Risk analysis of prostate cancer in PRACTICAL, a multinational consortium, using 25 known prostate cancer susceptibility loci

Background Genome-wide association studies have identified multiple genetic variants associated with prostate cancer risk which explain a substantial proportion of familial relative risk. These variants can be used to stratify individuals by their risk of prostate cancer. Methods We genotyped 25 prostate cancer susceptibility loci in 40,414 individuals and derived a polygenic risk score (PRS).We estimated empirical odds ratios (OR) for prostate cancer associated with different risk strata defined by PRS and derived agespecific absolute risks of developing prostate cancer by PRS stratum and family history. Results The prostate cancer risk for men in the top 1% of the PRS distribution was 30.6 (95% CI, 16.4-57.3) fold compared with men in the bottom 1%, and 4.2 (95% CI, 3.2-5.5) fold compared with the median risk. The absolute risk of prostate cancer by age of 85 years was 65.8% for a man with family history in the top 1% of the PRS distribution, compared with 3.7% for a man in the bottom 1%. The PRS was only weakly correlated with serum PSA level (correlation = 0.09). Conclusions Risk profiling can identify men at substantially increased or reduced risk of prostate cancer. The effect size, measured by OR per unit PRS, was higher in men at younger ages and in men with family history of prostate cancer. Incorporating additional newly identified loci into a PRS should improve the predictive value of risk profiles. Impact:We demonstrate that the risk profiling based on SNPs can identify men at substantially increased or reduced risk that could have useful implications for targeted prevention and screening programs.

Portrait of Elly Goldschmidt and her children Ilse and Robert. Portraits Family

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Ilse and Robert Goldschmidt with their parents Albert Goldschmidt and Elly nee Schoenbeck grandfather Albert Schoenbeck and great grandmother Sophie Schoenbeck nee Mahler. Portraits Family

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Portrait of the engineer and geneologist Robert Goldschmidt Portraits Men

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Albert Einstein with Robert Andrews Millikan, Albert Michelson and unidentified men; Pasadena, California Portraits Groups; Men

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Portrait of Elly Goldschmidt and her children Ilse and Robert. Portraits Family

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Ilse and Robert Goldschmidt with their parents Albert Goldschmidt and Elly nee Schoenbeck grandfather Albert Schoenbeck and great grandmother Sophie Schoenbeck nee Mahler. Portraits Family

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Portrait of the engineer and geneologist Robert Goldschmidt Portraits Men

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Solomon Robert Kagan papers undated, 1920-1955

Contains correspondence, printed material, and photographs relating to Jews in the medical profession, used as a basis for Kagan's several works on Jews in medicine, including the correspondence of members of the American Physicians Fellowship Committee of the Israel Medical Association; includes also correspondence relating to the Near East and the internationalization of Jerusalem, 1945-1954; and personal correspondence. Among the correspondents are Bernard M. Baruch and Christian A. Herter.

Faster Algorithms for Incremental Topological Ordering.Robert Tarjan

We present two online algorithms for maintaining a topological order of a directed acyclic graph as arcs are added, and detecting a cycle when one is created. Our first algorithm takes O(m 1/2) amortized time per arc and our second algorithm takes O(n 2.5/m) amortized time per arc, where n is the number of vertices and m is the total number of arcs. For sparse graphs, our O(m 1/2) bound improves the best previous bound by a factor of logn and is tight to within a constant factor for a natural class of algorithms that includes all the existing ones. Our main insight is that the two-way search method of previous algorithms does not require an ordered search, but can be more general, allowing us to avoid the use of heaps (priority queues). Instead, the deterministic version of our algorithm uses (approximate) median-finding; the randomized version of our algorithm uses uniform random sampling. For dense graphs, our O(n 2.5/m) bound improves the best previously published bound by a factor of n 1/4 and a recent bound obtained independently of our work by a factor of logn. Our main insight is that graph search is wasteful when the graph is dense and can be avoided by searching the topological order space instead. Our algorithms extend to the maintenance of strong components, in the same asymptotic time bounds.

Redescubrir la finalidad natural : Robert Spaemann y Tomás de Aquino

Resumen: En ocasión de la autobiografía de Robert Spaemann aparecida en 2012, este trabajo examina la lectura que Spaemann hace de la teleología en la doctrina de Santo Tomás de Aquino, especialmente en su obra Natürliche Ziele (2005) que prosigue la versión de 1981. En la primera parte, se estudia la historia de la teleología en el pensamiento filosófico y científico expuesta en «Fines naturales». La finalidad intrínseca en la naturaleza de los seres es conocida con profundidad creciente gracias a Platón, Aristóteles, al estoicismo y a la tradición cristiana. Estos aportes se integran en una estructura teleológica unitaria en el Aquinate. Después acontece una «inversión» de la teleología centrada en la conservación del propio ser y una consideración de los fines como algo externo a la realidad. Con la teoría evolucionista surge la teleonomía que se limita a las reglas del dinamismo, suprimiendo el fin. Con todo, los científicos no logran eliminar los términos «con el fin de» o «para» en su lenguaje. Eso permite proceder a un redescubrimiento de los fines naturales. En la segunda parte, se ve cómo Tomás de Aquino lleva el conocimiento de la finalidad más allá de Aristóteles, porque ella remite a una inteligencia creadora. La teleología implica una teología, aunque no queda del todo claro si es la teología filosófica o la cristiana. Spaemann tiene un planteo ontológico de tipo persuasivo, pero en algunos momentos siente dificultad para superar en el plano teorético a quien se limita a una teleonomía.

Carta enviada por el Dr. Robert Worms a Justo Garate

1 carta (manuscrita) ; 202x145mm.