Multivariate Analysis Commons^™

In Vitro Antimicrobial Efficacy Of Calcium Hydroxides In Root Dentin, Josef W. Lubisich

Loma Linda University Electronic Theses, Dissertations & Projects

Enterococcus faecalis is the most commonly isolated bacteria in failed root canal treatment. Endodontic intracanal medicaments are commonly tested using standardized bovine cylinders infected with bacteria. The literature is not clear on whether calcium hydroxides are able to remove E. faecalis from the dentinal tubules. One reason for this is that there are several varying forms of calcium hydroxide commonly used. The purpose of the present experiment was to determine whether four commonly used calcium hydroxide products were able to reduce E. faecalis from four incremental samples of dentin and to determine if there was a statistically significant difference between …

Effects Of Diabetes Mellitus On The Healing Of The Dental Pulp, Stuart Evan Garber

Loma Linda University Electronic Theses, Dissertations & Projects

Diabetes Mellitus (DM) has been implicated as a factor affecting healing. The purpose of this study was to use the healing of experimentally exposed pulps subsequent to pulp capping as a model to determine the effect of DM on healing.

Twenty-two Sprague-Dawley rats were divided into two groups of eleven animals each. In one group, DM was induced by injection of 70 mg/KG of streptozotocin. In the other group, the animals were injected with sterile saline. Under anesthesia with Ketamine and Xylazine, the pulps of the maxillary first molars of all rats were exposed using a 1/16 round bur under …

The Effect Of Calcium Hydroxide Pastes On Root Dentin Fracture Resistance, Kurt W. Sturz

Loma Linda University Electronic Theses, Dissertations & Projects

Calcium hydroxide is a common intracanal medicament used in the treatment of immature teeth that have been subjected to trauma or decay prior to root canal therapy. The effect of calcium hydroxide on immature root dentin is important. One area of concern is the effect that calcium hydroxide has on the fracture resistance of an immature tooth. It is the aim of this study to compare the effect of four different commercially available calcium hydroxide pastes on the fracture resistance of bovine teeth. Seventy-five freshly extracted, intact bovine incisors were prepared according to a modified Haapasalo and Orstavik technique. Each …

Multiple Tests Of Association With Biological Annotation Metadata, Sandrine Dudoit, Sunduz Keles, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

We propose a general and formal statistical framework for the multiple tests of associations between known fixed features of a genome and unknown parameters of the distribution of variable features of this genome in a population of interest. The known fixed gene-annotation profiles, corresponding to the fixed features of the genome, may concern Gene Ontology (GO) annotation, pathway membership, regulation by particular transcription factors, nucleotide sequences, or protein sequences. The unknown gene-parameter profiles, corresponding to the variable features of the genome, may be, for example, regression coefficients relating genome-wide transcript levels or DNA copy numbers to possibly censored biological and …

Test Statistics Null Distributions In Multiple Testing: Simulation Studies And Applications To Genomics, Katherine S. Pollard, Merrill D. Birkner, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Multiple hypothesis testing problems arise frequently in biomedical and genomic research, for instance, when identifying differentially expressed or co-expressed genes in microarray experiments. We have developed generally applicable resampling-based single-step and stepwise multiple testing procedures (MTP) for control of a broad class of Type I error rates, defined as tail probabilities and expected values for arbitrary functions of the numbers of false positives and rejected hypotheses (Dudoit and van der Laan, 2005; Dudoit et al., 2004a,b; Pollard and van der Laan, 2004; van der Laan et al., 2005, 2004a,b). As argued in the early article of Pollard and van der …

New Statistical Paradigms Leading To Web-Based Tools For Clinical/Translational Science, Knut M. Wittkowski

COBRA Preprint Series

As the field of functional genetics and genomics is beginning to mature, we become confronted with new challenges. The constant drop in price for sequencing and gene expression profiling as well as the increasing number of genetic and genomic variables that can be measured makes it feasible to address more complex questions. The success with rare diseases caused by single loci or genes has provided us with a proof-of-concept that new therapies can be developed based on functional genomics and genetics.

Common diseases, however, typically involve genetic epistasis, genomic pathways, and proteomic pattern. Moreover, to better understand the underlying biologi-cal …

The Clustering Of Regression Models Method With Applications In Gene Expression Data, Li-Xuan Qin, Steven G. Self

UW Biostatistics Working Paper Series

Identification of differentially expressed genes and clustering of genes are two important and complementary objectives addressed with gene expression data. For the differential expression question, many "per-gene" analytic methods have been proposed. These methods can generally be characterized as using a regression function to independently model the observations for each gene; various adjustments for multiplicity are then used to interpret the statistical significance of these per-gene regression models over the collection of genes analyzed. Motivated by this common structure of per-gene models, we propose a new model-based clustering method -- the clustering of regression models method, which groups genes that …

Cluster Analysis Of Genomic Data With Applications In R, Katherine S. Pollard, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In this paper, we provide an overview of existing partitioning and hierarchical clustering algorithms in R. We discuss statistical issues and methods in choosing the number of clusters, the choice of clustering algorithm, and the choice of dissimilarity matrix. In particular, we illustrate how the bootstrap can be employed as a statistical method in cluster analysis to establish the reproducibility of the clusters and the overall variability of the followed procedure. We also show how to visualize a clustering result by plotting ordered dissimilarity matrices in R. We present a new R package, hopach, which implements the hybrid clustering method, …

Multiple Testing Procedures: R Multtest Package And Applications To Genomics, Katherine S. Pollard, Sandrine Dudoit, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

The Bioconductor R package multtest implements widely applicable resampling-based single-step and stepwise multiple testing procedures (MTP) for controlling a broad class of Type I error rates, in testing problems involving general data generating distributions (with arbitrary dependence structures among variables), null hypotheses, and test statistics. The current version of multtest provides MTPs for tests concerning means, differences in means, and regression parameters in linear and Cox proportional hazards models. Procedures are provided to control Type I error rates defined as tail probabilities for arbitrary functions of the numbers of false positives and rejected hypotheses. These error rates include tail probabilities …

The Effect Of Naocl, Ca(Oh)2, Mta And Mtad On Root Dentin Fracture Resistance, Sunil Ilapogu

Loma Linda University Electronic Theses, Dissertations & Projects

Various materials are used for the treatment of immature teeth that have been subjected to trauma or decay. It is not well established what effect these materials may have on the immature root dentin. A concern would be the resistance to fracture of the remaining root dentin. The purpose of this study was to compare the resistance of fracture of bovine teeth treated with sodium hypochlorite, calcium hydroxide, gray MTA and gray MTA in conjunction with MTAD after certain periods of time. One hundred and ninety five freshly extracted, intact bovine incisors were prepared using a modified Haapasalo and Orstavik …

Finding Cancer Subtypes In Microarray Data Using Random Projections, Debashis Ghosh

The University of Michigan Department of Biostatistics Working Paper Series

One of the benefits of profiling of cancer samples using microarrays is the generation of molecular fingerprints that will define subtypes of disease. Such subgroups have typically been found in microarray data using hierarchical clustering. A major problem in interpretation of the output is determining the number of clusters. We approach the problem of determining disease subtypes using mixture models. A novel estimation procedure of the parameters in the mixture model is developed based on a combination of random projections and the expectation-maximization algorithm. Because the approach is probabilistic, our approach provides a measure for the number of true clusters …

Condylar Remodeling After Distraction Osteogenesis And Bilateral Sagittal Split Osteotomy, Robert Barker Hoffman

Loma Linda University Electronic Theses, Dissertations & Projects

The present pilot study is a histological evaluation of mandibular condyles taken from minipigs that underwent either traditional mandibular advancement (bilateral sagittal split osteotomy), or a distraction osteogenesis procedure to advance the mandible. One pig received a bilateral sagittal split osteotomy with an immediate mandibular advancement of 14 mm, while another pig underwent distraction osteogenesis consisting of a gradual advancement of 2 mm per day to advance the mandible the same distance. The control animal received no surgery.

In the present study, the mandibular condyles of the three pigs (2 control, 2 bilateral sagittal split osteotomy, and 2 distraction osteogenesis) …

Significance Analysis Of Time Course Microarray Experiments, John D. Storey, Wenzhong Xiao, Jeffrey T. Leek, Ronald G. Tompkins, Ron W. Davis

UW Biostatistics Working Paper Series

Characterizing the genome-wide dynamic regulation of gene expression is important and will be of much interest in the future. However, there is currently no established method for identifying differentially expressed genes in a time course study. Here we propose a significance method for analyzing time course microarray studies that can be applied to the typical types of comparisons and sampling schemes. This method is applied to two studies on humans. In one study, genes are identified that show differential expression over time in response to in vivo endotoxin administration. Using our method 7409 genes are called significant at a 1% …

Quantification And Visualization Of Ld Patterns And Identification Of Haplotype Blocks, Yan Wang, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Classical measures of linkage disequilibrium (LD) between two loci, based only on the joint distribution of alleles at these loci, present noisy patterns. In this paper, we propose a new distance-based LD measure, R, which takes into account multilocus haplotypes around the two loci in order to exploit information from neighboring loci. The LD measure R yields a matrix of pairwise distances between markers, based on the correlation between the lengths of shared haplotypes among chromosomes around these markers. Data analysis demonstrates that visualization of LD patterns through the R matrix reveals more deterministic patterns, with much less noise, than …

Classification Using Generalized Partial Least Squares, Beiying Ding, Robert Gentleman

Bioconductor Project Working Papers

The advances in computational biology have made simultaneous monitoring of thousands of features possible. The high throughput technologies not only bring about a much richer information context in which to study various aspects of gene functions but they also present challenge of analyzing data with large number of covariates and few samples. As an integral part of machine learning, classification of samples into two or more categories is almost always of interest to scientists. In this paper, we address the question of classification in this setting by extending partial least squares (PLS), a popular dimension reduction tool in chemometrics, in …

Calibrating Observed Differential Gene Expression For The Multiplicity Of Genes On The Array, Yingye Zheng, Margaret S. Pepe

UW Biostatistics Working Paper Series

In a gene expression array study, the expression levels of thousands of genes are monitored simultaneously across various biological conditions on a small set of subjects. One goal of such studies is to explore a large pool of genes in order to select a subset of genes that appear to be differently expressed for further investigation. Of particular interest here is how to select the top k genes once genes are ranked based on their evidence for differential expression in two tissue types. We consider statistical methods that provide a more rigorous and intuitively appealing selection process for k. We …

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 …

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 …

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 …

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 …

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, …

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 …

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 …

Periodontal Repair In Dogs : Evaluation Of Rhbmp-2 Carriers, Lauralee Nygaard

Loma Linda University Electronic Theses, Dissertations & Projects

This study evaluated candidate carriers for recombinant human bone morphogenic protein-2 (rhBMP-2) in periodontal reconstructive surgery.

Canine demineralized bone matrix (DBM), bovine inorganic crystallene bone matrix (Bio-Oss), bovine derived microfibrillar collagen matrix (Helistat), poly (D,L-lactide-coglycolide) micropaiticles (PLGA), and polylactic acid granules (Drilac) were used with rhBMP-2 (20 (µg/100 µl implant volume) in routine critical size canine supraalveolar periodontal defects. Contralateral defects in six beagle dogs were randomly assigned to receive: DBM/rhBMP-2, DBM-control, Bio-Oss/rhBMP-2, Helistat/rhBMP-2, PLGA/rhBMP-2, or Drilac/rhBMP-2, all with autologous blood except for Helistat and PLGA. Animals were sacrificed eight weeks post-surgery and block sections of the defects were processed …