Medicine and Health Sciences Commons^™

Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.

Dr. Torstein Tengs

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …

Paradoxical Results Of Adaptive False Discovery Rate Procedures In Neuroimaging Studies, Philip T. Reiss, Armin Schwartzman, Feihan Lu, Lei Huang, Erika Proal

Philip T. Reiss

Adaptive false discovery rate (FDR) procedures, which offer greater power than the original FDR procedure of Benjamini and Hochberg, are often applied to statistical maps of the brain. When a large proportion of the null hypotheses are false, as in the case of widespread effects such as cortical thinning throughout much of the brain, adaptive FDR methods can surprisingly reject more null hypotheses than not accounting for multiple testing at all—i.e., using uncorrected p-values. A straightforward mathematical argument is presented to explain why this can occur with the q-value method of Storey and colleagues, and a simulation study shows that …

Prediction Of Radiation Pneumonitis By Dose-Volume Histogram Parameters In Lung Cancer--A Systematic Review, George Rodrigues, Michael Lock, David D'Souza, Edward Yu, Jake Van Dyk

Michael Lock

BACKGROUND AND PURPOSE: To perform a systematic review of the predictive ability of various dose-volume histogram (DVH) parameters (V(dose), mean lung dose (MLD), and normal tissue complication probability (NTCP)) in the incidence of radiation pneumonitis (RP) caused by external-beam radiation therapy.

METHODS AND MATERIALS: Studies assessing the relationship between CT-based DVH reduction parameters and RP rate in radically treated lung cancer were eligible for the review. Synonyms for RP, lung cancer, DVH and its associated parameters (NTCP, V(20), V(30), MLD) were combined in a search strategy involving electronic databases, secondary reference searching, and consultation with experts. Individual or group data …

Technology Assessment Of Automated Atlas Based Segmentation In Prostate Bed Contouring, Jeremiah Hwee, Alexander Louie, Stewart Gaede, Glenn Bauman, David D'Souza, Tracy Sexton, Michael Lock, Belal Ahmad, George Rodrigues

Michael Lock

BACKGROUND: Prostate bed (PB) contouring is time consuming and associated with inter-observer variability. We evaluated an automated atlas-based segmentation (AABS) engine in its potential to reduce contouring time and inter-observer variability.

METHODS: An atlas builder (AB) manually contoured the prostate bed, rectum, left femoral head (LFH), right femoral head (RFH), bladder, and penile bulb of 75 post-prostatectomy cases to create an atlas according to the recent RTOG guidelines. 5 other Radiation Oncologists (RO) and the AABS contoured 5 new cases. A STAPLE contour for each of the 5 patients was generated. All contours were anonymized and sent back to the …

A Pooled Analysis Of Smoking And Colorectal Cancer: Timing Of Exposure And Interactions With Environmental Factors

Shuo Jiao

Background:Considerable evidence suggests that cigarette smoking is associated with a higher risk of colorectal cancer. What is unclear, however, is the impact of quitting smoking on risk attenuation and whether other risk factors for colorectal cancer modify this association. Methods:We performed a pooled analysis of 8 studies, including 6,796 colorectal cancer cases and 7,770 controls to evaluate the association between cigarette smoking history and colorectal cancer risk, and to investigate potential effect modification by other risk factors. Results:Current smokers (OR=1.26, 95% CI=1.11-1.43) and former smokers (OR=1.18, 95% CI=1.09-1.27), relative to never smokers, showed higher risks of colorectal cancer. Former smokers …

Prevalence Of Tick Borne Encephalitis Virus In Tick Nymphs In Relation To Climatic Factors On The Southern Coast Of Norway, Torstein Tengs Dr.

Dr. Torstein Tengs

BACKGROUND

Tick-borne encephalitis (TBE) is among the most important vector borne diseases of humans in Europe and is currently identified as a major health problem in many countries. TBE endemic zones have expanded over the past two decades, as well as the number of reported cases within endemic areas. Multiple factors are ascribed for the increased incidence of TBE, including climatic change. The number of TBE cases has also increased in Norway over the past decade, and the human cases cluster along the southern coast of Norway. In Norway the distribution and prevalence of TBE virus (TBEV) in tick populations …

Big Data And The Future, Sherri Rose

Sherri Rose

No abstract provided.

Function-On-Scalar Regression With The Refund Package, Philip T. Reiss

Philip T. Reiss

No abstract provided.

A Strain Of Piscine Myocarditis Virus (Pmcv) Infecting Argentina Silus (Ascanius), Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

Comparing Years Of Healthy Life, Measured In 16 Ways, For Normal Weight And Overweight Older Adults, Paula Diehr

Paula Diehr

Introduction. The traditional definitions of overweight and obesity are not age specific, even though the relationship of weight to mortality is different for older adults. Effects of adiposity on aspects of health beside mortality have not been well investigated. Methods. We calculated the number of years of healthy life (YHL) in the 10 years after baseline, for 5,747 older adults. YHL was defined in 16 different ways. We compared Normal and Overweight persons, classified either by bodymass index (BMI) or by waist circumference (WC). Findings. YHL for Normal and Overweight persons differed significantly in 25% of the comparisons, of which …

Estimating The Impact Of Community-Level Interventions: The Search Trial And Hiv Prevention In Sub-Saharan Africa, Laura Balzer, Maya Petersen, Joshua Schwab, Mark Van Der Laan

Laura B. Balzer

Evaluation of community level interventions to prevent HIV infection presents significant methodological challenges. Even when it is feasible to randomly assign a treatment versus control level of the intervention to each community in a sample, measurement of incident HIV infection remains difficult. In this talk we describe an experimental design developed for the SEARCH Trial, a large community randomized trial that will evaluate the impact of expanded treatment on incident HIV and other outcomes. Regular community-wide testing campaigns are conducted and a random sample of community members who fail to attend a campaign are tracked. The data generated by this …

Why Match In Individually And Cluster Randomized Trials?, Laura B. Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thought to improve study credibility. Matching is also implemented to increase study power. This article compares the asymptotic efficiency of the pair-matched design, where units are matched on baseline covariates and the treatment randomized within pairs, to the independent design, where units are randomly paired and the treatment randomized within pairs. We focus on estimating the average treatment effect and use the efficient influence curve to understand the information provided by …

Quantification Of Piscine Reovirus (Prv) At Different Stages Of Atlantic Salmon Salmo Salar Production, Torstein Tengs Dr.

Dr. Torstein Tengs

The newly described piscine reovirus (PRV) appears to be associated with the development of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon Salmo salar L. PRV seems to be ubiquitous among fish in Norwegian salmon farms, but high viral loads and tissue distribution support a causal relationship between virus and disease. In order to improve understanding of the distribution of PRV in the salmon production line, we quantified PRV by using real-time PCR on heart samples collected at different points in the life cycle from pre-smolts to fish ready for slaughter. PRV positive pre-smolts were found in about …

Why Match In Individually And Cluster Randomized Trials?, Laura Balzer, Maya Petersen, Mark Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thereby thought to improve study credibility. Matching is also implemented to increase study power. Analogue to Rose and van der Laan (2009), this article investigates the asymptotic efficiency of pair-matching individuals or clusters relative to not matching in randomized trials. We focus on estimating the average treatment effect. We use the efficient influence curve to understand the information provided by each design for estimation of the target causal parameter. Our approach …

Smoothness Selection For Penalized Quantile Regression Splines, Philip T. Reiss, Lei Huang

Philip T. Reiss

Modern data-rich analyses may call for fitting a large number of nonparametric quantile regressions. For example, growth charts may be constructed for each of a collection of variables, to identify those for which individuals with a disorder tend to fall in the tails of their age-specific distribution; such variables might serve as developmental biomarkers. When such analyses are carried out by penalized spline smoothing, reliable automatic selection of the smoothing parameter is particularly important. We show that two popular methods for smoothness selection may tend to overfit when estimating extreme quantiles as a smooth function of a predictor such as …

Semiparametric Methods For Mapping Brain Development, Philip T. Reiss, Yin-Hsiu Chen, Lan Huo

Philip T. Reiss

No abstract provided.

Backcalculation Of Hiv Infection Rates, Peter Bacchetti, Mark Segal, Nicholas Jewell

Mark R Segal

Backcalculation is an important method of reconstructing past rates of human immunodeficiency virus (HIV) infection and for estimating current prevalence of HIV infection and future incidence of acquired immunodeficiency syndrome (AIDS). This paper reviews the backcalculation techniques, focusing on the key assumptions of the method, including the necessary information regarding incubation, reporting delay, and models for the infection curve. A summary is given of the extent to which the appropriate external information is available and whether checks of the relevant assumptions are possible through use of data on AIDS incidence from surveillance systems. A likelihood approach to backcalculation is described …

Characterization Of Gene–Environment Interactions For Colorectal Cancer Susceptibility Loci

Shuo Jiao

Genome-wide association studies (GWAS) have identified more than a dozen loci associated with colorectal cancer (CRC) risk. Here, we examined potential effect-modification between single-nucleotide polymorphisms (SNP) at 10 of these loci and probable or established environmental risk factors for CRC in 7,016 CRC cases and 9,723 controls from nine cohort and case–control studies. We used meta-analysis of an efficient empirical-Bayes estimator to detect potential multiplicative interactions between each of the SNPs [rs16892766 at 8q23.3 (EIF3H/UTP23), rs6983267 at 8q24 (MYC), rs10795668 at 10p14 (FLJ3802842), rs3802842 at 11q23 (LOC120376), rs4444235 at 14q22.2 (BMP4), rs4779584 at 15q13 (GREM1), rs9929218 at 16q22.1 (CDH1), rs4939827 …

Powerful Cocktail Methods For Detecting Genome-Wide Gene-Environment Interaction, Li Hsu, Shuo Jiao, James Y. Dai, Carolyn M. Hutter, Ulrike Peters, Charles Kooperberg

Shuo Jiao

Identifying gene and environment interaction (G × E) can provide insights into biological networks of complex diseases, identify novel genes that act synergistically with environmental factors, and inform risk prediction. However, despite the fact that hundreds of novel disease-associated loci have been identified from genome-wide association studies (GWAS), few G×Es have been discovered. One reason is thatmost studies are underpowered for detecting these interactions. Several new methods have been proposed to improve power for G × E analysis, but performance varies with scenario. In this article, we present a module-based approach to integrating various methods that exploits each method’s most …

Loss Function Based Ranking In Two-Stage, Hierarchical Models, Rongheng Lin, Thomas A. Louis, Susan M. Paddock, Greg Ridgeway

Rongheng Lin

Several authors have studied the performance of optimal, squared error loss (SEL) estimated ranks. Though these are effective, in many applications interest focuses on identifying the relatively good (e.g., in the upper 10%) or relatively poor performers. We construct loss functions that address this goal and evaluate candidate rank estimates, some of which optimize specific loss functions. We study performance for a fully parametric hierarchical model with a Gaussian prior and Gaussian sampling distributions, evaluating performance for several loss functions. Results show that though SEL-optimal ranks and percentiles do not specifically focus on classifying with respect to a percentile cut …

Ranking Usrds Provider-Specific Smrs From 1998-2001, Rongheng Lin, Thomas A. Louis, Susan M. Paddock, Greg Ridgeway

Rongheng Lin

Provider profiling (ranking, "league tables") is prevalent in health services research. Similarly, comparing educational institutions and identifying differentially expressed genes depend on ranking. Effective ranking procedures must be structured by a hierarchical (Bayesian) model and guided by a ranking-specific loss function, however even optimal methods can perform poorly and estimates must be accompanied by uncertainty assessments. We use the 1998-2001 Standardized Mortality Ratio (SMR) data from United States Renal Data System (USRDS) as a platform to identify issues and approaches. Our analyses extend Liu et al. (2004) by combining evidence over multiple years via an AR(1) model; by considering estimates …

Racial And Ethnic Differences In Hospice Use Among Patients With Heart Failure, Jane Givens, Jennifer Tjia, Chao Zhou, Ezekiel Emanuel, Arlene Ash

Jennifer Tjia

BACKGROUND: Heart failure is the leading noncancer diagnosis for patients in hospice care and the leading cause of hospitalization among Medicare beneficiaries. Racial and ethnic differences in hospice patients are well documented for patients with cancer but poorly described for those with heart failure.

METHODS: On the basis of a national sample of 98 258 Medicare beneficiaries 66 years and older on January 1, 2001, with a diagnosis of heart failure who had at least 1 physician or hospital encounter and who were not enrolled in hospice care between January 1 and December 31, 2000, we determined the effect of …

Disparities In Combination Drug Therapy Use In Older Adults With Coronary Heart Disease: A Cross-Sectional Time-Series In A Nationally Representative Us Sample, Jennifer Tjia, Becky Briesacher, Dawei Xie, Jason Fu, Robert Goldberg

Jennifer Tjia

BACKGROUND: Despite evidence of effective combination drug therapy for secondary prevention of coronary heart disease (CHD), older adults with this condition remain undertreated.

OBJECTIVE: To describe time trends (1992-2003) in the adoption of combination cardiac drug therapies (beta-blockers [beta-adrenoceptor antagonists], ACE inhibitors or angiotensin II type 1 receptor antagonists [angiotensin receptor blockers; ARBs], and lipid-lowering agents) among older adults in the US with CHD and to identify factors associated with not using combination therapy.

METHODS: The study took the form of a cross-sectional time-series. The study population consisted of a nationally representative sample of adults aged >or=65 years with CHD …

Trends And Outcomes Associated With Angiotensin-Converting Enzyme Inhibitors, Chyke Doubeni, Carol Bigelow, Darleen Lessard, Frederick Spencer, Jorge Yarzebski, Joel Gore, Jerry Gurwitz, Robert Goldberg

Chyke A. Doubeni

BACKGROUND: Limited recent data are available describing the patterns of use of angiotensin converting enzyme inhibitor (ACEI) therapy in patients with acute myocardial infarction (AMI), particularly from the more generalizable population-based setting. The purpose of this study was to examine trends in the receipt of ACEIs and associated short-term outcomes in patients hospitalized with AMI in a large Northeastern community.

METHODS: We conducted a community-wide study of 7991 patients hospitalized with AMI in all metropolitan Worcester, Massachusetts, medical centers during 8 annual periods between 1990 and 2003.

RESULTS: Among all patients, 44% received ACEI therapy during their acute hospitalization. There …

Treatment Practices And Outcomes Of Patients With Established Peripheral Arterial Disease Hospitalized With Acute Myocardial Infarction In A Community Setting, Frederick Spencer, Darleen Lessard, Chyke Doubeni, Jorge Yarzebski, Joel Gore, Robert Goldberg

Chyke A. Doubeni

BACKGROUND: There are little contemporary data available describing the hospital and long-term outcomes of patients with peripheral arterial disease (PAD) who are hospitalized with acute myocardial infarction (AMI). The objectives of our population-based study were to examine the hospital and long-term outcomes, as well as the use of different treatment practices, among patients with established PAD who were hospitalized with AMI. METHODS: The study sample consisted of 4480 patients hospitalized with AMI at all Worcester, Mass, medical centers in 4 alternate years between 1997 and 2003. RESULTS: Among the metropolitan Worcester residents hospitalized with AMI, 13.5% had a history of …

Statistical Methods For Proteomic Biomarker Discovery Based On Feature Extraction Or Functional Modeling Approaches, Jeffrey S. Morris

Jeffrey S. Morris

In recent years, developments in molecular biotechnology have led to the increased promise of detecting and validating biomarkers, or molecular markers that relate to various biological or medical outcomes. Proteomics, the direct study of proteins in biological samples, plays an important role in the biomarker discovery process. These technologies produce complex, high dimensional functional and image data that present many analytical challenges that must be addressed properly for effective comparative proteomics studies that can yield potential biomarkers. Specific challenges include experimental design, preprocessing, feature extraction, and statistical analysis accounting for the inherent multiple testing issues. This paper reviews various computational …

Integrative Bayesian Analysis Of High-Dimensional Multi-Platform Genomics Data, Wenting Wang, Veerabhadran Baladandayuthapani, Jeffrey S. Morris, Bradley M. Broom, Ganiraju C. Manyam, Kim-Anh Do

Jeffrey S. Morris

Motivation: Analyzing data from multi-platform genomics experiments combined with patients’ clinical outcomes helps us understand the complex biological processes that characterize a disease, as well as how these processes relate to the development of the disease. Current integration approaches that treat the data are limited in that they do not consider the fundamental biological relationships that exist among the data from platforms.

Statistical Model: We propose an integrative Bayesian analysis of genomics data (iBAG) framework for identifying important genes/biomarkers that are associated with clinical outcome. This framework uses a hierarchical modeling technique to combine the data obtained from multiple platforms …

A Systematic Mapping Approach Of 16q12.2/Fto And Bmi In More Than 20,000 African Americans Narrows In On The Underlying Functional Variation: Results From The Population Architecture Using Genomics And Epidemiology (Page) Study

Shuo Jiao

Genetic variants in intron 1 of the fat mass– and obesity-associated (FTO) gene have been consistently associated with body mass index (BMI) in Europeans. However, follow-up studies in African Americans (AA) have shown no support for some of the most consistently BMI–associated FTO index single nucleotide polymorphisms (SNPs). This is most likely explained by different race-specific linkage disequilibrium (LD) patterns and lower correlation overall in AA, which provides the opportunity to fine-map this region and narrow in on the functional variant. To comprehensively explore the 16q12.2/FTO locus and to search for second independent signals in the broader region, we fine-mapped …

Genome-Wide Search For Gene-Gene Interactions In Colorectal Cancer

Shuo Jiao

Genome-wide association studies (GWAS) have successfully identified a number of single-nucleotide polymorphisms (SNPs) associated with colorectal cancer (CRC) risk. However, these susceptibility loci known today explain only a small fraction of the genetic risk. Gene-gene interaction (GxG) is considered to be one source of the missing heritability. To address this, we performed a genome-wide search for pair-wise GxG associated with CRC risk using 8,380 cases and 10,558 controls in the discovery phase and 2,527 cases and 2,658 controls in the replication phase. We developed a simple, but powerful method for testing interaction, which we term the Average Risk Due to …

James-Stein Estimation And The Benjamini-Hochberg Procedure, Debashis Ghosh

Debashis Ghosh

For the problem of multiple testing, the Benjamini-Hochberg (B-H) procedure has become a very popular method in applications. Based on a spacings theory representation of the B-H procedure, we are able to motivate the use of shrinkage estimators for modifying the B-H procedure. Several generalizations in the paper are discussed, and the methodology is applied to real and simulated datasets.