bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic Integrals of Continuous Local Martingales, II
Authors: Engelbert H. J. , Hess Juliane
Published: April 2007

Consider a continuous local martingale X. We say that X satisfies the representation property if any martingale Y of X can be represented as stochastic ITÔ integral of X. On the basis of part I of the present paper, in section 4 several general examples of continuous local martingales X satisfying the representation property are given: Stochastic continuous GAUSSian martingales, processes with conditionally independent increments, stopped continuous local martingales, random time change of WIENER processes, weak solutions of stochastic differential equations. Theorem 7 states that every (homogeneous) continuous strong MARKOV local martingale has the representation property. In section 5, the results of part I are applied to n‐dimensional continuous local martingales and analogous representation results are obtained. In section 6, we consider an application of section 5 to the n‐dimensional time change for reducing every n‐dimensional continuous local martingale with orthogonal components to the WIENER process. This improves a theorem of F. B. KNIGHT and simplifies its proof considerably.
Asymptotische Darstellungen für die STOKES‐Multiplikatoren der Differentialgleichung (−1)ny(n)(x)=(x2+λ) y(x)
Authors: Schlosser‐Haupt Silke , Wyrwich Herbert
Published: April 2007

Wir betrachten die Stokes‐Multiplikatoren der Differentialgleichung

als Funktionen des Parameters λ.

Dabei leiten wir zunächst Rekursions‐ und Symmetriebeziehungen zwischen den einzelnen Multiplikatoren her. Ein Satz von Braaksma [1] liefert uns zusätzlich aymptotische Informationen. Aus diesen Grundlagen gewinnen wir dann mit Hilfe einer bekannten Technik in Verbindung mit dem Prinzip von Phragmén und Lindelöf unser Hauptergebnis, nämlich asymptotische Darstellungen für alle Stokes‐Multiplikatoren in einer vollen Umgebung des singulären Punktes λ = ∞.
Eine ITO‐Formel für HILBERTraum‐wertige zufällige Felder
Authors: Grecksch W.
Published: April 2007

In vorliegender Arbeit wird eine ITO‐Formel für zweiparametrische Hilbertraum‐wertige zufällige Felder vorgestellt. Vorausgehen Aussagen über Hilbertraum‐wertige Martingalfelder und stochastische Integrale. In einem weiteren Kapitel wird diese ITO‐Formel zur Herleitung eines Satzes vom Girsanov‐TYP angewendet.

Die Ergebnisse dieser Arbeit besitzen u. a. in der Theorie der Filtration und Steuerung zufälliger Felder Bedeutung. In [20] werden mittels dieser ITO‐Formel ein Dualitätssatz und ein Maximumprinzip für eine gesteuerte stochastische Goursatsche Aufgabe hergeleitet.

Mittels des Girsanov‐Satzes können Aussagen über die Existenz schwacher Lösungen bei stochastischen partiellen Differentialgleichungen bewiesen werden. Bei der Steuerung solcher schwachen Lösungen ist mittels der ITO‐Formel die Herleitung von Funktionalgleichungen zur Bestimmung optimaler Steuerfelder möglich ([21]).
A fixed point theorem involving a hybrid inwardness‐contraction condition
Authors: Tuy Hoang
Published: April 2007

A fixed point theorem is proved which involves a hybrid inwardness‐contraction condition and simultaneously extends three earlier results of NADLER, CLARKE and REICH, respectively.

The aim of this paper is to prove a fixed point theorem which will simultaneously extends three earlier results of NADLER [5], CLARKE [2], and REICH [7], respectively.
Diskrete Approximation der Hammersteinschen Gleichung mit einer Anwendung auf die Quadraturformelmethode für Hammersteinsche Integralgleichungen
Authors: Zurbrügg Christoph
Published: April 2007

Die abstrakte HAMMERSTEINsche Gleichung u + KF(u) = 0, K positiv, symmetrisch, F monoton, wird approximiert durch Näherungsgleichungen derselben Form. Es wird gezeigt, daß die diskrete Konvergenz einer Folge von positiven beschränkten linearen Operatoren die Konvergenz der Folge der Quadratwurzeln dieser Operatoren impliziert. Mit Hilfe dieses Resultates wird die Konvergenz der Lösungen der Näherungsgleichungen gegen die Lösung der HAMMERSTEINschen Gleichung gezeigt, Als Anwendung der allgemeinen Resultate wird die Konvergenz der Quadraturformelmethode für HAMMERSTEINsche Integralgleichungen bewiesen.
Unconditional bases in lp⊕lq, 0 < p < q < 1
Authors: Ortynski Augustyn
Published: April 2007

We prove that every unconditional basis of lp⊕lq (0 < p < q < 1) is a disjoint union of two subsequences which span subspaces isomorphic to lp and lq respectively. This is an extension of a similar result of EDELSTEIN and WOJTASZCZYK [3] for 1 ≦ p < q <∞.
A Point Process with Second Order MARKOV Dependent Intervals
Authors: Chong F. S.
Published: April 2007

The limiting behaviour of the point process with 2nd order MARKOV‐dependent intervals is analysed through the use of “regeneration time”. The results for the case of periodic MARKOV‐dependent intervals are briefly mentioned.
The Number of Phases of Inhomogeneous Markov Fields with Finite State Spaces on N and Z and their Behaviour at Infinity
Authors: Winkler Gerhard
Published: April 2007

We consider the set 𝒢 of nonhomogeneous Markov fields on T = N or T = Z with finite state spaces En, n ϵ T, with fixed local characteristics. For T = N we show that 𝒢 has at most \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop N\nolimits_\infty = \mathop {\lim \inf}\limits_{n \to \infty} \left| {\mathop E\nolimits_n} \right| $\end{document} phases. If T = Z, 𝒢 has at most N‐∞ · N∞; phases, where \documentclass{article}\pagestyle{empty}\begin{document}$ \mathop N\nolimits_{-\infty} = \mathop {\lim \inf}\limits_{n \to -\infty} \left| {\mathop E\nolimits_n} \right| $\end{document}. We give examples, that for T = N for any number k, 1 ≦ k ≦ N∞, there are local characteristics with k phases, whereas for T = Z every number l · k, 1 ≦ l ≦ N‐∞, 1 ≦ k ≦ N∞ occurs. We describe the inner structure of 𝒢, the behaviour at infinity and the connection between the one‐sided and the two‐sided tail‐fields. Simple examples of Markov fields which are no Markov processes are given.
Notwendige und hinreichende Bedingungen für die Optimalität beim Stoppen von Markowschen Prozessen
Authors: Engelbert H. J. , Schröter H.
Published: April 2007

In der Arbeit wird eine Aufgabe des optimalen Stoppens von Markowschen Prozessen mit diskreter Zeit behandelt. Zu einer gegebenen Gewinnfunktion g wird die Wertefunktion v(x) = sup Exg(xT) betrachtet, wobei das Supremum über alle Markowschen Zeiten T gebildet wird, für die die Integrale existieren, und es werden optimale Markowsche Zeiten gesucht. Es ist bekannt, daß die für jedes ϵ ≧ 0 definierten Markowschen Zeiten Tϵ = min {n 0: v(Xn) ≧ g(Xn) + ϵ} ϵ‐optimal sind, wenn die Funktion g beispielsweise nach oben beschränkt ist. Im Artikel werden Bedingungen an die Funktionen g und v formuliert, die nicht nur hinreichend, sondern auch not‐wendig für die ϵ‐Optimalität von Tϵ (ϵ ≧ 0) sind. Die erhaltenen Ergebnisse werden auf den Fall Markowscher Prozesse mit stetiger Zeit verallgemeinert.
Adiabatic switching in abstract scattering theory
Authors: Obermann Peter
Published: April 2007

The paper discusses the relations between the usual wave operator, the adiabatic switched one and the ABEL wave operator. By means of H = ‐i d/dx + q(x) examples are constructed where the usual wave operator exists but the adiabatic switched one does not exist, or both exist and they are not equal.
Banach Space Model Theory II. Isomorphic Equivalence
Authors: Heinrich S. , Henson C. W.
Published: May 2007

Necessary and sufficient conditions are given for two Banach spaces to have linearly isomorphic ultrapowers. This is done firstly by carrying over the elementary equivalence of model theory to Banach spaces, and secondly by a game‐theoretic approach basing on Ehren‐feucht‐Fraissé games from logic.
Semi‐Classical Asymptotic of Spectral Function for Some Schrödinger Operators
Authors: Karadzhov G. E.
Published: May 2007

In this paper one obtains a result concerning the asymptotic behaviour of the spectral function on the diagonal for SCHRÖDINGER operators Ah = –h2/2 λ + V as h → 0. This asymptotic change the form on the energy level V(x) = λ.
Bemerkungen zur zweidimensionalen stochastischen Navier‐Stokes‐Gleichung
Authors: Schmalfuss B.
Published: May 2007

Für die stochastische NAVIER‐STOKES‐Gleichung auf einem zweidimensionalen Gebiet wird die Konvergenz der ITǑ‐GALERKIN‐Näherungen im quadratischen Mittel nachgewiesen. Weiterhin wird der MARKOV‐Charakter des Lösungsprozesses bewiesen und Eigenschaften der Trajektorien untersucht.
Shift Automorphisms of the Hyperfinite Factor
Authors: Quasthoff Uwe
Published: May 2007

For a large class of shift transformations of a LEBESGUE measure space (they have to fulfil some mixing condition) we construct automorphisms of the hyperfinite factor of type II1. The CONNES‐STØRMER entropy of the resulting automorphisms equals the measure theoretic entropy of the corresponding shift transformations. Two such automorphisms are conjugate if the conjugacy between the original measure space shifts can be given by a code with finite expected code length.
Copper‐biomolecule complexes in the gas phase. The ternary way
Authors: Tureček František
Published: May 2007

This review deals with copper complexes of a variety of organic and bioorganic molecules that have been produced as gas‐phase ions by electrospray and other ionization methods and studied experimentally by mass spectrometry and theoretically by ab initio and density functional theory computations. Ternary complexes of Cu(II) allow one to modify the oxidation state and coordination sphere of the copper ion and thus induce novel fragmentations that involve redox and radical‐based reactions. Structure elucidation, distinction, and quantitation of leucine and isoleucine isomers in peptides, distinction of enantiomers in chiral compounds, and sensitive detection of antibiotics are some of the highlights of mass spectrometry of ternary copper complexes. Binary copper complexes are mainly represented by Cu(I) species in which the copper ion displays the properties of a weak Lewis acid. © 2007 Wiley Periodicals, Inc., Mass Spectrom. Rev.
Sox9b/sox9a2‐EGFP transgenic medaka reveals the morphological reorganization of the gonads and a common precursor of both the female and male supporting cells
Authors: Nakamura Shuhei , Aoki Yumiko , Saito Daisuke , Kuroki Yoko , Fujiyama Asao , Naruse Kiyoshi , Tanaka Minoru
Published: May 2007

We have established an enhanced green fluorescent protein (EGFP) transgenic medaka line that mimics the expression of sox9b/sox9a2 to analyze the morphological reorganization of the gonads and characterize the sox9b‐expressing cells during gonadal formation in this fish. After the germ cells have migrated into the gonadal areas, a cluster of EGFP‐expressing cells in the single gonadal primordium was found to be separated by the somatic cells along the rostrocaudal axis and form the bilateral lobes. We observed in these transgenic fish that EGFP expression persists only in the somatic cells directly surrounding the germ cells. As sex differentiation proceeds, dmrt1 and foxl2 begin to be expressed in the EGFP‐expressing cells in the XY and the XX gonads, respectively. This indicates that the sox9b‐expressing cells reorganize into two lobes of the gonad and then differentiate into Sertoli or granulosa cells, as common precursors of the supporting cells. Hence, our sox9b‐EGFP medaka system will be useful in future studies of gonadal development. Mol. Reprod. Dev. 75: 472–476, 2008. © 2007 Wiley‐Liss, Inc.
Development of Langerhans cell histiocytosis associated with chronic active Epstein–Barr virus infection
Authors: Sakata Naoki , Toguchi Naomi , Kimura Masatomo , Nakayama Masahiro , Kawa Keisei , Takemura Tsukasa
Published: May 2007

Chronic active Epstein–Barr virus (CAEBV) infection is characterized by a status of lymphoproliferative disease of EBV‐infected cells, resulting in chronic or recurrent infectious mononucleosis‐like symptoms. CAEBV is always accompanied by life‐threatening complications. We report the case of a 2‐year‐old female patient with CAEBV who subsequently developed Langerhans cell histiocytosis (LCH) presenting with bilateral exophthalmos, bone, and skin involvement. In situ hybridization for EBER revealed EBV‐infected B‐cells present in lesional tissue implying that interactions between EBV‐infected B‐cells and lesional Langerhans cells may be associated with the development of LCH. Pediatr Blood Cancer 2008;50:924–927. © 2007 Wiley‐Liss, Inc.
The prostate‐associated lymphoid tissue (PALT) is linked to the expression of homing chemokines CXCL13 and CCL21
Authors: Carlo Emma Di , Magnasco Salvatore , D'Antuono Tommaso , Tenaglia Raffaele , Sorrentino Carlo
Published: May 2007

BACKGROUND

The genitourinary tract is regarded as part of the mucosal immune system. However, the structural and functional aspects of the human prostate‐associated lymphoid tissue (PALT) have never been extensively explored.

METHODS

This article describes our investigation of this issue by means of immunohistological, confocal, and ultrastructural examination of the normal human prostate.

RESULTS

PALT consists of two main components: (1) intraepithelial leukocytes, namely CD3+T cells with prevalent CD8+ and CD45RA−CD45RO+ phenotype, sometimes CD69+, followed by CD94+NK, CD11c+DCs, some expressing CD86, DC‐SIGN+DCs and a few B lymphocytes; (2) lymphoid aggregates, frequently below the epithelia, arranged in B cell follicles, endowed with a central ICAM‐1+VCAM‐1+CD21+FDCs network expressing BLC/CXCL13, and parafollicular T cell areas crossed by PNAd+HEV‐like vessels showing SLC/CCL21 expression. Parafollicular areas were formed of prevalent CD4+T lymphocytes, both CD45RA− and CD45RO+, and intermingled with CD11c+DCs. Germinal‐center‐containing follicles are few and their parafollicular areas are scantily infiltrated by Foxp3+CD69− highly suppressive regulatory T cells. Most lymphoid follicles lack a distinct germinal center and their parafollicular area harbor numerous Foxp3+CD69− cells.

CONCLUSIONS

Comparison with the tonsils shows that PALT displays immunomorphological features required for the onset of cellular and humoral immune responses, while its T regulatory cells appear to function as suppressor‐regulators of T and B cell responses. Prostate 67: 1070–1080, 2007. © 2007 Wiley‐Liss, Inc.
Modeling of epoxy oligomers with nonlinear optical chromophores in the main chain: molecular dynamics and quantum chemical study
Authors: Balakina Marina Yu. , Fominykh Olga D. , Rua Federico , Branchadell Vicenç
Published: May 2007

The Molecular Dynamics simulations in chloroform at room temperature of the monomer and dimer of the molecular system based on bisphenol‐A diglycidyl ether with a p‐nitroaniline (PNA) chromophore attached to the bearing chain is performed. The starting conformations for the simulation were obtained by the conformational search in the framework of Monte Carlo method with MMFF94 force field. The monomer was shown to represent an adequate model for the corresponding oligomer unit. The analysis of the torsion angles values along the bearing chain of dimer demonstrates the availability of flexible fragments, thus giving promise for efficient orientation of chromophore groups in a chosen polymer matrix when the electric field is switched on. The polarizability and first hyperpolarizability of the studied systems are calculated by TDHF/AM1. The values of β∥ increase by nearly 50% when passing from the monomer to the dimer. The nonempirical calculation of β, performed for the monomer, examines the obtained trends and exhibits significant enhancement of the first hyperpolarizability in chloroform approximately by a factor of 3 with respect to the gas phase value. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Density functional theory studies of nitrous oxide adsorption and decomposition on Ga‐ZSM‐5
Authors: Solkan V. N. , Zhidomirov G. M. , Kazansky V. B.
Published: May 2007

In this study, density functional theory (DFT/B3LYP) was used to assess a possible reaction pathway for the catalytic dissociation of N2O. The active centers were taken to be mononuclear [Ga]+ and [GaO]+, and the surrounding portion of the zeolite was represented by a 3T cluster, namely (AlSi2O4H8). The first step of N2O decomposition involves the formation of [GaO]+ and the release of N2. The metal‐oxo species produced in this step then react with N2O again, to release N2 and form GaO2. The calculated activation energies for N2O dissociation in Ga‐ZSM‐5 and GaO‐ZSM‐5 at B3LYP/6‐31+G* level are 22.2 and 24.9 kcal/mol, respectively. The calculated energy of the molecular oxygen elimination from 3T‐(GaO2) cluster is ΔH (298 K) = +46.5 kcal/mol and ΔG (298 K) = 35.9 kcal/mol. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007
Direct standardization of incidence rates in the presence of incomplete data
Authors: Emerson Scott S. , Emerson Julia C.
Published: April 2007

When comparing the disease incidence rates for several subpopulations, epidemiologists often use direct standardization to adjust for potential confounding variables. In population‐based studies, however, the data are often incompletely classified with respect to membership in the subpopulations of interest. In such a situation, one often assumes that the cases with missing data have the same distribution as the complete cases, that is the data are missing completely at random. In this setting, we derive variance estimates for the directly standardized rates which account for the use of incomplete data. We illustrate the use of these methods with data from a study of the incidence of gastrointestinal cancer by immigrant status where birthplace data are often incomplete.
A new sequential procedure for surveillance of Down's syndrome
Authors: Lie Rolv Terje , Heuch Ivar , Irgens Lorentz M.
Published: April 2007

A new method is proposed for the surveillance of Down's syndrome among newborn. Despite the strong dependence of overall risk of Down's syndrome on maternal age, it has been suggested that an environmentally induced increase in risk may be additive over all maternal ages. The surveillance method introduced here is specifically designed to detect such changes. The method is based on registry data for successive periods for a given population. It is assumed that the number of Down's syndrome cases as well as the total number of births are known in all maternal age groups. Tables of average run lengths until an alarm (ARLs) are calculated for a total sample size of 14,500 in each period, the approximate number of births in a three‐month period in Norway. Comparison with the Poisson cusum shows that the new surveillance method can detect moderate additive increases significantly faster. Applied retrospectively to quarterly data from the Medical Birth Registry of Norway for 1978–89, the proposed method was close to an alarm in 1985 and actually signalled a strong alarm in 1986, reflecting a previously reported increase in risk in this period. The cusum method was not so sensitive to the aberration in Down's syndrome risks in 1985 and 1986.
A refinement to the analysis of serial data using summary measures
Authors: Matthews J. N. S.
Published: April 2007

A widely used method for the analysis of data collected serially over time is to reduce the data on each subject to a single summary that reflects some salient aspect of the response. The summaries from all subjects are then analysed using appropriate univariate methods. In some cases it may be unreasonable to suppose that summaries in a group share a common distribution. A weighted analysis may be preferable, with data from each subject used to determine the weights. This approach is explored in the context of an analysis of data on foetal distress during labour.
Establishing a national in vitro fertilization registry: Methodological problems and analysis of success rates
Authors: de Mouzon Jacques , Bachelot Annie , Spira Alfred
Published: April 2007

A national registry for in vitro fertilization (IVF) was established in France in January 1986 and has been in operation since that date. During 1987, data on 14,763 attempts were collected from 72 teams, representing 80 per cent of all French IVF activity. In this registry, a form is completed for every oocyte recovery attempt, containing information about the infertility diagnosis, the attempt itself and its result. This paper presents results for the years 1986 and 1987 and studies the relationship between pregnancy occurrence and some couple or cycle characteristics. Methodological aspects are discussed, concerning the possible sources of bias, and the analysis of results. Results obtained in this registry are compared with those from other similar registries.
The succession procedure for interim analysis: Extensions for early acceptance of h0 and for flexible times of analysis
Authors: Falissard Bruno , Lellouch Joseph
Published: April 2007

The succession procedure is a new method for group sequential analysis based on a succession of significant tests. In this paper, the procedure is extended by the addition of a lower boundary, which allows the early acceptance of the null hypothesis H0 according to the stochastic curtailing approach. The succession procedure is also adapted to the type I error spending rate function α*(t), leading to the method of semisequential analysis for which the times of analysis need not be specified in advance.
Analysis of crossover designs with multivariate response
Authors: Grender Julie Myers , Johnson William D.
Published: April 2007

Crossover designs involve observing the same response variate under different experimental conditions for each subject. Univariate methods are commonly used for analysis of data arising in these designs, but multivariate procedures offer a more general approach. The general multivariate linear model provides a natural framework for the simplest data structure as well as more complex settings with two or more response variates and measurements repeated over time. Multivariate models for crossover designs provide a unified approach that clarifies specification of hypotheses, assumptions required, and testing procedures in a wide class of applications that include longitudinal data as a special case. We focus on the 2 × 2 crossover design, but also describe models for analysing more complex crossover designs.
Letters to the editor methods of adjustment for estimating the attributable risk in case—control studies: A review
Authors: Gefeller Olaf , Eide Geir Egil , Benichou Jacques
Published: April 2007

In a recent issue Benichou provided an excellent comprehensive review on adjustment methods for estimating attributable risk (AR) in the framework of case‐control studies. Its didactic nature illustrating all theoretical considerations using data from the Ille‐et‐Vilaine study ensures that Benichou's paper will soon be one of the leading references on AR estimation. It closes the gap between Walter's classic methodologic review paper1 on AR and more modern developments during the 1980's in this evolving area. Additional comments in this letter may help to clarify further some issues discussed in the paper.
Design and analysis of studies to reduce the incidence of colon polyps
Authors: Emerson Scott S. , McGee Daniel L. , Fennerty Brian , Hixson Lee , Garewal Harinder , Alberts David
Published: April 2007

Decisions regarding the design and analysis of a phase III study to reduce the incidence of colorectal polyps must take into account two complicating factors: the possibility that polyps are missed during screening exams, and variable lengths of follow‐up. In this paper we investigate the effects due to misclassification on the power of statistical tests to detect a change in polyp recurrence rates. We also use Monte Carlo studies to examine the relative efficiency of different methods of adjusting for variable times of follow‐up.
Evaluating the effects of tubal sterilization on menstrual function: Selected issues in data analysis
Authors: Martinez‐Schnell Beverly , Wilcox Lynne S. , Peterson Herbert B. , Jamison Patricia M. , Hughes Joyce M.
Published: April 2007

We examined selected issues in data analysis in the Collaborative Review of Sterilization (CREST). CREST is a multicentre, prospective, observational study of women undergoing tubal sterilization. We analysed menstrual function after sterilization in over 5000 women who were enrolled in the period 1978–1983 and followed for 5 years with yearly follow‐up interviews. To take into account the dependency among repeated responses from the same individuals, we used the generalized estimating equations (GEE) approach to longitudinal data analysis. Marginal modelling resulted in a statistically significant increase in the odds of menstrual dysfunction at 5 years after tubal sterilization. Transitional modelling produced rates of menstrual dysfunction given a woman's menstrual function at baseline, after adjusting for other baseline characteristics such as method of contraception before sterilization. To examine the direction of the bias that could result from non‐random missing data, we refitted our models using imputed values. The models with imputed values showed the same trends as the original models.
Refusal assertion versus conversational skill role‐play competence: Relevance to prevention of tobacco use
Authors: Sussman Steve , Stacy Alan W. , Dent Clyde W. , Burciaga Catherine , Burton Dee , Flay Brian R.
Published: April 2007

Conversational and refusal assertion skills of 768 seventh grade youth were assessed through ratings of global (for example, effectiveness) and non‐verbal (for example, eye contact) behaviour performed in two role‐play scenarios. The ratings were completed after each scenario by the subjects themselves, as well as by classmate and trained adult observers. Use of the Hays and Hayashi multitrait scaling method to interpret these data revealed two results. First, the items used to measure role‐play behaviour did not achieve sufficient internal consistency to create global and non‐verbal composites. Second, inter‐rater agreement and discriminant validity were obtained only for ratings of the global effectiveness of each of the two social skills. Next, a series of multiple regression analyses indicated that an index of the global effectiveness of refusal assertion skill, but not of conversational skill, was predictive of intention to use tobacco. Those who were relatively unskilful at refusing offers were more likely to intend to use tobacco. Analyses exploring relations of trained observer ratings of the effectiveness of both role‐play types, trained observer ratings of the other global and non‐verbal items, and subjects' intention to use tobacco indicated that only a hesitant voice pattern was both negatively predictive of effective refusal assertion and positively predictive of intention to use tobacco in the future. In other words, those who are hesitant when they refuse a tobacco offer are the ones most likely to report an intention to use tobacco in the future. The consistency of this last finding in the tobacco use prevention literature is discussed.
Birth‐weight‐adjusted infant mortality in evaluations of perinatal care: Towards a useful summary measure
Authors: Kiely John L. , Kleinman Joel C.
Published: April 2007

Since birth‐weight‐specific infant mortality rates are widely considered to be measures of the effects of perinatal medical care, birth‐weight‐adjusted and birth‐weight‐specific infant mortality rates have often been used in comparisons across hospitals and geographic areas. Wilcox and Russell1have provided a model which leads to the conclusion that birth weight adjustment is biased against populations with heavier birth weights and that birth‐weight‐specific infant mortality rates can yield misleading results. Nevertheless, evaluators and health planners still need a summary measure of the infant mortality rate in which some sort of birth weight adjustment is used to generate an (appropriately) weighted mean of birth‐weight‐specific relative risks. We used the 1983–85 national linked files of live births and infant deaths to investigate two new methods that extend the Wilcox—Russell approach, ‘mean adjustment’ and ‘Z‐adjustment’, to compare birth‐weight‐specific infant mortality rates among the white populations of the states. Colorado was used as the reference population in logistic regression analyses. Statistical interactions between state and birth weight on the conventional kilogram scale, the mean‐adjusted scale, and the Z scale were examined. There were substantial interactions with birth weight on all three scales. In addition, when Colorado was used as the reference population, mean adjustment shifted the odds ratios downward to implausibly low values, especially at lower weights. The Z‐adjustment method incorporating the Wilcox—Russell approach appears to be a useful alternative to birth weight adjustment. However, because birth‐weight‐specific mortality rates do not differ uniformly across all birth weight groups, multiple summary measures are needed.
Methods for analysing county‐level mortality rates
Authors: Stevenson John M. , Olson David R.
Published: April 2007

The identification of counties burdened by exceptionally high rates of mortality is a fundamental step in the development of state‐based intervention and prevention strategies. However, the estimation of rates from small geographic areas presents special problems, especially for rare events. This paper compares the use of crude and age‐standardized rates to the use of Poisson regression models and empirical Bayes models for analysing county‐level mortality rates. The results demonstrate both practical and heuristic advantages of the empirical Bayes models. Age‐standardized rates adjust for differences in age structure among counties but are vulnerable to extreme variability in county age‐specific rates. In our example — an analysis of diabetes mortality rates — Poisson regression did not improve the variability of estimated county‐level rates. Adjusted empirical Bayes estimates dramatically shrink the observed rates while preserving some separation of the counties with extreme rates. Also, empirical Bayes estimates of rates for counties with no observed deaths are shrunk close to the prior mean.
Longitudinal height velocity standards for U.S. adolescents
Authors: Berkey Catherine S. , Dockery Douglas W. , Wang Xiaobin , Wypij David , Ferris Benjamin
Published: April 2007

Longitudinally based height velocity centiles for U.S. children, appropriate for paediatric clinical use, were derived for growth from ages 7 to 18 years. A series of gender‐ and race‐specific figures present the median velocity curves for children by year of maturation. Smooth 3rd to 97th centile curves, for blacks and whites together, are provided for children who are early, average, and late maturers. The data were taken from 6532 black and white children participating in the Six Cities Study from 1974 to 1989.
Behind closed doors: The data monitoring board in randomized clinical trials
Authors: Wittes Janet
Published: April 2007

Many randomized clinical trials include a data and safety monitoring board (DSMB) that is responsible for reviewing accruing data, monitoring performance of the trial, assuring safety of the participants in the trial, and assessing the efficacy of treatment. The DSMB often makes recommendations about continuation of the trial or alteration of the protocol. Although such boards are very influential in both the conduct and interpretation of randomized clinical trials, there is no standard mode in which DSMBs operate nor do they routinely report publicly about their deliberations. This paper describes the composition of DSMBs as well as their functions. It concludes with a series of questions that needs to be addressed to ensure that the DSMBs operate effectively.
The NHLBI model: A 25 year history
Authors: Friedman Lawrence
Published: April 2007

Although newer techniques and procedures have been developed, many of the clinical trial design and monitoring concepts used today in the NHLBI were implemented 25 years ago. Among these are the organizational structure of multicentre trials and the use of an independent data monitoring committee. Examples of data monitoring committee discussions and decisions are provided.
A survey of monitoring practices in cancer clinical trials
Authors: George Stephen L.
Published: April 2007

This paper reports the results of a survey of data monitoring practices of the 12 clinical co‐operative groups in cancer sponsored by the National Cancer Institute in the United States. Most of these co‐operative groups conduct a large number of active clinical trials in a wide variety of cancers. The number of active phase III trials in 1991 was 244 with nearly 24,000 patients entered on these trials. The survey instrument used in this paper was modified from one originally developed by Geller and Stylianou,1 supplemented by questions on the responsibilities of data monitoring committees based on Hawkins.2 Topics covered included general policies and procedures on the monitoring of clinical trials in these groups as well as specific questions on the responsibilities and operational procedures of formal data monitoring committees. Although formal statistical stopping rules are almost always employed in cancer trials in these co‐operative groups, use of a formal data monitoring committee is a relatively new, but increasing practice. For a variety of economic and practical reasons, the members of data monitoring committees for cancer trials are rarely independent of the study participants.
Data monitoring committees for southwest oncology group clinical trials
Authors: Green Stephanie , Crowley John
Published: April 2007

A monitoring committee policy was established by the Southwest Oncology Group in 1985 to address documented problems in study conduct. Committees consisting of the study co‐ordinators, disease committee chair, study statistician, Group chair, Group statistician, an uninvolved Southwest Oncology Group clinician, an NCI representative, and a representative from each involved group for intergroup studies have been appointed for each phase III study. Business is conducted largely through the mail and through conference calls. Since then, problems identified in older studies have been largely resolved. Appropriate and timely decisions are being made at modest additional expense to the Group.
The use of external monitoring committees in clinical trials of the national institute of allergy and infectious diseases
Authors: Ellenberg Susan S. , Myers Maureen W. , Blackwelder William C. , Hoth Daniel F.
Published: April 2007

Randomized clinical trials are being conducted and/or sponsored by all scientific divisions of the National Institute of Allergy and Infectious Diseases (NIAID). External committees to review the progress of ongoing trials and to make recommendations to the Institute concerning continuation or termination are an integral part of many of these trials. These committees have evolved considerably from the ad hoc committees, called together when a need arose, which were used beginning in the mid 1970s. Currently, there are many monitoring committees operating for NIAID‐sponsored trials. They function in a variety of ways, based partially on historical precedent and partially on the specialized requirements of the particular trial; there is no ‘standard operating procedure’ for the Institute, or even for divisions within the Institute. One of the major issues faced in establishing the data and safety monitoring board for AIDS treatment trials was access to the meetings of this board and to the reports of interim data that the board reviewed. After much discussion, procedures were established that restrict such access to a very limited group of programme and statistical centre staff. These procedures, while remaining controversial, appear necessary to ensure confidentiality and the integrity of the clinical trials process.
Data monitoring and interim analyses in the pharmaceutical industry: Ethical and logistical considerations
Authors: Rockhold Frank W. , Enas Gregory G.
Published: April 2007

The characteristics of data monitoring and the need for the use of data monitoring committees in clinical trials sponsored by the pharmaceutical industry differ from those of trials sponsored by government. Data monitoring is a continuous process in industry trials due to the regulatory requirements and the need to more thoroughly evaluate safety of new compounds. As part of this process, interim analyses are employed to make decisions about treatment effects. In some cases, such analyses may require the use of an external data monitoring committee to assist in the data review, analysis and decision making. A number of examples of interim analyses, with and without data monitoring committees, are discussed. Issues surrounding the need for external data monitoring committees and recommendations are presented. In particular the issues of sponsor participation in the data monitoring committee and controls of the decision making process are considered.
Monitoring of clinical trials and interim analyses from a drug Sponsor's point of view
Authors: Williams George W. , Davis Robert L. , Getson Albert J. , Gould A. Lawrence , Hwang Irving K. , Matthews Holly , Shih Weichung Joseph , Snapinn Steven M. , Walton‐Bowen Karen L.
Published: April 2007

This paper illustrates aspects of data monitoring of clinical trials in the pharmaceutical industry. Formal interim analyses are performed at least in part to address the question of whether the trial should proceed or whether there should be an early termination of the trial. For formal interim analyses, frequently independent data and safety monitoring committees are utilized for monitoring clinical trials, and adjustments to nominal significance levels for test statistics are required. Various statistical methods developed during the last fifteen years are utilized. Administrative interim analyses are those analyses that are performed without any intention to stop the trial as a consequence of those analyses. For administrative interim analyses, adjustments to significance levels may not be required, but results must still be carefully interpreted. Regardless of the interim analyses performed, it is critical that the plans for interim analyses be identified in the study protocol, and the dissemination of interim results be carefully restricted. The following clinical trials sponsored by Merck Sharp and Dohme Research Laboratories (MSDRL) will illustrate these points: CONSENSUS; CONSENSUS II; 4S; Haemophilus influenza type b efficacy trial; famotidine in upper gastrointestinal haemorrhage, and a phase II analgesic study. It is anticipated that data monitoring and interim analysis activities will increase for future clinical trials due to the availability of appropriate statistical methods and improved data management systems.
Monitoring clinical trials: Experience of, and proposals under consideration by, the cancer therapy committee of the British medical research council
Authors: Parmar Mahesh K. B. , Machin David
Published: April 2007

The accumulating data from all randomized trials conducted by the Cancer Therapy Committee (CTC) of the British Medical Research Council are monitored on a regular basis. However, for important practical reasons the form of this data monitoring may vary from trial to trial. Thus a trial addressing what is considered a major question in the treatment of cancer patients, (a ‘pivotal’ or ‘high profile’ trial), has a formal data monitoring committee (DMC). This is usually made up of two clinicians and one statistician who are completely independent of the trial organization and do not enter patients into the trial. Other trials, which constitute the majority, are monitored by a less formal trial progress group made up of the clinical co‐ordinator and trial statistician, sometimes supplemented by a trial participant. Experience with this dual system has led to a new proposal: if the trial progress group wish to modify or stop a trial then they are required to set up and consult an ad hoc DMC for independent advice. This proposal has many advantages, including maximizing the use of resources available, while achieving the degree of objectivity in decision‐making required for the many different types of cancer trials conducted by the CTC.
The use of data monitoring committees in canadian trial groups
Authors: Pater Joseph L.
Published: April 2007

Following a brief overview of the funding and structure of clinical trials research in Canada, experience with data monitoring committees (DMCs) in four clinical trials organizations is reviewed. Whether committees are required, their mode of selection, composition, degree of independence, mandate and reporting relationships have varied substantially among the groups. Overall the Canadian experience with DMCs has been representative, although formalization of the role of these committees has not proceeded as far as it has in some US agencies.
Interim analyses, stopping rules and data monitoring in clinical trials in europe
Authors: Buyse Marc
Published: April 2007

A survey was carried out to identify the current policies of European cooperative groups with respect to interim analyses, stopping rules and data monitoring of ongoing clinical trials. The policies differ widely, from informal interim analyses distributed among all participating investigators, to planned interim analyses carried out by an independent statistician and scrutinized by a data monitoring committee. Different situations clearly call for different policies: for instance, trials of new drugs in AIDS need to be monitored more closely than trials of non‐toxic adjuvant therapies for cancer. Likewise, trials with an immediately measurable end‐point (such as the large‐scale trials in myocardial infarction) need more intensive monitoring than those in which the outcome assessment requires prolonged follow‐up. In all cases, however, it seems useful to articulate explicit data monitoring procedures in the trial protocol. In general, an independent data monitoring committee is essential to advise on the desirability to continue accrual into the trial, or to stop it early.
Practical issues in data monitoring of clinical trials: Summary of responses to a questionnaire at nih
Authors: Geller Nancy L. , Stylianou Mario
Published: April 2007

A targeted poll was undertaken to compare and contrast models of data monitoring of randomized clinical trials sponsored by the National Institutes of Health. In an attempt to represent the institutes which conduct clinical trials, twelve individuals were selected and asked to respond to a questionnaire specifically prepared for this workshop. The response rate was 100 per cent. Most of the large trials sponsored by the institutes have independent, formally constituted data monitoring committees. There was one institute which does not have any data monitoring committees. The questionnaire is described in detail and a summary of the results is given.
Data monitoring boards in the pharmaceutical industry
Authors: Herson Jay
Published: April 2007

This paper describes the characteristics and responsibilities of data monitoring boards (DMBs) employed in clinical trials sponsored by pharmaceutical firms. These DMBs are compared with DMBs in clinical trials sponsored by the National Institutes of Health (NIH). All trials discussed are assumed to be phase III pre‐market clinical trials. It is seen that DMBs in pharmaceutical industry trials have more limited responsibilities than DMBs in NIH clinical trials. Pharmaceutical industry DMBs are employed to add credibility to trials by certifying critical clinical trial processes such as patient evaluability, interim analyses, evaluation of efficacy endpoints, and safety monitoring. An example of a pharmaceutical industry DMB's charter and operations is presented for a clinical trial for the prevention of stress ulcers. The specific problems encountered when a pharmaceutical industry clinical trial is conducted by NIH under the auspices of an NIH‐appointed DMB are discussed. New uses for DMBs in the pharmaceutical industry are introduced and future trends in the industry with respect to DMBs are examined.
Data monitoring committees and capturing relevant information of high quality
Authors: Fleming Thomas R.
Published: April 2007

The integrity and credibility of randomized clinical trials, designed to provide a definitive evaluation of therapeutic interventions, can be substantially enhanced if periodic review of results on the relative efficacy of treatments is conducted by a data monitoring committee (DMC). The role of the DMC can include some important activities which promote obtaining relevant information of high quality. In the final stage of study development, these include review of protocol‐specified study objectives and design, and review of procedures planned for capturing high‐quality data and for reporting to the DMC. At analyses during the trial, these include careful review of data completeness and accuracy to assist in early detection and resolution of evolving problems.
Data monitoring committees: The moral case for maximum feasible independence
Authors: Walters Leroy
Published: April 2007

Since data monitoring committees (DMCs) began to be established in the 1970s, they have reviewed the clinical outcome data emerging from ongoing trials. The thesis of this essay is that DMCs most effectively promote the validity and credibility of randomized clinical trials when they perform this function with the maximum feasible independence. The essay argues that four types of individuals and groups should be excluded from the interim monitoring of outcome data: (1) investigators entering patients into a trial; (2) principal investigators or study chairs; (3) representatives of commercial firms connected with a trial; and (4) representatives of regulatory agencies. The role of statistical groups and officials of government funding agencies in the review of outcome data is also discussed.
Some FDA perspectives on data monitoring in clinical trials in drug development
Authors: O'neill Robert T.
Published: April 2007

The FDA's interest in data monitoring of clinical trials derives from its public health responsibility to assure the safety and efficacy of new drugs based on evidence from adequate and well‐controlled studies. Therefore the FDA is concerned that clinical trials of new drugs are designed and carried out in a manner that will insure the integrity and validity of study inferences. The FDA regulation and guidelines recognize the role of data monitoring and the variety and diversity of situations utilizing a data monitoring process in clinical studies. This paper describes relevant aspects of the regulations and guidelines, some concerns the FDA has with regard to monitoring of both government‐ and industry‐sponsored trials and the consequences of early termination of trials of new drugs in the investigational and marketed stages. Comments include advice on communication between the FDA and data monitoring committees.