index (BMI) and gestational weight gain (GWG) overall and in early pregnancy, midpregnancy, and late pregnancy with neonatal adiposity. DESIGN Participants were 826 women enrolled in a Colorado prebirth cohort who delivered term infants (2010-2013). GWG to 39 wk of gestation was predicted by using mixed models, and early pregnancy, midpregnancy, and late pregnancy rates of GWG (0-17, 17-27, and 27 wk to delivery) were calculated from repeated weight measures. Neonatal body composition was measured by using air-displacement plethysmography ≤3 d after birth. RESULTS Each1-kg/m(2) increase in maternal BMI was associated with increased neonatal fat mass (5.2 g; 95% CI: 3.5, 6.9 g), fat-free mass (7.7 g; 95% CI: 4.5, 10.9 g), and percentage of body fat (0.12%; 95% CI: 0.08%, 0.16%). Each 0.1-kg/wk increase in predicted GWG was associated with increased fat mass (24.0 g; 95% CI: 17.4, 30.5 g), fat-free mass (34.0 g; 95% CI: 21.4, 46.6 g), and percentage of body fat (0.55%; 95% CI: 0.37%, 0.72%). No interaction was detected between BMI and GWG in their effects on neonatal body composition. Early pregnancy, midpregnancy, and late pregnancy rates of GWG were independently associated with fat mass and percentage of body fat. Midpregnancy and late pregnancy GWGs were associated with fat-free mass. An observed GWG that exceeded recommendations was associated with higher neonatal fat mass and fat-free mass but not percentage of body fat relative to adequate GWG. CONCLUSIONS Maternal prepregnancy BMI and GWG, including period-specific GWG, were positively and independently associated with neonatal adiposity. Associations of early and midpregnancy weight gain with neonatal adiposity support the hypothesis that greater maternal weight gain during pregnancy, regardless of prepregnancy BMI, is directly related to offspring adiposity at birth. The Healthy Start study was registered as an observational study at clinicaltrials.gov as NCT02273297.

Selecting a sample size for studies with repeated measures

Many researchers favor repeated measures designs because they allow the detection of within-person change over time and typically have higher statistical power than cross-sectional designs. However, the plethora of inputs needed for repeated measures designs can make sample size selection, a critical step in designing a successful study, difficult. Using a dental pain study as a driving example, we provide guidance for selecting an appropriate sample size for testing a time by treatment interaction for studies with repeated measures. We describe how to (1) gather the required inputs for the sample size calculation, (2) choose appropriate software to perform the calculation, and (3) address practical considerations such as missing data, multiple aims, and continuous covariates.

Physical activity in pregnancy and neonatal body composition: the Healthy Start study.

OBJECTIVE: To examine associations between pregnancy physical activity and neonatal fat mass and fat-free mass, birth weight, and small for gestational age (SGA). METHODS: We analyzed 826 mother–neonate pairs (term births) participating in the longitudinal Healthy Start study. The Pregnancy Physical Activity Questionnaire was used to assess total energy expenditure and meeting American College of Obstetricians and Gynecologists (College) guidelines for physical activity during early pregnancy, midpregnancy, and late pregnancy. Models were adjusted for maternal and neonatal characteristics. RESULTS: Neonates had mean fat mass of 292.9 g, fat-free mass of 2,849.8 g, and birth weight of 3,290.7 g. We observed 107 (12.9%) SGA and 30 (3.6%) large-for-gestational age neonates. A significant inverse linear trend between total energy expenditure during late pregnancy and neonatal fat mass (Ptrend=.04) was detected. Neonates of mothers in the highest compared with the lowest quartile of total energy expenditure during late pregnancy had 41.1 g less fat mass (249.4 compared with 290.5 g; P=.03). No significant trend was found with total energy expenditure and neonatal fat-free mass or birth weight. Early-pregnancy and midpregnancy total energy expenditure were not associated with neonatal outcomes. No significant trend was observed between late-pregnancy total energy expenditure and SGA (Ptrend=.07), but neonates of mothers in the highest compared with the lowest quartile had a 3.0 (95% confidence interval 1.4–6.7) higher likelihood of SGA. Meeting the College’s physical activity guidelines during pregnancy was not associated with differences in neonatal outcomes. CONCLUSION: Increasing levels of late-pregnancy total energy expenditure are associated with decreased neonatal adiposity without significantly reduced neonatal fat-free mass. LEVEL OF EVIDENCE: II

Maternal diet quality in pregnancy and neonatal adiposity: the Healthy Start Study.

Background/Objectives:Poor maternal diet in pregnancy can influence fetal growth and development. We tested the hypothesis that poor maternal diet quality during pregnancy would increase neonatal adiposity (percent fat mass (%FM)) at birth by increasing the fat mass (FM) component of neonatal body composition.Methods:Our analysis was conducted using a prebirth observational cohort of 1079 mother–offspring pairs. Pregnancy diet was assessed via repeated Automated Self-Administered 24-h dietary recalls, from which Healthy Eating Index-2010 (HEI-2010) scores were calculated for each mother. HEI-2010 was dichotomized into scores of ⩽57 and >57, with low scores representing poorer diet quality. Neonatal %FM was assessed within 72 h after birth with air displacement plethysmography. Using univariate and multivariate linear models, we analyzed the relationship between maternal diet quality and neonatal %FM, FM, and fat-free mass (FFM) while adjusting for prepregnancy body mass index (BMI), physical activity, maternal age, smoking, energy intake, preeclampsia, hypertension, infant sex and gestational age.Results:Total HEI-2010 score ranged between 18.2 and 89.5 (mean: 54.2, s.d.: 13.6). An HEI-2010 score of ⩽57 was significantly associated with higher neonatal %FM (β=0.58, 95% confidence interval (CI) 0.07–1.1, P<0.05) and FM (β=20.74; 95% CI 1.49–40.0; P<0.05) but no difference in FFM.Conclusions:Poor diet quality during pregnancy increases neonatal adiposity independent of maternal prepregnancy BMI and total caloric intake. This further implicates maternal diet as a potentially important exposure for fetal adiposity.

Maternal Fuels and Metabolic Measures During Pregnancy and Neonatal Body Composition: The Healthy Start Study

CONTEXT The impact of specific maternal fuels and metabolic measures during early and late gestation on neonatal body composition is not well defined. OBJECTIVE To determine how circulating maternal glucose, lipids, and insulin resistance in the first and second halves of pregnancy influence neonatal body composition. DESIGN A prospective pre-birth cohort enrolling pregnant women, the Healthy Start Study, was conducted, in which fasting maternal serum samples were collected twice during pregnancy to measure glucose, insulin, hemoglobin A1c, triglyceride, total cholesterol, high-density lipoprotein, and free fatty acids. Neonatal body composition was measured with air displacement plethysmography. SETTING An observational epidemiology study of pregnant women attending obstetric clinics at the University of Colorado, Anschutz Medical Center. PARTICIPANTS This analysis includes 804 maternal-neonate pairs. RESULTS A strong positive linear relationship between maternal estimated insulin resistance (homeostasis model of assessment for insulin resistance) in the first half of pregnancy and neonatal fat mass (FM) and FM percentage (FM%) was detected, independent of prepregnancy body mass index (BMI). In the second half of pregnancy, positive linear relationships between maternal glucose levels and offspring FM and FM% were observed, independent of prepregnancy BMI. An inverse relationship was detected between high-density lipoprotein in the first half of pregnancy and FM, independent of prepregnancy BMI. Free fatty acid levels in the second half of pregnancy were positively associated with higher birth weight, independent of prepregnancy BMI. CONCLUSION Maternal insulin resistance in the first half of pregnancy is highly predictive of neonatal FM%, whereas maternal glycemia, even within the normal range, is an important driver of neonatal adiposity in later pregnancy, independent of prepregnancy BMI. Our data provide additional insights on potential maternal factors responsible for fetal fat accretion and early development of adiposity.

Digital Breast Tomosynthesis Utilization in the United States: A Survey of Physician Members of the Society of Breast Imaging

PURPOSE To assess utilization of digital breast tomosynthesis (DBT) and examine criteria for offering DBT to patients. METHODS We created an online survey for physician members of the Society of Breast Imaging to assess their use of DBT. The questions covered availability of DBT at the participants practice, whether DBT was used for clinical care or research, clinical decision rules guiding patient selection for DBT, costs associated with DBT, plans to obtain DBT, and breast imaging practice characteristics. Fishers exact tests and logistic regression were used to compare DBT users and nonusers. RESULTS In all, 670 members responded (response rate = 37%). Of these, 200 (30.0%) respondents reported using DBT, with 89% of these using DBT clinically. Participants were more likely to report DBT use if they worked at an academic practice (odds ratio [OR], 2.07; 95% confidence interval [CI], 1.41 to 3.03; P < .001), a practice with more than 3 breast imagers (OR, 2.36; 95% CI, 1.62 to 3.43; P < .001), or a practice with 7 or more mammography units (OR, 3.05; 95% CI, 2.11 to 4.39; P < .001). Criteria used to select patients to undergo DBT varied, with 107 (68.2%) using exam type (screening versus diagnostic), 25 (15.9%) using mammographic density, and 25 (15.9%) using breast cancer risk. Fees for DBT ranged from

Downstaging disease in patients with hepatocellular carcinoma outside of Milan criteria: strategies using drug-eluting bead chemoembolization.

25 to

Estimates of sensitivity and specificity can be biased when reporting the results of the second test in a screening trial conducted in series

250. In addition, 62.3% of nonusers planned to obtain DBT. CONCLUSION DBT is becoming more common but remains a limited resource. Clinical guidelines would assist practices in deciding whether to adopt DBT and in standardizing which patients should receive DBT.