Patient Perspective on the Value of Genetic Counselling for Familial Pancreas Cancer

<p>Abstract</p> <p>Purpose</p> <p>To assess patient views regarding the value of genetic counselling for familial pancreas cancer in the absence of predictive genetic testing.</p> <p>Patients and methods</p> <p>At-risk adults with three or more relatives with pancreas cancer received genetic counselling prior to research screening via endoscopic ultrasound. Questionnaires were mailed after the visit to assess perceived value of the counselling session.</p> <p>Results</p> <p>Ninety-three percent of respondents felt genetic counselling for pancreas cancer was helpful despite the lack of a causative gene, while only 7% felt that it should not be offered until such a gene is discovered. Over half of respondents believed the pancreas cancer in their family was caused by a gene mutation, and 42% thought they had inherited the mutation. The average perceived lifetime risk of developing pancreas cancer was 51%, and 87% of respondents would ultimately seek predictive genetic testing. When more information is gained, 89% would be interested in another genetic counselling session, and 82% would recommend current genetic counselling for pancreas cancer to a friend or relative with a family history of the disease.</p> <p>Conclusion</p> <p>Despite the lack of an identified major causative gene for pancreas cancer, respondents found genetic counselling for this malignancy to be helpful. These patients perceive their personal cancer risk to be high, and would seek predictive genetic testing if it were available. Referral for genetic counselling should be offered to appropriate individuals.</p

Distinct roles for the RSC and Swi/Snf ATP-dependent chromatin remodelers in DNA double-strand break repair

The failure of cells to repair damaged DNA can result in genomic instability and cancer. To efficiently repair chromosomal DNA lesions, the repair machinery must gain access to the damaged DNA in the context of chromatin. Here we report that both the RSC and Swi/Snf ATP-dependent chromatin-remodeling complexes play key roles in double-strand break (DSB) repair, specifically by homologous recombination (HR). RSC and Swi/Snf are each recruited to an in vivo DSB site but with distinct kinetics. We show that Swi/Snf is required earlier, at or preceding the strand invasion step of HR, while RSC is required following synapsis for completion of the recombinational repair event

The Yeast RSC Chromatin-Remodeling Complex Is Required for Kinetochore Function in Chromosome Segregation

The accurate segregation of chromosomes requires the kinetochore, a complex protein machine that assembles onto centromeric DNA to mediate attachment of replicated sister chromatids to the mitotic spindle apparatus. This study reveals an important role for the yeast RSC ATP-dependent chromatin-remodeling complex at the kinetochore in chromosome transmission. Mutations in genes encoding two core subunits of RSC, the ATPase Sth1p and the Snf5p homolog Sfh1p, interact genetically with mutations in genes encoding kinetochore proteins and with a mutation in centromeric DNA. RSC also interacts genetically and physically with the histone and histone variant components of centromeric chromatin. Importantly, RSC is localized to centromeric and centromere-proximal chromosomal regions, and its association with these loci is dependent on Sth1p. Both sth1 and sfh1 mutants exhibit altered centromeric and centromere-proximal chromatin structure and increased missegregation of authentic chromosomes. Finally, RSC is not required for centromeric deposition of the histone H3 variant Cse4p, suggesting that RSC plays a role in reconfiguring centromeric and flanking nucleosomes following Cse4p recruitment for proper chromosome transmission

Traffic Grooming: Combinatorial Results and Practical Resolutions.

In an optical network using the wavelength division multiplexing (WDM) technology, routing a request consists in assigning it a route in the physical network and a wavelength. If each request uses $1/g$ of the bandwidth of the wavelength, we will say that the grooming factor is $g$. That means that on a given edge of the network we can groom (group) at most $g$ requests on the same wavelength. With this constraint the objective can be either to minimize the number of wavelengths (related to the transmission cost) or minimize the number of Add Drop Multiplexers (shortly ADM) used in the network (related to the cost of the nodes). Here, we first survey the main theoretical results obtained for different grooming factors on various topologies: complexity, (in)approximability, optimal constructions, approximation algorithms, heuristics, etc. Then, we give an ILP formulation for multilayer traffic grooming and present some experimental results

L’atelier du consensus

Durant des décennies, la coopération franco-allemande a marqué de son empreinte l'intégration européenne. Ainsi, le cinquantième anniversaire du Traité de l'Élysée le 22 janvier 2013 n'a pas seulement été l'occasion, pour la France et l'Allemagne, de faire le bilan d'un demi-siécle de rapprochement bilatéral, mais aussi de rappeler que leur coopération est indissociable du projet d'intégration européenne. Les innovations institutionnelles sur lesquelles Paris et Berlin se sont entendus il y a dix ans, en janvier 2003, et grâce auxquelles ils souhaitaient éviter blocages et échecs, ne sauraient elles non plus se comprendre hors du contexte européen de l'époque. C'est pour cette raison que la Deutsche Gesellschaft für Auswärtige Politik (DGAP), la Fondation Genshagen et l'Université de Cergy-Pontoise (C1CC/CIRAC) ont décidé, il y a un peu plus de deux ans de cela, de lancer un projet de recherche qui analyse les facteurs de réussite des canaux de communication et des processus de décision franco-allemands. À cette fin, dix tandems formés de chercheurs français et allemands se sont penchés sur des études de cas issus de quatre champs politiques différents, qui tous ont eu un impact sur l'évolution de l'Union européenne entre 2003 et 2012. Le présent ouvrage réunit les résultats de ce projet franco-allemand

Comparative analysis of anticholinergic burden scales to explain iatrogenic cognitive impairment and self-reported side effects in the euthymic phase of bipolar disorders: Results from the FACE-BD cohort

Bipolar disorders (BD) are characterized by cognitive impairment during the euthymic phase, to which treatments can contribute. The anticholinergic properties of medications, i.e., the ability of a treatment to inhibit cholinergic receptors, are associated with cognitive impairment in elderly patients and people with schizophrenia but this association has not been well characterized in individuals with remitted BD. Moreover, the validity of only one anticholinergic burden scale designed to assess the anticholinergic load of medications has been tested in BD. In a literature review, we identified 31 existing scales. We first measured the associations between 27 out of the 31 scales and objective cognitive impairment in bivariable regressions. We then adjusted the bivariable models with covariates: the scales significantly associated with cognitive impairment in bivariable and multiple logistic regressions were defined as having good concurrent validity to assess cognitive impairment. In a sample of 2,031 individuals with euthymic BD evaluated with a neuropsychological battery, two scales had good concurrent validity to assess cognitive impairment, whereas chlorpromazine equivalents, lorazepam equivalents, the number of antipsychotics, or the number of treatments had not. Finally, similar analyses with subjective anticholinergic side-effects as outcome variables reported 14 scales with good concurrent validity to assess self-reported peripheral anticholinergic side-effects and 13 to assess self-reported central anticholinergic side-effects. Thus, we identified valid scales to monitor the anticholinergic burden in BD, which may be useful in estimating iatrogenic cognitive impairment in studies investigating cognition in BD