Metabolic signatures of human Alzheimer's disease (AD): H-1 NMR analysis of the polar metabolome of post-mortem brain tissue

Brain tissue from so-called Alzheimer's disease (AD) mouse models has previously been examined using H-1 NMR-metabolomics, but comparable information concerning human AD is negligible. Since no animal model recapitulates all the features of human AD we undertook the first H-1 NMR-metabolomics investigation of human AD brain tissue. Human post-mortem tissue from 15 AD subjects and 15 age-matched controls was prepared for analysis through a series of lyophilised, milling, extraction and randomisation steps and samples were analysed using H-1 NMR. Using partial least squares discriminant analysis, a model was built using data obtained from brain extracts. Analysis of brain extracts led to the elucidation of 24 metabolites. Significant elevations in brain alanine (15.4 %) and taurine (18.9 %) were observed in AD patients (p ≤ 0.05). Pathway topology analysis implicated either dysregulation of taurine and hypotaurine metabolism or alanine, aspartate and glutamate metabolism. Furthermore, screening of metabolites for AD biomarkers demonstrated that individual metabolites weakly discriminated cases of AD [receiver operating characteristic (ROC) AUC <0.67; p < 0.05]. However, paired metabolites ratios (e.g. alanine/carnitine) were more powerful discriminating tools (ROC AUC = 0.76; p < 0.01). This study further demonstrates the potential of metabolomics for elucidating the underlying biochemistry and to help identify AD in patients attending the memory clinic

Time for Reform? Refugees, Asylum-seekers and Protection Under International Human Rights Law

The aim is to explore the protection that international human rights law offers to refugees, asylum-seekers, and the forcibly displaced. The ambition of the global rights framework is to guarantee a defined range of rights to all human beings, and thus move the basis for normative entitlement from exclusive reliance on national membership to a common humanity. This comprehensive and international perspective remains formally tied to states - acting individually or collectively - in terms of creation and implementation. The norms must find an entry point into the empirical world, and there must be clarity on responsibilities for practical delivery. It should remain unsurprising that the expectations raised by the normative reach of the law are frequently dashed in the complex and difficult human world of instrumental politics, power, and conflict. The intention here is to outline the international human rights law context, and indicate the value and limitations for the protection of refugees and asylum-seekers. A question is then raised about possible reform.

A revised age of AD 667-699 for the latest major eruption at Rabaul

The most recent major eruption at Rabaul was one of the largest known events at this complex system, having a VEI rating of 6. The eruption generated widespread airfall pumice lapilli and ash deposits and ignimbrites of different types. The total volume of pyroclastic material produced in the eruption exceeded 11 km3 and led to a new phase of collapse within Rabaul Caldera. Initial 14C dating of the eruptive products yielded an age of about 1400 yrs BP, and the eruption became known as the "1400 BP" eruption. Previous analyses of the timing of the eruption have linked it to events in AD 536 and AD 639. However, we have re-evaluated the age of the eruption using the Bayesian wiggle-match radiocarbon dating method, and the eruption is now thought to
have occurred in the interval AD 667-699. The only significant equatorial eruptions recorded in both Greenland and Antarctic ice during this interval are at AD 681 and AD 684, dates that coincide with frost rings in bristlecone pines of western USA in the same years. Definitively linking the Rabaul eruption to this narrow age range will require identification of Rabaul tephra in the ice records. However, it is proposed that a new working hypothesis for the timing of the most recent major eruption at Rabaul is that it occurred in the interval AD 681-684.

Interpretation of Section 17 Employment Protection Act in the light of ECJ case law and under consideration of the cases pending before the Federal Labour Court

This article analyses the relevance of the ECJ ruling in Junk for German labour law.

Labour Law as Human Rights Law: A Critique of the Use of ‘Dignity’ by Freedland and Kountouris

In their recent book, The Legal Construction of Personal Work Relations, Mark Freedland and Nicola Kountouris present an ambitious study of the personal scope of (what they would not want to call) ‘employment’ law. The book does this within a broader argument that calls for the reconceptualization of labour law as a whole, and it is this broader argument on which I shall focus in this chapter. Their aim, in urging us to see labour law through the lens of ‘dignity’ is to bring labour law and human rights law into closer alignment than has sometimes been the case in the past. Increasingly, dignity is seen as providing a, sometimes the, foundation of human rights law, particularly in Europe. I shall suggest that whilst the aim of constructing a new set of foundations for labour law is a worthy and increasingly urgent task, the concepts on which Freedland and Kountouris seek to build their project pose significant difficulties. In particular, their espousal of ‘dignity’ presents problems that must be addressed if their reconceptualization is not to prove a blind alley.

Recent Developments in the Law of Torts in Northern Ireland Annual Conference of the Irish Association of Law Teachers

This paper reviews decisions from the Northern Ireland and England and Wales High Courts and Courts of Appeal as well as the UK Supreme Court relating to tort and principally to the tort of negligence in the past 12 months or so.

In structure, the paper will be presented in four parts. First, three preliminary points relating to contemporary features of the NI civil courts: personal litigants – Devine v McAteer [2012] NICA 30 (7 September 2012); pre-action protocols – Monaghan v Graham [2013] NIQB 53 (3 May 2013); and the rise of alternative dispute resolution. On the last named issue, the recent decision of PGF II SA v OMFS Company 1 Ltd [2013] EWCA Civ 1288 (23 October 2013) on unreasonable refusal to mediate, will be discussed.

Second, the paper moves to consider the law of negligence generally and case law from the NI High Court reiterating Lord Hoffmann’s view in Tomlinson v Congleton Borough Council [2004] 1 AC 46 that no duty of care arises from obvious risks of injury. In this, reference will be made to the application of the above “Hoffmann principle” in West Sussex County Council v Pierce [2013] EWCA Civ 1230 (16 October 2013), which concerned an accident sustained by a child at school. A similar set of facts was presented recently to the UK Supreme Court in Woodland v Essex County Council [2013] UKSC 66 (23 October 2013). The decision there, on non-delegable duties of care, will have a significant impact for schools in the provision of extracurricular activities.

Third, I will review a NI case of note on the duty of care of solicitors in the context of professional negligence in the context of conflicting advice by counsel.

Fourth, I will examine a series of cases on employer liability and including issues such as the duty of care towards the volunteer worker; tort and safety at work principles generally; and, more specifically, the duty of care of the employer towards an employee who suffers psychiatric illness as a result of stress and/or harassment at work. On the issue of workplace stress, the NI courts have made extensive reference to the Hale LJ principles found in the Court of Appeal decision of Hatton v Sutherland [2002] 1 All ER 1 and applied to those who have suffered trauma in reporting on or policing “the troubles” in Northern Ireland. On the issue of statutory harassment at work, the paper will also mention the UK Supreme Court’s decision in Hayes v Willoughby [2013] UKSC 17 (20 March 2013).

The United Kingdom, the United Nations Human Rights Council and the first cycle of the Universal Periodic Review

The introduction of the Universal Periodic Review (UPR) mechanism as an innovative component of the new Human Rights Council in 2006 has suffered little academic scrutiny. This is partly because it holds as its objective an improvement in human rights situations on the ground, a goal that is difficult to test amongst so many possible causal factors attributable to law reform and policy change, and partly due to the fact that the mechanism has only completed one full cycle of review. This article seeks to remedy this absence of analysis by examining the experience of the United Kingdom during its first review. In doing so, the article first considers the conception of the UPR, before progressing to examine the procedure and recommendations made to the UK by its peers. Finally, the article considers the five year review of the UPR which occurred as a subset of the Human Rights Council Review in 2011 and the resulting changes to the process modalities.