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117,956 results on '"Department of Biostatistics"'

1. Analgesia-first Minimal Sedation for Spontaneous Intracerebral Hemorrhage Early Antihypertensive Treatment (ASSICHH)

Author: Xuanwu Hospital, Beijing, Qilu Hospital of Shandong University, First Affiliated Hospital of Kunming Medical University, First Affiliated Hospital of Xinjiang Medical University, Second Affiliated Hospital of Third Military Medical University, Henan Provincial People's Hospital, The Second Hospital University of South China, Shenzhen Second People's Hospital, People's Hospital of Guangxi, Department of Biostatistics, Southern Medical University, LanZhou University, The First Affiliated Hospital of HuNan University of Medicine, Guangdong 999 Brain Hospital, Maoming People's Hospital, The Fifth Affiliated Hospital of Southern Medical University, Zhongshan People's Hospital, Guangdong, China, Fifth Affiliated Hospital, Sun Yat-Sen University, and Hong Yang, Doctor of Medicine (M.D.)；Associate Senior Doctor
Published: 2023

2. Association of LPA Variants With Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies

Author: Burgess, Stephen, Ference, Brian A., Staley, James R., Freitag, Daniel F., Mason, Amy M., Nielsen, Sune F., Willeit, Peter, Young, Robin, Surendran, Praveen, Karthikeyan, Savita, Bolton, Thomas R., Peters, James E., Kamstrup, Pia R., Tybjærg-Hansen, Anne, Benn, Marianne, Langsted, Anne, Schnohr, Peter, Vedel-Krogh, Signe, Kobylecki, Camilla J., Ford, Ian, Packard, Chris, Trompet, Stella, Jukema, J. Wouter, Sattar, Naveed, Di Angelantonio, Emanuele, Saleheen, Danish, Howson, Joanna M. M., Nordestgaard, Børge G., Butterworth, Adam S., Danesh, John, Medical Research Council Biostatistics Unit, University of Cambridge, Cambridge, United Kingdom, MRC/BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom, Department of Clinical Biochemistry, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, The Copenhagen General Population Study, Herlev and Gentofte Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Copenhagen City Heart Study, Frederiksberg Hospital, Copenhagen University Hospital, Copenhagen, Denmark, Institute of Health and Wellbeing, University of Glasgow, Glasgow, United Kingdom, Institute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom, Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands, and Department of Biostatistics and Epidemiology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia
Published: 2018

3. Role of Molar in Anterior Proclination of Teeth â€“ A Retrospective Study

Author: S. V., Soumya; Department Dental and Oral Surgery II CMCH, Vellore, Ebenezer, Jagadish; Department Dental and Oral Surgery II CMCH, Vellore, Antonisamy, B.; Department of Biostatistics, CMCH, Vellore, S. V., Soumya; Department Dental and Oral Surgery II CMCH, Vellore, Ebenezer, Jagadish; Department Dental and Oral Surgery II CMCH, Vellore, and Antonisamy, B.; Department of Biostatistics, CMCH, Vellore
Abstract: Objectives: 1) To establish if a correlation exists between the position of the molar and anterior proclination of central incisors in Indian population. 2) To broaden our treatment options for gaining space to correct malocclusion. 3) Emphasise the importance of stable posterior occlusion. Material and methods: The sample consisted of 400 lateral cephalograms of patients reported to CMCH, Vellore for diagnosis and treatment of malocclusion. The interincisal angle and the molar position in maxillae were measured using Kodak software and values were tabulated on Excel worksheets. All statistical analysis were done using Statistical Software STATA version 13.1. Results: Regression coefficient indicates that 0.4% decrease in the interincisal angle (increase in proclination) for every unit increase in the molar position which is statistically significant at 5% level of significance. The interincisal angle will be 3% higher for male than female which is statistically not significant. Conclusion: 1) Molar position in maxillae is affected by various factors and its position has an effect on anterior proclination with 0.4% decrease in interincisal angle for every unit increase in molar position which is statistically significant. 2) Anterior occlusion is dependent on posterior occlusion, hence a stable posterior occlusion is a requisite for stability of occlusion. 3) Since the anterior occlusion varies with posterior occlusion other modalities of treatment like distalization of molars and TAD's to decrease anchor loss can be an alternative/ addition to extraction protocol respectively.
Published: 2018

4. Multiple imputation based on restricted mean model for censored data

Author: Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A, Liu, Lyrica Xiaohong, Murray, Susan, Tsodikov, Alex, Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A, Liu, Lyrica Xiaohong, Murray, Susan, and Tsodikov, Alex
Abstract: Most multiple imputation (MI) methods for censored survival data either ignore patient characteristics when imputing a likely event time, or place quite restrictive modeling assumptions on the survival distributions used for imputation. In this research, we propose a robust MI approach that directly imputes restricted lifetimes over the study period based on a model of the mean restricted life as a linear function of covariates. This method has the advantages of retaining patient characteristics when making imputation choices through the restricted mean parameters and does not make assumptions on the shapes of hazards or survival functions. Simulation results show that our method outperforms its closest competitor for modeling restricted mean lifetimes in terms of bias and efficiency in both independent censoring and dependent censoring scenarios. Survival estimates of restricted lifetime model parameters and marginal survival estimates regain much of the precision lost due to censoring. The proposed method is also much less subject to dependent censoring bias captured by covariates in the restricted mean model. This particular feature is observed in a full statistical analysis conducted in the context of the International Breast Cancer Study Group Ludwig Trial V using the proposed methodology. Copyright ?? 2011 John Wiley & Sons, Ltd.
Published: 2011

5. On the use of a PM 2.5 exposure simulator to explain birthweight

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA ; Assistant Professor, Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, USA., Department of Statistical Science, Duke University, Durham, NC, USA, U.S. Environmental Protection Agency, National Exposure Research Laboratory, Research Triangle Park, NC, USA, The Nicholas School of the Environment, Duke University, Durham, NC, USA, Berrocal, Veronica J., Gelfand, Alan E., Holland, David M., Burke, Janet, Miranda, Marie Lynn, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA ; Assistant Professor, Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, USA., Department of Statistical Science, Duke University, Durham, NC, USA, U.S. Environmental Protection Agency, National Exposure Research Laboratory, Research Triangle Park, NC, USA, The Nicholas School of the Environment, Duke University, Durham, NC, USA, Berrocal, Veronica J., Gelfand, Alan E., Holland, David M., Burke, Janet, and Miranda, Marie Lynn
Abstract: In relating pollution to birth outcomes, maternal exposure has usually been described using monitoring data. Such characterization provides a misrepresentation of exposure as (i) it does not take into account the spatial misalignment between an individual's residence and monitoring sites, and (ii) it ignores the fact that individuals spend most of their time indoors and typically in more than one location. In this paper, we break with previous studies by using a stochastic simulator to describe personal exposure (to particulate matter) and then relate simulated exposures at the individual level to the health outcome (birthweight) rather than aggregating to a selected spatial unit. We propose a hierarchical model that, at the first stage, specifies a linear relationship between birthweight and personal exposure, adjusting for individual risk factors and introduces random spatial effects for the census tract of maternal residence. At the second stage, we specify the distribution of each individual's personal exposure using the empirical distribution yielded by the stochastic simulator as well as a model for the spatial random effects. We have applied our framework to analyze birthweight data from 14 counties in North Carolina in years 2001 and 2002. We investigate whether there are certain aspects and time windows of exposure that are more detrimental to birthweight by building different exposure metrics which we incorporate, one by one, in our hierarchical model. To assess the difference in relating ambient exposure (i.e., exposure to ambient concentration) to birthweight versus personal exposure to birthweight, we compare estimates of the effect of air pollution obtained from hierarchical models that linearly relate ambient exposure and birthweight to those obtained from our modeling framework. Our analysis does not show a significant effect of PM 2.5 on birthweight for reasons which we discuss. However, our modeling framework serves as a template for general analys
Published: 2011

6. Evidence for an association between prostate cancer and chromosome 8q24 and 10q11 genetic variants in African American men: The flint men's health study Yunfei Wang and Anna M. Ray contributed equally to this work.

Author: Department of Internal Medicine, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Urology, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan ; Department of Urology, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina ; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina ; Assistant Professor, Department of Genetics, 5111 Genetics Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27599-7264., Wang, Yunfei, Ray, Anna M., Johnson, Emilie K., Zuhlke, Kimberly A., Cooney, Kathleen A., Lange, Ethan M., Department of Internal Medicine, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Urology, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan ; Department of Urology, University of Michigan Medical School, University of Michigan Comprehensive Cancer Center, Ann Arbor, Michigan, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina ; Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina ; Assistant Professor, Department of Genetics, 5111 Genetics Medicine Building, 120 Mason Farm Road, Chapel Hill, NC 27599-7264., Wang, Yunfei, Ray, Anna M., Johnson, Emilie K., Zuhlke, Kimberly A., Cooney, Kathleen A., and Lange, Ethan M.
Abstract: BACKGROUND Prostate cancer is the most commonly diagnosed non-skin cancer in men in the United States and the second leading cause of cancer-related mortality. African American men have substantially increased risk of both being diagnosed and dying from the disease. Recent genome-wide genetic association studies have identified a number of common single nucleotide genetic polymorphisms (SNPs) that are associated with prostate cancer in men of European descent. Only a small number of studies have evaluated the association between these genetic variants and prostate cancer in African Americans. METHODS We used logistic regression models to assess the association between prostate cancer in African American men and 24 SNPs from regions previously reported to be associated with prostate cancer in men of European descent. RESULTS We found nominal evidence ( P ???
Published: 2011

7. MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes

Author: Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan ; Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, Department of Genetics, Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, Li, Yun, Willer, Cristen J., Ding, Jun, Scheet, Paul, Abecasis, Gon??alo R., Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, Center for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan ; Department of Biostatistics, University of Michigan School of Public Health, 1415 Washington Heights, Ann Arbor, MI 48109, Department of Genetics, Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina, Department of Epidemiology, University of Texas M.D. Anderson Cancer Center, Houston, Texas, Li, Yun, Willer, Cristen J., Ding, Jun, Scheet, Paul, and Abecasis, Gon??alo R.
Abstract: Genome-wide association studies (GWAS) can identify common alleles that contribute to complex disease susceptibility. Despite the large number of SNPs assessed in each study, the effects of most common SNPs must be evaluated indirectly using either genotyped markers or haplotypes thereof as proxies. We have previously implemented a computationally efficient Markov Chain framework for genotype imputation and haplotyping in the freely available MaCH software package. The approach describes sampled chromosomes as mosaics of each other and uses available genotype and shotgun sequence data to estimate unobserved genotypes and haplotypes, together with useful measures of the quality of these estimates. Our approach is already widely used to facilitate comparison of results across studies as well as meta-analyses of GWAS. Here, we use simulations and experimental genotypes to evaluate its accuracy and utility, considering choices of genotyping panels, reference panel configurations, and designs where genotyping is replaced with shotgun sequencing. Importantly, we show that genotype imputation not only facilitates cross study analyses but also increases power of genetic association studies. We show that genotype imputation of common variants using HapMap haplotypes as a reference is very accurate using either genome-wide SNP data or smaller amounts of data typical in fine-mapping studies. Furthermore, we show the approach is applicable in a variety of populations. Finally, we illustrate how association analyses of unobserved variants will benefit from ongoing advances such as larger HapMap reference panels and whole genome shotgun sequencing technologies. Genet. Epidemiol . 34: 816-834, 2010. ?? 2010 Wiley-Liss, Inc.
Published: 2010

8. A review of statistical methods for testing genetic anticipation: looking for an answer in Lynch syndrome

Author: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Departments of Epidemiology and Human Genetics, University of Michigan, Ann Arbor, Michigan ; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan ; 1420 Washington Hgts, Ann Arbor, MI 48103, The Danish HNPCC-register, Hvidovre University Hospital, Hvidovre, Denmark, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark, Boonstra, Philip S., Gruber, Stephen B., Raymond, Victoria M., Huang, Shu-Chen, Timshel, Susanne, Nilbert, Mef, Mukherjee, Bhramar, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Departments of Epidemiology and Human Genetics, University of Michigan, Ann Arbor, Michigan ; Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan ; 1420 Washington Hgts, Ann Arbor, MI 48103, The Danish HNPCC-register, Hvidovre University Hospital, Hvidovre, Denmark, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Denmark, Boonstra, Philip S., Gruber, Stephen B., Raymond, Victoria M., Huang, Shu-Chen, Timshel, Susanne, Nilbert, Mef, and Mukherjee, Bhramar
Abstract: Anticipation, manifested through decreasing age of onset or increased severity in successive generations, has been noted in several genetic diseases. Statistical methods for genetic anticipation range from a simple use of the paired t -test for age of onset restricted to affected parent-child pairs to a recently proposed random effects model which includes extended pedigree data and unaffected family members [Larsen et al., 2009 ]. A naive use of the paired t -test is biased for the simple reason that age of onset has to be less than the age at ascertainment (interview) for both affected parent and child, and this right truncation effect is more pronounced in children than in parents. In this study, we first review different statistical methods for testing genetic anticipation in affected parent-child pairs that address the issue of bias due to right truncation. Using affected parent-child pair data, we compare the paired t -test with the parametric conditional maximum likelihood approach of Huang and Vieland [ 1997 ] and the nonparametric approach of Rabinowitz and Yang [ 1999 ] in terms of Type I error and power under various simulation settings and departures from the modeling assumptions. We especially investigate the issue of multiplex ascertainment and its effect on the different methods. We then focus on exploring genetic anticipation in Lynch syndrome and analyze new data on the age of onset in affected parent-child pairs from families seen at the University of Michigan Cancer Genetics clinic with a mutation in one of the three main mismatch repair (MMR) genes. In contrast to the clinic-based population, we re-analyze data on a population-based Lynch syndrome cohort, derived from the Danish HNPCC-register. Both datasets indicate evidence of genetic anticipation in Lynch syndrome. We then expand our review to incorporate recently proposed statistical methods that consider family instead of affected pairs as the sampling unit. These prospective censored regres
Published: 2010

9. The effect of salvage therapy on survival in a longitudinal study with treatment by indication

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI, U.S.A. ; Department of Biostatistics, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Peter MacCallum Cancer Centre, Melbourne, Australia, Kennedy, Edward H., Taylor, Jeremy M. G., Schaubel, Douglas E., Williams, Scott, Department of Biostatistics, University of Michigan, Ann Arbor, MI, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI, U.S.A. ; Department of Biostatistics, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Peter MacCallum Cancer Centre, Melbourne, Australia, Kennedy, Edward H., Taylor, Jeremy M. G., Schaubel, Douglas E., and Williams, Scott
Abstract: We consider using observational data to estimate the effect of a treatment on disease recurrence, when the decision to initiate treatment is based on longitudinal factors associated with the risk of recurrence. The effect of salvage androgen deprivation therapy (SADT) on the risk of recurrence of prostate cancer is inadequately described by the existing literature. Furthermore, standard Cox regression yields biased estimates of the effect of SADT, since it is necessary to adjust for prostate-specific antigen (PSA), which is a time-dependent confounder and an intermediate variable. In this paper, we describe and compare two methods which appropriately adjust for PSA in estimating the effect of SADT. The first method is a two-stage method which jointly estimates the effect of SADT and the hazard of recurrence in the absence of treatment by SADT. In the first stage, PSA is predicted in the absence of SADT, and in the second stage, a time-dependent Cox model is used to estimate the benefit of SADT, adjusting for PSA. The second method, called sequential stratification, reorganizes the data to resemble a sequence of experiments in which treatment is conditionally randomized given the time-dependent covariates. Strata are formed, each consisting of a patient undergoing SADT and a set of appropriately matched controls, and analysis proceeds via stratified Cox regression. Both methods are applied to data from patients initially treated with radiation therapy for prostate cancer and give similar SADT effect estimates. Copyright ?? 2010 John Wiley & Sons, Ltd.
Published: 2010

10. Bayesian inference for the stereotype regression model: Application to a case–control study of prostate cancer

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI 48109, U.S.A. ; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, U.S.A., Ahn, Jaeil, Mukherjee, Bhramar, Banerjee, Mousumi, Cooney, Kathleen A., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Internal Medicine and Urology, University of Michigan, Ann Arbor, MI 48109, U.S.A. ; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109, U.S.A., Ahn, Jaeil, Mukherjee, Bhramar, Banerjee, Mousumi, and Cooney, Kathleen A.
Abstract: The stereotype regression model for categorical outcomes, proposed by Anderson ( J. Roy. Statist. Soc. B. 1984; 46 :1–30) is nested between the baseline-category logits and adjacent category logits model with proportional odds structure. The stereotype model is more parsimonious than the ordinary baseline-category (or multinomial logistic) model due to a product representation of the log-odds-ratios in terms of a common parameter corresponding to each predictor and category-specific scores. The model could be used for both ordered and unordered outcomes. For ordered outcomes, the stereotype model allows more flexibility than the popular proportional odds model in capturing highly subjective ordinal scaling which does not result from categorization of a single latent variable, but are inherently multi-dimensional in nature. As pointed out by Greenland ( Statist. Med. 1994; 13 :1665–1677), an additional advantage of the stereotype model is that it provides unbiased and valid inference under outcome-stratified sampling as in case–control studies. In addition, for matched case–control studies, the stereotype model is amenable to classical conditional likelihood principle, whereas there is no reduction due to sufficiency under the proportional odds model. In spite of these attractive features, the model has been applied less, as there are issues with maximum likelihood estimation and likelihood-based testing approaches due to non-linearity and lack of identifiability of the parameters. We present comprehensive Bayesian inference and model comparison procedure for this class of models as an alternative to the classical frequentist approach. We illustrate our methodology by analyzing data from The Flint Men's Health Study, a case–control study of prostate cancer in African-American men aged 40–79 years. We use clinical staging of prostate cancer in terms of Tumors, Nodes and Metastasis as the categorical response of interest. Copyright © 2009 John Wiley & Sons, Ltd.
Published: 2009

11. Genotype-based matching to correct for population stratification in large-scale case-control genetic association studies

Author: Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan ; These authors contributed equally to this work., Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan ; Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor MI 48109-2029, Guan, Weihua, Liang, Liming, Boehnke, Michael, Abecasis, Gon??alo R., Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan ; These authors contributed equally to this work., Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan, Department of Biostatistics and Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan ; Department of Biostatistics, School of Public Health, University of Michigan, 1420 Washington Heights, Ann Arbor MI 48109-2029, Guan, Weihua, Liang, Liming, Boehnke, Michael, and Abecasis, Gon??alo R.
Abstract: Genome-wide association studies are helping to dissect the etiology of complex diseases. Although case-control association tests are generally more powerful than family-based association tests, population stratification can lead to spurious disease-marker association or mask a true association. Several methods have been proposed to match cases and controls prior to genotyping, using family information or epidemiological data, or using genotype data for a modest number of genetic markers. Here, we describe a genetic similarity score matching (GSM) method for efficient matched analysis of cases and controls in a genome-wide or large-scale candidate gene association study. GSM comprises three steps: (1) calculating similarity scores for pairs of individuals using the genotype data; (2) matching sets of cases and controls based on the similarity scores so that matched cases and controls have similar genetic background; and (3) using conditional logistic regression to perform association tests. Through computer simulation we show that GSM correctly controls false-positive rates and improves power to detect true disease predisposing variants. We compare GSM to genomic control using computer simulations, and find improved power using GSM. We suggest that initial matching of cases and controls prior to genotyping combined with careful re-matching after genotyping is a method of choice for genome-wide association studies. Genet. Epidemiol . 33:508???517, 2009. ?? 2009 Wiley-Liss, Inc.
Published: 2009

12. Effect of an herbal extract of Sideritis scardica and B-vitamins on cognitive performance under stress: a pilot study

Author: Behrendt, Isabel; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany, Schneider, Inga; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover, Schuchardt, Jan Philipp; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany, Bitterlich, Norman; Medicine and Service Ltd, Department of Biostatistics, Boettcherstr. 10, 09117 Chemnitz, Germany, Hahn, Andreas; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany, Behrendt, Isabel; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany, Schneider, Inga; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover, Schuchardt, Jan Philipp; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany, Bitterlich, Norman; Medicine and Service Ltd, Department of Biostatistics, Boettcherstr. 10, 09117 Chemnitz, Germany, and Hahn, Andreas; Gottfried Wilhelm Leibniz University Hannover, Institute of Food Science Am Kleinen Felde 30 D-30167 Hannover Germany
Abstract: Chronic stress can impair cognitive functions including learning and memory. The current study investigated the reduction of (mental) stress and improvement of stress tolerance in 64 healthy men and women after six weeks intake of a dietary supplement containing an extract of Sideritis scardica and selected B-vitamins.Mental performance and visual attention were measured by Trail-Making Test (TMT) and Colour-Word-Test (CWT) before/after an acute stress stimulus (noise, CW-Interference).TMT improved upon product intake. The CWT reaction time accelerated upon product intake in situations of CW-Congruence (overall) (p=0.014), CW-conflict (overall) (p=0.024), CW-conflict (with noise) (p=0.001), CW-Congruence (without noise) (p=0.004) and CW-conflict (without noise) (p=0.017). CWT-changes upon product intake, differentiated for noise and CW-interference, showed (i) a bisection of CW-interference-related impairment of the reaction time in the presence of noise from 27 ms to 13.5 ms, (ii) a bisection of noise-related impairment of the reaction time in the presence of CW-conflict from 34 ms to 17 ms, (iii) an improvement of the impairment of the reaction time due to combined stress (noise plus CW-conflict) by 14.5 ms from 66 ms to 51.5 ms, (iv) despite of the improvement of the reaction time, no increase of the error rate. Safety blood parameters and the reporting of no adverse events argue for the product’s safety.These results may be relevant for persons solving cognitive tasks under conflict and/or noise (e.g. open-plan offices or car-driving) and support that the tested product alleviates stress-induced impairment of executive functioning (working memory, cognitive flexibility, controlled behavioural inhibition).
Published: 2016

13. Combining data from primary and ancillary surveys to assess the association between neighborhood-level characteristics and health outcomes: the Multi-Ethnic Study of Artherosclerosis

Author: Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Epidemiology, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, Boston University, School of Public Health, Boston, MA 02118, U.S.A., S??nchez, B. N., Raghunathan, T. E., Diez Roux, A. V., Zhu, Y., Lee, O., Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Epidemiology, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, Boston University, School of Public Health, Boston, MA 02118, U.S.A., S??nchez, B. N., Raghunathan, T. E., Diez Roux, A. V., Zhu, Y., and Lee, O.
Abstract: There is increasing interest in understanding the role of neighborhood-level factors on the health of individuals. Many large-scale epidemiological studies that accurately measure health status of individuals and individual risk factors exist. Sometimes these studies are linked to area-level databases (e.g. census) to assess the association between crude area-level characteristics and health. However, information from such databases may not measure the neighborhood-level constructs of interest. More recently, large-scale epidemiological studies have begun collecting data to measure specific features of neighborhoods using ancillary surveys. The ancillary surveys are composed of a separate, typically larger, set of individuals. The challenge is then to combine information from these two surveys to assess the role of neighborhood-level factors. We propose a method for combining information from the two data sources using a likelihood-based framework. We compare it with currently used ad hoc approaches via a simulation study. The simulation study shows that the proposed approach yields estimates with better sampling properties (less bias and better coverage probabilities) compared with the other approaches. However, there are cases where some ad hoc approaches may provide adequate estimates. We also compare the methods by applying them to the Multi-Ethnic Study of Atherosclerosis and its Neighborhood Ancillary Survey. Copyright ?? 2008 John Wiley & Sons, Ltd.
Published: 2008

14. Family-based SNP association study on 8q24 in bipolar disorder Please cite this article as follows: Zandi PP, Zoellner S, Avramopoulos D, Willour VL, Chen Y, Qin ZS, Burmeister M, Miao K, Gopalakrishnan S, McEachin R, Potash JB, DePaulo JR Jr., McInnis MG. 2007. Family-Based SNP Association Study on 8q24 in Bipolar Disorder. Am J Med Genet Part B 147B:612???618.

Author: Department of Psychiatry, University of Michigan, Ann Arbor, Michigan ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Molecular and Behavioral Neurosciences Institute, Psychiatry and Human Genetics, University of Michigan, Ann Arbor, Michigan, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, Maryland ; Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Hampton House, Room 857, 624 North Broadway, Baltimore, MD 21205., Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, Zandi, Peter P., Z??llner, Sebastian, Avramopoulos, Dimitrios, Willour, Virginia L., Chen, Yi, Qin, Zhaohui S., Burmeister, Margit, Miao, Kuangyi, Gopalakrishnan, Shyam, McEachin, Richard, Potash, James B., DePaulo, J. Raymond, McInnis, Melvin G., Department of Psychiatry, University of Michigan, Ann Arbor, Michigan ; Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Molecular and Behavioral Neurosciences Institute, Psychiatry and Human Genetics, University of Michigan, Ann Arbor, Michigan, Department of Psychiatry, University of Michigan, Ann Arbor, Michigan, Department of Mental Health, Johns Hopkins School of Public Health, Baltimore, Maryland ; Department of Mental Health, Bloomberg School of Public Health, Johns Hopkins University, Hampton House, Room 857, 624 North Broadway, Baltimore, MD 21205., Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland, Zandi, Peter P., Z??llner, Sebastian, Avramopoulos, Dimitrios, Willour, Virginia L., Chen, Yi, Qin, Zhaohui S., Burmeister, Margit, Miao, Kuangyi, Gopalakrishnan, Shyam, McEachin, Richard, Potash, James B., DePaulo, J. Raymond, and McInnis, Melvin G.
Abstract: Previous linkage studies have identified chromosome 8q24 as a promising positional candidate region to search for bipolar disorder (BP) susceptibility genes. We, therefore, sought to identify BP susceptibility genes on chromosome 8q24 using a family-based association study of a dense panel of SNPs selected to tag the known common variation across the region of interest. A total of 1,458 SNPs across 16 Mb of 8q24 were examined in 3,512 subjects, 1,954 of whom were affected with BP, from 737 multiplex families. Single-locus tests were carried out with FBAT and Geno-PDT, and multi-locus test were carried out with HBAT and multi-locus Geno-PDT. None of the SNPs were associated with BP in the single-locus tests at a level that exceeded our threshold for study-wide significance ( P ???
Published: 2008

15. A hot-deck multiple imputation procedure for gaps in longitudinal data on recurrent events

Author: Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109-2029, U.S.A., Department of Epidemiology, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Washington, Seattle, WA, U.S.A., Little, Roderick J., Yosef, Matheos, Cain, Kevin C., Nan, Bin, Harlow, Siobán D., Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A. ; Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109-2029, U.S.A., Department of Epidemiology, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, University of Washington, Seattle, WA, U.S.A., Little, Roderick J., Yosef, Matheos, Cain, Kevin C., Nan, Bin, and Harlow, Siobán D.
Abstract: We consider the analysis of longitudinal data sets that include times of recurrent events, where interest lies in variables that are functions of the number of events and the time intervals between events for each individual, and where some cases have gaps when the information was not recorded. Discarding cases with gaps results in a loss of the recorded information in those cases. Other strategies such as simply splicing together the intervals before and after the gap potentially lead to bias. A relatively simple imputation approach is developed that bases the number and times of events within the gap on matches to completely recordedhistories. Multiple imputation is used to propagate imputation uncertainty. The procedure is developed here for menstrual calendar data, where the recurrent events are menstrual bleeds recorded longitudinally over time. The recording is somewhat onerous, leading to gaps in the calendar data. The procedure is applied to two important data sets for assessing the menopausal transition, the Melbourne Women's Midlife Health Project and the TREMIN data. A simulation study is presented to assess the statistical properties of the proposed procedure. Some possible extensions of the approach are also considered. Copyright © 2007 John Wiley & Sons, Ltd.
Published: 2008

16. Effect of body mass index on the survival benefit of liver transplantation This study was approved by HRSA's SRTR project officer. HRSA has determined that this study satisfies the criteria for the IRB exemption described in the ???Public Benefit and Service Program??? provisions of 45 CFR 46.101(b)(5) and HRSA Circular 03.

Author: Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI ; Telephone: 734-936-8363; FAX: 734-763-3187 ; University of Michigan Health System, 2926 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0331, Department of Biostatistics, University of Michigan, Ann Arbor, MI ; Scientific Registry of Transplant Recipients, Ann Arbor, MI, Department of Biostatistics, University of Michigan, Ann Arbor, MI, Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI, Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI ; Scientific Registry of Transplant Recipients, Ann Arbor, MI, Scientific Registry of Transplant Recipients, Ann Arbor, MI ; Arbor Research Collaborative for Health, Ann Arbor, MI, Pelletier, Shawn J., Schaubel, Douglas E., Wei, Guanghui, Englesbe, Michael J., Punch, Jeffrey D., Wolfe, Robert A., Port, Friedrich K., Merion, Robert M., Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI ; Telephone: 734-936-8363; FAX: 734-763-3187 ; University of Michigan Health System, 2926 Taubman Center, 1500 E. Medical Center Dr., Ann Arbor, MI 48109-0331, Department of Biostatistics, University of Michigan, Ann Arbor, MI ; Scientific Registry of Transplant Recipients, Ann Arbor, MI, Department of Biostatistics, University of Michigan, Ann Arbor, MI, Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI, Division of Transplantation, Department of Surgery, University of Michigan, Ann Arbor, MI ; Scientific Registry of Transplant Recipients, Ann Arbor, MI, Scientific Registry of Transplant Recipients, Ann Arbor, MI ; Arbor Research Collaborative for Health, Ann Arbor, MI, Pelletier, Shawn J., Schaubel, Douglas E., Wei, Guanghui, Englesbe, Michael J., Punch, Jeffrey D., Wolfe, Robert A., Port, Friedrich K., and Merion, Robert M.
Abstract: Obese patients are at higher risk for morbidity and mortality after liver transplantation (LT) than nonobese recipients. However, there are no reports assessing the survival benefit of LT according to recipient body mass index (BMI). A retrospective cohort of liver transplant candidates who were initially wait-listed between September 2001 and December 2004 was identified in the Scientific Registry of Transplant Recipients database. Adjusted Cox regression models were fitted to assess the association between BMI and liver transplant survival benefit (posttransplantation vs. waiting list mortality). During the study period, 25,647 patients were placed on the waiting list. Of these, 4,488 (17%) underwent LT by December 31, 2004. At wait-listing and transplantation, similar proportions were morbidly obese (BMI ??? 40; 3.8% vs. 3.4%, respectively) and underweight (BMI < 20; 4.5% vs. 4.0%, respectively). Underweight patients experienced a significantly higher covariate-adjusted risk of death on the waiting list (hazard ratio [HR] = 1.61; P < 0.0001) compared to normal weight candidates (BMI 20 to <25), but underweight recipients had a similar risk of posttransplantation death (HR = 1.28; P = 0.15) compared to recipients of normal weight. In conclusion, compared to patients on the waiting list with a similar BMI, all subgroups of liver transplant recipients demonstrated a significant ( P < 0.0001) survival benefit, including morbidly obese and underweight recipients. Our results suggest that high or low recipient BMI should not be a contraindication for LT. Liver Transpl, 2007. ?? 2007 AASLD.
Published: 2008

17. Estimation of the proportion of overweight individuals in small areas—a robust extension of the Fay–Herriot model

Author: Department of Biostatistics and Institute for Social Research, University of Michigan, U.S.A., Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, U.S.A. ; Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, U.S.A., Xie, Dawei, Raghunathan, Trivellore E., Lepkowski, James M., Department of Biostatistics and Institute for Social Research, University of Michigan, U.S.A., Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, U.S.A. ; Department of Biostatistics and Epidemiology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 617 Blockley Hall, 423 Guardian Drive, Philadelphia, PA 19104, U.S.A., Xie, Dawei, Raghunathan, Trivellore E., and Lepkowski, James M.
Abstract: Hierarchical model such as Fay–Herriot (FH) model is often used in small area estimation. The method might perform well overall but is vulnerable to outliers. We propose a robust extension of the FH model by assuming the area random effects follow a t distribution with an unknown degrees-of-freedom parameter. The inferences are constructed using a Bayesian framework. Monte Carlo Markov Chain (MCMC) such as Gibbs sampling and Metropolis–Hastings acceptance and rejection algorithms are used to obtain the joint posterior distribution of model parameters. The procedure is used to estimate the county-level proportion of overweight individuals from the 2003 public-use Behavioral Risk Factor Surveillance System (BRFSS) data. We also discuss two approaches for identifying outliers in the context of this application. Copyright © 2006 John Wiley & Sons, Ltd.
Published: 2007

18. Training of the next generation of biostatisticians: a call to action in the U.S.

Author: Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics and Medical Informatics, University of Wisconsin, School of Medicine & Public Health, 600 Highland Avenue, Box 4675, Madison, WI 53792, U.S.A. ; Department of Biostatistics and Medical Informatics, University of Wisconsin, School of Medicine & Public Health, 600 Highland Avenue, Box 4675, Madison, WI 53792, U.S.A., Department of Genetics, Washington University School of Medicine, St. Louis, MO, U.S.A., Biostatistics Department, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, U.S.A., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A., DeMets, David L., Stormo, Gary, Boehnke, Michael, Louis, Thomas A., Taylor, Jeremy, Dixon, Dennis, Department of Biostatistics, University of Michigan, School of Public Health, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics and Medical Informatics, University of Wisconsin, School of Medicine & Public Health, 600 Highland Avenue, Box 4675, Madison, WI 53792, U.S.A. ; Department of Biostatistics and Medical Informatics, University of Wisconsin, School of Medicine & Public Health, 600 Highland Avenue, Box 4675, Madison, WI 53792, U.S.A., Department of Genetics, Washington University School of Medicine, St. Louis, MO, U.S.A., Biostatistics Department, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205, U.S.A., National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, U.S.A., DeMets, David L., Stormo, Gary, Boehnke, Michael, Louis, Thomas A., Taylor, Jeremy, and Dixon, Dennis
Abstract: Two workshops (2001, 2003) were held by the National Institutes of Health (NIH) to examine the need to train more biostatisticians in the U.S. to meet the increasing opportunities in the biomedical research enterprise. The supply of new PhD graduates in biostatistics in the U.S. has been relatively steady for the past two decades while the demand has increased dramatically. These workshops concluded that a renewed effort must be made in the U.S., led in part by the NIH, to add to and expand the existing training programs to increase the supply. This article summarizes those two workshops and their recommendations. Some progress has been made through a new biostatistics training program with emphasis in bioinformatics sponsored by the National Institute of General Medical Sciences (NIGMS). Copyright © 2006 John Wiley & Sons, Ltd.
Published: 2007

19. A shared random effects model for censored medical costs and mortality

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, U.S.A. ; Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA 22908-0717, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, U.S.A., Liu, Lei, Wolfe, Robert A., Kalbfleisch, John D., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, U.S.A. ; Department of Public Health Sciences, Division of Biostatistics and Epidemiology, University of Virginia, Charlottesville, VA 22908-0717, U.S.A., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109-2029, U.S.A., Liu, Lei, Wolfe, Robert A., and Kalbfleisch, John D.
Abstract: In this paper, we propose a model for medical costs recorded at regular time intervals, e.g. every month, as repeated measures in the presence of a terminating event, such as death. Prior models have related monthly medical costs to time since entry, with extra costs at the final observations at the time of death. Our joint model for monthly medical costs and survival time incorporates two important new features. First, medical cost and survival may be correlated because more ‘frail’ patients tend to accumulate medical costs faster and die earlier. A joint random effects model is proposed to account for the correlation between medical costs and survival by a shared random effect. Second, monthly medical costs usually increase during the time period prior to death because of the intensive care for dying patients. We present a method for estimating the pattern of cost prior to death, which is applicable if the pattern can be characterized as an additive effect that is limited to a fixed time interval, say b units of time before death. This ‘turn back time’ method for censored observations censors cost data b units of time before the actual censoring time, while keeping the actual censoring time for the survival data. Time-dependent covariates can be included. Maximum likelihood estimation and inference are carried out through a Monte Carlo EM algorithm with a Metropolis–Hastings sampler in the E-step. An analysis of monthly outpatient EPO medical cost data for dialysis patients is presented to illustrate the proposed methods. Copyright © 2006 John Wiley & Sons, Ltd.
Published: 2007

20. Genome-wide linkage scan for prostate cancer susceptibility genes in men with aggressive disease: significant evidence for linkage at chromosome 15q12

Author: Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA, ; Department of Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, University of Michigan, Ann Arbor, MI, USA, ; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Urology, University of Michigan, Ann Arbor, MI, USA, Department of Genetics, University of North Carolina, 4300D MBRB, CB# 7264, 103 Mason Farm Road, Chapel Hill, NC, 27599-7264, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Department of Genetics, University of North Carolina, 4300D MBRB, CB# 7264, 103 Mason Farm Road, Chapel Hill, NC, 27599-7264, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, National Human Genome Research Institute, Bethesda, MD, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Ann Arbor, Lange, Ethan M., Lange, Leslie A., Trent, Jeffrey M., Cooney, Kathleen A., Wood, David P., Ho, Lindsey A., Gillanders, Elizabeth M., Beebe-Dimmer, Jennifer L., Wang, Yunfei, Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA, ; Department of Urology, University of Michigan, Ann Arbor, MI, USA, Department of Urology, University of Michigan, Ann Arbor, MI, USA, ; Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Urology, University of Michigan, Ann Arbor, MI, USA, Department of Genetics, University of North Carolina, 4300D MBRB, CB# 7264, 103 Mason Farm Road, Chapel Hill, NC, 27599-7264, USA, ; Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Department of Genetics, University of North Carolina, 4300D MBRB, CB# 7264, 103 Mason Farm Road, Chapel Hill, NC, 27599-7264, USA, Translational Genomics Research Institute (TGen), Phoenix, AZ, USA, National Human Genome Research Institute, Bethesda, MD, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC, USA, Ann Arbor, Lange, Ethan M., Lange, Leslie A., Trent, Jeffrey M., Cooney, Kathleen A., Wood, David P., Ho, Lindsey A., Gillanders, Elizabeth M., Beebe-Dimmer, Jennifer L., and Wang, Yunfei
Abstract: Epidemiological and twin studies have consistently demonstrated a strong genetic component to prostate cancer (PCa) susceptibility. To date, numerous linkage studies have been performed to identify chromosomal regions containing PCa susceptibility genes. Unfortunately, results from these studies have failed to form any obvious consensus regarding which regions are most likely to contain genes that may contribute to PCa predisposition. One plausible explanation for the difficulty in mapping susceptibility loci is the existence of considerable heterogeneity in the phenotype of PCa, with significant variation in clinical stage and grade of disease even among family members. To address this issue, we performed a genome-wide linkage scan on 71 informative families with two or more men with aggressive PCa. When only men with aggressive PCa were coded as affected, statistically significant evidence for linkage at chromosome 15q12 was detected (LOD=3.49; genome-wide p =0.005). Furthermore, the evidence for linkage increased when analyses were restricted to Caucasian???American pedigrees (n =65; LOD=4.05) and pedigrees with two confirmed aggressive cases (n =42, LOD=4.76). Interestingly, a 1-LOD support interval about our peak at 15q12 overlaps a region of suggestive linkage, 15q11, identified by a recent linkage study on 1,233 PCa families by the International Consortium for Prostate Cancer Genetics. Using a more rigid definition of PCa in linkage studies will result in a severe reduction in sample sizes available for study, but may ultimately prove to increase statistical power to detect susceptibility genes for this multigenic trait.
Published: 2006

21. Clinicopathologic Features Associated With Having Four or More Metastatic Axillary Nodes in Breast Cancer Patients With a Positive Sentinel Lymph Node

Author: Department of Biostatistics, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, 3308 Cancer Center, Ann Arbor, Michigan, 48109-0932, Department of Pathology, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, St. Joseph???s Hospital and Medical Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109; Department of Biostatistics, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, Department of Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, Ann Arbor, Sabel, Michael S., Griffith, Kent A., Rivers, Aeisha K., Chang, Alfred E., Degnim, Amy C., Cimmino, Vincent M., Hunt, Kelly K., Diehl, Kathleen M., Newman, Lisa A., Lucas, Peter C., Department of Biostatistics, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, 3308 Cancer Center, Ann Arbor, Michigan, 48109-0932, Department of Pathology, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, St. Joseph???s Hospital and Medical Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109; Department of Biostatistics, University of Michigan Comprehensive Cancer Center, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, Michigan, 48109, Department of Surgery, Mayo Clinic, 200 First Street SW, Rochester, Minnesota, 55905, Department of Surgery, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas, 77030, Ann Arbor, Sabel, Michael S., Griffith, Kent A., Rivers, Aeisha K., Chang, Alfred E., Degnim, Amy C., Cimmino, Vincent M., Hunt, Kelly K., Diehl, Kathleen M., Newman, Lisa A., and Lucas, Peter C.
Abstract: The survival benefit of a completion axillary lymph node dissection (ALND) in patients after removal of a metastatic sentinel lymph node (SLN) is uncertain and is under study in ongoing clinical trials. The completion ALND remains necessary, however, for the identification of cases with at least four metastatic lymph nodes, in which extended-field locoregional and/or postmastectomy radiation will be recommended. Our goal was evaluate clinicopathologic features that might serve as surrogates for determining which patients with a positive SLN are likely or unlikely to belong to this high-risk subset.
Published: 2006

22. Alternative genetic models for the inheritance of the phenylthiocarbamide taste deficiency

Author: Department of Biostatistics, University of Michigan, Ann Arbor, Department of Biostatistics, University of Michigan, Ann Arbor ; Department of Biostatistics, School of Public Health, University of Michigan, 109 South Observatory, Ann Arbor, MI 48109, Departments of Psychiatry and Human Genetics, Western Psychiatric Institute and Clinic, University of Pittsburgh, Division of Human Biology, Department of Pediatrics, Wright State University School of Medicine, Yellow Springs, Ohio, Olson, Jane M., Boehnke, Michael, Neiswanger, Katherine, Roche, Alex F., Siervogel, Roger M., Department of Biostatistics, University of Michigan, Ann Arbor, Department of Biostatistics, University of Michigan, Ann Arbor ; Department of Biostatistics, School of Public Health, University of Michigan, 109 South Observatory, Ann Arbor, MI 48109, Departments of Psychiatry and Human Genetics, Western Psychiatric Institute and Clinic, University of Pittsburgh, Division of Human Biology, Department of Pediatrics, Wright State University School of Medicine, Yellow Springs, Ohio, Olson, Jane M., Boehnke, Michael, Neiswanger, Katherine, Roche, Alex F., and Siervogel, Roger M.
Abstract: Pedigree segregation analysis was used to examine several one- and two-locus models of the inheritance of phenylthiocarbamide (PTC) taste deficiency that extend the traditional one-locus recessive model by the addition of either another allele or another locus, and in some cases predict two types of nontasters. These models allow nontaster by nontaster matings to produce taster offspring, consistent with our data and several previous studies which use the Harris and Kalmus [Annals of Eugenics 15:24-32, 1949] dilution method. The models fit our data set of 1,152 individuals from 120 families significantly better than the one-locus recessive model. The best fit was obtained with a two-locus model in which one locus controls PTC tasting and the other locus controls a more general taste ability. This model is consistent with research on the physiology of PTC tasting and with results from genetic linkage studies. Further study is suggested to evaluate better the accuracy of the proposed model.
Published: 2006

23. Early smoking initiation and nicotine dependence in a cohort of young adults

Author: Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA; Department of Biostatistics and Psychiatry, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA., Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA, Breslau, Naomi, Fenn, Nancy, Peterson, Edward L., Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA; Department of Biostatistics and Psychiatry, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA., Department of Biostatistics and Research Epidemiology, Henry Ford Hospital, Detroit, MI and University of Michigan, School of Medicine, Ann Arbor, MI, USA, Breslau, Naomi, Fenn, Nancy, and Peterson, Edward L.
Abstract: We examined the extent to which nicotine dependence and daily smoking might vary by age at first cigarette. The potential confounding effects of sex, race and history of childhood behaviour problems were examined as well. A sample of 1200 was randomly selected from the subset of 21-30-year-old members of a large HMO in the Detroit SMSA; 1007 (84%) agreed to participate. Personal interviews were conducted in respondents' homes, using the NIMH-DIS to elicit information on DSM-III-R diagnoses, including nicotine dependence. Controlling for sex and race, persons who smoked their first cigarette at 14 to 16 years of age were 1.6 times more likely to become dependent than those who initiated smoking at an older age (P = 0.03). The association was unchanged when history of childhood behaviour problems was also controlled. Smoking initiation before age 14 was not associated with increased probability of dependence. Persons who initiated smoking before age 14 had a longer lag time to daily smoking and a lower likelihood of progressing to daily smoking, compared to persons who initiated smoking later on. The findings suggest that, among persons who have ever smoked, there might be two distinct groups in whom the chances of developing dependence are considerably reduced. The first comprises persons who delayed first use until age 17. The second comprises persons who smoked their first cigarette before age 14, a group in whom the progression to daily smoking might be markedly slower than in persons who initiated smoking when they were older.
Published: 2006

24. A Radiation Hybrid Map of the BRCA1 Region of Chromosome 17q12-q21

Author: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Departments of Human Genetics and Pediatrics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Departments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA., Abel, Kenneth J., Boehnke, Michael, Prahalad, Murali, Ho, Peggy P., Flejter, Wendy L., Watkins, Melanie, VanderStoep, Jill, Chandrasekharappa, Settara C., Collins, Francis S., Glover, Thomas W., Weber, Barbara L., Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Departments of Human Genetics and Pediatrics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Pediatrics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA., Departments of Internal Medicine and Human Genetics, University of Michigan, Ann Arbor, MI, USA; Michigan Human Genome Center, Ann Arbor, MI, USA; Howard Hughes Medical Institute, Ann Arbor, MI, USA., Abel, Kenneth J., Boehnke, Michael, Prahalad, Murali, Ho, Peggy P., Flejter, Wendy L., Watkins, Melanie, VanderStoep, Jill, Chandrasekharappa, Settara C., Collins, Francis S., Glover, Thomas W., and Weber, Barbara L.
Abstract: The chromosomal region 17q12-q21 contains a gene (BRCA1) conferring susceptibility to early-onset familial breast and ovarian cancer. An 8000-rad radiation-reduced hybrid (RH) panel was constructed to provide a resource for long-range mapping of this region. A large fraction of the hybrids (~90%) retained detectable human chromosome 17 sequences. The complete panel of 76 hybrids was scored for the presence or absence of 22 markers from this chromosomal region, including 14 cloned genes, seven microsatellite repeats, and one anonymous DNA segment. Statistical analysis of the marker retention data employing multipoint methods provided both comprehensive and framework maps of this chromosomal region, including distance estimates between adjacent markers. The comprehensive RH map includes 17 loci and spans 179 cRays(8000). Likelihood rations of at least 1000:1 support the 10-locus framework order: cen-D17S250-ERBB2-(THRIA1, TOP2A)-D17S855-PPY-DI7S190-MTBT1-GP3A-BTR-D17S588-tel. The order obtained from RH mapping, when used in conjunction with other methods, will be useful in linkage analysis of breast cancer families and will facilitate the development of a physical map of this region.
Published: 2006

25. Effect of empiric antiarrhythmic therapy in resuscitated out-of-hospital cardiac arrest victims with coronary artery disease

Author: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA; Henry Ford Heart and Vascular Institute, Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, USA., Henry Ford Heart and Vascular Institute, Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, USA; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA., Moosvi, Ali R., Goldstein, Sidney, Medendorp, Sharon VanderBrug, Landis, J. Richard, Wolfe, Robert A., Leighton, Richard, Ritter, George, Vasu, C. Mark, Acheson, Allyn, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA; Henry Ford Heart and Vascular Institute, Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, USA., Henry Ford Heart and Vascular Institute, Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Hospital, Detroit, USA; Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA., Moosvi, Ali R., Goldstein, Sidney, Medendorp, Sharon VanderBrug, Landis, J. Richard, Wolfe, Robert A., Leighton, Richard, Ritter, George, Vasu, C. Mark, and Acheson, Allyn
Abstract: The effect of empiric antiarrhythmic therapy with quindine and procainamide on long-term mortality was examined in 209 patients with coronary artery disease resuscitated after out-of-hospital cardiac arrest. The antiarrhythmic agent used was determined by the patient's private physician without knowledge of the study ambulatory electrocardiogram. Of the 209 patients, procainamide was prescribed in 45 (22%), qiinidine in 48 (23%) and no antiarrhythmic therapy in 116 (55%). Digoxin therapy was initiated in 101 patients. The 2-year total survival rate for the quinidine, procainamide and nontreated patients was 61, 57 and 71% (p <0.05), and for sudden death was 69, 69 and 89% (p <0.01), respectively. These observations suggest that empiric antiarrhythmic therapy in survivors of out-of-hospital cardiac arrest did not affect total mortality and was associated with an increased frequency of sudden death.
Published: 2006

26. Identification of women at risk for developing postmenopausal osteoporosis with vertebral fractures: role of history and single photon absorptiometry

Author: Division of Biostatistics and Research Epidemiology, Henry Ford Hospital, USA; Department of Biostatistics, School of Public Health, University of Michigan, USA., Department of Biostatistics, School of Public Health, University of Michigan, USA, Division of Bone and Mineral Metabolism, Department of Internal Medicine, USA, Division of Biostatistics and Research Epidemiology, Henry Ford Hospital, USA, Temple University, USA, Kleerekoper, M., Peterson, Edward L., Nelson, D.A., Tilley, B.C., Phillips, Erica, Schork, M. Anthony, Kuder, J., Division of Biostatistics and Research Epidemiology, Henry Ford Hospital, USA; Department of Biostatistics, School of Public Health, University of Michigan, USA., Department of Biostatistics, School of Public Health, University of Michigan, USA, Division of Bone and Mineral Metabolism, Department of Internal Medicine, USA, Division of Biostatistics and Research Epidemiology, Henry Ford Hospital, USA, Temple University, USA, Kleerekoper, M., Peterson, Edward L., Nelson, D.A., Tilley, B.C., Phillips, Erica, Schork, M. Anthony, and Kuder, J.
Abstract: Putative risk factors for the development of postmenopausal osteoporosis (PMO) with vertebral fractures were examined in a retrospective study of 663 postmenopausal white females aged 45-75 years (266 women with non-traumatic vertebral compression fractures (VF+), 134 non-fractured women from a general medicine clinic (controls) and 263 non-fractured women who were evaluated when they presented specifically for osteoporosis screening (VF- )). The VF+ women differed from control women in several respects. The VF+ group reported a higher prevalence of a positive family history of osteoporosis, and a higher prevalence of a history of medical or surgical conditions known to be independently associated with metabolic bone disease, had fewer children, were smaller (weight, height) and were slightly older. The two groups, VF+ and controls, did not differ with respect to cigarette smoking, alcohol consumption, exercise habits, menstrual or menopausal history, dietary intake of milk and cheese or in amount taking calcium supplements during pregnancy. The VF+ group also differed in certain respects from the VF- group. The VF+ group were smaller (weight, height) and were older. The VF+ group had lower cortical bone mass (measured by single photon absorptiometry of the non-dominant forearm) than either the control or VF- groups. The latter two groups did not differ from each other with respect to this measurement. These markers demonstrated limited sensitivity and specificity as estimated from a confirmatory data set, particularly for the historical and anthropometric variables. We conclude that an assessment of the risk of developing PMO with vertebral fractures cannot be based on the putative risk factors as measured in our study, but must be based on measurement of bone mass.
Published: 2006

27. The Safety After Fifty Evaluation trial: Evaluation of the safety and efficacy of antihypertensive therapy with metoprolol in patients 50 to 75 years of age: Study design

Author: Geriatric Cardiology Section, Jewish Hospital at Washington University, St. Louis, Mo., USA; Department of Geriatrics, Loyola-Strick School of Medicine, Chicago, Ill., USA; Department of Biostatistics, University of Michigan School of Medicine and School of Public Health, Ann Aroor, Mich., USA, Department of Geriatrics, Loyola-Strick School of Medicine, Chicago, Ill., USA; Department of Biostatistics, University of Michigan School of Medicine and School of Public Health, Ann Arbor, Mich., USA; Geriatric Cardiology Section, Jewish Hospital at Washington University, St. Louis, Mo., USA., Rich, Michael W., LaPalio, Lawrence, Schork, Anthony, SAFE Coordinators, Geriatric Cardiology Section, Jewish Hospital at Washington University, St. Louis, Mo., USA; Department of Geriatrics, Loyola-Strick School of Medicine, Chicago, Ill., USA; Department of Biostatistics, University of Michigan School of Medicine and School of Public Health, Ann Aroor, Mich., USA, Department of Geriatrics, Loyola-Strick School of Medicine, Chicago, Ill., USA; Department of Biostatistics, University of Michigan School of Medicine and School of Public Health, Ann Arbor, Mich., USA; Geriatric Cardiology Section, Jewish Hospital at Washington University, St. Louis, Mo., USA., Rich, Michael W., LaPalio, Lawrence, Schork, Anthony, and SAFE Coordinators
Abstract: Hypertension increases in prevalence with advancing age and is a major risk factor for the development of cardiovascular disease in elderly patients. However, the presence of coexisting illness, altered drug metabolism, enhanced susceptibility to drug side effects, and physiologic changes such as reduced plasma volume and lower plasma renin levels make truatment of hypertension in elderly patients more difficult. Nonetheless, several studies have now demonstrated the beneficial effects of antihypertensive drug therapy in older parlents. The Safety After Fifty Evaluation trial was designed to determine the short-term efficacy and tolerabillty of once-daily therapy with the cardioselective [beta]-blocker metoprolol anone or in combination with hydrochlorothiazide in the treatment of mild hypertension in patients 50 to 75 years of age. A total of 24,816 patients were enrolled in the trial by 2821 practicing physicians from across the United States. This article describes the detalls of the Safety After Fiffy Evaluation study design. Results of the trial will be reported separately.
Published: 2006

28. Estimation of mutation rates in cultured mammalian cells

Author: Department of Human Genetics, Medical School, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Human Genetics, Medical School, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Li, I-Chian, Fu, Jiliang, Hung, Yung-Tai, Chu, Ernest H.Y., Department of Human Genetics, Medical School, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A.; Department of Human Genetics, Medical School, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI 48109, U.S.A., Li, I-Chian, Fu, Jiliang, Hung, Yung-Tai, and Chu, Ernest H.Y.
Abstract: The factors that affect reliable estimations of mutation rates ([mu]) in cultured mammalian somatic cell populations by fluctuation analysis are studied experimentally and statistically. We analyze the differential effect of the final cell population size in each culture (Nt) and the number of parallel cultures (C) on the variation in the rate estimates () inferred from the P0 method. The analysis can be made after the derivation of the variance of, which is a measure of variation of for a given combination of Nt and C in a number of repeat experiments. The variance of is inversely proportional to C and to the square of Nt. Nt determines the probability of occurrence of mutation in a cell culture. By influencing the size of P0, Nt also determines whether a rate estimate is obtainable from the experiment. Since Po is estimated from the fraction of cultures containing no mutation in a set of C cultures, C becomes a determining factor for the accuracy of . The rate estimated from is biased, but the bias is in general 2 orders of magnitude smaller than . By the selection of an appropriate combination of Nt and C for the experiment, this bias can be reduced even further. Based on the notion of comparing two proportions, we propose a test statistic and have applied it to experimental results for a test of equality of mutation rates in different cell lines. This development places the comparison of mutation rates on a statistical basis.
Published: 2006

29. A computer program for testing average partial association in three-way contingency tables (PARCAT)

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27514, USA, Landis, J. Richard, Cooper, Murray M., Kennedy, Thomas, Koch, Gary G., Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27514, USA, Landis, J. Richard, Cooper, Murray M., Kennedy, Thomas, and Koch, Gary G.
Abstract: PARCAT is a computer program which implements alternative tests for average partial association in three-way contingency tables within the framework of the product multiple hypergeometric probability model. Primary attention is directed at the relationship between two of the variables, controlling for the effects of a covariable. This approach is essentially a multivariate extension of the Cochran/Mantel-Haenszel test to sets of (s x r) tables. A set of scores such as uniform, ridits, or probits can be assigned to categories which are ordinally scaled. In particular, if ridit scores with midranks assigned for ties are utilized, this procedure is equivalent to a partial Kruskal-Wallis test when one variable is ordinally scaled, and is equivalent to a partial Spearman rank correlation test when both variables are ordinally scaled.
Published: 2006

30. A computer program for multivariate ratio analysis (MISCAT)

Author: Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27514, USA, Stanish, William M., Koch, Gary G., Landis, J. Richard, Department of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of North Carolina, Chapel Hill, NC 27514, USA, Stanish, William M., Koch, Gary G., and Landis, J. Richard
Abstract: Analysts must deal frequently with missing data in multivariate analysis. In such cases, estimating the covariance maxtrix V of the dependent variables usually involves initial estimation and iterative adjustment of imputed missing data values, and/or smoothing of an estimate V which is not necessarily positive semi-definite. This paper presents an alternative procedure for computing estimates of relevant multivariate parameters in situations where missing data occur at random and with small probability. MISCAT is a computer program which computes multivariate ratio estimates of the means and a corresponding positive semi-definite estimate of the covariance matrix. It is an extension of GENCAT, which is a program for the generalized least squares analysis of categorical data. Thus, one advantage of dealing with missing data in this manner is that variation among the ratio estimates may be conveniently analyzed within MISCAT using asymptotic regression methodology, provided that sample sizes are sufficiently large. An example is given to illustrate such analysis for longitudinal data from a multicenter clinical trial.
Published: 2006

31. Copy Number Variations Associated With Obesity???Related Traits in African Americans: A Joint Analysis Between GENOA and HyperGEN

Author: Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA, Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA, Department of Pediatrics and Medicine and Human and Molecular Genetics Center, Medical Collegeof Wisconsin, Milwaukee, Wisconsin, USA, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA, Scripps Translational Science Institute, Scripps Health, San Diego, California, USA, Zhao, Wei, Wineinger, Nathan E., Tiwari, Hemant K., Mosley, Thomas H., Broeckel, Ulrich, Arnett, Donna K., Kardia, Sharon L.R., Kabagambe, Edmond K., Sun, Yan V., Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA, Department of Biostatistics, University of Alabama at Birmingham, Birmingham, Alabama, USA, Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia, USA, Department of Epidemiology, University of Alabama at Birmingham, Birmingham, Alabama, USA, Department of Pediatrics and Medicine and Human and Molecular Genetics Center, Medical Collegeof Wisconsin, Milwaukee, Wisconsin, USA, Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA, Scripps Translational Science Institute, Scripps Health, San Diego, California, USA, Zhao, Wei, Wineinger, Nathan E., Tiwari, Hemant K., Mosley, Thomas H., Broeckel, Ulrich, Arnett, Donna K., Kardia, Sharon L.R., Kabagambe, Edmond K., and Sun, Yan V.
Published: 2013

32. Agreement between clinical screening procedures for neuropathy in the feet

Author: Department of Environmental Health Sciences, School of Public Health, University of Michigan, M1835 SPH I, 1415 Washington Heights, Ann Arbor, Michigan 48109???2029, USA, Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA, Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan, USA, Wang, Yi, Goodrich, Jaclyn M., Werner, Robert, Gillespie, Brenda, Basu, Niladri, Franzblau, Alfred, Department of Environmental Health Sciences, School of Public Health, University of Michigan, M1835 SPH I, 1415 Washington Heights, Ann Arbor, Michigan 48109???2029, USA, Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA, Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, Michigan, USA, Wang, Yi, Goodrich, Jaclyn M., Werner, Robert, Gillespie, Brenda, Basu, Niladri, and Franzblau, Alfred
Abstract: Introduction: The correlation between monofilament testing, symptom surveys, and electrodiagnostic studies for the diagnosis of axonal polyneuropathy has not been well studied. This investigation was done to assess the agreement between these procedures in a non???random sample of volunteers. Methods: The procedures evaluated included electrodiagnostic tests of the sural nerve, monofilament testing of the great toe, a symptom survey, and a body diagram. Kappa coefficients and sensitivity and specificity, using nerve conduction as a ???gold standard,??? were used to determine the agreement between various combinations of procedures. Results: Poor agreement (kappa values ???0.12???0.44) and sensitivity (sensitivity <30%) were found for all combinations of symptoms and monofilament results in comparison with sural peak latency and amplitude. Conclusions: Overall, the results demonstrated a low discriminatory power for the screening procedures for identifying persons with impaired sural nerve function. The results highlight the need for further development and evaluation of screening methods for distal neuropathy in population???based studies. Muscle Nerve, 2012
Published: 2012

33. Segmentations of MRI images of the female pelvic floor: A study of inter- and intra-reader reliability

Author: University of Michigan, Department of Biostatistics, Ann Arbor, Michigan, USA, University of South Florida, College of Medicine, Division of Urogynecology and Pelvic Reconstructive Surgery, Tampa General Hospital, Urogynecology Division, Tampa, Florida, USA ; Division of Urogynecology and Pelvic Reconstructive Surgery, Department of OB/Gyn, University of South Florida College of Medicine, 2A Tampa General Drive, 6th Floor, Tampa, FL 33606, Loyola University Medical Center, Division of female pelvic medicine and reconstructive surgery, Maywood, Illinois, USA, University of North Carolina, School of Medicine, Department of Radiology, Chapel Hill, North Carolina, USA, University of Alabama, School of Medicine, Department of Radiology, Birmingham, Alabama, USA, University of Utah, School of Medicine, Department of Radiology, Salt Lake City, Utah, USA, Harvard Medical School, Department of Radiology, Boston, Massachusetts, USA, Hoyte, Lennox, Ye, Wen, Brubaker, Linda, Fielding, Julia R., Lockhart, Mark E., Heilbrun, Marta E., Brown, Morton B., Warfield, Simon K., University of Michigan, Department of Biostatistics, Ann Arbor, Michigan, USA, University of South Florida, College of Medicine, Division of Urogynecology and Pelvic Reconstructive Surgery, Tampa General Hospital, Urogynecology Division, Tampa, Florida, USA ; Division of Urogynecology and Pelvic Reconstructive Surgery, Department of OB/Gyn, University of South Florida College of Medicine, 2A Tampa General Drive, 6th Floor, Tampa, FL 33606, Loyola University Medical Center, Division of female pelvic medicine and reconstructive surgery, Maywood, Illinois, USA, University of North Carolina, School of Medicine, Department of Radiology, Chapel Hill, North Carolina, USA, University of Alabama, School of Medicine, Department of Radiology, Birmingham, Alabama, USA, University of Utah, School of Medicine, Department of Radiology, Salt Lake City, Utah, USA, Harvard Medical School, Department of Radiology, Boston, Massachusetts, USA, Hoyte, Lennox, Ye, Wen, Brubaker, Linda, Fielding, Julia R., Lockhart, Mark E., Heilbrun, Marta E., Brown, Morton B., and Warfield, Simon K.
Abstract: Purpose: To describe the inter- and intra-operator reliability of segmentations of female pelvic floor structures. Materials and Methods: Three segmentation specialists were asked to segment out the female pelvic structures in 20 MR datasets on three separate occasions. The STAPLE algorithm was used to compute inter- and intra-segmenter agreement of each organ in each dataset. STAPLE computed the sensitivity, specificity, and positive predictive values (PPV) for inter- and intra-segmenter repeatability. These parameters were analyzed using intra-class correlation analysis. Correlation of organ volume to PPV and sensitivity was also computed. Results: Mean PPV of the segmented organs ranged from 0.82 to 0.99, and sensitivity ranged from 33 to 96%. Intra-class correlation ranged from 0.07 to 0.98 across segmenters. Pearson correlation of volume to sensitivity were significant across organs, ranging from 0.54 to 0.91. Organs with significant correlation of PPV to volume were bladder (???0.69), levator ani (???0.68), and coccyx (???0.63). Conclusion: Undirected manual segmentation of the pelvic floor organs are adequate for locating the organs, but poor at defining structural boundaries. J. Magn. Reson. Imaging 2011;33:684???691. ?? 2011 Wiley-Liss, Inc.
Published: 2011

34. Relationship between polychlorinated dibenzo- p -dioxin, polychlorinated dibenzofuran, and dioxin-like polychlorinated biphenyl concentrations in vegetation and soil on residential properties

Author: Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA ; Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA., Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA, Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA, LimnoTech, Ann Arbor, Michigan, USA, Vista Analytical Laboratory, El Dorado Hills, California, USA, Demond, Avery, Towey, Timothy, Adriaens, Peter, Zhong, Xiaobo, Knutson, Kristine, Chen, Qixuan, Hong, Biling, Gillespie, Brenda, Franzblau, Alfred, Garabrant, David, Lepkowski, James, Luksemburg, William, Maier, Martha, Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA ; Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA., Department of Civil and Environmental Engineering, University of Michigan College of Engineering, Ann Arbor, Michigan 48109, USA, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, Michigan, USA, Department of Environmental Health Sciences, University of Michigan School of Public Health, Ann Arbor, Michigan, USA, Institute for Social Research, University of Michigan, Ann Arbor, Michigan, USA, LimnoTech, Ann Arbor, Michigan, USA, Vista Analytical Laboratory, El Dorado Hills, California, USA, Demond, Avery, Towey, Timothy, Adriaens, Peter, Zhong, Xiaobo, Knutson, Kristine, Chen, Qixuan, Hong, Biling, Gillespie, Brenda, Franzblau, Alfred, Garabrant, David, Lepkowski, James, Luksemburg, William, and Maier, Martha
Abstract: The University of Michigan Dioxin Exposure Study was undertaken to address concerns that the industrial discharge of dioxin-like compounds in the Midland, Michigan, USA area had resulted in the contamination of soil and vegetation in the Tittabawassee River floodplain and downwind of the incinerator in the City of Midland. The study included the analysis of 597 vegetation samples, predominantly grass and weeds, from residential properties selected through a multistage probabilistic sample design in the Midland area, and in Jackson and Calhoun Counties (Michigan), as a background comparison, for 29 polychlorinated dibenzo- p -dioxins (PCDDs), polychlorinated dibenzofurans (PCDFs), and polychlorinated biphenyls (PCBs). The mean toxic equivalent (TEQ) of the house perimeter vegetation samples ranged from 4.2 to 377???pg/g. The ratio of TEQs (vegetation to soil) was about 0.3, with a maximum of 3.5. Based on a calculation of the similarity of the congener patterns between the soil and the vegetation, it appeared that the source of the contamination on the vegetation was the surrounding soil. This conclusion was supported by linear regression analysis, which showed that the largest contributor to the R 2 for the outcome variable of log 10 of the vegetation concentration was log 10 of the surrounding soil concentration. Models of vegetation contamination usually focus on atmospheric deposition and partitioning. The results obtained here suggest that the deposition of soil particles onto vegetation is a significant route of contamination for residential herbage. Thus, the inclusion of deposition of soil particles onto vegetation is critical to the accurate modeling of contamination residential herbage in communities impacted by historic industrial discharges of persistent organic compounds. Environ. Toxicol. Chem. 2010;29:2660???2668. ?? 2010 SETAC
Published: 2010

35. Patterns and correlates of drug-related ED visits: Results from a national survey

Author: University of Michigan, School of Social Work, Ann Arbor, MI 48109, USA, VA National Serious Mental Illness Treatment Research Evaluation Center, Ann Arbor, MI 48105, USA, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of Michigan, MI 48109, USA, Division of Epidemiology, Department of Public Policy Studies, Saint Louis University, School of Social Work, School of Public Health, St Louis, MO 63103, USA, Center for Behavioral Health Services and Criminal Justice Research, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA, University of North Carolina at Chapel Hill, School of Social Work, Chapel Hill, NC 27599, USA, Ann Arbor, Perron, Brian, Bohnert, Amy S. B., Monsell, Sarah E., Vaughn, Michael G., Epperson, Matthew, Howard, Matthew O., University of Michigan, School of Social Work, Ann Arbor, MI 48109, USA, VA National Serious Mental Illness Treatment Research Evaluation Center, Ann Arbor, MI 48105, USA, Department of Psychiatry, University of Michigan Medical School, Ann Arbor, MI 48109, USA, Department of Biostatistics, University of Michigan, MI 48109, USA, Division of Epidemiology, Department of Public Policy Studies, Saint Louis University, School of Social Work, School of Public Health, St Louis, MO 63103, USA, Center for Behavioral Health Services and Criminal Justice Research, Rutgers, the State University of New Jersey, New Brunswick, NJ 08901, USA, University of North Carolina at Chapel Hill, School of Social Work, Chapel Hill, NC 27599, USA, Ann Arbor, Perron, Brian, Bohnert, Amy S. B., Monsell, Sarah E., Vaughn, Michael G., Epperson, Matthew, and Howard, Matthew O.
Published: 2010

36. Chemotherapy alone for organ preservation in advanced laryngeal cancer

Author: Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Vasu Divi and Francis P. Worden contributed equally to this work., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI ; Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Divi, Vasu, Worden, Francis P., Prince, Mark E., Eisbruch, Avraham, Lee, Julia S., Bradford, Carol R., Chepeha, Douglas B., Teknos, Theodoros N., Hogikyan, Norman D., Moyer, Jeffrey S., Tsien, Christina I., Urba, Susan G., Wolf, Gregory T., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Vasu Divi and Francis P. Worden contributed equally to this work., Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI ; Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI, Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Biostatistics, University of Michigan Medical School, Ann Arbor, MI, Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Department of Otolaryngology-Head and Neck Surgery, Comprehensive Cancer Center, University of Michigan Medical School, Ann Arbor, MI ; Department of Internal Medicine, Division of Hematology-Oncology, University of Michigan Medical School, Ann Arbor, MI, Divi, Vasu, Worden, Francis P., Prince, Mark E., Eisbruch, Avraham, Lee, Julia S., Bradford, Carol R., Chepeha, Douglas B., Teknos, Theodoros N., Hogikyan, Norman D., Moyer, Jeffrey S., Tsien, Christina I., Urba, Susan G., and Wolf, Gregory T.
Abstract: Background. For patients with advanced laryngeal cancer, a trial was designed to determine if chemotherapy alone, in patients achieving a complete histologic complete response after a single neoadjuvant cycle, was an effective treatment with less morbidity than concurrent chemoradiotherapy. Methods. Thirty-two patients with advanced laryngeal or hypopharyngeal cancer received 1 cycle of induction chemotherapy, and subsequent treatment was decided based on response. Results. A histologic complete response was achieved in 4 patients and were treated with chemotherapy alone. All 4 patients' cancer relapsed in the neck and required surgery and postoperative radiotherapy (RT). Twenty-five patients were treated with concomitant chemoradiation. Three patients were treated with surgery. Overall survival and disease-specific survival at 3 years were 68% and 78%, respectively. Conclusion. Chemotherapy alone is not feasible for long-term control of regional disease in patients with advanced laryngeal cancer even when they achieve a histologic complete response at the primary site. ?? 2009 Wiley Periodicals, Inc. Head Neck, 2010
Published: 2010

37. Thiazolidinediones, cardiovascular disease and cardiovascular mortality: translating research into action for diabetes (TRIAD)

Author: Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA ; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA ; Professor of Internal Medicine and Epidemiology. ; Department of Epidemiology, 3920 Taubman Center, SPC 5354 Ann Arbor, MI 48109, USA., Division of Research, Kaiser Permanente, Oakland, CA, USA, Indiana University School of Medicine, Indianapolis, IN, USA, Pacific Health Research Institute and Department of Family Medicine and Community Health, University of Hawaii, Honolulu, HI, USA, Department of Medicine, University of California, Los Angeles, CA, USA, Preventive Cardiology Program, UMDNJ-New Jersey Medical School, Newark, NJ, USA, Department of Family Medicine, UMDNJ-Robert Wood Johnson Medical School, Somerset, NJ, USA, Bilik, Dori, McEwen, Laura N., Brown, Morton B., Selby, Joe V., Karter, Andrew J., Marrero, David G., Hsiao, Victoria C., Tseng, Chien-Wen, Mangione, Carol M., Lasser, Norman L., Crosson, Jesse C., Herman, William H., Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA ; Department of Epidemiology, University of Michigan, Ann Arbor, MI, USA ; Professor of Internal Medicine and Epidemiology. ; Department of Epidemiology, 3920 Taubman Center, SPC 5354 Ann Arbor, MI 48109, USA., Division of Research, Kaiser Permanente, Oakland, CA, USA, Indiana University School of Medicine, Indianapolis, IN, USA, Pacific Health Research Institute and Department of Family Medicine and Community Health, University of Hawaii, Honolulu, HI, USA, Department of Medicine, University of California, Los Angeles, CA, USA, Preventive Cardiology Program, UMDNJ-New Jersey Medical School, Newark, NJ, USA, Department of Family Medicine, UMDNJ-Robert Wood Johnson Medical School, Somerset, NJ, USA, Bilik, Dori, McEwen, Laura N., Brown, Morton B., Selby, Joe V., Karter, Andrew J., Marrero, David G., Hsiao, Victoria C., Tseng, Chien-Wen, Mangione, Carol M., Lasser, Norman L., Crosson, Jesse C., and Herman, William H.
Abstract: Background Studies have associated thiazolidinedione (TZD) treatment with cardiovascular disease (CVD) and questioned whether the two available TZDs, rosiglitazone and pioglitazone, have different CVD risks. We compared CVD incidence, cardiovascular (CV), and all-cause mortality in type 2 diabetic patients treated with rosiglitazone or pioglitazone as their only TZD. Methods We analyzed survey, medical record, administrative, and National Death Index (NDI) data from 1999 through 2003 from Translating Research Into Action for Diabetes (TRIAD), a prospective observational study of diabetes care in managed care. Medications, CV procedures, and CVD were determined from health plan (HP) administrative data, and mortality was from NDI. Adjusted hazard rates (AHR) were derived from Cox proportional hazard models adjusted for age, sex, race/ethnicity, income, history of diabetic nephropathy, history of CVD, insulin use, and HP. Results Across TRIAD's 10 HPs, 1,815 patients (24%) filled prescriptions for a TZD, 773 (10%) for only rosiglitazone, 711 (10%) for only pioglitazone, and 331 (4%) for multiple TZDs. In the seven HPs using both TZDs, 1,159 patients (33%) filled a prescription for a TZD, 564 (16%) for only rosiglitazone, 334 (10%) for only pioglitazone, and 261 (7%) for multiple TZDs. For all CV events, CV, and all-cause mortality, we found no significant difference between rosiglitazone and pioglitazone. Conclusions In this relatively small, prospective, observational study, we found no statistically significant differences in CV outcomes for rosiglitazone- compared to pioglitazone-treated patients. There does not appear to be a pattern of clinically meaningful differences in CV outcomes for rosiglitazone- versus pioglitazone-treated patients. Copyright ?? 2010 John Wiley & Sons, Ltd.
Published: 2010

38. The questionnaire for urinary incontinence diagnosis (QUID): Validity and responsiveness to change in women undergoing non-surgical therapies for treatment of stress predominant urinary incontinence

Author: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, Iowa ; Department of Obstetrics and Gynecology, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242., Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah, Obstetrics, Gynecology, and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, Department of Obstetrics and Gynecology, University of California San Diego, San Diego, California, Departments of Obstetrics & Gynecology and Urology, Loyola University Medical Center, Maywood, Illinois, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, North Carolina, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama, Bradley, Catherine S., Rahn, David D., Nygaard, Ingrid E., Barber, Matthew D., Nager, Charles W., Kenton, Kimberly S., Siddiqui, Nazema Y., Abel, Robert B., Spino, Cathie, Richter, Holly E., Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Department of Obstetrics and Gynecology, Carver College of Medicine, University of Iowa, Iowa City, Iowa ; Department of Obstetrics and Gynecology, University of Iowa Hospitals & Clinics, 200 Hawkins Drive, Iowa City, IA 52242., Department of Obstetrics & Gynecology, University of Texas Southwestern Medical Center, Dallas, Texas, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, Utah, Obstetrics, Gynecology, and Women's Health Institute, Cleveland Clinic, Cleveland, Ohio, Department of Obstetrics and Gynecology, University of California San Diego, San Diego, California, Departments of Obstetrics & Gynecology and Urology, Loyola University Medical Center, Maywood, Illinois, Department of Obstetrics and Gynecology, Duke University School of Medicine, Durham, North Carolina, Department of Obstetrics and Gynecology, University of Alabama at Birmingham, Birmingham, Alabama, Bradley, Catherine S., Rahn, David D., Nygaard, Ingrid E., Barber, Matthew D., Nager, Charles W., Kenton, Kimberly S., Siddiqui, Nazema Y., Abel, Robert B., Spino, Cathie, and Richter, Holly E.
Abstract: Aims The Questionnaire for Urinary Incontinence Diagnosis (QUID), a 6-item urinary incontinence (UI) symptom questionnaire, was developed and validated to distinguish stress and urge UI. This study's objective was to evaluate QUID validity and responsiveness when used as a clinical trial outcome measure. Methods Participants enrolled in a multi-center trial of non-surgical therapy (continence pessary, pelvic floor muscle training or combined) for stress-predominant UI and completed baseline and 3-month diaries, the Urinary Distress Inventory (UDI) and QUID. Data from all treatment groups were pooled. QUID internal consistency (Cronbach's ??) and convergent/discriminant validity (Pearson correlations) were evaluated. Responsiveness to change was assessed with 3-month score outcomes and distribution-based measurements. Results Four hundred forty-four women (mean age 50) were enrolled with stress (N???=???200) and mixed (N???=???244) UI; 344 had 3-month data. Baseline QUID Stress and Urge scores (both scaled 0???15, larger values indicating worse UI) were 8.4????????3.2 and 4.5????????3.3, respectively. Internal consistency of QUID Total, Stress, and Urge scores was 0.75, 0.64 and 0.87, respectively. QUID Stress scores correlated moderately with UDI-Stress scores (r???=???0.68, P ???
Published: 2010

39. Nurse aides' identification of onset and level of agitation in late stage dementia patients

Author: School of Nursing, The University of Michigan, Ann Arbor, Michigan, College of Health Professions, University of Detroit Mercy, Detroit, Michigan, Department of Neurology, School of Medicine, The University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, School of Public Health, The University of Michigan, Ann Arbor, Michigan, School of Nursing, Mc Master University, Hamilton, Ontario, Canada, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada, Whall, Ann, Black, Margaret, Yankou, Dawn, Groh, Carla, Kupferschmid, Barbara, Foster, Norman, Little, Roderick, School of Nursing, The University of Michigan, Ann Arbor, Michigan, College of Health Professions, University of Detroit Mercy, Detroit, Michigan, Department of Neurology, School of Medicine, The University of Michigan, Ann Arbor, Michigan, Department of Biostatistics, School of Public Health, The University of Michigan, Ann Arbor, Michigan, School of Nursing, Mc Master University, Hamilton, Ontario, Canada, Faculty of Health Sciences, University of Western Ontario, London, Ontario, Canada, Whall, Ann, Black, Margaret, Yankou, Dawn, Groh, Carla, Kupferschmid, Barbara, Foster, Norman, and Little, Roderick
Abstract: Nurse aides provide the majority of care to patients in nursing homes and thus are vital links in the early identification and treatment of agitation in dementia. Agitation increases in frequency as dementia progresses and unrecognized and untreated agitation may develop into a state of acute aggression (termed catastrophic reaction) in which demented patients become severely disturbed and may harm themselves or others. Nurse aides, however, are sometimes characterized as unable or unwilling to provide accurate observations of demented patients??? behavior, and thus are incapable of assisting with this important research. This study examined a process by which nurse aides were enlisted to identify and rate agitation in late stage dementia patients. Results indicate that nurse aides accurately identified agitation at a high level of agreement (r = >.90), on three occasions, with nurse experts. This high level of agreement was achieved along with a high level of nurse aide participation (75 percent), and with relatively little training time, i.e., approximately one hour per nurse aide. There were no significant differences in the demographic characteristics of aides participating versus those declining participation; likewise, participation rates in unionized versus non-unionized homes were not significantly different. The characteristics of the training program are described and the opinions of both nurse aides and administrators discussed as to why this program was successful.
Published: 2010

40. A Re-analysis of Caries Rates in a Preventive Trial using Poisson Regression Models

Author: Department of Biological and Material Sciences, University of Michigan, Ann Arbor, Michigan 48109, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Epidemiology, School of Public Healthand Community Medicine, Department of Community Dentistry, Institute of Dentistry, University of Turku, Finland, Department of Epidemiology, School of Public Healthand Community Medicine, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Program in Epidemiology, and University of Washington, Seattle, Department of Oral Biology, University of Washington, Seattle, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Biostatistics, University of Washington, Seattle, Hujoel, P. P., Isokangas, P. J., Tiekso, J., Davis, S., Lamont, R. J., DeRouen, T. A., Makinen, K. K., Department of Biological and Material Sciences, University of Michigan, Ann Arbor, Michigan 48109, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Epidemiology, School of Public Healthand Community Medicine, Department of Community Dentistry, Institute of Dentistry, University of Turku, Finland, Department of Epidemiology, School of Public Healthand Community Medicine, Fred Hutchinson Cancer Research Center, Division of Public Health Sciences, Program in Epidemiology, and University of Washington, Seattle, Department of Oral Biology, University of Washington, Seattle, Department of Dental Public Health Sciences, School of Dentistry, SM-35, University of Washington, Seattle, Washington 98195, Department of Biostatistics, University of Washington, Seattle, Hujoel, P. P., Isokangas, P. J., Tiekso, J., Davis, S., Lamont, R. J., DeRouen, T. A., and Makinen, K. K.
Abstract: The analysis of caries incidence in clinical trials has several challenging features: (1) The distribution of the number of caries onsets per patient is skewed, with the majority of patients having few or no cavities; (2) the number of surfaces at risk varies (i) over time and (ii) between patients, due to eruption and exfoliation patterns, dental diseases, and treatments ; (3) surfaces within a patient differ in their caries susceptibility, and (4) caries onsets within a patient are correlated due to shared host factors. Recent statistical developments in the area of correlated data analyses permit incorporation of some of these characteristics into the analyses. With Poisson regression models, the expected number of caries onsets can be related to the number of surfaces at risk, the time they have been at risk, and surface- and subject-specific explanatory variables. The parameter estimated in these models is an epidemiological measure of disease occurrence: the disease incidence rate (caries rate) or the rate of change from healthy (sound) to diseased (carious). Differences and ratios of these rates provide standard epidemiological measures of excess risk. To illustrate, Poisson regression models were used for exploratory analyses of the Ylivieska xylitol study.
Published: 2010

41. Fast food and neighborhood stroke risk

Author: Stroke Program, University of Michigan Medical School, Ann Arbor, MI ; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI ; University of Michigan Cardiovascular Center, Room 3194, 1500 East Medical Center Dr. SPC #5855, Ann Arbor, MI 48109-5855, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, Stroke Program, University of Michigan Medical School, Ann Arbor, MI, Stroke Program, University of Michigan Medical School, Ann Arbor, MI ; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, Morgenstern, Lewis B., Escobar, James D., S??nchez, Brisa N., Hughes, Rebecca, Zuniga, Belinda G., Garcia, Nelda, Lisabeth, Lynda D., Stroke Program, University of Michigan Medical School, Ann Arbor, MI ; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI ; University of Michigan Cardiovascular Center, Room 3194, 1500 East Medical Center Dr. SPC #5855, Ann Arbor, MI 48109-5855, Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, Stroke Program, University of Michigan Medical School, Ann Arbor, MI, Stroke Program, University of Michigan Medical School, Ann Arbor, MI ; Department of Epidemiology, University of Michigan School of Public Health, Ann Arbor, MI, Morgenstern, Lewis B., Escobar, James D., S??nchez, Brisa N., Hughes, Rebecca, Zuniga, Belinda G., Garcia, Nelda, and Lisabeth, Lynda D.
Abstract: Objective To investigate the association between the number of fast food restaurants and ischemic stroke in neighborhoods. Methods This work was a prespecified part of the Brain Attack in Corpus Christi (BASIC) project. Ischemic stroke cases were prospectively ascertained in Nueces County, Texas. Home addresses were geocoded and used to establish the census tract for each stroke case. Census tracts were used as proxies for neighborhoods (n = 64). Using a standard definition, fast food restaurants were identified from a commercial list. Poisson regression was used to study the association between the number of fast food restaurants in the neighborhood, using a 1-mile buffer around each census tract, and the risk of stroke in the neighborhood. Models were adjusted for demographics and neighborhood socioeconomic status (SES). Results There were 1,247 completed ischemic strokes from January 2000 through June 2003 and 262 fast food restaurants. The median number of fast food restaurants per census tract including buffer was 22 (interquartile range, 12???33). Adjusting for neighborhood demographics and SES, the association of fast food restaurants with stroke was significant ( p = 0.02). The association suggested that the risk of stroke in a neighborhood increased by 1% for every fast food restaurant (relative risk, 1.01; 95% confidence interval [CI], 1.00???1.01). The relative risk of stroke comparing neighborhoods in the 75th to the 25th percentile of the distribution of fast food restaurants was 1.13 (95% CI, 1.02???1.25). Interpretation Controlling for demographic and SES factors, there was a significant association between fast food restaurants and stroke risk in neighborhoods in this community-based study. Ann Neurol 2009;66:165???170
Published: 2009

42. Renal outcomes after liver transplantation in the model for end-stage liver disease era

Author: Division of Gastroenterology, University of Michigan, Ann Arbor, MI ; Telephone: 734-936-4780; FAX: 734-936-7392 ; Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109, Department of Biostatistics, University of Michigan, Ann Arbor, MI, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, Sharma, Pratima, Welch, Kathy, Eikstadt, Richard, Marrero, Jorge A., Fontana, Robert J., Lok, Anna S., Division of Gastroenterology, University of Michigan, Ann Arbor, MI ; Telephone: 734-936-4780; FAX: 734-936-7392 ; Division of Gastroenterology, Department of Internal Medicine, University of Michigan Health System, 3912 Taubman Center, SPC 5362, Ann Arbor, MI 48109, Department of Biostatistics, University of Michigan, Ann Arbor, MI, Division of Gastroenterology, University of Michigan, Ann Arbor, MI, Sharma, Pratima, Welch, Kathy, Eikstadt, Richard, Marrero, Jorge A., Fontana, Robert J., and Lok, Anna S.
Abstract: The proportion of patients undergoing liver transplantation (LT) with renal insufficiency has significantly increased in the Model for End-Stage Liver Disease (MELD) era. This study was designed to determine the incidence and predictors of post-LT chronic renal failure (CRF) and its effect on patient survival in the MELD era. Outcomes of 221 adult LT recipients who had LT between February 2002 and February 2007 were reviewed retrospectively. Patients who were listed as status 1, were granted a MELD exception, or had living-donor, multiorgan LT were excluded. Renal insufficiency at LT was defined as none to mild [estimated glomerular filtration rate (GFR) ??? 60 mL/minute], moderate (30???59 mL/minute), or severe (<30 mL/minute). Post-LT CRF was defined as an estimated GFR < 30 mL/minute persisting for 3 months, initiation of renal replacement therapy, or listing for renal transplantation. The median age was 54 years, 66% were male, 89% were Caucasian, and 43% had hepatitis C. At LT, the median MELD score was 20, and 6.3% were on renal replacement therapy. After a median follow-up of 2.6 years (range, 0.01???5.99), 31 patients developed CRF with a 5-year cumulative incidence of 22%. GFR at LT was the only independent predictor of post-LT CRF (hazard ratio = 1.33, P < 0.001). The overall post-LT patient survival was 74% at 5 years. Patients with MELD ??? 20 at LT had a higher cumulative incidence of post-LT CRF in comparison with patients with MELD < 20 ( P = 0.03). A decrease in post-LT GFR over time was the only independent predictor of survival. In conclusion, post-LT CRF is common in the MELD era with a 5-year cumulative incidence of 22%. Low GFR at LT was predictive of post-LT CRF, and a decrease in post-LT GFR over time was associated with decreased post-LT survival. Further studies of modifiable preoperative, perioperative, and postoperative factors influencing renal function are needed to improve outcomes following LT. Liver Transpl 15:1142???1148, 2009. ?? 20
Published: 2009

43. Measurements from image-based three dimensional pelvic floor reconstruction: A study of inter- and intraobserver reliability

Author: University of Michigan, Department of Biostatistics, Ann Arbor, Michigan, University of South Florida, College of Medicine, Division of Urogynecology and Pelvic Reconstructive Surgery, Tampa General Hospital, Urogynecology Division, Tampa, Florida ; Division of Urogynecology and Pelvic Reconstructive Surgery, Department of OB/Gyn, University of South Florida College of Medicine, 2A Columbia Dr., 6th Fl., Tampa, FL 33606-3508, Loyola University Medical Center, Division of Female Pelvic Medicine and Reconstructive Surgery, Maywood, Illinois, University of North Carolina, School of Medicine, Department of Radiology, Chapel Hill, North Carolina, University of Alabama, School of Medicine, Department of Radiology, Birmingham, Alabama, University of Utah, School of Medicine, Department of Radiology, Salt Lake City, Utah, Hoyte, Lennox, Brubaker, Linda, Fielding, Julia R., Lockhart, Mark E., Heilbrun, Marta E., Salomon, Caryl G., Ye, Wen, Brown, Morton B., University of Michigan, Department of Biostatistics, Ann Arbor, Michigan, University of South Florida, College of Medicine, Division of Urogynecology and Pelvic Reconstructive Surgery, Tampa General Hospital, Urogynecology Division, Tampa, Florida ; Division of Urogynecology and Pelvic Reconstructive Surgery, Department of OB/Gyn, University of South Florida College of Medicine, 2A Columbia Dr., 6th Fl., Tampa, FL 33606-3508, Loyola University Medical Center, Division of Female Pelvic Medicine and Reconstructive Surgery, Maywood, Illinois, University of North Carolina, School of Medicine, Department of Radiology, Chapel Hill, North Carolina, University of Alabama, School of Medicine, Department of Radiology, Birmingham, Alabama, University of Utah, School of Medicine, Department of Radiology, Salt Lake City, Utah, Hoyte, Lennox, Brubaker, Linda, Fielding, Julia R., Lockhart, Mark E., Heilbrun, Marta E., Salomon, Caryl G., Ye, Wen, and Brown, Morton B.
Abstract: Purpose To describe inter- and intraobserver reliability of 3D measurements of female pelvic floor structures. Materials and Methods Twenty reconstructed MR datasets of primiparas at 6???12 months postpartum were analyzed. Pelvic organ measurements were independently made twice by three radiologists blinded to dataset order. A ???within-reader??? analysis, a ???between-reader??? analysis, and the intraclass correlation (ICC), and standard deviation ratio (SDR) were computed for each parameter. Fifteen continuous variables and one categorical variable were measured. Results Eight continuous parameters showed excellent agreement (ICC >0.85 / SDR <0.40), five parameters showed relatively good agreement (ICC >0.70 / SDR ???0.40, <0.60). Two parameters showed poor agreement (ICC ???0.70 and/or SDR ???0.60). The categorical variable showed poor agreement. Conclusion Agreement was best where landmark edges were well defined, acceptable where more ???reader judgment??? was needed, and poor where levator defects made landmarks difficult to identify. Automated measurement algorithms are under study and may improve agreement in the future. J. Magn. Reson. Imaging 2009;30:344???350. ?? 2009 Wiley-Liss, Inc.
Published: 2009

44. The identification of phosphoglycerate kinase-1 and histone H4 autoantibodies in pancreatic cancer patient serum using a natural protein microarray

Author: Department of Chemistry, University of Michigan, Ann Arbor, MI, USA, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Surgery, University of Michigan, Ann Arbor, MI, USA ; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA ; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA ; Department of Surgery, University of Michigan, 1150 West Medical Center Drive, Room A510B MSRB I, Ann Arbor, MI 48109-0656, USA Fax: +1-734-615-2088, Department of Statistics, Pennsylvania State University, University Park, PA, USA ; Department of Public Health Sciences, Penn State, University Park, PA, USA, Patwa, Tasneem H., Li, Chen, Poisson, Laila M., Kim, Hye-Yeung, Pal, Manoj, Ghosh, Debashis, Simeone, Diane M., Lubman, David M., Department of Chemistry, University of Michigan, Ann Arbor, MI, USA, Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA, Department of Surgery, University of Michigan, Ann Arbor, MI, USA ; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI, USA, Department of Chemistry, University of Michigan, Ann Arbor, MI, USA ; Department of Surgery, University of Michigan, Ann Arbor, MI, USA ; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA ; Department of Surgery, University of Michigan, 1150 West Medical Center Drive, Room A510B MSRB I, Ann Arbor, MI 48109-0656, USA Fax: +1-734-615-2088, Department of Statistics, Pennsylvania State University, University Park, PA, USA ; Department of Public Health Sciences, Penn State, University Park, PA, USA, Patwa, Tasneem H., Li, Chen, Poisson, Laila M., Kim, Hye-Yeung, Pal, Manoj, Ghosh, Debashis, Simeone, Diane M., and Lubman, David M.
Abstract: Protein microarrays have been used to explore whether a humoral response to pancreatic cancer-specific tumor antigens has utility as a biomarker of pancreatic cancer. To determine if such arrays can be used to identify novel autoantibodies in the sera from pancreatic cancer patients, proteins from a pancreatic adenocarcinoma cell line (MIAPACA) were resolved by 2-D liquid-based separations, and then arrayed on nitrocellulose slides. The slides were probed with serum from a set of patients diagnosed with pancreatic cancer and compared with age- and sex-matched normal subjects. To account for patient-to-patient variability, we used a rank-based non-parametric statistical testing approach in which proteins eliciting significant differences in the humoral response in cancer compared with control samples were identified. The prediction analysis for microarrays classification algorithm was used to explore the classification power of the proteins found to be differentially expressed in cancer and control sera. The generalization error of the classification analysis was estimated using leave-one-out cross-validation. A serum diagnosis of pancreatic cancer in this set was predicted with 86.7% accuracy, with a sensitivity and specificity of 93.3 and 80%, respectively. Candidate autoantibody biomarkers identified using this approach were studied for their classification power by performing a humoral response experiment on recombinant proteins using an independent sample set of 238 serum samples. Phosphoglycerate kinase-1 and histone H4 were noted to elicit a significant differential humoral response in cancer sera compared with age- and sex-matched sera from normal patients and patients with chronic pancreatitis and diabetes. This work demonstrates the use of natural protein arrays to study the humoral response as a means to search for the potential markers of cancer in serum.
Published: 2009

45. Reliability of quantitative sudomotor axon reflex testing and quantitative sensory testing in neuropathy of impaired glucose regulation

Author: Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA, Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA, Department of Neurology University of Utah, Salt Lake City, Utah, USA ; Department of Pathology, University of Utah, Salt Lake City, Utah, USA, Department of Neurology, University of Maryland and Maryland VA Healthcare System, 22 South Greene Street, Box 175, Baltimore, Maryland 21201-1595, USA ; Department of Neurology, University of Maryland and Maryland VA Healthcare System, 22 South Greene Street, Box 175, Baltimore, Maryland 21201-1595, USA, Department of Neurology University of Utah, Salt Lake City, Utah, USA, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA, Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA, Peltier, Amanda, Smith, A. Gordon, Russell, James W., Sheikh, Kiran, Bixby, Billie, Howard, James, Goldstein, Jonathan, Song, Yanna, Wang, Lily, Feldman, Eva L., Singleton, J. Robinson, Department of Neurology, University of Michigan, Ann Arbor, Michigan, USA, Department of Neurology, Vanderbilt University, Nashville, Tennessee, USA, Department of Neurology University of Utah, Salt Lake City, Utah, USA ; Department of Pathology, University of Utah, Salt Lake City, Utah, USA, Department of Neurology, University of Maryland and Maryland VA Healthcare System, 22 South Greene Street, Box 175, Baltimore, Maryland 21201-1595, USA ; Department of Neurology, University of Maryland and Maryland VA Healthcare System, 22 South Greene Street, Box 175, Baltimore, Maryland 21201-1595, USA, Department of Neurology University of Utah, Salt Lake City, Utah, USA, Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA, Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA, Peltier, Amanda, Smith, A. Gordon, Russell, James W., Sheikh, Kiran, Bixby, Billie, Howard, James, Goldstein, Jonathan, Song, Yanna, Wang, Lily, Feldman, Eva L., and Singleton, J. Robinson
Abstract: Reproducible neurophysiologic testing paradigms are critical for multicenter studies of neuropathy associated with impaired glucose regulation (IGR), yet the best methodologies and endpoints remain to be established. This study evaluates the reproducibility of neurophysiologic tests within a multicenter research setting. Twenty-three participants with neuropathy and IGR were recruited from two study sites. The reproducibility of quantitative sudomotor axon reflex test (QSART) and quantitative sensory test (QST) (using the CASE IV system) was determined in a subset of patients at two sessions, and it was calculated from intraclass correlation coefficients (ICCs). QST (cold detection threshold: ICC = 0.80; vibration detection threshold: ICC = 0.75) was more reproducible than QSART (ICC foot = 0.52). The performance of multiple tests in one setting did not improve reproducibility of QST. QST reproducibility in our IGR patients was similar to reports of other studies. QSART reproducibility was significantly lower than QST. In this group of patients, the reproducibility of QSART was unacceptable for use as a secondary endpoint measure in clinical research trials. Muscle Nerve, 2008
Published: 2009

46. A penalized likelihood approach for mixture cure models

Author: Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann Arbor, MI 48109, U.S.A., INSERM U897 Biostatistique, Bordeaux F-33076, France ; Universit?? Victor S??galen Bordeaux 2, Bordeaux F-33076, France ; Department of Large Animals Medicine, National Veterinary School, 23 Chemin des Capelles, 31076 Toulouse, France, INSERM U897 Biostatistique, Bordeaux F-33076, France ; Universit?? Victor S??galen Bordeaux 2, Bordeaux F-33076, France, Corbi??re, Fabien, Commenges, Daniel, Taylor, Jeremy M. G., Joly, Pierre, Department of Biostatistics, 1420 Washington Heights, University of Michigan, Ann Arbor, MI 48109, U.S.A., INSERM U897 Biostatistique, Bordeaux F-33076, France ; Universit?? Victor S??galen Bordeaux 2, Bordeaux F-33076, France ; Department of Large Animals Medicine, National Veterinary School, 23 Chemin des Capelles, 31076 Toulouse, France, INSERM U897 Biostatistique, Bordeaux F-33076, France ; Universit?? Victor S??galen Bordeaux 2, Bordeaux F-33076, France, Corbi??re, Fabien, Commenges, Daniel, Taylor, Jeremy M. G., and Joly, Pierre
Abstract: Cure models have been developed to analyze failure time data with a cured fraction. For such data, standard survival models are usually not appropriate because they do not account for the possibility of cure. Mixture cure models assume that the studied population is a mixture of susceptible individuals, who may experience the event of interest, and non-susceptible individuals that will never experience it. Important issues in mixture cure models are estimation of the baseline survival function for susceptibles and estimation of the variance of the regression parameters. The aim of this paper is to propose a penalized likelihood approach, which allows for flexible modeling of the hazard function for susceptible individuals using M-splines. This approach also permits direct computation of the variance of parameters using the inverse of the Hessian matrix. Properties and limitations of the proposed method are discussed and an illustration from a cancer study is presented. Copyright ?? 2008 John Wiley & Sons, Ltd.
Published: 2009

47. Genome-wide linkage scan for prostate cancer susceptibility from the university of michigan prostate cancer genetics project: Suggestive evidence for linkage at 16q23

Author: Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Internal Medicine and Urology, University of Michigan Medical School, Ann Arbor, Michigan ; Professor of Internal Medicine And Urology, University of Michigan Health System, 7216 Cancer Center, SPC 5948, 1500 East Medical Center Drive Ann Arbor, MI 48109., Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina ; The Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, Karmanos Cancer Institute, Detroit, Michigan ; Department of Internal Medicine, Wayne State University, Detroit, Michigan, The Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, Lange, Ethan M., Beebe-Dimmer, Jennifer L., Ray, Anna M., Zuhlke, Kimberly A., Ellis, Jaclyn, Wang, Yunfei, Walters, Sarah, Cooney, Kathleen A., Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan, Department of Internal Medicine, University of Michigan Medical School, Ann Arbor, Michigan ; Department of Internal Medicine and Urology, University of Michigan Medical School, Ann Arbor, Michigan ; Professor of Internal Medicine And Urology, University of Michigan Health System, 7216 Cancer Center, SPC 5948, 1500 East Medical Center Drive Ann Arbor, MI 48109., Department of Genetics, University of North Carolina, Chapel Hill, North Carolina ; Department of Biostatistics, University of North Carolina, Chapel Hill, North Carolina ; The Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, Karmanos Cancer Institute, Detroit, Michigan ; Department of Internal Medicine, Wayne State University, Detroit, Michigan, The Curriculum in Genetics and Molecular Biology, University of North Carolina, Chapel Hill, North Carolina, Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, Lange, Ethan M., Beebe-Dimmer, Jennifer L., Ray, Anna M., Zuhlke, Kimberly A., Ellis, Jaclyn, Wang, Yunfei, Walters, Sarah, and Cooney, Kathleen A.
Abstract: BACKGROUND Prostate cancer linkage studies have been used to localize rare and presumably highly penetrant cancer susceptibility genes. Underlying genetic heterogeneity, as well as the high sporadic background of the disease, has resulted in many signals that are often not reproducible between research studies. METHODS We conducted a SNP-based genome wide linkage scan on 131 Caucasian prostate cancer families participating in the University of Michigan Prostate Cancer Genetics Project (PCGP). RESULTS The strongest evidence for linkage was detected at 16q23 (LOD???=???2.70 at rs1079635). Prostate cancer linkage to the same region of 16q23 has been observed by others and the region contains several strong candidate genes including the known prostate cancer tumor suppressor genes ATBF1 and WWOX . This linkage signal was not detected in our prior linkage study on 175 PCGP families, illustrating the genetic heterogeneity underlying prostate cancer susceptibility. CONCLUSIONS Further linkage studies in combination with tumor analyses from linked families are in progress to identify the putative hereditary prostate cancer gene at 16q23. Prostate 69:385???391, 2009. ?? 2008 Wiley-Liss, Inc.
Published: 2009

48. Tests for gene-environment interaction from case-control data: a novel study of type I error, power and designs This article is a US government work, and, as such, is in the public domain in the United States of America.

Author: Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, Epidemiology and Human Genetics, University of Michigan, Ann Arbor, Michigan, Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine, CHS National Israeli Cancer Control Center, Haifa, Israel, IDIBELL, Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, Mukherjee, Bhramar, Ahn, Jaeil, Gruber, Stephen B., Rennert, Gad, Moreno, Victor, Chatterjee, Nilanjan, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, Epidemiology and Human Genetics, University of Michigan, Ann Arbor, Michigan, Department of Community Medicine and Epidemiology, Carmel Medical Center and Technion Faculty of Medicine, CHS National Israeli Cancer Control Center, Haifa, Israel, IDIBELL, Catalan Institute of Oncology, L'Hospitalet, Barcelona, Spain, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland ; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, Maryland, Mukherjee, Bhramar, Ahn, Jaeil, Gruber, Stephen B., Rennert, Gad, Moreno, Victor, and Chatterjee, Nilanjan
Abstract: To evaluate the risk of a disease associated with the joint effects of genetic susceptibility and environmental exposures, epidemiologic researchers often test for non-multiplicative gene-environment effects from case-control studies. In this article, we present a comparative study of four alternative tests for interactions: (i) the standard case-control method; (ii) the case-only method, which requires an assumption of gene-environment independence for the underlying population; (iii) a two-step method that decides between the case-only and case-control estimators depending on a statistical test for the gene-environment independence assumption and (iv) a novel empirical-Bayes (EB) method that combines the case-control and case-only estimators depending on the sample size and strength of the gene-environment association in the data. We evaluate the methods in terms of integrated Type I error and power, averaged with respect to varying scenarios for gene-environment association that are likely to appear in practice. These unique studies suggest that the novel EB procedure overall is a promising approach for detection of gene-environment interactions from case-control studies. In particular, the EB procedure, unlike the case-only or two-step methods, can closely maintain a desired Type I error under realistic scenarios of gene-environment dependence and yet can be substantially more powerful than the traditional case-control analysis when the gene-environment independence assumption is satisfied, exactly or approximately. Our studies also reveal potential utility of some non-traditional case-control designs that samples controls at a smaller rate than the cases. Apart from the simulation studies, we also illustrate the different methods by analyzing interactions of two commonly studied genes, N -acetyl transferase type 2 and glutathione s -transferase M1, with smoking and dietary exposures, in a large case-control study of colorectal cancer. Genet. Epidemiol . 2008. P
Published: 2008

49. Factors predicting additional disease in the axilla in patients with positive sentinel lymph nodes after neoadjuvant chemotherapy Presented in part at the Annual Meeting of the American Society of Clinical Oncology, Atlanta, Georgia, June 2???6, 2006.

Author: Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, Department Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston Texas, Department Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ; Fax: (713) 792-4689 ; Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, Jeruss, Jacqueline S., Newman, Lisa A., Ayers, Gregory D., Cristofanilli, Massimo, Broglio, Kristine R., Meric-Bernstam, Funda, Yi, Min, Waljee, Jennifer F., Ross, Merrick I., Hunt, Kelly K., Department of Surgery, University of Michigan Medical School, Ann Arbor, Michigan, Department Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, Tennessee, Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, Division of Quantitative Sciences, The University of Texas M. D. Anderson Cancer Center, Houston Texas, Department Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas ; Fax: (713) 792-4689 ; Department of Surgical Oncology, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 444, Houston, TX 77030, Jeruss, Jacqueline S., Newman, Lisa A., Ayers, Gregory D., Cristofanilli, Massimo, Broglio, Kristine R., Meric-Bernstam, Funda, Yi, Min, Waljee, Jennifer F., Ross, Merrick I., and Hunt, Kelly K.
Abstract: BACKGROUND. The utility of sentinel lymph node (SNL) biopsy (SLNB) as a predictor of axillary lymph node status is similar in patients who receive neoadjuvant chemotherapy and patients who undergo surgery first. The authors of this study hypothesized that patients with positive SLNs after neoadjuvant therapy would have unique clinicopathologic factors that would be predictive of additional positive non-SLNs distinct from patients who underwent surgery first. METHODS. One hundred four patients were identified who received neoadjuvant chemotherapy, had a positive SLN, and underwent axillary dissection between 1997 and 2005. At the time of presentation, 66 patients had clinically negative lymph nodes by ultrasonography, and 38 patients had positive lymph nodes confirmed by fine-needle aspiration. Eighteen factors were assessed for their ability to predict positive non-SLNs using chi-square and logistic regression analysis with a bootstrapped, backwards elimination procedure. The resulting nomogram was tested by using a patient cohort from another institution. RESULTS. Patients with clinically negative lymph nodes at presentation were less likely than patients with positive lymph nodes to have positive non-SLNs (47% vs 71%; P = .017). On multivariate analysis, lymphovascular invasion, the method for detecting SLN metastasis, multicentricity, positive axillary lymph nodes at presentation, and pathologic tumor size retained grouped significance with a bootstrap-adjusted area under the curve (AUC) of 0.762. The resulting nomogram was validated in the external patient cohort (AUC, 0.78). CONCLUSIONS. A significant proportion of patients with positive SLNs after neoadjuvant chemotherapy had no positive non-SLNs. The use of a nomogram based on 5 predictive variables that were identified in this study may be useful for predicting the risk of positive non-SLNs in patients who have positive SLNs after chemotherapy. Cancer 2008. ?? 2008 American Cancer Society.
Published: 2008

50. Racial differences in cervical cancer survival in the Detroit metropolitan area

Author: Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, Mclaren Regional Medical Center, Michigan State University, Flint, Michigan, Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan ; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan ; Division of Hematology and Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan ; Fax: (313) 576-8764 ; Barbara Ann Karmanos Cancer Institute, 4100 John R, Room 4221 Hudson Webber Cancer Research Building, Detroit, MI 48202, Movva, Sujana, Noone, Anne-Michelle, Banerjee, Mousumi, Patel, Divya A., Schwartz, Kendra, Yee, Cecilia L., Simon, Michael S., Department of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, Michigan, Department of Obstetrics and Gynecology, University of Michigan, Ann Arbor, Michigan, Department of Internal Medicine, Mclaren Regional Medical Center, Michigan State University, Flint, Michigan, Department of Family Medicine and Public Health Sciences, Wayne State University, Detroit, Michigan ; Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan, Population Studies and Prevention Program, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan ; Division of Hematology and Oncology, Karmanos Cancer Institute at Wayne State University, Detroit, Michigan ; Fax: (313) 576-8764 ; Barbara Ann Karmanos Cancer Institute, 4100 John R, Room 4221 Hudson Webber Cancer Research Building, Detroit, MI 48202, Movva, Sujana, Noone, Anne-Michelle, Banerjee, Mousumi, Patel, Divya A., Schwartz, Kendra, Yee, Cecilia L., and Simon, Michael S.
Abstract: BACKGROUND African-American (AA) women have lower survival rates from cervical cancer compared with white women. The objective of this study was to examine the influence of socioeconomic status (SES) and other variables on racial disparities in overall survival among women with invasive cervical cancer. METHODS One thousand thirty-six women (705 white women and 331 AA women) who were diagnosed with primary invasive cancer of the cervix between 1988 and 1992 were identified through the Metropolitan Detroit Cancer Surveillance System (MDCSS), a registry in the Surveillance, Epidemiology, and End Results (SEER) database. Pathology, treatment, and survival data were obtained through SEER. SES was categorized by using occupation, poverty, and educational status at the census tract level. Cox proportional hazards models were used to compare overall survival between AA women and white women adjusting for sociodemographics, clinical presentation, and treatment. RESULTS AA women were more likely to present at an older age ( P < .001), with later stage disease ( P < .001), and with squamous histology ( P = .01), and they were more likely to reside in a census tract categorized as Working Poor (WP) ( P < .001). After multivariate adjustment, race no longer had a significant impact on survival. Women who resided in a WP census tract had a higher risk of death than women from a Professional census tract ( P = .05). There was a significant interaction between disease stage and time with the effect of stage on survival attenuated after 6 years. CONCLUSIONS In this study, factors that affected access to medical care appeared to have a more important influence than race on the long-term survival of women with invasive cervical cancer. Cancer 2008. © 2008 American Cancer Society.
Published: 2008

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