bluuebunny/crossref_metadata_2025 huggingface dataset:
Malaria Plasmodium agent induces alteration in the head proteome of their Anopheles mosquito host
Authors: Lefevre Thierry , Thomas Frédéric , Schwartz Alex , Levashina Elena , Blandin Stéphanie , Brizard Jean‐Paul , Le Bourligu Laure , Demettre Edith , Renaud François , Biron David G.
Published: April 2007

Despite increasing evidence of behavioural manipulation of their vectors by pathogens, the underlying mechanisms causing infected vectors to act in ways that benefit pathogen transmission remain enigmatic in most cases. Here, 2‐D DIGE coupled with MS were employed to analyse and compare the head proteome of mosquitoes (Anopheles gambiae sensu stricto (Giles)) infected with the malarial parasite (Plasmodium berghei) with that of uninfected mosquitoes. This approach detected altered levels of 12 protein spots in the head of mosquitoes infected with sporozoites. These proteins were subsequently identified using MS and functionally classified as belonging to metabolic, synaptic, molecular chaperone, signalling, and cytoskeletal groups. Our results indicate an altered energy metabolism in the head of sporozoite‐infected mosquitoes. Some of the up‐/down‐regulated proteins identified, such as synapse‐associated protein, 14‐3‐3 protein and calmodulin, have previously been shown to play critical roles in the CNS of both invertebrates and vertebrates. Furthermore, a heat shock response (HSP 20) and a variation of cytoarchitecture (tropomyosins) have been shown. Discovery of these proteins sheds light on potential molecular mechanisms that underlie behavioural modifications and offers new insights into the study of intimate interactions between Plasmodium and its Anopheles vector.
Relaxation processes in PVAc‐HA nanocomposites
Authors: Kalfus J. , Jancar J.
Published: April 2007

Fundamental principles of polymer physics were used for description of relaxation behavior of polymer chain near solid surface. In a nanocomposite, considerable portion of polymer matrix is in contact with the filler surface even at very low filler loadings. In this study, nanocomposite was considered as a two component system consisting of (i) bulk polymer matrix and (ii) effective particles composed of adsorbed polymer shell and filler particle core. Both polymer phases, i.e., bulk and immobilized, are able to relax, however, each of them on a different time scale. Thus, above the neat matrix Tg, these two phases undergo (i) free and (ii) retarded reptation dynamics due to the adsorption processes on the filler surface, respectively. Relaxation time was calculated for each phase using the reptation theory. To calculate the mixed response of the whole polymer nanocomposite, a simple rule of mixtures model and percolation model were used. Calculated composite relaxation times were correlated with experimental modulus recovery data measured after the Payne effect in poly(vinylacetate)‐hydroxyapatite nanocomposite. Good agreement was found between theoretical predictions and experimental data. © 2007 Wiley Periodicals, Inc. JPolym Sci Part B: Polym Phys 45: 1380–1388, 2007
Isothermal crystallization studies of poly(butylene terephthalate) composites
Authors: Al‐Mulla Adam , Mathew Johnson , Shanks Robert
Published: April 2007

Different crystallization kinetic models (Avrami and Tobin) have been applied to study the crystallization kinetics of virgin poly(butylene terephthalate) (PBT) and filled PBT systems under isothermal experimental conditions. The experimental data have been analyzed with a nonlinear, multivariable regression program. The kinetic parameters for the isothermal crystallization have been determined. The analysis results indicate that both models satisfactorily represent the isothermal crystallization kinetics. PBT crystallizes most slowly. The presence of nanoclays or nanofibers, added as fillers, enhances the crystallization rate of PBT composites. An analysis of the kinetic data with the Avrami and Tobin models has shown little change in the crystallization exponent compared with that of virgin PBT. The crystallization rate constant decreases with a rise in the temperature for the two models. This trend has been observed for similar polyester systems reported in the literature. The dispersion of the clay layers in the PBT nanocomposites has been characterized with wide‐angle X‐ray diffraction and transmission electron microscopy. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1344–1353, 2007
Effect of molecular weight and temperature on physical aging of thin glassy poly(2,6‐dimethyl‐1,4‐phenylene oxide) films
Authors: Huang Y. , Paul D. R.
Published: April 2007

The effects of polymer molecular weight and temperature on the physical aging of poly(2,6‐dimethyl‐1,4‐phenylene oxide) (PPO) is examined. Gas permeability and refractive index were monitored during the aging process for PPO film samples at three aging temperatures below the glass transition temperature. Comparisons between the two samples of PPO that differ widely in molecular weight reveal an insignificant difference, which support the notion that above a critical molecular weight range there is little influence on aging rate. Increased temperature, over the limited range of 35–55 °C, results in higher aging rates for films made from both PPO materials. The rate of aging decreases strongly with increasing film thickness over the range examined, ∼0.4–25 μm. © 2007 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys 45: 1390–1398, 2007
Increased expression and differential phosphorylation of stathmin may promote prostate cancer progression
Authors: Ghosh Ritwik , Gu Guangyu , Tillman Erin , Yuan Jialing , Wang Yongqing , Fazli Ladan , Rennie Paul S. , Kasper Susan
Published: April 2007

BACKGROUND

Proteins which regulate normal development may promote tumorigenesis, tumor progression, or metastasis through dysregulation of these functions. We postulate that proteins, which regulate prostate growth also promote prostate cancer (PCa) progression.

METHODS

Two Dimensional Gel Electrophoresis was utilized to compare patterns of protein expression in 12T‐7f prostates (LPB‐Tag mouse model for PCa) during tumor development and progression with those of normal developing and adult wild type CD‐1 prostates. Stathmin expression and phosphorylation patterns were analyzed in mouse and human PCa cell lines as well as in human PCa tissue arrays.

RESULTS

Stathmin was identified by two‐dimensional gel electrophoresis and mass spectrometry. Stathmin levels increase early during normal mouse prostate development and again during prostate tumor development and progression. In human prostate adenocarcinoma, stathmin increases in Gleason pattern 5. Further, stathmin is differentially phosphorylated in androgen‐dependent LNCaP cells compared to androgen‐independent PC‐3 and DU145 cells. This differential phosphorylation is modulated by androgen and anti‐androgen treatment.

CONCLUSION

Stathmin expression is highest when the prostate is undergoing morphogenesis or tumorigenesis and these processes may be regulated through differential phosphorylation. Furthermore, modulation of stathmin phosphorylation may correlate with the development of androgen‐independent PCa. Prostate 67: 1038–1052, 2007. © 2007 Wiley‐Liss, Inc.
Feasibility study of adjustment for contamination and non‐compliance in a prostate cancer screening trial
Authors: Roemeling Stijn , Roobol Monique J. , Otto Suzie J. , Habbema Dik F. , Gosselaar Claartje , Lous Jan J. , Cuzick Jack , Schröder Fritz H.
Published: April 2007

BACKGROUND

The use of PSA as a screening test has become increasingly prevalent in the general population and therefore also in the control arm of the European Randomized study of Screening for Prostate Cancer (ERSPC). We present a feasibility study and impact simulation of a secondary analysis, which imitates a situation where all participants in the study are managed according to their random assignment.

METHODS

The results of the Rotterdam section of the ERSPC were adjusted for contamination and non‐compliance according to Cuzick et al. [Stat Med 1997; 16:1017–1029]. Endpoints of this analysis were simulated reductions in prostate cancer mortality.

RESULTS

Of the men allocated to the screen arm, 27.1% were non‐compliant. In the control arm 30.7% had their PSA‐level measured by a general practitioner (GP) (i.e., contamination). For a scenario in which the intention‐to‐screen analysis was assumed to give a decrease in the mortality in the men randomized to screening of 6.7%, the secondary analysis resulted in a decrease of 16.1% for those actually screened.

CONCLUSION

Although the definition of contamination as “PSA ever tested” gives an indication of the proportion of contamination, it will be important to differentiate the screening use of PSA from its diagnostic use. For the rest, adjustment for non‐compliance and contamination was shown to be feasible in this prostate cancer screening trial. It can therefore be used to carry out a secondary analysis on the definitive outcome of the ERSPC and will provide accurate information for those men who are in fact screened. Prostate 67: 1053–1060, 2007. © 2007 Wiley‐Liss, Inc.
Ab‐initio investigation of structural, electronic and optical properties for three phases of ZnO compound
Authors: Charifi Z. , Baaziz H. , Hussain Reshak Ali
Published: April 2007

The complex density‐functional theory (DFT) calculations of structural, electronic and optical properties for the three phases: wurtzite (B4), zincblende (B3) and rocksalt (B1) of ZnO compound have been reported using the full‐potential linearized‐augmented plane‐wave (FP‐LAPW) method as implemented in the WIEN2k code. We employed both the local‐density approximation (LDA) and the generalized‐gradient approximation (GGA), which is based on exchange–correlation energy optimization to calculate the total energy. Also, we have used the Engel–Vosko GGA formalism, which optimizes the corresponding potential for band‐structure calculations. The 3d orbitals of the Zn atom were treated as the valence band. The calculated structural properties (equilibrium lattice constant, bulk modulus, etc.) of the wurtzite and rocksalt phases are in good agreement with experiment. The B4 structure of ZnO is found to transform to the B1 structure with a large volume collapse of about 17%. The phase transition pressure obtained by using LDA is about 9.93 in good agreement with the experimental data. B1‐ZnO is shown to be an indirect bandgap semiconductor with a bandgap of 1.47 eV, which is significantly smaller than the experimental value (2.45 ± 0.15 eV). While B3 and B1 phases have direct bandgap semiconductors with bandgaps 1.46 and 1.57 eV, respectively. Also, we have presented the results of the effective masses. We present calculations of the frequency‐dependent complex dielectric function ε (ω) and it zero‐frequency limit ε1(0). The optical properties of B4 phase show considerable anisotropic between the two components. The reflectivity spectra has been calculated and compared with the available experimental data. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Study of the transport properties of a molecular junction as a function of the distance between the leads
Authors: García‐Suárez Víctor M. , Kostyrko Tomasz , Bailey Steven , Lambert Colin , Bułka Bogdan R.
Published: April 2007

We consider a model of a molecular junction made of BDT (benzene dithiol) molecule trapped between two Au(100) leads. Using the ab initio approach implemented in the SIESTA package we look for the optimal configurations of the molecule as a function of the distance between the leads. We find that for distances long enough the energy of the system is minimized when the molecule is bonded asymmetrically, i.e. chemisorbed to one of the leads, whereas for distances shorter than 12 Å the energy is minimized when the molecule sits in the middle between the leads. We discuss possible consequences of the above findings for the transport properties of the junction. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Proton spin system in pentacene and its interaction with photoexcited triplet electron spin
Authors: Labuz M. , Kuzma M.
Published: April 2007

Reading of single spin states is the main experimental problem in quantum computing. Pentacene is one of a few molecules on which the optical read‐out of single spin experiments were performed. The shape of optical single molecule spectroscopy (ODMR) signal depends on an interaction of triplet state of two unpaired electron spins with proton bath. These protons form a Heisenberg chain withN= 14 nodes. We investigate the symmetry of this system in selected inversed spin sectors of 214nuclear spin configurations. In particular all exact Bethe solutions for two reversed spins have been derived. The interaction of electron and proton spin systems has been addressed. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Spin–orbital entanglement near quantum phase transitions
Authors: Oleś Andrzej M. , Horsch Peter , Khaliullin Giniyat
Published: April 2007

Spin–orbital entanglement in the ground state of a one‐dimensional SU(2) ⊗ SU(2) spin–orbital model is analyzed using exact diagonalization of finite chains. For S = 1/2 spins and T = 1/2 pseudospins one finds that the quantum entanglement is similar at the SU(4) symmetry point and in the spin–orbital valence bond state. We also show that quantum transitions in spin–orbital models turn out to be continuous under certain circumstances, in constrast to the discontinuous transitions in spin models with SU(2) symmetry. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Effect of the next‐nearest neighbor hopping on the stability and band structure of the incommensurate phases in the cuprates
Authors: Raczkowski Marcin , Frésard Raymond , Oleś Andrzej M.
Published: April 2007

Using a spin‐rotation invariant version of the slave‐boson approach we investigate the relative stability and band structure of various incommensurate phases in the cuprates. Our findings obtained in the Hubbard model with next‐nearest neighbor hopping –t′/t≃ 0.15, as appropriate for the La2–xSrxCuO4family, support the formation of diagonal (vertical) stripe phases in the doping regimex= 1/16 (x= 1/8), respectively. In contrast, based on the fact that a larger value –t′/t= 0.3 expected for YBa2Cu3O6+δtriggers a crossover to the diagonal (1,1) spiral phase at increasing doping, we argue that it might explain why the static charge order has been detected in YBa2Cu3O6+δonly in the highly underdoped regime. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Reduction in defect density over whole area of (1$ \bar 1 $00) m ‐plane GaN using one‐sidewall seeded epitaxial lateral overgrowth
Authors: Kawashima T. , Nagai T. , Iida D. , Miura A. , Okadome Y. , Tsuchiya Y. , Iwaya M. , Kamiyama S. , Amano H. , Akasaki I.
Published: April 2007

We succeeded in growing low‐defect‐density m ‐plane GaN on grooved m ‐plane GaN with SiO2 masks on the terrace region. By changing the V/III ratio, we were able to increase the growth rate of GaN on one sidewall, thereby achieving one‐sidedwall lateral growth. Dislocations and stacking faults were decreased markedly over the whole area. The densities of dislocations and stacking faults were 1.3 × 107 (cm–2) and <2.6 × 104 (cm–1), respectively. The photoluminescence intensity was 213 times higher than that of an m ‐plane GaN template on an m ‐plane 4H‐SiC substrate. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Antisite defect‐related luminescence in (LaLu)3Lu2Ga3O12 garnet single crystals
Authors: Zorenko Yu. , Voloshynovskii A. , Vistovsky V. , Grinberg M. , Kornylo A. , Łukasiewicz T. , Świrkowicz M.
Published: April 2007

Intrinsic luminescence of the undoped (LaLu)3Lu2Ga3O12 garnet (LLGG) single crystals with high concentration of LuLa antisite defects (AD) has been studied for the first time under excitation by 1.5 ns pulse X‐ray radiation. It has been found that the host luminescence of LLGG crystal consists of two emission bands in the UV range. The band peaked at 3.80 eV at 77 K has been related to the luminescence of localized excitons (LE) perturbed by the presence of AD whereas the band peaked at 3.37 eV has been related to the radiative annihilation of bound‐state excitons localized directly at LuLa AD. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Quantitative carbamylation as a stable isotopic labeling method for comparative proteomics
Authors: Angel Peggi M. , Orlando Ron
Published: April 2007

A method was developed that uses urea to both solublize and isotopically label biological samples for comparative proteomics. This approach uses either light or heavy urea (12CHN2O or 13CHN2O, respectively) at a concentration of 8 M and a pH of 7 to dissolve the samples prior to digestion. After the sample is digested using standard proteomic protocols and dried, isotopic labeling is completed by resuspending the sample in a solution of 8 M urea at a pH of 8.5, using the same isotopic species of urea as used for digestion and incubating for 4 h at 80°C. Under these conditions, carbamylation occurs only on the primary amines of the peptides. The effects of complete carbamylation on matrix‐assisted laser desorption/ionization time‐of‐flight mass spectrometry (MALDI‐TOFMS) and electrospray ionization tandem mass spectrometry (ESI‐MS/MS) (collision‐induced dissociation (CID)) were examined. Peptides that had a C‐terminal carbamylated lysine residue were found to have a reduced intensity when viewed by MALDI‐TOFMS. CID of a tryptic peptide that was carbamylated on both the N‐terminus and the C‐terminus was found to have a more uniform distribution of b‐ and y‐ions, as well as prominent ions from loss of water. Reversed‐phase chromatography coupled to ESI‐MS/MS was used to identify and quantify the isotopically labeled standard proteins, bovine serum albumin (BSA), bovine transferrin, and bovine alpha‐casein. Quantitative error between theoretical and observed data ranged from 1.7–10.0%. Relative standard deviations for protein quantitation ranged from 5.2–27.8% over a dynamic range from 0.1–10 (L/H). The development of a method utilizing urea‐assisted carbamylation of lysines and N‐termini to globally labeled samples for comparative proteomics may prove useful for samples that require a strong chaotrope prior to proteolysis. Copyright © 2007 John Wiley & Sons, Ltd.
Denaturation of α‐lactalbumin and ubiquitin studied by electrospray and laser spray
Authors: Nakamura Masana , Takamizawa Atsushi , Yamada Hideki , Hiraoka Kenzo , Akashi Satoko
Published: April 2007

Electrospray and laser spray mass spectra of human α‐lactalbumin and bovine ubiquitin were studied, with an emphasis on the denaturation induced by laser spray. There were no remarkable differences in the electrospray and laser spray mass spectra for acidic and basic aqueous solutions of α‐lactalbumin in positive and negative modes of operations. This originates from the fact that this protein is tightly folded with four disulfide bonds. For ubiquitin, however, denaturation was induced by laser spray for the positive mode of operation and the [M+nH]n+ with a maximum of n = 13 was observed, i.e., all the acidic amino acid residues are fully neutralized (protonated). In contrast, the laser‐induced denaturation was not observed for the negative mode of operation, i.e., denaturation of ubiquitin is largely suppressed in the negatively charged liquid droplets. The marked difference observed in the positive and negative modes of operations for ubiquitin is ascribed to the difference in the susceptibility of side‐chain/main‐chain interactions in the positive‐ion excess and in the negative‐ion excess liquid droplets. That is, the interactions between the basic residues and main‐chain amide carbonyl groups (NH•••OC< or NH2•••OC<) which play an important role in stabilizing the protein structures are not so affected in the negative mode of operation but are weakened in the positive mode of operation. Copyright © 2007 John Wiley & Sons, Ltd.
Actuator fault diagnosis for uncertain linear systems using a high‐order sliding‐mode robust differentiator (HOSMRD)
Authors: Chen Weitian , Saif Mehrdad
Published: April 2007

Many observer‐based fault diagnosis strategies proposed for linear systems, subject to unknown inputs, operate based on three assumptions. The first assumption is that the system under consideration is at least detectable. The second one is that the unknown inputs satisfy certain matching conditions. The third one, which is often implicit, is that the relative degrees from the generalized input vector, including both known and unknown inputs, to the outputs are no larger than one. If none of these assumptions are met, little result exists on how to carry out fault diagnosis. The purpose of this paper is to develop a novel actuator fault diagnosis scheme for a general class of linear systems subject to unknown inputs that can work without the mentioned three assumptions. Four actuator fault diagnosis problems related to fault detection, isolation, and estimation are formulated and studied. In order to solve these problems, an input–output relation, which involves only the outputs and their higher‐order derivatives, is derived. The posed problems are solved based on this relation via utilizing both the outputs and their higher‐order derivatives. Because only the outputs are measured, higher‐order output derivatives are estimated using the recently developed high‐order sliding‐mode robust differentiators (HOSMRDs). The first two fault detection and isolation problems are answered in terms of a concept called Generalized Actuator Fault Isolation IndeX (GAFIX), and it is proved that, under the condition that the derived input–output relation is used for fault diagnosis, actuator faults are detectable if and only if GAFIX⩾1, and l actuator faults can be isolated if and only if GAFIX⩾l+1. A method which can be used to estimate the faults is proposed for the fault estimation problem. To solve the last problem, an actuator fault diagnosis scheme is designed using both the measured outputs and their estimated derivatives obtained by HOSMRDs, and is presented in steps. Finally, an example is provided to show the effectiveness of our fault diagnosis scheme in terms of fault detection, isolation, and estimation. Copyright © 2007 John Wiley & Sons, Ltd.
Imaging of Silkworm Meiotic Chromosome by Atomic Force Microscopy
Authors: Narukawa J. , Yamamoto K. , Ohtani T. , Sugiyama S.
Published: April 2007

Although structural information of mitotic chromosomes has been accumulated, little information is available for meiotic chromosome structures. Here, we applied atomic force microscopy (AFM) to investigate the ultrastructures of the silkworm, Bombyx mori, meiotic pachytene chromosome in its native state with nanometer scale resolution. Two levels of DNA folding were observed on the meiotic chromosome surface, 50–70 nm granules, which were considered to be 30 nm chromatin fibers, and spherical protrusions of 400–600 nm, which were considered to be chromomeres and arranged on the surface of the chromosome parallel to the chromosome longitudinal axis. These observations suggested that AFM study is an excellent approach for obtaining information concerning the silkworm pachytene chromosome higher order structure. SCANNING 29: 000‐V000, 2007. © 2007 Wiley Periodicals, Inc.
Skirting: A Limitation for the Performance of X‐ray Microanalysis in the Variable Pressure or Environmental Scanning Electron Microscope
Authors: Le Berre J. F. , Demopoulos G. P. , Gauvin R.
Published: April 2007

The variable pressure or environmental scanning electron microscope (VP‐SEM; ESEM) has become the microscope of choice for many scientists and technologists. Hence, the development of robust methods for X‐ray microanalysis, limited by skirting, has become critical. In this paper, two pressure variation correction methods (Doehne and Gauvin) are compared. Both of these methods appear to be effective; the results were found to be well within 10% of the values obtained at 0 Pa. The Doehne method is dependent on an empirical factor (D), therefore the accuracy of the results will depend on the accuracy of this value. Also the Doehne method is compromised by the nonlinearity of the response with pressure. The Gauvin method is more user‐friendly and more precise when considering the total range of pressure. SCANNING 29: 000‐V000, 2007. © 2007 Wiley Periodicals, Inc.
The questioning statistician
Authors: Finney D. J.
Published: April 2007

Effective statistical help to biological and medical research demands thorough involvement of the statistician. The breadth of his activities can be illustrated by considering the questions he needs to discuss with his scientific colleagues in the course of planning a comparative experiment. The paper presents and comments on 22 such questions, showing their relation to the objectives of the experiment, the utilization of resources, and the subsequent statistical analysis. A final paragraph urges that proper attention to all these points forms an integral part of an ethical approach to experimentation.
A simple method based on broken‐line interpolation for displaying data from long‐term clinical trials
Authors: Gans Daniel J.
Published: April 2007

In displaying data from long‐term clinical studies, variation across patients in the times at which readings are recorded often presents a problem. A simple method for treating such data is proposed, which avoids arbitrary conventions and methodological difficulties inherent in other approaches. It is based on within‐patient broken‐line interpolation, and is easy to implement on a computer. The method is tested and compared to others with computer‐simulated data whose time‐pattern is known. Though the comparison is of limited scope, the method appears to compare favourably with the ‘closest‐reading’ and ‘window’ approaches.
The detection of adverse reactions to therapeutic drugs
Authors: Finney D. J.
Published: April 2007

The risk that a drug newly introduced into medical use will occasionally cause adverse reactions is neither negligible nor totally avoidable. Only well organized systems of monitoring can bring early detection and appropriate action. These in turn require either detailed supervision or spontaneous reporting. The paper is concerned with statistical inference from reports spontaneously submitted, and its logical limitations; it discusses strengths and weaknesses of the UK system, the detection process, and automated signalling.
Interpretation and estimation of summary ratios under heterogeneity
Authors: Greenland Sander
Published: April 2007

Of the several types of summary odds ratios in use in epidemiology, only those proposed by Mantel and Haenszel and Miettinen do not assume homogeneity (constancy) of stratum‐specific parameters. Under heterogeneity, Miettinen's estimators consistently estimate meaningful epidemiologic parameters, whereas the asymptotic expectation of the Mantel‐Haenszel odds ratio varies according to irrelevant features of the sampling design. Although one can modify the Mantel‐Haenszel summary to overcome the latter problem, one can also extend the Miettinen estimators to sparse data and thus limit the use of Mantel‐Haenszel summaries to situations in which the homogeneity hypothesis is reasonable. This paper provides formulae for the extended Miettinen estimators and large‐sample variances and confidence limits for summary ratios under heterogeneity.
Statistical methods for estimating attributable risk from retrospective data
Authors: Whittemore Alice S.
Published: April 2007

This paper extends Levin's measure of attributable risk1 to adjust for confounding by aetiologic factors other than the exposure of interest. One can estimate this extended measure from case‐control data provided either (i) from the control data one can estimate exposure prevalence within each stratum of the confounding factor; or (ii) one has additional information available concerning the confounder distribution and the stratum‐specific disease rates. In both cases we give maximum likelihood estimates and their estimated asymptotic variances, and show them to be independent of the sampling design (matched vs. random). Computer simulations investigate the behaviour of these estimates and of three types of confidence intervals when sample size is small relative to the number of confounder strata. The simulations indicate that attributable risk estimates tend to be too low. The bias is not serious except when exposure prevalence is high among controls. In this case the estimates and their standard error estimates are also highly unstable. In general, the asymptotic standard error estimates performed quite well, even in small samples, and even when the true asymptotic standard error was too small. By contrast, the bootstrap estimate2 tended to be too large. None of the three confidence intervals proved superior in accuracy to the other two. Thus there appears no advantage in using the log‐based interval suggested by Walter3′4 which is always longer than the simpler symmetric interval.
Multicentre clinical trials: Bradford Hill's contributions and some subsequent developments
Authors: Fleiss Joseph L.
Published: April 2007

Most large comparative trials of therapeutic agents are now conducted as multicentre studies. Some of the major studies designed by Bradford Hill were also multicentre, and his methods of design and conduct remain valid today, even though improved methods for analysing the data have appeared subsequently.
Relative risks of diseases in the presence of incomplete penetrance and sporadics
Authors: Majumder Partha P. , Chakraborty Ranajit , Weiss Kenneth M.
Published: April 2007

In most diseases of contemporary interest to epidemiology, the importance of familial risk factors is often assessed by relative risk measures computed from family history data. In this paper, we examine the efficiency of relative risk measures in discerning the genetic background of a disease. It is shown that even for a simple (one locus, two alleles) genetic disease, incomplete penetrance of the disease allele and/or occurrence of sporadics (i.e. non‐heritable cases caused by environmental risk factors) often yields a rather small value of relative risk. This means that a small value of relative risk need not necessarily imply that genetic factors are unimportant in the aetiology of the disease. Furthermore, it is shown that the relative risk measures are complicated functions of disease gene frequency, the penetrance parameter and the sporadic rate. A rejection of genetic involvement for a disease on the basis of a single relative risk estimate may, therefore, be erroneous.
Reducing classification errors in cohort studies: The approach and a practical application
Authors: Schulz Kenneth F. , Cates Willard , Grimes David A. , Selik Richard M. , Tyler Carl W.
Published: April 2007

Classification errors of dependent variables can distort the results of observational studies. To reduce misclassification from our multicentre observational study of abortion complications, we extended the methodology of Lawrence and Greenwald9 for use in situations of unequal sample sizes and implemented both an office review and a field review. We reabstracted 424 reported complications and a random sample of 364 reported non‐serious cases from 12 institutions participating in our study. In total, 30 per cent of the reported serious complications turned out to be misclassified: the office review detected 74 per cent of the total number of misclassifications with the remainder found in the field review. Because, with our particular data base, we estimated expending only 15 per cent of the total resources with our office effort, this represented the most cost‐efficient approach to reducing classification errors. By eliminating the false positives from our study, we forced the specificity to 1·00 which produced both an unbiased estimate of the relative risk and an increase of 4 per cent to 63 per cent in the power of our study.
The association between HLA antigens and the presence of certain diseases
Authors: Green J. R. , Chiew Mui Kui , Low Heng Chin , Woodrow J. C.
Published: April 2007

The association between the presence or absence of two HLA antigens and coeliac disease, thyrotoxicosis and ankylosing spondylitis has been studied in patients and controls. The simple empirical logistic model and a refinement due to Dyke and Patterson have been used to examine which conditional associations are important.
The analysis of a sequential clinical trial for the comparison of two lung cancer treatments
Authors: Whitehead J. , Jones D. R. , Ellis S. H.
Published: April 2007

Methods adopted in the analysis of data from a randomized controlled trial of a new treatment for inoperable lung cancer are described. The trial design employed the sequential logrank test using length of survival from time of randomization as the principal outcome measure. We describe the practical arrangements for regular inspections of the accumulating data as required by the sequential design, and also for more extensive but less formal interim analyses, and present some of the results. On termination of the trial the survival patterns of the two treatment groups were compared using methods of analysis developed specifically to allow for the sequential nature of the trial design. The role of prognostic factors was investigated using fixed sample methods which are approximately independent of the sequential design.
The logistic analysis of epidemiologic prospective studies: Investigation by simulation
Authors: Lilienfeld David E. , Pyne David A.
Published: April 2007

We performed a Monte Carlo computer simulation of the Walker‐Duncan logistic regression technique in a typical epidemiologic prospective setting and analysed the results with respect to the accuracy and reliability of the regression estimates and the associated statistical significance tests (Z‐tests). The results strongly suggest that the estimates were neither accurate nor reliable. The magnitude of the difference between the average estimated regression coefficient and its true population value did not necessarily decrease as the sample size increased. The average estimated standard deviation of the estimate of the regression coefficient either overestimated or underestimated the actual standard deviation, the former occurring most, but not all, of the time. The significance tests (a two‐tailed Z‐test with a significance level of 0.05) had actual type I errors ranging from 0.00 to 0.24 for different samples. This approach is therefore inadequate as an epidemiologic tool for analysis of a Framingham‐type prospective study. Further simulation studies are indicated.
Ensuring data quality in medical research through an integrated data management system
Authors: Marinez Yolan N. , McMahan C. Alex , Barnwell George M. , Wigodsky Herman S.
Published: April 2007

An effective data management system ensures high quality research data by making certain of the proper execution of the study design. This paper presents the components of a data management system and describes procedures for use in each component of the system to obtain high quality data. We discuss the interrelationship among the components of the data management system and the relationship of the data management system to other parts of the research project. We identify underlying principles in design and implementation of a data management system to ensure high quality data.
Interpretation of time trends in disease rates in the presence of generation effects
Authors: Gardner M. J. , Osmond C.
Published: April 2007

A comparison is made of indices used for assessing trends in mortality rates over time, and results for four types of cancer are used as examples. The approaches contrasted as measures of change over calendar years of time are the use of crude death rates, standardized death rates (both direct and indirect approaches) and period effects estimated from an age‐period‐cohort model (including and excluding the cohort factor). The use of these indices is also compared with examination of the original age‐specific rates. Similar analyses are made of the equivalent indices for examining changes between different birth cohorts over time.

Submodels of the age‐period‐cohort model are shown to be algebraically and empirically related to age‐standardized indices. The use of the full model, as contrasted to standardization methods, can result in important modifications to the interpretation in some cases. However, there are difficulties with this approach, as with all models, if applied uncritically. It is a wise precaution to examine the age‐specific rates in each instance to ensure that any summary index is appropriate.
A study of three techniques for time‐space clustering in hodgkin's disease
Authors: Chen Rina , Mantel Nathan , Klingberg Marcus A.
Published: April 2007

Three techniques for disease time‐space clustering analysis, those of Knox, Mantel and Ederer‐Myers‐Mantel, were applied to simulated data so as to study their sensitivities. The simulated data corresponded to three alternative non‐null models for the distribution, transmission and development of Hodgkin's disease (HD) which were formulated in accordance with the results of published studies.

The results indicate that the three techniques may not be sufficiently sensitive to the clustering in a real data set of HD cases. Therefore, the inconclusive results obtained to date with regard to clustering of HD may be related to the low power of the statistical techniques employed.
Comparison of two statistical techniques for the surveillance of birth defects through a monte carlo simulation
Authors: Barbujani Guido , Calzolari Elisa
Published: April 2007

In a multi‐hospital surveillance system for detecting increases in congenial malformation rates, the performance of the set technique applied individually to hospitals and of the cumulative sum (Cusum) technique applied to the aggregate of hospitals has been compared using a Monte Carlo method. The Cusum technique appears to be both more sensitive to real increases and less likely to issue false alarms.
A classification of scottish infants using latent class analysis
Authors: Pickering R. M. , Forbes J. F.
Published: April 2007

This paper illustrates the use of latent class analysis to classify 50,000 infants into a small number of classes or case types, as a preliminary to a study of the allocation of neonatal hospital resources throughout Scotland. Information, extracted from a detailed neonatal discharge record, was summarized by 11 clinical and diagnostic catagorical variables. Statistical models incorporating 1 to 6 latent classes were then estimated using the EM algorithm. The 4 class model was chosen because it provided a good description of the data and the resulting classes had a medical interpretation. The factors influencing the choice of model are discussed and goodness of fit tests are presented. The stability of the classes was also investigated using random halves of the data and an earlier comparable data set.
Inter‐rater agreement among orthodontists in a blocked experiment
Authors: Korn Edward L. , Baumrind Sheldon
Published: April 2007

Five orthodontists were asked to predict for 64 patients a particular dichotomous outcome of treatment based on pre‐treatment X‐ray films. The orthodontists rated the cases in blocks of size 4‐6 with the knowledge of the number of positive outcomes in each block. We discuss the reasons why this blocked design is appropriate whenever clinicians are asked to rate cases which have not been randomly selected from a clinical practice similar to their own. We give a simple description of the inter‐rater agreement for this type of blocked experiment as well as a procedure to test that the agreement is no better than that expected by random independent assignment.
Birth cohort analysis using irregular crosssectional data: A technical note
Authors: Schifflers E. , Smans M. , Muir C. S.
Published: April 2007

Cancer motality and morbidity data are usually collected and published by calendar time period and by age class. Transformation of the age‐specific incidence or mortality rates into those for birth cohorts is readily undertaken when one age class of each time period corresponds to a given cohort: a requirement that is often not satisfied. The authors propose a method for the computation of birth cohort age‐specific incidence rates given irregular cross‐sectional data. The procedure is based on a cross‐sectional interpolation of cumulated population and case figures, from which cohort rates can be derived. Using the method several examples of trends in cancer incidence by birth cohort are discussed.
Dose‐response analysis of combination preparations
Authors: Unkelbach Hans Dieter , Wolf Thomas
Published: April 2007

A parametric model for quantal response to combination preparations is defined and discussed. Tests for additivity of the combination preparation are specified and demonstrated by an example. Parallelism of the dose‐response curves is not required.
Treatment allocation methods in clinical trials: A review
Authors: Kalish Leslie A. , Begg Colin B.
Published: April 2007

A comprehensive review of methods for allocation of treatments to patients in clinical trials is presented. Attention is restricted to controlled, prospective trials, as opposed to comparisons involving historical or other ‘external’ controls. We describe the features of each method and classify them according to whether their primary focus is randomization, efficiency, or balance with respect to prognostic factors. Methods which prevent bias, ensure an efficient treatment comparison and are simple to implement will contribute to the ability of clinical trials to provide precise and valid treatment comparisons. We assess critically the extent to which the methods achieve these goals, review the relationships of the allocation methods with subsequent analyses of the trial results, discuss current usage and provide guidelines for choice of method.
The use of logit models to investigate social and biological factors in infant mortality. I: Methodology
Authors: Murrells T. J. , Smith T. M. F. , Catford J. C. , Machin D.
Published: April 2007

Infant mortality data for England and Wales, cross classified by mother's age, parity and social class, have been published on two occasions, the first giving the relevant data for 1949/50, the second for 1975, some 25 years later. Published analyses of these separate data sets have been based on graphical and tabular methods. This paper describes the statistical methodology appropriate to the use of logit models to investigate these data sets and shows how such models may be used to supplement the more informal approach. The stillbirth data for 1975 are used for illustration. Paper II, which follows, explores the stillbirth data in greater detail, with emphasis on the changes between 1949/50 and 1975. Subsequent papers describe neonatal and post‐neonatal deaths using the same framework. A final paper summarizes the overall changes in infant mortality by means of a multilogit model.
The use of logit models to investigate social and biological factors in infant mortality. II: Stillbirths
Authors: Murrells T. J. , Catford J. C. , Smith T. M. F. , Machin D.
Published: April 2007

Infant mortality data for England and Wales cross‐classified by mother's age, parity and social class have only been published for 1949/50 and 1975. Appropriate statistical methodology for the analysis of such data has been described in Paper I, which used the 1975 stillbirth data for illustration. This paper examines the stillbirth data from both years by formally incorporating the year of data collection into the statistical model, enabling changes in the age, parity and social class effects with time to be investigated. Despite a marked reduction in stillbirth mortality from 21.1 to 10.1 per thousand over the period, the relative contribution of social class has increased. In particular there has been a relative increase in risk for mothers in the lower social classes. By contrast the effects of age and parity, although remaining important, have diminished over the period.
Empirical bayes estimation of cancer mortality rates
Authors: Tsutakawa Robert K. , Shoop Gary L. , Marienfeld Carl J.
Published: April 2007

Mortality rates for specific cancer types and age‐sex groups computed for large numbers of cities typically show extreme fluctuation. This is primarily due to the rare occurrence of specific cancer deaths in most of the small and moderate size cities during a fixed time period. Assuming a Poisson death process, we use an empirical Bayes method to obtain adjusted rates that are more stable for comparison of cities and prediction of future mortality. We have chosen stomach and bladder cancers in Missouri cities to illustrate the problems, techniques and results.
Linear models for the analysis of variability in factorial designs: An application to anthropometric indicators
Authors: Bossi Anna , Milani Silvano
Published: April 2007

This paper has two aims. One is to evaluate, in a set of 9740 ‘reference’ neonates born in five Italian centres (Trieste, Milan, Parma, Rome, Bari) during 1973‐1976 the effects of gestational age and birthplace on the variability of crown‐heel length and head circumference at birth; this is a preliminary step in the construction of ‘Italian’ intrauterine growth standards for such anthropometric measures. The other aim is to put the various techniques for the analysis of variability into a common framework of Linear Models, either Generalized or Classical, to compare their main features and provide some indications about their application.
Small sample estimation of log odds ratios from logistic regression and fourfold tables
Authors: Walter S. D.
Published: April 2007

Schaefer has proposed a method to correct the maximum likelihood logistic regression coefficients for bias in small samples. We show here that this reduces, in the special case of a single dichotomous regression variable, to an earlier result of Haldane, for the estimation of a single log odds ratio. This paper reviews various estimators for the log odds ratio in a fourfold table, and compares the properties of two by complete enumeration in sets of tables with small sample sizes. The first of these, also due to Haldane, is based on the addition of 1/2 to each cell of the table; the second is where 1/2 is added to all cells of the table only if a zero frequency arises.

We evaluate the bias and mean squared error of both of these estimators in sets of tables with various sample sizes snd odds ratios. Haldane's estimator usually has lower bias and MSE, and so we do not in general recommend the practice of adding 1/2 only as necessary. Exceptions might occur if one has gooda prioriestimates of the outcome probabilities in the two samples under comparison.
The use of an autoregressive model for the analysis of longitudinal data in epidemiologic studies
Authors: Rosner Bernard , Muñoz Alvaro , Tager Ira , Speizer Frank , Weiss Scott
Published: April 2007

Korn and Whittemore1,2 have presented methods for analyzing longitudinal data where the number of observations per individual is large relative to the number of variables considered for each subject. However, this is often not the case in epidemiologic studies, since one usually collects data at relatively few time points, and the quantity of data collected for each individual at each time point is typically extensive. We present here an autoregressive model for analyzing longitudinal data of this type for the case of a continuous outcome variable. Some of the important features of this model are that one can (1) in the same analysis, consider both independent variables that are time‐dependent and those that are fixed over time, (2) partially use data for an individual where some examinations are missing, (3) assess relationships between changes in outcome and exposure over short periods of time, (4) use ordinary multiple regression methods. Anderson3 has considered this type of model, but, to our knowledge, the model has never been applied to biostatistical problems. We illustrate these methods with data from a longitudinal study that seeks to identify the role of personal cigarette smoking on changes in pulmonary function in children.