Michael J. Daniels

The heritability of IQ

IQ heritability, the portion of a populations IQ variability attributable to the effects of genes, has been investigated for nearly a century, yet it remains controversial. Covariance between relatives may be due not only to genes, but also to shared environments, and most previous models have assumed different degrees of similarity induced by environments specific to twins, to non-twin siblings (henceforth siblings), and to parents and offspring. We now evaluate an alternative model that replaces these three environments by two maternal womb environments, one for twins and another for siblings, along with a common home environment. Meta-analysis of 212 previous studies shows that our ‘maternal-effects’ model fits the data better than the ‘family-environments’ model. Maternal effects, often assumed to be negligible, account for 20% of covariance between twins and 5% between siblings, and the effects of genes are correspondingly reduced, with two measures of heritability being less than 50%. The shared maternal environment may explain the striking correlation between the IQs of twins, especially those of adult twins that were reared apart. IQ heritability increases during early childhood, but whether it stabilizes thereafter remains unclear. A recent study of octogenarians, for instance, suggests that IQ heritability either remains constant through adolescence and adulthood, or continues to increase with age. Although the latter hypothesis has recently been endorsed, it gathers only modest statistical support in our analysis when compared to the maternal-effects hypothesis. Our analysis suggests that it will be important to understand the basis for these maternal effects if ways in which IQ might be increased are to be identified.

Revised Analyses of the National Morbidity, Mortality, and Air Pollution Study: Mortality Among Residents Of 90 Cities

This article presents findings from updated analyses of data from 90 U.S. cities assembled for the National Morbidity, Mortality, and Air Pollution Study (NMMAPS). The data were analyzed with a generalized additive model (GAM) using the gamfunction in S-Plus (with default convergence criteria previously used and with more stringent criteria) and with a generalized linear model (GLM) with natural cubic splines. With the original method, the estimated effect of PM10 (particulate matter 10μm in mass median aerodynamic diameter) on total mortality from nonexternal causes was a 0.41% increase per 10−μg/m3 increase in PM10; with the more stringent criteria, the estimate was 0.27%; and with GLM, the effect was 0.21%. The effect of PM10 on respiratory and cardiovascular mortality combined was greater, but the pattern across models was similar. The findings of the updated analysis with regard to spatial heterogeneity across the 90 cities were unchanged from the original analyses.

Meta-analysis for the evaluation of potential surrogate markers

We describe a meta-analysis approach for the evaluation of a potential surrogate marker. Surrogate markers are useful in helping to identify therapeutic mechanisms of action and disease pathogenesis, and for selecting therapies to take forward from phase II to phase III clinical trials. They have also become increasingly important for regulatory purposes by providing a basis for preliminary approval of drugs pending clinical outcome studies. Methodology for evaluating surrogate markers has focused on determining the difference in the effects of two treatments on clinical outcome in an individual clinical trial, and then estimating the proportion of this difference explained by the treatments effects on the potential marker. Studies are, however, frequently underpowered or cease before they accumulate sufficient evidence to draw strong conclusions about the value of a potential surrogate marker using this approach, and there are also some technical difficulties with the approach. Consideration of the association between the difference in treatment effects on the clinical outcome and the difference in treatment effects on the potential marker over a range of trials provides an alternative means to evaluate a potential marker. We describe a meta-analysis approach using Bayesian methods to model this association. Importantly, this approach enables one to obtain prediction intervals for the true difference in clinical outcome for a given estimated treatment difference in the effect on the potential marker. We illustrate the methodology by applying it to results from studies of the AIDS Clinical Trials Group to assess the value of CD4 T-lymphocyte cell count as a potential surrogate marker for the treatment effects on the development of AIDS or death.

Air Pollution and Mortality: Estimating Regional and National Dose-Response Relationships

We analyzed a national data base of air pollution and mortality for the 88 largest U.S. cities for the period 1987–1994, to estimate relative rates of mortality associated with airborne particulate matter smaller than 10 microns (PM10) and the form of the relationship between PM10 concentration and mortality. To estimate city-specific relative rates of mortality associated with PM10, we built log-linear models that included nonparametric adjustments for weather variables and longer term trends. To estimate PM10 mortality dose-response curves, we modeled the logarithm of the expected value of daily mortality as a function of PM10 using natural cubic splines with unknown numbers and locations of knots. We also developed spatial models to investigate the heterogeneity of relative mortality rates and of the shapes of PM10 mortality dose-response curves across cities and geographical regions. To determine whether variability in effect estimates can be explained by city-specific factors, we explored the dependence of relative mortality rates on mean pollution levels, demographic variables, reliability of the pollution data, and specific constituents of particulate matter. We implemented estimation with simulation-based methods, including data augmentation to impute the missing data of the city-specific covariates and the reversible jump Markov chain Monte Carlo (RJMCMC) to sample from the posterior distribution of the parameters in the hierarchical spline model. We found that previous-day PM10 concentrations were positively associated with total mortality in most the locations, with a .5% increment for a 10 μg/m3 increase in PM10. The effect was strongest in the Northeast region, where the increase in the death rate was twice as high as the average for the other cities. Overall, we found that the pooled concentration-response relationship for the nation was linear.

Extended-Care Programs for Weight Management in Rural Communities: The Treatment of Obesity in Underserved Rural Settings (TOURS) Randomized Trial

BACKGROUND Rural counties in the United States have higher rates of obesity, sedentary lifestyle, and associated chronic diseases than nonrural areas, yet the management of obesity in rural communities has received little attention from researchers. METHODS Obese women from rural communities who completed an initial 6-month weight-loss program at Cooperative Extension Service offices in 6 medically underserved rural counties (n = 234) were randomized to extended care or to an education control group. The extended-care programs entailed problem-solving counseling delivered in 26 biweekly sessions via telephone or face to face. Control group participants received 26 biweekly newsletters containing weight-control advice. RESULTS Mean weight at study entry was 96.4 kg. Mean weight loss during the initial 6-month intervention was 10.0 kg. One year after randomization, participants in the telephone and face-to-face extended-care programs regained less weight (mean [SE], 1.2 [0.7] and 1.2 [0.6] kg, respectively) than those in the education control group (3.7 [0.7] kg; P = .03 and .02, respectively). The beneficial effects of extended-care counseling were mediated by greater adherence to behavioral weight-management strategies, and cost analyses indicated that telephone counseling was less expensive than face-to-face intervention. CONCLUSIONS Extended care delivered either by telephone or in face-to-face sessions improved the 1-year maintenance of lost weight compared with education alone. Telephone counseling constitutes an effective and cost-efficient option for long-term weight management. Delivering lifestyle interventions via the existing infrastructure of the Cooperative Extension Service represents a viable means of adapting research for rural communities with limited access to preventive health services. Trial Registration clinicaltrials.gov Identifier: NCT00201006.

Nonconjugate Bayesian Estimation of Covariance Matrices and its Use in Hierarchical Models

Abstract The problem of estimating a covariance matrix in small samples has been considered by several authors following early work by Stein. This problem can be especially important in hierarchical models where the standard errors of fixed and random effects depend on estimation of the covariance matrix of the distribution of the random effects. We propose a set of hierarchical priors (HPs) for the covariance matrix that produce posterior shrinkage toward a specified structure—here we examine shrinkage toward diagonality. We then address the computational difficulties raised by incorporating these priors, and nonconjugate priors in general, into hierarchical models. We apply a combination of approximation, Gibbs sampling (possibly with a Metropolis step), and importance reweighting to fit the models, and compare this hybrid approach to alternative Markov Chain Monte Carlo methods. Our investigation involves three alternative HPs. The first works with the spectral decomposition of the covariance matrix an...

Endovascular chimney technique versus open repair of juxtarenal and suprarenal aneurysms

OBJECTIVE To compare early outcomes of endovascular repair of juxtarenal and suprarenal aneurysms using the chimney technique with open repair in anatomically-matched patients. METHODS Between January 2008 and December 2009, 21 patients underwent endovascular repair of juxtarenal and suprarenal aortic aneurysms with chimney stenting (Ch-EVAR) of 1 or 2 renal and/or superior mesenteric artery (SMA) vessels. These were compared with 21 anatomically-matched patients that underwent open repair (OR) during the same time period. Primary end points were 30-day mortality, chimney stent patency, and type Ia endoleak. Secondary end points included early complications, renal function, blood loss, and length of stay (LOS). RESULTS Despite a higher proportion of women, oxygen-dependent pulmonary disease and lower baseline renal function, 30-day mortality was identical with one death (4.8%) in each group. Blood loss and total LOS were significantly less for Ch-EVAR. Six patients (29%) in the chimney group had acute kidney injury (AKI) compared with the open group, in which there were one (4.8%) AKI and four (19%) acute renal failures, of which two (9.5%) required chronic hemodialysis. Renal function at 12 months demonstrated similar declines in the overall estimated glomerular filtration rate (eGFR) in the Ch-EVAR and OR groups (11.1 ± 19.6 vs 10.4 ± 25.2, P = NS, respectively). There was one asymptomatic SMA stent occlusion at 6 months and partial compression of a second SMA stent which underwent repeat balloon angioplasty. Primary patency at 6 and 12 months was 94% and 84%, respectively. There was one type Ia endoleak noted at 30 days which resolved by 6 months. CONCLUSIONS Ch-EVAR may extend the anatomical eligibility of endovascular aneurysm repair using conventional devices. It appears to have similar mortality to open repair with less morbidity. Long-term durability and stent patency remain to be determined.

Extent of Aortic Coverage and Incidence of Spinal Cord Ischemia After Thoracic Endovascular Aneurysm Repair

BACKGROUND Risk factors for spinal cord ischemia (SCI) after thoracic endovascular aneurysm repair (TEVAR) remain unclear. Aortic coverage was examined as a risk factor for SCI using quantitative three-dimensional computed tomography angiography (CTA) analysis. METHODS The medical records, radiographic imaging studies, and a prospectively maintained database of all TEVAR procedures performed during a 7-year period were retrospectively reviewed. Preoperative anatomic dimensions and postoperative graft path lengths were measured from CTAs using curved planar and orthogonal multiplanar reformations along centerline paths. SCI was defined as transient or permanent lower extremity neurologic deficit without associated intracerebral hemispheric events. RESULTS Of 326 TEVAR cases, 241 patients (74%) had satisfactory imaging. Thirty-three (10%) had SCI. These patients were older (72.7 +/- 10.6 vs 64.7 +/- 15.8 years, p = 0.005) and had longer intraoperative procedure times (137 +/- 65 vs 113 +/- 68 minutes, p = 0.05). Despite similar total lengths of native thoracic aorta (295.0 +/- 36.3 vs 283.1 +/- 39.8 mm, p = 0.17), patients with permanent SCI had a greater absolute (260.5 +/- 40.9 vs 195.8 +/- 81.6 mm, p = 0.002) and proportionate (88.8% +/- 12.1% vs 67.6% +/- 24.0%, p = 0.001) length of aortic coverage. The average length of uncovered aorta proximal to the celiac artery in patients with SCI was 17.3 +/- 21.8 mm vs 63.1 +/- 62.9 mm in patients without SCI (p = 0.0006). Neither the patency of the hypogastric arteries nor left subclavian artery was associated with SCI. CONCLUSIONS The extent and distal location (relative to the celiac artery) of aortic coverage were associated with an increased risk of SCI. Prophylactic measures for spinal cord protection should be considered in patients whose thoracic aortas require extensive coverage.

Hierarchical Generalized Linear Models in the Analysis of Variations in Health Care Utilization

Abstract In recent years many studies have reported large differences in the use of medical treatments and procedures across geographic regions, hospitals, and individual health care providers. Beyond reporting on the extent of observed variations, these studies examine the role of contributing factors including patient, regional, and provider characteristics. In addition, they may assess the relation between health care processes and outcomes, such as patient mortality, morbidity, and functioning. Studies of variations in health care utilization and outcomes involve the analysis of multilevel clustered data; for example, data on patients clustered by hospital and/or geographic region. The goals of the analysis include the estimation of cluster-specific adjusted responses, covariate effects, and components of variance. The analytic strategy needs to account for correlations induced by clustering and to handle the presence of large variations in cluster size. In this article we formulate a broad class of h...

T₂ mapping provides multiple approaches for the characterization of muscle involvement in neuromuscular diseases: a cross-sectional study of lower leg muscles in 5-15-year-old boys with Duchenne muscular dystrophy.

Skeletal muscles of children with Duchenne muscular dystrophy (DMD) show enhanced susceptibility to damage and progressive lipid infiltration, which contribute to an increase in the MR proton transverse relaxation time (T2). Therefore, the examination of T2 changes in individual muscles may be useful for the monitoring of disease progression in DMD. In this study, we used the mean T2, percentage of elevated pixels and T2 heterogeneity to assess changes in the composition of dystrophic muscles. In addition, we used fat saturation to distinguish T2 changes caused by edema and inflammation from fat infiltration in muscles. Thirty subjects with DMD and 15 age‐matched controls underwent T2‐weighted imaging of their lower leg using a 3‐T MR system. T2 maps were developed and four lower leg muscles were manually traced (soleus, medial gastrocnemius, peroneal and tibialis anterior). The mean T2 of the traced regions of interest, width of the T2 histograms and percentage of elevated pixels were calculated. We found that, even in young children with DMD, lower leg muscles showed elevated mean T2, were more heterogeneous and had a greater percentage of elevated pixels than in controls. T2 measures decreased with fat saturation, but were still higher (P < 0.05) in dystrophic muscles than in controls. Further, T2 measures showed positive correlations with timed functional tests (r = 0.23–0.79). The elevated T2 measures with and without fat saturation at all ages of DMD examined (5–15 years) compared with unaffected controls indicate that the dystrophic muscles have increased regions of damage, edema and fat infiltration. This study shows that T2 mapping provides multiple approaches that can be used effectively to characterize muscle tissue in children with DMD, even in the early stages of the disease. Therefore, T2 mapping may prove to be clinically useful in the monitoring of muscle changes caused by the disease process or by therapeutic interventions in DMD. Copyright