bluuebunny/crossref_metadata_2025_split huggingface dataset:
Electron transport through parallel double quantum dots with interdot correlations
Authors: Sztenkiel D. , Świrkowicz R. 
Published: April 2007

AbstractElectron transport through a system of two quantum dots coupled via tunneling processes and attached to external electrodes is studied within the framework of the Green function formalism based on the equation of motion method. Interdot Coulomb interactions are taken into account in a form of a Hubbard‐like term and the interplay between interference and electron correlation effects is investigated. It is shown that Coulomb interactions strongly modify the linear conductance. However, the Fano‐like behaviour can be observed and a dip in the conductance which appears due to interference effects practically is not influenced by interdot correlations. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Adiabatic effects on the bipolaronic charge ordered phase in the Holstein model
Authors: Grzybowski P. 
Published: April 2007

AbstractWe reanalyze the strong‐coupling expansion for the Holstein model in the limit of low and medium phonon frequencies. We focus on the interplay between the dynamical phonon dressing of the electrons and the static phonon distortion in the bipolaronic charge order (CO) phase. We propose a variational approach to this problem and obtain an expression for the ground state energy. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Fragmentation of 3‐hydroxyflavone; a computational and mass spectrometric study
Authors: Lewars Errol G. , March Raymond E. 
Published: April 2007

AbstractIn a recent study of the collision‐induced dissociation of protonated and deprotonated molecules of 3‐, 5‐, 6‐, 7‐, 2′‐, 3′‐ and 4′‐hydroxyflavone, it was observed that the ratio, γ, of the propensities for cross‐ring cleavage (CRC) to ring opening (RO) varied by a factor of 660, i.e., from 0.014:1 (for deprotonated 3‐hydroxyflavone) to 9.27:1 (for deprotonated 5‐hydroxyflavone). An explanation for the variation of γ was presented in terms of experimental NMR 13C and 1H spectra modified by computation. Deprotonated 3‐hydroxyflavone exhibited the highest ion signal intensity for fragmentation following RO relative to that for CRC in that γ = 0.014:1. Because no chemical computations of the fragmentation of protonated and deprotonated monohydroxyflavone molecules have been carried out thus far, the basis on which fragmentation mechanisms for deprotonated 3‐hydroxyflavone have been proposed is principally chemical intuition. The energy states of product ions formed in the fragmentation of deprotonated 3‐hydroxyflavone molecules were computed by the CBS‐4M method implemented in Gaussian 03. The overly demanding calculations needed to handle diradicals reliably and directly were circumvented by a process in which each of the bond‐breaking reactions was approximated by a process that gave two monoradicals. Bond energies were calculated, with one exception, from the approximation reactions as the energy of products minus the energy of reactants. Copyright © 2007 John Wiley & Sons, Ltd.
Employing atmospheric pressure photoionization in liquid chromatography/tandem mass spectrometry to minimize ion suppression and matrix effects for the quantification of venlafaxine and O‐desmethylvenlafaxine
Authors: Theron Hendrik B. , van der Merwe Marthinus J. , Swart Kenneth J. , van der Westhuizen Jan H. 
Published: April 2007

AbstractDuring the development of a method for quantitative determination of venlafaxine and its major metabolite O‐desmethylvenlafaxine, elevated concentrations of the analyte as well as co‐eluting matrix compounds caused ion suppression. This ion suppression was inconsistent and therefore influenced the reproducibility of detection. The use of atmospheric pressure photoionization (APPI) in the positive mode was investigated as a tool to circumvent this problem. Employing APPI resulted in negligible ion suppression and increased linearity of the concentration range. A selective, sensitive and rapid liquid chromatography/tandem mass spectrometry method for the determination of venlafaxine and its major metabolite O‐desmethylvenlafaxine in human plasma was developed. The analyte was extracted from plasma into tert‐butyl methyl ether followed by back extraction into 2% formic acid. An Agilent 1100 high‐performance liquid chromatography (HPLC) system, employing reversed‐phase chromatography on a cyano column, coupled to an Applied Biosystems API 3000 triple quadrupole mass spectrometer set to multiple reaction monitoring (MRM) mode, was used for separation and detection of the analytes. The method was validated between 2.36–605 ng per mL with a mean recovery of approximately 88% for both parent compound and metabolite analytes. APPI technology was employed to improve the reproducibility of detection enabling rapid, selective and sensitive quantification of venlafaxine and O‐desmethylvenlafaxine in human plasma samples. Copyright © 2007 John Wiley & Sons, Ltd.
Application of polarity switching in the identification of the metabolites of RO9237
Authors: Fitch William L. , He Limin , Tu Ya‐Ping , Alexandrova Ludmila 
Published: April 2007

AbstractPolarity switching mass spectrometry is an efficient way to collect structural data on drug metabolites. The value of this approach is illustrated with the in vitro metabolism of RO9237. Metabolites are identified by positive and negative electrospray ionization (ESI) full scan mass spectrometry, MS/MS and MS3 using unlabelled and 14C‐radiolabelled versions of the drug. Comparison of the relative detectability of these metabolites by +ESI and −ESI shows that neither ESI mode is universal. It is advantageous to screen for metabolites using both positive and negative ionization modes. This is especially true for phase II metabolism which tends to make molecules more polar and often more acidic. Identification of phase II metabolites also benefits greatly from MS3 experiments because the conjugating groups typically are cleaved in MS/MS and information on the core structure is only obtained in MS3. A special case of phase II metabolism is the generation of glutathione (GSH) conjugates from reactive metabolites. The detection of GSH conjugates also benefits from generating both positive and negative ESI mass spectral data. Copyright © 2007 John Wiley & Sons, Ltd.
Estimating the distribution of times from HIV seroconversion to aids using multiple imputation
Authors: Taylor Jeremy M. G. , Muñoz Alvaro , Bass Sue M. , Saah Alfred J. , Chmiel Joan S. , Kingsley Lawrence A. 
Published: April 2007

AbstractMultiple imputation is a model based technique for handling missing data problems. In this application we use the technique to estimate the distribution of times from HIV seroconversion to AIDS diagnosis with data from a cohort study of 4954 homosexual men with 4 years of follow‐up. In this example the missing data are the dates of diagnosis with AIDS. The imputation procedure is performed in two stages. In the first stage, we estimate the residual AIDS‐free time distribution as a function of covariates measured on the study participants with data provided by the participants who were seropositive at study entry, Specifically, we assume the residual AIDS‐free times follow a log‐normal regression model that depends on the covariates measured at enrolment on the seropositive participants. In the second stage we impute the date of AIDS diagnosis for the participants who seroconverted during the course of the study and are AIDS‐free with use of the log‐normal distribution estimated in the first stage and the covariates from each seroconverter's latest visit. The estimated proportions developing AIDS within 4 and within 7 years of seroconversion are 15 and 36 per cent respectively, with associated 95 per cent confidence intervals of (10, 21) and (26,47) per cent.We discuss the Bayesian foundations of the multiple imputation technique and the statistical and scientific assumptions.
Relative survival and the estimation of net survival: Elements for further discussion
Authors: Estève J. , Benhamou E. , Croasdale M. , Raymond L. 
Published: April 2007

AbstractThe methods of calculation of survival corrected for independent cause of death are discussed, and a maximum likelihood method is proposed and illustrated by survival of colon cancer patients in Geneva. The methods which are at present favoured for doing such calculations are subject to various biases when estimating net survival if the populations are heterogeneous for life expectancy. The proposed maximum likelihood approach would eliminate these biases by enabling relevant adjustment for covariates which influence survival. The routine use of such methods would permit better comparison of survival within and between populations.
On a test of non‐random segregation under linkage for autosomal recessive diseases
Authors: Pal Nabendu , Majumder Partha P. 
Published: April 2007

AbstractTo test the null hypothesis of random segregation of marker haplotypes from an unaffected parent to affected offspring for a one‐locus autosomal recessive disease, Majumder proposed a test statistic which was shown to be locally most powerful against the alternative hypothesis of non‐random segregation due to linkage between the disease and marker loci. The test procedure relied on a chi‐squared approximation to the null distribution of the test statistic. In the present study, we show that the chi‐squared approximation is poor for most practical situations and derive the exact null distribution of a function of the test statistic. We illustrate the method using published data on tuberculoid leprosy and HLA. We show that the test procedure is invariant, and extend the method to the case of a two‐locus recessive disease.
Sequential stopping rules in clinical trials
Authors: McPherson Klim 
Published: April 2007

AbstractThis paper reviews aspects of the development of sequential analysis of clinical trial data in medicine and suggests simple strategies for progress. The emphasis is on the pragmatic and ethical requirements of aspects of the design of phase III trials and in circumstances of genuine uncertainty characterized by much clinical experimentation. In particular consideration is given to the consequences of determining sample sizes from incorrect estimates of treatment effects. Armitage's work on sequential trials is traced to simple group sequential procedures based on repeated significance tests to minimize expected sample sizes in a wide class of experimental situations.
The summarizing of clinical experiments by significance levels
Authors: Anscombe F. J. 
Published: April 2007

AbstractFor a controlled clinical experiment in which two alternative treatments are compared, the statistical report often culminates in a significance test of the null hypothesis of no difference between the treatments, and significance at the 5 per cent level is taken as positive evidence of difference. It is argued that such an experiment serves primarily an inferential purpose; it is not a simple decision procedure, although its effect on practice may be considered in relation to ethical issues. Statistical inference should not be identified with testing this null hypothesis, despite the emphasis on such tests by R. A. Fisher in his work on design of experiments. This null hypothesis often has no interest or credibility.
HIV infection dynamics and intervention experiments in linked risk groups
Authors: Van Druten J. A. M. , Reintjes A. G. M. , Jager J. C. , Heisterkamp S. H. , Poos M. J. J. C. , Coutinho R. A. , Dijkgraaf M. G. W. , Ruitenberg E. J. 
Published: April 2007

AbstractA multigroup transmission model is described to study the spread of the human immunodeficiency virus (HIV) in linked risk groups. The model permits simultaneous investigation of the increase in the number of persons infected with HIV in three main risk groups: promiscuous homo/bisexual men (two levels of promiscuity), intravenous drug users (men and women) and promiscuous heterosexual men and women.Three modes of transmission are considered: anal and vaginal intercourse and needle sharing. The high dimensional parameter space is connected with the HIV incidence through a transmission matrix. This matrix summarizes the annual effective contact rates due to the three transmission modes. The model helps to clarify which data are needed to disentangle the relative contribution of the within‐ and between‐group transmission routes. The model can be used to perform theoretical experiments. Given a specification of a baseline, the potential use of the model is illustrated by a simulation describing the effect of blocking the transmission through needle sharing. Reference is made to the HIV/AIDS epidemic in The Netherlands.The results of the study show that the model can play a part in the classification of HIV prevalence patterns in linked risk groups, in the study of the interaction between the main risk groups and in the theoretical evaluation of intervention measures.
Long term survival analysis: Breast cancer and age at diagnosis
Authors: Marubini E. , Mezzanotte G. , Boracchi P. , Veronesi U. 
Published: April 2007

AbstractThe role of age at surgery of breast cancer patients as a determinant of relative survival after making allowance for clinical profile was investigated on a case series of 716 women followed for more than 20 years in one single institution. Multiplicative and additive models for grouped data were adopted to model the standardized mortality ratio and the excess death rate respectively. The models were fitted by the GLIM system assuming a Poisson error function. We conclude that operable breast cancer has a relatively lower impact on total mortality in older patients (65 years or more) than in younger ones and, moreover, the older patients have a more favourable course.
CTS: A clinical trials simulator
Authors: Taylor D. W. , Bosch E. G. 
Published: April 2007

AbstractWe describe an interactive clinical trial simulation program (CTS), which provides continuous graphical and numerical output as a simulation runs. CTS is capable of simulating trials with two treatment groups and a binary outcome with options for: (1) up to five prognostic subgroups; (2) one of three methods of randomization; (3) equal or unequal allocation of patients to treatment groups; (4) a null or alternative hypothesis; (5) common methodological problems including biased referrals, false positive and false negative outcome reports, non‐compliance, dropouts, crossovers, and co‐interventions; (6) six methods of dealing with each of these problems; (7) the type I error rate, and (8) stratified or unstratified analysis. In addition, the current results of a trial in progress may be used as the starting point of the simulation to estimate the power of the trial if carried to completion. A few thousand simulations of a user specified scenario is typically entered and executed in about 5 minutes, permitting a student or clinical investigator to explore a variety of scenarios.
A stratified Wilcoxon‐type test for trend
Authors: Pee David Yu‐Wu , Freedman Laurence S. 
Published: April 2007

AbstractWe propose an extension of Cuzick's non‐parametric Wilcoxon‐like trend test for situations when the observations can be grouped into strata which are thought to be related to the outcome. We illustrate its use in two examples from cancer epidemiology.
A note on interrater agreement
Authors: Hirji Karim F. , Rosove Michael H. 
Published: April 2007

AbstractWe investigate the properties of a measure of interrater agreement originally proposed by Rogot and Goldberg.1 Unlike commonly used measures, this measure not only adjusts for chance agreement, but it also standardizes for both perfect agreement as well as for perfect disagreement. Further, one can also use this measure to assess category specific conditional agreement, and thus apply it to situations with missing main diagonal data. We provide an asymptotic method for inference with this measure.
Hierarchical models for multicentre binary response studies
Authors: Skene A. M. , Wakefield J. C. 
Published: April 2007

AbstractA three‐stage hierarchical model is proposed for two treatment, binary response studies conducted in a number of centres. The approach adopted is Bayesian. Marginal densities for second stage parameters are shown to provide useful summaries both of comparative efficacy and of the heterogeneity of treatment effects across centres. Sensitivity studies of model assumptions are illustrated.
Assessing the gain in efficiency due to matching in a community intervention study
Authors: Freedman L. S. , Green S. B. , Byar D. P. 
Published: April 2007

AbstractCOMMIT (Community Intervention Trial for Smoking Cessation) is a randomized study employing a matched pairs design. Pairs of communities were selected on the basis of their geographical proximity and were chosen to be matched on variables strongly expected to relate to the outcome variable, the smoking quit rate. However, quantitative information was not available to evaluate the efficiency gain from matching. We have used baseline smoking quit rates in the communities as a surrogate for the outcome measure to evaluate the gain in efficiency from the matching. Our method takes account of the possible imperfection of the surrogate as a representative of the true outcome. The method estimates an efficiency gain of at least 50 per cent using the matched design. We also evaluate the further gains in efficiency which would be made by using the baseline quit rate to balance the randomization.
Modelling forces of infection for measles, mumps and rubella
Authors: Farrington C. P. 
Published: April 2007

AbstractSerological data from 8870 persons collected prior to the introduction of measles, mumps and rubella (MMR) vaccine in the UK are used to describe the rate at which individuals acquire infection by these diseases at different ages. A parsimonious model is developed and titted under various interpretations of the data, particularly concerning the probability of lifelong susceptibility to infection. It is shown that, while the force of infection curves are relatively robust in their general features, they exhibit considerable sensitivity in matters of important detail. This is true in particular of the values taken by the force of infection in older age groups. As a result, estimates of the average age at infection are highly sensitive to these interpretations. This in turn may limit the accuracy of predictions from mathematical models based on these parameters, in particular regarding the level of immunization required for eradication of disease.
Evaluation of statistics teaching given to medical undergraduates
Authors: Newcombe Robert G. 
Published: April 2007

AbstractMedical undergraduates in all United Kingdom medical schools receive statistics teaching, but attempts to establish the efficacy of this teaching have been scanty. Establishment of clear educational objectives is a prerequisite to meaningful evaluation. Most medical schools have attempted to obtain feedback from their students by administering questionnaires. Examination performance can provide very pertinent information if a finely detailed marking scheme is developed, identifying issues that are generally poorly grasped. Controlled trials may be carried out within an institution but encounter problems of contamination and low power. It should eventually be possible to develop multi‐institutional evaluation methods.
How we should approach the future
Authors: Murray Gordon D. 
Published: April 2007

AbstractThere is little doubt that there are still major problems with the statistical aspects of published medical research. This paper argues that it is not sufficient to teach statistics to medical undergraduates, when the bulk of their courses are being taught by the very same individuals who continue to undertake and publish substandard research. Instead, any undergraduate teaching needs to advance in parallel with courses given to the clinical staff within medical schools.
Multiple comparisons in over‐the‐ounter drug clinical trials with both positive and placebo controls
Authors: D'Agostino Ralph B. , Heeren Timothy C. 
Published: April 2007

AbstractEvaluations of the efficacy of over‐the‐ounter drugs using ANOVA techniques often misuse multiple comparison procedures. Studies that involve both a placebo control and established drugs as positive controls are especially prone to these problems. The most common mistake involves using a procedure which does not control the experimentwise type I error rate, usually the Duncan procedure or some version of multiple t tests. These procedures control comparisonwise type I error rate, but lack the important experimentwise error control.The purpose of this paper is to clarify the issues involved in performing ANOVA followed by a multiple comparison procedure for over‐the‐ounter drug studies involving both placebo and positive controls.
On estimating efficacy from clinical trials
Authors: Sommer Alfred , Zeger Scott L. 
Published: April 2007

AbstractWe define ‘biologic efficacy’ as the effect of treatment for all persons who receive the therapeutic agent to which they were assigned. It measures the biologic action of treatment among compliant persons. In a randomized trial with one treatment and one placebo control, one can theoretically estimate efficacy by comparing persons who complete the treatment regimen with controls who similarly complete the control regimen. In practice, however, we make this comparison with reservation because a control protocol often presents a different challenge for compliance than does the treatment, so that the compliant subgroups are not comparable. Standard practice employs intent‐to‐treat comparisons in which one compares those randomized to treatment and control without reference to whether they actually received the treatment. Intent‐to‐treat comparisons estimate the ‘programmatic effectiveness’ of a treatment rather than its biologic efficacy.This paper introduces and derives the statistical properties of an alternative estimator of biologic efficacy that avoids the potential selection bias inherent in a comparison of compliant subgroups. The method applies to randomized trials with a dichotomous outcome measure, whether or not a placebo is given to the control group. The idea is to compare the compliers in the treatment group to an inferred control subgroup chosen to eliminate selection bias. The methodology was motivated by and is illustrated in the analysis of a randomized community trial of the impact of vitamin A supplementation on children's mortality.
Empirical bayes estimates of cancer mortality rates using spatial models
Authors: Mollie Annie , Richardson Sylvia 
Published: April 2007

AbstractWe give results of empirical Bayes (EB) estimation of mortality rates designed to smooth observed SMR when random fluctuation of the observed deaths is important. We have specially studied the case where the prior distributions of the EB method have a spatial structure. The need for spatial modelling of cancer mortality rates in France is first shown with testing autocorrelation and fitting autoregressive spatial models, conditional (CAR) or simultaneous (SAR). A positive autocorrelation of the rates is shown for most cancer sites studied. As expected, EB estimates of mortality rates for common tumours are similar to SMRs. For rare tumours, the EB method identifies the extreme rates more clearly than SMRs by smoothing the SMRs with large variances. CAR or SAR models are adequate prior distributions for autocorrelated rates and produce quite similar rate estimates.