Economic evaluation of the familial cancer programme in Western Australia: predictive genetic testing for familial adenomatous polyposis and hereditary non-polyposis colorectal carcinoma

AIM: To evaluate costs and outcomes of genetic testing for familial colorectal cancer through services provided by Genetic Services of Western Australia (GSWA). METHODS: Costs and outcomes of predictive DNA-based testing for inherited colorectal cancers (CRC) were assessed, specifically for familial adenomatous polyposis (FAP) and hereditary non-polyposis CRC (HNPCC) using a decision-analysis model. Costs were assigned according to standards of care in Western Australia (WA). Cancer risks and the efficacy of surveillance on long-term outcomes were derived from the published literature. RESULTS: The cost-effectiveness of genetic testing was compared in first-degree relatives of known mutation carriers who have a 50% risk of carrying the mutated gene (intervention group) to individuals with the same risk but who do not undergo a genetic test (control subjects). Compared with control subjects undergoing the same high-level surveillance and surgery, the FAP and HNPCC intervention groups provided total savings of 13,390 US dollars and 14,783-15,460 per person (males-females), respectively. HPNCC mutation carriers also gained 1 CRC-free year. Compared to control subjects having only population surveillance, individuals in the FAP intervention group delayed the onset of CRC by 40 years for a net cost of 9,042 US dollars. Individuals in the HNPCC intervention group delayed the onset of CRC by 8 years at a net cost of 12,141 US dollars for males and 12,596 US dollars for females. CONCLUSIONS: Genetic testing for familial CRC in WA allows targeted surveillance for mutation carriers, which ensures the efficient use of resources and reduces cancer-related morbidity, if clinical recommendations for intervention are adopted.     

Life and health insurance behaviour of individuals having undergone a predictive genetic testing programme for hereditary non-polyposis colorectal cancer

Objective and Methods: We describe the insurance behaviour of subjects (n=271) who had previously taken a predictive genetic test for hereditary non-polyposis colorectal cancer (HNPCC); 31% of them were mutation positive, indicating a high risk of cancer. One year after testing, subjects were sent a questionnaire including questions about their present life and health insurance before participation in the study, and their actual and planned purchase of the insurance policies during the testing programme which compromised a pre-test counseling session, a period for reflection, the testing, and a test disclosure session. Results: Thirty percent reported that they already had a life insurance and 14% a health insurance before participating in the study. The mutation-positive subjects possessed a health insurance significantly more often than the mutation-negative individuals (21 vs. 11%, p=0.02) and similar trend was observed for life insurance (36 vs. 28%, p=0.12). Life and health insurance policies purchased just before testing was reported by 3 and 2% of the subjects, respectively. Life and health insurance policies purchased after testing were reported by 3 and <1% respectively, and planned purchase by 3 and 2%, respectively. No statistically significant differences were found between the groups defined by mutation status in reports of life or health insurance behaviour during or after the programme. Conclusion: According to self-reported data, the mutation-positive subjects did not differ from the others in the purchase of life or health insurance policies. However, the mutation-positive individuals reported that they possessed health insurance policies before entering the study more often than their counterparts.     

Familial aggregation of early-onset myocardial infarction

Although ischemic heart disease tends to cluster in families, previous studies have reported a modest (2-fold increased risk) to strong (10-fold increased risk) contribution of family history to the explanation of disease occurrence. The authors assessed the familial aggregation of early-onset myocardial infarction in 11,307 adults aged <65 years who participated in the Third National Health and Nutrition Examination Survey. Logistic regression was used to obtain odds ratios (ORs) and 95% confidence intervals (CIs). A parental history was more common in those with (n = 237) than in those without (n = 11,070) a myocardial infarction (19.8 vs. 7.9%, p < or = 0.01). Adults with a parental history were also more likely to have multiple risk factors for cardiovascular disease (OR for four or five risk factors compared with none: 2.9, 95% CI: 1.4, 6.3). After multivariate adjustment, the likelihood of myocardial infarction was more than three times greater among adults with a parental history than among those without (95% CI: 1.7, 6.7). A maternal history of myocardial infarction was strongly associated (OR = 6.1, 95% CI: 2.1, 17.4) with an increased likelihood of myocardial infarction, and a paternal history was associated with a 3-fold (95% CI: 1.5, 6.3) increased likelihood of myocardial infarction after adjustment for cardiovascular disease risk factors. These results suggest a familial aggregation of early-onset myocardial infarction and show that family history is strongly associated with cardiovascular disease risk factors.     

Depressive symptoms in Machado-Joseph disease (SCA3) patients and their relatives

OBJECTIVES: It was the aim of this study to determine the depression scores of Machado-Joseph disease (MJD) patients, their spouses, and individuals at 50% risk for MJD, and second, to verify the existence of a correlation between depressive symptoms and the degree of motor incapacitation. SUBJECTS AND METHODS: Two hundred and forty-six individuals aged > or =18 years were studied: 79 MJD patients (group 1), 43 spouses of MJD patients (group 2), 80 individuals at risk for MJD (group 3), and a control group (group 4) composed of 44 patients with multiple sclerosis (MS). The following two tools were applied: the Beck Depression Inventory and the Barthel index of physical incapacitation, both in an adapted Brazilian Portuguese version. RESULTS: Moderate to severe depressive scores were found in 33.5% of patients in the MJD families, in 16.3% of the spouses, and in 6.3% of the individuals at risk. This linear reduction between MJD family members was statistically significant (p < 0.0001, ANOVA). Depressive scores were also associated with age and the female sex. A direct correlation between Beck Depression Inventory scores and motor incapacitation was found in MJD patients (r = 0.507, Pearson correlation, p < 0.0001). Although the depressive symptoms in the control group with MS were higher than those found in MJD patients (59% of MS patients showed moderate to severe scores), depression did not correlate with physical incapacitation, age, or education attainment in the MS group. CONCLUSIONS: Depressive symptoms are rather common in MJD patients and in their spouses (caregivers). In this condition, depression seemed to be more reactive than primarily related to the disease process itself.     

Hereditary nonpolyposis colorectal cancer: an approach to the selection of candidates to genetic testing based on clinical and molecular characteristics

OBJECTIVE: Identification of clinical and molecular characteristics associated with constitutional MLH1 and MSH2 mutations and definition of a stepwise strategy for the selection of colorectal cancer (CRC) patients amenable to MLH1 and MSH2 genetic testing. METHODS: 90 unrelated CRC patients were initially selected on the basis of either familial or early onset occurrence of CRC. They were screened for the presence of constitutional MLH1 and MSH2 mutations and for microsatellite instability (MSI). RESULTS: 16 pathogenetic mutations (9 MLH1 and 7 MSH2) were identified in 41% of Amsterdam hereditary nonpolyposis colorectal cancer (HNPCC) families, 5% of suspected HNPCC families, and 14% of sporadic early-onset CRC patients. The presence of the mutations correlated with MSI, with early age of onset and proximal location of the tumor, and with the presence of some extracolonic tumors of the HNPCC spectrum and/or multiple tumors in the family. CONCLUSIONS: Evaluation of clinical and molecular characteristics is useful for the identification of candidates to MLH1 and MSH2 mutational analysis and allows the application of a rational approach to genetic testing.     

Nonlinear oscillations and boundary value problems for Hamiltonian systems

We prove the existence of solutions of various boundary-value problems for nonautonomous Hamiltonian systems with forcing terms $$\begin{gathered} \dot x(t) = H'_p (t, x(t), p(t)) + g(t), \hfill \\ \dot p(t) = - H'_x (t, x(t), p(t)) - f(t). \hfill \\ \end{gathered} $$ Among these problems is the existence of T-periodic solutions, namely those satisfying x(t+T)=x(t) and p(t+T)+p(t). A special study is made of the classical case, where H(x, p)=1/2 |p|²+V(x). In the case of parametric oscillations, where (f, g)=(0, 0) and t ? H(t, x, p) is T-periodic, we give a lower bound for the true (minimal) period of the T-periodic solution (x, p) produced by our method, and we prove the existence of an infinite number of subharmonics.     

A comparison of the effectiveness of extracorporeal shock wave and ultrasound therapy in the management of heel pain

The aim of this study was to compare the effectiveness of extracorporeal shock wave therapy (ESWT) and ultrasound therapy (US) for managing heel pain. Thirty-seven subjects received either: ESWT (once a week), US (three times a week), or CONTROL (no treatment) for 3 consecutive weeks and were followed-up for 3 more weeks. A visual analogue scale (VAS), the maximum tolerable duration for prolonged walking or standing, and the Mayo clinical scoring system (MCSS) were evaluated. Mixed models treating baseline measures as covariates were adopted for statistical analysis. By week 3, intensity of heel pain on palpation was reduced by 37% (VAS score from 7.5 to 4.6) in the ESWT group, 24% (from 5.3 to 4.2) in the US group, and increased by 3% (5.6–5.7) in the control group; this difference was significant after adjusting for baseline VAS scores (p = 0.022). The improvements in the maximum tolerable duration of prolonged walking or standing was only significant in the ESWT group (157% increase, p = 0.043) but not the other two groups. Both active treatment groups maintained the treatment effect at the three-week follow-up. We conclude that ESWT is potentially more effective in reducing heel pain than ultrasound therapy but additional evidence is needed due to the various limitations of the study.      

Higher Order Approximation of the Period-energy Function for Single Degree of Freedom Hamiltonian Systems

In 1985 Franz Rothe [J. Reine Angew Math. 355 (1985) 129–138] found, by means of the thermodynamical equilibrium theory, an asymptotic estimate of the period of solutions of ordinary differential equations originated by predator–prey Volterra–Lotka model. We extend some of the Rothe's ideas to more general systems:

Epidemiological characterization of congenital heart disease in São Miguel Island, Azores, Portugal

OBJECTIVES: This study aimed to characterize the prevalence of congenital heart disease (CHD) in children born alive in S?o Miguel island from January 1992 to December 2001. METHODS: Based on the Azorean Registry of CHD, which includes complete clinical and personal information, 189 patients were diagnosed. RESULTS: During this 10-year period, the average prevalence of CHD is 9.16 per 1,000 live births (range 4.77-12.75). The most frequent cardiac malformations found were: ventricular septal defect (38.1%), atrial septal defect (12.2%) and patent ductus arteriosus (11.6%). Until now, four familial clusters were identified, representing a total of 13 patients. CONCLUSIONS: This first epidemiological study of CHD in the Azorean population reveals evidence for familial aggregation, which is of great interest for understanding the genes involved in these complex pathologies.     

Influence de la température sur la courbe de rétention d'eau de milieux poreuxInfluence of temperature on the water retention curve of porous media

This paper concerns the influence of temperature on the water retention curve of porous media. We present a model based on the differential of suction as a function of temperature, water content and void ratio. When adjusted for a given temperature, this model is able to predict the curve for any temperature. The model was validated by several tests on a ceramic (terra cotta) and a clayey silty sand at 20 and 60?°C. The application of the model to data found in the literature confirms its predictive power for a wide range of porous materials. To cite this article: S. Salager et al., C. R. Mecanique 334 (2006).     

Spatiotemporal variations of PM_(2.5) and PM_(10) concentrations between31 Chinese cities and their relationships with SO_2,NO_2,CO and O_3

The variations of mass concentrations of PM_(2.5),PM_(10),SO_2,NO_2,CO,and O_3 in 31 Chinese provincial capital cities were analyzed based on data from 286 monitoring sites obtained between March 22,2013 and March 31,2014.By comparing the pollutant concentrations over this length of time,the characteristics of the monthly variations of mass concentrations of air pollutants were determined.We used the Pearson correlation coefficient to establish the relationship between PM_(2.5),PM_(10),and the gas pollutants.The results revealed significant differences in the concentration levels of air pollutants and in the variations between the different cities.The Pearson correlation coefficients between PMs and NO_2 and SO_2 were either high or moderate(PM_(2.5) with NO_2:r=0.256-0.688,mean r=0.498;PM_(10) with NO_2:r = 0.169-0.713,mean r = 0.493;PM2.5 with SO_2:r= 0.232-0.693,mean r=0.449;PM_(10) with SO_2:r = 0.131-0.669,mean r=0.403).The correlation between PMs and CO was diverse(PM_(2.5):r = 0.156-0.721,mean r=0.437;PM_(10):r=0.06-0.67,mean r= 0.380).The correlation between PMs and O_3 was either weak or uncorrelated(PM_(2.5):r--0.35 to 0.089,mean r=-0.164;PM_(10):r=-0.279 to 0.078,mean r=-0.127),except in Haikou(PM2.5:r=0.500;PM_(10):r-0.509).     

Informed consent and subject motivation to participate in a large, population-based genomics study: the Marshfield Clinic Personalized Medicine Research Project

BACKGROUND: The objective of this study was to measure subject perspective and reaction to participation in the Personalized Medicine Research Project (PMRP) and to identify factors predicting understanding of the study elements. METHOD: Self-administered questionnaires were mailed to 1,593 subjects (10% sample). The questionnaire had three sections: section A consisted of 21 factual questions; section B consisted of 14 questions to assess the level of understanding about the PMRP concepts, and section C asked about the purpose of the PMRP. RESULTS: The mean age of the 924 survey respondents was 52 years (SD = 16.9), with a range of 18-95 years. The majority of participants were female (n = 561, 61%). The percent of total correct responses for section A was significantly higher for females compared with males (males: 58.4% and females: 60.4%, t test = -2.18, p = 0.03) and age was significantly inversely related to percent of correct responses (beta coefficient = -0.122, p < 0.001). More than one third of the participants indicated that the USD 20 greatly influenced their decision to participate in the project. In a multiple logistic regression model, people living outside of Marshfield were significantly more likely to indicate that the USD 20 greatly influenced their decision to participate (odds ratio = 1.40, 95% confidence limit = 1.06, 1.86) and age was inversely related to the monetary influence on decision to participate (odds ratio = 0.98, 95% confidence limit = 0.97, 0.98). CONCLUSION: Future community consultation efforts should highlight areas of lower understanding. In addition, research coordinators may need to take more time informing males and older individuals about project details so that they are making truly informed decisions about study participation.     

Consanguineous marriages in Iranian folktales

BACKGROUND: Using folktales we can find some aspects of social customs. Here, I show the situation of consanguineous marriages in folktales from different Iranian populations and try to compare it with the present situation of consanguineous marriages. METHODS: The study includes tales from 11 different Iranian (ethnic and/or geographical) populations. Overall, the records of 585 marriages in 296 folktales from the study populations were found. RESULTS: The estimated mean inbreeding coefficient (alpha) for different populations using folktale records is lower than that of the present values. However, there is a very high level of statistically significant correlation between them (r = 0.753, d.f. = 9, p = 0.007). CONCLUSION: The historical background is very important to attitude and practice regarding marriages between relatives.     

On a Boundary-Value Problem of Antiperiodic Type for First-Order Nonlinear Functional Differential Equations of Non-Volterra Type

We establish unimprovable (in a certain sense) sufficient conditions for the solvability and unique solvability of the boundary-value problem

Influence of wavy surfaces on coherent structures in a turbulent flow

We describe how outer flow turbulence phenomena depend on the interaction with the wall. We investigate coherent structures in turbulent flows over different wavy surfaces and specify the influence of the different surface geometries on the coherent structures. The most important contribution to the turbulent momentum transport is attributed to these structures, therefore this flow configuration is of large engineering interest. In order to achieve a homogeneous and inhomogeneous reference flow situation two different types of surface geometries are considered: (1) three sinusoidal bottom wall profiles with different amplitude-to-wavelength ratios of α = 2a/Λ = 0.2 (Λ = 30 mm), α = 0.2 (Λ = 15 mm), and α = 0.1 (Λ = 30 mm); and (2) a profile consisting of two superimposed sinusoidal waves with α = 0.1 (Λ = 30 mm). Measurements are carried out in a wide water channel facility (aspect ratio 12:1). Digital particle image velocimetry (PIV) is performed to examine the spatial variation of the streamwise, spanwise and wall-normal velocity components in three measurement planes. Measurements are performed at a Reynolds number of 11,200, defined with the half channel height h and the bulk velocity U _B. We apply the method of snapshots and perform a proper orthogonal decomposition (POD) of the streamwise, spanwise, and wall-normal velocity components to extract the most dominant flow structures. The structure of the most dominant eigenmode is related to counter-rotating, streamwise-oriented vortices. A qualitative comparison of the eigenfunctions for different sinusoidal wall profiles shows similar structures and comparable characteristic spanwise scales Λ _z = 1.5 H in the spanwise direction for each mode. The scale is observed to be slightly smaller for α = 0.2 (Λ = 15 mm) and slightly larger for α = 0.2 (Λ = 30 mm). This scaling for the flow over the basic wave geometries indicates that the size of the largest structures is neither directly linked to the solid wave amplitude, nor to the wavelength. The characteristic spanwise scale of the dominant eigenmode for the developed flow over the surface consisting of two superimposed waves reduces to 0.85 H. However, a scale in the order of 1.3 H is identified for the second mode. The eigenvalue spectra for the superimposed waves is much broader, more modes contribute to the energy-containing range. The turbulent flow with increased complexity of the bottom surface is characterized by an increased number of dominant large-scale structures with different spanwise scales.     

Information-seeking behaviour and psycho-social interactions during the genetic testing process

OBJECTIVES: The first aim of this study was to investigate the information-seeking behaviour (ISB) of women attending cancer genetic consultations at which the possibility of BRCA testing is considered. We focused here specifically on ISB apart from the cancer genetic consultation, i.e. on what complementary sources of information about genetic testing were consulted and what factors were involved in this behaviour. The second aim was to study the role of the social network used by the patients to collect various opinions on which to base their decisions about being tested. METHODS: A prospective cohort study (2000-2002) was therefore carried out on all women attending a single cancer genetic clinic in France after a BRCA1/2 analysis had been proposed. Closed questionnaires were administered before and after the second cancer genetic consultation. The purpose of this consultation was to confirm the patient's decision to be tested. RESULTS: Results were analysed in 108 subjects (mean age 47 years, SD 11 years; 74% affected by breast/ovarian cancer). Prior to the 2nd consultation, 35.2% of the women had actively looked for information about BRCA1/2 testing, as compared to 25.0% afterwards. After multivariate adjustment by logistic regression, the pre-consultation ISB was found to be associated with greater satisfaction with the information about the psycho-social consequences of genetic testing [adjusted odds ratio (ORadj) 1.03, 95% confidence interval (CI) 1.01-1.06] (scale from 0 to 100) and about the certainty of being a gene carrier (ORadj 3.04, 95% CI 1.16-7.98). Those who actively looked for complementary information were also more often accompanied at the consultation by a family member (ORadj 4.82, 95% CI 1.85-12.56). The other variables tested (depression, coping, socio-demographic and medical characteristics) were not significant (p > 0.05). The role of the social network in the decision making process was perceived as being less helpful when the persons consulted tended to have neutral or unfavourable opinions about genetic testing. CONCLUSIONS: Few women actively sought complementary information about BRCA genetic testing in addition to the cancer genetic consultation. Those who did so differed from the others in terms of their social network and their satisfaction with the consultation. The cancer geneticist is the key actor in women's decision making about genetic testing.     

Optimized synthesis and photovoltaic performance of TiO2 nanoparticles for dye-sensitized solar cell

This paper presents response surface methodology （RSM） as an efficient approach for modeling and optimizing TiO2 nanoparticles preparation via co-precipitation for dye-sensitized solar cell （DSSC） perfor- mance. Titanium （IV） bis-（acetylacetonate） di-isopropoxide （DIPBAT）, isopropanol and water were used as precursor, solvent and co-solvent, respectively. Molar ratio of water, aging temperature and calcina- tion temperature as preparation factors with main and interaction effects on particle characteristics and performances were investigated, Particle characteristics in terms of primary and secondary sizes, crys- tal orientation and morphology were determined by X-ray diffractometry （XRD） and scanning electron microscopy （SEM）. Band gap energy and power conversion efficiency of DSSCs were used for perfor- mance studies. According to analysis of variance （ANOVA） in response surface methodology （RSM）, all three independent parameters were statistically significant and the final model was accurate. The model predicted maximum power conversion efficiency （0.14%） under the optimal condition of molar ratio of DIPBAT-to-isopropanol-to-water of 1 ： 10：500, aging temperature of 36 C and calcination temperature of 400 ℃. A second set of data was adopted to validate the model at optimal conditions and was found to be 0.14 ± 0.015%, which was very close to the predicted value. This study proves the reliability of the model in identi（ving the optimal condition for maximum performance.     

The onset of turbulence in physiological pulsatile flow in a straight tube

 An empirical correlation for the onset of turbulence in physiological pulsatile flow is presented. We pumped three different test fluids of kinematic viscosity 0.008–0.035 cm²/s through four straight tubes 0.4–3.0 cm in diameter. A Scotch yoke mechanism provided an oscillatory sine wave flow component of known stroke volume and frequency. We adjusted the mean flow independently until we detected signal instabilities from hot film wall shear stress probes. The critical peak Reynolds number was found to correlate with the Womersley parameter and the Strouhal number as a power law function with a root-mean-square (rms) error of 15.2%. Experimental measurements of the laminar velocity profile are compared to theoretical predictions from Poiseuille’s law and Womersley’s solution. Received: 30 October 1995/Accepted: 7 April 1997     

Nonlinear rheological properties and stability of dibenzylidene sorbitol fiber networks in poly(propylene oxide)

Dibenzylidene sorbitol (DBS) is known to gel organic liquids and polymers such as poly(propylene oxide) (PPO) by forming long fibers and fiber networks. Potential applications of these networks depend on their ability to withstand large deformations without significant morphological changes. Therefore, we studied the nonlinear rheological properties of the DBS fiber network in PPO for different DBS concentrations. We found that the concentration dependence of critical deformation (transition from linear to nonlinear viscoelastic region) and gel strength (G′ plateau in the linear region) can be explained on the basis of a model for densely cross-linked fiber gels (MacKintosh et al., Phys Rev Lett 75:4425–4428, 1995). Performing periodic strain sweeps, we found that the decrease in gel strength during the deformation cycles can be ascribed to reversible fiber coarsening. Additionally, start-up experiments showed a strong shear thinning behavior, which is in quantitative agreement with the SGM model (Sollich, Phys Rev E 58:738–759, 1998).     

Benchmark PIV database for the validation of CFD simulations in a transitional cavity flow

We present an experimental benchmark database for the transitional cavity flow. The database is obtained by planar Particle Image Velocimetry measurements at the median plane of the cavity model, for Reynolds numbers between 6300 and 19,000 based on the cavity height. A detailed uncertainty analysis of the experimental results is performed via the correlation statistics method for PIV uncertainty quantification and linear error propagation.The experimental results are compared to two-dimensional Reynolds-Averaged Navier Stokes (RANS) numerical simulations with different turbulence models. It is shown that, when the standard k-ω turbulence model is employed, the discrepancy between numerical simulations and experimental results exceeds the uncertainty of the latter. Conversely, RANS simulations with the SST k-ω turbulence model agree well with the experimental data in terms of time-averaged flow properties; however, the turbulent kinetic energy results present significant discrepancies at all considered Reynolds numbers. The data presented in this paper is made available for open-access download via the 4TU.ResearchData repository with DOI: https://doi.org/10.4121/14061233.