An age-period-cohort analysis of gastric cancer mortality from 1950 to 2007 in Europe.

PURPOSE: To analyze the components of the favorable trends in gastric cancer in Europe. METHODS: From official certified deaths from gastric cancer and population estimates for 42 countries of the European geographical region, during the period 1950 to 2007, age-standardized death rates (World Standard Population) were computed, and an age-period-cohort analysis was performed. RESULTS: Central and Northern countries with lower rates in the 2005 to 2007 period, such as France (5.28 and 1.93/100,000, men and women respectively) and Sweden (4.49 and 2.21/100,000), had descending period and cohort effects that decreased steeply from the earliest cohorts until those born in the 1940s, to then stabilize. Former nonmarket economy countries had mortality rates greater than 20/100,000 men and 10/100,000 women, and displayed a later start in the cohort effect fall, which continued in the younger cohorts. Mortality remained high in some countries of Southern and Eastern Europe. CONCLUSIONS: The decrease in gastric cancer mortality was observed in both cohort and period effects but was larger in the cohorts, suggesting that the downward trends are likely to persist in countries with higher rates. In a few Western countries with very low rates an asymptote appears to have been reached for cohorts born after the 1940s, particularly in women.

Concurrent or sequential adjuvant letrozole and radiotherapy after conservative surgery for early-stage breast cancer (CO-HO-RT): a phase 2 randomised trial.

BACKGROUND: Letrozole radiosensitises breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting. METHODS: This phase 2 randomised trial was undertaken in two centres in France and one in Switzerland between Jan 12, 2005, and Feb 21, 2007. 150 postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n=75) or sequential radiotherapy and letrozole (n=75). Randomisation was open label with a minimisation technique, stratified by investigational centres, chemotherapy (yes vs no), radiation boost (yes vs no), and value of radiation-induced lymphocyte apoptosis (< or = 16% vs >16%). Whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44-50 Gy. Letrozole was administered orally once daily at a dose of 2.5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks post-radiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced grade 2 or worse toxic effects of the skin. Analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00208273. FINDINGS: All patients were analysed apart from one in the concurrent group who withdrew consent before any treatment. During radiotherapy and within the first 12 weeks after radiotherapy, 31 patients in the concurrent group and 31 in the sequential group had any grade 2 or worse skin-related toxicity. The most common skin-related adverse event was dermatitis: four patients in the concurrent group and six in the sequential group had grade 3 acute skin dermatitis during radiotherapy. At a median follow-up of 26 months (range 3-40), two patients in each group had grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis). INTERPRETATION: Letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy. Long-term follow-up is needed to investigate cardiac side-effects and cancer-specific outcomes. FUNDING: Novartis Oncology France.

Concurrent or Sequential Adjuvant Letrozole and Radiotherapy after Conservative Surgery for Early-stage Breast Cancer: Long-term Results of the Cohort Phase 2 Randomized Trial

Purpose/Objective(s): Letrozole radiosensitizes breast cancer cells in vitro. In clinical settings, no data exist for the combination of letrozole and radiotherapy. We assessed concurrent and sequential radiotherapy and letrozole in the adjuvant setting.Materials/Methods: The present study is registered with ClinicalTrials.gov, number NCT00208273. This Phase 2 randomized trial was undertaken in two centers in France and one in Switzerland between January 12, 2005, and February 21, 2007. One hundred fifty postmenopausal women with early-stage breast cancer were randomly assigned after conserving surgery to either concurrent radiotherapy and letrozole (n = 75) or sequential radiotherapy and letrozole (n = 75). Randomization was open label with a minimization technique, stratified by investigational centers, chemotherapy (yes vs. no), radiation boost (yes vs. no), and value of radiation-induced lymphocyte apoptosis (#16% vs. .16%). The whole breast was irradiated to a total dose of 50 Gy in 25 fractions over 5 weeks. In the case of supraclavicular and internal mammary node irradiation, the dose was 44 - 50 Gy. Letrozole was administered orally once daily at a dose of 2 - 5 mg for 5 years (beginning 3 weeks pre-radiotherapy in the concomitant group, and 3 weeks postradiotherapy in the sequential group). The primary endpoint was the occurrence of acute (during and within 6 weeks of radiotherapy) and late (within 2 years) radiation-induced Grade 2 or worse toxic effects of the skin and lung (functional pulmonary test and lung CT-scan). Analyses were by intention-to-treat. The long-term follow-up after 2 years was only performed in Montpellier (n = 121) and evaluated skin toxicity (clinical examination every 6 months), lung fibrosis (one CT-scan yearly), cosmetic outcome.Results: All patients were analyzed apart from 1 in the concurrent group who withdrew consent before any treatment.Within the first 2 years (n = 149), no lung toxicity was identified by CT scan and no modification from baseline was noted by the lung diffusion capacity test. Two patients in each group had Grade 2 or worse late effects (both radiation-induced subcutaneous fibrosis [RISF]). After 2 years (n = 121), and with a median follow-up of 50 months (38-62), 2 patients (1 in each arm) presented a Grade 3 RISF. No lung toxicity was identified by CT scan. Cosmetic results (photographies) and quality of life was good to excellent. All patients who had Grade 3 subcutaneous fibrosis had an RILA value of 16% or less, irrespective of the sequence with letrozole.Conclusions:With long-term follow-up, letrozole can be safely delivered shortly after surgery and concomitantly with radiotherapy.

Assessment of the 10-year probability of osteoporotic hip fracture combining clinical risk factors and heel bone ultrasound: the EPISEM prospective cohort of 12,958 elderly women.

This study aimed to develop a hip screening tool that combines relevant clinical risk factors (CRFs) and quantitative ultrasound (QUS) at the heel to determine the 10-yr probability of hip fractures in elderly women. The EPISEM database, comprised of approximately 13,000 women 70 yr of age, was derived from two population-based white European cohorts in France and Switzerland. All women had baseline data on CRFs and a baseline measurement of the stiffness index (SI) derived from QUS at the heel. Women were followed prospectively to identify incident fractures. Multivariate analysis was performed to determine the CRFs that contributed significantly to hip fracture risk, and these were used to generate a CRF score. Gradients of risk (GR; RR/SD change) and areas under receiver operating characteristic curves (AUC) were calculated for the CRF score, SI, and a score combining both. The 10-yr probability of hip fracture was computed for the combined model. Three hundred seven hip fractures were observed over a mean follow-up of 3.2 yr. In addition to SI, significant CRFs for hip fracture were body mass index (BMI), history of fracture, an impaired chair test, history of a recent fall, current cigarette smoking, and diabetes mellitus. The average GR for hip fracture was 2.10 per SD with the combined SI + CRF score compared with a GR of 1.77 with SI alone and of 1.52 with the CRF score alone. Thus, the use of CRFs enhanced the predictive value of SI alone. For example, in a woman 80 yr of age, the presence of two to four CRFs increased the probability of hip fracture from 16.9% to 26.6% and from 52.6% to 70.5% for SI Z-scores of +2 and -3, respectively. The combined use of CRFs and QUS SI is a promising tool to assess hip fracture probability in elderly women, especially when access to DXA is limited.

Longitudinal study of informed consent in innovative therapy research: experience and provisional recommendations from a multicenter trial of intracerebral grafting.

BACKGROUND: There is an urgent need to assess and improve the consent process in clinical trials of innovative therapies for neurodegenerative disorders. METHODS: We performed a longitudinal study of the consent of Huntington's disease patients during the Multicenter Fetal Cell Intracerebral Grafting Trial in Huntington's Disease (MIG-HD) in France and Belgium. Patients and their proxies completed a consent questionnaire at inclusion, before signing the consent form and after one year of follow-up, before randomization and transplantation. The questionnaire explored understanding of the protocol, satisfaction with the information delivered, reasons for participating in the trial and expectations regarding the transplant. Forty-six Huntington's disease patients and 27 proxies completed the questionnaire at inclusion, and 27 Huntington's disease patients and 16 proxies one year later. RESULTS: The comprehension score was high and similar for Huntington's disease patients and proxies at inclusion (72.6% vs 77.8%; P > 0.1) but only decreased in HD patients after one year. The information satisfaction score was high (73.5% vs 66.5%; P > 0.1) and correlated with understanding in both patients and proxies. The motivation and expectation profiles were similar in patients and proxies and remained unchanged after one year. CONCLUSIONS: Cognitively impaired patients with Huntington's disease were capable of consenting to participation in this trial. This consent procedure has presumably strengthened their understanding and should be proposed before signing the consent form in future gene or cell therapy trials for neurodegenerative disorders. Because of the potential cognitive decline, proxies should be designated as provisional surrogate decision-makers, even in competent patients.

Zeichentheorie und BWL : Zur Anwendung semiotischer Erkentnisse im wirtschaftlichen Diskurs

Semiotics is hardly known in German business literature and management practice, despite the fact that its methodological approaches to discourse analysis have already been broadly absorbed by management theory in France and the United States. The present contribution points out why the general echo of semiotic theory and its numerous applications to business administration has remained limited so far, especially when compared with its potential for describing and explaining management problems. It is important, then, to show what the object of semiotic research is, independent of any semiotic orientation or school. What tools have been developed so far, and which discourses in business administration were chosen to apply these tools? The problems limiting a broader use of semiotic instruments in business administration are explained in detail, and the research perspectives are illustrated. Die in der deutschsprachigen Betriebswirtschaftslehre (BWL) noch wenig bekannte Semiotik und die in ihrem Rahmen entwickelten methodologischen Ansätze zur Analyse von Diskursen haben insbesondere in Frankreich und in den USA schon eine weite Verbreitung gefunden. Das Echo, auf welches die Semiotik trifft, bleibt im Vergleich zum Beitrag, den sie hinsichtlich der Beschreibung und Erklärung betriebswirtschaftlicher Tatbestände leisten könnte, noch sehr beschränkt - und dies, obwohl ihre grundsätzliche wissenschaftliche Leistungsfähigkeit inzwischen an Hand zahlreicher Beispiele aus dem betriebswirtschaftlichen Bereich belegt werden konnte. Es ist deshalb wichtig und interessant zu zeigen, was der Forschungsgegenstand der Semiotik ist - und zwar unabhängig von den verschiedenen Schulen der Semiotik. Welche Instrumente hat sie entwickelt? Auf welche betriebswirtschaftlichen Diskurse sind diese Instrumente bereits angewandt worden? Zum Schluss werden die Probleme dargestellt, die einen breiteren Einsatz semiotischer Instrumente in der Betriebswirtschaftslehre behindern und dabei auch die verschiedenen Forschungsrichtungen erläutert.

Uptake of new treatment strategies for deep vein thrombosis: an international audit.

OBJECTIVE: Study of the uptake of new medical technologies provides useful information on the transfer of published evidence into usual practice. We conducted an audit of selected hospitals in three countries (Canada, France, and Switzerland) to identify clinical predictors of low-molecular-weight (LMW) heparin use and outpatient treatment, and to compare the pace of uptake of these new therapeutic approaches across hospitals. DESIGN: Historical review of medical records. SETTING AND PARTICIPANTS: We reviewed the medical records of 3043 patients diagnosed with deep vein thrombosis (DVT) in five Canadian, two French, and two Swiss teaching hospitals from 1994 to 1998. Measures. We explored independent clinical variables associated with LMW heparin use and outpatient treatment, and determined crude and adjusted rates of LMW heparin use and outpatient treatment across hospitals. RESULTS: For the years studied, the overall rates of LMW heparin use and outpatient treatment in the study sample were 34.1 and 15.8%, respectively, with higher rates of use in later years. Many comorbidities were negatively associated with outpatient treatment, and risk-adjusted rates of use of these new approaches varied significantly across hospitals. CONCLUSION: There has been a relatively rapid uptake of LMW heparins and outpatient treatment for DVT in their early years of availability, but the pace of uptake has varied considerably across hospitals and countries.

Origine des populations de rainette verte (Hyla spp.) de l'ouest de la Suisse

DNA-based techniques are important tools for species assignment, in particular when identification with morphological criteria is difficult. The aim of this study was to genetically determine the species identity of tree frogs (Hyla spp.) populations from western and northern Switzerland (Swiss Plateau), this area being frequently subjected to introductions of species or sub-species from south of the Alps. We sequenced 261 base pairs of the mitochondrial DNA cytochrome b gene from 24 samples of tree frogs from the Swiss Plateau, Ticino (southern Switzerland) and the Dombes region (Ain, France), and compared them with homologous sequences retrieved from DNA databases. The phylogenetic analyses revealed two distinct clades. The first one is represented by samples of Green tree frog (Hyla arborea) from the Swiss Plateau, France, Germany and Greece, confirming the current knowledge about the species' distribution. The second clade includes samples belonging to the Italian tree frog (Hyla intermedia) from south of the Alps (Ticino and Italy), and unexpectedly from the Grangettes site in western Switzerland. These results suggest the introduction of the Italian tree frog H. intermedia north of the Alps, and raise questions about the management of the Grangettes protected area.

Exploring women's academic careers in cross-national perspective: lessons for equal epportunity eolicies

Purpose - In recent years, several countries and/or higher education institutions have adopted equal opportunity policies to promote women's access to the upper levels of the academic career structure. The purpose of this paper is to argue that there is no universal solution to the glass ceiling that women face within academia. Insofar as the feminisation process evolves according to a variety of models, according to national and occupational context, the solutions adopted in one context may prove to be ineffective elsewhere. Design/methodology/approach - Analysis of the different models of occupational feminisation is based on a secondary analysis of the sociological literature on the subject, combined with recent data on women's access to academic positions in France and Germany. Findings - Although there are similarities in the structure of the academic labour market across countries and in the rate of feminisation of the most prestigious academic positions, the precise mechanisms through which women gain access to an academic career vary significantly from one national context to another. This cross-national variation would tend to suggest that there will also be variation when it comes to defining the most effective policy measures for increasing women's access to the upper echelons of the academic hierarchy. Indeed, different models of gender equality in academia may lead to very different results with regard to existing gender relations. Originality/value - The paper uses the available sociological literature on the feminisation process to examine how different measures adopted to promote women's access to the highest echelons of the academic career structure may have different effects on the reproduction and/or transformation of the dominant sex/gender system.

Use of Treponema pallidum PCR in Testing of Ulcers for Diagnosis of Primary Syphilis(1.).

Treponema pallidum PCR (Tp-PCR) has been noted as a valid method for diagnosing syphilis. We compared Tp-PCR to a combination of darkfield microscopy (DFM), the reference method, and serologic testing in a cohort of 273 patients from France and Switzerland and found the diagnostic accuracy of Tp-PCR was higher than that for DFM.

A human MYBPC3 mutation appearing about 10 centuries ago results in a hypertrophic cardiomyopathy with delayed onset, moderate evolution but with a risk of sudden death.

BACKGROUND: Hypertrophic Cardiomyopathy (HCM) is a genetically heterogeneous disease. One specific mutation in the MYBPC3 gene is highly prevalent in center east of France giving an opportunity to define the clinical profile of this specific mutation. METHODS: HCM probands were screened for mutation in the MYH7, MYBPC3, TNNT2 and TNNI3 genes. Carriers of the MYBPC3 IVS20-2A>G mutation were genotyped with 8 microsatellites flanking this gene. The age of this MYBPC3 mutation was inferred with the software ESTIAGE. The age at first symptom, diagnosis, first complication, first severe complication and the rate of sudden death were compared between carriers of the IVS20-2 mutation (group A) and carriers of all other mutations (group B) using time to event curves and log rank test. RESULTS: Out of 107 HCM probands, 45 had a single heterozygous mutation in one of the 4 tested sarcomeric genes including 9 patients with the MYBPC3 IVS20-2A>G mutation. The IVS20-2 mutation in these 9 patients and their 25 mutation carrier relatives was embedded in a common haplotype defined after genotyping 4 polymorphic markers on each side of the MYBPC3 gene. This result supports the hypothesis of a common ancestor. Furthermore, we evaluated that the mutation occurred about 47 generations ago, approximately at the 10th century.We then compared the clinical profile of the IVS20-2 mutation carriers (group A) and the carriers of all other mutations (group B). Age at onset of symptoms was similar in the 34 group A cases and the 73 group B cases but group A cases were diagnosed on average 15 years later (log rank test p = 0.022). Age of first complication and first severe complication was delayed in group A vs group B cases but the prevalence of sudden death and age at death was similar in both groups. CONCLUSION: A founder mutation arising at about the 10th century in the MYBPC3 gene accounts for 8.4% of all HCM in center east France and results in a cardiomyopathy starting late and evolving slowly but with an apparent risk of sudden death similar to other sarcomeric mutations.

Zuckerman's reivsed alternative five-factor model: Validation of the Zuckerman-Kuhlman-Aluja Personality Questionnaire in four French-speaking countries

The aim of this study was to analyze the replicability of Zuckerman's revised Alternative Five-factor model in a French-speaking context by validating the Zuckerman-Kuhlman-Aluja Personality Questionnaire (ZKA-PQ) simultaneously in 4 French-speaking countries. The total sample was made up of 1,497 subjects from Belgium, Canada, France, and Switzerland. The internal consistencies for all countries were generally similar to those found for the normative U.S. and Spanish samples. A factor analysis confirmed that the normative structure replicated well and was stable within this French-speaking context. Moreover, multigroup confirmatory factor analyses have shown that the ZKA-PQ reaches scalar invariance across these 4 countries. Mean scores were slightly different for women and men, with women scoring higher on Neuroticism but lower on Sensation Seeking. Globally, mean score differences across countries were small. Overall, the ZKA-PQ seems an interesting alternative to assess both lower and higher order personality traits for applied or research purposes.

First occurrence of the crazy ant Paratrechina longicornis (Latreille) (Hym. Formicidae: Formicinae) in Switzerland

Paratrechina longicornis (Latreille) has been recorded for the first time in Switzerland in the Kloten airpot in Zürich. This species originates from the tropics and has been introduced into many parts of the world. In Europe, it was only mentionned from France and the British Isle.

Hepatitis E Virus Seroprevalence among Blood Donors in Southwest Switzerland.

Aim: The aim of this study was to determine the seroprevalence of Hepatitis E virus (HEV) among blood donors in southwest Switzerland.Background: HEV is recognized as a food-borne disease in industrialized countries, transmitted mainly through pork meat. Cases of transmission through blood transfusion have also been reported. Recent studies have revealed seroprevalence rates of 13.5%, 16.6% and 20.6% among blood donors in England, France and Denmark, respectively.Methods: We analyzed 550 consecutive blood donor samples collected in the region of Lausanne, canton of Vaud, Switzerland, for the presence of anti-HEV IgG, using the MP Diagnostics HEV ELISA kit. For each donor, we documented age, sex and alanine aminotransferase (ALT) value.Results: The study panel was composed of 332 men (60.4%) and 218 women (39.6%). Overall, anti-HEV IgG was found in 27 of 550 samples (4.9%). The seroprevalence was 5.4% (18/332) in men and 4.1% (9/218) in women. The presence of anti-HEV IgG was not correlated with age, gender or ALT values. However, we observed a peak in seroprevalence of 5.3% in individuals aged 51 to 70 years old.Conclusions: Compared with other European countries, HEV seroprevalence among blood donors in southwest Switzerland is low. The low seroprevalence may be explained by the sensitivity of commercial tests used and/or the strict regulation of animal and meat imports. Data regarding HEV prevalence in Swiss livestock are lacking and merit exploration.

Cost-effectiveness of pharmacotherapies for nicotine dependence in primary care settings: a multinational comparison.

OBJECTIVE: To estimate the incremental cost-effectiveness of the first-line pharmacotherapies (nicotine gum, patch, spray, inhaler, and bupropion) for smoking cessation across six Western countries-Canada, France, Spain, Switzerland, the United States, and the United Kingdom. DESIGN AND STUDY POPULATION: A Markov-chain cohort model to simulate two cohorts of smokers: (1) a reference cohort given brief cessation counselling by a general practitioner (GP); (2) a treatment cohort given counselling plus pharmacotherapy. Effectiveness expressed as odds ratios for quitting associated with pharmacotherapies. Costs based on the additional physician time required and retail prices of the medications. INTERVENTIONS: Addition of each first-line pharmacotherapy to GP cessation counselling. MAIN OUTCOME MEASURES: Cost per life-year saved associated with pharmacotherapies. RESULTS: The cost per life-year saved for counselling only ranged from US190 dollars in Spain to 773 dollars in the UK for men, and from 288 dollars in Spain to 1168 dollars in the UK for women. The incremental cost per life-year saved for gum ranged from 2230 dollars for men in Spain to 7643 dollars for women in the US; for patch from 1758 dollars for men in Spain to 5131 dollars for women in the UK; for spray from 1935 dollars for men in Spain to 7969 dollars for women in the US; for inhaler from 3480 dollars for men in Switzerland to 8700 dollars for women in France; and for bupropion from 792 dollars for men in Canada to 2922 dollars for women in the US. In sensitivity analysis, changes in discount rate, treatment effectiveness, and natural quit rate had the strongest influences on cost-effectiveness. CONCLUSIONS: The cost-effectiveness of the pharmacotherapies varied significantly across the six study countries, however, in each case, the results would be considered favourable as compared to other common preventive pharmacotherapies.