Kevin Dobbin

Medical College of Georgia Augusta University · Biostatistics

Background About 20% of breast cancers in humans are basal-like, a subtype that is often triple negative and difficult to treat. An effective translational model for basal-like breast cancer (BLBC) is currently lacking and urgently needed. To determine if spontaneous mammary tumors in pet dogs could meet this need, we subtyped canine mammary tumors...

Background Individual symptoms and signs of infectious mononucleosis (IM) are of limited value for diagnosis. Objective To develop and validate risk scores based on signs and symptoms with and without haematologic parameters for the diagnosis of IM. Design and setting Data were extracted from electronic health records of a university health centr...

Treatment selection biomarkers are those that can be useful in guiding choice of therapy. Just as new therapies require evaluation in appropriately designed clinical trials to determine their benefit, therapy selection biomarkers require evaluation in appropriately designed studies. These studies may be prospective clinical trials or retrospective...

Objectives: To describe access to and use of prescription asthma medications, and to assess factors associated with asthma exacerbation, healthcare utilization, and health status among asthma patients treated at Federally Qualified Health Centers. Methods: This is a retrospective cross-sectional study. We analyzed data from the 2014 National Hea...

There is little information about the amount of recent tuberculosis transmission in low-income settings. Genetic clustering can help identify ongoing transmission events. A retrospective observational study was performed on Mycobacterium tuberculosis isolates from persons living with HIV (PLHIV) and HIV-seronegative participants who submitted sampl...

Spontaneous canine cancers are valuable but relatively understudied and underutilized models. To enhance their usage, we reanalyze whole exome and genome sequencing data published for 684 cases of >7 common tumor types and >35 breeds, with rigorous quality control and breed validation. Our results indicate that canine tumor alteration landscape is...

Objectives Concern for late detection of bacterial pathogens is a barrier to early de-escalation efforts. The purpose of this study was to assess blood, respiratory and urine culture results at 72 h to test the hypothesis that early negative culture results have a clinically meaningful negative predictive value. Methods We retrospectively reviewed...

Background. Exposure to an individual with tuberculosis is necessary for transmission to occur. Previously, we developed a score that measures contact between tuberculosis cases and their social networks in an African urban context. This score was built using exploratory factor analysis and identified contact as the conjunction of two domains – set...

Background: The End TB Strategy envisions a world free of tuberculosis (TB)-zero deaths, disease, and suffering due to TB by 2035. Non-adherence reduces cure rates, prolongs infectiousness, and contributes to the emergence of multi-drug resistant TB (MDR-TB). Moreover, MDR-TB is a growing, complex, and costly problem that presents a major obstacle...

Abstract Background The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and the...

We consider evaluating new or more accurately measured predictive biomarkers for treatment selection based on a previous clinical trial involving standard biomarkers. Instead of rerunning the clinical trial with the new biomarkers, we propose a more efficient approach which requires only either conducting a reproducibility study in which the new bi...

BACKGROUND The End TB Strategy envisions a world free of tuberculosis (TB)-zero deaths, disease and suffering due to TB by 2035. Non-adherence reduces cure rates, prolongs infectiousness, and contributes to emergence of multi-drug resistant TB (MDR-TB). Moreover, MDR-TB is a growing, complex and costly problem that presents a major obstacle to TB c...

Introduction Nonadherence to treatment remains an obstacle to tuberculosis (TB) control worldwide. The aim of this study was to evaluate the feasibility of using video directly observed therapy (VDOT) for supporting TB treatment adherence in Uganda. Methods From May to December 2018, we conducted a pilot cohort study at a TB clinic in Kampala City...

Background. There is little information about the proportion of clustering of tuberculosis cases from low-income settings, which can represent ongoing transmission events. Objectives. We investigated the proportion of clustered tuberculosis cases based on genotypic matching in Guatemala and potential factors associated with clustering in HIV-infect...

Background. The risk of infection from respiratory pathogens increases according to the contact rate between the infectious case and susceptible contact, but the definition of adequate contact for transmission is not standard. In this study we aimed to identify factors that can explain the level of contact between tuberculosis cases and their socia...

Background: At least 13-20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. T...

Setting Southern province, Zambia. Background At least 13 – 20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). Objective To estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings. Methods In...

Setting Southern province, Zambia. Background At least 13 – 20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). Objective To estimate the prevalence of recurrent TB among TB cases and compare risk of unfavorable treatment outcomes between rural and urban settings. Methods In...

Background At least 13 – 20% of all Tuberculosis (TB) cases are recurrent TB. Recurrent TB has critical public health importance because recurrent TB patients have high risk of Multi-Drug Resistant TB (MDR-TB). It is critical to understand variations in the prevalence and treatment outcomes of recurrent TB between different geographical settings. T...

Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases and evaluated their molecular homology to human colorectal cancer (CRC). We sequenced 15 canine intestinal samples f...

Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases and evaluated their molecular homology to human colorectal cancer (CRC). We sequenced 15 canine intestinal samples f...

The hyperactive FVB/N inbred mouse strain is widely used for transgenic research applications, although rarely for behavioral studies. These mice have visual impairments via retinal degeneration, but are considered highly intelligent and rely largely on olfaction. While investigating diet-induced obesity in autotaxin transgenic FVB/N mice, we obser...

Background: Rapid influenza diagnostic tests that detect the presence of viral antigens are currently used throughout the United States but have poor sensitivity. The objective of this study was to identify if the use of a new highly accurate rapid point of care test would significantly increase the likelihood of guideline consistent care. Method...

Spontaneous tumors in pet dogs represent a valuable but undercharacterized cancer model. To better use this resource, we performed an initial global comparison between proliferative and invasive colorectal tumors from 20 canine cases, and evaluated their molecular homology to human colorectal cancer (CRC). First, proliferative canine tumors harbor...

Distribution of normalized fragment densities within SEG-identified-CNA genomic regions in the tumor and normal genomes of the three canine cancer cases.

As next-generation sequencing technology advances and the cost decreases, whole genome sequencing (WGS) has become the preferred platform for the identification of somatic copy number alteration (CNA) events in cancer genomes. To more effectively decipher these massive sequencing data, we developed a software program named SEG, shortened from the w...

Upregulated expression of autotaxin, a secreted phospholipase and phosphodiesterase enzyme, appears in malignant disease. The identification of a circulating miRNA signature should distinguish autotaxin-mediated disease and also elucidate unknown molecular mechanisms that rationalize its malignant potential. Using female transgenic 'AT-ATX' mice, w...

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, the entire medical oncology field has been revolutionized by the introduction of immune checkpoints inhibitors. Despite success in a variety of malignancies, responses typically only occur in a small percentage of patients for any given his...

There is growing recognition that immunotherapy is likely to significantly improve health outcomes for cancer patients in the coming years. Currently, while a subset of patients experience substantial clinical benefit in response to different immunotherapeutic approaches, the majority of patients do not but are still exposed to the significant drug...

Immunotherapies have emerged as one of the most promising approaches to treat patients with cancer. Recently, there have been many clinical successes using checkpoint receptor blockade, including T cell inhibitory receptors such as cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) and programmed cell death-1 (PD-1). Despite demonstrated successe...

This study focused on assessing whether nickel (Ni) toxicity to the nematode Caenorhabditis elegans was affected by the molecular structure of the Ni salt used. Nematodes were exposed to seven Ni salts [Ni sulfate hexahydrate (NiSO4·6H2O), Ni chloride hexahydrate (NiCl2·6H2O), Ni acetate tetrahydrate (Ni(OCOCH3)2·4H2O), Ni nitrate hexahydrate (N2Ni...

Background: Recent biotechnological developments have resulted in increasing interest in immunology biomarkers. These biomarkers have potential clinical utility in the near future as predictors of treatment response. Hence, clinical validation of these predictive markers is critical. Findings: The process of clinically validating a predictive bi...

PurposeAs the new Patient Protection and Affordable Care Act (ACA) achieves full implementation in 2014–2015, public perceptions regarding improvement in access and quality of care due to the ACA provide a fertile area for sociological research. The aim of this chapter is to determine if race is independently associated with perceptions of quality...

The objective of many high-dimensional microarray and RNA-seq studies is to develop a classifier of cancer patients based on characteristics of their disease. The germinal center B-cell (GCB) classifier study in lymphoma and the National Cancer Institute's Director's Challenge lung (DC-lung) study are two examples. In recent years, such classifiers...

Author Summary Head and neck squamous cell carcinoma (HNSCC) represents the sixth leading cancer by incidence in humans; thus, developing effective therapeutic interventions is important. Although great advance has been made in our understanding of the biology of HNSCC over the past several decades, translating the research findings into clinical s...

The intraclass correlation coefficient (ICC) in a two-way analysis of variance is a ratio involving three variance components. Two recently developed methods for constructing confidence intervals (CI’s) for the ICC are the Generalized Confidence Interval (GCI) and Modified Large Sample (MLS) methods. The resulting intervals have been shown to maint...

Case detection by passive case finding (PCF) strategy alone is inadequate for detecting all tuberculosis (TB) cases in high burden settings especially Sub-Saharan Africa. Alternative case detection strategies such as community Active Case Finding (ACF) and Household Contact Investigations (HCI) are effective but empirical evidence of their cost-eff...

The intraclass correlation coefficient (ICC) is widely used in biomedical research to assess the reproducibility of measurements between raters, labs, technicians, or devices. For example, in an inter-rater reliability study, a high ICC value means that noise variability (between-raters and within-raters) is small relative to variability from patie...

Batch bias has been found in many microarray gene expression studies that involve multiple batches of samples. A serious batch effect can alter not only the distribution of individual genes but also the inter-gene relationships. Even though some efforts have been made to remove such bias, there has been relatively less development on a multivariate...

To determine the yield of undetected active tuberculosis (TB), TB and human immunodeficiency virus (HIV) coinfection and the number needed to screen (NNS) to detect a case using active case finding (ACF) in an urban community in Kampala, Uganda. In a door-to-door survey conducted in Rubaga community from January 2008 to June 2009, residents aged ≥1...

We review biostatistical aspects of biomarker studies, including design and analysis issues, covering the range of settings required for translational research-from early exploratory studies through clinical trials.

A common objective of biomarker studies is to develop a predictor of patient survival outcome. Determining the number of samples required to train a predictor from survival data is important for designing such studies. Existing sample size methods for training studies use parametric models for the high-dimensional data and cannot handle a right-cen...

The purpose of this study was to gather preliminary data on both direct and moderating effects of health status, the social environment, and perceived personal control on the symptom distress and quality of life (QOL) for older patients with cancer during a treatment regimen of chemotherapy. Participants were patients with cancer aged≥65years being...

Motivation: Implementation and development of statistical methods for high-dimensional data often require high-dimensional Monte Carlo simulations. Simulations are used to assess performance, evaluate robustness, and in some cases for implementation of algorithms. But simulation in high dimensions is often very complex, cumbersome and slow. As a r...

Dysregulation of platelet-derived growth factor receptor (PDGFR) may play a role in feline injection-site sarcoma (ISS) cell growth and viability. Masitinib, a tyrosine kinase inhibitor approved for treatment of canine mast cell tumours, is highly selective for the PDGFR signalling pathway and may offer a new therapeutic approach for this disease....

Article supplement. Contains additional tables, figures, theoretical derivations and discussions.

We consider the problem of designing a study to develop a predictive classifier from high dimensional data. A common study design is to split the sample into a training set and an independent test set, where the former is used to develop the classifier and the latter to evaluate its performance. In this paper we address the question of what proport...

To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known recurring cytogenetic abnormalities, we performed gene expression profiling in a cohort of 207 uniformly treated children with high-risk ALL. Expression profiles were correlated with gen...

The National Cancer Institute (NCI) Investigational Drug Steering Committee (IDSC) charged the Biomarker Task Force to develop recommendations to improve the decisions about incorporation of biomarker studies in early investigational drug trials. The Task Force members reviewed biomarker trials, the peer-reviewed literature, NCI and U.S. Food and D...

Gene expression profiling of 207 uniformly treated children with high-risk B-progenitor acute lymphoblastic leukemia revealed 29 of 207 cases (14%) with markedly elevated expression of CRLF2 (cytokine receptor-like factor 2). Each of the 29 cases harbored a genomic rearrangement of CRLF2: 18 of 29 (62%) had a translocation of the immunoglobulin hea...

4052 Background: 18q LOH may be a useful marker in stage II colon carcinoma to assess who needs adjuvant chemotherapy. The objective of this study was to evaluate the intra- and inter-laboratory reproducibility of an assay for 18q LOH that is similar to the integral assay used in E5202, the current Intergroup phase III stage II colon carcinoma clin...

Constructing a confidence interval for the actual, conditional error rate of a prediction rule from multivariate data is problematic because this error rate is not a population parameter in the traditional sense—it is a functional of the training set. When the training set changes, so does this “parameter.” A valid method for constructing confidenc...

With the progressive intensification of chemotherapy, the majority of children with ALL now achieve long-term survival. In parallel, a number of molecular subtypes of ALL have been identified that are associated with treatment outcomes, which are either excellent (TEL-AML1 or trisomy of chromosomes 4, 10, and 17), intermediate (MLL rearrangements o...

Children with HR-ALL are traditionally defined by NCI Risk Criteria (age and white blood cell count) and comprise a highly heterogeneous group of ALL cases that have not been well characterized. In an effort to shed light on the genetic diversity of HR-ALL and identify new therapeutic targets in this resistant form of disease, we previously analyze...

This chapter reviews major issues related to design and interpretation of microarray experiments. Important aspects of design covered include identification of experimental objectives, treatment of batch effects, selection of replication and pooling levels, determining sample size for class comparison and class prediction, and optimal allocation of...

Although prognostic gene expression signatures for survival in early-stage lung cancer have been proposed, for clinical application, it is critical to establish their performance across different subject populations and in different laboratories. Here we report a large, training-testing, multi-site, blinded validation study to characterize the perf...

A common goal of gene expression microarray studies is the development of a classifier that can be used to divide patients into groups with different prognoses, or with different expected responses to a therapy. These types of classifiers are developed on a training set, which is the set of samples used to train a classifier. The question of how ma...

While 80% of children with B-ALL achieve long term survival, a significant number still relapse. In contrast to low and intermediate risk ALL, the biologic and genetic features of high risk disease have not been well characterized. COG P9906, testing an augmented BFM regimen, enrolled 271 B-ALL patients from 2000–2003 who were predicted to have poo...

This is a review of several new approaches developed at or adopted by the Cooperative Prostate Cancer Tissue Resource (CPCTR) to resolve issues involved in tissue microarray (TMA) construction and use. CPCTR developed the first needle biopsy TMA, allowing researchers to obtain 200 or more consecutive cancer sections from a single biopsy core. Using...

Many gene expression studies attempt to develop a predictor of pre-defined diagnostic or prognostic classes. If the classes are similar biologically, then the number of genes that are differentially expressed between the classes is likely to be small compared to the total number of genes measured. This motivates a two-step process for predictor dev...

We identify two conserved domains in diverse bacterial and archaeal signaling proteins. One of them, the MEDS domain, is typified by the DmcR protein from Methylococcus and the other by the PocR protein of Salmonella typhi. We provide evidence ...

Prostate cancer can occur in patients with low screening serum prostate specific antigen (PSA) values (less than 4.0 ng/ml). It is currently unclear whether these tumors are different from prostate cancer in patients with high PSA levels (greater than 4.0 ng/ml). From the Cooperative Prostate Cancer Tissue Resource database through March 2004, 3,41...

Motivation: Spot intensity serves as a proxy for gene expression in dual-label microarray experiments. Dye bias is defined as an intensity difference between samples labeled with different dyes attributable to the dyes instead of the gene expression in the samples. Dye bias that is not removed by array normalization can introduce bias into compari...

A key step in bringing gene expression data into clinical practice is the conduct of large studies to confirm preliminary models. The performance of such confirmatory studies and the transition to clinical practice requires that microarray data from different laboratories are comparable and reproducible. We designed a study to assess the comparabil...

Motivation: In microarray experiments investigators sometimes wish to pool RNA samples before labeling and hybridization due to insufficient RNA from each individual sample or to reduce the number of arrays for the purpose of saving cost. The basic assumption of pooling is that the expression of an mRNA molecule in the pool is close to the average...

Tissue Microarrays (TMAs) have emerged as a powerful tool for examining the distribution of marker molecules in hundreds of different tissues displayed on a single slide. TMAs have been used successfully to validate candidate molecules discovered in gene array experiments. Like gene expression studies, TMA experiments are data intensive, requiring...

CPCTR tissue microarray database file. Cpctrtma.xml is the XML representation of the CPCTR prostate cancer TMA. This file conforms to the TMA Data Exchange Specification and can be viewed as a formatted XML file on most web browsers. The file exceeds 700 KB in length.

Excel to XML converting script. Opener7.pl is a Perl script that converts an Excel file to XML-tagged data elements that can be easily inserted into an XML file. This script only works under Windows and requires an installed version of Excel. It is distributed as an open access plain-text file.

TMA validating script. Validtma.pl is a validating Perl script distributed as a plain-text file. It parses through XML files and determines conformance to the TMA Data Exchange Specification [8]. This is an open access Perl script, and is identical to the Perl script distributed with the Specification.

Consider a clinical trial in which participants are randomized to a single-dose treatment or a placebo control and assume that the adherence level is accurately recorded. If the treatment is effective, then good adherers in the treatment group should do better than poor ad- herers because they received more drug; the treatment group data follow a d...

The rapid growth in the use of microarrays has generated many questions about how to design experiments that use this technology effectively. Investigators need answers to questions about RNA sample selection, allocation of samples to arrays, robustness of design, dye bias, sample size, and statistical power to ensure that the experimental objectiv...