bluuebunny/crossref_metadata_2025_split huggingface dataset:
Habitat use of a critically‐endangered species in a predator‐free but degraded reserve in Australia
Authors: Winnard Amy L. , Stefano Julian Di , Coulson Graeme 
Published: January 2014

The success of species reintroduction programmes depends on many factors, including habitat quality and predator occurrence at release locations. For the critically endangered eastern barred bandicoot Perameles gunnii in Australia, successful releases have been achieved only in the absence of predation by the introduced red fox Vulpes vulpes. However, few fox‐free sites exist, but those that are fox free may have low habitat suitability, potentially leading to reintroduction failure. We studied a reintroduced population of eastern barred bandicoots at Mt Rothwell, a 420‐ha fox‐free reserve which appeared to have a degraded foraging range and a lack of nesting material due to overgrazing by marsupial herbivores. We quantified habitat use and measured several variables representing movement distances and nest use. Bandicoots foraged in open grassy areas and nested at sites containing high values of litter, lateral cover and concealment cover. Mean (± SE) home ranges (37.2 ha ± 11.8), daily movement distances (494.6 m ± 32.5) and distances between consecutive nests (122.6 m ± 29.0) were large for males. On average, the length of stay at each nest (2.8 days ± 0.4) was longer than previously recorded values for males, and 13.2% of the nests were used by at least two individuals, suggesting that nesting opportunities were limited. Despite behaviour indicating a low resource base, bandicoots appeared to be surviving and reproducing in our study area, indicating a capacity to live in structurally simple habitat in the absence of predators. Our results are consistent with predator exclusion being a critical factor for successful bandicoot reintroduction.
The incidence of postoperative hyponatremia and associated neurological sequelae in children with intracranial neoplasms
Authors: Williams Cydni N. , Belzer Jennifer S. , Riva-Cambrin Jay , Presson Angela P. , Bratton Susan L. 
Published: January 2014

Object
Intracranial tumors are common pediatric neoplasms and account for substantial morbidity among children with cancer. Hyponatremia is a known complication of neurosurgical procedures and is associated with higher morbidity among neurosurgical patients. The authors aimed to estimate the incidence of hyponatremia, identify clinical characteristics associated with hyponatremia, and assess the association between hyponatremia and patient outcome among children undergoing surgery for intracranial tumors.

Methods
This is a retrospective cohort study of children ranging in age from 0 to 19 years who underwent an initial neurosurgical procedure for an intracranial tumor between January 2001 and February 2012. Hyponatremia was defined as serum sodium ≤ 130 mEq/L during admission.

Results
Hyponatremia during admission occurred in 39 (12%) of 319 patients and was associated with young age and obstructive hydrocephalus (relative risk [RR] 2.9 [95% CI 1.3–6.3]). Hyponatremic patients were frequently symptomatic; 21% had seizures and 41% had altered mental status. Hyponatremia was associated with complicated care including mechanical ventilation (RR 4.4 [95% CI 2.5–7.9]), physical therapy (RR 4 [95% CI 1.8–8.8]), supplemental nutrition (RR 5.7 [95% CI 3.3–9.8]), and infection (RR 5.7 [95% CI 3.3–9.5]). Hyponatremic patients had a 5-fold increased risk of moderate or severe disability on the basis of their Pediatric Cerebral Performance Category score at discharge (RR 5.3 [95% CI 2.9–9.8]). Obstructive hydrocephalus (adjusted odds ratio [aOR] 3.24 [95% CI 1.38–8.94]) and young age (aOR 0.92 [95% CI 0.85–0.99]) were independently associated with hyponatremia during admission. Hyponatremia was independently associated with moderate or worse disability by Pediatric Cerebral Performance Category score at discharge (aOR 6.2 [95% CI 3.0–13.03]).

Conclusions
Hyponatremia was common, particularly among younger children and those with hydrocephalus. Hyponatremia was frequently symptomatic and was associated with more complicated hospital courses. Hyponatremia was independently associated with worse neurological outcome when adjusted for age and tumor factors. This study serves as an exploratory analysis identifying important risk factors for hyponatremia and associated sequelae. Further research into the causes of hyponatremia and the association with poor outcome is needed to determine if prevention and treatment of hyponatremia can improve outcomes in these children.
New Professionalism Challenges in Medical Training: An Exploration of Social Networking
Authors: Kesselheim Jennifer C. , Batra Maneesh , Belmonte Frank , Boland Kimberly A. , McGregor Robert S. 
Published: January 2014

Abstract

Background
Innovative online technology can enhance the practice of medicine, yet it also may be a forum for unprofessional behavior.

Objective
We surveyed program directors regarding their perceptions and experiences with residents' use of social networking sites (SNS).

Methods
In September 2011, we sent an online survey to program directors and associate program directors of pediatrics residency programs within the United States who are members of the Association of Pediatric Program Directors.

Results
A total of 162 program directors or associate program directors (representing 50% of residency programs) responded to the survey. One-third of respondents are “very familiar” with SNS and 23% use them “daily or often.” Most respondents (70%) rated “friending” peers as “completely appropriate,” whereas only 1% of respondents rated “friending” current or past patients as “completely appropriate.” More than one half of respondents believe inappropriate behavior on SNS is “somewhat” or “very” prevalent, and 91% are “somewhat” or “very” concerned that the prevalence of inappropriate behavior on SNS may increase. The most commonly reported problematic online activity was posting inappropriate comments about the workplace. Posting of inappropriate comments about self, patients, and staff also was observed. Residency programs commonly educate trainees about SNS during intern orientation (45%), or using written guidelines (29%) and ad hoc remediation (16%).

Conclusions
As educators teach trainees principles of online professionalism, appropriate use of SNS needs to be included in the training process. Curricular efforts may be hindered by some program directors' lack of familiarity with SNS.
Preference Trials
Authors: Campbell Marion K. , Torgerson David J. 
Published: January 2014

AbstractAlthough the randomized controlled trial is widely accepted as the design of choice for evaluating health‐care interventions, it requires that all participants are prepared to accept allocation to any of the interventions under study. When patients have a strong preference to receive one of the study interventions, this can lead to difficulties with compliance and potentially to biased assessment of outcomes. The patient preference trial has been proposed as a potential solution, with patients with strong preferences being allocated to their treatment of choice and those with no strong preference being randomized in the standard manner. All patients are followed up and outcomes assessed. We discuss the effects of patient preference and review the advantages and disadvantages of the patient preference design.
Prevention Trials
Authors: Prentice Ross L. 
Published: January 2014

AbstractRandomized controlled trials provide the gold standard for assessing the health benefits and risks of preventive treatments or interventions. Such trials typically need to be very large‐scale and long‐term. Hence, cost and logistic considerations imply that few such trials can be conducted, and there is a need for careful hypothesis development and preliminary testing, prior to the initiation of a full‐scale disease prevention trial. Aspects of the design, conduct monitoring and analysis of prevention trials are reviewed, along with a discussion of differences from therapeutic trials, and of the interplay with observational studies. The National Institutes of Health‐sponsored Women's Health Initiative, which includes both a multi‐faceted prevention trial, and a large cohort study, among postmenopausal women, provides an illustration of prevention trial considerations and trade‐offs.
Primary Efficacy Endpoint
Authors: Follmann Dean A 
Published: January 2014

AbstractAt its core, a clinical trial is designed to test a specific primary hypothesis. The primary efficacy endpoint in a clinical trial is a clinical or laboratory outcome measured in an individual after randomization that allows one to test the primary hypothesis and provides the means of assessing whether a therapy is effective compared with its control. A primary endpoint can be measured once or repeatedly over time, or may comprise several kinds of individual measurements. Once a primary endpoint is selected, statistical methods of analysis to test the primary hypothesis can be determined and sample size calculations can be performed to ensure the trial is properly powered. Because of the key role of the primary endpoint in the design and analysis of a trial, it is critical that it be chosen carefully. A primary efficacy endpoint must be precisely specified in advance and should(1)address the primary objective,(2)be ascertainable in all patients,(3)be “fair” to each study arm,(4)have demonstrated or accepted relevance for the population and intervention(s) of the trial, and(5)be sensitive to meaningful changes in a patient's health.
Repeated Measurements
Authors: Verbeke Geert , Lesaffre Emmanuel 
Published: January 2014

AbstractRepeated measures are obtained whenever an outcome is measured repeatedly within a set of units. The fact that observations from the same unit, in general, will not be independent poses particular challenges to the statistical procedures used for the analysis of such data. The current article is dedicated to an overview of frequently used statistical models for the analysis of repeated measurements, with emphasis on model formulation and parameter interpretation.
Screening, Models of
Authors: Stevenson Chris 
Published: January 2014

AbstractThis 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.
Subgroup
Authors: Wittes Janet 
Published: January 2014

AbstractRandomized clinical trials are usually designed to show an effect of treatment in the study population at large. Trials rarely have sufficient statistical power to measure reliably the effect of a treatment within a subgroup of that population. They are even less likely to provide reliable information on whether the effect of a treatment differs from subgroup to subgroup. This article defines various terms related to analysis of subgroups. It distinguishes between subgroups defined on the basis of baseline variables from “improper” subgroups defined on the basis of variables measured after randomization. It also discusses hypotheses defined a priori and those identified after the results have emerged. It emphasizes that random variation arising from small sample sizes can lead to unrealistically large or small observed effects and warns investigators to interpret findings from subgroups with caution.
The FDA and Regulatory Issues
Authors: Rzeszotarski W. Janusz 
Published: January 2014

Abstract
A brief outline of information that is available on the Web pertinent to the FDA and regulatory issues. The process of new drug approval and its continuous modification reflects both the progress of science and the globalization of the world's economy. The reader is encouraged to follow the changes by constant monitoring of the FDA and the industry sites dedicated to these issues. The history of drug regulation in the United States, the evolving structure of the FDA, the steps to be taken in the process of obtaining the approval to market the new molecular entity, and the post‐approval requirements are briefly described.
Treatment Interruption
Authors: Grund Birgit 
Published: January 2014

AbstractInterruption of active drug treatment in clinical trials can be classified broadly as therapeutic treatment interruption (TI), in which the potential therapeutic benefit of supervised interruption of treatment is investigated, and analytic TI, in which participants are randomized to stopping versus continuing active treatment; the TI arm serves as control group. Design issues for therapeutic TI trials are discussed in the example of a trial in HIV/AIDS.Analytic TIs are used in therapeutic HIV vaccine trials, in randomized discontinuation designs, and in other situations. The use of a randomized discontinuation design for a Phase II drug trial in cancer is discussed.
Accelerated Approval
Authors: Cabanilla Louis A. , Milne Christopher P. 
Published: January 2014

AbstractIn 1992, the Food and Drug Administration (FDA) promulgated regulations for the Accelerated Approval program, which allowed drugs to gain approval based on unvalidated surrogate endpoints, or an effect on a clinical endpoint other than survival, or approval with restricted distribution. Initially, the program was primarily targeted at AIDS and cancer treatments, but it is now available for a wide array of diseases, and it has grown beyond small molecules to encompass biologic products, vaccines, and other product areas. Because of the severity of the illnesses being addressed and the potential for a “meaningful clinical benefit,” the FDA is generally willing to accept a higher risk to benefit ratio for an accelerated approval to provide earlier treatment for patients despite the lack of definitive evidence of the ultimate clinical benefit. Although a drug that is given accelerated approval might reach the market, the company sponsoring the drug is required to complete the necessary research to determine efficacy with a “Phase IV” study with “due diligence.” A problem with the definition of diligence, as well as enforcement mechanisms, has lead to some contention about the level of compliance by the drug industry. Despite these issues, the program alone, or in concert with other FDA approval programs, has to date brought some 50 lifesaving drugs to market months or years faster than would have happened through the traditional process. This information, together with advances in the science and technology of the clinical evaluation of biopharmaceuticals and the more powerful voice of patient advocacy in determining regulatory agency policy, ought to ensure that accelerated approval will expand its reach both therapeutically and geographically.
Aligned Rank Test
Authors: McNeil Rebecca B. , Woolson Robert F. 
Published: January 2014

AbstractAligned rank tests are an intuitive rank‐based approach to the evaluation of an experimental treatment effect in blocked or stratified data. Their interblock ranking foundation yields an efficiency advantage relative to comparable tests constructed from intrablock rankings such as Friedman's test. Both exact and asymptotic tests of the null hypothesis are available with this approach. We present a general overview of the history and construction of aligned rank tests, and provide an example in selected data from a clinical trial of high‐dose vitamin D supplementation.
Analysis of VarianceANOVA
Authors: Kaufmann Jörg , Schering AG 
Published: January 2014

AbstractThe development of analysis of variance (ANOVA) methodology has in turn had an influenced on the types of experimental research being carried out in many fields. ANOVA is one of the most commonly used statistical techniques, with applications across the full spectrum of experiments in agriculture, biology, chemistry, toxicology, pharmaceutical research, clinical development, psychology, social science, and engineering. The procedure involves the separation of total observed variation in the data into individual components attributable to various factors as well as those caused by random or chance fluctuation. It allows performing hypotheses tests of significance to determine which factors influence the outcome of the experiment. However, although hypothesis testing is certainly a very useful feature of the ANOVA, it is by no means the only aspect. The methodology was originally developed by Sir Ronald A. Fisher, the pioneer and innovator of the use and applications of statistical methods in experimental design who coined the name “Analysis of Variance – ANOVA.”
Assessment Bias
Authors: Gøtzsche Peter C. 
Published: January 2014

Abstract
Assessment bias in a clinical trial occurs if bias in the assessment of the outcome exists. It is also called ascertainment bias, diagnostic bias, or detection bias. A major cause of assessment bias is lack of blinding. Other problems relate to differential identification of harmless or false‐positive cases of disease, bias in assessment of disease‐specific mortality, the use of composite outcomes, competing risks, timing of the assessments, and bias in assessment of harms.
Biological Assay, Overview
Authors: Sen Pranab K. 
Published: January 2014

AbstractBiological essay (or “bioassay”), in its classical form, is concerned with the measurement of the concentration of an active ingredient in a test preparation, by estimation of its potency relative to that of a standard preparation. Assays, usually by animal experimentation, form an essential tool of biological standardization. Standard designs and methods of analysis are described here, including stochastic approximation, radioimmunoassays, semiparametric and nonparametric methods, and bioequivalence studies. In a broader sense, Bioassay refers to experiments, with biological units, to detect possible dose–response (or toxicity‐adverse effect) relationships. Underlying toxicodynamics (and/or pharmacodynamics) and toxicokinetics (and/or pharmacokinetics), possibly in conjunction with toxicogenomics (and/or pharmacogenomics) may render such studies statistically quite different from conventional biometric studies. Some relevant approaches are considered here.
Bootstrap
Authors: Hesterberg Tim 
Published: January 2014

AbstractThis article provides an introduction to the bootstrap. The bootstrap provides statistical inferences—standard error and bias estimates, confidence intervals, and hypothesis tests—without assumptions such as normal distributions or equal variances. As such, bootstrap methods can be remarkably more accurate than classic inferences based on normal ortdistributions. The bootstrap uses the same basic procedure regardless of the statistic being calculated, without requiring the use of application‐specific formulae.This article may provide two big surprises for many readers. The first is that the bootstrap shows that commontconfidence intervals are woefully inaccurate when populations are skewed, with one‐sided coverage levels off by factors of two or more, even for very large samples. The second is that the number of bootstrap samples required is much larger than generally realized.
Clinical Data Management
Authors: McBride Ruth 
Published: January 2014

AbstractClinical data management is data management systems and process focused on providing clean, current and reliable data to support clinical research, especially for clinical trials. Computerized systems have been used since the early 1960's. Current clinical data management systems vary. Many, but not all clinical trials use electronic data capture to collect data from clinical research sites. Efforts are underway to standardize the way clinical data are organized.
Confounding
Authors: Greenland Sander 
Published: January 2014

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.
Crossover Design
Authors: Kenward Michael G. 
Published: January 2014

Abstract
In a crossover design, each subject is randomized to a sequence of treatments with the aim of comparing the effect of an individual treatment assignment. Such trials are restricted to fairly stable conditions and treatments with reversible effects. When within‐subject dependence of the outcome is high, such designs can be much more efficient than a parallel‐group study with the same number of subjects. However, because randomization applies to the sequences, not the individual treatments, the justification for the analysis of data from such trials depends more on model‐based assumptions than a typical parallel‐group study. The most commonly used crossover design is the so‐called two‐period, two‐treatment design, in which subjects are randomized to one of two sequences, A then B or B then A. Provided it can be assumed that the consequences of treatment allocation in the first period does not bias the treatment comparison in the second period (carryover), the analysis of such trials is very simple. It turns out that in most trials there will be very little information in the data on possible carryover, and therefore no useful statistical procedure exists either for its assessment or for adjustment for it. As a consequence, prior knowledge and adequate washout periods need to be used to justify the analysis in such settings. Higher order designs with more than two periods and more than two sequences exist for both the two‐treatment setting and for more than two treatments. Efficient designs can be constructed that allow adjustment for carryover, but only when it is expressed in particular, limited, mathematical forms. Data from crossover designs are examples of conventional repeated measures and analyses can be taken from the range of tools available for these, both with continuous and discrete outcomes.
Dose Ranging Crossover Designs
Authors: Patterson Scott D. , Jones Byron , Zariffa Névine 
Published: January 2014

Abstract
Dose ranging trials are used frequently in drug development to learn about dose response for both desirable and undesirable effects and to provide sponsors with confidence that investment in confirmatory trials for market access is likely to be successful. The design of crossover studies and analysis of data that develops from such crossover trials are discussed.