bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometrically non‐linear damage interface based on regularized strong discontinuity
Authors: Larsson Ragnar , Jansson Niklas
Published: October 2002

The contribution of this paper concerns the fracture modelling of an interface with a fixed internal material surface in the context of geometrically non‐linear kinematics. Typical applications are composite laminates and adhesive/frictional joints in general. In the model development, a key feature is the concept of regularized strong discontinuity, which provides a regular deformation gradient within the interface. The deformation gradient within the interface is formulated in a multiplicative structure with a continuous part and a discontinuous part, whereby the interface deformation is interpreted as a transformation between the material damaged configuration and the actual spatial configuration. In analogy with the continuum formulation of hyper‐inelasticity, a constitutive framework is defined for the relation between the induced material traction and the displacement jump vector, which are defined on the material damaged interface configuration. Within this framework, a simple, but yet still representative, model for the delamination problem is proposed on the basis of a damage–plasticity coupling for the interface. The model is calibrated analytically in the large deformation context with respect to energy dissipation in mode I so that a predefined amount of fracture energy is dissipated. The paper is concluded with a couple of numerical examples that display the properties of the interface. Copyright © 2002 John Wiley & Sons, Ltd.
Topology design of structures using a dual algorithm and a constraint on the perimeter
Authors: Jog C. S.
Published: October 2002

Dual optimization algorithms are well suited for the topology design of continuum structures in discrete variables, since in these problems the number of constraints is small in comparison to the number of design variables. The ‘raw’ dual algorithm, which was originally proposed for the minimum compliance design problem, worked well when a perimeter constraint was added in addition to the volume constraint. However, if the perimeter constraint was gradually relaxed by increasing the upper bound on the allowable perimeter, the algorithm tended to behave erratically. Recently, a simple strategy has been suggested which modifies the raw dual algorithm to make it more robust in the absence of the perimeter constraint; in particular the problem of checkerboarding which is frequently observed with the use of lower‐order finite elements is eliminated. In this work, we show how the perimeter constraint can be incorporated in this improved algorithm, so that it not only provides a designer with a control over the topology, but also generates good topologies irrespective of the value of the upper bound on the perimeter. Copyright © 2002 John Wiley & Sons, Ltd.
Analysis of general quadrilateral orthotropic thick plates with arbitrary boundary conditions by the Rayleigh–Ritz method
Authors: Saadatpour M. M. , Azhari M. , Bradford M. A.
Published: October 2002

A numerical method is developed for the analysis of general quadrilateral, moderately thick orthotropic plates having arbitrary boundary conditions. The procedure is based on the application of the Rayleigh–Ritz method in conjunction with the Reissner–Mindlin thick plate theory. A set of complete polynomials in terms of natural co‐ordinates comprising of boundary and domain terms, which satisfy the boundary conditions, is deployed as the basic functions to approximate the real displacement field. The generalized displacements and the eigenvalues are determined by imposing the principle of stationary potential energy. Although the procedure has the ability to solve problems involving thick quadrilateral plates, the numerical examples presented are mostly for skew plates. The results herein are compared with their counterparts determined by other investigators. Copyright © 2002 John Wiley & Sons, Ltd.
Non‐linear dynamic behaviour of flexible marine pipes and risers
Authors: Yazdchi M. , Crisfield M. A.
Published: October 2002

This paper describes the way in which hydrostatic and hydrodynamic forces can be added to the conventional static and inertia forces for the non‐linear analysis of 3D flexible pipes and riser systems. Emphasis is placed on elements that use the Reissner–Simo beam theory or a related co‐rotational approach. Copyright © 2002 John Wiley & Sons, Ltd.
Numerical investigation of quenching for a nonlinear diffusion equation with a singular Neumann boundary condition
Authors: Christov C. I. , Deng K.
Published: October 2002

For a nonlinear diffusion equation with a singular Neumann boundary condition, we devise a difference scheme which represents faithfully the properties of the original continuous boundary value problem. We use non‐uniform mesh in order to adequately represent the spatial behavior of the quenching solution near the boundary. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 429–440, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10013
Least‐squares mixed finite element methods for the incompressible Navier‐Stokes equations
Authors: Gu Haiming , Wu Xiaonan
Published: October 2002

Least‐squares mixed finite element schemes are formulated to solve the evolutionary Navier‐Stokes equations and the convergence is analyzed. We recast the Navier‐Stokes equations as a first‐order system by introducing a vorticity flux variable, and show that a least‐squares principle based on L2 norms applied to this system yields optimal discretization error estimates. © 2002 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq 18: 441–453, 2002; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/num.10015
Chromosomal imbalances of primary and metastatic lung adenocarcinomas
Authors: Goeze Almut , Schlüns Karsten , Wolf Guenter , Thäsler Zsuzsanna , Petersen Simone , Petersen Iver
Published: October 2002

Comparative genomic hybridization (CGH) was used to screen 83 lung adenocarcinomas of 60 patients for chromosomal imbalances. The most common alteration was DNA overrepresentation on chromosome 1q, with a peak incidence at 1q22–q23 in 73% of the primary tumours, followed by DNA overrepresentation on chromosomes 8q and 20q, and deletions on chromosomes 3p, 4q, 6q, 9p, 9q, and 13q, in at least 60%. The generation of a difference histogram of metastasizing versus non‐metastasizing tumours and a case‐by‐case histogram for the comparison of 23 paired samples of primary tumours and corresponding metastases suggested that deletions on chromosomes 3p12–p14, 3p22–p24, 4p13–15.1, 4q21‐qter, 6q21‐qter, 8p, 10q, 14q21, 17p12–p13, 20p12, and 21q, and overrepresentations on chromosomes 1q21–q25, 7q11.2, 9q34, 11q12–q13, 14q11–q13, and 17q25 are associated with the metastatic phenotype. In contrast, losses on chromosome 19 and gains on 3p, 4q, 5p, and 6q were preferentially found in non‐metastasizng tumours. The analysis of the paired samples revealed considerable chromosomal instability, but indicated a clonal relationship in each case. The primary tumours often showed additional deletions, suggesting that loss of function mutations are critical in the initial phase of tumour dissemination, whereas the metastases preferentially acquired DNA gains, probably modulating the metastatic phenotype. The primary data from this study (ratio profiles, clinicopathological parameters, histograms) are also available at http://amba.charite.de/cgh. Copyright © 2001 John Wiley & Sons, Ltd.
Inter‐observer variation in the histopathological diagnosis of clinically suspicious pigmented skin lesions
Authors: Brochez Lieve , Verhaeghe Evelien , Grosshans Edouard , Haneke Eckhart , Piérard Gérald , Ruiter Dirk , Naeyaert Jean‐Marie
Published: October 2002

When a biopsy is taken of a suspicious pigmented skin lesion, histological examination is expected to establish the definitive diagnosis. This study evaluated the inter‐observer variation of 20 pathologists in the histological diagnosis of a randomly selected set of suspicious pigmented skin lesions (PSLs), by comparing their diagnoses to a reference diagnosis. Overall sensitivity for melanoma was 87%, ranging from 55% to 100% between the observers. Sensitivity was significantly lower for thin (Breslow thickness <1 mm) than for thick melanomas (83% versus 97%, p=0.005). Overall melanoma specificity was 94%, ranging from 83% to 100% between observers. Dysplastic naevus was the most important source of false‐positive diagnoses, mainly in situ melanomas. Positive and negative predictive values in the given test set were 75% and 97%, respectively. In the case of melanoma, there was quite some variation in measured Breslow thickness. This would have led to a different therapeutic approach in 12% of the readings. Some of the variation seemed to be due to a different interpretation of the presence of a co‐existent naevus. In 9% (3/35) of the readings, participants did not agree on the presence of ulceration. These results reflect a tendency to overdiagnose mainly thin melanomas in general histopathological practice. They also demonstrate variation in the assessment of major prognostic factors of melanoma. Copyright © 2002 John Wiley & Sons, Ltd.
FHIT expression in clear cell renal carcinomas: versatility of protein levels and correlation with survival
Authors: Ramp U. , Caliskan E. , Ebert T. , Karagiannidis C. , Willers R. , Gabbert H. E. , Gerharz C. D.
Published: October 2002

Clear cell renal cell carcinomas (RCCs) are characterized by a deletion of chromosome 3p, which might result in the inactivation of the FHIT (fragile histidine triad) gene, a putative tumour suppressor gene. To explore the relevance of FHIT aberrations for tumour progression and prognosis in clear cell RCCs, FHIT protein expression was analysed in formalin‐fixed tissue from 149 clear cell RCCs by immunohistochemistry. FHIT protein expression was found to be markedly reduced in all RCCs, when compared with adjacent non‐neoplastic tubule epithelia. Although remaining below the FHIT levels of normal tubule epithelia, a significant increase of FHIT expression became evident from well (G1) to poorly (G3) differentiated clear cell RCCs (p=0.0001) and from low (pT1) to advanced (pT3) tumour stages (p=0.001). The log‐rank test demonstrated a significant inverse correlation (p=0.0074) between FHIT expression and tumour aggressiveness as indicated by patient survival. Cox regression analysis revealed that FHIT expression is an independent prognostic parameter (p=0.0139) in clear cell RCCs. In conclusion, clear cell RCCs show a marked reduction of FHIT protein expression when compared with their putative cells of origin. In contrast to other tumour types, however, loss of FHIT protein expression is significantly less pronounced in poorly differentiated RCCs or advanced tumour stages. This versatility of FHIT expression during tumour progression suggests a role for reversible mechanisms of FHIT inactivation during the initiation and progression of clear cell RCCs. Copyright © 2002 John Wiley & Sons, Ltd.
Quantitative expansion of structural genomic alterations in the spectrum of neuroendocrine lung carcinomas
Authors: Gugger Mathias , Burckhardt Elisabeth , Kappeler Andreas , Hirsiger Hans , Laissue Jean A. , Mazzucchelli Luca
Published: October 2002

The pathogenesis and interrelationships of neuroendocrine lung carcinomas are not well understood. Tissue macro‐arrays prepared from surgical resection specimens from 35 patients with typical carcinoid (TC), six with atypical carcinoid (AC), 13 with large cell neuroendocrine carcinoma (LCNEC), and 15 with small cell lung carcinoma (SCLC) were investigated by fluorescence in situ hybridization (FISH) and immunohistochemistry. Hybridizations with locus‐specific DNA probes demonstrated a high incidence of deletion for the tumour suppressor genes p53 and retinoblastoma (Rb), and for the oncogene cyclin D1, comparable in all carcinoma types. Similarly, an increase of DNA copy number for the Her‐2/neu and c‐myc oncogenes was noted in all neoplasms. A more detailed quantitative analysis of the results, however, demonstrated increasing numbers of cells harbouring these genomic alterations, from low‐grade TC to highly malignant SCLC, with the exception of cyclin D1 deletion. Mutations of the p53 and Rb genes, as assayed by immunohistochemical studies, were observed at high incidence in high‐grade carcinomas, compared with a low incidence in the low‐grade carcinomas. Conversely, in all carcinoma types, neither membrane‐bound Her‐2/neu nor nuclear cyclin D1 was detected. It is concluded that structural genomic alterations are frequent in neuroendocrine lung carcinomas and that their occurrence may be underestimated by immunohistochemical studies alone. The quantitative expansion of the Rb, p53, c‐myc, and Her‐2/neu alterations towards high‐grade carcinomas suggests common pathogenetic mechanisms in the spectrum of these neoplasms. Copyright © 2002 John Wiley & Sons, Ltd.
Expression and regulation of collagenase‐2 (MMP‐8) in head and neck squamous cell carcinomas
Authors: Moilanen M. , Pirilä E. , Grénman R. , Sorsa T. , Salo T.
Published: October 2002

MMP‐8 (collagenase‐2) is the most effective collagenase to initiate type I collagen degradation. Since initiation of lysis of the surrounding collagen matrix is an essential prerequisite for carcinoma cells to spread, this study investigated the expression of MMP‐8 in squamous cell carcinoma (SCC) of the head and neck in vivo and in vitro. Most of the recently established head and neck carcinoma cell lines (22/25), corresponding tumour (5/7) and dermal (2/2) fibroblasts, commercial tongue carcinoma (HSC‐3 and SCC‐25), and transformed keratinocyte cell lines of the tongue (IHGK) and skin (HaCaT) expressed MMP‐8 mRNA analysed by the PCR method. Western blotting revealed a latent 50 kD band in concentrated culture media of carcinoma cells and corresponding tumour and dermal fibroblasts. The expression of immunoreactive MMP‐8 protein was reduced 30% by transforming growth factor beta‐1 (TGF‐β1) at 1 ng/ml concentration and 60% at 10 ng/ml concentration, but up‐regulated 2‐ and 2.5‐fold after 10 nM and 100 nM phorbol 12‐myristate 13 acetate (PMA), respectively. Immunohistological staining localized MMP‐8 protein in a few malignant invading tumour cell islands, certain fibroblasts, polymorphonuclear neutrophils (PMNs), and plasma cells. In situ hybridization revealed a faint sporadic signal in carcinoma cells of all eight tissue sections analysed. It is concluded that tissue from head and neck carcinomas can express MMP‐8 both in vivo and in vitro. Since the amount of MMP‐8 in carcinoma and stromal cells is rather low, MMP‐8 may have a potential role, with other collagenases, in the proteolysis of connective tissue associated with the spreading of invasive carcinoma. Copyright © 2002 John Wiley & Sons, Ltd.
Chondrodysplasia punctata (CDP) with features of the tibia‐metacarpal type and maternal phenytoin treatment during pregnancy
Authors: Wester U. , Brandberg G. , Larsson M. , Lönnerholm T. , Annerén G.
Published: October 2002

We describe a 2‐year‐old boy with chondrodysplasia punctata (CDP). The boy was exposed to phenytoin, in combination with carbamazepine, during pregnancy. There has been previous evidence for a connection between phenytoin exposure during pregnancy and chondrodysplasia punctata. The boy had clinical and some radiological characteristic features of CDP, of the tibia‐metacarpal type. We know of no other report on a child exposed to phenytoin during pregnancy who developed CDP of this type. Copyright © 2002 John Wiley & Sons, Ltd.
Rapid prenatal diagnosis of sickle cell diseases using oligonucleotide ligation assay coupled with laser‐induced capillary fluorescence detection
Authors: Day Nancy S. , Tadin Marija , Christiano Angela M. , Lanzano Patricia , Piomelli Sergio , Brown Stephen
Published: October 2002

Prenatal diagnosis of sickle cell diseases has been available for several years, and our laboratory has performed over 1000 prenatal diagnoses. However, currently available techniques are labor‐intensive and time‐consuming, and thus the diagnosis is delayed, making the mother's decision difficult. We describe a rapid, high‐throughput technique based on the ligation assay coupled with automated capillary fluorescence detection. This new approach allows the diagnosis of both Hgb S and Hgb C to be available in a few hours. We have utilized this technique in 30 prenatal diagnoses and found it to be in complete agreement with the standard diagnoses. Copyright © 2002 John Wiley & Sons, Ltd.
Comparison and integration of first trimester fetal nuchal translucency and second trimester maternal serum screening for fetal Down syndrome
Authors: Hang Lam Yung , Peng Lee Chin , Yuen Sin Sai , Tang Rebecca , Soo Wong Hong , Fun Wong Sai , Yee Tak Fong Danial , Hoi Yin Tang Mary , Hai Nin Woo Hennie
Published: October 2002

Background

It is uncertain whether first trimester nuchal translucency (NT) is more effective than the well‐established second trimester serum screening for fetal Down syndrome or whether their combination works best. We report data from a large multicentre non‐interventional trial in which all subjects underwent both first and second trimester screening.

Methods

All women who attended the obstetric clinic before 15 weeks' gestation were recruited. An ultrasound examination was performed at 10 to 14 weeks to measure the NT. The nuchal measurements were not acted upon unless the fetus showed gross features of hydrops fetalis. All women had serum alpha‐fetoprotein (AFP) and human chorionic gonadotrophin (hCG) assay at 15 to 20 weeks. The Down syndrome risk assigned by serum screening was disclosed and amniocentesis was offered if this assigned risk was ⩾1:250 or if the women were 35 years and older. The efficacy of different combinations of screening markers was compared.

Results

Between January 1997 and August 2000, 17 590 women were recruited (19% ⩾35 years old). After excluding subjects who miscarried, defaulted the serum test and other reasons, 16 237 pregnancies were analysed. Of these, 35 pregnancies were affected by Down syndrome (2.2 cases per 1000 pregnancies). At a false‐positive rate of 5%, the detection rate of Down syndrome by NT alone, NT and age, serum hCG, AFP and age, and NT, hCG, AFP and age were 61%, 69%, 73% and 86%, respectively.

Conclusion

Integration of NT and second trimester serum AFP and hCG assay yielded the best screening efficacy for Down syndrome. Copyright © 2002 John Wiley & Sons, Ltd.
Hypomandibular faciocranial dysostosis in consanguineous parents revealed by ultrasound prenatal diagnosis
Authors: Thauvin‐Robinet Christel , Rousseau Thierry , Laurent Nicole , Durand Christine , Maingueneau Catherine , Cormier‐Daire Valérie , Sagot Paul , Faivre Laurence , Nivelon‐Chevallier Annie
Published: October 2002

We report here the fourth case of hypomandibular faciocranial dysostosis (HFD). The diagnosis was made at birth on the association of severe retrognathia, microstomia, severe hypoglossia with glossoptosis, persistent buccopharyngeal membrane, median cleft palate, bifid uvula, down‐slanting palpebral fissures, short nose with anteverted nares, laryngeal hypoplasia, and low‐set ears. A severe microstomia and micrognathia were detected by ultrasound at 31 weeks of gestation. Interestingly, even though the present case exhibits many facial dysmorphic features characteristic of HFD, craniosynostosis was absent. This report suggests that craniosynostosis is not mandatory for the diagnosis of this condition. Furthermore, we present a new argument for an autosomal recessive mode of inheritance for HFD. Copyright © 2002 John Wiley & Sons, Ltd.
The importance of validating the diagnosis of coronary heart disease when measuring secondary prevention: a cross‐sectional study in general practice
Authors: Connolly Paul , Cupples Margaret E. , Cuene‐Grandidier Hazel , Johnston Dennis , Passmore Peter
Published: October 2002

Purpose

To compare levels of recorded risk factors and drug treatment between patients with validated and non‐validated diagnoses of coronary heart disease (CHD) in Northern Ireland.

Methods

Patients with a nitrate prescription in the previous year or a CHD Read code were identified from computer records of 25 practices, stratified by partnership size and area board. Computer and paper records of a random sample of 10% of these were searched for specified criteria to validate the diagnosis of CHD. The diagnosis was considered valid if the patient was found to have one or more positive investigations for CHD. Records of blood pressure, cholesterol, blood sugar, body mass index and drugs prescribed were taken into account.

Results

The combined practice population was 151 071; 7338 (4.86%) were identified by the computer search as meeting the defined entry criteria for CHD. Among the 10% random sample the diagnosis of CHD could not be validated for 36.5% (265/727). Significantly more patients with a validated than non‐validated diagnosis had recorded cholesterol levels below 5.0 mmol/l (55.8 vs. 34.5%, p < 0.001) and were prescribed aspirin (75.3 vs. 40.8%, p < 0.001), beta‐blockers (51.5 vs. 28.3%, p < 0.001), angiotensin‐converting‐enzyme inhibitors (29.2 vs. 15.5%, p < 0.001) and lipid‐lowering drugs (50.9 vs. 23.0%, p < 0.001). A recent nitrate prescription had a higher predictive value for validated CHD than a Read code for CHD alone (71.2 vs. 53.1%, p < 0.001). No other significant differences were found between the two groups regarding the extent or levels of recorded risk factors.

Conclusions

Patients with a validated diagnosis of CHD appear to be better managed than those whose diagnosis has not been confirmed. Validation of diagnosis has important implications for assessing the provision of secondary prevention and for clinical governance. Copyright © 2002 John Wiley & Sons, Ltd.
Patient variables associated with expectations for prescriptions and general practitioners' prescribing behaviour: an observational study
Authors: von Ferber Liselotte , Köster Ingrid , Prüss Ulrike
Published: October 2002

Objectives

To determine patients' needs and expectations for prescriptions as a function of demographic and illness‐associated variables versus outcome of consultation.

Design

Questionnaire study consisting of patient interview before and after consultation with general practitioner.

Setting

A total of 618 consecutive patients in the waiting room of nine general practices in Germany (Hesse).

Main outcome measures

Patient needs and expectations for prescriptions and agreement between expected outcome and prescriptions received.

Results

As their top priority for consultation (33% of group), patients expected to receive information about their illness. Their needs for prescriptions (26%) and expectations of receiving them (41%) were clearly lower than physician prescribing (56%). Marked interpatient differences emerged with regard to need/expectation for medication according to age, minor versus chronic illness, duration of treatment, and first‐time attendance, but this was not reflected in how often physicians prescribed. A total of 85% of patients expecting a prescription received one; 44% not expressing a need for medication were issued one. Although only 4% of patients would want a drug with questionable effectiveness, doctors wrote such prescriptions to no less than 21% of patients—and especially to those with minor, newly arisen ailments (33%). Nevertheless, patient satisfaction with their visit was very high (98%).

Conclusions

In Germany, patient needs and expectations for medication are clearly lower than prescribing tendencies, and marked differences between patient groups in their needs or expectations for prescriptions are not reflected in the rates of prescriptions received. Above all, patients with minor illnesses wish to receive information about their illness, and they do not expect prescriptions of drugs with questionable effectiveness. Copyright © 2002 John Wiley & Sons, Ltd.
Substituent effect on the [2 + 3] cycloaddition of (E)‐β‐Nitrostyrene with (Z)‐C,N‐Diarylnitrones
Authors: Baranski Andrzej
Published: October 2002

The kinetics of the title reaction were studied in toluene at 80 °C by means of HPLC. The overall rate constant (ktotal) of the reaction of (E)‐β‐nitrostyrene (1) with (Z)‐C‐phenyl‐N‐arylnitrones (2a–g) was found to increase with increasing Hammett σ‐constant, whereas in the case of (Z)‐C‐aryl‐N‐phenylnitrones (2g–p) and the same nitrostyrene the rate decreased. The substituent effect in these reactions is inconsistent with FMO treatments of cycloaddition rates. For both reaction series good linear relationships were obtained between log ktotal and the net charge on the carbon atom in the >CN(O)— moiety of the nitrones calculated by the AM1 method. Copyright © 2001 John Wiley & Sons, Ltd.
Kinetic study of methoxide‐promoted elimination reactions of some 1,1,1‐trichloro‐2,2‐bis(phenyl‐substituted)ethanes
Authors: Fontana Gianfranco , Frenna Vincenzo , Lamartina Liliana , Natoli Maria Concetta , Noto Renato
Published: October 2002

The methoxide‐promoted elimination reaction of some 1,1,1‐trichloro‐2,2‐bis(phenyl‐substituted)ethanes (1) was investigated. The ortho‐substituted derivatives were found to be less reactive than the corresponding ortho‐unsubstituted derivatives, irrespective of the nature of their substituent. The reactivity data were correlated with the 13C NMR chemical shift values of C‐β of either 1,1,1‐trichloro‐2,2‐bis(phenyl‐substituted)ethanes or 1,1‐dichloro‐2,2‐bis(phenyl‐substituted)ethenes and the better result was obtained for the former correlation. Activation parameters for the methoxide‐promoted elimination of 1 show very similar values for ortho‐substituted derivatives. The total data set seems to be more indicative, even if not compelling, of an irreversible E1cB mechanism. Copyright © 2001 John Wiley & Sons, Ltd.
Pyrolytic elimination reactions of sulfinate and sulfonate esters
Authors: McCulla Ryan D. , Cubbage Jerry W. , Jenks William S.
Published: October 2002

The barriers to pyrolytic unimolecular elimination by ethyl methanesulfonate and ethyl methanesulfinate were calculated for both five‐membered ring eliminations that yield acetaldehyde and six‐membered ring eliminations that yield ethylene. The experimental observation that related sulfinates undergo the five‐centered elimination and sulfonates the six‐centered elimination is reproduced by the calculations and rationalized in terms of a nucleophilicity/electrophilicity matching issue in the former and a charge‐separated transition state in the latter. Copyright © 2001 John Wiley & Sons, Ltd.
Microcalorimetry as a tool in mechanistic studies of organic reactions
Authors: Thibblin Alf
Published: October 2002

Isothermal microcalorimetry is a powerful tool in studies of organic reactions in solution. Both reaction kinetics and thermodynamic parameters at a single temperature are conveniently derived by this technique. Some applications of batch microcalorimetry in reaction mechanistic studies are reviewed. These include kinetic and thermodynamic studies of aromatization reactions of biologically interesting oxides, hydrates of aromatic hydrocarbons and studies of complex reactions and equilibria. Copyright © 2002 John Wiley & Sons, Ltd.
Structural characterization of the ternary solvent mixture methanol–acetonitrile–1‐propanol
Authors: Leitão Ruben Elvas , Martins Filomena , Ventura M. Cristina , Nunes Nelson
Published: October 2002

Refractive indices and ET values were measured for the ternary mixture methanol–acetonitrile–1‐propanol at 25.0 °C for 13 mole fractions, and also for the corresponding binary mixtures, methanol–1‐propanol, methanol–acetonitrile and 1‐propanol–acetonitrile, at 25.0 and 50.0 °C, at 10 different compositions. Solvent exchange equilibrium models were applied to the transition energy of the Dimroth–Reichardt ET(30) solvatochromic indicator in the binary systems and the Redlich–Kister polynomial was used to correlate excess ETN and nD values for the binary solvent mixtures data. The results allowed the analysis of synergetic behaviours, polarizability effects and preferential solvation trends both in the binary and in the ternary mixtures. Our results point towards the prevalence of specific solute–solvent–solvent interactions mainly due to hydrogen bonding by the hydroxylic components of the ternary mixture. Copyright © 2002 John Wiley & Sons, Ltd.
Competitive complexation in the cationic polymerization of isobutylene in a nonpolar medium
Authors: Wu Yixian , Wu Guanying
Published: October 2002

The cationic polymerization of isobutylene coinitiated by Al(i‐Bu)Cl2(Al) was carried out in mixed butane–butene fractions at −50 °C. The expected polymerization processes induced by the trace of moisture with Al system in the presence of a small amount of external electron‐donor modifiers, such as methyl acrylate (MA) and dimethyl sulfoxide (DMSO), were obtained. The experimental results showed that these polymerizations produced polymers with relatively high number‐average molecular weights and narrow molecular weight distributions (1.5–2.2). That the gel permeation chromatography traces of the polymers depended on the types and concentrations of external donors suggested that there existed competitive complexation reactions of various electron donors (H2O, MA, and DMSO) with the Al Lewis acid. The roles of external electron donors were to take part in the initiation step by competitive complexation and to modify the reactivity of the growing chain ends in the propagation step by mediation and/or solvation, which impaired the high reactivity of the original growing chain ends. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2209–2214, 2002
Synthesis and properties of waterborne self‐crosslinkable sulfo‐urethane silanol dispersions
Authors: Lewandowski Kevin , Krepski Larry R. , Mickus Daniel E. , Roberts Ralph R. , Heilmann Steven M. , Larson Wayne K. , Purgett Mark D. , Koecher Steven D. , Johnson Stephen A. , McGurran Daniel J. , Rueb Chris J. , Pathre Sadanand V. , Thakur Khalid A. M.
Published: October 2002

A novel type of crosslinkable waterborne polyurethane ionomer was prepared by the acetone process. Two new types of sulfonated diols compatible with this process were synthesized from dimethyl 5‐sodium sulfo isophthalate using a one‐ or two‐stage method. Isocyanate‐terminated polyurethane oligomers were prepared from the sulfonated diols with various combinations of diols and diisocyanates and subsequently reacted with amino silane derivatives. Stable, low‐volatile organic chemical, waterborne dispersions of the sulfo‐urethane silanol polymers spontaneously crosslink upon drying without extra additives or processing steps. Despite the lack of organic coalescing solvents, the dispersions have minimum film‐forming temperatures below 10 °C, regardless of glass‐transition temperature. Tensile strengths up to 6000 psi with elongations between 300 and 600% were obtained for the crosslinked films. The hard‐segment content of the films can be controlled to produce films with a Sward–Rocker hardness value up to 42. Through silane end‐group modification, the crosslinking density of the films can also be modified to produce polyurethanes with a wide range of physical properties. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 3037–3045, 2002
Lay constructions of decision‐making in cancer
Authors: Henman M.J. , Butow P.N. , brown R.F. , Boyle F. , Tattersall M.H.N.
Published: October 2002

In recent years there has been increased emphasis on involving people in decision‐making about their medical care. However, few studies have addressed the questions of why women with cancer want information, and what they believe to be the important factors influencing their decision‐making. In order to examine these questions 20 women with cancer were interviewed via telephone 2 weeks after their first consultation with one of 6 medical oncologists. Recruitment continued until informational redundancy was achieved.

While women cited the risk of recurrence, life expectancy, side‐effects, and quality of life as influencing their decisions, they placed at least as much emphasis on their personal relationship with the specialist. These ‘personal’ factors included: feeling that the doctor cared for, understood and respected them; that they could trust and have confidence in the doctor; that the doctor would give them enough time; that they would be listened to; and that the doctor would be open and honest. If these factors were felt to be present, many women were happy to accept the doctor's recommendation, confident that they would receive the optimum treatment. However, many women felt there was no decision to be made: further treatment must be undertaken to reduce risk, and minor variations in the treatment protocol were of little significance. These results underline the importance of establishing patient priorities and concerns before embarking on discussions about treatment. Copyright © 2002 John Wiley & Sons, Ltd.
Incidence of exercise‐induced arterial hypoxemia in prepubescent females
Authors: Laursen Paul B. , Tsang Garry C.K. , Smith Gareth J. , van Velzen Min V. , Ignatova B.B. , Sprules Erica B. , Chu Kelly S. , Coutts Kenneth D. , McKenzie Donald C.
Published: October 2002

Due to the recent discovery of exercise‐induced arterial hypoxemia (EIAH) in healthy active women with normal levels of peak oxygen uptake (${\rm V'}_{{\rm O}_{\rm 2} {\rm peak}}$), this study examined the incidence of EIAH in prepubescent females. Nineteen healthy, active, prepubescent females (${\rm \overline X}$ ± SD: age = 11.1 ± 1.6 years; height = 145.8 ± 9.1 cm; weight = 35.6 ± 7.0 kg) performed a progressive maximal exercise test on an electronically braked cycle ergometer starting at 0 W and increasing power by 15 W · min−1. During this test, expired gases, heart rate (HR), and percent arterial oxyhemoglobin saturation (%SaO2) were measured.

Results for physiological variables at maximal exercise were as follows: ${\rm V'}_{{\rm O}_{\rm 2} {\rm peak}}$ = 43.7 ± 7.0 ml · kg−1 · min−1; HRmax = 199 ± 5 beats · min−1; %SaO2 = 96.6 ± 1.2%. For nearly all subjects, the %SaO2 at maximal exercise was above levels that would reduce ${\rm V'}_{{\rm O}_{\rm 2} {\rm peak}}$. Therefore, in comparison to previous reports of EIAH in adult women with similar ${\rm V'}_{{\rm O}_{\rm 2} {\rm peak}}$, EIAH does not appear to occur in the prepubescent female population. Pediatr Pulmonol. 2002; 34:37–41. © 2002 Wiley‐Liss, Inc.
Transmission of tuberculosis from adults to children in a Paris suburb
Authors: Madhi Fouad , Fuhrman Claire , Monnet Isabelle , Atassi Kinan , Poirier Christine , Housset Bruno , Delacourt Christophe
Published: October 2002

Tuberculosis in children is often acquired by contact with a family or household member. The aim of our study was to evaluate risk factors for latent infection and active disease in exposed children in a suburb of Paris. We examined medical records for the period 1997–2000 at six departmental centers for medical prevention in Val de Marne.

Thirty‐nine patients aged 18 years or more with M. tuberculosis‐positive sputum samples, and living with children or adolescents, were identified. Ninety‐one children, aged 3 months–17 years, were exposed to these index cases. All the children initially underwent a tuberculin skin test and chest radiography, and children with no criteria for latent infection or active disease at time of initial evaluation were asked to attend a second evaluation 3 months later. Overall, 20 of the 91 (22%) children were infected, including 4 children identified only at the second evaluation. Eight (40%) of the 20 infected children had active disease, including 2 of the 4 children identified at the second evaluation. The risk of infection was not influenced by the children's age, but was significantly associated with three characteristics of the adult cases, i.e., age younger than 40 years, presence of cavitary lesions, and smears with more than 100 bacilli per microscopic field.

In conclusion, our results call for early examination of all exposed children, in order to prevent infection and progression to active disease, and for a routine second evaluation after the adult contact has ended. Pediatr Pulmonol. 2002; 34:159–163. © 2002 Wiley‐Liss, Inc.
SWOG‐9510: evaluation of topotecan in hormone refractory prostate cancer: A southwest oncology group study
Authors: Klein Catherine E. , Tangen Catherine M. , Braun Thomas J. , Hussain Maha H.A. , Peereboom David M. , Nichols Craig R. , Rivkin Saul E. , Dakhil Shaker R. , Crawford E. David
Published: October 2002

BACKGROUND

Prostate cancer is the most common malignancy in American men, and as many as 70% of those initially treated for localized disease will ultimately progress and be considered candidates to receive therapy for metastatic cancer [Fuks et al.: Int J Radiat Oncol Bio Phys 21:537–547, 1991; Chodak et al.: N Engl J Med 330:246–248, 1994]. Although most will respond initially to hormone manipulation, essentially all will fail and require additional therapy. No standard chemotherapy approach has been shown to prolong survival significantly, and new agents are desperately needed. Topotecan is a new topoisomerase‐1 inhibitor whose early investigation suggested possible activity in hormone‐refractory prostate cancer.

METHODS

In this phase II trial, patients having failed one or two prior androgen ablative therapies were treated with 21‐day continuous intravenous infusions of topotecan at a dose of 0.5 mg/m2 per day every 28 days.

RESULTS

Twenty‐six eligible patients were entered on the study. There were no confirmed tumor responses. Median survival was 9 months. The most common toxicities were hematologic, with 8 of 24 assessable patients experiencing grade 4 toxicity.

CONCLUSION

Topotecan infusions at this dose are ineffective in the management of hormone‐refractory prostate cancer. Prostate 52: 264–268, 2002. © 2002 Wiley‐Liss, Inc.
Does amount or type of alcohol influence the risk of prostate cancer?
Authors: Albertsen Katrine , Grønbæk Morten
Published: October 2002

BACKGROUND

Prostate cancer is one of the most common cancers among men, and it is unknown whether alcohol is associated with the development of prostate cancer.

METHODS

The relationship between amount or type of alcohol and prostate cancer was studied in a pooled prospective setting conducted from 1976 to 1994 in Copenhagen, Denmark. The study population consisted of 12,989 subjects drawn from three different cohorts. During a mean follow‐up of 12.3 yr, 233 subjects developed prostate cancer.

RESULTS

None of the estimates for consumed amount of total alcohol diverged significantly from unity. Furthermore, drinkers of more than 13 beers, 13 glasses of wine, and 13 drinks of spirits had a risk of 1.03 (CI: 0.67, 1.60), 0.92 (CI: 0.42, 1.99), and 1.01 (CI: 0.52, 1.98), respectively, compared with abstainers of the given beverage of alcohol.

CONCLUSION

These results suggest that neither amount nor type of alcohol is associated with the risk of prostate cancer. Prostate 52: 297–304, 2002. © 2002 Wiley‐Liss, Inc.
Molecular dynamics simulations of a double unit cell in a protein crystal: Volume relaxation at constant pressure and correlation of motions between the two unit cells
Authors: Walser Regula , Hünenberger Philippe H. , van Gunsteren Wilfred F.
Published: October 2002

Eight molecular dynamics simulations of a double crystal unit cell of ubiquitin were performed to investigate the effects of simulating at constant pressure and of simulating two unit cells compared to a single unit cell. To examine the influence of different simulation conditions, the constant‐pressure and constant‐volume simulations were each performed with and without counterions and using two different treatments of the long‐range electrostatic interactions (lattice‐sum and reaction‐field methods). The constant‐pressure simulations were analyzed in terms of unit cell deformation and accompanying protein deformations. Energetic and structural properties of the proteins in the simulations of the double unit cell were compared to the results of previously reported one‐unit‐cell simulations. Correlation between the two unit cells was also investigated based on relative translational and rotational movements of the proteins and on dipole fluctuations. The box in the constant‐pressure simulations is found to deform slowly to reach convergence only after 5–10 ns. This deformation does not result from a distortion in the structure of the proteins but rather from changes in protein packing within the unit cell. The results of the double‐unit‐cell simulations are closely similar to the results of the single‐unit‐cell simulations, and little motional correlation is found between the two unit cells. Proteins 2002;48:327–340. © 2002 Wiley‐Liss, Inc.
Changing times in pharmaceutical statistics: 1980–2000
Authors: Day Simon
Published: October 2002

Pharmaceutical statistics has changed significantly in the last twenty years. This paper reviews some of the changes in that time, from a past dominated by the P‐value to the present day. Although the last twenty years have seen significant improvements, statistical shortcomings are not a rarity, and the impact of the public perception of statistics, medicine and the pharmaceutical industry on pharmaceutical statistics is assessed. Copyright © 2002 John Wiley & Sons, Ltd.
The utility of experimental design short courses?
Authors: Krebs‐Brown Axel J. , Yahyah Mohammad , Kempson Robert
Published: October 2002

This paper describes the one‐day introduction to experimental design training course at GlaxoSmithKline. In particular, the use of paper helicopter experiments has been an effective and efficient method for teaching experimental design techniques to scientific and other staff. A good supporting strategy by which the statistics department provides back‐up following the course is essential. Copyright © 2002 John Wiley & Sons, Ltd.
Computer (In)Security 3. Computer system archive and restore
Authors: McDowall R.D.
Published: October 2002

In the third of an occasional series of articles for the QAJ, the author discusses requirements for computer system archive and restore activities. The Electronic Records and Electronic Signatures final rule (21 CFR 11) requires electronic records to be held electronically for the records retention period. How long records must be retained and the implications for organisations will be discussed in this article. Copyright © 2002 John Wiley & Sons, Ltd.
A qualitative examination of FDA warning letters ‐ what can we learn from GCP inspections?
Authors: Wilsher Colin R
Published: October 2002

Good clinical practice (GCP) inspections are now a global reality and it may be timely to review the outcome of the largest set of detailed information (warning letters) from the foremost GCP inspectors (the Food and Drug Administration (FDA). Looking at qualitative information, it provides us with a detailed insight into the workings of GCP inspections. From this information, we can learn what ‘pitfalls’ to avoid and how to pro‐actively build safeguards to prevent future problems. This review particularly highlights the fact that FDA inspectors do not limit themselves solely to traditional clinical records when verifying submitted data. Locating these ‘other’ sources and ensuring consistency is vital to pre‐inspection readiness. Sponsors, CROs and investigators must ensure that adequate procedures are in place and that staff are well trained on these procedures. Copyright © 2002 John Wiley & Sons, Ltd.
Use of medical chart audits in evaluating resident clinical competence: lessons learned from the development and refinement of a study protocol (Implications for use in meeting ACGME evaluation requirements)
Authors: Proden Camille , Carravallah Laura , Taylor D. Kay
Published: October 2002

Medical chart auditing, one strategy that may be employed to assess resident clinical competence, represents both a tool to evaluate performance, and a vehicle for change. It has been demonstrated that an ongoing chart audit and feedback system can successfully affect resident compliance with practice guidelines and is thus associated with improvements in performance. In the study described here, however, the vehicle for change was an enhanced curriculum, the success of which was subsequently measured via chart audits. Regardless of the primary purpose of such audits, the study investigators gleaned important information about the conduct of the audits that can be applied to current efforts by medical educators to incorporate chart audits into a comprehensive plan to meet new Accreditation Council for Graduate Medical Education (ACGME) program evaluation mandates. Copyright © 2002 John Wiley & Sons, Ltd.
Quantum chemical study of several monocyclic complex β‐lactam C‐3, C‐4, and N‐derivatives, and β‐ring model molecules
Authors: Palafox Mauricio Alcolea , Iza Nerea , Gil Manuel , Núñez José Luís
Published: October 2002

A quantum chemical study of several complex monocyclic 4‐benzoyl‐4‐phenyl‐β‐lactam derivatives was carried out using cyclobutane, azetidine, 2‐azetidinone, 1‐methyl‐2‐azetidinone, and 3‐methyl‐2‐azetidinone as model compounds. The optimum geometry was obtained for the different conformations. The planarity of the ring was discussed in terms of the influence of the substituents on the amide resonance. To better analyze the amide resonance and the activity of the β‐lactam ring, a vibrational study was also carried out. To examine the influence of solvent polarity on the carbonyl bands, the Fourier transform–infrared (FT‐IR) spectra of the β‐lactam monocyclic derivatives were recorded in CCl4, C6H6, and CHCl3 solutions. The normal vibrations of the β‐lactam ring in the model compounds were characterized and used in the analysis of the β‐ring of more complex derivatives. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
A posteriori corrections to multireference limited configuration interaction based on a Brillouin–Wigner perturbative analysis
Authors: Hubac̆ I. , Mach P. , Wilson S.
Published: October 2002

A new a posteriori correction to the method of limited configuration interaction is described that attempts to restore a linear scaling with particle number. The corrections are based on an analysis of the limited configuration interaction method in terms of the Brillouin–Wigner perturbation theory using a Lippmann–Schwinger‐like equation. The new correction procedure is general and, in this work, the application to the limited multireference configuration interaction approximation is considered in some detail. An illustrative application to the rigid rotation of the diimine molecule is presented and the results are compared with those obtained by employing Davidson‐like corrections and the corresponding full configuration interaction energies. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002
Convergence of exchange lattice summations in direct‐space polymer calculations
Authors: Jacquemin Denis , Fripiat Joseph G. , Champagne Benoît
Published: October 2002

We studied various stereoregular polymers [monoatomic (beryllium chains), diatomic (hydrogen fluoride chains and polyyne) and polyatomic (polyethylene and polymethineimine)] and monitored the effective convergence of the lattice summations, especially the one corresponding to the exchange contribution. The relations to geometry (bond length alternation), pseudo–linear‐dependencies, basis set, and band gap are addressed. In all cases, including for extremely conjugated systems, the exchange is found to present an exponentially decreasing, rather than 1/j2, behavior, although convergence, in some cases, can be very slow. © 2002 Wiley Periodicals, Inc. Int J Quantum Chem, 2002