Statistics and Probability Commons^™

Evaluation Of Multiple Models To Distinguish Closely Related Forms Of Disease Using Dna Microarray Data: An Application To Multiple Myeloma, Johanna S. Hardin, Michael Waddell, C. David Page, Fenghuang Zhan, Bart Barlogie, John Shaughnessy, John J. Crowley

Pomona Faculty Publications and Research

Motivation: Standard laboratory classification of the plasma cell dyscrasia monoclonal gammopathy of undetermined significance (MGUS) and the overt plasma cell neoplasm multiple myeloma (MM) is quite accurate, yet, for the most part, biologically uninformative. Most, if not all, cancers are caused by inherited or acquired genetic mutations that manifest themselves in altered gene expression patterns in the clonally related cancer cells. Microarray technology allows for qualitative and quantitative measurements of the expression levels of thousands of genes simultaneously, and it has now been used both to classify cancers that are morphologically indistinguishable and to predict response to therapy. It is …

Loss-Based Estimation With Cross-Validation: Applications To Microarray Data Analysis And Motif Finding, Sandrine Dudoit, Mark J. Van Der Laan, Sunduz Keles, Annette M. Molinaro, Sandra E. Sinisi, Siew Leng Teng

U.C. Berkeley Division of Biostatistics Working Paper Series

Current statistical inference problems in genomic data analysis involve parameter estimation for high-dimensional multivariate distributions, with typically unknown and intricate correlation patterns among variables. Addressing these inference questions satisfactorily requires: (i) an intensive and thorough search of the parameter space to generate good candidate estimators, (ii) an approach for selecting an optimal estimator among these candidates, and (iii) a method for reliably assessing the performance of the resulting estimator. We propose a unified loss-based methodology for estimator construction, selection, and performance assessment with cross-validation. In this approach, the parameter of interest is defined as the risk minimizer for a suitable …

Comparison Of Bracket Bond Strength By Total, Self-Etch And Laser Treatment, Kyo Sung Shawn Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Laser etching of enamel surfaces alters the physical and chemical characteristics of the enamel. These changes in characteristics enhance the bonding to enamel. The purpose of this study was to compare the shear and tensile bond strength of Er,Cr:YSGG hydrokinetic laser system (Biolase) with 37% phosphoric acid and self etching primer 30 minutes and 72 hours after bonding. Four different laser power output setting was observed: 1.5W, 2.0W, 2.5W, and 3.0W. Two hundred forty bovine teeth free of defect, caries, and dentin exposure were mounted in acrylic resin and divided into 24 groups of 10 teeth. Sixteen groups of 10 …

A Bond Strength Comparison Of Led And Halogen Light Curing Units, John Richard Kavanagh

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this research was to compare the tensile bond strength of orthodontic flat based buttons bonded to bovine teeth with four commercial light-emitting diode (LED) curing lights and one conventional quartz tungsten halogen (QTH) curing light.

The dental market has recently been introduced to a number of commercially available light-emitting diode (LED) curing lights. Tensile bond strength was evaluated for LED curing lights (Rembrandt® Allegro^TM, Den-Mat Corp, Santa Maria, CA), (LEDemetron, Kerr/Demetron Corp, Danbury, Conn), (Ortholux LED, 3M^TMESPE^TM, St. Paul, MN),and (FLASH-lite 1001, Discus Dental, Culver City, CA) are compared with one …

Unification Of Variance Components And Haseman-Elston Regression For Quantitative Trait Linkage Analysis, Wei-Min Chen, Karl W. Broman, Kung-Yee Liang

Johns Hopkins University, Dept. of Biostatistics Working Papers

Two of the major approaches for linkage analysis with quantitative traits in humans include variance components and Haseman-Elston regression. Previously, these have been viewed as quite separate methods. We describe a general model, fit by use of generalized estimating equations (GEE), for which the variance components and Haseman-Elston methods (including many of the extensions to the original Haseman-Elston method) are special cases, corresponding to different choices for a working covariance matrix. We also show that the regression-based test of Sham et al.(2002) is equivalent to a robust score statistic derived from our GEE approach. These results have several important implications. …

A Nested Unsupervised Approach To Identifying Novel Molecular Subtypes, Elizabeth Garrett, Giovanni Parmigiani

Johns Hopkins University, Dept. of Biostatistics Working Papers

In classification problems arising in genomics research it is common to study populations for which a broad class assignment is known (say, normal versus diseased) and one seeks to find undiscovered subclasses within one or both of the known classes. Formally, this problem can be thought of as an unsupervised analysis nested within a supervised one. Here we take the view that the nested unsupervised analysis can successfully utilize information from the entire data set for constructing and/or selecting useful predictors. Specifically, we propose a mixture model approach to the nested unsupervised problem, where the supervised information is used to …

Tree-Based Multivariate Regression And Density Estimation With Right-Censored Data , Annette M. Molinaro, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a unified strategy for estimator construction, selection, and performance assessment in the presence of censoring. This approach is entirely driven by the choice of a loss function for the full (uncensored) data structure and can be stated in terms of the following three main steps. (1) Define the parameter of interest as the minimizer of the expected loss, or risk, for a full data loss function chosen to represent the desired measure of performance. Map the full data loss function into an observed (censored) data loss function having the same expected value and leading to an efficient estimator …

The Psychological Characteristics Of Obese Children, Thomas Taylor Mitchell

Loma Linda University Electronic Theses, Dissertations & Projects

Several studies along with the surgeon general of the United States have identified obesity as a national health issue. Research indicates that adult obesity treatment has relatively poor long-term effects. Consequently increased attention has been given to addressing obesity in children. This focus is particularly vital due to the fact that children are one of the populations showing the most rapid increase in overweight and obesity. The purpose of this study was to identify the some of the unique psychological characteristics of obese children by analyzing the intake data of children and adolescents attending the Loma Linda University Growing Fit …

Behavioral Evaluation Of The Psychological Welfare And Environmental Requirements Of Agricultural Research Animals: Theory, Measurement, Ethics, And Practical Implications, Lesley A. King

Experimentation Collection

The welfare of agricultural research animals relies not only on measures of good health but also on the presence of positive emotional states and the absence of aversive or unpleasant subjective states such as fear, frustration, or association with pain. Although subjective states are not inherently observable, their interaction with motivational states can be measured through assessment of motivated behavior, which indicates the priority animals place on obtaining or avoiding specific environmental stimuli and thus allows conclusions regarding the impact of housing, husbandry, and experimental procedures on animal welfare. Preference tests and consumer demand models demonstrate that animal choices are …

Geographic Variation In The Morphology Of Crotalus Horridus (Serpentes: Viperidae), John Robert Allsteadt

Biological Sciences Theses & Dissertations

The Timber Rattlesnake (Crotalus horridus) occurs in discontinuous populations throughout the eastern and central United States. The species exhibits high levels of polymorphism in morphological traits, especially in coloration and pattern. Previous studies recognized either distinct northern and southern subspecies or three regional morphs (northern, southern, and western), but conflicting data sets and limited geographic sampling of previous studies have left the relationships among those regional variants unclear. In this study, univariate and multivariate statistics, together with a geographic information system, were used to analyze geographic variation in 36 morphological characters recorded from 2,420 specimens of C. horridus …

Cluster Stability Scores For Microarray Data In Cancer Studies, Mark Smolkin, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

A potential benefit of profiling of tissue samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Hierarchical clustering has been the primary analytical tool used to define disease subtypes from microarray experiments in cancer settings. Assessing cluster reliability poses a major complication in analyzing output from these procedures. While much work has been done on assessing the global question of number of clusters in a dataset, relatively little research exists on assessing stability of individual clusters. A potential benefit of profiling of tissue samples using microarrays is the generation of molecular fingerprints that will …

Supervised Detection Of Regulatory Motifs In Dna Sequences, Sunduz Keles, Mark J. Van Der Laan, Sandrine Dudoit, Biao Xing, Michael B. Eisen

U.C. Berkeley Division of Biostatistics Working Paper Series

Identification of transcription factor binding sites (regulatory motifs) is a major interest in contemporary biology. We propose a new likelihood based method, COMODE, for identifying structural motifs in DNA sequences. Commonly used methods (e.g. MEME, Gibbs sampler) model binding sites as families of sequences described by a position weight matrix (PWM) and identify PWMs that maximize the likelihood of observed sequence data under a simple multinomial mixture model. This model assumes that the positions of the PWM correspond to independent multinomial distributions with four cell probabilities. We address supervising the search for DNA binding sites using the information derived from …

Ibd Configuration Transition Matrices And Linkage Score Tests For Unilineal Relative Pairs, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Properties of transition matrices between IBD configurations are derived for four general classes of unilineal relative pairs obtained from the grand-parent/ grand-child, half-sib, avuncular, and cousin relationships. In this setting, IBD configurations are defined as orbits of groups acting on a set of inheritance vectors. Properties of the transition matrix between IBD configurations at two linked loci are derived by relating its infinitesimal generator to the adjacency matrix of a quotient graph. The second largest eigenvalue of the infinitesimal generator and its multiplicity are key in determining the form of the transition matrix and of likelihood-based linkage tests such as …

Selecting Differentially Expressed Genes From Microarray Experiments, Margaret S. Pepe, Gary M. Longton, Garnet L. Anderson, Michel Schummer

UW Biostatistics Working Paper Series

High throughput technologies, such as gene expression arrays and protein mass spectrometry, allow one to simultaneously evaluate thousands of potential biomarkers that distinguish different tissue types. Of particular interest here is cancer versus normal organ tissues. We consider statistical methods to rank genes (or proteins) in regards to differential expression between tissues. Various statistical measures are considered and we argue that two measures related to the Receiver Operating Characteristic Curve are particularly suitable for this purpose. We also propose that sampling variability in the gene rankings be quantified and suggest using the “selection probability function”, the probability distribution of rankings …

Pain And Distress Associated With Polyclonal Antibody Production: Discussion And Recommendations, The Humane Society Of The United States

ANIMAL RESEARCH

The Humane Society of the United States (HSUS) held a workshop in August 2002 in order to develop recommendations for minimizing pain and distress associated with polyclonal antibody (Pab) production. A small group of experts in the fields of antibody production, animal welfare, in vitro alternatives, and/or regulatory compliance participated in the roundtable discussion. The workshop was a scientifically based meeting, and recommendations were based on the extensive experience of the workshop participants as well as published literature regarding the relevant issues.

Participants recognized that insufficient attention has been paid to animal welfare aspects of Pab production, in part because …

Sibling Recurrence Risk Ratio Analysis Of The Metabolic Syndrome And Its Components Over Time., Wei J. Chen, Pi Hua Liu, Yen Yi Ho, Kuo Liong Chien, Min Tzu Lo, Wei Liang Shih, Yu Chun Yen, Wen Chung Lee

Faculty Publications

The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (lambdas) and lifetime lambdas for the metabolic syndrome and its individual components over time among sibships in the prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13. Five measures included in the operational criteria of the metabolic syndrome by the Adult Treatment Panel III were examined. A method for estimating sibling recurrence risk with correction for complete ascertainment was used to estimate the numerator, and the prevalence in the whole cohort was used as the denominator of lambdas. Considerable variability in the lambdas was found …

Il-10 And Alveolar Bone Loss, Abdulaziz Saud Al-Rasheed

Loma Linda University Electronic Theses, Dissertations & Projects

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory activities. IL-10 knockout (KO) mice exhibit severe intestinal inflammation in the presence of normal gut flora. We hypothesized that IL-10 KO mice would also be susceptible to inflammatory periodontal disease resulting in alveolar bone loss (ABL). The purpose of this study was to compare naturally occurring ABL in IL-10 KO and wild type (WT) mice. Twelve IL-10 KO and 12 WT mice, age-(7 months) and sex-(male) matched, were used. Half of the mice were on 129/SvEv and half on C57BL/6J background. Animal heads were defleshed and treated to remove all organic material. ABL …

Comparative Genomic Hybridization Array Analysis, Annette M. Molinaro, Mark J. Van Der Laan, Dan H. Moore

U.C. Berkeley Division of Biostatistics Working Paper Series

At the present time, there is increasing evidence that cancer may be regulated by the number of copies of genes in tumor cells. Through microarray technology it is now possible to measure the number of copies of thousands of genes and gene segments in samples of chromosomal DNA. Microarray comparative genomic hybridization (array CGH) provides the opportunity to both measure DNA sequence copy number gains and losses and map these aberrations to the genomic sequence. Gains can signify the over-expression of oncogenes, genes which stimulate cell growth and have become hyperactive, while losses can signify under-expression of tumor suppressor genes, …

Miscellaneous Publication 8/2002 - Statistics Report For The Western Australian Floriculture Industry - August 2000, Department Of Agriculture, Western Australia

Horticulture published reports

Statistical data plays an important role in many decisions faced by both established and prospective businesses within all industry sectors. In order to offer a better service to its customers, the Department of Agriculture (the Department) requires information regarding the cutflower and nursery industry within Australia and Western Australia.

Though there are many avenues available in order to obtain this statistical information, both locally and nationally, there is no concise summary available. In addition, information obtained must be assessed in detail to determine its reliability and relevance.

Current statistics for both the Australian and Western Australian nursery and cutflower industries …

Five-Hundred Life-Saving Interventions And Their Misuse In The Debate Over Regulatory Reform, Lisa Heinzerling

RISK: Health, Safety & Environment (1990-2002)

The author argues that John D. Graham, administrator of the Office of Information and Regulatory Affairs, holds strong anti-environmental biases and has perpetuated and encouraged a misrepresentation of his own research, which has largely influenced health, safety, and environmental regulation.

A New Partitioning Around Medoids Algorithm, Mark J. Van Der Laan, Katherine S. Pollard, Jennifer Bryan

U.C. Berkeley Division of Biostatistics Working Paper Series

Kaufman & Rousseeuw (1990) proposed a clustering algorithm Partitioning Around Medoids (PAM) which maps a distance matrix into a specified number of clusters. A particularly nice property is that PAM allows clustering with respect to any specified distance metric. In addition, the medoids are robust representations of the cluster centers, which is particularly important in the common context that many elements do not belong well to any cluster. Based on our experience in clustering gene expression data, we have noticed that PAM does have problems recognizing relatively small clusters in situations where good partitions around medoids clearly exist. In this …

Peer Nutrition Education: A Model For Nutrition Education Among Spanish-Language Participants Of The Special Supplemental Nutrition Program For Women, Infants And Children (Wic), Maximino Alfredo Mejía

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the steady improvement in the health status of Americans, Hispanics are a minority in the United States with greater prevalence of several infectious and chronic diseases and less health knowledge than the average citizen. Nearly half of the Hispanics living in this country die of preventable nutrition-related conditions, with heart disease and cancer being the leading causes. Since this minority has limited access to health care and preventive services, there is a need for an inexpensive, viable model of health education for this underserved segment of the population in order to lower the excess of preventable diseases. We trained …

Anatomy And Three-Dimensional Reconstructions Of The Brain Of A Bottlenose Dolphin (Tursiops Truncatus) From Magnetic Resonance Images, Lori Marino, Keith D. Sudheimer, Timothy L. Murphy, Kristina K. Davis, D. Ann Pabst, William A. Mclellan, James K. Rilling, John I. Johnson

Veterinary Science and Medicine Collection

Cetacean (dolphin, whale, and porpoise) brains are among the least studied mammalian brains because of the formidability of collecting and histologically preparing such relatively rare and large specimens. Magnetic resonance imaging offers a means of observing the internal structure of the brain when traditional histological procedures are not practical. Furthermore, internal structures can be analyzed in their precise anatomic positions, which is difficult to accomplish after the spatial distortions often accompanying histological processing. In this study, images of the brain of an adult bottlenose dolphin, Tursiops truncatus, were scanned in the coronal plane at 148 antero-posterior levels. From these scans …

Identification Of Regulatory Elements Using A Feature Selection Method, Sunduz Keles, Mark J. Van Der Laan, Michael B. Eisen

U.C. Berkeley Division of Biostatistics Working Paper Series

Many methods have been described to identify regulatory motifs in the transcription control regions of genes that exhibit similar patterns of gene expression across a variety of experimental conditions. Here we focus on a single experimental condition, and utilize gene expression data to identify sequence motifs associated with genes that are activated under this experimental condition. We use a linear model with two way interactions to model gene expression as a function of sequence features (words) present in presumptive transcription control regions. The most relevant features are selected by a feature selection method called stepwise selection with monte carlo cross …

Statistical Inference For Simultaneous Clustering Of Gene Expression Data, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

Current methods for analysis of gene expression data are mostly based on clustering and classification of either genes or samples. We offer support for the idea that more complex patterns can be identified in the data if genes and samples are considered simultaneously. We formalize the approach and propose a statistical framework for two-way clustering. A simultaneous clustering parameter is defined as a function of the true data generating distribution, and an estimate is obtained by applying this function to the empirical distribution. We illustrate that a wide range of clustering procedures, including generalized hierarchical methods, can be defined as …

Optimum Bonding Time Of Four Different Curing Lights, Nathan Don Cotten

Loma Linda University Electronic Theses, Dissertations & Projects

With the development of new high-intensity curing lights, the time required to bond orthodontic brackets is steadily decreasing. The objective of this study was to determine the optimum curing time for bonding orthodontic brackets using four different visible curing lights (Standard Optilux 501, High Intensity Optilux 501 with Turbo Tip, Virtuoso Plasma Arc, and ESPE LED light). This study also tested the new generation of light emitting diode (LED) lights to determine if they can be used for bonding orthodontic brackets. Three hundred freshly extracted bovine teeth were mounted in acrylic resin and divided into 20 groups of 15 teeth …

Magnetic Resonance Imaging And Three-Dimensional Reconstructions Of The Brain Of A Fetal Common Dolphin, Delphinus Delphis, Lori Marino, Timothy L. Murphy, Lyad Gozal, John I. Johnson

Veterinary Science and Medicine Collection

To demonstrate the kinds of data that can be obtained non-destructively and non-invasively from preserved museum specimens using modern imaging technology the head region of a whole body fetal specimen of the common dolphin, Delphinus delphis, aged 8–9 months post-conception, was scanned using Magnetic Resonance Imaging (MRI). Series of scans were obtained in coronal, sagittal and horizontal planes. A digital three-dimensional reconstruction of the whole brain was prepared from the coronal series of scans. Sectional areas and three-dimensional volumes were obtained of the cerebral hemispheres and of the brainstemplus-cerebellum. Neuroanatomical features identified in the scans include the major sulci of …

Taking Animal Welfare Seriously: Minimizing Pain And Distress In Research Animals, The Humane Society Of The United States

ANIMAL RESEARCH

Pain and distress caused by specific research models and techniques raise serious concerns for those in the animal welfare community as well as in the scientific community. Yet good estimates of how much animal pain and/or animal distress is caused by particular techniques or methods are not yet available. The HSUS has compiled a preliminary list of research models and techniques that cause pain and distress. Analyses by the USDA and HSUS indicate that the majority of the animals reported in Column E are used in various testing procedures, with vaccine testing prominent among them. More data are needed to …

Evaluation Of Animal Model Research, Kenneth J. Shapiro

Experimentation Collection

It is argued that a concept of evaluation of animal models that is broader and more useful than validation is available. Productive generativity refers to the degree to which a model furthers understanding and leads to more-effective treatment interventions. Results of the application of this novel evaluative frame to several animal models of eating disorders show that this animal-based research has not been productive. The question of the relation between clinic and animal laboratory is discussed.

State Of The Fisheries Report 1999/2000, J. W. Penn, Fisheries Western Australia

Status Reports of the Fisheries and Aquatic Resources

The State of the Fisheries document is designed as an essential supplement to the Annual Report to Parliament and provides a more detailed level of information to support the agency's non-financial performance measures.

By summarising management changes, compliance activities and research data such as landings, effort, catch rates, stock assessment and breeding stock levels, this document provides a valuable reference point for Western Australian fisheries of major importance to the commercial, recreational and aquaculture sectors. Information relevant to Fisheries WA's Fish and Fish Habitat Protection Program is also provided.

The report indicates that overall the major fish stocks which support …