An Excess of Risk-Increasing Low-Frequency Variants Can Be a Signal of Polygenic Inheritance in Complex Diseases

In most complex diseases, much of the heritability remains unaccounted for by common variants. It has been postulated that lower-frequency variants contribute to the remaining heritability. Here, we describe a method to test for polygenic inheritance from lower-frequency variants by using GWAS summary association statistics. We explored scenarios with many causal low-frequency variants and showed that there is more power to detect risk variants than to detect protective variants, resulting in an increase in the ratio of detected risk to protective variants (R/P ratio). Such an excess can also occur if risk variants are present and kept at lower frequencies because of negative selection. The R/P ratio can be falsely elevated because of reasons unrelated to polygenic inheritance, such as uneven sample sizes or asymmetric population stratification, so precautions to correct for these confounders are essential. We tested our method on published GWAS results and observed a strong signal in some diseases (schizophrenia and type 2 diabetes) but not others. We also explored the shared genetic component in overlapping phenotypes related to inflammatory bowel disease (Crohn disease [CD] and ulcerative colitis [UC]) and diabetic nephropathy (macroalbuminuria and end-stage renal disease [ESRD]). Although the signal was still present when both CD and UC were jointly analyzed, the signal was lost when macroalbuminuria and ESRD were jointly analyzed, suggesting that these phenotypes should best be studied separately. Thus, our method may also help guide the design of future genetic studies of various traits and diseases.

Quantum and classical properties of the fields generated by two interlinked second-order non-linear interactions

We consider two interlinked non-linear interactions occurring simultaneously in a single chi((2)) crystal. Classical and quantum working regimes are considered and their peculiar properties analysed. In particular, we describe an experiment, realized in the classical regime, that verifies the holographic nature of the process, and predict, for the quantum regime, the generation of a fully inseparable tripartite Gaussian state of light that can be used to support a general 1--> 2 continuous variable telecloning protocol.

'"These schemes will win for themselves the confidence of the people": Irish independence, poor law reform and hospital provision'

This article examines hospital provision in Ireland during the early twentieth century. It examines attempts by the newly independent Irish Free State to reform and de-stigmatise medical relief in former workhouse infirmaries. Such reforms were designed to move away from nineteenth century welfare regimes which were underpinned by principles of deterrence. The reform initiated in independent Ireland - the first attempted break-up of the New Poor Law in Great Britain or Ireland - was partly successful. Many of the newly named County and District Hospitals provided solely for medical cases and managed to dissociate such health care provision from the relief of poverty. However, some hospitals continued to act as multifunctional institutions and provided for various categories including the sick, the aged and infirm, 'unmarried mothers' and 'harmless lunatics'. Such institutions often remained associated with the relief of poverty. This article also examines patient fee-payment and outlines how fresh terms of entitlement and means-testing were established. Such developments were even more pronounced in voluntary hospitals where the majority of patients made a financial contribution to their treatment. The article argues that the ability to pay at times determined the type of provision, either voluntary or rate-aided, available to the sick. However, it concludes that the clinical condition of patients often determined whether they entered a more prestigious voluntary hospital or the former workhouse. Although this article concentrates on two Irish case studies, County Kerry and Cork City; it is conceptualised within wider developments with particular reference to the British context.

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.

Enforcing Employment Discrimination Law - Potential Transplants from Italy to Britain and Vice Versa?

While substantive EU non-discrimination law has been harmonized in great detail, the enforcement regime for EU non-discrimination law consists merely of a few isolated elements. Thus, the pursuit of unity through harmonization in substantive EU law is accompanied by considerable regulatory autonomy for Member States in securing the efficiency of those laws, reflecting the diversity of national enforcement regimes, and resulting in twenty-seven different national models for enforcing discrimination law in labour markets. This article pursues two connected arguments through a comparison of rules for enforcing non-discrimination law in labour markets in Britain and Italy. First, it argues that enforcing non-discrimination law in labour markets is best achieved when responsive governance, repressive regulation and mainstreaming equality law are combined. Second, the article submits that diversity of national legal orders within the EU is not necessarily detrimental, as it offers opportunities for mutual learning across legal systems.The notion of mutual learning across systems is proposed in order to analyse the transnational migration of legal ideas within the EU. Such migration has been criticized in debates about the ‘transplantation’ of legal concepts or legal irritation through foreign legal ideas, in particular by comparative labour lawyers. However, EU harmonization policies in the field of non-discrimination law aim to impact on national labour laws. The article develops the notion of mutual learning across legal systems in order to establish conditions for transnational migration of legal ideas, and demonstrates the viability of these concepts by applying them to the field of non-discrimination law

Consideration of coastal risk in the Irish spatial planning process

The vulnerability of coastal areas to associated hazards is increasing due to population growth, development pressure and climate change. It is incumbent on coastal governance regimes to address the vulnerability of coastal inhabitants to these hazards. This is especially so at the local level where development planning and control has a direct impact on the vulnerability of coastal communities. To reduce the vulnerability of coastal populations, risk mitigation and adaptation strategies need to be built into local spatial planning processes. Local government, however, operates within a complex hierarchal governance framework which may promote or limit particular actions. It is important, therefore, to understand how local coastal planning practices are shaped by national and supranational entities. Local governments also have to respond to the demands of local populations. Consequently, it is important to understand local populations’ perceptions of coastal risk and its management. Adopting an in-depth study of coastal planning in County Mayo, Ireland, this paper evaluates: (a) how European and national policies and legislation shape coastal risk management at local level; (b) the incorporation of risk management strategies into local plans; and (c) local perception of coastal risks and risk management. Despite a strong steer from supranational and national legislation and policy, statutory local plans are found to be lacking in appropriate risk mitigation or adaptation strategies. Local residents appear to be lulled into a sense of complacency towards these risks because of the low level of attention afforded to them by the local planning authorities. To avoid potentially disastrous consequences for local residents and businesses, it is imperative that this situation is redressed urgently. Based on our analysis, we recommend: the development and implementation of a national ICZM strategy, supported by detailed local ICZM plans; and obliging local government to address known risks in their plans rather than defer them to project level decision making.

Promoting Community Renewable Energy in a Corporate Energy World

Small-scale, decentralized and community-owned renewable energy is widely acknowledged to be a desirable feature of low carbon futures, but faces a range of challenges in the context of conventional, centralized energy systems. This paper draws on transition frameworks to investigate why the UK has been an inhospitable context for community-owned renewables and assesses whether anything fundamental is changing in this regard. We give particular attention to whether political devolution, the creation of elected governments for Scotland, Wales and Northern Ireland, has affected the trajectory of community renewables. Our analysis notes that devolution has increased political attention to community renewables, including new policy targets and support schemes. However, these initiatives are arguably less important than the persistence of key features of socio-technical regimes: market support systems for renewable energy and land-use planning arrangements that systemically favour major projects and large corporations, and keep community renewables to the margins. There is scope for rolling out hybrid pathways to community renewables, via joint ownership or through community benefit funds, but this still positions community energy as an adjunct to energy pathways dominated by large, corporate generation facilities

Amplitude modulation of quantum-ion-acoustic wavepackets in electron-positron-ion plasmas: Modulational instability, envelope modes, extreme waves

A semirelativistic fluid model is employed to describe the nonlinear amplitude modulation of low-frequency (ionic scale) electrostatic waves in an unmagnetized electron-positron-ion plasma. Electrons and positrons are assumed to be degenerated and inertialess, whereas ions are warm and classical. A multiscale perturbation method is used to derive a nonlinear Schrödinger equation for the envelope amplitude, based on which the occurrence of modulational instability is investigated in detail. Various types of localized ion acoustic excitations are shown to exist, in the form of either bright type envelope solitons (envelope pulses) or dark-type envelope solitons (voids, holes). The plasma configurational parameters (namely, the relativistic degeneracy parameter, the positron concentration, and the ionic temperature) are shown to affect the conditions for modulational instability significantly, in fact modifying the associated threshold as well as the instability growth rate. In particular, the relativistic degeneracy parameter leads to an enhancement of the modulational instability mechanism. Furthermore, the effect of different relevant plasma parameters on the characteristics (amplitude, width) of these envelope solitary structures is also presented in detail. Finally, the occurrence of extreme amplitude excitation (rogue waves) is also discussed briefly. Our results aim at elucidating the formation and dynamics of nonlinear electrostatic excitations in superdense astrophysical regimes.