Evidence for classification of c.1852_1853AA > GC in MLH1 as a neutral variant for Lynch syndrome

Background: Lynch syndrome (LS) is an autosomal dominant inherited cancer syndrome characterized by early onset cancers of the colorectum, endometrium and other tumours. A significant proportion of DNA variants in LS patients are unclassified. Reports on the pathogenicity of the c.1852_1853AA>GC (p.Lys618Ala) variant of the MLH1 gene are conflicting. In this study, we provide new evidence indicating that this variant has no significant implications for LS. Methods: The following approach was used to assess the clinical significance of the p.Lys618Ala variant: frequency in a control population, case-control comparison, co-occurrence of the p.Lys618Ala variant with a pathogenic mutation, co-segregation with the disease and microsatellite instability in tumours from carriers of the variant. We genotyped p.Lys618Ala in 1034 individuals (373 sporadic colorectal cancer [CRC] patients, 250 index subjects from families suspected of having LS [revised Bethesda guidelines] and 411 controls). Three well-characterized LS families that fulfilled the Amsterdam II Criteria and consisted of members with the p.Lys618Ala variant were included to assess co-occurrence and co-segregation. A subset of colorectal tumour DNA samples from 17 patients carrying the p.Lys618Ala variant was screened for microsatellite instability using five mononucleotide markers. Results: Twenty-seven individuals were heterozygous for the p.Lys618Ala variant; nine had sporadic CRC (2.41%), seven were suspected of having hereditary CRC (2.8%) and 11 were controls (2.68%). There were no significant associations in the case-control and case-case studies. The p.Lys618Ala variant was co-existent with pathogenic mutations in two unrelated LS families. In one family, the allele distribution of the pathogenic and unclassified variant was in trans, in the other family the pathogenic variant was detected in the MSH6 gene and only the deleterious variant co-segregated with the disease in both families. Only two positive cases of microsatellite instability (2/17, 11.8%) were detected in tumours from p.Lys618Ala carriers, indicating that this variant does not play a role in functional inactivation of MLH1 in CRC patients. Conclusions: The p.Lys618Ala variant should be considered a neutral variant for LS. These findings have implications for the clinical management of CRC probands and their relatives.

Distribución de "coxiella burnetii" en los rumiantes domésticos y en la fauna silvestre de la Comunidad Atutónoma Vasca. Evaluacióndel efecto del tratamiento antibiótico y de la vacunación en el control de la fiebre Q en rebaños ovinos naturalmente infectados

243 p. : il.

The use of role-play games in teaching: The International Climate Negotiation Game

This paper presents a role-play game designed by the authors, which focuses on international climate negotiations. The game has been used at a university with students all drawn from the same course and at summer schools with students from different levels (undergraduate, master’s and doctoral students and post-doctoral researchers) and different knowledge areas (economics, law, engineering, architecture, biology and others). We discuss how the game fits into the process of competence-based learning, and what benefits games, and role-play games in particular, have for teaching. In the game, students take on the role of representatives of national institutions and experience at first hand a detailed process of international negotiation concerned with climate change.

Unraveling Public Good Games: The Role of Priors

This paper provides experimental evidence on how players predict end game effects in a linear public good game. Our regression analysis yields a measure of the relative importance of priors and signals on subjects\' beliefs on contributions and allow us to conclude that, firstly, the weight of the signal is relatively unimportant, while priors have a large weight and, secondly, priors are the same for all periods. Hence, subjects do not expect end game effects and there is very little updating of beliefs.

On monotonic core allocations for coalitional games whith veto players

We characterize a monotonic core concept defined on the class of veto balanced games. We also discuss what restricted versions of monotonicity are possible when selecting core allocations. We introduce a family of monotonic core concepts for veto balanced games and we show that, in general, the nucleolus per capita is not monotonic.

The Supercore for Normal Form Games

We study the supercore of a system derived from a normal form game. For the case of a finite game with pure strategies, we define a sequence of games and show that the supercore of that system coincides with the set of Nash equilibrium strategy profiles of the last game in the sequence. This result is illustrated with the characterization of the supercore for the n-person prisoners’ dilemma. With regard to the mixed extension of a normal form game, we show that the set of Nash equilibrium profiles coincides with the supercore for games with a finite number of Nash equilibria. For games with an infinite number of Nash equilibria this need not be no longer the case. Yet, it is not difficult to find a binary relation which guarantees the coincidence of these two sets.

Increased physical activity is not enough to recover astrocytic population from dark-rearing. Synergy with multisensory enrichment is required

10 p.

On the impact of independence of irrelevant alternatives: the case of two-person NTU games

On several classes of n-person NTU games that have at least one Shapley NTU value, Aumann characterized this solution by six axioms: Non-emptiness, efficiency, unanimity, scale covariance, conditional additivity, and independence of irrelevant alternatives (IIA). Each of the first five axioms is logically independent of the remaining axioms, and the logical independence of IIA is an open problem. We show that for n = 2 the first five axioms already characterize the Shapley NTU value, provided that the class of games is not further restricted. Moreover, we present an example of a solution that satisfies the first five axioms and violates IIA for two-person NTU games (N, V) with uniformly p-smooth V(N).

Sormena bost urtko gelan. Musika, mugimendua eta jolasa.

Ez da arraroa, egungo eskolan, nolabaiteko aukera eza aurkitzea Haur Hezkuntzako haurraren sormena garatzeko. Aukera eza honi erantzuna emateko asmoz sortu da proiektu hau. Hiru bitarteko nagusi uztartzea proposatzen da: alde batetik, musika, sormenaren garapenerako aukera anitz eskaintzen dituelako; bestetik, mugimendua, haurraren garapenen fisiko eta kognitiboan berebiziko garrantzia duen funtzioa; eta, azkenik, jolasa elementu integratzaile bezala, gizakiok haurtzaroan dugun oinarrizko jarduera. Ondoren proposatzen diren jolasak zehazki sortuak, aukeratuak eta moldatuak izan dira sormena era ludikoan garatzeko. Barakaldoko Alkartu Ikastola Publikoan praktikan jarri eta gero, esan dezakegu haurrek ia mugarik gabeko sormena garatu dezaketela, irakasleak bitarteko egokiak eskura jartzen badizkie.

ADAPTECC: A Role-Play Game about Adapting to Climate Change

The ADAPTECC Climate Change Adaptation Game is a role-play game designed to enable players to experience the difficulties that arise at local and regional levels when authorities have to implement adaptation measures. Adaptation means anticipating the advert effects of climate change (CC) and taking measures to prevent and minimise the damage caused by its impacts. Each player takes the role of the mayor or a councillor of a town affected by CC who must decide what adaptation strategies and measures to take, or of a member of the Regional Environment Department which must distribute funding for adaptation among the various towns. At the end of the game, players should have a greater understanding of the challenges posed by adaptation to CC