Design of Experiments and Sample Surveys Commons^™

The Usefulness Of Systematic Reviews Of Animal Experiments For The Design Of Preclinical And Clinical Studies, Rob B.M. De Vries, Kimberley E. Weaver, Marc T. Avey, Martin Stephens, Emily S. Sena, Marlies Leenaars

Martin Stephens, PhD

The question of how animal studies should be designed, conducted, and analyzed remains underexposed in societal debates on animal experimentation. This is not only a scientific but also amoral question. After all, if animal experiments are not appropriately designed, conducted, and analyzed, the results produced are unlikely to be reliable and the animals have in effect been wasted. In this article, we focus on one particular method to address this moral question, namely systematic reviews of previously performed animal experiments. We discuss how the design, conduct, and analysis of future (animal and human) experiments may be optimized through such systematic …

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

Martin Stephens, PhD

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 …

Walking To Recovery - The Effects Of Postsurgical Ambulation On Patient Recovery Times, Trent William Stethen

Chancellor’s Honors Program Projects

No abstract provided.

Animal Model Research: The Apples And Oranges Quandary, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

In this paper, I explore the premises underlying the problem of the evaluation of animal models. I argue that the presence of similarities and differences between the model and the modelled, although historically and currently a dominant antinomy framing evaluation, is not a bottom-line consideration. What is critical is 1) whether we learn and 2) whether we improve treatment through the animal model research. Similarity between model and modelled and the closely related concept of validity are not coterminus with these critical evaluative measures. In fact, differences between the model and modelled also can provide impetus to new understanding and …

Models For Hsv Shedding Must Account For Two Levels Of Overdispersion, Amalia Magaret

UW Biostatistics Working Paper Series

We have frequently implemented crossover studies to evaluate new therapeutic interventions for genital herpes simplex virus infection. The outcome measured to assess the efficacy of interventions on herpes disease severity is the viral shedding rate, defined as the frequency of detection of HSV on the genital skin and mucosa. We performed a simulation study to ascertain whether our standard model, which we have used previously, was appropriately considering all the necessary features of the shedding data to provide correct inference. We simulated shedding data under our standard, validated assumptions and assessed the ability of 5 different models to reproduce the …

Evaluation Of Animal Model Research, Kenneth J. Shapiro

Kenneth J. Shapiro, PhD

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.

The Relationship Between Self-Determination And Client Outcomes Among The Homeless, Samuel M. Hanna

Electronic Theses, Projects, and Dissertations

This paper has attempted to determine if there is a significant relationship between self-determination and client outcomes among the homeless. The study has been based upon the conceptual framework set forth in Self-Determination Theory. The purpose of the study was to explore the relationship between self-determination and client outcomes among the homeless. Using a data collection instrument, based on empirically validated instrumentation, clients from several homeless service providers in the City of San Bernardino were assessed for the level of self-determination and autonomy support they experience within these agencies. Outcome measures included such things as whether the client was going …

Expectations For Methodology And Translation Of Animal Research: A Survey Of Health Care Workers, Ari Joffe, Meredith Bara, Natalie Anton, Nathan Nobis

Nathan M. Nobis, PhD

Background: Health care workers (HCW) often perform, promote, and advocate use of public funds for animal research (AR); therefore, an awareness of the empirical costs and benefits of animal research is an important issue for HCW. We aim to determine what health-care-workers consider should be acceptable standards of AR methodology and translation rate to humans. Methods: After development and validation, an e-mail survey was sent to all pediatricians and pediatric intensive care unit nurses and respiratory-therapists (RTs) affiliated with a Canadian University. We presented questions about demographics, methodology of AR, and expectations from AR. Responses of pediatricians and nurses/RTs were …

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

Andrew N. Rowan, DPhil

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

Andrew N. Rowan, DPhil

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 …

The Phenomenon Of Outbound Medical Tourism In The United States, Tanner Douglas Cabbage

Chancellor’s Honors Program Projects

No abstract provided.

The Validity Of Animal Experiments In Medical Research, Gill Langley

Gill Langley, PhD

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.

Stratified Meta-Analysis To Examine Data Biases In Lung Cancer Studies Of Refinery Workers, Sherman Selix

Yale Day of Data

Petroleum refineries employ a variety of workers who historically experienced different potentials for asbestos exposure depending on job tasks. Associations between petroleum refinery work and lung cancer related to occupational asbestos exposure have been quantified among various locations, corporations, and time periods. To combine the data from several individual refinery studies and examine an overall effect, a systematic review and stratified meta-analysis was employed. Using set search terms among four databases, 112 potential publications were identified, of which 29 qualified for meta-analysis. Risk estimates and confidence intervals were extracted from these publications to construct four separate datasets. Inverse variance weighting …

Strategic Focus On 3r Principles Reveals Major Reductions In The Use Of Animals In Pharmaceutical Toxicity Testing, Elin Törnqvist, Anita Annas, Britta Granath, Elisabeth Jalkesten, Ian Cotgreave, Mattias Öberg

Application of Alternative Methods Collection

The principles of the 3Rs, Replacement, Reduction and Refinement, are being increasingly incorporated into legislations, guidelines and practice of animal experiments in order to safeguard animal welfare. In the present study we have studied the systematic application of 3R principles to toxicological research in the pharmaceutical industry, with particular focus on achieving reductions in animal numbers used in regulatory and investigatory in vivo studies. The work also details major factors influencing these reductions including the conception of ideas, cross-departmental working and acceptance into the work process. Data from 36 reduction projects were collected retrospectively from work between 2006 and 2010. …

Laboratory Routines Cause Animal Stress, Jonathan P. Balcombe, Neal D. Barnard, Chad Sandusky

Jonathan Balcombe, PhD

Eighty published studies were appraised to document the potential stress associated with three routine laboratory procedures commonly performed on animals: handling, blood collection, and orogastric gavage. We defined handling as any non-invasive manipulation occurring as part of routine husbandry, including lifting an animal and cleaning or moving an animal's cage. Significant changes in physiologic parameters correlated with stress (e.g., serum or plasma concentrations of corticosterone, glucose, growth hormone or prolactin, heart rate, blood pressure, and behavior) were associated with all three procedures in multiple species in the studies we examined. The results of these studies demonstrated that animals responded with …

A Comparison Of Prenatal Alcohol, Tobacco, And Other Drug Use Between San Luis Obispo County And Ventura County, Dana M. Williamson

Statistics

Prenatal substance abuse is a growing issue in America. It can lead to fetal alcohol spectrum disorder, long term growth, behavior, and executive functioning problems, and creates a predisposition for drug use for the child.

This project summarizes the statistical analyses comparing alcohol, tobacco, and other drug use by pregnant women between San Luis Obispo County and Ventura County. The main goal of these analyses is to determine if there is a difference between San Luis Obispo County and Ventura County. This is an interesting comparison because these counties are neighboring counties, and past data have shown that the rate …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

Adaptive Pair-Matching In The Search Trial And Estimation Of The Intervention Effect, Laura Balzer, Maya L. Petersen, Mark J. Van Der Laan

U.C. Berkeley Division of Biostatistics Working Paper Series

In randomized trials, pair-matching is an intuitive design strategy to protect study validity and to potentially increase study power. In a common design, candidate units are identified, and their baseline characteristics used to create the best n/2 matched pairs. Within the resulting pairs, the intervention is randomized, and the outcomes measured at the end of follow-up. We consider this design to be adaptive, because the construction of the matched pairs depends on the baseline covariates of all candidate units. As consequence, the observed data cannot be considered as n/2 independent, identically distributed (i.i.d.) pairs of units, as current practice assumes. …

Successful Aging And Creativity : An Investigation On Functional Status And Psychological Wellbeing In Older Adults, Mirie E. Levy

Loma Linda University Electronic Theses, Dissertations & Projects

Objectives: While the literature supports the maintenance of functional status as integral to successful aging, the relationship of creativity on functional status has received little attention. Creativity has been associated with health and aging in the research but only a small number of studies have examined creativity interventions to enhance functional status and boost psychological wellbeing.

Methods: A pretest-posttest quasi-experimental design was used to investigate an 8-week creativity intervention on functional status and psychological wellbeing in older adults. Sample subjects were 92 men and women all over age 60. A series of two-way mixed ANOVAs measured differences between treatment and …

The Association Of Diet And Physical Activity With Stroke Mortality Results From The Adventist Health Study-1, Tahereh Zamansani

Loma Linda University Electronic Theses, Dissertations & Projects

Stroke is one of the leading causes of death and disability, with major global public health implications. Stroke ranks No. 4 among all causes of death, behind heart disease, cancer, and chronic lower respiratory disease (CLRD). Stroke accounts for almost 1 of every 18 deaths in the United States. Women accounted for 60.6% of stroke deaths. Death certificate data show that the mean age at stroke death was 79.6 years; males had a younger mean age (76.3) than females.

There is still a great scientific uncertainty among researchers and epidemiologists about the magnitude of any preventive effect, mechanisms of action …

Inflammatory Findings On Species Extrapolations: Humans Are Definitely No 70-Kg Mice, Marcel Leist, Thomas Hartung

Validation of Alternative Methods Collection

Modern toxicology has embraced in vitro methods, and major hopes are based on the Omics technologies and systems biology approaches they bring along (Hartung and McBride in ALTEX 28(2):83–93, 2011; Hartung et al. in ALTEX 29(2):119–28, 2012). A culture of stringent validation has been developed for such approaches (Leist et al. in ALTEX 27(4):309–317, 2010; ALTEX 29(4):373–88, 2012a; Toxicol Res 1:8–22, 2012b), while the quality and usefulness of animal experiments have been little scrutinized. A new study (Seok et al. 2013) now shows the low predictivity of animal responses in the field of inflammation. These findings corroborate earlier findings from …

Food For Thought … Mechanistic Validation, Thomas Hartung, Sebastian Hoffman, Martin Stephens

Experimentation Collection

Validation of new approaches in regulatory toxicology is commonly defined as the independent assessment of the reproducibility and relevance (the scientific basis and predictive capacity) of a test for a particular purpose. In large ring trials, the emphasis to date has been mainly on reproducibility and predictive capacity (comparison to the traditional test) with less attention given to the scientific or mechanistic basis. Assessing predictive capacity is difficult for novel approaches (which are based on mechanism), such as pathways of toxicity or the complex networks within the organism (systems toxicology). This is highly relevant for implementing Toxicology for the 21st …

Estimating The Impact Of Community-Level Interventions: The Search Trial And Hiv Prevention In Sub-Saharan Africa, Laura Balzer, Maya Petersen, Joshua Schwab, Mark Van Der Laan

Laura B. Balzer

Evaluation of community level interventions to prevent HIV infection presents significant methodological challenges. Even when it is feasible to randomly assign a treatment versus control level of the intervention to each community in a sample, measurement of incident HIV infection remains difficult. In this talk we describe an experimental design developed for the SEARCH Trial, a large community randomized trial that will evaluate the impact of expanded treatment on incident HIV and other outcomes. Regular community-wide testing campaigns are conducted and a random sample of community members who fail to attend a campaign are tracked. The data generated by this …

Why Match In Individually And Cluster Randomized Trials?, Laura B. Balzer, Maya L. Petersen, Mark J. Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thought to improve study credibility. Matching is also implemented to increase study power. This article compares the asymptotic efficiency of the pair-matched design, where units are matched on baseline covariates and the treatment randomized within pairs, to the independent design, where units are randomly paired and the treatment randomized within pairs. We focus on estimating the average treatment effect and use the efficient influence curve to understand the information provided by …

The Efficacy Of An Audio Program And Discussion Guide In Promoting Exclusive Breastfeeding In Cameroon, Africa, Kathryn R. Reinsma

Loma Linda University Electronic Theses, Dissertations & Projects

Background: In the Northwest Region of Cameroon, approximately 90% of women initiate breastfeeding; however, only 34% continue exclusive breastfeeding for the recommended six months (Kakute, et al., 2005; WHO, 2008). Entertainment-education is a mass-media communication strategy of placing educational information into media such as television programs, movies, and radio programs (Siegel & Lotenberg, 2007). This form of behavioral change communication has proven effective in addressing health-related issues in developing countries.

Purpose: The aim was to design an audio program and discussion guide to test the hypothesis that an audio program and discussion guide improves exclusive breastfeeding knowledge, beliefs, benefits, self-efficacy, …

Why Match In Individually And Cluster Randomized Trials?, Laura Balzer, Maya Petersen, Mark Van Der Laan

Laura B. Balzer

The decision to match individuals or clusters in randomized trials is motivated by both practical and statistical concerns. Matching protects against chance imbalances in baseline covariate distributions and is thereby thought to improve study credibility. Matching is also implemented to increase study power. Analogue to Rose and van der Laan (2009), this article investigates the asymptotic efficiency of pair-matching individuals or clusters relative to not matching in randomized trials. We focus on estimating the average treatment effect. We use the efficient influence curve to understand the information provided by each design for estimation of the target causal parameter. Our approach …

Factors That Inhibit Or Enhance Maternal Coping With Stillbirth In Chhattisgarh, India, Lisa R. Roberts

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Over half of the known stillbirths occur in four highly populated countries—India among them. While acknowledged as a significant public health issue in western societies, little is known about maternal coping with stillbirth in developing countries. The purpose of this mixed methods study is to explore how issues of gender and power, social support, coping efforts, and religious beliefs influence perinatal grief outcomes among poor women in rural Chhattisgarh, India.

Methods: In Phase 1 of this mixed methods study, grounded theory methods were used to explore perceptions regarding stillbirth. A de-identified medical records review of 536 deliveries at Christian …

Facial Type Analysis Comparison Between Mri, Cbct, And Lateral Cephalometrics, Matthew A. Sanders

Loma Linda University Electronic Theses, Dissertations & Projects

Introduction: Single Cephalometric measurements are comparable between Cone Beam Computed Tomography (CBCT), Magnetic Resonance Imaging (MRl) and Conventional Lateral Cephalometric (LC) imaging methods. This study evaluated the agreement between the three imaging methods in facial type analysis (using a composite of 5 cephalometric measures).

Methods and Materials: Twenty-two subjects participated in this study. Cranial images were generated via three modalities: LC, CBCT and MRl. Cephalometric landmarks were identified on the three images per subject and a facial type analysis performed. An equally weighted facial type calculation composed of 5 cephalometric measurements (facial axis, facial depth, mandibular plane, lower face height, …

Emergency Department Staff Adherence To Bad News Delivery Recommendations, Kristen R. Myers

Loma Linda University Electronic Theses, Dissertations & Projects

Emergency department (ED) staff is responsible for giving bad news regarding death, diagnoses, and other traumatic losses to patients and loved ones. Individuals receiving traumatic and sudden bad news are at increased risk of serious psychological and physiological consequences of disrupted grief. Despite published recommended practices for providers to help prevent maladaptive grief responses, little research is available on actual bad news delivery practices and factors promoting or hindering adherence to recommendations, and no study specifically explored the ED context.

The study used a qualitative design to explore bad news delivery practices, awareness of recommendations, factors perceived to hinder or …

A Critical Constructionist View Of "At-Risk" Youth In Alternative Education, Rachelle Silverstein Touzard

Loma Linda University Electronic Theses, Dissertations & Projects

Family therapists and school counselors are increasingly called upon to provide services for youth in alternative education (Carver, Lewis, & Tice, 2010). Alternative education systems are programs for youth who have been defined as at risk. This study explored the at-risk discourse and asked the questions (a) how do youth and staff define the term at risk, (b) construct their experience in alternative education systems, and (c) experience their relationships with each other.

Combined elements from critical theory and a social constructionist perspective guided this study. A qualitative, grounded theory method was used that included semi structured interviews with …