Statistics and Probability Commons^™

Can Animal Models Of Disease Reliably Inform Human Studies?, H. Bart Van Der Worp, David W. Howells, Emily Sena, Michelle J. Porritt, Sarah Rewell, Victoria O'Collins, Malcolm Macleod

Validation of Animal Experimentation Collection

• The value of animal experiments for predicting the effectiveness of treatment strategies in clinical trials has remained controversial, mainly because of a recurrent failure of interventions apparently promising in animal models to translate to the clinic.
• Translational failure may be explained in part by methodological flaws in animal studies, leading to systematic bias and thereby to inadequate data and incorrect conclusions about efficacy.
• Failures also result because of critical disparities, usually disease specific, between the animal models and the clinical trials testing the treatment strategy.
• Systematic review and meta-analysis of animal studies may aid in the selection of the most …

Publication Bias In Reports Of Animal Stroke Studies Leads To Major Overstatement Of Efficacy, Emily Sena, H. Bart Van Der Worp, Philip M.W. Bath, David W. Howells, Malcolm Macleod

Validation of Animal Experimentation Collection

The consolidation of scientific knowledge proceeds through the interpretation and then distillation of data presented in research reports, first in review articles and then in textbooks and undergraduate courses, until truths become accepted as such both amongst “experts” and in the public understanding. Where data are collected but remain unpublished, they cannot contribute to this distillation of knowledge. If these unpublished data differ substantially from published work, conclusions may not reflect adequately the underlying biological effects being described. The existence and any impact of such “publication bias” in the laboratory sciences have not been described. Using the CAMARADES (Collaborative Approach …

Monopoly, Regulation, And Innovation, Matt Bogard

Economics Faculty Publications

Recently the Justice department has started investigations into alleged anti-trust violations by Monsanto. This has helped fuel a lot of already hyped discontent with one of the world’s leaders in innovative solutions for sustainable agriculture. This article discusses how the regulatory environment could possibly have contributed to more concentration and power in the biotech industry. Increasing regulation would likely have the opposite effect of creating a level playing field in the agriculture industry. From AgWeb, March 27,2010 http://www.agweb.com/blog/Economic_Sense_190/Monopoly_Regulation__and_Innovation_10771/

Effects Of Socioeconomic Status On Brain Development, And How Cognitive Neuroscience May Contribute To Levelling The Playing Field, Rajeev Raizada, Mark M. Kishiyama

Dartmouth Scholarship

The study of socioeconomic status (SES) and the brain finds itself in a circumstance unusual for Cognitive Neuroscience: large numbers of questions with both practical and scientific importance exist, but they are currently under-researched and ripe for investigation. This review aims to highlight these questions, to outline their potential significance, and to suggest routes by which they might be approached. Although remarkably few neural studies have been carried out so far, there exists a large literature of previous behavioural work. This behavioural research provides an invaluable guide for future neuroimaging work, but also poses an important challenge for it: how …

Applied Statistics: Experience & Cerification In Quality Assurance, Huey D. Dodson

Statistics

The composition of my senior project can be broken down into two parts. The first part of my project, without which the second could not be pursued, involved a 13 week internship at a produce processing facility where I took part in several projects varying in scope and type. The second part was to acquire certification as a Quality Process Analyst from the American Society for Quality.

This document is structured to represent the dichotomous nature of my project; the first section is dedicated to my internship experience, and the second dedicated to the certification examination preparation and completion.

Using R, Matt Bogard

Economics Faculty Publications

R is a statistical programming language with a command line interface that is becoming more and more popular every day. I have used R for data visualization, data mining/machine learning, as well as social network analysis. Initially embraced largely in academia, R is becoming the software of choice in various corporate settings.

Noncompliance With Public Health Service (Phs) Policy On Humane Care And Use Of Laboratory Animals: An Exploratory Analysis, Leah M. Gomez, Kathleen Conlee, Martin Stephens

Laboratory Experiments Collection

The National Institutes of Health (NIH) is a major biomedical research-funding body in the United States. Approximately 40% of NIH-funded research involves experimentation on nonhuman animals (Monastersky, 2008). Institutions that conduct animal research with NIH funds must adhere to the Public Health Service (PHS) care and use standards of the Office of Laboratory Animal Welfare (OLAW, 2002a). Institutions deviating significantly from the PHS’s animal care and use standards must report these incidents to the NIH’s OLAW. This study is an exploratory analysis of all the significant deviations reported by animal-research facilities to OLAW during a 3-month period. The study identifies …

The Scher Report On Non-Human Primate Research — Biased And Deeply Flawed, Jarrod Bailey, Katy Taylor

Experimentation Collection

The European Commission’s Scientific Committee on Health and Environmental Risks (SCHER) recently issued an Opinion on the need for non-human primate (NHP) use in biomedical research, and the possibilities of replacing NHP use with alternatives, as part of the Directive 86/609/EEC revision process. Here, we summarise our recent complaint to the European Ombudsman about SCHER’s Opinion and the entire consultation process. It is our opinion that the Working Group almost entirely failed to address its remit, and that the Group was unbalanced and contained insufficient expertise. The Opinion presumed the validity of NHP research with inadequate supporting evidence, and ignored …

Impact Of Ambient Air Pollution On Survival Of Renal Transplant Recipients, Rhonda Kristine Hwang

Loma Linda University Electronic Theses, Dissertations & Projects

There is increasing evidence that ambient air pollution is associated with coronary heart disease morbidity and mortality. This research has focused on the general public and less so on possible sensitive subgroups even though these may have even greater susceptibility to adverse effects of ambient air pollution. With highly prevalent traditional as well as nontraditional risk factors, renal transplant recipients may potentially be a sensitive subgroup. The purpose of this study was to evaluate the possible effect of between long-term exposure to air pollution on the risk of CHD mortality among renal transplant recipients. This cohort study includes 32,239 adult, …

The Effects Of Physical Activity And Nutrient Intake On The Risk Of Hip Fracture : Results From The Adventist Health Study-2, Wen-Ling Liao

Loma Linda University Electronic Theses, Dissertations & Projects

This is a two year of follow up study of Adventist Health Study-2 (AHS-2). We assessed the association between physical activity, nutrient intake and risk of hip fracture among peri- and post menopausal Caucasian women using unconditional logistic regression models. All subjects completed a lifestyle questionnaire which including information of physical activity and frequency and portion size of food intake at enrollment into the study (2002-2007). The “Bi-Annual Hospitalization History” questionnaire which included a question about hip fractures due to minor trauma/falls was sent to subjects approximately two years after enrollment, with a response rat of 82.84%. In this cohort, …

Barrow Island Ute Guide - Non-Indigenous Insects, Spiders And Snails, Mike Grimm, Kristofer Collett, Peter Davis, Marc Widmer, Andras Szito, Rob Emery, Peter Mangano

Biosecurity published reports

Barrow Island, the second largest island in Western Australia, is a Class A Nature Reserve and home to a variety of rare and endangered fauna and flora, some of which occur nowhere else. The island lies about 70 km off the north-west coast of Western Australia and 150 km west of Karratha.

Oil discoveries in the 1960s and the development of massive Northwest Shelf gas reserves since the 1990s made Barrow Island an important site for these industries. Strict environmental and quarantine conditions are placed on industry seeking permits to drill oil wells and construct gas processing plants. Oil production …

Anthropometric Parameters Of Under-Five Years Old Children With Different Dietary Habits In Ukambani Region : A Study In Eastern Rural Kenya, Hellen M. Ndiku

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this descriptive cross sectional study was to assess dietary intake and nutritional status of children under-five years in two rural sites of Eastern Kenya where the staple cereals may differ. A modified rapid, knowledge, practice and coverage (KPC) questionnaire and a 24-hr dietary recall form were used to collect the data. A total of 403 households were surveyed from four randomly selected divisions. This yielded 629 surrogate 24-hr dietary recalls of children < 5 years with 314 from Mwingi district and 315 from Makueni district (49 % boys and 51 % girls).

Statistical analysis was done using SPSS and SAS. Comparison of means was done using t- test and chi square was used for proportions. The 24-hr …

Resampling-Based Multiple Hypothesis Testing With Applications To Genomics: New Developments In The R/Bioconductor Package Multtest, Houston N. Gilbert, Katherine S. Pollard, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

The multtest package is a standard Bioconductor package containing a suite of functions useful for executing, summarizing, and displaying the results from a wide variety of multiple testing procedures (MTPs). In addition to many popular MTPs, the central methodological focus of the multtest package is the implementation of powerful joint multiple testing procedures. Joint MTPs are able to account for the dependencies between test statistics by effectively making use of (estimates of) the test statistics joint null distribution. To this end, two additional bootstrap-based estimates of the test statistics joint null distribution have been developed for use in the …

Joint Multiple Testing Procedures For Graphical Model Selection With Applications To Biological Networks, Houston N. Gilbert, Mark J. Van Der Laan, Sandrine Dudoit

U.C. Berkeley Division of Biostatistics Working Paper Series

Gaussian graphical models have become popular tools for identifying relationships between genes when analyzing microarray expression data. In the classical undirected Gaussian graphical model setting, conditional independence relationships can be inferred from partial correlations obtained from the concentration matrix (= inverse covariance matrix) when the sample size n exceeds the number of parameters p which need to estimated. In situations where n < p, another approach to graphical model estimation may rely on calculating unconditional (zero-order) and first-order partial correlations. In these settings, the goal is to identify a lower-order conditional independence graph, sometimes referred to as a ‘0-1 graphs’. For either choice of graph, model selection may involve a multiple testing problem, in which edges in a graph are drawn only after rejecting hypotheses involving (saturated or lower-order) partial correlation parameters. Most multiple testing procedures applied in previously proposed graphical model selection algorithms rely on standard, marginal testing methods which do not take into account the joint distribution of the test statistics derived from (partial) correlations. We propose and implement a multiple testing framework useful when testing for edge inclusion during graphical model selection. Two features of our methodology include (i) a computationally efficient and asymptotically valid test statistics joint null distribution derived from influence curves for correlation-based parameters, and (ii) the application of empirical Bayes joint multiple testing procedures which can effectively control a variety of popular Type I error rates by incorpo- rating joint null distributions such as those described here (Dudoit and van der Laan, 2008). Using a dataset from Arabidopsis thaliana, we observe that the use of more sophisticated, modular approaches to multiple testing allows one to identify greater numbers of edges when approximating an undirected graphical model using a 0-1 graph. Our framework may also be extended to edge testing algorithms for other types of graphical models (e.g., for classical undirected, bidirected, and directed acyclic graphs).

Sparse Linear Discriminant Analysis For Simultaneous Testing For The Significance Of A Gene Set/Pathway And Gene Selection, Michael C. Wu, Lingson Zhang, Zhaoxi Wang, David C. Christiani, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

Are Animal Models Predictive For Humans?, Niall Shanks, Ray Greek, Jean Greek

Validation of Animal Experimentation Collection

It is one of the central aims of the philosophy of science to elucidate the meanings of scientific terms and also to think critically about their application. The focus of this essay is the scientific term predict and whether there is credible evidence that animal models, especially in toxicology and pathophysiology, can be used to predict human outcomes. Whether animals can be used to predict human response to drugs and other chemicals is apparently a contentious issue. However, when one empirically analyzes animal models using scientific tools they fall far short of being able to predict human responses. This is …

Understanding The Physical Properties That Control Protein Crystallization By Analysis Of Largescale Experimental Data, W. Nicholson Price Ii, Yang Chen, Samuel K. Handelman, Helen Neely, Philip Manor, Richard Karlin, Rajesh Nair, Jinfeng Liu, Michael Baran, John Everett, Saichiu N. Tong, Farhad Forouhar, Swarup S. Swaminathan, Thomas Acton, Rong Xiao, Joseph R. Luft, Angela Lauricella, George T. Detitta, Burkhard Rost, Gaetano T. Montelione, John T. Hunt

Law Faculty Scholarship

Crystallization is the most serious bottleneck in high-throughput protein-structure determination by diffraction methods. We have used data mining of the large-scale experimental results of the Northeast Structural Genomics Consortium and experimental folding studies to characterize the biophysical properties that control protein crystallization. This analysis leads to the conclusion that crystallization propensity depends primarily on the prevalence of well-ordered surface epitopes capable of mediating interprotein interactions and is not strongly influenced by overall thermodynamic stability. We identify specific sequence features that correlate with crystallization propensity and that can be used to estimate the crystallization probability of a given construct. Analyses of …

The Validity Of Animal Experiments In Medical Research, Gill Langley

Experimentation Collection

Other animals, such as mice, rats, rabbits, dogs and monkeys, are widely used as surrogates for humans in fundamental medical research. This involves creating disorders in animals by chemical, surgical or genetic means, with the aim of mimicking selected aspects of human illnesses.

It is a truism that any model or surrogate is not identical to the target being modelled. So, in medical research, experiments using animals or cell cultures or even healthy volunteers instead of patients (being the target population with the target illness) will inevitably have limitations, although these will be greater or lesser depending on the model.

The Minimization Of Research Animal Distress And Pain: Conclusions And Recommendations, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Laboratory Experiments Collection

While the attention given to preventing, assessing, and alleviating pain in research animals has increased noticeably in recent decades, much remains to be done both in terms of implementing best practices and conducting studies to answer outstanding questions. In contrast, the attention to distress (particularly non-pain induced distress) has shown no comparable increase. There are many reasons for this discrepancy, including the conceptual untidiness of the distress concept, the paucity of pharmacological treatments for distress, and perceived lack of regulatory emphasis on distress. These are challenges that need to be addressed and overcome. This book is intended to help meet …

Addressing Distress And Pain In Animal Research: The Veterinary, Research, Societal, Regulatory And Ethical Contexts For Moving Forward, Kathleen Conlee, Martin Stephens, Andrew N. Rowan

Experimentation Collection

While most people recognize that biomedical scientists are searching for knowledge that will improve the health of humans and animals, the image of someone deliberately causing harm to an animal in order to produce data that may lead to some future benefit has always prompted an uncomfortable reaction outside the laboratory. However, proponents of animal research have usually justified the practice by reference to greater benefits (new knowledge and medical treatments) over lesser costs (in animal suffering and death). Given that one of the costs of animal research is the suffering experienced by the animals, the goal of eliminating distress …

The Role Of Clinical Veterinary Medicine In The Assessment And Treatment Of Laboratory Animal Distress, V. Hampshire

Veterinary Science and Medicine Collection

It is doubtful that the scientific community will ever arrive at a consensus definition for distress as it may be attempted for the purposes of improving animal welfare in and across the myriad of research, testing and teaching facilities in the United States and throughout the minuet of protocols that exist for animals. The stakeholders in this attempt can however address most causes of physiologic distress by instituting time-honored veterinary and agrarian approaches to animal surveillance. In this manner, the majority of individuals who participate in responsible and humane animal care might be assuaged in that a condition of maximum …

In Step With Hiv Vaccines? A Content Analysis Of Local Recruitment Campaigns For An International Hiv Vaccine Study, Paula M. Frew, Wendy Macias, Kayshin Chan, Ashley Harding

Environmental & Global Health Faculty Research

During the past two decades of the HIV/AIDS pandemic, several recruitment campaigns were designed to generate community involvement in preventive HIV vaccine clinical trials. These efforts utilized a blend of advertising and marketing strategies mixed with public relations and community education approaches to attract potential study participants to clinical trials (integrated marketing communications). Although more than 30,000 persons worldwide have participated in preventive HIV vaccine studies, no systematic analysis of recruitment campaigns exists. This content analysis study was conducted to examine several United States and Canadian recruitment campaigns for one of the largest-scale HIV vaccine trials to date (the “Step …

The Influence Of Familism On Descriptive And Injunctive Norms In Predicting The Intention To Eat A Vegetarian Diet Among Chinese Seventh-Day Adventists, See Wei Toh

Loma Linda University Electronic Theses, Dissertations & Projects

According to the theory of planned behavior (TpB), one determinant of intention to engage in a behavior is the subjective norm. Various studies have found that subjective norm is often the weaker predictor of intention compared to perceived behavioral control and attitude. This study examined whether familism (emphasis on the family rather than the individual) would contribute positively to the predictive power of the TpB model through interactions with the family portion of descriptive and injunctive norms. Descriptive and injunctive norms are component variables of the subjective norm. A sample of 284 adult Chinese Seventh-day Adventists 18 years and older …

Multiple Imputation To Correct For Measurement Error In Admixture Estimates In Genetic Structured Association Testing, Miguel A. Padilla, Jamin Divers, Laura K. Vaughan, David B. Allison, Hemant K. Tiwari

Psychology Faculty Publications

Objectives: Structured association tests ( SAT), like any statistical model, assumes that all variables are measured without error. Measurement error can bias parameter estimates and confound residual variance in linear models. It has been shown that admixture estimates can be contaminated with measurement error causing SAT models to suffer from the same afflictions. Multiple imputation (MI) is presented as a viable tool for correcting measurement error problems in SAT linear models with emphasis on correcting measurement error contaminated admixture estimates. Methods: Several MI methods are presented and compared, via simulation, in terms of controlling Type I error rates for both …

The Strength Of Statistical Evidence For Composite Hypotheses With An Application To Multiple Comparisons, David R. Bickel

COBRA Preprint Series

The strength of the statistical evidence in a sample of data that favors one composite hypothesis over another may be quantified by the likelihood ratio using the parameter value consistent with each hypothesis that maximizes the likelihood function. Unlike the p-value and the Bayes factor, this measure of evidence is coherent in the sense that it cannot support a hypothesis over any hypothesis that it entails. Further, when comparing the hypothesis that the parameter lies outside a non-trivial interval to the hypotheses that it lies within the interval, the proposed measure of evidence almost always asymptotically favors the correct hypothesis …

An Assessment Of The Role Of Chimpanzees In Aids Vaccine Research, Jarrod Bailey

Laboratory Experiments Collection

Prior to Simian Immunodeficiency Virus (SIV)-infected macaques becoming the ‘model of choice’ in the 1990s, chimpanzees were widely used in AIDS vaccine research and testing. Faced with the continued failure to develop an effective human vaccine, some scientists are calling for a return to their widespread use. To assess the past and potential future contribution of chimpanzees to AIDS vaccine development, databases and published literature were systematically searched to compare the results of AIDS vaccine trials in chimpanzees with those of human clinical trials, and to determine whether the chimpanzee trials were predictive of the human response. Protective and/or therapeutic …

The Comparative Radiopacity Between Primary And Permanent Teeth, Robert C. Lee

Loma Linda University Electronic Theses, Dissertations & Projects

Purpose: This in vitro study compared the radiopacity between human primary and permanent enamel and dentin. It also compared the radiopacity between human anterior and posterior teeth.

Methods: Extracted primary and permanent teeth were used in this study. One mm enamel and one mm dentin slices were cut from each extracted tooth. Radiographs were taken of each enamel and dentin specimen 1 mm in thickness along with an aluminum step-wedge using procedures specified in International Standards Organization (ISO) 4049:2000. A densitometer was used to measure the Optical Density (OD) of the radiographs of the specimen and the accompanying aluminum step-wedge. …

Volunteer Studies In Pain Research — Opportunities And Challenges To Replace Animal Experiments: The Report And Recommendations Of A Focus On Alternatives Workshop, C. K. Langley, Q. Aziz, C. Bountra, N. Gordon, P. Hawkins, A. Jones, G. Langley, T. Nurmikko, I. Tracey

Experimentation Collection

Despite considerable research, effective and safe treatments for human pain disorders remain elusive. Understanding the biology of different human pain conditions and researching effective treatments continue to be dominated by animal models, some of which are of limited value. British and European legislation demands that non-animal approaches should be considered before embarking on research using experimental animals. Recent scientific and technical developments, particularly in human neuroimaging, offer the potential to replace some animal procedures in the study of human pain. A group of pain research experts from academia and industry met with the aim of exploring creatively the tools, strategies …

Estimation And Testing For The Effect Of A Genetic Pathway On A Disease Outcome Using Logistic Kernel Machine Regression Via Logistic Mixed Models, Dawei Liu, Debashis Ghosh, Xihong Lin

Harvard University Biostatistics Working Paper Series

No abstract provided.

A Powerful And Flexible Multilocus Association Test For Quantitative Traits, Lydia Coulter Kwee, Dawei Liu, Xihong Lin, Debashis Ghosh, Michael P. Epstein

Harvard University Biostatistics Working Paper Series

No abstract provided.