bluuebunny/crossref_metadata_2025 huggingface dataset:
Le système du droit russe sur la carte juridique du Monde
Authors: Zakharova Maria
Published: January 2014

Les représentants de la science juridique contemporaine ont maintes fois énoncé, depuis leurs chaires et dans les pages des publications scientifiques, le problème de la «quête par la Russie de sa nouvelle voie juridique » 1. La cessation de l’existence de l’URSS en tant qu’État n’a fait que compliquer, à cet égard, le problème de l’identification collective du système juridique russe. Cependant, il convient de s’interroger sur la pertinence même de la question de l’étape initiale de la formation du système juridique de la Russie. N’aurait-on pas raison, à cet égard, de parler de son évolution plutôt que de son devenir ? Quel âge a ce système ? Des dizaines d’années ? Ou peut-être des centaines ? Que représente-t-il en soi à l’heure actuelle ? Et quels sont les paradigmes de son évolution au cours de la longue histoire de son existence ? Dans l’article présenté ci-après, les réponses aux questions mentionnées seront données à travers le prisme d’une approche par l’auteur du problème de l’appréciation conceptuelle et formelle de la catégorie «système juridique » ainsi que sur une base méthodologique de synergie à l’égard de la dynamique du développement du phénomène juridique en tant que tel.
Le pragmatisme juridique dans la Chine post-Mao
Authors: Li-Kotovtchikhine Xiao-Ying
Published: January 2014

Depuis trente ans, le droit chinois est sans cesse en mutation. Au-delà de l’image de mosaïque qu’il présente, on observe une constante dans son évolution : le pragmatisme. Si ce pragmatisme juridique traduit avant tout le pragmatisme politique initié par Deng Xiaoping, il reflète une influence indéniable de la pensée traditionnelle chinoise. D’une part, il a largement marqué les réformes juridiques, qu’il s’agisse du fond ou de la méthodologie. Ainsi, le droit a été mis au service de trois objectifs principaux que constituent les trois lignes directrices du pragmatisme politique : construction économique, stabilité, et le maintien de la direction du PCC. D’autre part, il a profondément modelé la conception même du droit, qui vacille sans cesse entre trois idées : «gouvernement par la vertu » , «gouvernement par la loi » , et État de droit. Le pragmatisme juridique chinois est critiquable en ce qu’il retient une vision instrumentale du droit et qu’il semble compromettre la construction d’un ordre juridique performant et stable. Néanmoins, il demeure une clé de compréhension essentielle du droit chinois contemporain.
L’immunité pénale des organes constitutionnels monocéphales en Italie - La censure par la Cour constitutionnelle de la “Loi Alfano”
Authors: Laffaille Franck
Published: January 2014

La Cour constitutionnelle italienne censure en octobre 2009 la « loi Alfano » (2008) posant l’immunité pénale de ces quatre organes constitutionnels monocéphales que sont le chef de l’Etat, le président du Conseil et les présidents des chambres. La norme législative est jugée non conforme à la loi fondamentale de 1947 pour défaut de «couverture constitutionnelle » et violation du principe d’égalité. La décision de la Cour mérite approbation lorsqu’elle impose l’obligation d’une loi constitutionnelle pour suspendre le procès pénal ; cependant, pourquoi ne pas avoir mentionné une telle contrainte normative dans sa décision de 2004 qui censure une loi (lodo Schifani) ayant la même finalité que la « loi Alfano » ? La décision de 2009 de la Cour mérite critique lorsqu’elle censure pour violation du principe d’égalité ; ne fallait-il pas accorder un régime juridique dérogatoire à des organes assumant objectivement des fonctions constitutionnelles spécifiques ? Très commentée, ce jugement illustre la fracture toujours vive en Italie entre Droit & Politique, Politique & Justice ; les procès en légitimité sont récurrents. Sans doute l’introduction de dissenting et concurring opinions, de nouveau évoquée avec force en doctrine, aurait-elle l’insigne avantage de la pédagogie et de la transparence.
Total synthesis of (+)-grandiamide D, dasyclamide and gigantamide A from a Baylis–Hillman adduct: A unified biomimetic approach
Authors: Ilangovan Andivelu , Saravanakumar Shanmugasundar
Published: January 2014

A unified strategy was followed for the synthesis of three putrescine bisamides, (+)-grandiamide D, dasyclamide and gigantamide A, isolated from leaves of Aglaia gigantea, by making use of a common synthetic intermediate prepared by the Baylis–Hillman reaction. Asymmetric synthesis of the natural (+)-grandiamide D was accomplished from camphor sultam.
Stochastic formalism-based seafloor feature discrimination using multifractality of time-dependent acoustic backscatter
Authors: Haris K. , Chakraborty B.
Published: January 2014

Abstract. Dual-frequency echo-envelope data acquired using the normal-incidence single-beam echosounder system (SBES) have been examined to study its scale invariant properties. The scaling and multifractality of the SBES echo envelopes (at 33 and 210 kHz) were validated by applying a stochastic-based multifractal analysis technique. The analyses carried out substantiate the hierarchy of multiplicative cascade dynamics in the echo envelopes, demonstrating a first-order multifractal phase transition. The resulting scale invariant parameters (α, C1, and H) establish gainful information that can facilitate distinctive delineation of the sediment provinces in the central part of the western continental shelf of India. The universal multifractal parameters among the coarse and fine sediments exhibit subtle difference in α and H, whereas the codimension parameter C1 representing the sparseness of the data varies. The C1 values are well clustered at both the acoustic frequencies, demarcating the coarse and fine sediment provinces. Statistically significant correlations are noticeable between the computed C1 values and the ground truth sediment information. The variations in the multifractal parameters and their behavior with respect to the ground truth sediment information are in good corroboration with the previously estimated sediment geoacoustic inversion results obtained at the same locations.
Stochastic electron motion driven by space plasma waves
Authors: Khazanov G. V. , Tel’nikhin A. A. , Kronberg T. K.
Published: January 2014

Abstract. Stochastic motion of relativistic electrons under conditions of the nonlinear resonance interaction of particles with space plasma waves is studied. Particular attention is given to the problem of the stability and variability of the Earth's radiation belts. It is found that the interaction between whistler-mode waves and radiation-belt electrons is likely to involve the same mechanism that is responsible for the dynamical balance between the accelerating process and relativistic electron precipitation events. We have also considered the efficiency of the mechanism of stochastic surfing acceleration of cosmic electrons at the supernova remnant shock front, and the accelerating process driven by a Langmuir wave packet in producing cosmic ray electrons. The dynamics of cosmic electrons is formulated in terms of a dissipative map involving the effect of synchrotron emission. We present analytical and numerical methods for studying Hamiltonian chaos and dissipative strange attractors, and for determining the heating extent and energy spectra.
‘Beyond the Lens of Peasantry’: Theoretical Basis of ‘Fishantry’ as a Distinct Social Domain (Part 1)
Authors: Deb Apurba Krishna , Haque C. Emdad
Published: January 2014

Historically, fishers have been embodied among rural primary producers, and they have been largely overlooked in efforts of anthropological and political theorizing of the peasantry. This article, which is the first part of a study, takes up the challenge to analyze the theoretical basis and argues in favour of why fishers do deserve a separate analytical treatment. We observed that, despite some commonalities, interactions, and dependencies between fishers and peasants as rural inhabitants and professional groups, fishers exhibit distinct characteristics in terms of their socio-political dimension, culture, Traditional Ecological Knowledge (TEK), production relations, adoption of technology, local institutions, and resource governance. We, therefore, assert fishantry as a distinct social domain that deserves a separate analytical framework relative to peasantry. Empirically, the attributes of fishantry are more visible in small-scale fisheries in developing or least-developed societies. In part two of this study, which will be published in the next issue, we present the analysis pertinent to the independent existence and the social relations of fishers in the fishing communities in Bangladesh. We envision that manifestations of a fishantry theoretical framework would be reflected in the policy domain as designated resources and programs that would aim for the sustainable management of fisheries resources and the well-being of the user groups.
Valoraciones del profesorado del área de Fresno (California Central) sobre la influencia de la tecnología móvil en el aprendizaje de sus estudiantes
Authors: Navaridas Fermín , Santiago Raúl , Tourón Javier
Published: January 2014

En este artículo se presentan  los resultados más relevantes de una investigación en la que se analizan las opiniones del profesorado del área de Fresno (California Central, EEUU) respecto a los efectos que tiene el uso de los dispositivos móviles en los procesos de aprendizaje de los estudiantes. Entre otros objetivos, se ha tratado de reconocer la influencia del uso de los dispositivos móviles en tres dimensiones importantes del aprendizaje: la afectivo-emocional (motivación), la ético-social (habilidades sociales) y la cognitiva (habilidades cognitivas). Para llevar a cabo el proceso de estudio se adoptó un enfoque metodológico de carácter descriptivo, considerando la técnica de encuesta como el procedimiento más adecuado para recoger la opinión del profesorado de una forma relativamente rápida y precisa. Los resultados obtenidos ponen de manifiesto un acuerdo bastante generalizado del profesorado sobre el potencial pedagógico de la tecnología móvil para mejorar la calidad del aprendizaje. En términos generales, las conclusiones vienen a corroborar un aumento del interés de los estudiantes por la tarea, el incremento de la actividad durante el estudio, un trabajo más colaborativo, así como la mejora de la creatividad y el proceso de adquisición de información de los estudiantes
Prognostic Variables in Clinical Trials
Authors: Berger Vance W. , Sankoh A. J.
Published: January 2014

Identifying and making appropriate use of influential prognostic factors in the design and analysis of clinical trials is important. The discussion focuses on the nature and validity of covariates, and some statistical considerations for the selection of and adjustment for important prognostic factors.
Publication Bias
Authors: Rothstein Hannah R.
Published: January 2014

Publication bias is defined as the problem that results from systematic differences between the results of all the completed studies on a topic and the results of the subset of those studies that are published. The consequences of this problem include the danger that readers and reviewers will reach the wrong conclusion about what the evidence shows, leading at times to the use of unsafe or ineffective treatments. The role of meta‐analysis in highlighting the existence of publication bias is explained, after which a brief summary of the evidence that publication bias exists in the biomedical trials literature is provided. In addition to “classic” publication bias (bias due to selection on the basis of statistical significance), other potential information suppression mechanisms that represent a threat to the validity of research reviews are explained, including language, citation, availability, cost, outcome, and duplication biases. After this, ways of preventing publication bias are introduced, including universal prospective registration of trials, and design of prospective meta‐analyses. The role of thorough information search in reducing the impact of publication bias on meta‐analytic results is explained, and suggestions of what to search are made. The major procedures for assessing publication bias are summarized, including file drawer (failsafeN) analysis, the funnel plot, the Begg and Mazumdar test, the Egger test, and the trim and fill method. Differences in the various procedures' specific hypotheses about the distribution of study results as well as their limitations are noted. Finally, results of surveys of the impact of publication bias on health‐care meta‐analysis are described and their implications discussed.
Regression
Authors: Farewell Vern T.
Published: January 2014

Statistical usage of the term regression is discussed.
Sample Size Calculation for Comparing Proportions
Authors: Wang Hansheng , Chow Shein‐Chung
Published: January 2014

In practice, the objective of sample size calculation is to select the minimum sample size in such a way that the desired power can be obtained for detection of a clinically meaningful difference at the prespecified significance level. Therefore, the selection of the sample size depends on the magnitude of the clinically meaningful difference, the desired power, the prespecified significance level, and the hypotheses of interest under the study of choice (e.g., a parallel design or a crossover design).
Sample Size Calculation for Comparing Time‐to‐Event Data
Authors: Wang Hansheng , Chow Shein‐Chung
Published: January 2014

This article discusses three commonly employed testing procedures: the exponential model, Cox's proportional hazard model, and the log‐rank test. The sample size formula for testing equality, superiority, and equivalence are discussed for each method.
Sample Size Calculation for Comparing Variabilities
Authors: Wang Hansheng , Chow Shein‐Chung
Published: January 2014

In clinical research, in addition to comparing mean responses between treatment groups, it is also of interest to compare variabilities of responses between treatment groups. In practice, it is a concern that (1) larger variability may result in a worse safety profile and (2) larger variability may decrease the probability of reproducibility of the observed clinical results. Besides, efficacy and safety assessment are often done based on mean responses by assuming that the associated variabilities are the same, which may not be true in many cases. As a result, comparing variabilities of responses between treatment groups has received much attention lately. In order to achieve a desired statistical power when comparing variabilities of responses between treatment groups, commonly used procedures or formulas, which are derived based on comparing mean responses, cannot be applied directly and are necessarily modified.
Superiority Trial
Authors: Sackett David L.
Published: January 2014

When busy clinicians encounter a new treatment, they ask themselves two questions. First, is itbetterthan (“superior to”) what they are using now? Second, if is not superior, is itas good aswhat they are using now (“noninferior”) and preferable for some other reason (e.g., fewer side effects or more affordable)? In statistical terms, these clinical questions are “one‐sided.” However, traditional statistical concepts call for two‐sided tests of statistical significance and require rejection of the null hypothesis. A solution to both this incompatibility (between one‐sided clinical reasoning and two‐sided statistical testing) and confusion (about the clinical interpretation of statistically nonsignificant results) is now gaining widespread recognition and application. It is encompassed by the concepts of “superiority” and “noninferiority,” and these inextricable concepts are the subjects of this entry.
UGDPTrial
Authors: Meinert Curtis
Published: January 2014

The UGDP (University Group Diabetes Program) was a multicenter, randomized, placebo‐controlled trials aimed at assessing the efficacy of antidiabetic treatments in delaying or preventing the long‐term complications of adult‐onset diabetes (type‐2 diabetes). The trial was in the carly vanguard of trials aimed at assessing efficacy of approved treatments for chronic conditions—phase IV trials in the vernacular of trials. The trial involved two oral agents, tolbutamide and phenformin, and matching placebos and two insulin‐assigned treatment groups (insulin dosage as determined by body surface and insulin dosage as needed to “normalized” blood glucose levels). The trial generated a firestorm of controversy in 1970 with presentation and publication of results suggesting that a widely used oral agent—tolbutamide (Orinase, Upjohn, Kalamazoo now part of Pfizer)—was of no value in reducing the risk of morbiarty or in prolonging life. The FDA used its results to revise the label for the drug to include a special warning concerning the possibility cardiovascular risks associated with the drug, but only after a prolonged battle that raged on for more than a decade—a battle that ultimately ended up in front of the U.S. Supreme Court.
Women's Health Initiative: Statistical Aspects and Selected Early Results
Authors: Prentice Ross L. , Anderson Garnet L.
Published: January 2014

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.
World Health Organization (
WHO
): Global Health Situation
Authors: Hapsara H. R.
Published: January 2014

WHO has responsibility for the global epidemiologic surveillance of disease, receiving information on outbreaks of communicable disease and distributing this information throughout the world. WHO is also responsible for the
International Health Regulations
, the International Classification of Diseases, and other standards, which together make international epidemiologic comparisons possible. WHO also publishes
World Health Statistics Quarterly
,
World Health Statistics Annual
,
World Health Report
. The thirtieth World Health Assembly decided that the main social target of governments and WHO in the coming decades should be “health for all” by the year 2000. Member states committed themselves to monitoring progress toward, and evaluating the attainment of, this common goal. The health‐for‐all monitoring and evaluation process is intended to establish a baseline of current health and socioeconomic conditions, against which progress toward defined targets and objectives can be measured. Periodic measurement should establish trends that will permit anticipation of future conditions, and enable planning for them. The Health Situation and Trend Assessment Program is at present responsible for global health situation analysis and projection; strengthening of country health information; and partnerships and coordination of epidemiology, statistics, and trend assessment. Global epidemiologic surveillance is under the responsibility of the Emerging and other Communicable Diseases Surveillance and Control Program
Assay Sensitivity
Authors: Chuang‐Stein Christy
Published: January 2014

The assay sensitivity of a clinical trial is defined as the trial's ability to distinguish an effective treatment from a less effective or an ineffective one. It is an important consideration when designing, conducting, and analyzing a clinical trial. The lack of adequate assay sensitivity has different implications for superiority trials and noninferiority trials. This article discusses factors that could impact assay sensitivity. It also discusses the increasing use of a three‐arm design to help evaluate assay sensitivity of a trial.
Bayesian Dose‐Finding Designs in Healthy Volunteers
Authors: Zhou Yinghui
Published: January 2014

In the majority of phase I clinical trials, experimental drugs are administered via predefined dose‐escalation schemes to healthy volunteers to explore the relationship between the dose administered and the primary responses of interest. The responses might be binary outcomes such as adverse events; quantitative summary measures concerning pharmacokinetics (PK), such as the average or maximum plasma concentration over time; or pharmacodynamic (PD), such as heart rate or blood pressure changes from baseline. Conventional dose‐escalation designs can take a long time to complete to investigate every available dose. Also, conventional statistical analyses are not accurate due to small sample sizes: 20 to 80 volunteers are typically used in phase I trials. Adaptive designs have been studied as they can potentially speed up dose‐escalation and have better properties in terms of avoidance of unsafe doses and accuracy of estimation when compared with conventional designs. This review of state‐of‐the‐art adaptive designs illustrates how such a design can be implemented and discusses some practical issues met during implementation.
Change/Percent Change From Baseline
Authors: Vickers Andrew J.
Published: January 2014

Many clinical trials involve baseline and follow‐up assessment of a continuous outcome, such as pain, blood pressure, or weight. Different methods are available to analyze the results of such trials, which include between‐group two‐sample comparisons of the follow‐up measure, change score or percentage change, and linear regression of treatment on the follow‐up measure with the baseline measure as a covariate [analysis of covariance (ANCOVA)]. Each method provides a statistic that may have greater or less clinical applicability, depending on the particular trial involved. ANCOVA has greatest statistical power irrespective of the correlation between baseline and follow‐up measure, the nature of the treatment effect (shift or ratio), whether the control group also experiences change, and the distribution of the follow‐up measure. ANCOVA has additional advantages including control for chance baseline differences and incorporation of randomization strata as covariates. If trials results are best expressed in terms other than ANCOVA, such as a percentage change, then the preferred approach is to analyze the trial using ANCOVA and then convert the results into statistics that can be readily understood by clinicians.
Chemistry, Manufacturing and Controls (
CMC
)
Authors: Schmuff Norman R. , Lin David T.
Published: January 2014

This article describes general expectations and issues related to the Quality (also known as Chemistry, Manufacturing and Controls) section of Investigational New Drug (IND) (see Investigational New Drug Application (IND) article) applications filed with the U.S. Food and Drug Administration's (FDA's) Center for Drug Evaluation and Research (CDER) (see CDER article). Only brief mention will be made to FDA's Center for Biologics Evaluation and Research (CBER) (see CBER article) and other regulatory authorities (see Ministry of Health and Welfare (Japan, now known as the MHLW),
Medicines Control Agency
(United Kingdom, now known as the MHRA), and
EMEA
(European Union) articles). For determining whether INDs are required for clinical studies, see the Investigational New Drug Application (IND) article.
Clinical Trials, Early Cancer and Heart Disease
Authors: Schneiderman Marvin A. , Gehan Edmund A.
Published: January 2014

Early 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.
Flexible Designs
Authors: Posch Martin , Bauer Peter , Brannath Werner
Published: January 2014

Flexible designs allow for mid‐trial design adaptations in an adaptive interim analysis based on all information collected while controlling the type I error rate. Examples of such adaptations are, for example, sample size reassessment, addition or dropping of interim analysis, or dropping of treatment arms. The crucial feature of the adaptive procedure is that the adaptation rules need not be specified in advance.
Global Assessment Variables
Authors: Tilley Barbara , Huang Peng , O'Brien Peter C.
Published: January 2014

Multiple outcomes are often collected for an evaluation of a treatment's effect on disease or quality of life or other underlying condition. When multiple outcomes are being assessed, and no predefined and validated composite outcome (summary measure) exists, two classes of statistical tests have been developed that address two different scientific questions. Tests in one class are designed to test whether a treatment effect is observed for any of the outcomes. Tests in the other class are designed to test whether a treatment confers an overall benefit (or harm) to patients. We provide a brief survey of global statistical tests (GST) of the second class. Each GST is discussed in terms of its motivation, approach to conducting the test, and some basic properties of the test. To facilitate the interpretation of the GST, we use the concept of a global treatment effect (GTE) to quantify the treatment's overall effect on multiple outcomes. We provide examples of the application of GSTs to clinical trials along with recommendations for choosing outcomes to include in the GST.
Interval Censored
Authors: Gerds Thomas A , Meier‐Hirmer Carolina
Published: January 2014

In survival or time‐to‐event analysis, interval censoring occurs if the time of an event is theendpointof interest that cannot be observed exactly for each patient but occurred chronologically between two follow‐ups. Information of the event status is typically collected by periodically performing clinical examinations or laboratory tests. Events of interest can be the onset of a disease, infection, the recurrence of a tumor, and other changes in the course of a disease. For example, in aclinical trial/study, the progression of a tumor can only be assessed at periodic examination times, e.g., every 6 months. The true time‐to‐progression is hidden somewhere between two adjacent examination times, e.g., between 12 and 18 months. Another typical example is the infection time, e.g., of HIV, when for the diagnosis the result oflaboratory testsis needed. The time‐to‐infection is included in an interval defined by the dates of acquisition. Two sources of censoring can be allocated. External censoring is due to the study design, which prohibits instantaneous access of the event of interest because the patient is not all the time medically supervised. An example for externally introduced censoring is the arrangement of yearly instead of monthly or daily examinations. On the other hand, the censoring can be due to the natural limits of the experiment. For instance, if the event of interest is the onset of a tumor, or anadverse drug reactionbecoming visible only after a certain limit of toxication is exceeded.
Lan‐DeMetsAlpha‐Spending Function
Authors: DeMets David L. , Lan K. K. Gordon
Published: January 2014

Randomized clinical trials are typically monitored periodically for early evidence of convincing benefit or of potential harm for both scientific and ethical reasons by a data monitoring committee. After increments in the number of patients randomized or in the number of observed events, interim statistical analyses may be conducted to evaluate emerging results. This process may be referred to as a group sequential design. However, repeated analysis of accumulating data with conventional statistical testing can lead to substantially increased Type I or false positive error rates. The alpha spending function provides a flexible approach to control the Type I error while allowing the data monitoring committee to review the data as needed without having to specifya prioriwhen and how many such interim analyses will be conducted. Other earlier group sequential methods had these somewhat restrictive requirements. This alpha spending function approach can be applied to several spending functions that approximate some of these earlier methods.
Longitudinal Data
Authors: Li Hung‐Ir
Published: January 2014

Longitudinal data have been the focus in various research such as economy, social science, public health, and biomedical research in the past few decades. These data comprise outcome measures or responses prospectively collected or naturally accrued repeatedly from the same subjects across multiple time points along with subject characteristic measures. In some observational studies in epidemiology/public heath, the data accrued over a long period of time as recorded in medical charts and are retrospectively retrieved. The data are used to answer questions regarding the change or progression of the disease over time and/or potential risk factors for the disease. Although in other studies, the existing data could be used to identify subgroups with different background characteristics or traits. The identified groups are then followed up for their health conditions for a certain period of time prospectively. The data from these groups are then compared with answer questions set out for the studies. In the clinical research and development settings, most of the longitudinal data are collected via prospectively designed clinical trials in order to assess the changes in efficacy and/or safety of certain medical intervention, drug, biologics, or devices. The longitudinal data from clinical trials in phase III of product development are intended to confirm that the clinical benefit or desired changes over time are primarily due to the target product, can be maintained for an adequate amount of time, and are applicable to a well‐defined population before regulatory approval is granted and the product is registered for public use. This article provides a summary of the definitions, features, and various types of longitudinal data resulting from clinical trials in phase III medicinal product development. The respective characteristics and the related issues along with the rules of thumb in the selection of the statistical methods for the analyses will also be provided.
Min Test
Authors: Laska Eugene M , Meisner Morris J
Published: January 2014

The Min test is a statistical tool used to test a null hypothesis such asHoi: νi≤ 0 for at least oneiversus the alternative H1: νi > 0 fori = 1, 2,…,K. This is sometimes called the sign‐testing problem. If every α‐level test of Hoi: νi≤ 0 individually rejects thei‐th null hypothesis at the α level, then the global null hypothesis is rejected according to the Min test. No adjustment for multiplicity is required. Such hypotheses arise in many clinical trials when it is desired to establish that a set of inequalities on the parameters simultaneously holds. Examples include testing whether an identified treatment is best on single or multiple endpoints; whether one treatment is equivalent to or noninferior to a control; and whether a dose of a combination is synergistic.
Generalized Linear Models
Authors: Kauermann Göran , Norrie John
Published: January 2014

Generalized linear models (GLMs) provide a flexible and commonly used tool for modeling data in a regression context. The approach has had a major impact on statistical modeling technology with research on a wide range of extensions continuing today.
Compliance and Survival Analysis
Authors: Goetghebeur Els
Published: January 2014

Partial compliance with assigned treatment can act as both cause and effect of survival experiences in randomized clinical trials. Structural failure time models have been developed for causal inference on the effect of resulting exposure patterns on survival time. In this setting, we review randomization based estimation methods that protect the standard α level. We also point to alternative methods relying on the assumption of no unmeasured time‐dependent confounders.
Control Groups
Authors: Green Stephanie
Published: January 2014

Use of appropriate control groups is a critical principle in clinical research methods. The modern randomized controlled trial is the most convincing and reliable method for minimizing bias and demonstrating effectiveness of treatment. Control groups for randomized trials may be patients randomized to no treatment, a placebo, or standard active therapy with or without a placebo. Due to practical and ethical constraints not all clinical questions can be addressed with a well‐controlled randomized trial. Non‐randomized trials can have specific comparator groups or be controlled in the sense that carefully chosen historical information from the literature is used for reference.
Good Clinical Practice (
GCP
)
Authors: Barr David B.
Published: January 2014

Good Clinical Practices (GCPs) are international ethical and quality standards for the design, conduct, performance, monitoring, auditing, analysis, recording, reporting, and regulation of clinical investigations. Clinical investigations are experiments in which a medical product such as a drug is administered or dispensed to, or used involving, one or more human subjects. These standards provide assurance that the rights and confidentiality of the trial subjects are protected and that the data and reported results are credible and accurate.
Allocation Concealment
Authors: Schulz Kenneth F.
Published: January 2014

Allocation concealment, as an integral part of randomization, implements an allocation sequence. Inadequate allocation concealment can lead to exaggerated estimates of treatment effect, but with scope for bias in both directions. Without adequate allocation concealment, even proper random assignment sequences can be subverted. Investigators must recognize the inquisitiveness and ingeniousness of human nature and “immunize” trials against selection and confounding biases with proper allocation concealment.
Composite Endpoints in Clinical Trials
Authors: O'Brien Peter C. , Tilley Barbara C. , Dyck Peter J.
Published: January 2014

The primary analysis plays a key role in clinical trials to determine efficacy. By providing a single
P
‐value, the primary analysis provides the basis for controlling the overall type I error rate. However, it is often desirable to consider multiple important patient outcomes in the primary analysis in order to use the most comprehensive and most clinically meaningful assessment of the patient. These properties also tend to increase the power of the resulting statistical tests. Composite endpoints are an effective way of combining the information from multiple endpoints when identification of a single primary outcome is not possible. We discuss a variety of ways for forming such composites. The ideal is an existing composite that has been extensively studied, validated, and used in clinical practice, and where a meaningful effect size has been identified. Statistical alternatives that may be useful when such an existing composite is not available include a rank sum approach and least squares methods and other methods described in global assessment variables.
Predicting the time derivative of local magnetic perturbations
Authors: Tóth Gábor , Meng Xing , Gombosi Tamas I. , Rastätter Lutz
Published: January 2014

Some of the potentially most destructive effects of severe space weather storms are caused by the geomagnetically induced currents. Geomagnetically induced currents (GICs) can cause failures of electric transformers and result in widespread blackouts. GICs are induced by the time variability of the magnetic field and are closely related to the time derivative of the local magnetic field perturbation. Predicting dB/dt is rather challenging, since the local magnetic perturbations and their time derivatives are both highly fluctuating quantities, especially during geomagnetic storms. The currently available first principles‐based and empirical models cannot predict the detailed minute‐scale or even faster time variation of the local magnetic field. On the other hand, Pulkkinen et al. (2013) demonstrated recently that several models can predict with positive skill scores whether the horizontal component of dB/dt at a given magnetometer station will exceed some threshold value in a 20 min time interval. In this paper we investigate if one can improve the efficiency of the prediction further. We find that the Space Weather Modeling Framework, the best performing among the five models compared by Pulkkinen et al. (2013), shows significantly better skill scores in predicting the magnetic perturbation than predicting its time derivative, especially for large deviations. We also find that there is a strong correlation between the magnitude of dB/dt and the magnitude of the horizontal magnetic perturbation itself. Combining these two results one can devise an algorithm that gives better skill scores for predicting dB/dt exceeding various thresholds in 20 min time intervals than the direct approach.
Twomey effect observed from collocated microphysical and remote sensing measurements over shallow cumulus
Authors: Werner F. , Ditas F. , Siebert H. , Simmel M. , Wehner B. , Pilewskie P. , Schmeissner T. , Shaw R. A. , Hartmann S. , Wex H. , Roberts G. C. , Wendisch M.
Published: January 2014

Clear experimental evidence of the Twomey effect for shallow trade wind cumuli near Barbados is presented. Effective droplet radius (reff) and cloud optical thickness (τ), retrieved from helicopter‐borne spectral cloud‐reflected radiance measurements, and spectral cloud reflectivity (γλ) are correlated with collocated in situ observations of the number concentration of aerosol particles from the subcloud layer (N). N denotes the concentration of particles larger than 80 nm in diameter and represents particles in the activation mode. In situ cloud microphysical and aerosol parameters were sampled by the Airborne Cloud Turbulence Observation System (ACTOS). Spectral cloud‐reflected radiance data were collected by the Spectral Modular Airborne Radiation measurement sysTem (SMART‐HELIOS). With increasing N a shift in the probability density functions of τ and γλ toward larger values is observed, while the mean values and observed ranges of retrieved reff decrease. The relative susceptibilities (RS) of reff, τ, and γλ to N are derived for bins of constant liquid water path. The resulting values of RS are in the range of 0.35 for reff and τ, and 0.27 for γλ. These results are close to the maximum susceptibility possible from theory. Overall, the shallow cumuli sampled near Barbados show characteristics of homogeneous, plane‐parallel clouds. Comparisons of RS derived from in situ measured reff and from a microphysical parcel model are in close agreement.
Ionospheric corrections for GPS time transfer
Authors: Rose Julian A. R. , Watson Robert J. , Allain Damien J. , Mitchell Cathryn N.
Published: January 2014

A real‐time ionospheric mapping system is tested to investigate its ability to compensate for the ionospheric delay in single‐frequency Global Positioning System (GPS) time transfer over Europe. This technique is compared with two other single‐frequency systems: one that does not incorporate any ionospheric correction and one that uses the broadcast Klobuchar model. A dual‐frequency technique is also shown as a benchmark. A period in March 2003, during a solar maximum, has been used to display results when the ionospheric delays are large and variable. Data from two European GPS monitoring centers were used to test the time‐transfer methods. For averaging times between several minutes and a few hours, the instabilities in the time transfers were dominated by ionospheric effects. The instabilities at longer averaging times were found to be due to clock noise and hardware instabilities. Improvements in time‐transfer instabilities are shown by using the ionospheric tomography system.
Alkaloids, Pharmaceutical Analysis of
Authors: Gilpin R.K. , Gilpin C.S.
Published: January 2014

As a major class of compounds, alkaloids are naturally occurring bases with a wide range of structures, chemical, and physical properties, and pharmacological activities. The use of alkaloids as medical agents in the form of crude plant powders and extracts predates the modern pharmaceutical industry by almost four millennia and in some instances prior to modern science. Mass poisonings have resulted from their inadvertent usage and was prevalent in Europe during the Middle Ages as the result of the general populace eating bread contaminated withClaviceps purpurea. TheC. purpureafungus produces an ergot alkaloid that first affects the central nervous system causing hallucinogenic effects and later death if enough is ingested. Ergot poisoning in the Middles Ages is perhaps best known for its effect on the painters “of‐the‐day” and their impressionistic styles and use of vivid colors.
Chemiluminescence, Electrogenerated
Authors: Nepomnyashchii Alexander B. , Bard Allen J. , Leland Jonathan K. , Debad Jeff D. , Sigal George B. , Wilbur James L. , Wohlstadter Jacob N.
Published: January 2014

Electrogenerated chemiluminescence (
ECL
) is the process in which electrogenerated species undergo electron transfer reactions to form excited states that emit light. Many molecules have the potential to produce
ECL
; however, Ru(bpy)
3
2 +
(bpy = 2,2′‐bipyridine) is the most common emitter used for analytical applications. Ru(bpy)
3
2 +
is water soluble and can provide high‐intensity signals in aqueous solutions under physiological conditions (
pH
 = 7.2–7.6). Application of a voltage to an electrode in the presence of an emitter induces light production and allows for the detection of the emitter at very low concentrations. Advantages over other analytical methods include low backgrounds, precise spatial and temporal control over the emission process, and capability for signal amplification. Commercial systems exist that use
ECL
to detect numerous clinically relevant analytes with high sensitivity using a variety of assay formats.
Electron Spin Resonance Spectroscopy
Authors: Chiesa Mario , Giamello Elio
Published: January 2014

Electron spin resonance (ESR) or electron paramagnetic resonance (EPR) spectroscopy is an experimental technique for detecting and characterizing chemical systems bearing one or more unpaired electrons. The application of the technique, the background of which is similar to the more diffused nuclear magnetic resonance (NMR) spectroscopy, therefore concerns (i) organic and inorganic free radicals; (ii) trapped radicals in various matrices, including irradiated solids (radiation chemistry), frozen inert matrices, and solid surfaces; (iii) transition metal ion compounds in classical inorganic systems or in biological systems; (iv) excited paramagnetic states (triplets) and several other systems of relevant scientific interest. The aim of this article is to provide an overall survey on the basic principles and on the various applications of the technique. This is done by describing, first, the physical basis of the electron resonance phenomenon (microwave absorption when the system is in the line of force of a strong external magnetic field) and, subsequently, the main types of interactions that the unpaired electron undergoes in the chemical system to which it belongs and which determines the features of the experimental spectra. These are essentially (i) the magnetic interaction of the electron with nuclei of nonzero nuclear spin (hyperfine interaction), which determines the multiline structure of the spectrum (hyperfine structure) and (ii) the interaction of the electron spin with the electron orbital angular momentum, occurring through the so‐called spin–orbit coupling. This latter interaction causes the dependence of the resonance on the orientation of the radical in the external magnetic field. Particular emphasis will be given to the different types of spectra observed according to the physical state of the investigated sample (liquid solutions, single solid crystals, or microcrystalline‐powdered solids). In the last case (powders), the essential methodology for understanding the often complex profiles of the experimental spectra is described. Advanced electron resonance techniques, essentially ENDOR (electron–nuclear double resonance) and pulse EPR, will also be briefly mentioned.

The final part of this article is devoted to some analytical applications of the technique, including spin trapping (an essential tool for the detection and quantitative evaluation of reactive short‐lived radicals), radiation dosimetry (with applications to medical problems and irradiated foodstuff analysis), and dating of geologically relevant systems.
Identification and Confirmation Algorithms for Handheld Spectrometers
Authors: Gardner Craig , Green Robert L.
Published: January 2014

Handheld analytical devices based on a gamut of technologies (e.g. infrared, Raman, X‐ray fluorescence, and mass spectrometries) are now widely available. These tools have seen increasing adoption for field‐based assessment by diverse users including military, emergency response, law enforcement, and regulated manufacturers. Frequently, end users of handheld devices are nonscientists who rely on embedded software and the associated algorithms to convert collected data into actionable information. Algorithms developed to identify or confirm the identity of material under test, therefore, need to process nonideal field data into a reliable answer. This article presents important algorithm concepts for material identification and confirmation. We discuss real‐world data collection challenges and solutions for field‐based measurements, types of algorithms designed to answer specific user questions, approaches for how to display analysis results to nonexperts, how to minimize computation time to satisfy typical users, and finally, performance characterization methods and results.