Non-monetary poverty and deprivation: A capability approach

Given the continuing interest in multi-dimensional approaches to poverty, the paper considers ways in which Senian capability indicators can be used to assess and understand poverty and deprivation. More specifically, we develop novel capability data on 29 dimensions for adults from the US, UK and Italy to explore three core research questions. Firstly, we show that when poverty is seen as capability deprivation, different individuals are identified as poor compared with approaches based on low income or subjective wellbeing. However, we also observe that what the poor report being able to do or otherwise is, nonetheless, relatively robust to the use of these three different approaches. Secondly, we employ latent class analysis to identify poverty and deprivation profiles for groups within society and suggest that such profiles help to identify groups who are deprived with respect to some but not all areas of life. Thirdly, and finally, we examine the association between individual capability deprivation and local area deprivation in the UK. We find that individual capabilities are associated with local area deprivation in some cases but that the connections vary significantly depending on the dimension under consideration. We discuss the results and conclude by suggesting that capability indicators can provide insights into poverty which do not emerge from a more traditional approach focussing on income alone

Inheritance of deleterious mutations at both BRCA1 and BRCA2 in an international sample of 32,295 women

Background: Most BRCA1 or BRCA2 mutation carriers have inherited a single (heterozygous) mutation. Transheterozygotes (TH) who have inherited deleterious mutations in both BRCA1 and BRCA2 are rare, and the consequences of transheterozygosity are poorly understood. Methods: From 32,295 female BRCA1/2 mutation carriers, we identified 93 TH (0.3 %). "Cases" were defined as TH, and "controls" were single mutations at BRCA1 (SH1) or BRCA2 (SH2). Matched SH1 "controls" carried a BRCA1 mutation found in the TH "case". Matched SH2 "controls" carried a BRCA2 mutation found in the TH "case". After matching the TH carriers with SH1 or SH2, 91 TH were matched to 9316 SH1, and 89 TH were matched to 3370 SH2. Results: The majority of TH (45.2 %) involved the three common Jewish mutations. TH were more likely than SH1 and SH2 women to have been ever diagnosed with breast cancer (BC; p = 0.002). TH were more likely to be diagnosed with ovarian cancer (OC) than SH2 (p = 0.017), but not SH1. Age at BC diagnosis was the same in TH vs. SH1 (p = 0.231), but was on average 4.5 years younger in TH than in SH2 (p < 0.001). BC in TH was more likely to be estrogen receptor (ER) positive (p = 0.010) or progesterone receptor (PR) positive (p = 0.013) than in SH1, but less likely to be ER positive (p < 0.001) or PR positive (p = 0.012) than SH2. Among 15 tumors from TH patients, there was no clear pattern of loss of heterozygosity (LOH) for BRCA1 or BRCA2 in either BC or OC. Conclusions: Our observations suggest that clinical TH phenotypes resemble SH1. However, TH breast tumor marker characteristics are phenotypically intermediate to SH1 and SH2

Associations of common breast cancer susceptibility alleles with risk of breast cancer subtypes in BRCA1 and BRCA2 mutation carriers

Introduction: More than 70 common alleles are known to be involved in breast cancer (BC) susceptibility, and several exhibit significant heterogeneity in their associations with different BC subtypes. Although there are differences in the association patterns between BRCA1 and BRCA2 mutation carriers and the general population for several loci, no study has comprehensively evaluated the associations of all known BC susceptibility alleles with risk of BC subtypes in BRCA1 and BRCA2 carriers. Methods: We used data from 15,252 BRCA1 and 8,211 BRCA2 carriers to analyze the associations between approximately 200,000 genetic variants on the iCOGS array and risk of BC subtypes defined by estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and triple-negative- (TN) status; morphologic subtypes; histological grade; and nodal involvement. Results: The estimated BC hazard ratios (HRs) for the 74 known BC alleles in BRCA1 carriers exhibited moderate correlations with the corresponding odds ratios from the general population. However, their associations with ER-positive BC in BRCA1 carriers were more consistent with the ER-positive as

Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10-20), ER-negative BC (P=1.1 × 10-13), BRCA1-associated BC (P=7.7 × 10-16) and triple negative BC (P-diff=2 × 10-5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10-3) and ABHD8 (P<2 × 10-3). Chromosome conformation capture identifies interactions between four candidate SNPs and ABHD8, and luciferase assays indicate six risk alleles increased transactivation of the ADHD8 promoter. Targeted deletion of a region containing risk SNP rs56069439 in a putative enhancer induces ANKLE1 downregulation; and mRNA stability assays indicate functional effects for an ANKLE1 3′-UTR SNP. Altogether, these data suggest that multiple SNPs at 19p13 regulate ABHD8 and perhaps ANKLE1 expression, and indicate common mechanisms underlying breast and ovarian cancer risk

Violent computer games, empathy, and cosmopolitanism \ud

Many philosophical and public discussions of the ethical aspects of violent computer games typically centre on the relation between playing violent videogames and its supposed direct consequences on violent behaviour. But such an approach rests on a controversial empirical claim, is often one-sided in the range of moral theories used, and remains on a general level with its focus on content alone. In response to these problems, I pick up Matt McCormick’s thesis that potential harm from playing computer games is best construed as harm to one’s character, and propose to redirect our attention to the question how violent computer games influence the moral character of players. Inspired by the work of Martha Nussbaum, I sketch a positive account of how computer games can stimulate an empathetic and cosmopolitan moral development. Moreover, rather than making a general argument applicable to a wide spectrum of media, my concern is with specific features of violent computer games that make them especially morally problematic in terms of empathy and cosmopolitanism, features that have to do with the connections between content and medium, and between virtuality and reality. I also discuss some remaining problems. In this way I hope contribute to a less polarised discussion about computer games that does justice to the complexity of their moral dimension, and to offer an account that is helpful to designers, parents, and other stakeholder