Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors

Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.

Pro-active protection against racialist discrimination in employment law - lessons from South Africa?

This study investigates the potential of the prohibition of indirect race discrimination to be used for law reform, and to uncover discriminatory practices. It reflects on the history and contents of the concept, and focuses in particular on its application in the Republic of South Africa

Merit, Speech Disability and Discrimination

There is a substantial body of evidence – going back over decades – which indicates that the employment sphere is difficult for those who suffer a speech disability. To a large extent, I argue, this is due to the setting of merit in terms of orality and aesthetic. It also relates to the low perception of competence of the speech disabled. I argue that to be effective against discrimination the notion of merit and its assessment requires focus. ‘Merit’ as a concept in discrimination law has had its critics, yet it remains important to investigate it as social construct in order to help understand discrimination and how to counter this. For example, in this article I look at an instance where the resetting of what was viewed as ‘meritorious’ in judicial recruitment successfully improved the diversity in lower judicial posts.

Further, given the relative failure of the employment tribunal system to improve the general position of those who are disabled, I look to alternative methods of countering disability discrimination. The suggestion provided is that an enforced ombudsman type approach capable of dealing with what may be the core issue around employment discrimination (‘merit’) would provide a better mechanism for handling the general situation of disability discrimination than the tribunal system.

European Union non-discrimination law and intersectionality:Investigating the triangle of racial, gender and disability discrimination

This book contributes to a critical reflection of current legislative and jurisprudential developments in Non-Discrimination Law, focusing on the European Union. The book is focused on intersectionality between gender, race and disability and the question of whether, and to what extent, this intersection can be adequately addressed in (EU) law. The discussion rests on two basic assumptions. First, the multiplication of 'discrimination grounds' in EU law and other legal regimes should not result in a dilution of the demands of equality law. Accordingly, the book focuses on the three key grounds - race, gender and disability. These constitute nodes around which other discrimination grounds can be grouped. Second, any multi-ground non-discrimination law framework needs to engage with the question of discrimination on several grounds. This book provides a critical evaluation of some of the problems presented by such intersectionality and an opportunity to explore the issues in depth. This collection offers some new proposals relating to the regrouping of identity categories and to the general approach to socio-legal research in the field. It also contains a comparative section, which expands on practical experiences with intersectionality and law, and a section dedicated to juridical responses to intersectionality.

A rapid dot-blot assay to assess chimerism following sex-mismatched bone marrow transplantation

Mixed chimerism may occur more frequently than previously thought following allogeneic bone marrow transplantation and may have implications in terms of relapse, graft-versus-host disease and immune reconstitution. DNA analysis using single or multilocus polymorphic probes cannot reliably discriminate between donor and recipient cells below a level of 10%. We used probe pHY2.1, a cloned segment of tandemly repeated DNA (2000 copies) on the long arm of chromosome Y. A dot blot procedure allowed us to immobilize DNA directly from 50 microliter of peripheral blood or bone marrow. Cross-reactivity was eliminated by hybridization at conditions of extreme stringency (65 degrees C, 50% formamide). Mixing experiments detected male DNA at a level of 0.1% after 10 h exposure. Five patients were studied serially post-bone marrow transplantation. One patient showed mixed chimerism for 12 months, one had complete autologous recovery and the remaining three showed complete engraftment. All results were verified by standard karyotyping on bone marrow cells. This technique is a simple, rapid and sensitive assay for chimerism following sex mismatched bone marrow transplantation.

Influence of sex on the survival of patients with esophageal cancer

PURPOSE: The prognostic value of sex for esophageal cancer survival is currently unclear, and growing data suggest that hormonal influences may account for incidence disparities between men and women. Therefore, moving from the hypothesis that hormones could affect the prognosis of patients with esophageal cancer, we investigated the primary hypothesis that sex is associated with survival and the secondary hypotheses that the relationship between sex and survival depends, at least in part, on age, histology, and race/ethnicity.

PATIENTS AND METHODS: By using the SEER databases from 1973 to 2007, we identified 13,603 patients (34%) with metastatic esophageal cancer (MEC) and 26,848 patients (66%) with locoregional esophageal cancer (LEC). Cox proportional hazards model for competing risks were used for analyses.

RESULTS: In the multivariate analysis, women had longer esophageal cancer-specific survival (ECSS) than men in both MEC (hazard ratio [HR], 0.949; 95% CI, 0.905 to 0.995; P = .029) and LEC (HR, 0.920; 95% CI, 0.886 to 0.955; P < .001) cohorts. When age and histology were accounted for, there was no difference for ECSS between men and women with adenocarcinoma. In contrast, women younger than age 55 years (HR, 0.896; 95% CI, 0.792 to 1.014; P = .081) and those age 55 years or older (HR, 0.905; 95% CI, 0.862 to 0.950; P < .001) with squamous cell LEC had longer ECSS than men. In the squamous cell MEC cohort, only women younger than age 55 years had longer ECSS (HR, 0.823; 95% CI, 0.708 to 0.957; P = .011) than men.

CONCLUSION: Sex is an independent prognostic factor for patients with LEC or MEC. As secondary hypotheses, in comparison with men, women age 55 years or older with squamous cell LEC and women younger than age 55 years with squamous cell MEC have a significantly better outcome. These last two findings need further validation.