Craig A Beam

• Western Michigan University

Strategies to improve metabolic health include calorie restriction, time restricted eating and fasting several days per week or month. These approaches have demonstrated benefits for individuals experiencing obesity, metabolic syndrome, and prediabetes. However, their impact on established diabetes remains incompletely studied. The chronicity of ty...

Type 1 diabetes is characterized by a loss of tolerance to pancreatic β-cell autoantigens and defects in T regulatory cell (Treg) function. In preclinical models, immunotherapy with MHC-selective, autoantigenic peptides restores immune tolerance, prevents diabetes and shows greater potency when multiple peptides are used. To translate this strategy...

Aims/hypothesis The circadian clock influences both diabetes and immunity. Our goal in this study was to characterise more thoroughly the circadian patterns of immune cell populations and cytokines that are particularly relevant to the immune pathology of type 1 diabetes and thus fill in a current gap in our understanding of this disease. Methods...

AbstractAims/hypothesisThe aim of this study was to determine if retention of C-peptide following immunotherapy using recombinantGAD65 conjugated to aluminium hydroxide (GAD-alum) is influenced by HLA risk haplotypesDR3-DQ2andDR4-DQ8.MethodsHLA-dependent treatment effect of GAD-alum therapy on C-peptide retention in individuals with recent-onset ty...

Aim: Double-blind placebo-controlled intervention using glutamic acid decarboxylase (GAD)-alum, vitamin D and Ibuprofen in recent onset Type I diabetes (T1D). Methods: 64 patients (T1D since <4 months, age 10-17.99, fasting sC-peptide ≥0.12 nmol/l, GADA-positive) were randomized into Day(D) 1-90 400 mg/day Ibuprofen, D1-450 vitamin D 2000 IU/day...

Aims/hypothesis: Antigen-specific therapy aims to modify inflammatory T cell responses in type 1 diabetes and restore immune tolerance. One strategy employs GAD65 conjugated to aluminium hydroxide (GAD-alum) to take advantage of the T helper (Th)2-biasing adjuvant properties of alum and thereby regulate pathological Th1 autoimmunity. We explored t...

We previously reported that costimulation blockade by abatacept limits the decline of β-cell function and the frequency of circulating CD4+ central memory T cells (TCM) (CD45RO+CD62L+) in new-onset type 1 diabetes. In human subjects receiving placebo, we found a significant association between an increase in CD4+ TCM cells and the decline of β-cell...

In this study, we sought to fill an important gap in fundamental immunology research by conducting a comprehensive systems immunology analysis of daily variation in the normal human peripheral immune system. Although variation due to circadian rhythmicity was not a significant source of variation in daily B-cell levels or any CD4+ functional subset...

Purpose: Immune populations and cytokines are known to exhibit distinct circadian ("daily") variations. We sought to characterize circadian-related immune variation in persons with type 1 diabetes (T1D) to ascertain whether sampling of peripheral immune biomarkers should be timed with circadian patterns Methods: We enrolled 10 adults (6 female) vol...

In type 1 diabetes, cytotoxic CD8+ T cells with specificity for β cell autoantigens are found in the pancreatic islets, where they are implicated in the destruction of insulin-secreting β cells. In contrast, the disease relevance of β cell–reactive CD8+ T cells that are detectable in the circulation, and their relationship to β cell function, are n...

Context There is little information regarding beta cell mass in individuals at early stages of type 1 diabetes (T1D). Objective To investigate both AIRmax, as a correlate of beta cell mass, and beta cell function by IVGTT in subjects at early stages of T1D. Design/Setting/Participants Forty subjects were enrolled: (1) low risk group: relatives of...

Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen–DR4(DRB1*0401)–restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 dia...

Aims/hypothesisGAD is a major target of the autoimmune response that occurs in type 1 diabetes mellitus. Randomised controlled clinical trials of a GAD + alum vaccine in human participants have so far given conflicting results. Methods In this study, we sought to see whether a clearer answer to the question of whether GAD65 has an effect on C-pepti...

Background: Islet autoantibody testing provides the basis for assessment of risk of progression to type 1 diabetes. We set out to determine the feasibility and acceptability of dried capillary blood spot-based screening to identify islet autoantibody-positive relatives potentially eligible for inclusion in prevention trials. Materials and methods...

Biomarkers have become, and will continue to become, increasingly important to clinical immunology research. Yet, biomarkers often present new problems and raise new statistical and study design issues to scientists working in clinical immunology. In this paper I discuss statistical considerations related to the important biomarker problems of : 1)...

We developed a scale to serve as a potential end point for 6-month glycemic progression (PS6M) toward type 1 diabetes (T1D) in autoantibody-positive relatives of individuals with T1D. The PS6M was developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and tested in the TrialNet Pathway to Prevention Study (PTP). It is the difference between 6...

Unlabelled: Role of the funding source: Funding from the NIH was used for support of the participating clinical centers and the coordinating center. The funding source did not participate in the collection or the analysis of the data. Background: The β cell killing that characterizes type 1 diabetes (T1D) is thought to begin years before patient...

Background Type 1 Diabetes TrialNet is an NIH-sponsored clinical trial network aimed at altering the disease course of type 1 diabetes. The purpose of this study is to evaluate age-dependent heterogeneity in clinical, metabolic, and immunologic characteristics of individuals with recent-onset type 1 diabetes (T1D), to identify cohorts of interest a...

We assessed whether type 1 diabetes (T1D) can be diagnosed earlier using a new approach based on prediction and natural history in autoantibody-positive individuals. Diabetes Prevention Trial-Type 1 (DPT-1) and TrialNet Natural History Study (TNNHS) participants were studied. A metabolic index, the T1D Diagnostic Index60 (Index60), was developed fr...

Background: In modeling a N by m data matrix, i.e. N samples on a m dimensional space, the issue arises when m is bigger than N. The sample size cannot be increased, especially in medical research, due to the limited number of diseased subjects. Feature selection is often used to select a subset of relevant m variables, often lower than N, for use...

We previously reported that continuous 24-month costimulation blockade by abatacept significantly slows the decline of beta-cell function after diagnosis of type 1 diabetes. In a mechanistic extension of that study, we evaluated peripheral blood immune cell subsets (CD4, CD8-naive, memory and activated subsets, myeloid and plasmacytoid dendritic ce...

Type 1 and other forms of diabetes are due to the killing of β cells. However, the loss of β cells has only been assessed by functional studies with a liquid meal or glucose that can be affected by environmental factors. As an indirect measure of β cell death, we developed an assay using a novel droplet digital PCR (ddPCR) that detects INS DNA deri...

Clinical responder studies should contribute to the translation of effective treatments and interventions to the clinic. Since ultimately this translation will involve regulatory approval, we recommend that clinical trials pre-specify a responder definition that can be assessed against the requirements and suggestions of regulatory agencies. In thi...

OBJECTIVE We studied the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for improving the accuracy of type 1 diabetes (T1D) risk classification in TrialNet Natural History Study (TNNHS) participants.RESEARCH DESIGN AND METHODS The cumulative incidence of T1D was compared between normoglycemic individuals with DPTRS values >7.00...

To clarify whether the rate of decline in stimulated C-peptide (SCP) from 2 to 15 months after diagnosis has changed over an interval of 27 yr. The rate of decline in SCP levels at 1, 2, 3, 6, 9, 12, and 15 months after diagnosis was compared in four paediatric cohorts from Scandinavian and European countries including 446 children with new onset t...

OBJECTIVE We assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS TrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those pos...

We studied the change in the first-phase insulin response (FPIR) during the progression to type 1 diabetes (T1D). Seventy-four oral insulin trial progressors to T1D of the Diabetes Prevention Trial-Type 1 with at least one FPIR measurement after baseline and before diagnosis were studied. The FPIR was examined longitudinally in 26 progressors who h...

OBJECTIVEdWe assessed whether a risk score that incorporates levels of multiple islet autoantibodies could enhance the prediction of type 1 diabetes (T1D). RESEARCH DESIGN AND METHODSdTrialNet Natural History Study participants (n = 784) were tested for three autoantibodies (GADA, IA-2A, and mIAA) at their initial screening. Samples from those posi...

Background: Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral...

OBJECTIVE To establish and compare the prognostic accuracy of immunologic and metabolic markers in predicting onset of type 1 diabetes in those with high risk in a prospective study. RESEARCH DESIGN AND METHODS A total of 339 subjects from the Diabetes Prevention Trial–Type 1 (DPT-1) parenteral study, who were islet cell antibody (ICA)-positive, w...

The aim of this study was to evaluate HbA(1c) as an alternative criterion for impaired glucose tolerance (IGT) or type 1 diabetes (T1D) in high-risk subjects <21 years of age. Subjects <21 years of age who participated in the prospective DPT-1, TEDDY, TRIGR, and Type 1 Diabetes TrialNet Natural History (TrialNet) studies and had an HbA(1c) within 9...

Interpretation of clinical trials to alter the decline in β-cell function after diagnosis of type 1 diabetes depends on a robust understanding of the natural history of disease. Combining data from the Type 1 Diabetes TrialNet studies, we describe the natural history of β-cell function from shortly after diagnosis through 2 years post study randomi...

We assessed the utility of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS) for identifying individuals who are highly likely to progress to type 1 diabetes (T1D) within 2 years. The DPTRS was previously developed from Diabetes Prevention Trial-Type 1 (DPT-1) data and was subsequently validated in the TrialNet Natural History Study (TNNHS)....

We assessed diabetes risk associated with zinc transporter-8 antibodies (ZnT8A), islet cell antibodies (ICA), and HLA type and age in relatives of people with type 1 diabetes with the standard biochemical autoantibodies (BAA) to insulin (IAA), GAD65 (GAD65A), and/or insulinoma-associated protein 2 antigen (IA-2A). For this analysis, 2,256 relatives...

Under typical dark chest radiography reading room conditions, a radiologist's pupils contract and dilate as their visual focus intermittently shifts between the high luminance monitor and the darker background wall, resulting in increased visual fatigue and degradation of diagnostic performance. A controlled increase of ambient lighting may minimiz...

Detection of below-threshold first-phase insulin release or FPIR (1+3 minute insulin concentrations during an intravenous glucose tolerance test [IVGTT]) is important in type 1 diabetes prediction and prevention studies including the TrialNet Oral Insulin Prevention Trial. We assessed whether an insulin immunoenzymometric assay (IEMA) could replace...

There are several studies examining prostate cancer and exposure to cadmium, iron, selenium, and zinc. Less data are available on the possible influence of these metal ions on prostate cancer outcome. This study measured levels of these ions in prostatectomy samples in order to examine possible associations between metal concentrations and disease...

Understanding the relationship between age and islet autoantibody (Ab) seroconversion can establish the optimal screening interval(s) to assess risk for type 1 diabetes, identify subjects who can participate in prevention trials, and determine associated costs. This study assessed the rates of seroconversion to glutamic acid decarboxylase positive...

Background The immunopathogenesis of type 1 diabetes mellitus is associated with T-cell autoimmunity. To be fully active, immune T cells need a co-stimulatory signal in addition to the main antigen-driven signal. Abatacept modulates co-stimulation and prevents full T-cell activation. We evaluated the eff ect of abatacept in recent-onset type 1 diab...

We assessed the accuracy of the Diabetes Prevention Trial-Type 1 Risk Score (DPTRS), developed from the Diabetes Prevention Trial-Type 1 (DPT-1), in the TrialNet Natural History Study (TNNHS). Prediction accuracy of the DPTRS was assessed with receiver-operating characteristic curve areas. The type 1 diabetes cumulative incidence within the DPTRS i...

The purpose of our study is to determine whether body mass index (BMI = weight in kg/height in meters(2)) was related to the rate of negative appendectomy in patients who underwent preoperative CT. A surgical database search performed using the procedure code for appendectomy identified 925 patients at least 18 years of age who underwent urgent app...

Although type 1 diabetes autoimmunity frequently begins in childhood, little is known about the relationship between age and autoimmunity development. Our aim was to determine the timing of seroconversion to diabetes-associated autoantibody (DAA) positivity and risk in first- and second-degree relatives of patients with type 1 diabetes. Study subje...

To compare coronary artery calcium (CAC) progression between 2 treatment groups, pioglitazone versus glimepiride. The CHICAGO (Carotid Intima-Media Thickness in Atherosclerosis Using Pioglitazone) study demonstrated that pioglitazone significantly decreased carotid intima-media thickness progression compared with glimepiride in patients with type 2...

Persistent infection with human papillomavirus (HPV) is the primary etiologic factor for cervical cancer. The synergistic effect of carotenoids on HPV persistence has not been examined. To explore these potential synergies, we developed 2 measures of carotenoid status using circulating and dietary intake nutrients in which each nutrient was given e...

To determine the frequency of preoperative computed tomography (CT) in the evaluation of patients suspected of having appendicitis at one institution during the past 10 years and to determine whether changes in CT utilization were associated with changes in the negative appendectomy rate. Institutional review board approval was obtained, and a waiv...

Epidemiologic studies have established that pregnancy has a bidirectional, time-dependent effect on breast cancer risk; a period of elevated risk is followed by a long-term period of protection. The purpose of the present study was to determine whether pregnancy and involution are associated with gene expression changes in the normal breast, and wh...

Cited By (since 1996):2, Export Date: 18 October 2014

Breast density is a significant breast cancer risk factor. Although various methods are used to estimate breast density, there is no standard measurement for this important factor. The authors are developing a breast density standardization method for use in full field digital mammography (FFDM). The approach calibrates for interpatient acquisition...

The objective of our study was to validate a radiographic scale, the Duke abdominal assessment scale (DAAS), as a tool for predicting the severity of disease in neonates and infants with suspected necrotizing enterocolitis (NEC). Study group patients (n = 43) underwent at least two two-view abdominal radiographic series within 48 hours of surgical...

The claudin family of proteins is important in epithelial cell tight junction formation and function. Normal breast epithelial cells have strong expression of claudin-7. While it is mostly confined to the cell membrane, some can also be seen in the cytoplasm. Previous publications have shown an inverse correlation of claudin-7 immunohistochemical e...

When clinicians contemplate the use of a new predictive technology in their practice, such as a nomogram, there is always a question of whether the new test is beneficial to their own clinical population. Unfortunately, traditional validation methods require a large number of subjects for validation testing and delay the decision-making process. We...

#5038 Introduction: Epidemiological studies have shown that women of all ages experience a transient increase in the risk of developing breast cancer following pregnancy. Furthermore, breast cancers detected soon after a completed pregnancy have a worse prognosis than those detected at more distant intervals. One explanatory hypothesis supported by...

RNA expression analysis of oral keratinocytes can be used to detect early stages of disease such as oral cancer or to monitor on-going treatment responses of the same or other oral diseases. A limitation is the inability to obtain high quality RNA from oral tissue without using biopsies. While oral cytology cell samples can be obtained from patient...

Radiologists' interpretation on screening mammograms is measured by accuracy indices such as sensitivity and specificity. The hypothesis that radiologists' interpretation on screening mammograms is constant across time can be tested by measuring overdispersion. However, small sample sizes are problematic for the accuracy of asymptotic approaches. I...

During the late luteal phase of the menstrual cycle and early pregnancy, the major secretory product of the uterine glandular epithelial cells in humans and non-human primates is glycodelin. Previous studies using Ishikawa cells, a human endometrial cell line, have shown that a chimeric plasmid containing the baboon glycodelin promoter responds to...

The study of regulatory networks in human pathogens such as Cryptococcus neoformans provides insights into host-pathogen interactions that may allow for correlation of gene expression patterns with clinical outcomes. In the present study, deletion of the cryptococcal copper-dependent transcription factor 1 (Cuf1) led to defects in growth and virule...

An image that is not perceived and interpreted can have no positive impact on health care. In this article, the authors review publicly available data and the published literature concerning the unitary event of the perception and interpretation of medical images. Their review shows that this event occurs as frequently as do major medical, public h...

Cell adhesion to fibronectin is known to confer a temporally related cell adhesion-mediated drug resistance (CAM-DR). However, it is unknown whether cell adhesion during drug selection influences the more permanent form of acquired drug resistance. To examine this question, we compared the acquisition of mitoxantrone resistance in U937 cells adhere...

We investigated whether the addition of two chromatin-modifying agents, 5-aza-2'-deoxycytidine (5azaD) and trichostatin A (TSA), to cord blood (CB) CD34(+) cells in culture results in expansion of the numbers of severe combined immunodeficient (SCID) repopulating cells (SRC). Human CB CD34(+) cells were cultured with cytokines in the presence or ab...

To determine whether skill in the interpretation of screening mammograms is correlated with skill in the interpretation of diagnostic mammograms. The institutional review board of the University of South Florida approved this study. This study was determined to be exempt from informed consent requirements because of the retrospective use of images...

Signal transducer and activator of transcription 3 (Stat3) protein is persistently activated in breast cancer and promotes tumor cell survival. To gain a better understanding of the role of constitutive Stat3 signaling in breast cancer progression, we evaluated the expression profile of potential Stat3-regulated genes that may confer resistance to...

Constitutive activation of signal transducer and activator of transcription 3 (Stat3) protein has been observed in a wide variety of tumors, including breast cancer, and contributes to oncogenesis at least in part by prevention of apoptosis. In a study of 45 patients with high-risk breast cancer enrolled in a phase II neoadjuvant chemotherapy trial...

Analysis of reading data when cases have multiple targets and/or the reader is required to localize targets is difficult. One approach to this free-response operating characteristic (FROC) problem is for images to be segmented (eg, with quadrants) by the investigator and a segment-level analysis be conducted with the case as a nesting factor. In th...

Despite major advances, multiple myeloma (MM) remains an incurable malignancy. Recently we have found that disease stabilization was achieved in 64% of patients with advanced MM treated with the farnesyltransferase inhibitor R115777 (Zarnestra) in a phase 2 clinical trial. In order to enhance R115777 antitumor activity in MM, we examined the combin...

Oligonucleotide gene expression microarray platforms typically measure gene expression as a magnitude proportional to transcript abundance. Studies attempting to find gene expression patterns in microarray data must use normalized data. Normalizing microarray gene expression data across multiple chips corrects for different levels of solution and o...

We introduce an interesting interpretation of the ROC Curve that, subsequently, opens a new research paradigm. We define the "Diagnostician Operating Choice" (DOC) Curve to be the set of all (True Positive Probability/True Negative Probability) or ("skill in diseased population"/"skill in non-diseased population" when considered from the diagnostic...

Recent research has documented that the human observer is a significant source of interpretation errors in mammography in the U.S. However, it has yet to be determined whether or not the rate or likelihood of radiologist-specific error changes across the length of time the radiologist has been reading during a single session, or across the cumulati...

The multiple-reader, multiple-case (MRMC) approach to receiver operating characteristic (ROC) analysis is becoming the dominant assessment paradigm in medical imaging. Its most common version involves having many readers read every patient case in the study, a critical feature since differences among competing imaging modalities are often dominated...

It is well known that the optimal use of a diagnostic medical technology can be determined by a mathematical relationship involving the relative valuation of outcomes, the prior probability of disease and the operating characteristic of the medical technology. By inverting this relationship a measure of the relative valuation of health outcomes tha...

HTML Purpose: Determine whether skill in the interpretation of screening mammograms is correlated with skill in the interpretation of diagnostic mammograms. Methods and Materials: 110 randomly selected radiologists who participated in a study of skill in screening mammogram interpretation (148 randomly sampled screening cases -60 biopsy proven canc...

Cancer cell adhesion confers a transient, de novo drug-resistant phenotype referred to as cell adhesion-mediated drug resistance (CAM-DR). In this report, we extend the CAM-DR phenotype to primary specimens from patients with myeloma, providing further evidence that CAM-DR is a viable clinical form of drug resistance. To examine mechanisms of cellu...

To evaluate the potential effect of proscriptive health care policies directed toward improving screening mammogram interpretation in the United States. Percentiles of accuracy based on a random sample of 110 U.S. radiologists were used to examine the number of radiologists who would need to be restricted from providing mammographic interpretation...

Human error in the interpretation of screening and diagnostic mammograms is now recognized to be a significant problem in the United States. Obviously, problems that are not well understood, well characterized, or well measured cannot be effectively remedied. It is the goal of this article to provide the basic conceptual elements required for scien...

Medical Imaging 2003: Image Perception, Observer Performance, and Technology Assessment,Dev P. Chakraborty, Elizabeth A. Krupinski, Editors, Proceedings of SPIE Vol. 5034 (2003)© 2003 SPIE · 1605-7422/03/$15.00225Downloaded From: http://proceedings.spiedigitallibrary.org/pdfaccess.ashx?url=/data/conferences/spiep/7395/ on 04/11/2017 Terms of Use: h...

An approach to sampling the U.S. population of mammographers was devised by Beam, Layde, Sullivan. They now have accumulated the reports of 108 radiologists, each reading the same random sample of 150 cases. We have applied multiple-reader, multiple case (MRMC) ROC analysis to their data and reconfirmed the earlier conclusion of Beam that the varia...

Early detection of breast cancer is associated with the accurate reading of screening mammograms, but factors that influence reading accuracy are not well understood. We thus investigated whether reading volume and other factors were independently associated with accuracy in reading screening mammograms in a population of U.S. radiologists. A rando...

To determine whether training in the Breast Imaging Reporting and Data System (BI-RADS) improves observer performance and agreement with the consensus of experienced breast imagers with regard to mammographic feature analysis and final assessment. A test set of mammograms was developed, with 54 proven lesions consisting of 28 masses (nine [32%] mal...

Although research has successfully documented variability in radiologists' interpretation of mammograms, it has failed to determine the relative contributions of case-specific features and reader inconsistency. Training interventions to improve consistency will be ineffectual if they do not target the principal determinants of disagreement among ra...

Each year, approximately 60% of all US women over the age of 40 utilize mammography. Through the matrix of an imaging technology, this Population of Patients (POP) interacts with a population of approximately 20,000 physicians who interpret mammograms in the US. This latter Population of Diagnosticians (POD) operationally serves as the interface be...

This paper presents a statistical method to explore and assess variability among diagnosticians in their accuracy and the association between accuracy and characteristics of diagnosticians and patients. The method assumes random sampling from a population of patients. It is assumed the diagnosticians provide ordinal diagnostic ratings to all patien...

Biostatistics is defined as much by its application as it is by theory. This book provides an introduction to biostatistical applications in modern cancer research that is both accessible and valuable to the cancer biostatistician or to the cancer researcher, learning biostatistics. The topical areas include active areas of the application of biost...

Few studies have evaluated the long-term predictive capacity of risk factors for death from coronary heart disease in men younger than 40 years of age. To assess the predictive capacity and discriminatory ability of major coronary risk factors in predicting death from coronary heart disease in young men. Prospective cohort study with 20 years of fo...