Physical Sciences and Mathematics Commons^™

Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan

Troy Seidle, PhD

Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification …

An Evaluation Of The Us High Production Volume (Hpv) Chemical-Testing Programme: A Study In (Ir)Relevance, Redundancy And Retro Thinking, Andrew Nicholson, Jessica Sandler, Troy Seidle

Troy Seidle, PhD

Under the US Environmental Protection Agency (EPA) High Production Volume (HPV) Challenge Programme, chemical companies have volunteered to conduct screening-level toxicity tests on approximately 2800 widely-used industrial chemicals. Participating companies are committed to providing available toxicity information to the EPA and presenting testing proposals for review by the EPA and posting on the EPA Web site as public information. People for the Ethical Treatment of Animals (PETA) and a coalition of animal protection organisations have reviewed all the test plans submitted by the participating chemical companies for compliance with the original HPV framework, as well as with animal welfare guidelines …

The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung

Troy Seidle, PhD

Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.

A key aspect of the implementation of new testing strategies is the determination …

A Modular One-Generation Reproduction Study As A Flexible Testing System For Regulatory Safety Assessment, Richard Vogel, Troy Seidle, Horst Spielmann

Troy Seidle, PhD

The European Union’s Registration, Evaluation and Authorisation of Chemicals (REACH) legislation mandates testing and evaluation of approximately 30,000 existing substances within a short period of time, beginning with the most widely used “high production volume” (HPV) chemicals. REACH testing requirements for the roughly 3000 HPV chemicals specify three separate tests for reproductive toxicity: two developmental toxicity studies on different animal species (OECD Test Guideline 414) and a two-generation reproduction toxicity study (OECD TG 416). These studies are highly costly in both economic and animal welfare terms. OECD TG 416 is a fertility study intended to evaluate reproductive performance of animals …

The Fine-Scale Habitat Use Of Risso’S Dolphins Off Bardsey Island, Cardigan Bay (Uk), Marijke N. De Boer, Sonja Eisfeld, Mark P. Simmonds

Mark P. Simmonds, OBE

The main objectives of this study were (1) to estimate the population size of Risso’s dolphins off Bardsey Island using mark-recapture techniques (De Boer et al., 2013); and (2) to study habitat-use in relation to fine-scale oceanographic features. This work provides preliminary information on the habitat-use of Risso’s dolphins and will benefit future studies, along with the development of effective conservation measures for this species throughout the region.

Cetaceans And Marine Debris: The Great Unknown, Mark Peter Simmonds

Mark P. Simmonds, OBE

Plastics and other marine debris have been found in the gastrointestinal tracts of cetaceans, including instances where large quantities of material have been found that are likely to cause impairment to digestive processes and other examples, where other morbidity and even death have resulted. In some instances, debris may have been ingested as a result of the stranding process and, in others, it may have been ingested when feeding. Those species that are suction or “ram” feeders may be most at risk. There is also evidence of entanglement of cetaceans in marine debris. However, it is usually difficult to distinguish …

Expert Testimony In Capital Sentencing: Juror Responses, John H. Montgomery, J. Richard Ciccone, Stephen P. Garvey, Theodore Eisenberg

Stephen P. Garvey

The U.S. Supreme Court, in Furman v. Georgia (1972), held that the death penalty is constitutional only when applied on an individualized basis. The resultant changes in the laws in death penalty states fostered the involvement of psychiatric and psychologic expert witnesses at the sentencing phase of the trial, to testify on two major issues: (1) the mitigating factor of a defendant’s abnormal mental state and (2) the aggravating factor of a defendant’s potential for future violence. This study was an exploration of the responses of capital jurors to psychiatric/psychologic expert testimony during capital sentencing. The Capital Jury Project is …

Health Professionals’ Roles In Animal Agriculture, Climate Change, And Human Health, Aysha Z. Akhtar, Michael Greger, Hope Ferdowsian, Erica Frank

Michael Greger, MD, FACLM

What we eat is rapidly becoming an issue of global concern. With food shortages, the rise in chronic disease, and global warming, the impact of our dietary choices seems more relevant today than ever. Globally, a transition is taking place toward greater consumption of foods of animal origin, in lieu of plantbased diets. With this transition comes intensification of animal agriculture that in turn is associated with the emergence of zoonotic infectious diseases, environmental degradation, and the epidemics of chronic disease and obesity. Health professionals should be aware of these trends and consider them as they promote healthier and more …

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

Gill Langley, PhD

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 …

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.

Cefepime Neurotoxicity In An Adolescent Cystic Fibrosis Patient With Aminoglycoside-Induced Acute Kidney Injury, Kristen R. Nichols, Danielle M. Brown, Chad A. Knoderer, Sharon P. Andreoli

Chad A. Knoderer

Objective: To describe a case of cefepime neurotoxicity in an adolescent with cystic fibrosis and aminoglycoside-associated acute kidney injury (AKI). Case Summary: A 15-year-old, 46-kg male with cystic fibrosis (CF) and chronic sinusitis was admitted to the hospital for CF exacerbation. The patient was subsequently discharged to complete home antibiotic therapy with intravenous gentamicin and cefepime. Thirteen days after discharge, while still receiving intravenous antibiotics, the patient presented to an outside hospital complaining of vomiting, fatigue, decreased appetite, and decreased urine output. The patient was diagnosed with AKI and was transferred to our institution, where he displayed signs and symptoms …

Trends In The Prevalence And Mortality Of Cognitive Impairment In The United States: Is There Evidence Of A Compression Of Cognitive Morbidity, Kenneth Langa, Eric Larson, Jason Karlawish, David Cutler, Mohammed Kabeto, Scott Kim, Allison Rosen

Jason Karlawish

BACKGROUND: Recent medical, demographic, and social trends might have had an important impact on the cognitive health of older adults. To assess the impact of these multiple trends, we compared the prevalence and 2-year mortality of cognitive impairment (CI) consistent with dementia in the United States in 1993 to 1995 and 2002 to 2004. METHODS: We used data from the Health and Retirement Study (HRS), a nationally representative population-based longitudinal survey of U.S. adults. Individuals aged 70 years or older from the 1993 (N = 7,406) and 2002 (N = 7,104) waves of the HRS were included. CI was determined …

Striving For Cultural Competence In An Hiv Program: The Transformative Impact Of A Microsystem In A Larger Health Network, Judith N Sabino, Timothy Friel, Lynn Deitrick, Debbie Salas-Lopez

Debbie Salas-Lopez MD, MPH

No abstract provided.

Stochastic Variation In Network Epidemic Models: Implications For The Design Of Community Level Hiv Prevention Trials, David Boren, Patrick Sullivan, Chris Beyrer, Stefan Baral, Linda-Gail Becker, Ron Brookmeyer

Ron Brookmeyer

Important sources of variation in the spread of HIV in communities arise from overlapping sexual networks and heterogeneity in biological and behavioral risk factors in populations. These sources of variation are not routinely accounted for in the design of HIV prevention trials. In this paper, we use agent based models to account for these sources of variation. We illustrate the approach with an agent based model for the spread of HIV infection among men who have sex with men (MSM) in South Africa. We find that traditional sample size approaches that rely on binomial (or Poisson) models are inadequate and …

Long-Term Survival For Patients With Acute Decompensated Heart Failure According To Ejection Fraction Findings, Andrew Coles, Kimberly Fisher, Chad Darling, Jorge Yarzebski, David Mcmanus, Joel Gore, Darleen Lessard, Robert Goldberg

Jorge L. Yarzebski

Limited data exist about the long-term prognosis of patients with acute decompensated heart failure (ADHF) further stratified according to ejection fraction (EF) findings. The primary objective of this population-based observational study was to characterize and compare trends in long-term prognosis after an episode of ADHF across 3 EF strata. Hospital medical records were reviewed for 3,604 residents of the Worcester, Massachusetts, metropolitan area who were discharged after ADHF from all 11 medical centers in central Massachusetts during 1995, 2000, 2002, and 2004 and had EF measurements during their index hospitalizations. The average age of this population was 75 years, most …

Cluster Randomized Trials And Statistical Power, Stephen A. Lauer, Nicholas G. Reich

Nicholas G Reich

The cluster-randomized trial (CRT) is a common study design in public health research. In situations where dividing a group of individuals into treatment and controls is unethical or impossible, a CRT design maintains the strengths of a randomized study design. By comparing the outcomes of small populations (clusters), we can observe the impacts of interventions on the community as a whole. Public health researchers around the world have utilized CRTs to measure the effect of, for example, de-worming medication on school attendance, financial incentives on doctor absenteeism, and providing chlorine to waterholes. The CRT can be a potent tool, however …

Effectiveness Of A Novel Spontaneous Carvacrol Nanoemulsion Against Salmonella Enterica Enteritidis And Escherichia Coli O157:H7 On Contaminated Mung Bean And Alfalfa Seeds, Kyle Landry, Yuhua Chang, David Julian Mcclements, Lynne Mclandsborough

Kyle S Landry

A Multi-Center, Two-Arm, Single-Blind Randomized Trial Of Two Different Intravenous Fluids During Labor (Poster)., Lisa M. Dapuzzo-Argiriou Md, John C. Smulian Md, Mph, Meredith Rochon Md, Lisa Galdi Do, Jessika Kissling Md, Peter F. Schnatz Do, George Neubert Md, Angel Gonzalez-Rios Md, James Airoldi Md, Mary Anne Carrillo Md, Jaimie Maines Md, Allen R. Kunselman Ms, John Repke Md, Richard S. Legro Md

John C Smulian MD, MPH

No abstract provided.

The Effect Of Commercial Tests For Aneuploidy Screening Using Cell-Free Fetal Dna On Rates Of Invasive Testing In Clinical Practice, Adetola Louis-Jacques Md, Courtney R. Burans Ms, Cgc, Sarah Robinson, Elizabeth A. Schofield, Joanne Quiñones Md, Msce, John C. Smulian Md, Mph, Meredith Rochon Md

John C Smulian MD, MPH

No abstract provided.

The ‘‘Ice’’ Study: Feasibility Of Inexpensive Commercial Coolers On Mobile Ems Units, Kathleen E. Kane Md, Robert J. Tomsho Do, Ms, Karen Pheasant Do, Thomas Stauffer Do, Brent R. Schoenfeldt Do, Scott Hamilton Do, Travis Kain Do, Bryan G. Kane Md

Kathleen E Kane MD, FACEP

Introduction: Prehospital postresuscitation induced hypothermia (IH) has been shown to reduce neurological complications in comatose cardiac-arrest survivors. Retrofitting ambulances to include equipment appropriate to initiate hypothermia, such as refrigeration units for cooled saline, is expensive. The objective of this nonhuman subject research study was to determine if inexpensive, commercially available coolers could, in conjunction with five reusable ice packs, keep two 1 L bags of precooled 0.9% normal saline solution (NSS) at or below 48C for an average shift of eight to 12 hours in a real-world environment, on board in-service Emergency Medical Service (EMS) units, over varying weather conditions …

The ‘‘Ice’’ Study: Feasibility Of Inexpensive Commercial Coolers On Mobile Ems Units, Kathleen E. Kane Md, Robert J. Tomsho Do, Ms, Karen Pheasant Do, Thomas Stauffer Do, Brent R. Schoenfeldt Do, Scott Hamilton Do, Travis Kain Do, Bryan G. Kane Md

Bryan G Kane MD

Introduction: Prehospital postresuscitation induced hypothermia (IH) has been shown to reduce neurological complications in comatose cardiac-arrest survivors. Retrofitting ambulances to include equipment appropriate to initiate hypothermia, such as refrigeration units for cooled saline, is expensive. The objective of this nonhuman subject research study was to determine if inexpensive, commercially available coolers could, in conjunction with five reusable ice packs, keep two 1 L bags of precooled 0.9% normal saline solution (NSS) at or below 48C for an average shift of eight to 12 hours in a real-world environment, on board in-service Emergency Medical Service (EMS) units, over varying weather conditions …

Gender Differences In Perceptions And Self-Reported Driving Behaviors Among Teenagers. (Poster), Gavin C. Barr Jr. Md, Kathleen E. Kane Md, Robert D. Barraco Md, Timarie Rayburg Do, Lauren Dugan Do, Chadd K. Kraus Do, Mph, Marna R. Greenberg Do, Mph, Facep, Valerie Rupp Rn, Bsn, Kimberly Hamilton, Bryan G. Kane Md

Marna R Greenberg DO, MPH, FACEP

No abstract provided.

Diagnostic Performance Of Cardiac Troponin I For Early Rule-In And Rule-Out Of Acute Myocardial Infarction: Results Of A Prospective Multicenter Trial, Alan Storrow, Robert Christenson, Richard Nowak, Deborah Diercks, Adam Singer, Alan Wu, Erik Kulstad, Frank Lovecchio, Christian Fromm, Gary Headden, Tracie Potis, Christopher Hogan, Jon Schrock, Daniel Zelinski, Marna Greenberg, James Ritchie, Janna Chamberlin, Kurtis Bray, Daniel Rhodes, Deirdre Trainor, Dawn Holmes, Paula Southwick

Marna R Greenberg DO, MPH, FACEP

OBJECTIVES: To compare emergency department TnI serial sampling intervals, determine optimal diagnostic thresholds, and report representative diagnostic performance characteristics for early rule-in and rule-out of MI. METHODS: We prospectively measured TnI (AccuTnI+3™, Beckman Coulter) at serial time intervals in 1929 subjects with chest pain or equivalent ischemic symptoms suggestive of acute coronary syndromes at 14 medical centers. Diagnosis was adjudicated by an independent central committee. RESULTS: TnI ≥0.03ng/mL provided 96.0% sensitivity and 89.4% specificity at 1-3h after admission, and 94.9% sensitivity and 86.7% specificity at 3-6h. NPV (rule-out, non-MI) was 99.5% at 1-3h, and 99.0% at 3-6h when TnI is …

Pubertal And Adult Leydig Cell Function In Mullerian Inhibiting Substance-Deficient Mice, Xiufeng Wu, Ramamani Arumugam, Stephen Baker, Mary Lee

Mary M. Lee

Mullerian inhibiting substance (MIS) causes Mullerian duct regression during sexual differentiation and regulates postnatal Leydig cell development. MIS knockout (MIS-KO) mice with targeted deletions of MIS develop Leydig cell hyperplasia, but their circulating androgen concentrations are reportedly unaltered. We compared reproductive hormone profiles, androgen biosynthesis, and the expression of key steroidogenic and metabolic enzymes in MIS-KO and wild-type (WT) mice at puberty (36 d) and sexual maturity (60 d). In pubertal animals, basal testosterone and LH concentrations in plasma were lower in MIS-KO than WT mice, whereas human chorionic gonadotropin-stimulated testosterone concentrations were similar. In adults, basal LH, and both …

Depicting Estimates Using The Intercept In Meta-Regression Models: The Moving Constant Technique, Blair T. Johnson Dr., Tania B. Huedo-Medina Dr.

Blair T. Johnson

In any scientific discipline, the ability to portray research patterns graphically often aids greatly in interpreting a phenomenon. In part to depict phenomena, the statistics and capabilities of meta-analytic models have grown increasingly sophisticated. Accordingly, this article details how to move the constant in weighted meta-analysis regression models (viz. “meta-regression”) to illuminate the patterns in such models across a range of complexities. Although it is commonly ignored in practice, the constant (or intercept) in such models can be indispensible when it is not relegated to its usual static role. The moving constant technique makes possible estimates and confidence intervals at …

Characterization Of A Recently Purified Thermophilic Dnase From A Novel Thermophilic Fungus, Kyle Landry, Robert Levin

Kyle S Landry

The Public Health Impacts Of Concentrated Animal Feeding Operations On Local Communities, Michael Greger, Gowri Koneswaran

Michael Greger, MD, FACLM

Large-scale farm animal production facilities, also known as concentrated animal feeding operations (CAFOs), release a significant amount of contaminants into the air and water. Adverse health effects related to exposure to these contaminants among CAFO workers have been welldocumented; however, less is known about their impact on the health of residents in nearby communities. Epidemiological research in this area suggests that neighboring residents are at increased risk of developing neurobehavioral symptoms and respiratory illnesses, including asthma. Additional research is needed to better understand community-scale exposures and health outcomes related to the management practices and emissions of CAFOs.

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 …

Models For Improving Patient Throughput And Waiting At Hospital Emergency Departments, Jomon Aliyas Paul, Lin Li

Jomon Aliyas Paul

Background: Overcrowding diminishes Emergency Department (ED) care delivery capabilities.

Objectives: We developed a generic methodology to investigate the causes of overcrowding and to identify strategies to resolve them, and applied it in the ED of a hospital participating in the study.

Methods: We utilized Discrete Event Simulation (DES) to capture the complex ED operations. Using DES results, we developed parametric models for checking the effectiveness and quantifying the potential gains from various improvement alternatives. We performed a follow-up study to compare the outcomes before and after the model recommendations were put into effect at the hospital participating …

Gender Differences In Perceptions And Self-Reported Driving Behaviors Among Teenagers. (Poster), Gavin C. Barr Jr. Md, Kathleen E. Kane Md, Robert D. Barraco Md, Timarie Rayburg Do, Lauren Dugan Do, Chadd K. Kraus Do, Mph, Marna R. Greenberg Do, Mph, Facep, Valerie Rupp Rn, Bsn, Kimberly Hamilton, Bryan G. Kane Md

Kathleen E Kane MD

No abstract provided.