bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASCOTTrial
Authors: Mehlsen Jesper 
Published: October 2008

AbstractThe Anglo Scandinavian Cardiac Outcomes Trial (ASCOT) had two main objectives. The first objective was to determine and compare the effects of an amlodipine‐based therapy with an atenolol‐based therapy in hypertensive patients with mild‐to‐moderate risk of developing cardiovascular events (ASCOT‐BPLA). The second objective was in those patients with a serum cholesterol level at or below average to evaluate the possible beneficial effects on cardiovascular events of a statin compared with placebo (ASCOT‐LLA). ASCOT‐LLA was terminated prematurely after a mean observational period of 3.3 years because of a highly significant reduction in the primary endpoint of CHD events compared with placebo. ASCOT‐BPLA was also terminated prematurely after a mean observational period of 5.5 years because of significantly higher all cause mortality in the atenolol‐based treatment arm compared with the amlodipine‐based arm.
Physicians' Health Study (PHS)
Authors: Gaziano J. Michael , Hennekens Charles H. 
Published: October 2008

AbstractThe United States Physicians' Health Study I was a landmark randomized trial of primary prevention because it was conducted entirely by mail, used a prerandomization run‐in, collected prerandomization blood specimens, used a 2 × 2 factorial design to test two hypotheses, had very high compliance to the assigned treatments, and had virtually complete morbidity and mortality data after 12 years of treatment and follow‐up. PHS I was funded by the National Institutes of Health and enrolled 22,071 male physicians aged 40 to 84 years at baseline in 1982. This randomized, double‐blind, placebo‐controlled trial tested primarily the effects of aspirin on cardiovascular disease and beta carotene on cancer. After 5 years of treatment and follow‐up, based on the unanimous recommendation of the independent Data and Safety Monitoring Board, the randomized aspirin component was terminated early mainly because of the emergence of a statistically extreme (P < 0.00001) 44% reduction in first myocardial infarction among those assigned to aspirin. After 12 years of treatment and follow‐up, the beta carotene arm ended on schedule and produced no significant overall evidence of benefit or harm either on cancer or cardiovascular disease.
Data Monitoring Committee
Authors: Ellenberg Susan 
Published: October 2008

AbstractData Monitoring Committees, also known as Data and Safety Monitoring Boards, are often established as a component of clinical trial oversight to review interim data of the ongoing trial so that safety concerns or problematic operational issues can be identified rapidly and corrective measures can be undertaken. Such committees may be independent of the trial sponsor and investigator to ensure recommendations are as objective as possible and unaffected by conflicts of interest. Federal funding and regulatory agencies have issued policy documents concerning the establishment and operation of Data Monitoring Committees, but substantial variation exists in committee processes.
The Center for Biologics Evaluation and Research
Authors: King Barney 
Published: October 2008

Abstract
Overview of the Center for Biologics Evaluation and Research (CBER) of the FDA. CBER's primary responsibility is the regulation of biologics products. The article briefly describes the history of biologics regulation, the regulatory authority behind the regulation, the types of products regulated by CBER, the general organization of the Center, and a gemera, a description of the approval process for biologics.
Wei‐Lin‐Weissfeld Method for Multiple Times to Events
Authors: Signorovitch James E. , Wei Lee‐Jen 
Published: October 2008

AbstractSubjects followed in a longitudinal study can often experience multiple clinical events of interest at different times. The events could be of different types, for example, the onset times for various opportunistic infections in HIV‐infected patients, or multiple recurrences of the same type of event, such as recurrent superficial bladder tumors in cancer patients. This article describes the Wei–Lin–Weissfeld (WLW) method for analyzing multivariate failure time data that develop in such settings.
Maximum Tolerable Dose (
MTD
)
Authors: Chevret Sylvie 
Published: October 2008

Abstract
The “Maximum Tolerable Dose” (MTD), also known as the “Maximum Tolerated Dose” or the “Maximally Tolerated Dose”, is defined as the dose that produces an “acceptable” level of toxicity or that, if exceeded, would put animals or patients at “unacceptable” risk for toxicity. Besides determining animal toxicology, establishing the MTD is the main objective of Phase I clinical trials, mostly in cancer and HIV treatment in which relatively high doses of drugs are usually chosen to achieve the greatest possible beneficial antitumor effect. Definition of the MTD usually relies on the sample, as MTD is defined as the dose level at which more than two patients over six experienced dose‐limiting toxicity (DLT). More recently, the MTD has been defined as the dose that produces a certain frequency of DLT within the treated patient population. In this framework, the MTD is estimated from the data using Bayes or maximum likelihood inference. In all these designs, the MTD is established for one initial administration or treatment course of a cytotoxic experimental agent, ignoring efficacy. To address these issues, the maximum tolerated schedule and the most successful dose have been proposed to be used rather than a conventional MTD. Finally, the concept of MTD that uses toxicity as a surrogate endpoint for efficacy in cytotoxic Phase I trials has been also controversial. Interests in alternatives to MTD have gained recently when dealing with new cytostatic agents that may produce relatively minimal organ toxicity, compared with standard cytotoxics. New optimal doses should be defined in the near future.
Adverse Event Evaluation
Authors: McNair Lindsay A. 
Published: October 2008

Abstract
Although much of the focus in clinical trials is on the evaluation of the efficacy of an intervention or pharmaceutical product, the appropriate collection and assessment of safety data is a critical part of any clinical study. In early stage trials, the primary objective of the study may be the assessment of safety (or the identification of a maximum tolerated dose). For the assessment of safety data, several key factors must be collected for any adverse event. It is important to ensure that every adverse event—regardless of apparent association with the study or the intervention–is recorded. For each event, it is then important to collect the timing of the event, the relationship to the intervention, the severity, the expectedness, the intervention required, and the outcome. All of this information will initially be used to determine whether the event requires expedited reporting to regulatory agencies or safety monitoring committees, and later, it will be used to understand fully the safety profile of the intervention or investigational product.
Factor Analysis: Confirmatory
Authors: Byrne Barbara M. 
Published: October 2008

Abstract
The intent of this article is to present an introductory overview of the basic concepts and testing procedures associated with confirmatory factor analysis (CFA). Working from a hypothesized four‐factor structure of a nonacademic self‐concept (SC), as measured by 32 items from the Self Description Questionnaire, readers are introduced to both a graphical and a structural equation specification of this CFA model, followed by a review of the related procedures involved in its testing, estimation, and evaluation, together with the interpretation of results. Important issues and caveats associated with the testing of CFA models are also briefly addressed.
Women's Health Initiative: Statistical Aspects and Selected Early Results
Authors: Prentice Ross L. , Anderson Garnet L. 
Published: October 2008

Abstract
An overview is provided of the women's health initiative clinical trial and observational study of 161 808 postmenopausal women in the age range 50 to 79. The clinical trial includes 68 132 women in a partial factorial design having four intervention comparisons: a low‐fat eating pattern among 48 835 women; a hormone therapy trial of 0.625 mg per day of conjugated equine estrogen among 10 739 women who were posthysterectomy at baseline; a hormone therapy trial of this same estrogen plus 2.5 mg per day of medroxyprogesterone acetate among 16 608 women with uterus at baseline; and a calcium (1000 mg/day) plus vitamin D (400 international units/day) trial among 36 282 women. Each CT component had its specified primary and secondary hypotheses, along with an overriding emphasis on overall health benefits versus risks. A so‐called global index was defined for each CT component as the earliest occurrence of a set of clinical outcomes plausibly affected by the intervention, or death from other causes. Specialized data management communication, quality assurance, and data monitoring procedures were established to support this large and complex research program. Some detail is provided on the results of the combined hormone trial component, which was stopped early in 2002 when the external Data and Safety Monitoring Board judged that overall health risks exceeded benefits over an average follow‐up period in excess of five years.
Confounding
Authors: Greenland Sander 
Published: October 2008

Abstract

The word
confounding
has been used to refer to at least three distinct concepts. In the oldest usage, confounding is a
bias
in estimating causal effects (
see
Causation
). This bias is sometimes informally described as a mixing of effects of extraneous factors (called
confounders
) with the effect of interest. This usage predominates in nonexperimental research, especially in epidemiology and sociology. In a second and more recent usage, confounding is a synonym for noncollapsibility (
see
Collapsibility
), although this usage is often limited to situations in which the parameter of interest is a causal effect. In a third usage, originating in the
experimental‐design
literature, confounding refers to inseparability of main effects and
interactions
under a particular design. The term
aliasing
is also sometimes used to refer to the latter concept; this usage is common in the
analysis of variance
literature.
Correlation
Authors: Armitage Peter 
Published: October 2008

Abstract
In a loose sense, two variables are correlated if changes in one tend to be accompanied by changes in the other. More specifically, correlation implies a linear relationship with superimposed random variation. The product–moment correlation coefficient was introduced by Galton and greatly exploited by Karl Pearson. Its square is the proportion of the variance of one variable “explained” by linear regression on a second variable. Standard tests are described in the article. An important extension is to intraclass correlation for measurements on individuals falling into groups, which measures the association between individuals in the same group.
Fisher's Exact Test
Authors: Routledge Rick 
Published: October 2008

AbstractFisher's exact test can be used to assess the significance of a difference between the proportions in the two groups. In particular, it provides a widely applicable way to assess the results of simple, completely randomized experiments leading to two‐by‐two contingency tables with small frequency counts, However, it has low power, especially when the standardP‐value is used. The power can be increased considerably through either using the mid‐Pvalue, or carefully constructing a test based, at least in part, on a binomial model.
Interaction Model
Authors: Kreiner Svend 
Published: October 2008

AbstractLoglinear models that describe association patterns among categorical variables are sometimes calledinteraction models. Graphical interaction models are useful for portraying conditional independence and indicating when an association remains the same after collapsing over a variable. This article discusses a “Separation theorem” that describes how conditional independence patterns are maintained by conditioning on a certain subset of variables as indicated by an interaction graph. Collapsibility issues are also discussed.
Paired

t

Test
Authors: Hsu Henry , Lachenbruch Peter A. 
Published: October 2008

Abstract

This is used to compare mean differences between treatments when the observations have been obtained in pairs. The difference between the paired values is assumed to be normally distributed, and the null hypothesis that the expectation is zero is tested by Student's
t
test. The robustness properties are discussed, as is the asymptotic relative efficiency of nonparametric alternatives.
Proportions, Inferences, and Comparisons
Authors: Connor Jason T. , Imrey Peter B. 
Published: October 2008

Abstract
This article selectively reviews asymptotic, exact, and Bayesian methods for inference about one proportion, or for comparing two proportions from separate samples. For a single proportion, interval estimation is emphasized, and coverage properties of Wald, Jeffreys, Wilson, Agresti–Coull, and Clopper–Pearson (exact) confidence intervals are compared. Hypothesis testing is also discussed, primarily in the context of inverting interval estimates. For comparing proportions between two samples, we consider tests including the power‐divergence family (which incorporates all asymptotic tests commonly used); both conditional and unconditional exact tests; Bayesian tests; and several interval estimates. Some general aspects of power computation and sample size determination are discussed briefly in both contexts.
Eligibility and Exclusion Criteria
Authors: Foulkes Mary A. 
Published: October 2008

AbstractDesign characteristics of a clinical trial, such as eligibility and exclusion criteria, are broadly influential in the conduct, interpretation, and impact of trials. The research objectives, the intended inference or generalization of results, the balance of factors affecting the trial recruitment and conduct, all impact the determination of eligibility and exclusion criteria. Clinical contraindications, regulatory and ethical considerations also relate to this determination.
Placebos
Authors: Holbrook Anne , Goldsmith Charles H. , Leung Mova 
Published: October 2008

Abstract
Placebos have a long and controversial history in clinical research and in practice. In this chapter, we review the meaning, the pharmacology, effectiveness, safety, influences on, and ethical issues involving placebos. Various international guidelines for the use of placebos in research are available and evolving. We then suggest novel factorial designs to allow a full assessment of efficacy and safety of a new therapy while minimizing patient exposure to placebo alone.
Screening, Models of
Authors: Stevenson Chris 
Published: October 2008

Abstract
This article describes models for disease screening and how they have developed in recent years. The discussion focuses on screening for cancer, because most of the methodological advances in screening design and evaluation have concerned cancer screening. The first part of the article describes the characteristics of these models and illustrates them with a discussion of a simple screening model. The second part describes the development, strengths, and weaknesses of the two main types of screening model—analytic and simulation models—with a particular focus on microsimulation models. The third part discusses model fitting and validation, and the final part briefly describes models for diseases other than cancer—in particular, models for screening for infectious diseases—and discusses the current state and possible future directions for models of disease screening.
Clinical Trials, Early Cancer and Heart Disease
Authors: Schneiderman Marvin A. , Gehan Edmund A. 
Published: October 2008

AbstractEarly developments in controlled clinical trials at the National Institutes of Health (NIH) took place mainly at the National Cancer Institute (NCI) and what was then the National Heart Institute (NHI) (subsequently the National Heart, Lung, and Blood Institute (NHLBI))beginning in the 1950s. This article reviews the developments from the early 1950s to the late 1960s at both institutes, summarizing the early efforts in clinical trials, the organizations set up to conduct and monitor the clinical trials, and the developments in statistical methodology that have formed the basis for conducting many of the present day randomized controlled trials. The early history of clinical trials at these institutes has been reviewed in more detail at NCI by Gehan & Schneiderman and at NHLBI by Halperin et al.
Hemoglobin Kenya composed of α‐ and (Aγβ)‐fusion‐globin chains, associated with hereditary persistence of fetal hemoglobin
Authors: Wilcox Ibifiri , Boettger Kevin , Greene Lance , Malek Anita , Davis Lance , Steinberg Martin H. , Luo Hong‐Yuan , Chui David H.K. 
Published: October 2008

AbstractHb Kenya is made up of two normal α‐globin chains and two Aγβ‐fusion globin chains. The latter are the product of an Aγβ‐hybrid globin gene formed as a result of misalignment during meiosis and nonhomologous crossing over. It is associated with a deletion of 22.7 kb including the δ‐globin gene, between the Aγ‐ and β‐globin genes. Hb Kenya is found in Kenyans and Ugandans. Heterozygotes have moderately increased Hb F, and this mutation has been known as an (Aγβ)+ hereditary persistence of fetal hemoglobin (HPFH). Compound heterozygotes for Hb Kenya/Hb S are thought to be asymptomatic, but reports of long term follow‐up of these patients are lacking. The correct identification of Hb Kenya is sometimes problematic. In cation exchange high performance liquid chromatography, Hb Kenya elutes in similar position as Hb A2, Hb Lepore, Hb E, and several other variant hemoglobins. Definitive diagnosis that is necessary for proper patient management is best done by DNA‐based gap‐PCR tests. Am. J. Hematol, 2009. © 2008 Wiley‐Liss, Inc.
The proteasome inhibitor, bortezomib suppresses primary myeloma and stimulates bone formation in myelomatous and nonmyelomatous bones in vivo
Authors: Pennisi Angela , Li Xin , Ling Wen , Khan Sharmin , Zangari Maurizio , Yaccoby Shmuel 
Published: October 2008

AbstractMultiple myeloma (MM), a hematologic malignancy of terminally differentiated plasma cells is closely associated with induction of osteolytic bone disease, induced by stimulation of osteoclastogenesis and suppression of osteoblastogenesis. The ubiquitin‐proteasome pathway regulates differentiation of bone cells and MM cell growth. The proteasome inhibitor, bortezomib, is a clinical potent antimyeloma agent. The main goal of this study was to investigate the effect of bortezomib on myeloma‐induced bone resorption and tumor growth in SCID‐rab mice engrafted with MM cells from 16 patients. Antimyeloma response of bortezomib, which was evident in >50% of 16 experiments and resembled clinical response, was associated with significant increased bone mineral density (BMD) and osteoblast numbers, and reduced osteoclast numbers in myelomatous bones. This bone anabolic effect, which was also visualized on X‐ray radiographs and confirmed by static and dynamic histomorphometric analyses, was unique to bortezomib and was not observed in hosts responding to melphalan, a chemotherapeutic drug widely used to treat MM. Bortezomib also increased BMD and osteoblasts number and reduced osteoclasts number in nonmyelomatous implanted bones. In vitro bortezomib directly suppressed human osteoclast formation and promoted maturation of osteoblasts. We conclude that bortezomib promotes bone formation in myelomatous and nonmyelomatous bones by simultaneously inhibiting osteoclastogenesis and stimulating osteoblastogenesis. As clinical and experimental studies indicate that bone disease is both a consequence and necessity of MM progression our results suggest and that bortezomib's effects on bone remodeling contribute to the antimyeloma efficacy of this drug. Am. J. Hematol., 2009. © 2008 Wiley‐Liss, Inc.
High CD8+ lymphocyte dose in the autograft predicts early absolute lymphocyte count recovery after peripheral hematopoietic stem cell transplantation
Authors: Atta Elias Hallack , de Azevedo Alexandre Mello , Maiolino Angelo , Coelho Cláudia Júlia Bruzzi Porto , Sarcinelli Silvia Maria Patiño , de Alvarenga Máximo Cláudia , Marra Vera Lúcia Neves 
Published: October 2008

AbstractEarly lymphocyte recovery (ELR) after autologous peripheral hematopoietic stem cell transplantation (ASCT) is an independent predictor for survival in patients with hematological and non‐hematological cancers. Sixty‐five ASCT for hematological cancers were retrospectively analyzed to identify the factors associated with ELR and to assess the impact of different mobilization regimens on the pre‐collection absolute lymphocyte count (ALC). The CD8+ lymphocyte dose in the autograft and the pre‐mobilization ALC were independently associated with ELR (P < 0.001 and P = 0.008, respectively). CD8+ lymphocyte doses higher than 0.1 × 109/kg were strongly associated with ELR [P < 0.001, odds ratio 25.22, 95% confidence interval (CI) 4.98–127.69] and this cutoff may be used to predict ELR (P = 0.001, area under the curve 0.75, 95% CI 0.62–0.88). Mobilization with granulocyte colony‐stimulating factor (G‐CSF) alone, the pre‐collection ALC and the number of apheresis sessions were independently associated with the CD8+ lymphocyte dose (P = 0.04, P = 0.001, and P < 0.001, respectively). The number of aphereses was the variable with the strongest correlation to the CD8+ lymphocyte dose (rs = 0.68, P < 0.001). Median pre‐mobilization ALC was higher than pre‐collection ALC in the subgroup of patients without ELR mobilized with chemotherapy followed by G‐CSF (1090 vs. 758 lymphocytes/μL; P < 0.001). This reduction was not significant in the subgroup with ELR mobilized with chemotherapy plus G‐CSF (1920 vs. 1539/μL, respectively; P = 0.23). These results suggest that the CD8+ lymphocyte dose in the autograft is critical for ELR after ASCT and also demonstrates that mobilization with chemotherapy followed by G‐CSF significantly decreases the pre‐collection ALC, especially in patients with low pre‐mobilization ALC. Am. J. Hematol, 2009. © 2008 Wiley‐Liss, Inc.
Apolipoprotein E genotype is related to nitric oxide production in platelets
Authors: Marcourakis Tania , Bahia Valéria S. , Kawamoto Elisa M. , Munhoz Carolina D. , Gorjão Renata , Artes Rinaldo , Kok Fernando , Caramelli Paulo , Nitrini Ricardo , Curi Rui , Scavone Cristoforo 
Published: October 2008

AbstractThe presence of the ε4 allele of apolipoprotein E (APOE) is considered a risk factor for sporadic Alzheimer's disease (AD). Our recent data demonstrated that the systemic modulation of oxidative stress in platelets and erythrocytes is disrupted in aging and AD. In this study, the relationship between APOE genotype and oxidative stress markers, both in AD patients and controls, was evaluated. The AD group showed an increase in the content of thiobarbituric acid‐reactive substances (TBARS) and in the activities of nitric oxide synthase (NOS) and Na, K‐ATPase, when compared to controls. Both groups had a similar cGMP content and superoxide dismutase activity. APOE ε4 allele carriers showed higher NOS activity than non‐carriers. These results suggest a possible influence of APOE genotype on nitric oxide (NO) production that might enhance the effects of age‐related specific factor(s) associated with neurodegenerative disorders. Copyright © 2008 John Wiley & Sons, Ltd.