Regressive logistic and proportional hazards disease models for within-family analyses of measured genotypes, with application to a CYP17 polymorphism and breast cancer

Various statistical methods have been proposed to evaluate associations between measured genetic variants and disease, including some using family designs. For breast cancer and rare variants, we applied a modified segregation analysis method that uses the population cancer incidence and population-based case families in which a mutation is known to be segregating. Here we extend the method to a common polymorphism, and use a regressive logistic approach to model familial aggregation by conditioning each individual on their mother's breast cancer history. We considered three models: 1) class A regressive logistic model; 2) age-of-onset regressive logistic model; and 3) proportional hazards familial model. Maximum likelihood estimates were calculated using the software MENDEL. We applied these methods to data from the Australian Breast Cancer Family Study on the CYP17 5UTR TC MspA1 polymorphism measured for 1,447 case probands, 787 controls, and 213 relatives of case probands found to have the CC genotype. Breast cancer data for first- and second-degree relatives of case probands were used. The three methods gave consistent estimates. The best-fitting model involved a recessive inheritance, with homozygotes being at an increased risk of 47% (95% CI, 28-68%). The cumulative risk of the disease up to age 70 years was estimated to be 10% or 22% for a CYP17 homozygote whose mother was unaffected or affected, respectively. This analytical approach is well-suited to the data that arise from population-based case-control-family studies, in which cases, controls and relatives are studied, and genotype is measured for some but not all subjects.

Correlation between microstructure and phosphorus segregation in a hypereutectoid Wootz steel

The influence of bands rich in phosphorus on the microstructure of hypereutectoid Wootz steel implement is described. Electron probe micro-analysis is combined with optical microscopy. Phosphorus-rich bands are seen to correspond to regions of internal cracking, carbon depletion, and enhanced frequency of spheroidized cementite in place of pearlite. A rationale for the findings is presented in terms of the influence of phosphorus on the Fe–C phase diagram and on the rate of the eutectoid reaction.

Global perspectives on the politics of multiculturalism in the 21st century: a case study analysis

Multiculturalism is now seen by many of its critics as the source of intercultural and social tensions, fostering communal segregation and social conflicts. While the cultural diversity of contemporary societies has to be acknowledged as an empirical and demographic fact, whether multiculturalism as a policy offers an optimal conduit for intercultural understanding and social harmony has become increasingly a matter of polarised public debate.
This book examines the contested philosophical foundations of multiculturalism and its, often controversial, applications in the context of migrant societies. It also explores the current theoretical debates about the extent to which multiculturalism, and related conceptual constructs, can account for the various ethical challenges and policy dilemmas surrounding the management of cultural diversity in our contemporary societies. The authors consider common conceptual and empirical features from a transnational perspective through analysis of the case studies of Australia, Canada, Columbia, Germany, New Zealand, the United Kingdom and Uruguay.

Grain boundary segregation in Fe-Mn-C twinning-induced plasticity steels studied by correlative electron backscatter diffraction and atom probe tomography

We report on the characterization of grain boundary (GB) segregation in an Fe-28Mn-0.3C (wt.%) twinning-induced plasticity (TWIP) steel. After recrystallization of this steel for 24 h at 700 °C, ∼50% general grain boundaries (GBs) and ∼35% Σ3 annealing twin boundaries were observed (others were high-order Σ and low-angle GBs). The segregation of B, C and P and traces of Si and Cu were detected at the general GB by atom probe tomography (APT) and quantified using ladder diagrams. In the case of the Σ3 coherent annealing twin, it was necessary to first locate the position of the boundary by density analysis of the atom probe data, then small amounts of B, Si and P segregation and, surprisingly, depletion of C were detected. The concentration of Mn was constant across the interface for both boundary types. The depletion of C at the annealing twin is explained by a local change in the stacking sequence at the boundary, creating a local hexagonal close-packed structure with low C solubility. This finding raises the question of whether segregation/depletion also occurs at Σ3 deformation twin boundaries in high-Mn TWIP steels. Consequently, a previously published APT dataset of the Fe-22Mn-0.6C alloy system, containing a high density of deformation twins due to 30% tensile deformation at room temperature, was reinvestigated using the same analysis routine as for the annealing twin. Although crystallographically identical to the annealing twin, no evidence of segregation or depletion was found at the deformation twins, owing to the lack of mobility of solutes during twin formation at room temperature.

Sexual segregation in habitat use is smaller than expected in a highly dimorphic marine predator, the southern sea lion

Sexual segregation in habitat use is widely reported in many taxa and can profoundly influence the distribution and behaviour of animals. However, our knowledge of the mechanisms driving sexual segregation is still in its infancy (particularly in marine taxa) and the influence of extrinsic factors in mediating the expression of sex differences in foraging behaviour is underdeveloped. Here, we combine data from biologging tags, with stable isotope analysis of vibrissae, to assess sexual segregation in southern sea lions (SSL) (Otaria flavescens) breeding at the Falkland Islands in the South Atlantic. We found evidence to support segregation, most notably in δ13C and δ15N values. However, in spite of extreme sexual size dimorphism and differing constraints related to female-only parental care, adult male and adult female SSL overlapped considerably in isotopic niches and foraging area, and shared similar foraging trip characteristics (such as distance and duration). This is in contrast to SSL breeding in Argentina, where prior studies report sexual differences in foraging locations and foraging trip characteristics. We posit that sexual segregation in SSL is influenced by habitat availability (defined here as the width of the Patagonian Shelf) and individual foraging preferences, rather than commonly invoked individual-based limiting factors per se.