Biostatistics Commons^™

Using A Respiratory Navigator Significantly Reduces Variability When Quantifying Left Ventricular Torsion With Cardiovascular Magnetic Resonance, Sean M. Hamlet, Christopher M. Haggerty, Jonathan D. Suever, Gregory J. Wehner, Kristin N. Andres, David K. Powell, Richard J. Charnigo, Brandon K. Fornwalt

Electrical and Computer Engineering Faculty Publications

Background: Left ventricular (LV) torsion is an important indicator of cardiac function that is limited by high inter-test variability (50% of the mean value). We hypothesized that this high inter-test variability is partly due to inconsistent breath-hold positions during serial image acquisitions, which could be significantly improved by using a respiratory navigator for cardiovascular magnetic resonance (CMR) based quantification of LV torsion.

Methods: We assessed respiratory-related variability in measured LV torsion with two distinct experimental protocols. First, 17 volunteers were recruited for CMR with cine displacement encoding with stimulated echoes (DENSE) in which a respiratory navigator was used to measure …

Conventional Early Infant Diagnosis In Lesotho From Specimen Collection To Results Usage To Manage Patients: Where Are The Bottlenecks?, Appolinaire Tiam, Michelle M Gill, Heather J Hoffman, Anthony Isavwa, Mafusi Mokone, Matokelo Foso, Jeffrey T Safrit, Lynne M Mofenson, Thorkild Tylleskär, Laura Guay

Epidemiology Faculty Publications

INTRODUCTION: Early infant diagnosis is an important step in identifying children infected with HIV during the perinatal period or in utero. Multiple factors contribute to delayed antiretroviral treatment initiation for HIV-infected children, including delays in the early infant HIV diagnosis cascade.

METHODS: We conducted a retrospective study to evaluate early infant diagnosis turnaround times in Lesotho. Trained staff reviewed records of HIV-exposed infants (aged-6-8 weeks) who received an HIV test during 2011. Study sites were drawn from Highlands, Foothills and Lowlands regions of Lesotho. Central laboratory database data were linked to facility and laboratory register information. Turnaround time geometric means …

Genomics And Csf Analyses Implicate Thyroid Hormone In Hippocampal Sclerosis Of Aging, Peter T. Nelson, Yuriko Katsumata, Kwangsik Nho, Sergey C. Artiushin, Gregory A. Jicha, Wang-Xia Wang, Erin L. Abner, Andrew J. Saykin, Walter A. Kukull, Alzheimer’S Disease Neuroimaging Initiative (Adni), David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain …

Self-Reported Sleep Apnea And Dementia Risk: Findings From The Prevention Of Alzheimer's Disease With Vitamin E And Selenium Trial, Xiuhua Ding, Richard J. Kryscio, Joshua Turner, Gregory A. Jicha, Gregory E. Cooper, Allison M. Caban-Holt, Frederick A. Schmitt, Erin L. Abner

Sanders-Brown Center on Aging Faculty Publications

OBJECTIVES: To investigate the association between baseline sleep apnea and risk of incident dementia in the Prevention of Alzheimer's Disease with Vitamin E and Selenium (PREADViSE) study and to explore whether the association depends on apolipoprotein E (APOE) ɛ4 allele status.

DESIGN: Secondary analysis based on data collected during PREADViSE.

SETTING: Participants were assessed at 128 local clinical study sites during the clinical trial phase and later were followed by telephone from a centralized location.

PARTICIPANTS: Men enrolled in PREADViSE (without dementia or other active neurological conditions that affect cognition such as major psychiatric disorders, including depression; N = …

Albuminuria Changes And Cardiovascular And Renal Outcomes In Type 1 Diabetes: The Dcct/Edic Study., Ian H De Boer, Xiaoyu Gao, Patricia A Cleary, Ionut Bebu, John M Lachin, Mark E Molitch, Trevor Orchard, Andrew D Paterson, Bruce A Perkins, Michael W Steffes, Bernard Zinman

Epidemiology Faculty Publications

Background and objectives In trials of people with type 2 diabetes, albuminuria reduction with renin-angiotensin system inhibitors is associated with lower risks of cardiovascular events and CKD progression. We tested whether progression or remission of microalbuminuria is associated with cardiovascular and renal risk in a well characterized cohort of type 1 diabetes.

Design, setting, participants, & measurements We studied 1441 participants in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications study. Albumin excretion rate (AER) was quantified annually or biennially for up to 30 years. For each participant, albuminuria status was defined over time as normoalbuminuria (AER …

Fto Genotype And Weight Loss: Systematic Review And Meta-Analysis Of 9563 Individual Participant Data From Eight Randomised Controlled Trials., Katherine M Livingstone, Carlos Celis-Morales, George D Papandonatos, Bahar Erar, Jose C Florez, Kathleen A Jablonski, Cristina Razquin, Amelia Marti, Yoriko Heianza, Tao Huang, Frank M Sacks, Mathilde Svendstrup, Xuemei Sui, Timothy S Church, Tiina Jääskeläinen, Jaana Lindström, Jaakko Tuomilehto, Matti Uusitupa, Tuomo Rankinen, Wim H M Saris, Torben Hansen, Oluf Pedersen, Arne Astrup, Thorkild I A Sørensen, Lu Qi, George A Bray, Miguel A Martinez-Gonzalez, J Alfredo Martinez, Paul W Franks, Jeanne M Mccaffery, Jose Lara, John C Mathers

Epidemiology Faculty Publications

OBJECTIVE: To assess the effect of the FTO genotype on weight loss after dietary, physical activity, or drug based interventions in randomised controlled trials.

DESIGN: Systematic review and random effects meta-analysis of individual participant data from randomised controlled trials.

DATA SOURCES: Ovid Medline, Scopus, Embase, and Cochrane from inception to November 2015.

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Randomised controlled trials in overweight or obese adults reporting reduction in body mass index, body weight, or waist circumference by FTO genotype (rs9939609 or a proxy) after dietary, physical activity, or drug based interventions. Gene by treatment interaction models were fitted to individual …

The Impact Of Patient Navigation On The Delivery Of Diagnostic Breast Cancer Care In The National Patient Navigation Research Program: A Prospective Meta-Analysis., Tracy A Battaglia, Julie S Darnell, Naomi Ko, Fred Snyder, Electra D Paskett, Kristen J Wells, Elizabeth M Whitley, Jennifer J Griggs, Anand Karnad, Heather Young, Victoria Warren-Mears, Melissa A Simon, Elizabeth Calhoun

Epidemiology Faculty Publications

Patient navigation is emerging as a standard in breast cancer care delivery, yet multi-site data on the impact of navigation at reducing delays along the continuum of care are lacking. The purpose of this study was to determine the effect of navigation on reaching diagnostic resolution at specific time points after an abnormal breast cancer screening test among a national sample. A prospective meta-analysis estimated the adjusted odds of achieving timely diagnostic resolution at 60, 180, and 365 days. Exploratory analyses were conducted on the pooled sample to identify which groups had the most benefit from navigation. Clinics from six …

Correlation Of Maximal Inspiratory Pressure To Transdiaphragmatic Twitch Pressure In Intensive Care Unit Patients, Gerald S. Supinski, Philip M. Westgate, Leigh Ann Callahan

Internal Medicine Faculty Publications

Background: Respiratory muscle weakness contributes to respiratory failure in ICU patients. Unfortunately, assessment of weakness is difficult since the most objective test, transdiaphragmatic pressure in response to phrenic nerve stimulation (PdiTw), is difficult to perform. While most clinicians utilize maximum inspiratory pressure (Pimax) to assess strength, the relationship of this index to PdiTw has not been evaluated in a large ICU population. The purpose of the present study was to assess both PdiTw and Pimax in ICU patients to determine how these indices correlate with each other, what factors influence these indices, and how well these indices predict outcomes.

Methods: …

Arsenic In Drinking Water And Lung Cancer Mortality In The United States: An Analysis Based On Us Counties And 30 Years Of Observation (1950-1979)., Hamid Ferdosi, Elisabeth K Dissen, Nana Ama Afari-Dwamena, Ji Li, Rusan Chen, Manning Feinleib, Steven H Lamm

Epidemiology Faculty Publications

Background. To examine whether the US EPA (2010) lung cancer risk estimate derived from the high arsenic exposures (10-934 µg/L) in southwest Taiwan accurately predicts the US experience from low arsenic exposures (3-59 µg/L). Methods. Analyses have been limited to US counties solely dependent on underground sources for their drinking water supply with median arsenic levels of ≥3 µg/L. Results. Cancer risks (slopes) were found to be indistinguishable from zero for males and females. The addition of arsenic level did not significantly increase the explanatory power of the models. Stratified, or categorical, analysis yielded relative risks that hover about 1.00. …

Identification And Survival Outcomes Of A Cohort Of Patients With Cancer Of Unknown Primary In Ontario, Canada., Chong S Kim, Malek B Hannouf, Sisira Sarma, George B Rodrigues, Peter K Rogan, Salaheddin M Mahmud, Eric Winquist, Muriel Brackstone, Gregory S Zaric

Epidemiology and Biostatistics Publications

BACKGROUND: Cancer of unknown primary origin (CUP) is defined by the presence of pathologically identified metastatic disease without clinical or radiological evidence of a primary tumour. Our objective was to identify incident cases of CUP in Ontario, Canada, and determine the influence of histology and sites of metastases on overall survival (OS).

MATERIAL AND METHODS: We used the Ontario Cancer Registry (OCR) and the Same-Day Surgery and Discharge Abstract Database (SDS/DAD) to identify patients diagnosed with CUP in Ontario between 1 January 2000, and 31 December 2005. Patient diagnostic information, including histology and survival data, was obtained from the OCR. …

Abcc9/Sur2 In The Brain: Implications For Hippocampal Sclerosis Of Aging And A Potential Therapeutic Target, Peter T. Nelson, Gregory A. Jicha, Wang-Xia Wang, Eseosa T. Ighodaro, Sergey C. Artiushin, Colin G. Nichols, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

The ABCC9 gene and its polypeptide product, SUR2, are increasingly implicated in human neurologic disease, including prevalent diseases of the aged brain. SUR2 proteins are a component of the ATP-sensitive potassium (“K _ATP ”) channel, a metabolic sensor for stress and/or hypoxia that has been shown to change in aging. The K _ATP channel also helps regulate the neurovascular unit. Most brain cell types express SUR2, including neurons, astrocytes, oligodendrocytes, microglia, vascular smooth muscle, pericytes, and endothelial cells. Thus it is not surprising that ABCC9 gene variants are associated with risk for human brain diseases. For example, Cantu syndrome is …

Novel Human Abcc9/Sur2 Brain-Expressed Transcripts And An Eqtl Relevant To Hippocampal Sclerosis Of Aging, Peter T. Nelson, Wang-Xia Wang, Bernard R. Wilfred, Angela Wei, James Dimayuga, Qingwei Huang, Eseosa T. Ighodaro, Sergey C. Artiushin, David W. Fardo

Sanders-Brown Center on Aging Faculty Publications

ABCC9 genetic polymorphisms are associated with increased risk for various human diseases including hippocampal sclerosis of aging. The main goals of this study were 1 > to detect the ABCC9 variants and define the specific 3′ untranslated region (3′UTR) for each variant in human brain, and 2 > to determine whether a polymorphism (rs704180) associated with risk for hippocampal sclerosis of aging pathology is also associated with variation in ABCC9 transcript expression and/or splicing. Rapid amplification of ABCC9 cDNA ends (3′RACE) provided evidence of novel 3′ UTR portions of ABCC9 in human brain. In silico and experimental studies were performed focusing on …

Spectral Gene Set Enrichment (Sgse), H Robert Frost, Zhigang Li, Jason H. Moore

Dartmouth Scholarship

Gene set testing is typically performed in a supervised context to quantify the association between groups of genes and a clinical phenotype. In many cases, however, a gene set-based interpretation of genomic data is desired in the absence of a phenotype variable. Although methods exist for unsupervised gene set testing, they predominantly compute enrichment relative to clusters of the genomic variables with performance strongly dependent on the clustering algorithm and number of clusters. We propose a novel method, spectral gene set enrichment (SGSE), for unsupervised competitive testing of the association between gene sets and empirical data sources. SGSE first computes …

Reassessment Of Risk Genotypes (Grn, Tmem106b, And Abcc9 Variants) Associated With Hippocampal Sclerosis Of Aging Pathology, Peter T. Nelson, Wang-Xia Wang, Amanda B. Partch, Sarah E. Monsell, Otto Valladares, Sally R. Ellingson, Bernard R. Wilfred, Adam C. Naj, Li-San Wang, Walter A. Kukull, David W. Fardo

Pathology and Laboratory Medicine Faculty Publications

Hippocampal sclerosis of aging (HS-Aging) is a common high-morbidity neurodegenerative condition in elderly persons. To understand the risk factors for HS-Aging, we analyzed data from the Alzheimer’s Disease Genetics Consortium and correlated the data with clinical and pathologic information from the National Alzheimer’s Coordinating Center database. Overall, 268 research volunteers with HS-Aging and 2,957 controls were included; detailed neuropathologic data were available for all. The study focused on single-nucleotide polymorphisms previously associated with HS-Aging risk: rs5848 ( GRN ), rs1990622 ( TMEM106B ), and rs704180 ( ABCC9 ). Analyses of a subsample that was not previously evaluated (51 HS-Aging cases …

Characteristics Associated With Willingness To Participate In A Randomized Controlled Behavioral Clinical Trial Using Home-Based Personal Computers And A Webcam, Hiroko H. Dodge, Yuriko Katsumata, Jian Zhu, Nora Mattek, Molly Bowman, Mattie Gregor, Katherine Wild, Jeffrey A Kaye

Biostatistics Faculty Publications

BACKGROUND: Trials aimed at preventing cognitive decline through cognitive stimulation among those with normal cognition or mild cognitive impairment are of significant importance in delaying the onset of dementia and reducing dementia prevalence. One challenge in these prevention trials is sample recruitment bias. Those willing to volunteer for these trials could be socially active, in relatively good health, and have high educational levels and cognitive function. These participants' characteristics could reduce the generalizability of study results and, more importantly, mask trial effects. We developed a randomized controlled trial to examine whether conversation-based cognitive stimulation delivered through personal computers, a webcam …

The Effectiveness Of Teleglaucoma Versus In-Patient Examination For Glaucoma Screening: A Systematic Review And Meta-Analysis, Sera-Melisa Thomas, Maya M Jeyaraman, Maya Jeyaraman, William G Hodge, Cindy Hutnik, John Costella, Monali S Malvankar-Mehta

Epidemiology and Biostatistics Publications

BACKGROUND: Glaucoma is the leading cause of irreversible visual impairment in the world affecting 60.5 million people worldwide in 2010, which is expected to increase to approximately 79.6 million by 2020. Therefore, glaucoma screening is important to detect, diagnose, and treat patients at the earlier stages to prevent disease progression and vision loss. Teleglaucoma uses stereoscopic digital imaging to take ocular images, which are transmitted electronically to an ocular specialist. The purpose is to synthesize literature to evaluate teleglaucoma, its diagnostic accuracy, healthcare system benefits, and cost-effectiveness.

METHODS: A systematic search was conducted to help locate published and unpublished studies. …

Identifying Genetic Variants For Heart Rate Variability In The Acetylcholine Pathway, Harriëtte Riese, Loretto M. Muñoz, Catharina A. Hartman, Xiuhua Ding, Shaoyong Su, Albertine J. Oldehinkel, Arie M. Van Roon, Peter J. Van Der Most, Joop Lefrandt, Ron T. Gansevoort, Pim Van Der Harst, Niek Verweij, Carmilla M. M. Licht, Dorret I. Boomsma, Jouke-Jan Hottenga, Gonneke Willemsen, Brenda W. J. H. Penninx, Ilja M. Nolte, Eco J. C. De Geus, Xiaoling Wang, Harold Snieder

Biostatistics Faculty Publications

Heart rate variability is an important risk factor for cardiovascular disease and all-cause mortality. The acetylcholine pathway plays a key role in explaining heart rate variability in humans. We assessed whether 443 genotyped and imputed common genetic variants in eight key genes (CHAT, SLC18A3, SLC5A7, CHRNB4, CHRNA3, CHRNA, CHRM2 and ACHE) of the acetylcholine pathway were associated with variation in an established measure of heart rate variability reflecting parasympathetic control of the heart rhythm, the root mean square of successive differences (RMSSD) of normal RR intervals. The association was studied in a …

The Impact Of Salsalate Treatment On Serum Levels Of Advanced Glycation End Products In Type 2 Diabetes., Joshua I Barzilay, Kathleen A. Jablonski, Vivian Fonseca, Steven E Shoelson, Allison B Goldfine, Christopher Strauch, Vincent M Monnier, Tinsal-T2d Research Consortium.

GW Biostatistics Center

OBJECTIVE Salsalate is a nonacetylated salicylate that lowers glucose levels in people with type 2 diabetes (T2D). Here we examined whether salsalate also lowered serum-protein-bound levels of early and advanced glycation end products (AGEs) that have been implicated in diabetic vascular complications. RESEARCH DESIGN AND METHODS Participants were from the Targeting Inflammation Using Salsalate for Type 2 Diabetes (TINSAL-T2D) study, which examined the impact of salsalate treatment on hemoglobin A1c (HbA1c) and a wide variety of other parameters. One hundred eighteen participants received salsalate, 3.5 g/day for 48 weeks, and 109 received placebo. Early glycation product levels (HbA1c and fructoselysine …

Genetic Risk Of Progression To Type 2 Diabetes And Response To Intensive Lifestyle Or Metformin In Prediabetic Women With And Without A History Of Gestational Diabetes Mellitus., Shannon D Sullivan, Kathleen A. Jablonski, Jose C Florez, Dana Dabelea, Paul W Franks, Sam Dagogo-Jack, Catherine Kim, William C Knowler, Costas A Christophi, Robert Ratner, Diabetes Prevention Program Research Group.

GW Biostatistics Center

OBJECTIVE The Diabetes Prevention Program (DPP) trial investigated rates of progression to diabetes among adults with prediabetes randomized to treatment with placebo, metformin, or intensive lifestyle intervention. Among women in the DPP, diabetes risk reduction with metformin was greater in women with prior gestational diabetes mellitus (GDM) compared with women without GDM but with one or more previous live births.

RESEARCH DESIGN AND METHODS We asked if genetic variability could account for these differences by comparing β-cell function and genetic risk scores (GRS), calculated from 34 diabetes-associated loci, between women with and without histories of GDM.

RESULTS β-Cell function was …

New Malignancies After Squamous Cell Carcinoma And Melanomas: A Population-Based Study From Norway, Trude E. Robsahm, Margaret R. Karagas, Judy R. Rees, Astri Syse

Dartmouth Scholarship

Skin cancer survivors experience an increased risk for subsequent malignancies but the associated risk factors are poorly understood. This study examined the risk of a new primary cancer following an initial skin cancer and assessed risk factors associated with second primary cancers.

Analysis Of Schizophrenia Data Using A Nonlinear Threshold Index Logistic Model., Zhenyu Jiang, Chengan Du, Assen Jablensky, Hua Liang, Zudi Lu, Yang Ma, Kok Lay Teo

GW Biostatistics Center

Genetic information, such as single nucleotide polymorphism (SNP) data, has been widely recognized as useful in prediction of disease risk. However, how to model the genetic data that is often categorical in disease class prediction is complex and challenging. In this paper, we propose a novel class of nonlinear threshold index logistic models to deal with the complex, nonlinear effects of categorical/discrete SNP covariates for Schizophrenia class prediction. A maximum likelihood methodology is suggested to estimate the unknown parameters in the models. Simulation studies demonstrate that the proposed methodology works viably well for moderate-size samples. The suggested approach is therefore …

Hiv Testing Implementation In Two Urban Cities: Practice, Policy, And Perceived Barriers., Camden J Hallmark, Jennifer Skillicorn, Thomas P Giordano, Jessica A Davila, Marlene Mcneese, Nestor Rocha, Avemaria Smith, Stacey Cooper, Amanda D. Castel

Epidemiology Faculty Publications

BACKGROUND: Although funding has supported the scale up of routine, opt-out HIV testing in the US, variance in implementation mechanisms and barriers in high-burden jurisdictions remains unknown.

METHODS: We conducted a survey of health care organizations in Washington, DC and Houston/Harris County to determine number of HIV tests completed in 2011, policy and practices associated with HIV testing, funding mechanisms, and reported barriers to testing in each jurisdiction and to compare results between jurisdictions.

RESULTS: In 2012, 43 Houston and 35 DC HIV-testing organizations participated in the survey. Participants represented 85% of Department of Health-supported testers in DC and 90% …

Targeting Inflammation Using Salsalate In Patients With Type 2 Diabetes: Effects On Flow-Mediated Dilation (Tinsal-Fmd)., Allison B Goldfine, J Stewart Buck, Cyrus Desouza, Vivian Fonseca, Yii-Der Ida Chen, Steven E Shoelson, Kathleen A. Jablonski, Mark A Creager, The Tinsal-Fmd Team

GW Biostatistics Center

OBJECTIVE: To test whether inhibiting inflammation with salsalate improves endothelial function in patients with type 2 diabetes (T2D).

RESEARCH DESIGN AND METHODS: We conducted an ancillary study to the National Institutes of Health-sponsored, multicenter, randomized, double-masked, placebo-controlled trial evaluating the safety and efficacy of salsalate in targeting inflammation to improve glycemia in patients with T2D. Flow-mediated, endothelium-dependent dilation (FMD) and endothelium-independent, nitroglycerin-mediated dilation (NMD) of the brachial artery were assessed at baseline and 3 and 6 months following randomization to either salsalate 3.5 g/day or placebo. The primary end point was change in FMD at 6 months.

RESULTS: A total …

Balancing The Presentation Of Information And Options In Patient Decision Aids: An Updated Review, Purva Abhyankar, Robert J. Volk, Jennifer Blumenthal-Barby, Paulina Bravo, Angela Buchholz, Elissa Ozanne, Dale C. Vidal, Nananda Col, Peep Stalmeier

Dartmouth Scholarship

Standards for patient decision aids require that information and options be presented in a balanced manner; this requirement is based on the argument that balanced presentation is essential to foster informed decision making. If information is presented in an incomplete/non-neutral manner, it can stimulate cognitive biases that can unduly affect individuals’ knowledge, perceptions of risks and benefits, and, ultimately, preferences. However, there is little clarity about what constitutes balance, and how it can be determined and enhanced. We conducted a literature review to examine the theoretical and empirical evidence related to balancing the presentation of information and options.

Predictors Of The Number Of Under-Five Malnourished Children In Bangladesh: Application Of The Generalized Poisson Regression Model, Mohammad Mafijul Islam, Morshed Alam, Md Tariquzaman, Mohammad Alamgir Kabir, Rokhsona Pervin, Munni Begum, Md Mobarak Hossain Khan

Journal Articles: Biostatistics

BACKGROUND: Malnutrition is one of the principal causes of child mortality in developing countries including Bangladesh. According to our knowledge, most of the available studies, that addressed the issue of malnutrition among under-five children, considered the categorical (dichotomous/polychotomous) outcome variables and applied logistic regression (binary/multinomial) to find their predictors. In this study malnutrition variable (i.e. outcome) is defined as the number of under-five malnourished children in a family, which is a non-negative count variable. The purposes of the study are (i) to demonstrate the applicability of the generalized Poisson regression (GPR) model as an alternative of other statistical methods and …

Determinants Of Negative Pathways To Care And Their Impact On Service Disengagement In First-Episode Psychosis., Kelly K. Anderson, Rebecca Fuhrer, Norbert Schmitz, Ashok K Malla

Epidemiology and Biostatistics Publications

PURPOSE: Although there have been numerous studies on pathways to care in first-episode psychosis (FEP), few have examined the determinants of the pathway to care and its impact on subsequent engagement with mental health services.

METHODS: Using a sample of 324 FEP patients from a catchment area-based early intervention (EI) program in Montréal, we estimated the association of several socio-demographic, clinical, and service-level factors with negative pathways to care and treatment delay. We also assessed the impact of the pathway to care on time to disengagement from EI services.

RESULTS: Few socio-demographic or clinical factors were predictive of negative pathways …

Dna Methylation Arrays As Surrogate Measures Of Cell Mixture Distribution, Eugene Houseman, William P. Accomando, Devin C. Koestler, Brock C. Christensen, Carmen J. Marsit

Dartmouth Scholarship

There has been a long-standing need in biomedical research for a method that quantifies the normally mixed composition of leukocytes beyond what is possible by simple histological or flow cytometric assessments. The latter is restricted by the labile nature of protein epitopes, requirements for cell processing, and timely cell analysis. In a diverse array of diseases and following numerous immune-toxic exposures, leukocyte composition will critically inform the underlying immuno-biology to most chronic medical conditions. Emerging research demonstrates that DNA methylation is responsible for cellular differentiation, and when measured in whole peripheral blood, serves to distinguish cancer cases from controls.

Genetic Association Studies Of Copy-Number Variation: Should Assignment Of Copy Number States Precede Testing?, Patrick Breheny, Prabhakar Chalise, Anthony Batzler, Liewei Wang, Brooke L. Fridley

Biostatistics Faculty Publications

Recently, structural variation in the genome has been implicated in many complex diseases. Using genomewide single nucleotide polymorphism (SNP) arrays, researchers are able to investigate the impact not only of SNP variation, but also of copy-number variants (CNVs) on the phenotype. The most common analytic approach involves estimating, at the level of the individual genome, the underlying number of copies present at each location. Once this is completed, tests are performed to determine the association between copy number state and phenotype. An alternative approach is to carry out association testing first, between phenotype and raw intensities from the SNP array …

The Pathways To Mental Health Care Of First-Episode Psychosis Patients: A Systematic Review., Kelly K. Anderson, Rebecca Fuhrer, Ashok K. Malla

Epidemiology and Biostatistics Publications

BACKGROUND: Although there is agreement on the association between delay in treatment of psychosis and outcome, less is known regarding the pathways to care of patients suffering from a first psychotic episode. Pathways are complex, involve a diverse range of contacts, and are likely to influence delay in treatment. We conducted a systematic review on the nature and determinants of the pathway to care of patients experiencing a first psychotic episode.

METHOD: We searched four databases (Medline, HealthStar, EMBASE, PsycINFO) to identify articles published between 1985 and 2009. We manually searched reference lists and relevant journals and used forward citation …

Focus On Rna Isolation: Obtaining Rna For Microrna (Mirna) Expression Profiling Analyses Of Neural Tissue, Wang-Xia Wang, Bernard R. Wilfred, Donald A. Baldwin, R. Benjamin Isett, Na Ren, Arnold J. Stromberg, Peter T. Nelson

Sanders-Brown Center on Aging Faculty Publications

MicroRNAs (miRNAs) are present in all known plant and animal tissues and appear to be somewhat concentrated in the mammalian nervous system. Many different miRNA expression profiling platforms have been described. However, relatively little research has been published to establish the importance of 'upstream' variables in RNA isolation for neural miRNA expression profiling. We tested whether apparent changes in miRNA expression profiles may be associated with tissue processing, RNA isolation techniques, or different cell types in the sample. RNA isolation was performed on a single brain sample using eight different RNA isolation methods, and results were correlated using a conventional …