Sex hormone binding globulin and insulin resistance

Sex hormone binding globulin (SHBG) is a glycoprotein composed of two 373-amino-acid subunits. The SHBG gene and a promotor region have been identified. The SHBG receptor has yet to be cloned but is known to act through a G-protein-linked second-messenger system following plasma membrane binding. The principal function of SHBG has traditionally been considered to be that of a transport protein for sex steroids, regulating circulating concentrations of free (unbound) hormones and their transport to target tissues. Recent research suggests that SHBG has functions in addition to the binding and transport of sex steroids. Observational studies have associated a low SHBG concentration with an increased incidence of type 2 diabetes mellitus (DM) independent of sex hormone levels in men and women. Genetic studies using Mendelian randomization analysis linking three single nucleotide polymorphisms of the SHBG gene to risk of developing type 2 DM suggest SHBG may have a role in the pathogenesis of type 2 DM. The correlation between SHBG and insulin resistance that is evident in a number of cross-sectional studies is in keeping with the suggestion that the association between SHBG and incidence of type 2 DM is explained by insulin resistance. Several potential mechanisms may account for this association, including the identification of dietary factors that influence SHBG gene transcription. Further research to characterize the SHBG-receptor and the SHBG second messenger system is required. An interventional study examining the effects on insulin resistance of altering SHBG concentrations may help in determining whether this association is causal.

Age discrimination before the ECJ - Conceptual and theoretical issues

Although only addressed by EU law from 2000, age discrimination has been the theme of quite a few cases before the Court of Justice, with a high proportion decided by the Grand Chamber recently. This is due to the conceptual and theoretical challenges that a prohibition to use age as differentiating factor poses. After all, age has been an important stratifier used to synchronize life courses through welfare State regimes in Europe. Partly due to these traditions, there are stereotypes associated with old age, and young age, that in turn lead to disadvantage in employment. For the same reason, age discrimination frequently intersects with discrimination on other grounds, such as sex, race or disability. EU legislation on age discrimination has sought to accommodate the traditional role of age in employment policy by allowing wider justifications than for other forms of discrimination. This leads to contradictions within the larger field of discrimination law, which may even threaten to dilute its efficiency. This article analyses how recent case law of the Court of Justice, and in particular its Grand Chamber, deals with the theoretical challenges posed by these conflicting demands on age discrimination and on discrimination law at large.

Elements of A New Framework for the principle of Equal Treatment of persons in EC Law

In June and November 2000, the European Parliament and the Council adopted two Directives referring to ‘the principle of equal treatment irrespective of’ in their title, one relating to racial and ethnic origin, the other to disability, age, religion and belief or sexual orientation. A thorough reform of Directive 76/207/EEC on the principle of equal treatment for women and men in employment matters is pending between the European Parliament's second reading and adoption while this is written. Community secondary legislation on equal treatment of persons has thus expanded in scope and number of reasons which must not serve as starting points for differentiation. Does this signify progress in legal protection against personal discrimination? While not providing a ready answer, this article proposes an analytical framework to answer this question, concentrating on conceptions of equality in general and in particular on the problems multi-dimensional discrimination might pose for the law.

Organising EU non-discrimination law around the nodes of ‘race’ gender and disability?

EU non-discrimination law has seen a proliferation of discrimination grounds from 2000. Dis-crimination on grounds of gender (in the field of equal pay) and on grounds of nationality (generally within the scope of application of EU law) were the only prohibited forms of discrimination in EU law, until the Treaty of Amsterdam empowered the Community to legislate in order to combat discrimination on grounds of sex, racial or ethnic origin, religion or belief, disability, age or sexual orientation (Article 13 EC). Proliferation of non-discrimination grounds is also characteristic for international and national non-discrimination law. As such, proliferation of grounds results in an increase in potential cases of “multiple discrimination” and the danger of diluting the demands of equality law by ever more multiplication of grounds. The hierarchy of equality, which has been so widely criticised in EU law, is a signifier of the latter danger.
This chapter proposes to structure the confusing field of non-discrimination grounds by organising them around nodes of discrimination fields. It will first reflect different ways of establishing hierarchies between grounds. This will be followed by a recount of different (narrow and wide) reading of grounds. A comprehensive reading of the grounds gender, ‘race’ and disability as establishing overlapping fields of discrimination grounds will be mapped out, with some examples for practical uses.

Article 23: Equality between women and men

This analysis of Article 23 CFREU (Charter of Fundamental Rights for the European Union) argues that this provision can promote a more progressive understanding of gender equality then promoted by the European Court of Justice, in that it requires actual change in gender relations. It also finds shortcomings in that the EU conceptualises gender equality by relating women to men, thus falling short of providing a basis for women's rights.

Differenzierte Gerechtigkeit: Diskriminierungsschutz und Vertragsrecht

The theme of this book is the perceived tensions between contract law's principle of private autonomy and non-discrimination law. I first analyse the notion of discrimination, and specify that I restrict the investigation to ascribed difference,more specifically to perceived race/ethnicty, sex/gender and disability. Based on an analysis of the aims of non-discrimination law which extends onto markets, I then presented potential structures of non-discrimination clauses addressing market inequalities. Turning to a doctrinal investigation of German contract law and its position towards discrimination on grounds, I first investigated whether international law, EU law or the German constitution form a stable base for contractual non-discrimination law. Having concluded that these bodies of law require some protection against discrimination based on ascribed difference, but that contract law needs to provide its own specification, I then offer a very short comparative chapter on British and Dutch non-discrimination law (I guess I have developed quite a bit in this field since then!). Finally, I analyse in how far German courts have offered protection against discrimination on markets in the past, and which position the doctrine has taken. From page 290, I finally offer a conceptual, paradigmatic and principled proposal of how to integrate a principle of non-discrimination into German contract law. To my own surprise, this was later endorsed by one of the "doyens" of German contract law, Professor Canaris. In any case, you can see from my edited collection of 2011, that I am still fascinated by discrimination on grounds of race/ethnicity, sex/gender and disability.

The EU Equal Treatment Directives - implementation in German labour law

This article in one of the leading German journals on labour law analyses the shortcomings of German labour law at the time (2004) in relation to the EU non-discrimination directives. It states that the reluctance to legislate against race, sex and disability discrimination must be overcome, if the demands of the directives are to be fulfilled. It also explains how those forms of discrimination could already be addressed by interpreting German labour law in line with those directives and constitutional requirements. Only in 2006 was the relevant legislation finally passed (three years later than required).

From Conflict to Peace?:The Rights Abuses of Women and Girls in Northern Ireland

This article is based on primary research conducted by the authors in Northern Ireland in Mourne House women’s unit at Maghaberry Prison in 2004 and in Ash House women’s prison unit in Hydebank Wood Young Offender Centre from 2005-2006. It explores the imprisonment of women in prison in the context of a society slowly and unevenly emerging from violent conflict and against a backdrop of the global rise of women’s imprisonment over the past two decades. The history of the gendered punishment of politically motivated prisoners is explored, followed by discussion of the findings of primary research in Mourne House women’s unit and, following its closure, in Ash House. The conclusion analyses how women’s prison experiences in the North contribute to an understanding of the contested terrain of agency and resistance. Finally, the article explores the potential for, and barriers, to change within women’s imprisonment in Northern Ireland.

In utero exposure to cigarette chemicals induces sex-specific disruption of one-carbon metabolism and DNA methylation in the human fetal liver

Background: Maternal smoking is one of the most important modifiable risk factors for low birthweight, which is strongly associated with increased cardiometabolic disease risk in adulthood. Maternal smoking reduces the levels of the methyl donor vitamin B12 and is associated with altered DNA methylation at birth. Altered DNA methylation may be an important mechanism underlying increased disease susceptibility; however, the extent to which this can be induced in the developing fetus is unknown.

Methods: In this retrospective study, we measured concentrations of cobalt, vitamin B12, and mRNA transcripts encoding key enzymes in the 1-carbon cycle in 55 fetal human livers obtained from 11 to 21 weeks of gestation elective terminations and matched for gestation and maternal smoking. DNA methylation was measured at critical regions known to be susceptible to the in utero environment. Homocysteine concentrations were analyzed in plasma from 60 fetuses.

Results: In addition to identifying baseline sex differences, we found that maternal smoking was associated with sex-specific alterations of fetal liver vitamin B12, plasma homocysteine and expression of enzymes in the 1-carbon cycle in fetal liver. In the majority of the measured parameters which showed a sex difference, maternal smoking reduced the magnitude of that difference. Maternal smoking also altered DNA methylation at the imprinted gene IGF2 and the glucocorticoid receptor (GR/NR3C1).

Conclusions: Our unique data strengthen studies linking in utero exposures to altered DNA methylation by showing, for the first time, that such changes are present in fetal life and in a key metabolic target tissue, human fetal liver. Furthermore, these data propose a novel mechanism by which such changes are induced, namely through alterations in methyl donor availability and changes in 1-carbon metabolism.

Man-up Against Suicide

Male suicide rates are high in Western countries including the US and Canada. Underpinned by men’s resistance to health help-seeking and challenges diagnosing mental illness including male depression, suicide ends the lives of many men amid inflicting pain and grief on the family and friends who are left behind. Fuelled by the discordant relationship between men’s low rates of depression and high rates of suicide we embarked on a unique and novel photovoice study title Man-Up Against Suicide. Specifically, men who have contemplated suicide in the past, and individuals (men and women) who have lost a male partner, family member or friend to suicide were invited to take photographs representing their experiences with men’s suicide with the ultimate goal of messaging ‘at risk’ men that there are alternatives to taking one’s life. Participants subsequently completed semi-structured individual interviews narrating the photographs and providing captions to accompany their selected images. In this presentation we share the preliminary study findings along with some participant photographs and narratives as a means to discussing; 1) men’s experiences of suicidal behaviours and their management strategies; and, 2) how men’s and women’s experiences of losing a male to suicide can de-stigmatize men’s mental illness and raise public awareness about male suicide.

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.

Doing Gendered Time: The Harms of Women's Imprisonment

This chapter focuses on women’s imprisonment in the context of gendered punishment inflicted by the State. It considers the gender-specific consequences of incarceration for women prisoners and the potential of gender-responsive alternatives to custodial sentences. Following a brief historical overview, it traces the rise and consolidation of women’s incarceration in UK jurisdictions, noting the significance of devolution on the prison systems of Scotland and Northern Ireland. In examining the impact of neo-liberal policies and globalisation on women’s imprisonment, it draws comparisons with other advanced democratic states. Analysing the rationale underpinning the disproportionate rise in women’s incarceration, particularly in the UK and the USA the chapter identifies the persistent tensions between retributivism/ incapacitation and reformism/rehabilitation. Drawing on international research demonstrating the complex needs and vulnerabilities of women and girl prisoners, the chapter reveals the gendered harm experienced within penal regimes and the recent development - and limitations - of official gender-specific policies and practices. The emergence of distinct but related political discourses on ‘risk’ and ‘responsibilisation’ as applied to women in conflict with the law, and their consequent criminalisation, is critiqued in the contexts of structural disadvantage, gender discrimination and institutionalised racism. Within these oppressive dynamics often severe deprivations are inflicted on women’s acts of resistance both inside prison and in their communities post-release, further confining the potential of individual and collective agency. Finally, the chapter proposes fundamental change through establishing women-centred alternatives to prison, alongside policies committed to decarceration, while working towards securing the abolition of women’s imprisonment.

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.

Intersectionality and the Notion of Disability in EU discrimination law

Defining the characteristics targeted by banning discrimination constitutes a central challenge for EU discrimination law, and defining disability is particular-ly challenging due to the dispute around the very concept of disability. From 2006, the Court of Justice has wrestled with this definition in six judgments, five of which were delivered from 2013. Instead of classifying the case law definition as conforming to a medical or social model of disability, this article analyses the case law with a view to illustrate challenges of defining discrimination grounds generally, demanding that a sufficiently precise and non-exclusive definition of each discrimination ground can be achieved by re-focusing EU discrimination law around the nodes of sex, race and disability. The analysis exposes that the ECJ definition of disability neither complies with the UN CRPD nor adequately responds to intersectionality theory, for example because the definition is exclu-sionary in relation to female experience of disability.

Validation of night blindness reports among children and women in a vitamin A deficient population in rural Tanzania.

OBJECTIVE: This study validates different definitions of reported night blindness (XN) in a vitamin A deficient African population with no local term for XN. DESIGN: Case-control study with follow-up after treatment. SETTING: Eight primary schools and health centres in rural Tanzania. SUBJECTS: A total of 1214 participants were screened for reported XN and other eye signs of xerophthalmia: 461 children aged 24-71 months, 562 primary school-age children and 191 pregnant or breast-feeding women. All 152 cases of reported XN were selected for the validation study and group matched with 321 controls who did not complain of XN. XN reports were validated against serum retinol concentrations and pupillary dark adaptation measurements in cases and controls. INTERVENTION: All children and women who reported XN or had other signs of active xerophthalmia were treated with vitamin A and followed up 3-4 weeks later. Half of the untreated control group who had their serum retinol examined in the baseline examination were also followed up. RESULTS: The overall prevalence of reported XN was 12.5%. At baseline, mean pupillary threshold (-1.52 vs -1.55 log cd/m(2), P=0.501) and median serum retinol concentrations (0.95 vs 0.93 micromol/l, P=0.734) were not significantly different in cases and controls either overall or in each population group. More restricted case definitions reduced the prevalence of reported XN to 5.5% (P<0.001), but there was still no significant difference between cases and controls although the results were in the expected direction. After treatment, the median serum retinol concentration improved significantly only in the most deficient group, the young children. Dark adaptation improved in all the subgroups but the difference was only significant for young children and primary school-age children when the restricted case definitions were used. CONCLUSIONS: XN reports are a poor indicator of vitamin A deficiency in this population. SPONSORSHIP: Task Force Sight and Life, Basel, Switzerland.