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Purpose This paper aims at analysing the relationship between anticipation and public administration based on a case study focusing on a specific public agency in charge of knowledge production for policymaking. Design/methodology/approach It is based on a case study methodology: anticipatory practices of a public organisation are critically assessed based on data that originates from public documents and from participant observation within the concerned agency. Findings Several dimensions impact the interrelation between anticipation and public administration. First, the organisational set-up is decisive in fostering the development of specific type of anticipatory activities. Second, it confirms a common finding that policymakers are oftentimes more interested in ready-to-use results than in processes of future thinking. And third, it shows that distinctive anticipatory practices can rely on very different networks and, therefore, have different degree of maturity. Research limitations/implications The use of a case study, unfortunately, may lead to a lack of generalisability. The authors therefore encourage researchers to test their propositions further. Originality/value Nevertheless, the originality of the paper is its central focus on anticipation within public administration – a topic that has not received much attention or study by academics or researchers. Anticipatory practices have been studied at a more general level, but not necessarily in particular public sector environments, which also have their own particular constraints.

L’article donne une vue d’ensemble des contributions a la conference sur les indicateurs de progres societal organisee en decembre 2014 par l’IWEPS et le BFP ainsi que de ses principaux enseignements. La mise en œuvre des decisions politiques pionnieres en cette matiere en Wallonie et au niveau federal belge est situee dans le cadre des developpements en cours des projets internationaux concernant les indicateurs. L’article montre la richesse et la diversite de la dynamique regionale, nationale et internationale alimentant le debat sur les meilleures facons de mesurer le progres des societes, ainsi que les efforts de convergence en cours. Ces balises permettent notamment de comprendre les processus de decision, de construction et d’usage determinant la conception des indicateurs complementaires au PIB et des indicateurs de developpement durable.

Pilocytic astrocytoma (PA) is the most common brain tumor in children but is rare in adults, and hence poorly studied in this age group. We investigated 222 PA and report increased aneuploidy in older patients. Aneuploid genomes were identified in 45% of adult compared with 17% of pediatric PA. Gains were non-random, favoring chromosomes 5, 7, 6 and 11 in order of frequency, and preferentially affecting non-cerebellar PA and tumors with BRAF V600E mutations and not with KIAA1549-BRAF fusions or FGFR1 mutations. Aneuploid PA differentially expressed genes involved in CNS development, the unfolded protein response, and regulators of genomic stability and the cell cycle (MDM2, PLK2),whose correlated programs were overexpressed specifically in aneuploid PA compared to other glial tumors. Thus, convergence of pathways affecting the cell cycle and genomic stability may favor aneuploidy in PA, possibly representing an additional molecular driver in older patients with this brain tumor.

OBJECTIVE: Small cell carcinoma of the ovary, hypercalcemic type (SCCOHT) is an aggressive tumor, with long term survival at ~30% in early stage disease. SCCOHT is caused by germline and somatic SMARCA4 mutations, but the effect of the mutation type on patients remains unknown. Furthermore, the rarity of SCCOHT has resulted in varied treatment, with no standardized protocols. We analyzed 293 cases to determine the effect of treatment modalities and SMARCA4 mutations on patient diagnosis and outcome. METHODS: In 293 SCCOHT patients we collected information on age and stage at diagnosis, treatment modality (surgery, chemotherapy, radiotherapy, and/or high-dose chemotherapy with autologous stem cell rescue (HDC-aSCR)), SMARCA4 mutation origin (germline/somatic), and overall survival. Cox analysis and log-rank tests were performed on 257 cases with available survival data. RESULTS: The strongest prognostic factors were stage at diagnosis (p = 2.72e-15) and treatment modality (p = 3.87e-13). For FIGO stages II-IV, 5-year survival was 71% for patients who received HDC-aSCR, compared to 25% in patients who received conventional chemotherapy alone following surgery (p = 0.002). Patients aged ≥40 had a worse outcome than younger patients (p = 0.04). Twenty-six of 60 tested patients carried a germline SMARCA4 mutation, including all patients diagnosed

This is an 11-year survey of molecular analysis of APC germline mutations for the province of Quebec done at the Molecular Pathology Unit of the Jewish General Hospital which offers genetic testing for hereditary forms of colorectal cancer for the whole of Quebec province. We report on 47 unique mutations seen in 66 families affected with familial adenomatous polyposis. Of these unique mutations, 60% are short indels, 28% are point mutations, and 6% are whole exon deletions. The absence of founder mutations and the variety of mutations encountered reinforce the value of RNA-based testing and the need for gene dosage techniques such as multiplex ligation-dependent probe amplification.

This article links the theory of reflexive modernization to Parliamentary Technology Assessment (PTA) by considering the latter as an indication of modern Western societies becoming more reflexive, that is, acknowledging and responding to the limitations of modern traditions by institutionalizing new processes of technology assessment to address a realm of change where uncertainty is no longer contained within modern structures. Our conceptual framework must address both the emergence and functioning of PTA in the form of institutions and the practices that are pursued within (or around, and linked to) such institutions, with due attention being paid to the multiple approaches currently being debated around the transformation of modernity and reflexivity. Reflexive modernization offers a relevant theoretical approach to analyzing hybrid entities like PTA institutions. We demonstrate this by analyzing three such institutions (Science and Technology Options Assessment [STOA, European Parliament], Institute for Society and Technology [IST, Flanders, Belgium] and Rathenau Institute [The Netherlands]), mapping their different approaches and practices in terms of features of reflexive modernization. There appears to be an overall reflexivity pathway, on which some PTAs have moved farther than others, but their progress is fractured by the resilience of modern institutions. We conclude that to ensure their role in the current institutional landscapes of evolving modern societies, the most important thing for PTA institutions is therefore to somehow develop a relevant approach while dealing with the necessary margin of maneuver for further adaptation and transformation.

O princípio da precaução está inserido em um contexto decisional em evolução, marcado por uma incerteza multidimensional com relação às conseqüências ambientais, econômicas, sociais, éticas e políticas das inovações tecnológicas. Na ciência política de língua francesa, o princípio funciona como uma ferramenta estratégica, uma resposta política ao surgimento de um novo fluxo de incerteza social, voltada principalmente para as inseguranças do mundo científico. Neste trabalho, afirmamos que o princípio da precaução redefine a forma de gerir a incerteza científica, em uma sociedade caracterizada pela indefinição das fronteiras entre atores políticos e subpolíticos. Em sua aplicação, há uma linha de ruptura que reduz a margem de manobra decisória de determinadas entidades subpolíticas, enquanto incentiva outras a agirem. Contudo, enfatizamos que, em um mundo cada vez mais globalizado e interligado, os efeitos da aplicação do princípio da precaução são temporários e locais. Ainda assim, o princípio pode contribuir para os importantes debates a serem desenvolvidos em espaços institucionais, para uma ação reflexiva antecipatória e de apoio à decisão².

Resume Participation, intersectorialite, reseau et politiques locales sont des concepts-clefs mobilises par les pouvoirs publics dans le domaine de la promotion de la sante. Ces concepts sont mis en œuvre par les acteurs de terrain sans qu’il y ait necessairement une connaissance sur la maniere dont ceux-ci les comprennent.Une initiative participative organisee par le Centre Liegeois de Promotion de la Sante (Province de Liege, Belgique) a cependant permis de mettre en lumiere cette appropriation des concepts par les acteurs de terrain et de nourrir ainsi la reflexion pour tendre vers plus de coherence dans les politiques de sante.

Les grandes orientations collectives de la societe sont l’affaire des institutions democratiques, mais il faut reconnaitre qu’un grand nombre de changements sociaux sont apportes par le developpement scientifique et l’innovation technologique. Quelle maitrise une societe democratique peut-elle alors avoir sur les consequences de son developpement technologique ? C’est pour tenter de se donner les moyens d’une telle maitrise qu’ont ete mis sur pied des offices parlementaires d’evaluation technologique ou encore Offices of Technology Assessment. Les Etats-Unis sont les pionniers en la matiere. Cependant l’organisme parlementaire qu’ils ont cree en 1972 a ferme ses portes. Ensuite, dans l’ordre chronologique de leur creation viennent les organismes crees par la France puis par le Danemark, deux pays dont les pratiques de Technology Assessment sont parfois sensiblement differentes tant sur le plan de la methodologie utilisee qu’en termes de poids dans les processus decisionnels. La quatrieme agence presentee est celle liee au Parlement europeen. Il nous paraissait interessant de montrer comment une Europe, en crise et en construction, concevait le Technology Assessment pour servir un Parlement representant 25 Etats membres et pres de 460 millions d’habitants. C’est par la Flandre que le Technology Assessment est entre en Belgique. L’etude se termine par la presentation du jeune viTWA, qui est au service du Parlement flamand. Du cote francophone les realisations sont encore minces, meme si le debat est ouvert, principalement dans les spheres universitaires. Apres bientot trente-cinq ans d’existence, les offices de Technology Assessment commencent lentement mais surement a se faire connaitre. Leur evaluation est necessaire pour assurer une plus grande adequation de leur travail.

We present an integrated approach for the enriched detection of genes subject to cis-acting variation in the mouse genome. Gene expression profiling was performed with lung tissue from a panel of recombinant congenic strains (RCS) derived from A/J and C57BL/6J inbred mouse strains. A multiple-regression model measuring the association between gene expression level, donor strain of origin (DSO), and predominant strain background identified over 1,500 genes ( P < 0.05) whose expression profiles differed according to the DSO. This model also identified over 1,200 genes whose expression showed dependence on background ( P < 0.05), indicating the influence of background genetic context on transcription levels. Sequences obtained from 1-kb segments of 3′-untranslated regions identified single nucleotide polymorphisms in 64% of genes whose expression levels correlated with DSO status, compared with 29% of genes that displayed no association ( P < 0.01, Fisher exact test). Allelic imbalance was identified in 50% of genes positive for expression-DSO association, compared with 22% of negative genes ( P < 0.05, Fisher exact test). Together, these results demonstrate the utility of RCS mice for identifying the roles of proximal genetic determinants and background genetic context in determining gene expression levels. We propose the use of this integrated experimental approach in multiple tissues from this and other RCS panels as a means for genome-wide cataloging of genetic regulatory mechanisms in laboratory strains of mice.

Aims To evaluate the effects of food and formulation on the pharmacokinetics of bismuth biskalcitrate, metronidazole and tetracycline when combined in a new 3-in-1 single capsule (BMT) for eradication of Helicobacter pylori. Methods In a randomized, 3 × 3 cross-over design, 23 healthy males received one dose of BMT in the fed and fasting states and equivalent doses of the three drugs given together but as separate capsules while fasting. Bioequivalence was evaluated according to 90% confidence intervals (CIs) of ratios of geometric least square means for Cmax, AUCt, and AUC∞. Results With respect to food, none of the three drugs met bioequivalence guidelines. Bismuth had lower limit CIs ranging from 12% for Cmax to 25% for AUC∞. The corresponding values for tetracycline were 59% and 51%. Metronidazole had a lower limit CI of 74% for Cmax. With respect to formulation, bismuth had lower limits of CIs ranging from 39% for Cmax to 50% for AUCt and higher limits of 146% for AUCt, metronidazole met bioequivalence guidelines, and tetracycline had lower limits of CIs between 72% for AUCt and 74% for AUC∞. Conclusions Food significantly decreased the relative bioavailability of each drug but formulation was without effect. This decrease may be beneficial when a local gastric action is needed, as confirmed by a near 90% eradication rate when this combined capsule is administered with food to treat gastro-duodenal local infection by H. pylori.

Purpose: BRCA1-related breast cancer frequently has a basal epithelial phenotype, and P-cadherin is a basal marker. We undertook a detailed evaluation of the relationship among P-cadherin, prognostic markers in breast cancer, and outcome. Experimental Design: This study was restricted to 292 cases of first primary invasive breast cancer diagnosed in Ashkenazi Jewish women between 1980 and 1995. All available blocks were stained for P-cadherin, and 261 were included in the final statistical analyses, including 27 germ line BRCA1 mutation carriers and 8 BRCA2 mutation carriers. Descriptive analyses were done followed by survival analyses and a Poisson regression analysis. Results: P-cadherin was present in 80 of the 261 breast cancers (31%) and was more frequently present in tumors that have a basal epithelial phenotype [i.e., high-grade, estrogen receptor– and KIP1 (p27Kip1)–negative tumors, with expression of cytokeratin 5/6, cyclin E, TP53, and presence of BRCA1 mutations and vascular nests (all P < 0.001)]. In a univariate survival model, expression of P-cadherin was associated with a relative risk (RR) of death from breast cancer at a 10-year follow-up of 2.9 (95% confidence interval, 1.8-4.7; P < 0.0001) and was a predictor of poor univariate survival in both lymph node–negative and –positive breast cancers. In a multivariate analysis, the effect of P-cadherin levels was not independent of other basal-related markers. Multivariable interaction modeling showed that P-cadherin positivity was highly predictive of a poor prognosis in small, node-negative breast cancers (RR, 7.1; P = 0.006). Conclusions: P-cadherin is a marker for basal-like breast cancers and is strongly associated with the presence of a BRCA1 mutation. It is an adverse prognostic factor, particularly in small, node-negative breast cancers.

Previous studies have shown that BRCA1-related breast cancers are often high-grade tumors that do not express estrogen receptors, HER2, p27Kip1, or cyclin D1, but do express p53 and cyclin E. In addition, the expression of cytokeratin 5/6 (CK5/6), indicating a basal epithelial phenotype, is frequent in BRCA1-related breast cancer. Here, in a series of 247 breast cancers, we demonstrate that CK5/6 expression was associated with nearly all of the features of BRCA1-related breast cancer and was also associated with a poor prognosis. In a parsimonious multivariable proportional hazards model, protein levels of cyclin E, p27Kip1, p53, and the presence of glomeruloid microvascular proliferation all independently predicted outcome after breast cancer. In this model, only cyclin E and p27Kip1 levels were independent predictors in lymph node-negative cancers, whereas glomeruloid microvascular proliferation and tumor size independently predicted outcome in node-positive disease. The molecular determinants of the basal epithelial phenotype encapsulate many of the key features of breast cancers occurring in germ-line BRCA1 mutation carriers and have independent prognostic value. Basal breast cancer deserves recognition as an important subtype of breast cancer.

BACKGROUND A positive correlation between breast tumor size and the number of axillary lymph nodes containing tumor is well established. It has been reported that patients with BRCA1-related breast carcinoma are more likely than patients with nonhereditary breast carcinoma to have negative lymph node status. Therefore, the authors questioned whether the known positive correlation between tumor size and lymph node status also was present in women with BRCA1-related breast carcinomas. METHODS The relation between the greatest dimension of the resected breast tumor (size) and the presence of positive axillary lymph nodes (expressed as a percentage of all lymph nodes examined) was evaluated in 1555 women with invasive breast carcinoma who were ascertained at 10 centers in North America between 1975 and 1997. There were 276 BRCA1 mutation carriers, 136 BRCA2 carriers, and 1143 women without a known mutation (208 BRCA1/BRCA2 noncarriers and 935 untested women). Patients were stratified according to tumor size, and odds ratios were estimated for the presence of positive lymph nodes with increasing tumor size. RESULTS A highly significant positive correlation between tumor size and the frequency of positive axillary lymph nodes was seen for BRCA1/BRCA2 noncarriers, for BRCA2 carriers, and for untested women (overall P < 0.0001 for each). In contrast, there was no clear correlation between tumor size and positive lymph node status in BRCA1 carriers (overall P = 0.20). CONCLUSIONS The relation between tumor size and lymph node status in patients with breast carcinoma appears to be different in BRCA1 carriers compared with BRCA2 carriers and noncarriers. These findings have important implications for estimating the route of metastatic spread and for evaluating the effectiveness of early diagnosis in patients with BRCA1-related breast carcinoma. Cancer 2003. ©2003 American Cancer Society. DOI 10.1002/cncr.11688

Summary Background Women with a mutation in BRCA1 or BRCA2 have a high risk of developing breast cancer and of contralateral cancer after the initial diagnosis of breast cancer. Tamoxifen protects against contralateral breast cancer in the general population, but whether it protects against contralateral breast cancer in BRCA1 or BRCA2 mutation carriers is not known. Methods We compared 209 women with bilateral breast cancer and BRCA1 or BRCA2 mutation (bilateral-disease cases), with 384 women with unilateral disease and BRCA1 or BRCA2 mutation (controls) in a matched case-control study. Age and age at diagnosis of breast cancer (range 24–74 years) were much the same in bilateral-disease cases and controls, and both groups had been followed up for the same time for a second primary breast cancer. History of tamoxifen use for first breast cancer was obtained by interview, or by self-administered questionnaire. Findings The multivariate odds ratio for contralateral breast cancer associated with tamoxifen use was 0–50 (95% Cl 0·28–0·89). Tamoxifen protected against contralateral breast cancer for carriers of BRCA1 mutations (odds ratio 0·38, 95% Cl 0·19–0·74) and for those with BRCA2 mutations (0·63, 0·20–1·50). In women who used tamoxifen for 2–4 years, the risk of contralateral breast cancer was reduced by 75%. A reduction in risk of contralateral cancer was also seen with oophorectomy (0·42, 0·22–0·83) and with chemotherapy (0·40, 0·26–0·60). Interpretation Tamoxifen use reduces the risk of contralateral breast cancer in women with pathogenic mutations in the BRCA1 or BRCA2 gene. The protective effect of tamoxifen seems independent of that of oophorectomy.

Summary Background Early age at first full-term pregnancy and increasing parity are associated with a reduced risk of breast cancer. However, whether pregnancy decreases the risk of early-onset hereditary breast cancer is unknown. There is concern that pregnancy may increase breast-cancer risk in carriers of BRCA1 and BRCA2 germline mutations. We aimed to establish whether pregnancy is a risk factor for hereditary breast cancer. Methods We did a matched case-control study of breast cancer in women who carry deleterious BRCA1 or BRCA2 mutations. Cases were carriers who developed breast cancer by age 40 years, and controls were carriers of the same age without breast cancer, or who were diagnosed with breast cancer after age 40 years. Women who had undergone preventive mastectomy, hysterectomy, or oophorectomy, or who were diagnosed with ovarian cancer before the age at which breast cancer was diagnosed in the matched case were excluded. Information about pregnancies and pregnancy outcome was derived from a questionnaire completed by women in the course of genetic counselling. Findings A higher proportion of cases than controls had had a full term pregnancy (173/236 vs 146/236; odds ratio 1·71 [95% CI 1·13–2·62], p=0·01). The mean number of births was also greater for cases than for controls (1.62 vs 1·38, p=0·04). The risk increased with the number of births and did not diminish with time since last pregnancy. There were no significant differences in age at first birth or age at last birth between cases and controls. Interpretation Carriers of the BRCA1 and BRCA2 mutations who have children are significantly more likely to develop breast cancer by age 40 than carriers who are nulliparous. Each pregnancy is associated with an increased cancer risk. An early first pregnancy does not confer protection for carriers of BRCA1 or BRCA2 mutations.

The I1307K polymorphism in APC has been found to predispose to colorectal cancer in Ashkenazi Jews, and has recently been associated with an increased risk for breast cancer in the same population. In that study, we genotyped 205 paraffin-embedded breast cancers from Ashkenazi Jewish women diagnosed below the age of 65. We now present an extended analysis, with clinicopathological correlations between carriers of I1307K and non-carriers. Twenty-four of 209 cases (11.5%, 95% confidence interval 7.5–16.6) were found to carry the I1307K polymorphism. When stratifying the data by other relevant clinicopathological variables, we observed no association between the presence of this polymorphism and age at diagnosis (P = 0.52), grade (P = 0.074), tumour size (P = 0.99), lymph node status (P = 0.82), oestrogen receptor status (P = 0.23) or P53 immunoreactivity (P = 0.80). The breast-cancer specific 5-year survival for women with I1307 K polymorphism was 88.9% compared with 81.6% in women without I1307K (P = 0.34). Using microdissected samples and direct sequencing, no somatic mutations were observed in any of the 24 I1307K-positive cases. Single-strand conformation analysis of 158 of the I1307K-negative breast cancers that were available for study revealed no mobility shifts. We conclude that the presence of the I1307K polymorphism does not appear to be associated with any particular clinicopathological feature of breast cancer and importantly, does not affect the prognosis. © 1999 Cancer Research Campaign

Approximately 2.0%-2.5% of Ashkenazi Jewish women carry one of three founding mutations in the BRCA1 and BRCA2 genes, and each mutation is associated with a high lifetime risk of invasive breast cancer. We investigated the extent to which these three mutations contribute to breast cancer incidence in the Ashkenazi Jewish population.We ascertained 457 Jewish women with prevalent cases of breast cancer who were unselected for age or family history of the disease; 412 of these women were tested for the three founder mutations (case patients). Control subjects consisted of 360 non-Jewish women with breast cancer (control patients) and 380 healthy Jewish women with no history of cancer (control subjects).Mutations were found in 48 (11.7%) of 412 Jewish case patients. Forty-six of 48 mutations occurred in women with early-onset breast cancer (50 years) or a history of ovarian or early-onset breast cancer in a first-, second-, or third-degree relative. The estimated penetrance to age 70 years for breast cancer was 59.9% for the BRCA1 gene mutations and 28.3% for the BRCA2 gene mutation. Compared with Jewish control subjects, the relative risk (RR) of breast cancer for first-degree relatives of mutation carriers was 5.16 (95% confidence interval [CI] = 3.14-8. 48), but risk was also increased for relatives of noncarriers (RR = 1.66; 95% CI = 1.18-2.33). The RR of prostate cancer for first-degree relatives of Jewish case patients was 3.36 (95% CI = 1. 49-7.56).Approximately 12% of breast cancers in the Ashkenazi Jewish population are attributable to mutations in the BRCA1 or BRCA2 gene. Genetic testing may be useful when Jewish women with breast cancer are diagnosed before age 50 years or have a close relative with ovarian or early-onset breast cancer. An association between breast and prostate cancers was observed in our study population.

Two biallelic polymorphisms in introns 3 and 6 of the p53 gene were analysed for a possible risk-modifying effect for ovarian cancer. Germline DNA was genotyped from 310 German Caucasian ovarian cancer patients and 364 healthy controls. We also typed 124 affected and 276 unaffected female carriers with known deleterious BRCA1 or BRCA2 germline mutation from high-risk breast-ovarian cancer families. Genotyping was based on PCR and high-resolution gel electrophoresis. German ovarian cancer patients who carried the rare allele of the MspI restriction fragment length polymorphism (RELP) in intron 6 were found to have an overall 1.93-fold increased risk (95% confidence internal (CI) 1.27–2.91) which further increased with the age at diagnosis of 41–60 years (odds ratio (OR) 2.71, 95% CI 1.10–6.71 for 41–50 and OR 2.44, 95% CI 1.12–5.28 for 51–60). The 16 bp duplication polymorphism in intron 3 was in a strong linkage to the MspI RFLP. In BRCA1 or BRCA2 mutation carriers, no difference in allele frequency was observed for carriers affected or unaffected with ovarian cancer. Our data suggest that intronic polymorphisms of the p53 gene modify the risk for ovarian cancer patients but not in carriers with BRCA1 or BRCA2 mutations. © 1999 Cancer Research Campaign

OBJECTIVE: The objective was to compare risk factors between familial and sporadic ovarian cancer by means of a case-control approach. STUDY DESIGN: We conducted a case-control study among French Canadian women in Montreal during 1995-1996. One hundred seventy women 20 to 84 years old with histologically confirmed diagnoses of primary ovarian carcinomas or borderline tumors were interviewed concerning their reproductive, family, and medical histories. During the same period 170 randomly selected population control subjects, frequency-matched to the case patients according to age and ethnic group, were also interviewed. Unconditional logistic regression methods were used for data analysis. RESULTS: The major factors influencing the risk of development of ovarian cancer were as follows: (1) family history of breast or ovarian cancer, (2) a late age at use of oral contraceptives (a protective effect), and (3) a late age at last childbirth (a protective effect for familial case patients only). CONCLUSION: These factors had equally great impacts in familial and sporadic cases, implying that the underlying mechanisms of carcinogenesis in sporadic and familial ovarian cancer may be similar and that hereditary ovarian cancer may be preventable. (Am J Obstet Gynecol 1998;179:403-10.)

Tournant deliberatif -, - imperatif participatif -: aujourd'hui, nombreux sont les citoyens, decideurs et chercheurs qui voient dans la participation un moyen d'approfondir et de revitaliser le processus democratique. Cependant, les dispositifs concrets qui visent a associer a un meme processus (de connaissance ou de decision) des parties prenantes aux interets divergents relevent encore largement de l'experimentation. Qu'est-ce qui fait le succes ou l'echec d'une experience participative ? Selon quels criteres l'evaluer ? Comment concevoir des dispositifs qui - tiennent - ? Davantage qu'une defense des merites de la participation, cet ouvrage en propose une mise a l'epreuve, a travers une serie de retours d'experiences. Centres, d'une part, sur l'exploration de controverses et, d'autre part, sur l'evaluation de politiques publiques, les chapitres decrivent les defis methodologiques auxquels des chercheurs ont ete confrontes pour integrer des publics heterogenes au processus de decision et faire emerger des representations essentielles a la comprehension de phenomenes politiques et sociaux. L'ouvrage invite ainsi a une meilleure apprehension de cette aventure participative passionnante mais incertaine, a travers des approches de chercheurs partageant une experience et une culture methodologique commune."

Objective To determine the contribution of inheritance to the incidence of squamous cell carcinoma of the head and neck. Design Historical cohort study. First degree relatives of cases with squamous cell carcinoma of the head and neck made up the exposed cohort and first degree relatives of spouses of cases made up the comparison unexposed cohort. Setting Ear, nose, and throat clinic in a large metropolitan teaching hospital. Subjects 1429 first degree relatives of 242 index cases of squamous cell carcinoma of the head and neck; as controls, 934 first degree relatives of the spouses of 156 index cases. Main outcome measures Relative risk of developing squamous cell carcinoma in first degree relatives of cases compared with risk in first degree relatives of spouses. Results The adjusted relative risk for developing head and neck cancer if the index case had squamous cell carcinoma of the head and neck was 3.79 (95% confidence interval 1.11 to 13.0). There were no significantly increased risks associated with a family history of cancer at other sites. The adjusted relative risk for squamous cell carcinoma of the head and neck was 7.89 (1.50 to 41.6) in first degree relatives of patients with multiple primary head and neck tumours. Conclusions These data suggest that genetic factors are important in the aetiology of head and neck cancer, in particular for patients with multiple primary cancers. Given the prolonged exposure of these subjects to carcinogens, these genetic factors may have a role in modifying carcinogen activity or in host resistance to carcinogens. Inherited factors may be important in persons with environmentally induced cancers.

Une maison explose en plein cœur de la ville de Liege, piegeant plusieurs victimes sous les decombres… C’est le declenchement de nombreuses actions menees dans l’urgence par des professionnels du risque et de la gestion de crise (services d’incendie, policiers, ambulanciers, secouristes, services communaux et provinciaux, etc.). Partant de l’analyse de cet evenement et de ses enseignements, cet ouvrage, fruit de rencontres entre chercheurs et professionnels, tente d’articuler risques, planification d’urgence et gestion de crise. La diversite des phenomenes auxquels nos societes sont confrontees est grande et l’organisation de l’action publique dans ce domaine necessite la coordination d’acteurs et d’institutions aux competences et horizons differents. Cet ouvrage a pour ambition de decortiquer cette realite en l’eclairant ici avec des considerations theoriques et la avec des exemples concrets issus de l’experience de terrain. Les auteurs abordent notamment les aspects suivants: le cadre institutionnel et juridique de la gestion de crise; la pragmatique de la planification; les responsabilites fonctionnelles civile et penale des organes communaux; les risques naturels; la diversite des notions de risque;l’evaluation et la gestion des risques.

Combination therapy is frequently required in the management of epilepsy. The primary objective of this study was to investigate the pharmacokinetic interaction between eslicarbazepine acetate (ESL) 1200 mg once daily and topiramate (TPM) 200 mg once daily in healthy subjects.Multiple-dose, open-label, one-sequence study in two parallel groups of 16 healthy male volunteers. After an 8-day treatment with ESL (Group A) or TPM (Group B), ESL and TPM were co-administered for 19 days. A bioequivalence approach based on a within-subject comparison was used to investigate a potential drug-drug interaction. End/start of treatment geometric mean ratios (GMR, %) and 90% confidence intervals (90% CI) were calculated for maximum plasma concentration (C(max)) and area under the plasma concentration-time curve over the dosing interval at steady-state (AUC(ss)) of eslicarbazepine (ESL major active metabolite), R-licarbazepine (ESL minor active metabolite) and TPM at Day 8 and Day 27.In Group A, eslicarbazepine GMR (90% CI) was 86.79% (81.06%; 92.94%) for C(max) and 92.70% (89.21%; 96.32%) for AUC(ss). In Group B, TPM GMR (90% CI) was 81.50% (77.48%; 85.89%) for C(max) and 81.81% (79.69%; 84.00%) for AUC(ss). The 90% CI of eslicarbazepine C(max) and AUC(ss) fell within the pre-specified bioequivalence range (80.00%; 125.00%), allowing it to be concluded that the extent of systemic exposure to eslicarbazepine was unaffected by the concomitant administration of TPM. The 90% CI for topiramate AUC(ss) was borderline in relation to the pre-specified bioequivalence range and topiramate C(max) fell outside the pre-specified bioequivalence range. Therefore, the extent of systemic exposure to TPM following co-administration with ESL was not formally bioequivalent to the extent of systemic exposure to TPM when TPM was administered alone. However, there was no difference between TPM elimination half-life following TPM co-administered with ESL and TPM administered alone (24.0 and 24.3 h, respectively). The bioavailability of R-licarbazepine was essentially bioequivalent. Two subjects discontinued due to adverse events. No clinical interaction appeared to be present in terms of adverse events when both drugs were given concomitantly.Concomitant administration of eslicarbazepine acetate 1200 mg once daily and topiramate 200 mg once daily showed no significant change in exposure to eslicarbazepine but an 18% decrease in exposure to topiramate, most likely caused by a reduced bioavailability of topiramate. No dose adjustment is required.

Purpose: Triple-negative (TN; estrogen receptor, progesterone receptor, and HER-2 negative) cancer and basal-like breast cancer (BLBC) are associated with poor outcome and lack the benefit of targeted therapy. It is widely perceived that BLBC and TN tumors are synonymous and BLBC can be defined using a TN definition without the need for the expression of basal markers. Experimental Design: We have used two well-defined cohorts of breast cancers with a large panel of biomarkers, BRCA1 mutation status, and follow-up data to compare the clinicopathologic and immunohistochemical features of TN tumors expressing one or more of the specific basal markers (CK5/6, CK17, CK14, and epidermal growth factor receptor; BLBC) with those TN tumors that express none of these markers (TN3BKE−). Results: Here, we show that although the morphologic features of BLBC are not significantly different from that of TN3BKE- tumors, BLBC showed distinct clinical and immunophenotypic differences. BLBC showed a statistically significant association with the expression of the hypoxia-associated factor (CA9), neuroendocrine markers, and other markers of poor prognosis such as p53. A difference in the expression of cell cycle-associated proteins and biomarkers involved in the immunologic portrait of tumors was seen. Compared with TN3BKE- tumors, BLBC was positively associated with BRCA1 mutation status and showed a unique pattern of distant metastasis, better response to chemotherapy, and shorter survival. Conclusion: TN breast cancers encompass a remarkably heterogeneous group of tumors. Expression of basal markers identifies a biologically and clinically distinct subgroup of TN tumors, justifying the use of basal markers (in TN tumors) to define BLBC.