bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial and mixture models for recurrent event processes
Authors: Dean C. B. , Nathoo F. , Nielsen J. D.
Published: August 2007

Studies of recurring infection or chronic disease often collect longitudinal data on the disease status of subjects. Two types of models may be envisioned for the analysis of such data: counting process models or multi‐state transitional models. We consider both scenarios in the specific case where the population consists of mixtures. A flexible semi‐parametric model for analyzing longitudinal panel count data is presented. Discrete mixtures of smooth counting process intensity forms are considered, including mixtures of splines, which permit time‐varying covariate effects, with the so‐called proportional intensity model as a limiting case. For recurrent events handled in a multi‐state transitional model framework, individuals may be said to occupy one of a discrete set of states and interest centers on the transition process between states. We examine the use of mixed Markov models for the analysis of such longitudinal data where the processes corresponding to different subjects may be correlated spatially over a region. Both discrete and continuous‐time models incorporating spatially correlated random effects are discussed. Examples illustrate the methods discussed including a study of recurrent weevil infestation, and one to assess the effectiveness of a pheromone treatment in disturbing the mating habits of the cherry bark tortrix moth. Copyright © 2007 John Wiley & Sons, Ltd.
Bayesian analysis of the multivariate geographical distribution of the socio‐economic environment in England
Authors: Abellan Juan J. , Fecht Daniela , Best Nicky , Richardson Sylvia , Briggs David J.
Published: August 2007

In this paper we analyse the geographical distribution of theIndices of Deprivation 2004, a set of seven area‐based indices measuring multiple dimensions of socio‐economic status (SES) related to income, employment, education, health, access to services and housing, crime, and living environment in England at district level. We first study all the seven SES ‘domains’ separately using spatial hierarchical models to assess the level of underlying geographical structure in each of them. We then explore their joint relationships using a spatial factor model that extracts the information common and specific to the income, employment and education domains and regress the other domains on the extracted components. We use Bayesian inference throughout. Results show that all seven domains present strong spatial structure. The income, employment, education and health domains largely share the same information, which moderately overlaps with the crime and environment domains. The domain on access to services and housing is quite different from the others. The geographical patterns found in the latent common and specific factors are however difficult to interpret without further complementary information. Further investigation is required to identify plausible causal processes related to current economic and regional policies, and also to historic factors and their long‐lasting socio‐economic legacy. Copyright © 2007 John Wiley & Sons, Ltd.
Developing a parenting skills‐and‐support intervention for mothers with eating disorders and pre‐school children: part 2. Piloting a group intervention
Authors: Bryant‐Waugh Rachel , Turner Hannah , Jones Ceri , Gamble Caroline
Published: August 2007

Objective

This paper reports the development and preliminary evaluation of a group intervention for mothers with eating disorders who have pre‐school children.

Method

This study aimed to define and clarify intervention components, and make a preliminary assessment of the feasibility, acceptability and potential for achieving clinical change of the group intervention.

Results

An eight‐session group intervention was developed and piloted with four or five participants in each of three trials. Feedback demonstrated that the majority of participants tolerated and valued this type of intervention, and felt it had a positive impact on parenting skills and confidence. Preliminary evaluation suggested reduction in parenting concerns and improved depression scores following group participation.

Discussion

The groups revealed a range of difficulties experienced by such mothers. An intervention designed to address the identified issues could have important beneficial effects on child development and provide a valuable means of support to this patient group. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
Look at yourself: can body image therapy affect the cognitive and emotional response to seeing oneself in the mirror in eating disorders?
Authors: Vocks Silja , Wächter Alexandra , Wucherer Maike , Kosfelder Joachim
Published: August 2007

The study examined whether the extent of negative body‐related thoughts and emotions evoked by looking in a mirror can be changed by cognitive‐behavioural body image therapy (BIT) and whether any remaining cognitive and affective responses dropped faster after the treatment. Females with eating disorders (n = 17) looked in a mirror for 40 minutes under standardised conditions before and after BIT. A control group (CG) (n = 24) was also exposed to their own bodies twice. Cognitive and affective reactions were assessed four times during the session. Hierarchical Linear Modelling revealed that among eating‐disordered patients, the entrance levels of negative thoughts and feelings were lower at post compared to pre‐BIT, whereas they remained stable in the CG. The extent of reduction of the remaining body image distress was not changed after the treatment. BIT seems to be a potent treatment of negative emotions and cognitions in an in vivo situation. Copyright © 2007 John Wiley & Sons, Ltd and Eating Disorders Association.
A cell‐centred arbitrary Lagrangian–Eulerian (ALE) method
Authors: Maire Pierre‐Henri , Breil Jérôme , Galera Stéphane
Published: August 2007

We present an original and accurate unstructured cell‐centred arbitrary Lagrangian–Eulerian algorithm devoted to the simulation of multi‐material fluid flows. Copyright © 2007 John Wiley & Sons, Ltd.
An immersed boundary method for the incompressible Navier–Stokes equations in complex geometry
Authors: Sheu Tony W. H. , Ting H. F. , Lin R. K.
Published: August 2007

A nodally exact convection–diffusion–reaction scheme developed in Cartesian grids is applied to solve the flow equations in irregular domains within the framework of immersed boundary (IB) method. The artificial momentum forcing term applied at certain points in the flow and inside the body of any shape allows the imposition of no‐slip velocity condition to account for the body of complex boundary. Development of an interpolation scheme that can accurately lead to no‐slip velocity condition along the IB is essential since Cartesian grid lines generally do not coincide with the IB. The results simulated from the proposed IB method agree well
with other numerical and experimental results for several chosen benchmark problems. The accuracy and fidelity of the IB flow solver to predict flows with irregular IBs are therefore demonstrated. Copyright © 2007 John Wiley & Sons, Ltd.
Three‐dimensional lattice Boltzmann interface capturing method for incompressible flows
Authors: Zheng H. W. , Shu C. , Chew Y. T. , Sun J. H.
Published: August 2007

This paper presents a new three‐dimensional lattice Boltzmann interface capturing method for incompressible flows following the work of Zheng et al. (Phys. Rev. E 2005; 72:056705). As shown in the paper, the fourth rank isotropic property of the lattice tensor is not needed for interface capturing. As a result, a new D3Q7 (D3 means three dimensional, Q7 means seven velocity bits) lattice velocity model and its associated equilibrium distribution functions are proposed in the paper. The proposed model is validated by comparing its numerical results with those of an existing lattice Boltzmann interface
capturing model (J. Comput. Phys. 2004; 198:628–644) and three‐dimensional direction split flux‐corrected transport method (Int. J. Numer. Meth. Fluids 1997; 24:671–691). Numerical results showed that the present model performs better than the existing methods in capturing the interface. It greatly improves the computational efficiency and saves at least half of the memory as compared to other lattice Boltzmann interface capturing models. Copyright © 2007 John Wiley & Sons, Ltd.
Arbitrary Lagrangian Eulerian method for laser plasma simulations
Authors: Kapin T. , Kuchařík M. , Limpouch J. , Liska R. , Váchal P.
Published: August 2007

The arbitrary Lagrangian Eulerian (ALE) 2D code has been developed in Cartesian and cylindrical geometries. For laser plasma simulations, the code has been extended by heat conductivity, laser absorption and QEOS equation of state. Three particular problems (originated in laser plasma experiments) for which pure Lagrangian simulation fails demonstrate the necessity of using the ALE method. Copyright © 2007 John Wiley & Sons, Ltd.
The steady Navier–Stokes/energy system with temperature‐dependent viscosity—Part 2: The discrete problem and numerical experiments
Authors: Pérez Carlos E. , Thomas Jean‐Marie , Blancher Serge , Creff René
Published: August 2007

In this second part, we analyse the associated discrete problem arising from a conforming finite element method formulation of the mathematical model presented in the first part. Thus, existence and uniqueness of the discrete solution when using small enough data are stated following the same strategy used in the continuous case,
with a Cea's type error estimate established as the main result. Some numerical experiments, steady and unsteady, are performed, which allow us to validate the previous mathematical model and its discrete approximation. Copyright © 2007 John Wiley & Sons, Ltd.
Closure models for multimaterial cells in arbitrary Lagrangian–Eulerian hydrocodes
Authors: Shashkov M.
Published: August 2007

High‐speed multimaterial flows with strong shear deformations occur in many problems. Due to the nature of shock wave propagation in complex materials, the arbitrary Lagrangian–Eulerian (ALE) methods are currently the only proven technology to simulate such problems. In ALE methods, the mesh does not move with the fluid, so that it is unavoidable that mixed cells containing two or more materials will appear; such mixed cells require a special closure model to be well posed. In this paper, we will discuss some of the possible models. Published in 2007 by John Wiley & Sons, Ltd.
A numerical method for forced convection in porous and homogeneous fluid domains coupled at interface by stress jump
Authors: Chen Xiaobing , Yu Peng , Winoto S. H. , Low Hong‐Tong
Published: August 2007

A numerical method was developed for flows involving an interface between a homogeneous fluid and a porous medium. It is based on the finite volume method with body‐fitted and multi‐block grids. The Brinkman–Forcheimmer extended model was used to govern the flow in the porous medium region. At its interface, the flow boundary condition imposed is a shear stress jump, which includes the inertial effect, together with a continuity of normal stress. The thermal boundary condition is continuity of temperature and heat flux.

The forced convection through
a porous insert over a backward‐facing step is investigated. The results are presented with flow configurations for different Darcy numbers, 10−2 to 10−5, porosity from 0.2 to 0.8, Reynolds number from 10 to 800, and the ratio of insert length to channel height from 0.1 to 0.3. The heat transfer is improved by using porous insert. To enhance the heat transfer with minimal frictional losses, it is preferable to have a medium length of insert with medium Darcy number, and larger Reynolds number. The interfacial stress jump coefficients β and β1 were varied from −1 to 1, and within this range the average and local lower‐wall Nusselt numbers are not sensitive to the parameters. Copyright © 2007 John Wiley & Sons, Ltd.
A hybrid immersed boundary and material point method for simulating 3D fluid–structure interaction problems
Authors: Gilmanov Anvar , Acharya Sumanta
Published: August 2007

A numerical method is developed for solving the 3D, unsteady, incompressible Navier–Stokes equations in curvilinear coordinates containing immersed boundaries (IBs) of arbitrary geometrical complexity moving and deforming under forces acting on the body. Since simulations of flow in complex geometries with deformable surfaces require special treatment, the present approach combines a hybrid immersed boundary method (HIBM) for handling complex moving boundaries and a material point method (MPM) for resolving structural stresses and movement. This combined HIBM & MPM approach is presented as an effective approach for solving fluid–structure interaction (FSI) problems. In the HIBM, a curvilinear grid is defined and the variable values at grid points adjacent to a boundary are forced or interpolated to satisfy the boundary conditions. The MPM is used for solving the equations of solid structure and communicates with the fluid through appropriate interface‐boundary conditions.

The governing flow equations are discretized on a non‐staggered grid layout using second‐order accurate finite‐difference formulas. The discrete equations are integrated in time via a second‐order accurate dual time stepping, artificial compressibility scheme. Unstructured, triangular meshes are employed to discretize the complex surface of the IBs. The nodes of the surface mesh constitute a set of Lagrangian control points used for tracking the motion of the flexible body. The equations of the solid body are integrated in time via the MPM. At every instant in time, the influence of the body on the flow is accounted for by applying boundary conditions at stationary curvilinear grid nodes located in the exterior but in the immediate vicinity of the body by reconstructing the solution along the local normal to the body surface. The influence of the fluid on the body is defined through pressure and shear stresses acting on the surface of the body.

The HIBM & MPM approach is validated for FSI problems by solving for a falling rigid and flexible sphere in a fluid‐filled channel. The behavior of a capsule in a shear flow was also examined. Agreement with the published results is excellent. Copyright © 2007 John Wiley & Sons, Ltd.
Immersed boundary conditions method for unsteady flow problems described by the Laplace operator
Authors: Husain S. Z. , Floryan J. M.
Published: August 2007

An implicit, spectral algorithm for the analysis of unsteady flow problems governed by the Laplace operator in corrugated geometries is described. The algorithm treats the physical boundary conditions as constraints along lines internal to the solution domain. The method eliminates the need for coordinate generation and can be quickly adapted to changing geometries. Various tests confirm the spectral accuracy in space and the first‐ and second‐order accuracies in time. Copyright © 2007 John Wiley & Sons, Ltd.
A general Riemann solver for Euler equations
Authors: Wu Hao , Shen Zhijun
Published: August 2007

In this paper, we present a general Riemann solver which is applied successfully to compute the Euler equations in fluid dynamics with many complex equations of state (EOS). The solver is based on a splitting method introduced by the authors. We add a linear advection term to the Euler equations in the first step, to make the numerical flux between cells easy to compute. The added linear advection term is thrown off in the second step. It does not need an iterative technique and characteristic wave decomposition for computation. This new solver is designed to permit the construction of high‐order approximations to obtain high‐order Godunov‐type schemes. A number of numerical results show its robustness. Copyright © 2007 John Wiley & Sons, Ltd.
Fluid–structure interaction problems in free surface flows: Application to boat dynamics
Authors: Formaggia L. , Miglio E. , Mola A. , Parolini N.
Published: August 2007

In this paper, we present some recent studies on fluid–structure interaction problems in the presence of free surface flow. We consider the dynamics of boats simulated as rigid bodies. Several hydrodynamic models are presented, ranging from full Reynolds averaged Navier–Stokes equations to reduced models based on potential flow theory. Copyright © 2007 John Wiley & Sons, Ltd.
Equity in health and health care in a decentralised context: evidence from Canada
Authors: Jiménez‐Rubio Dolores , Smith Peter C. , Van Doorslaer Eddy
Published: August 2007

The impact of administrative decentralisation on equity in health and health care is an important unresolved issue in the health policy debate. Predictions from the limited theoretical literature and the relevant empirical research are both insufficient to draw any firm conclusions. Many countries are nevertheless experimenting with decentralisation policies in the absence of research evidence. This paper presents an exploratory empirical analysis of decentralisation by investigating the spatial dimensions of health‐related equity in Canada, a highly decentralised setting. Using data from the 2001 Canadian Community Health Survey, we apply a decomposition method of the Concentration Index to explore whether income‐related inequalities in health and inequities in the use of health care are more likely to be due to gaps between rich and poor Canadian provinces rather than to differences between rich and poor individuals within them. The results show that within area variation is the most important source of income‐related health inequality, while income‐related inequities in health care use are mostly driven by differences between provinces. Copyright © 2007 John Wiley & Sons, Ltd.
Antiviral activity of telaprevir (VX-950) and peginterferon alfa-2a in patients with hepatitis C
Authors: Forestier Nicole , Reesink Hendrik W. , Weegink Christine J. , McNair Lindsay , Kieffer Tara L. , Chu Hui-May , Purdy Susan , Jansen Peter L.M. , Zeuzem Stefan
Published: August 2007

Telaprevir (VX-950), an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, substantially decreased plasma HCV RNA levels in a prior clinical study. The present study evaluated viral kinetics and safety during dosing with telaprevir alone and in combination with peginterferon alfa-2a for 14 days. Previously untreated patients with genotype 1 hepatitis C were randomized to receive placebo and peginterferon alfa-2a (n = 4); telaprevir (n = 8); or telaprevir and peginterferon alfa-2a (n = 8). Telaprevir was given as 750 mg oral doses every 8 hours; peginterferon alfa-2a was given as weekly 180 μg subcutaneous injections. The median change in HCV RNA from baseline to day 15 was −1.09 log10 (range, −2.08 to −0.46) in the placebo and peginterferon alfa-2a group; −3.99 log10 (range, −5.28 to −1.26) in the telaprevir group, and −5.49 log10 (range, −6.54 to −4.30) in the telaprevir and peginterferon alfa-2a group. Day 15 HCV RNA levels were undetectable in 4 patients who received telaprevir and peginterferon alfa-2a and in 1 patient who received telaprevir alone. No viral breakthrough occurred in patients who received telaprevir and peginterferon alfa-2a. The majority of adverse events were mild. There were no serious adverse events or premature discontinuations. Twelve weeks after starting off-study standard therapy, HCV RNA was undetectable in all 8 patients in the telaprevir and peginterferon alfa-2a group, 5 patients in the telaprevir group, and 1 patient in the placebo and peginterferon alfa-2a group.

Conclusion:

This study confirmed the substantial antiviral effects of telaprevir and showed an increased antiviral effect of telaprevir combined with peginterferon alfa-2a. (Hepatology 2007;46:640–648.)
The association of up‐regulation of X‐linked inhibitor of apoptosis protein with cell adhesion‐mediated drug resistance in U937 cells
Authors: Wang Xiaofang , Wang Chun , Qin You‐wen , Yan Shi‐ke , Gao Yan‐rong
Published: August 2007

An increasing body of evidence indicates that environmental factors may contribute to the drug resistance of acute myeloid leukaemia (AML). CAM‐DR (cell adhesion‐mediated drug resistance) is a reversible, de novo drug resistance induced by adhesion of tumour cell lines to fibronectin (FN). Adhesion was demonstrated to directly regulate the apoptotic machinery. And it was observed in previous studies that high levels of X‐linked inhibitor of apoptosis protein (XIAP) were related to resistance to chemotherapeutics in many cancer cell lines. However, whether XIAP is relevant to CAM‐DR of AML cells is unknown. In this report, we demonstrated that the mRNA and protein levels of XIAP were increased by 96.15% and 120.92%, respectively in U937 cells cocultured with FN as compared with controls. Antisense oligonucleotides targeting XIAP down‐regulated the expression of XIAP and sensitized U937 cells to daunorubicin. In addition, we investigated the signalling pathway involved in the upregulation of XIAP. The levels of phosphorylated Akt (Ser473) were elevated in U937/FN cells and the phosphatidylinositol 3‐kinase (PI3K) inhibitor LY294002 suppressed XIAP expression and restored the chemosensitivity to daunorubicin. Our findings suggested that adhesion‐dependent activation of the PI3K/Akt/XIAP pathway may be one of the factors involved in the CAM‐DR of U937 cells. Targeting this pathway may be a useful approach to improve the therapeutic responsiveness of leukaemia cells. Copyright © 2007 John Wiley & Sons, Ltd.
Organochlorines and risk of non‐Hodgkin lymphoma
Authors: Spinelli John J. , Ng Carmen H. , Weber Jean‐Philippe , Connors Joseph M. , Gascoyne Randy D. , Lai Agnes S. , Brooks‐Wilson Angela R. , Le Nhu D. , Berry Brian R. , Gallagher Richard P.
Published: August 2007

Organochlorine chemicals and polychlorinated biphenyls (PCBs) have been suspected as possible risk factors for non‐Hodgkin lymphoma (NHL). We investigated PCBs and organochlorine pesticides and risk of NHL in a population‐based case–control study in British Columbia, Canada. Congeners of PCBs (including dioxinlike congeners) and pesticides or pesticide metabolites were measured in plasma of 422 pretreatment cases and 460 control subjects. This is so far the largest study to examine organochlorines in plasma to date. Several dioxin‐like PCB congeners were associated with increased risk of NHL, including dioxin‐like PCB nos. 118 and 156 with odds ratios (OR) for the highest versus lowest quartile between 1.6 and 1.8. Several non‐dioxin‐like congeners also showed significant associations. The PCB congener with the strongest association was no. 180 with an OR for the highest versus the lowest quartile of 1.83 (95% confidence interval = 1.18–2.84). Six pesticide analytes also showed a significant association with NHL; β‐hexachlorocyclohexane, p,p′‐DDE, hexachlorobenzene, mirex, oxychlordane and trans‐nonachlor. The strongest association was found for oxychlordane, a metabolite of the pesticide chlordane (highest vs. lowest quartile OR = 2.68, 95% confidence interval = 1.69–4.24). Our results provide further evidence that organochlorines contribute to NHL risk. © 2007 Wiley‐Liss, Inc.
Leisure‐time physical activity patterns and risk of colon cancer in women
Authors: Wolin Kathleen Y. , Lee I‐Min , Colditz Graham A. , Glynn Robert J. , Fuchs Charles , Giovannucci Edward
Published: August 2007

Although physical activity has been consistently associated with lower risk of colon cancer, many details of the relationship remain unclear. We assessed the relation between physical activity and risk of colon cancer in 79,295 women aged 40–65 who were free of cancer, ulcerative colitis and Crohn's disease and who reported their leisure‐time physical activity in 1986; 547 cases were identified through 2002. Women who expended more than 21.5 metabolic equivalent hr/week of physical activity had a relative risk (RR) of colon cancer of 0.77 (95% CI 0.58–1.01), compared to women who expended <2 metabolic equivalent hr/week. The association was stronger for distal than proximal tumors. Among women whose only reported activity was walking, there was a decreased risk of colon cancer in women walking 1–1.9 hr/week (RR = 0.69, 95% CI 0.47–1.03) compared to those who did not walk. Results were similar for increased amounts of walking, but there was no evidence of a dose response relation. Among women who participated in moderate or vigorous activity, increasing hours of activity were also associated with a decreased risk of colon cancer (p for trend = 0.01); women exercising >4 hr/week had a 40% lower risk of colon cancer than those exercising <1 hr/week (RR = 0.56, 95%CI 0.33–0.94). Long‐term physical activity was not associated with risk of colon cancer, but the number of cases was small. A significant inverse association exists between physical activity, including that of moderate intensity, such as walking, and risk of colon cancer in women that is more pronounced for distal tumors. © 2007 Wiley‐Liss, Inc.
High load for most high risk human papillomavirus genotypes is associated with prevalent cervical cancer precursors but only HPV16 load predicts the development of incident disease
Authors: Gravitt Patti E. , Kovacic Melinda Butsch , Herrero Rolando , Schiffman Mark , Bratti Concepcion , Hildesheim Allan , Morales Jorge , Alfaro Mario , Sherman Mark E. , Wacholder Sholom , Rodriguez Ana‐Cecilia , Burk Robert D.
Published: August 2007

Cervicovaginal human papillomavirus (HPV) viral load has been purported as a potential marker for the detection of high‐grade cervical intraepithelial neoplasia or cancer (≥CIN2). To examine disease association with type‐specific viral load for the full‐range of anogenital HPV infections, we conducted cross‐sectional and prospective analyses of ∼2,000 HPV‐infected women from a 10,000‐woman population‐based study in Guanacaste, Costa Rica with 7 years of follow‐up. Cervical specimens were tested for >40 HPV types using a MY09/MY11 L1 consensus primer PCR method with type‐specific dot blot hybridization and PCR signal intensity as a measure of viral load. A positive association was observed between prevalent ≥CIN2 and high viral load compared to low viral load for women with baseline single HPV16 infections (OR = 19.2, 95% CI = 4.4–83.2) and single non‐16 carcinogenic infections (OR = 9.2, 95% CI = 2.1–39.9). Inclusion of women with multiple HPV types did not substantially change these associations. In prospective follow‐up, only women infected with HPV16 alone (OR = 27.2, 95% = 3.5–213.5) had a strong association between high viral load and incident ≥CIN2; non‐16 carcinogenic high viral load was not associated with incident ≥CIN2 (OR = 0.7, 95% CI = 0.2–1.9). Single noncarcinogenic type viral load was not associated with increased risk of prevalent or incident ≥CIN2 (OR = 1.2 and 1.1, respectively). In conclusion, carcinogenic high viral load was associated with prevalent ≥CIN2; however HPV16 was uniquely associated with incident ≥CIN2. The extent to which these observations can be translated into clinical practice must be rigorously examined in the context of the method of viral load measurement and the type‐specific differences observed for incident ≥CIN2. © 2007 Wiley‐Liss, Inc.
Trends in cervical cancer mortality in korea 1993–2002: Corrected mortality using national death certification data and national cancer incidence data
Authors: Shin Hai‐Rim , Park Sohee , Hwang Soon‐Young , Kim Jung‐Eun , Jung Kyu‐Won , Won Young‐Joo , Hwang Seung‐Sik , Yim Seon‐Hee , Choi Kui Son , Park Eun‐Cheol , Park Sang‐Yoon , Kim Jae Weon , Lee Hyo‐Pyo
Published: August 2007

Cervical cancer is a major health problem for Korean women, accounting for 9.8% of new female cancer cases, even though incidence rates have been decreasing. The Korean cervical cancer mortality rate for 1993–2002 based on National Statistical Office data shows an increasing trend, but the actual rates are thought to have decreased by epidemiologists, clinicians and other cancer experts. To explain this gap and solve this problem, we corrected the number of cervical cancer deaths by comparing death certificate cases of unspecified uterine cancer data with the national cancer incidence databases of entire cancer registries in Korea. We used 2 different methods to make a correction. First, we considered “uterus, unspecified” deaths previously registered as “cervix, uterine” cases misclassified and added them to the cervical cancer deaths. Alternatively, we multiplied the total number of registered unspecified uterine cancer deaths by age‐specific proportions of registered incident cervical cancer cases among all cancers and added the product to cervical cancer deaths. The overall corrected age‐standardized cervical cancer mortality rates per 100,000 women decreased from 5.2 in 1993 to 3.9 in 2002 (estimated annual percentage change (EAPC): −4.05%, 95% CI: −4.88, −3.22). While cervical cancer mortality showed a decreasing tendency in women aged 30–69 years, it increased substantially in women aged ≥70 years (EAPC: 3.62%, 95% CI: 1.92–5.35). Results of this study will provide evidence‐based foundation for the evaluation of the existing cervical cancer‐screening programs. © 2007 Wiley‐Liss, Inc.
Identification of candidate prostate cancer biomarkers in prostate needle biopsy specimens using proteomic analysis
Authors: Lin Jian‐feng , Xu Jun , Tian Hong‐yu , Gao Xia , Chen Qing‐xi , Gu Qi , Xu Gen‐jun , Song Jian‐da , Zhao Fu‐kun
Published: August 2007

Although serum prostate specific antigen (PSA) is a well‐established diagnostic tool for prostate cancer (PCa) detection, the definitive diagnosis of PCa is based on the information contained in prostate needle biopsy (PNBX) specimens. To define the proteomic features of PNBX specimens to identify candidate biomarkers for PCa, PNBX specimens from patients with PCa or benign prostatic hyperplasia (BPH) were subjected to comparative proteomic analysis. 2‐DE revealed that 52 protein spots exhibited statistically significantly changes among PCa and BPH groups. Interesting spots were identified by MALDI‐TOF‐MS/MS. The 2 most notable groups of proteins identified included latent androgen receptor coregulators [FLNA(7–15) and FKBP4] and enzymes involved in mitochondrial fatty acid β‐oxidation (DCI and ECHS1). An imbalance in the expression of peroxiredoxin subtypes was noted in PCa specimens. Furthermore, different post‐translationally modified isoforms of HSP27 and HSP70.1 were identified. Importantly, changes in FLNA(7–15), FKBP4, and PRDX4 expression were confirmed by immunoblot analyses. Our results suggest that a proteomics‐based approach is useful for developing a more complete picture of the protein profile of PNBX specimen. The proteins identified by this approach may be useful molecular targets for PCa diagnostics and therapeutics. © 2007 Wiley‐Liss, Inc.
Talcum powder, chronic pelvic inflammation and NSAIDs in relation to risk of epithelial ovarian cancer
Authors: Merritt Melissa A. , Green Adèle C. , Nagle Christina M. , Webb Penelope M. ,   Australian Cancer Study (Ovarian Cancer) and Australian Ovarian Cancer Study Group
Published: August 2007

Chronic inflammation has been proposed as the possible causal mechanism that explains the observed association between certain risk factors, such as the use of talcum powder (talc) in the pelvic region and epithelial ovarian cancer. To address this issue we evaluated the potential role of chronic local ovarian inflammation in the development of the major subtypes of epithelial ovarian cancer. Factors potentially linked to ovarian inflammation were examined in an Australia‐wide case–control study comprising 1,576 women with invasive and low malignant potential (LMP) ovarian tumours and 1,509 population‐based controls. We confirmed a statistically significant increase in ovarian cancer risk associated with use of talc in the pelvic region (adjusted odds ratio 1.17, 95% CI: 1.01–1.36) that was strongest for the serous and endometrioid subtypes although the latter was not statistically significant (adjusted odds ratios 1.21, 95% CI 1.03–1.44 and 1.18, 95% CI 0.81–1.70, respectively). Other factors potentially associated with ovarian inflammation (pelvic inflammatory disease, human papilloma virus infection and mumps) were not associated with risk but, like others, we found an increased risk of endometrioid and clear cell ovarian cancer only among women with a history of endometriosis. Regular use of aspirin and other nonsteroidal anti‐inflammatory drugs was inversely associated with risk of LMP mucinous ovarian tumours only. We conclude that on balance chronic inflammation does not play a major role in the development of ovarian cancer. © 2007 Wiley‐Liss, Inc.
Expression of RANTES and MCP‐1 in epithelial cells is regulated via LMP1 and CD40
Authors: Buettner Maike , Meyer Birgit , Schreck Sabine , Niedobitek Gerald
Published: August 2007

Epstein‐Barr virus (EBV)‐associated undifferentiated nasopharyngeal carcinoma (NPC) is characterized by a prominent nonneoplastic lymphoid stroma. The functional role of these inflammatory cells and the mechanism of their recruitment are not fully understood. In B‐cells, the EBV‐encoded latent membrane protein 1 (LMP1) can induce the expression of chemokines in an NF‐κB dependent manner. We now show that LMP1 can induce the expression of RANTES and MCP‐1 in an epithelial cell line, and that this effect is partially reversible by an inhibitor of NF‐κB. Since tumor cells of virtually all NPCs show CD40 expression while many cases are LMP1‐negative at the protein level, we also investigated the effect of CD40 signaling and demonstrate that CD40 stimulation can transiently induce RANTES and MCP‐1 expression in LMP1‐negative epithelial cells. In in situ hybridization only rare tumor cells showed expression of these chemokines unrelated to LMP1 expression, a pattern consistent with transient induction through CD40 signaling. Since RANTES and MCP‐1 were also detected in the neoplastic cells of oral squamous cell carcinomas lacking a lymphoid stroma it remains uncertain to what extent these CC chemokines contribute to the attraction of inflammatory cells into the NPC microenvironment. © 2007 Wiley‐Liss, Inc.
Risk of lung cancer following exposure to carbon black, titanium dioxide and talc: Results from two case–control studies in Montreal
Authors: Ramanakumar Agnihotram V. , Parent Marie‐Élise , Latreille Benoit , Siemiatycki Jack
Published: August 2007

The International Agency for Research on Cancer (IARC) recently evaluated the carcinogenicity of three poorly soluble weakly‐toxic substances: carbon black, titanium dioxide and talc. Though there is evidence of carcinogenity in experimental animals for these substances, the evidence in humans is sparse and equivocal. In the context of two large population based case–control studies of lung cancer carried out in Montreal, we were able to study the possible relationships between the exposure to each of these substances and subsequent risk of lung cancer. We were able to distinguish talc used for industrial purposes from that used for cosmetic purposes. Interviews for Study I were conducted in 1979–1986 (857 cases, 533 population controls, 1,349 cancer controls) and interviews for Study II were conducted in 1996–2001 (1,236 cases and 1,512 controls). Detailed lifetime job histories were elicited, and a team of hygienists and chemists evaluated the evidence of exposure to a host of occupational substances. Lung cancer risk was analysed in relation to each exposure, adjusting for several potential confounders, including smoking. Subjects with occupational exposure to carbon black, titanium dioxide, industrial talc and cosmetic talc did not experience any detectable excess risk of lung cancer. The results are consistent with the recent evaluations of the IARC Monographs. © 2007 Wiley‐Liss, Inc.
Vaccination trial with HPV16 L1E7 chimeric virus‐like particles in women suffering from high grade cervical intraepithelial neoplasia (CIN 2/3)
Authors: Kaufmann Andreas M. , Nieland John D. , Jochmus Ingrid , Baur Siegfried , Friese Klaus , Gabelsberger Joseph , Gieseking Friederike , Gissmann Lutz , Glasschröder Birgit , Grubert Thomas , Hillemanns Peter , Höpfl Reinhard , Ikenberg Hans , Schwarz Jörg , Karrasch Matthias , Knoll Anette , Küppers Volkmar , Lechmann Martin , Lelle Ralph J. , Meissner Harald , Müller Rainer T. , Pawlita Michael , Petry Karl Ulrich , Pilch Henryk , Walek Elke , Schneider Achim
Published: August 2007

Persistent infection with human papillomaviruses (HPV) is a prerequisite for the development of cervical cancer. Vaccination with virus‐like particles (VLP) has demonstrated efficacy in prophylaxis but lacks therapeutic potential. HPV16 L1E7 chimeric virus‐like particles (CVLP) consist of a carboxy‐terminally truncated HPV16L1 protein fused to the amino‐terminal part of the HPV16 E7 protein and self‐assemble by recombinant expression of the fusion protein. The CVLP are able to induce L1‐ and E7‐specific cytotoxic T lymphocytes. We have performed a first clinical trial to gain information about the safety and to generate preliminary data on the therapeutic potential of the CVLP in humans. A randomized, double blind, placebo‐controlled clinical trial has been conducted in 39 HPV16 mono‐infected high grade cervical intraepithelial neoplasia (CIN) patients (CIN 2/3). Two doses (75 μg or 250 μg) of CVLP were applied. The duration of the study was 24 weeks with 2 optional visits after another 12 and 24 weeks. The vaccine showed a very good safety profile with only minor adverse events attributable to the immunization. Antibodies with high titers against HPV16 L1 and low titers against HPV16 E7 as well as cellular immune responses against both proteins were induced. Responses were equivalent for both vaccine concentrations. A trend for histological improvement to CIN 1 or normal was seen in 39% of the patients receiving the vaccine and only 25% of the placebo recipients. Fifty‐six percent of the responders were also HPV16 DNA‐negative by the end of the study. Therefore, we demonstrated evidence for safety and a nonsignificant trend for the clinical efficacy of the HPV16 L1E7 CVLP vaccine. © 2007 Wiley‐Liss, Inc.
Gene silencing of transcription factor Gli2 inhibits basal cell carcinomalike tumor growth in vivo
Authors: Ji Jingmin , Kump Erwin , Wernli Marion , Erb Peter
Published: August 2007

Basal cell carcinoma (BCC) belongs worldwide to the most frequent malignancy among Caucasians. The understanding of the molecular mechanisms of BCC formation, which is a prerequisite for the development of efficient new therapies, is still incomplete. The formation of sporadic BCCs in the skin is associated with uncontrolled hedgehog signaling, and the transcription factor Gli2 has been identified as a key mediator or effector of this signaling. There is indication in the literature that preventing Gli2 function may inhibit BCC formation and growth in vivo; however, the mechanism is unclear and difficult to study in humans. Therefore, we used a mouse tumor allograft model to investigate the role of Gli2 in tumor formation. A constitutively Gli2 expressing mouse tumor cell line was stably transfected with Gli2‐specific shRNA to induce Gli2 gene silencing or with control shRNA. Injecting the Gli2 gene silenced cells into nude mice for tumor formation we detected a strongly retarded tumor growth compared with control tumor cells. Investigating the mechanisms, we found that Gli2 gene silencing has led to the disruption of the tumor structure as demonstrated by staining tumor sections with hematoxylin. Two main reasons for the tumor destruction were identified. We found that apoptosis was markedly increased while vascularization was strongly decreased in these tumors. Thus, important functions of the transcription factor Gli2 in this tumor model are the prevention of apoptosis and the promotion of microvascularization. © 2007 Wiley‐Liss, Inc.
Comparison of nonbreast cancer incidence, survival and mortality between breast screening program participants and nonparticipants
Authors: Phillips Norm , Coldman Andrew
Published: August 2007

Comparisons of cancer mortality between users and nonusers of screening are potentially biased because of the effects of self‐selection. Previous studies of breast screening have found that individuals likely to participate have lower breast cancer mortality than those unlikely to participate. This study compares the incidence, survival and mortality for all cancer types other than breast between participants and nonparticipants in a service screening mammography program. British Columbian females having their first mammogram between the ages of 40 and 79 and the years 1988 and 2004 were identified as a cohort of “participants”. Person‐years of follow‐up of participants were aggregated by age and year. Nonparticipant person‐years were obtained by subtraction from the total female population. Cancer diagnoses other than breast were identified for participants and nonparticipants. Age, calendar year, and income adjusted relative risks of cancer incidence were estimated from generalized additive models with Poisson errors. Hazard ratios were estimated by Cox regression. Observed cancer mortality in participants was compared with expected mortality generated from nonparticipant incidence and survival rates. Incidence rates of cancer showed a mixed relationship with some elevated, some decreased and others similar to nonparticipant rates. Cancer survival was higher among participants for most cancer types, with an overall hazard ratio of 0.76 (0.73–0.79). Observed mortality in participants was less than expected for most cancers, with an overall mortality ratio of 0.60 (0.58–0.62). The general cancer experience of screening program participants is different from that of the general population. © 2007 Wiley‐Liss, Inc.
Role of high‐molecular weight tropomyosins in TGF‐β‐mediated control of cell motility
Authors: Zheng Qiao , Safina Alfiya , Bakin Andrei V.
Published: August 2007

Transforming growth factor beta1 (TGF‐β1) suppresses tumor development at early stages of cancer, but enhances tumor invasion and formation of metastasis. TGF‐β1‐mediated tumor invasion is associated with epithelial to mesenchymal transition (EMT) and matrix proteolysis. The mechanisms of these TGF‐β1 responses in normal and tumor cells are not well understood. Recently, we have reported that TGF‐β1 increases expression of high‐molecular weight tropomyosins (HMW‐tropomyosins) and formation of actin stress fibers in normal epithelial cells. The present study investigated the role of tropomyosin in TGF‐β1‐mediated cell motility and invasion. We found that TGF‐β1 restricts motility of normal epithelial cells although it promotes EMT and formation of actin stress fibers and focal adhesions. Cell motility was enhanced by siRNA‐mediated suppression of HMW‐tropomyosins. TGF‐β1 stimulated migration and matrix proteolysis in breast cancer MDA‐MB‐231 cells that express low levels of HMW‐tropomyosins. Tet‐Off‐regulated expression of HMW‐tropomyosin inhibited cell migration and matrix proteolysis without affecting expression of matrix metalloproteinases. Tropomyosin increased cell adhesion to matrix by enhancing actin fibers and focal adhesions. Finally, tropomyosin impaired the ability of tumor cells to form lung metastases in SCID mice. Thus, these results suggest that HMW‐tropomyosins are important for TGF‐β‐mediated control of cell motility and acquisition of the metastatic potential. © 2007 Wiley‐Liss, Inc.
Genetic and functional analysis of CHEK2 (CHK2) variants in multiethnic cohorts
Authors: Bell Daphne W. , Kim Sang H. , Godwin Andrew K. , Schiripo Taryn A. , Harris Patricia L. , Haserlat Sara M. , Wahrer Doke C.R. , Haiman Christopher A. , Daly Mary B. , Niendorf Kristin B. , Smith Matthew R. , Sgroi Dennis C. , Garber Judy E. , Olopade Olufunmilayo I. , Marchand Loic Le , Henderson Brian E. , Altshuler David , Haber Daniel A. , Freedman Matthew L.
Published: August 2007

The CHEK2‐1100delC mutation is recurrent in the population and is a moderate risk factor for breast cancer. To identify additional CHEK2 mutations potentially contributing to breast cancer susceptibility, we sequenced 248 cases with early‐onset disease; functionally characterized new variants and conducted a population‐based case–control analysis to evaluate their contribution to breast cancer risk. We identified 1 additional null mutation and 5 missense variants in the germline of cancer patients. In vitro, the CHEK2‐H143Y variant resulted in gross protein destabilization, while others had variable suppression of in vitro kinase activity using BRCA1 as a substrate. The germline CHEK2‐1100delC mutation was present among 8/1,646 (0.5%) sporadic, 2/400 (0.5%) early‐onset and 3/302 (1%) familial breast cancer cases, but undetectable amongst 2,105 multiethnic controls, including 633 from the US. CHEK2‐positive breast cancer families also carried a deleterious BRCA1 mutation. 1100delC appears to be the only recurrent CHEK2 mutation associated with a potentially significant contribution to breast cancer risk in the general population. Another recurrent mutation with attenuated in vitro function, CHEK2‐P85L, is not associated with increased breast cancer susceptibility, but exhibits a striking difference in frequency across populations with different ancestral histories. These observations illustrate the importance of genotyping ethnically diverse groups when assessing the impact of low‐penetrance susceptibility alleles on population risk. Our findings highlight the notion that clinical testing for rare missense mutations within CHEK2 may have limited value in predicting breast cancer risk, but that testing for the 1100delC variant may be valuable in phenotypically‐ and geographically‐selected populations. © 2007 Wiley‐Liss, Inc.
ADH‐1 suppresses N‐cadherin‐dependent pancreatic cancer progression
Authors: Shintani Yasushi , Fukumoto Yuri , Chaika Nina , Grandgenett Paul M. , Hollingsworth Michael A. , Wheelock Margaret J. , Johnson Keith R.
Published: August 2007

Pancreatic cancer is one of the most aggressive malignant diseases. We recently reported that N‐cadherin plays a key role in tumor progression and metastasis in pancreatic cancer. For this study, we sought to determine if an N‐cadherin‐blocking peptide (ADH‐1) could prevent N‐cadherin‐mediated tumor progression in a mouse model for pancreatic cancer. The effect of ADH‐1 on N‐cadherin‐mediated cell scattering and migration on collagen I was examined using pancreatic cancer cells. We also examined the influence of ADH‐1 on cell apoptosis. Furthermore, in vivo animal studies were performed using orthotopic injection of N‐cadherin overexpressing BxPC‐3 cells with or without ADH‐1 treatment. BxPC‐3 and Capan‐1 cells exhibited increased expression of N‐cadherin in response to collagen I. This increase in N‐cadherin promoted cell scattering and migration in response to collagen I. ADH‐1 prevented these changes, but did not inhibit upregulation of N‐cadherin. TUNEL assays and immunoblots for caspase‐3 showed that ADH‐1 induced apoptosis in a concentration dependent and N‐cadherin dependent manner in pancreatic cancer cells. ADH‐1 treatment resulted in significant reductions in tumor growth and lung metastasis in a mouse model for pancreatic cancer. The N‐cadherin antagonist, ADH‐1 has significant antitumor activity against N‐cadherin‐expressing cells using in vitro assays and in an orthotopic mouse model for pancreatic cancer, raising the possibility that N‐cadherin antagonists have therapeutic potential for the treatment of pancreatic cancer in humans. © 2007 Wiley‐Liss, Inc.