HFE C282Y HOMOZYGOSITY IS ASSOCIATED WITH AN INCREASED RISK OF TOTAL HIP REPLACEMENT FOR OSTEOARTHRITIS IN MEN BUT NOT WOMEN

Abstract not availableYuanyuan Wang, Lyle C. Gurrin, Anita E. Wluka, Nadine A. Bertalli, Nicholas J. Osborne, Martin B. Delatycki, Graham G. Giles, Dallas R. English, John L. Hopper, Julie A. Simpson, Stephen Graves, Katrina J. Allen, Flavia M. Cicuttin

The Proof Is in the Process: A Preamble for a Philosophy of Computer-Assisted Mathematics

According to some well-known mathematicians well-versed in computer-assisted mathematics (CaM), “Computers are changing the way we are doing mathematics”. To what extent this is really true is still an open question. Indeed, even though some philosophers of math have taken up the challenge to think about CaM, it is unclear in what sense exactly a machine (can) affect(s) the so-called “queen of the sciences”. In fact, some have concluded that issues raised by the use of the computer in mathematics are not specific to the use of the computer per se. However, such findings seem precarious since a systematic study of computer-assisted mathematics is still lacking. In this paper I argue that in order to understand the impact of CaM, it is necessary to take more seriously the computer itself and how it is actually used in the process of doing mathematics. Within such an approach, one searches for characteristics that are specific to the use of the computer in mathematics. I will focus on a feature that is beyond any doubt inherently connected to the use of computing machinery, viz. mathematician-computer interactions. I will show how such interactions are fundamentally different from the usual interactions between mathematicians and non-human aids (a piece of paper, a blackboard etc) and how such interactions determine at least two more characteristics of CaM, viz. the significance of time and processes and the steady process of internalization of mathematical tools and knowledge into the machine. I will restrict myself to the use of the computer within so-called experimental mathematics since this is the main object of CaM within the philosophical literature

Rare mutations in XRCC2 increase the risk of breast cancer

Item does not contain fulltextAn exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification of XRCC2 as a breast cancer susceptibility gene thus increases the proportion of breast cancers that are associated with homologous recombination-DNA-repair dysfunction and Fanconi anemia and could therefore benefit from specific targeted treatments such as PARP (poly ADP ribose polymerase) inhibitors. This study demonstrates the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases

Rare mutations in XRCC2 increase the risk of breast cancer

Item does not contain fulltextAn exome-sequencing study of families with multiple breast-cancer-affected individuals identified two families with XRCC2 mutations, one with a protein-truncating mutation and one with a probably deleterious missense mutation. We performed a population-based case-control mutation-screening study that identified six probably pathogenic coding variants in 1,308 cases with early-onset breast cancer and no variants in 1,120 controls (the severity grading was p < 0.02). We also performed additional mutation screening in 689 multiple-case families. We identified ten breast-cancer-affected families with protein-truncating or probably deleterious rare missense variants in XRCC2. Our identification of XRCC2 as a breast cancer susceptibility gene thus increases the proportion of breast cancers that are associated with homologous recombination-DNA-repair dysfunction and Fanconi anemia and could therefore benefit from specific targeted treatments such as PARP (poly ADP ribose polymerase) inhibitors. This study demonstrates the power of massively parallel sequencing for discovering susceptibility genes for common, complex diseases