Gene-based pleiotropy across migraine with aura and migraine without aura patient groups

Introduction: It is unclear whether patients diagnosed according to International Classification of Headache Disorders criteria for migraine with aura (MA) and migraine without aura (MO) experience distinct disorders or whether their migraine subtypes are genetically related. Aim: Using a novel gene-based (statistical) approach, we aimed to identify individual genes and pathways associated both with MA and MO. Methods: Gene-based tests were performed using genome-wide association summary statistic results from the most recent International Headache Genetics Consortium study comparing 4505 MA cases with 34,813 controls and 4038 MO cases with 40,294 controls. After accounting for non-independence of gene-based test results, we examined the significance of the proportion of shared genes associated with MA and MO. Results: We found a significant overlap in genes associated with MA and MO. Of the total 1514 genes with a nominally significant gene-based p value (pgene-based ≤ 0.05) in the MA subgroup, 107 also produced pgene-based ≤ 0.05 in the MO subgroup. The proportion of overlapping genes is almost double the empirically derived null expectation, producing significant evidence of gene-based overlap (pleiotropy) (pbinomial-test = 1.5 × 10–4). Combining results across MA and MO, six genes produced genome-wide significant gene-based p values. Four of these genes (TRPM8, UFL1, FHL5 and LRP1) were located in close proximity to previously reported genome-wide significant SNPs for migraine, while two genes, TARBP2 and NPFF separated by just 259 bp on chromosome 12q13.13, represent a novel risk locus. The genes overlapping in both migraine types were enriched for functions related to inflammation, the cardiovascular system and connective tissue. Conclusions: Our results provide novel insight into the likely genes and biological mechanisms that underlie both MA and MO, and when combined with previous data, highlight the neuropeptide FF-amide peptide encoding gene (NPFF) as a novel candidate risk gene for both types of migraine.

The 2008 declaration of independence by the Hong Kong Court and anomalies in the Hong Kong Company Law

Discusses two aspects of Hong Kong law: 1) the judgment of the Hong Kong Court of Final Appeal in A Solicitor v The Law Society of Hong Kong on whether Hong Kong courts were bound, post-1997, by pre-1997 House of Lords or Privy Council decisions, by pre-1997 decisions of their own, or by post-1997 overseas decisions from any jurisdiction; and 2) the need for clarification in the Hong Kong Companies Ordinance of whether a company can have a single legal representative, the ultra vires rule and the duties of company directors

Improved functional ability and independence in activities of daily living for older adults at high risk of hospital readmission : a randomised controlled trial

Objective: During hospitalisation older people often experience functional decline which impacts on their future independence. The objective of this study was to evaluate a multifaceted transitional care intervention including home-based exercise strategies for at-risk older people on functional status, independence in activities of daily living, and walking ability. Methods: A randomised controlled trial was undertaken in a metropolitan hospital in Australia with 128 patients (64 intervention, 64 control) aged over 65 years with an acute medical admission and at least one risk factor for hospital readmission. The intervention group received an individually tailored program for exercise and follow-up care which was commenced in hospital and included regular visits in hospital by a physiotherapist and a Registered Nurse, a home visit following discharge, and regular telephone follow-up for 24 weeks following discharge. The program was designed to improve health promoting behaviours, strength, stability, endurance and mobility. Data were collected at baseline, then 4, 12 and 24 weeks following discharge using the Index of Activities of Daily Living (ADL), Instrumental Index of Activities of Daily Living (IADL), and the Walking Impairment Questionnaire (Modified). Results: Significant improvements were found in the intervention group in IADL scores (p<.001), ADL scores (p<.001), and WIQ scale scores (p<.001) in comparison to the control group. The greatest improvements were found in the first four weeks following discharge. Conclusions: Early introduction of a transitional model of care incorporating a tailored exercise program and regular telephone follow-up for hospitalised at-risk older adults can improve independence and functional ability.

The role of academic community in higher learning : Alternatives to a drive-thru education

The purpose of our paper is to illustrate the fundamental importance of developing academic community among first year students. We argue that a sense of academic community is of fundamental importance in combating the effects of the neo-liberal economic discourse on higher education, and that the values of higher education are incongruent with those of economic rationalism. The discursive commodification of the student, and of education itself, works against the formation of community, both within the university environment and in the wider society. We argue that, at present, the dominant discourse shaping the social practice of higher education is that of neo-liberal economics. Community values stand in opposition to the dominant discourse, and are integral to the long-term survival of a socially critical and socially responsive society. We conclude that the importance of establishing a sense of academic community during the first year of university is justified by its ultimate value to society.

Insurance and the law of negligence : an influential or irrelevant persuader?

This article examines, from both within and outside the context of compulsory third party motor vehicle insurance, the different academic and judicial perspectives regarding the relevance of insurance to the imposition of negligence liability via the formulation of legal principle. In particular, the utility of insurance in setting the standard of care held owing by a learner driver to an instructor in Imbree v McNeilly is analysed and the implications of this High Court decision, in light of current jurisprudential argument and for other principles of negligence liability, namely claimant vulnerability, are considered. It concludes that ultimately one’s stance as to the relevance, or otherwise, of insurance to the development of the common law of negligence will be predominately influenced by normative views of torts’ function as an instrument of corrective or distributive justice.

Envisaging alternatives for practice : a study into the way concepts of sustain-ability can be explored within an interactive media arts practice

This practice-led study explores different ways the subject of sustain-ability can be addressed within an Interactive Media Arts practice. The exploration encompasses three creative projects, Charmed, Distracted and e. Menura superba. Grounded in an ecological philosophy inspired by vegetarianism and the critical design philosophy of defuturing, the work shows how such a philosophical position can guide the redirection of practice. The concern for sustain-ability within my practice, and more generally the question of Interactive Media Arts and sustain-ability, I refer to as a problématique. The objective of this study is not one of finding an answer or a truth to an instrumentally posed question, but to explore the complexities of the problématique through a program of practice and intellectual investigation. The aim being to redirect my practice and to find a renewed raison d’être for practice through a process of opening up, encountering, and discovering otherwise unknown possibilities for practice. In the context of sustain-ability, this opening up of possibilities can be considered a form of futuring. A futuring I argue is only possible if the things we take for granted as integral aspects of our being, practices and life worlds, are revealed in ways that estrange them, rendering them visible in ways that allow questioning and change.

Inequities, alternatives and future directions : inside perspectives of Indigenous sentencing in Queensland

In Australia, sentencing researchers have generally focussed on whether there is statistical equality/inequality in outcomes by reference to Indigenous status. However, contextualising the sentencing process requires us to move away from a reliance on statistical analyses alone, as this approach cannot tell us whether sentencing is an equitable process for Indigenous people. Consultation with those working at the sentencing ‘coal face’ provides valuable insight into the nexus between Indigenous status and sentencing. This article reports the main themes from surveys of the judiciary and prosecutors, and focus groups of Community Justice Groups undertaken in Queensland. The aim is to understand better the sentencing process for Indigenous Queenslanders. Results suggest that while there have been some positive developments in sentencing (e.g. the Murri Court, Community Justice Groups) Indigenous offenders still face a number of inequities.

The impact of auditor independence regulations on established and emerging firms.

Purpose – The purpose of this paper is to study whether auditor independence reforms introduced in 2004 led to an enhancement in earnings quality in the post-reform era. Design/methodology/approach – This study predicts that as the cost of compliance will vary based on a firm's existing corporate governance regime and the level of external scrutiny (monitoring) it faces, we compare the earnings quality of a sample of “established” (S&P/ASX 100) to a sample of “emerging” (S&P/ASX Small Ordinaries Index) firms. The paper examines the reporting behaviour of the two groups of listed entities, covering the regulatory change period 2003-2006. The paper uses regression modelling to test the associations between increased audit independence, earnings quality and corporate governance mechanisms over the pre- and post-regulatory period. Findings – The paper's results confirm that earnings quality for the established firms was enhanced in the post-reform period; while this was not the case for emerging firms. The evidence also suggests that corporate governance mechanisms of board independence and board financial skill are associated with higher earnings quality; while the higher the concentration of insider firm ownership is associated with lower earnings quality. Practical implications – This study provides policy makers with evidence as to changes in reporting behaviour following law reform aimed at strengthening auditor independence. Originality/value – The studies on earnings quality are informed by the US market practices. Australia provides a unique setting through its auditor independence reforms to examine the impact of reform choices. This study also investigates two specific subsets of the market: established firms and emerging firms.

Acquisition of estrogen independence and antiestrogen resistance in breast cancer : association with the invasive and metastatic phenotype

A significant percentage of human breast cancer (HBC) is dependent upon the ovarian hormone estrogen for its onset and progression. The presence or lack of estrogen receptors (ERs) in human breast cancer is an important determinant both of prognosis and of choice of treatment - a poorer prognosis being associated with ER–ve disease. Cell lines established from human breast cancer provide models for breast cancer in various stages of progression (Engel & Young 1978). When grown as tumors in athymic nude mice, these lines represent the major in vivo experimental model for HBC studies (Brünner et al 1987). The ease of both in vitro and in vivo maintenance, the human derivation of the tissue, and the similarities in plasma estrogen levels between ovariectomized nude mice and postmenopausal women (Seibert et al. 1983, Brünner et al. 1986), make the growth of human breast cancer cell lines in nude mice an attractive...

The biology of breast tumor progression : acquisition of hormone independence and resistance to cytotoxic drugs

Many breast tumors appear to follow a predictable clinical pattern, being initially responsive to endocrine therapy and to cytotoxic chemotherapy but ultimately exhibiting a phenotype resistant to both modalities. Using the MCF-7 human breast cancer cell line as an example of an 'early' phenotype (estrogen and progesterone receptor positive, steroid responsive, low metastatic potential), we have isolated and characterized a series of hormone-independent but hormone-responsive variants (MIII and MCF7/LCC1). However, these variants remain responsive to both antiestrogens and cytotoxic drugs (methotrexate and colchicine). MIII and MCF7/LCCl cells appear to mimic some of the critical aspects of the early progression to a more aggressive phenotype. An examination of the phenotype of these cells suggests that some hormone-independent breast cancer cells are derived from hormone-dependent parental cells. The development of a hormone-independent phenotype can arise independently of acquisition of a cytotoxic drug resistant phenotype.