The exon 13 duplication in the BRCA1 gene is a founder mutation present in geographically diverse populations

Cataloged from PDF version of article.Recently, a 6-kb duplication of exon 13, which creates a frameshift in the coding sequence of the BRCA1 gene, has been described in three unrelated U.S. families of European ancestry and in one Portuguese family. Here, our goal was to estimate the frequency and geographic diversity of carriers of this duplication. To do this, a collaborative screening study was set up that involved 39 institutions from 19 countries and included 3,580 unrelated individuals with a family history of the disease and 934 early-onset breast and/or ovarian cancer cases. A total of 11 additional families carrying this mutation were identified in Australia (1), Belgium (1), Canada (1), Great Britain (6), and the United States (2). Haplotyping showed that they are likely to derive from a common ancestor, possibly of northern British origin. Our results demonstrate that it is strongly advisable, for laboratories carrying out screening either in English-speaking countries or in countries with historical links with Britain, to include within their BRCA1 screening protocols the polymerase chain reaction-based assay described in this report

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Exploring Millions of 6-State FSSP Solutions: the Formal Notion of Local CA Simulation

In this paper, we come back on the notion of local simulation allowing to transform a cellular automaton into a closely related one with different local encoding of information. This notion is used to explore solutions of the Firing Squad Synchronization Problem that are minimal both in time (2n -- 2 for n cells) and, up to current knowledge, also in states (6 states). While only one such solution was proposed by Mazoyer since 1987, 718 new solutions have been generated by Clergue, Verel and Formenti in 2018 with a cluster of machines. We show here that, starting from existing solutions, it is possible to generate millions of such solutions using local simulations using a single common personal computer

Multiple indices of diffusion identifies white matter damage in mild cognitive impairment and Alzheimer's disease

The study of multiple indices of diffusion, including axial (DA), radial (DR) and mean diffusion (MD), as well as fractional anisotropy (FA), enables WM damage in Alzheimer's disease (AD) to be assessed in detail. Here, tract-based spatial statistics (TBSS) were performed on scans of 40 healthy elders, 19 non-amnestic MCI (MCIna) subjects, 14 amnestic MCI (MCIa) subjects and 9 AD patients. Significantly higher DA was found in MCIna subjects compared to healthy elders in the right posterior cingulum/precuneus. Significantly higher DA was also found in MCIa subjects compared to healthy elders in the left prefrontal cortex, particularly in the forceps minor and uncinate fasciculus. In the MCIa versus MCIna comparison, significantly higher DA was found in large areas of the left prefrontal cortex. For AD patients, the overlap of FA and DR changes and the overlap of FA and MD changes were seen in temporal, parietal and frontal lobes, as well as the corpus callosum and fornix. Analysis of differences between the AD versus MCIna, and AD versus MCIa contrasts, highlighted regions that are increasingly compromised in more severe disease stages. Microstructural damage independent of gross tissue loss was widespread in later disease stages. Our findings suggest a scheme where WM damage begins in the core memory network of the temporal lobe, cingulum and prefrontal regions, and spreads beyond these regions in later stages. DA and MD indices were most sensitive at detecting early changes in MCIa

Structural brain lesions and restless legs syndrome: a cross-sectional population-based study

Objective: To evaluate the association between white matter lesion (WML) volume, silent infarcts and restless legs syndrome (RLS) in a population-based study of elderly individuals. Design: Cross-sectional study. Setting: Population-based Three-City study. Participants: 1035 individuals from the Dijon, France, centre of the Three-City study who had available information on volume of WMLs from MRIs and who answered questions about the prevalence of RLS. Primary outcome measure Prevalence of RLS. Results: WML volume was measured using an automated tissue segmentation method. Logistic regression was used to evaluate adjusted associations between tertiles of WML volume and RLS and between silent infarcts and RLS. 218 individuals (21.1%) were determined to have RLS. Compared with those in the first tertile of WML volume, individuals in the second tertile (OR=1.09; 95% CI 0.75 to 1.60) or third tertile (OR=1.17; 95% CI 0.79 to 1.74) did not have an increased prevalence of RLS. We also did not observe associations between the volume of deep or periventricular WML and RLS; nor did we observe an association between silent brain infarcts and RLS (OR=0.74; 95% CI 0.40 to 1.39). These findings were not modified by age or gender. Conclusions: Higher volume of WML and the presence of silent infarcts were not associated with an increased prevalence of RLS in this population-based cohort of elderly individuals

Bounded Languages Meet Cellular Automata with Sparse Communication

Cellular automata are one-dimensional arrays of interconnected interacting finite automata. We investigate one of the weakest classes, the real-time one-way cellular automata, and impose an additional restriction on their inter-cell communication by bounding the number of allowed uses of the links between cells. Moreover, we consider the devices as acceptors for bounded languages in order to explore the borderline at which non-trivial decidability problems of cellular automata classes become decidable. It is shown that even devices with drastically reduced communication, that is, each two neighboring cells may communicate only constantly often, accept bounded languages that are not semilinear. If the number of communications is at least logarithmic in the length of the input, several problems are undecidable. The same result is obtained for classes where the total number of communications during a computation is linearly bounded