Genome-wide meta-analysis identifies new susceptibility loci for migraine

Migraine is the most common brain disorder, affecting approximately 14% of the adult population, but its molecular mechanisms are poorly understood. We report the results of a meta-analysis across 29 genome-wide association studies, including a total of 23,285 individuals with migraine (cases) and 95,425 population-matched controls. We identified 12 loci associated with migraine susceptibility (P<5x10(-8)). Five loci are new: near AJAP1 at 1p36, near TSPAN2 at 1p13, within FHL5 at 6q16, within C7orf10 at 7p14 and near MMP16 at 8q21. Three of these loci were identified in disease subgroup analyses. Brain tissue expression quantitative trait locus analysis suggests potential functional candidate genes at four loci: APOA1BP, TBC1D7, FUT9, STAT6 and ATP5B.

Genome-wide association study of migraine implicates a common susceptibility variant on 8q22.1

Migraine is a common episodic neurological disorder, typically presenting with recurrent attacks of severe headache and autonomic dysfunction. Apart from rare monogenic subtypes, no genetic or molecular markers for migraine have been convincingly established. We identified the minor allele of rs1835740 on chromosome 8q22.1 to be associated with migraine (P = 5.38 x 10(-)(9), odds ratio = 1.23, 95% CI 1.150-1.324) in a genome-wide association study of 2,731 migraine cases ascertained from three European headache clinics and 10,747 population-matched controls. The association was replicated in 3,202 cases and 40,062 controls for an overall meta-analysis P value of 1.69 x 10(-)(1)(1) (odds ratio = 1.18, 95% CI 1.127-1.244). rs1835740 is located between MTDH (astrocyte elevated gene 1, also known as AEG-1) and PGCP (encoding plasma glutamate carboxypeptidase). In an expression quantitative trait study in lymphoblastoid cell lines, transcript levels of the MTDH were found to have a significant correlation to rs1835740 (P = 3.96 x 10(-)(5), permuted threshold for genome-wide significance 7.7 x 10(-)(5). To our knowledge, our data establish rs1835740 as the first genetic risk factor for migraine.

A high-density association screen of 155 ion transport genes for involvement with common migraine

The clinical overlap between monogenic Familial Hemiplegic Migraine (FHM) and common migraine subtypes, and the fact that all three FHM genes are involved in the transport of ions, suggest that ion transport genes may underlie susceptibility to common forms of migraine. To test this leading hypothesis, we examined common variation in 155 ion transport genes using 5257 single nucleotide polymorphisms (SNPs) in a Finnish sample of 841 unrelated migraine with aura cases and 884 unrelated non-migraine controls. The top signals were then tested for replication in four independent migraine case-control samples from the Netherlands, Germany and Australia, totalling 2835 unrelated migraine cases and 2740 unrelated controls. SNPs within 12 genes (KCNB2, KCNQ3, CLIC5, ATP2C2, CACNA1E, CACNB2, KCNE2, KCNK12, KCNK2, KCNS3, SCN5A and SCN9A) with promising nominal association (0.00041 < P < 0.005) in the Finnish sample were selected for replication. Although no variant remained significant after adjusting for multiple testing nor produced consistent evidence for association across all cohorts, a significant epistatic interaction between KCNB2 SNP rs1431656 (chromosome 8q13.3) and CACNB2 SNP rs7076100 (chromosome 10p12.33) (pointwise P = 0.00002; global P = 0.02) was observed in the Finnish case-control sample. We conclude that common variants of moderate effect size in ion transport genes do not play a major role in susceptibility to common migraine within these European populations, although there is some evidence for epistatic interaction between potassium and calcium channel genes, KCNB2 and CACNB2. Multiple rare variants or trans-regulatory elements of these genes are not ruled out.

Consistently replicating locus linked to migraine on 10q22-q23

Here, we present the results of two genome-wide scans in two diverse populations in which a consistent use of recently introduced migraine-phenotyping methods detects and replicates a locus on 10q22-q23, with an additional independent replication. No genetic variants have been convincingly established in migraine, and although several loci have been reported, none of them has been consistently replicated. We employed the three known migraine-phenotyping methods (clinical end diagnosis, latent-class analysis, and trait-component analysis) with robust multiple testing correction in a large sample set of 1675 individuals from 210 migraine families from Finland and Australia. Genome-wide multipoint linkage analysis that used the Kong and Cox exponential model in Finns detected a locus on 10q22-q23 with highly significant evidence of linkage (LOD 7.68 at 103 cM in female-specific analysis). The Australian sample showed a LOD score of 3.50 at the same locus (100 cM), as did the independent Finnish replication study (LOD score 2.41, at 102 cM). In addition, four previously reported loci on 8q21, 14q21, 18q12, and Xp21 were also replicated. A shared-segment analysis of 10q22-q23 linked Finnish families identified a 1.6-9.5 cM segment, centered on 101 cM, which shows in-family homology in 95% of affected Finns. This region was further studied with 1323 SNPs. Although no significant association was observed, four regions warranting follow-up studies were identified. These results support the use of symptomology-based phenotyping in migraine and suggest that the 10q22-q23 locus probably contains one or more migraine susceptibility variants.

Socio-Legal Aspects of the 3D Printing Revolution

Additive manufacturing or ‘3D printing’ has emerged into the mainstream in the last few years, with much hype about its revolutionary potential as the latest ‘disruptive technology’ to destroy existing business models, empower individuals and evade any kind of government control. This book examines the trajectory of 3D printing in practice and how it interacts with various areas of law, including intellectual property, product liability, gun laws, data privacy and fundamental/constitutional rights. A particular comparison is made between 3D printing and the Internet as this has been, legally-speaking, another ‘disruptive technology’ and also one on which 3D printing is partially dependent. This book is the first expert analysis of 3D printing from a legal perspective and provides a critical assessment of the extent to which existing legal regimes can be successfully applied to, and enforced vis-à-vis, 3D printing.

Net neutrality in Australia: The debate continues, but no policy in sight

The ways in which Internet traffic is managed have direct consequences on Internet users’ rights as well as on their capability to compete on a level playing field. Network neutrality mandates to treat Internet traffic in a non-discriminatory fashion in order to maximise end users’ freedom and safeguard an open Internet.

Legislating on biopiracy in Europe: too little, too late?

This Handbook considers the international struggle to provide for proper and just protection of Indigenous intellectual property. Leading scholars consider legal and policy controversies over Indigenous knowledge in the fields of international law, copyright law, trademark law, patent law, trade secrets law, and cultural heritage. This collection examines national developments in Indigenous intellectual property from around the world. As well as examining the historical origins of conflicts over Indigenous knowledge, the volume examines new challenges to Indigenous intellectual property from emerging developments in information technology, biotechnology, and climate change.

'SABAM v scarlet: Evidence of an emerging backlash against corporate copyright lobbies in Europe?

The symbols, signs, and traces of copyright and related intellectual property laws that appear on everyday texts, objects, and artifacts have multiplied exponentially over the past 15 years. Digital spaces have revolutionized access to content and transformed the ways in which content is porous and malleable. In this volume, contributors focus on copyright as it relates to culture. The editors argue that what «counts» as property must be understood as shifting terrain deeply influenced by historical, economic, cultural, religious, and digital perspectives. Key themes addressed include issues of how: • Culture is framed, defined, and/or identified in conversations about intellectual property; • The humanities and other related disciplines are implicated in intellectual property issues; • The humanities will continue to rub up against copyright (e.g., issues of authorship, authorial agency, ownership of texts); • Different cultures and bodies of literature approach intellectual property, and how competing dynasties and marginalized voices exist beyond the dominant U.S. copyright paradigm. Offering a transnational and interdisciplinary perspective, Cultures of Copyright offers readers – scholars, researchers, practitioners, theorists, and others – key considerations to contemplate in terms of how we understand copyright’s past and how we chart its futures.

Dominating search: Google before the law

For many, particularly in the Anglophone world and Western Europe, it may be obvious that Google has a monopoly over online search and advertising and that this is an undesirable state of affairs, due to Google's ability to mediate information flows online. The baffling question may be why governments and regulators are doing little to nothing about this situation, given the increasingly pivotal importance of the internet and free flowing communications in our lives. However, the law concerning monopolies, namely antitrust or competition law, works in what may be seen as a less intuitive way by the general public. Monopolies themselves are not illegal. Conduct that is unlawful, i.e. abuses of that market power, is defined by a complex set of rules and revolves principally around economic harm suffered due to anticompetitive behavior. However the effect of information monopolies over search, such as Google’s, is more than just economic, yet competition law does not address this. Furthermore, Google’s collection and analysis of user data and its portfolio of related services make it difficult for others to compete. Such a situation may also explain why Google’s established search rivals, Bing and Yahoo, have not managed to provide services that are as effective or popular as Google’s own (on this issue see also the texts by Dirk Lewandowski and Astrid Mager in this reader). Users, however, are not entirely powerless. Google's business model rests, at least partially, on them – especially the data collected about them. If they stop using Google, then Google is nothing.

Private power and new media: The case of the corporate suppression of WikiLeaks and its implications for the exercise of fundamental rights on the internet

Globalization, along with its digital and information communication technology counterparts, including the Internet and cyberspace, may signify a whole new era for human rights, characterized by new tensions, challenges, and risks for human rights, as well as new opportunities. Human Rights and Risks in the Digital Era: Globalization and the Effects of Information Technologies explores the emergence and evolution of ‘digital’ rights that challenge and transform more traditional legal, political, and historical understandings of human rights. Academic and legal scholars will explore individual, national, and international democratic dilemmas--sparked by economic and environmental crises, media culture, data collection, privatization, surveillance, and security--that alter the way individuals and societies think about, regulate, and protect rights when faced with new challenges and threats. The book not only uncovers emerging changes in discussions of human rights, it proposes legal remedies and public policies to mitigate the challenges posed by new technologies and globalization.

The global burden of injury: Incidence, mortality, disability-adjusted life years and time trends from the Global Burden of Disease study 2013

Background The Global Burden of Diseases (GBD), Injuries, and Risk Factors study used the disability-adjusted life year (DALY) to quantify the burden of diseases, injuries, and risk factors. This paper provides an overview of injury estimates from the 2013 update of GBD, with detailed information on incidence, mortality, DALYs and rates of change from 1990 to 2013 for 26 causes of injury, globally, by region and by country. Methods Injury mortality was estimated using the extensive GBD mortality database, corrections for ill-defined cause of death and the cause of death ensemble modelling tool. Morbidity estimation was based on inpatient and outpatient data sets, 26 cause-of-injury and 47 nature-of-injury categories, and seven follow-up studies with patient-reported long-term outcome measures. Results In 2013, 973 million (uncertainty interval (UI) 942 to 993) people sustained injuries that warranted some type of healthcare and 4.8 million (UI 4.5 to 5.1) people died from injuries. Between 1990 and 2013 the global age-standardised injury DALY rate decreased by 31% (UI 26% to 35%). The rate of decline in DALY rates was significant for 22 cause-of-injury categories, including all the major injuries. Conclusions Injuries continue to be an important cause of morbidity and mortality in the developed and developing world. The decline in rates for almost all injuries is so prominent that it warrants a general statement that the world is becoming a safer place to live in. However, the patterns vary widely by cause, age, sex, region and time and there are still large improvements that need to be made.

Review of 'Kafka Dances'

Review of Timothy Daly's new Australian play, 'Kafka Dances' in Australasian Drama Studies

The legality of deep packet inspection

Deep packet inspection is a technology which enables the examination of the content of information packets being sent over the Internet. The Internet was originally set up using “end-to-end connectivity” as part of its design, allowing nodes of the network to send packets to all other nodes of the network, without requiring intermediate network elements to maintain status information about the transmission. In this way, the Internet was created as a “dumb” network, with “intelligent” devices (such as personal computers) at the end or “last mile” of the network. The dumb network does not interfere with an application's operation, nor is it sensitive to the needs of an application, and as such it treats all information sent over it as (more or less) equal. Yet, deep packet inspection allows the examination of packets at places on the network which are not endpoints, In practice, this permits entities such as Internet service providers (ISPs) or governments to observe the content of the information being sent, and perhaps even manipulate it. Indeed, the existence and implementation of deep packet inspection may challenge profoundly the egalitarian and open character of the Internet. This paper will firstly elaborate on what deep packet inspection is and how it works from a technological perspective, before going on to examine how it is being used in practice by governments and corporations. Legal problems have already been created by the use of deep packet inspection, which involve fundamental rights (especially of Internet users), such as freedom of expression and privacy, as well as more economic concerns, such as competition and copyright. These issues will be considered, and an assessment of the conformity of the use of deep packet inspection with law will be made. There will be a concentration on the use of deep packet inspection in European and North American jurisdictions, where it has already provoked debate, particularly in the context of discussions on net neutrality. This paper will also incorporate a more fundamental assessment of the values that are desirable for the Internet to respect and exhibit (such as openness, equality and neutrality), before concluding with the formulation of a legal and regulatory response to the use of this technology, in accordance with these values.

The AOL Huffington Post merger

This article examines the merger between AOL and the Huffington Post. The broader issues around the merger will be investigated, especially the implication for rights, in particular free expression, and their conditions for exercise and actual exercise online. One major issue is that of the status of user-generated content and how the existing legal regime reflects the ethical concerns of users over how their content, data and information is used and commodified by the for-profit Internet intermediaries and platforms, especially when they start to merge and form concentrations. The extent to which the current legal regimes, especially human rights, deal with these problems in an adequate fashion will be assessed, along with the presentation of some suggestions of alternative approaches which may be more effective in practice.

Free software and the law. Out of the frying pan and into the fire: How shaking up intellectual property suits competition law just fine

Free software is viewed as a revolutionary and subversive practice, and in particular has dealt a strong blow to the traditional conception of intellectual property law (although in its current form could be considered a 'hack' of IP rights). However, other (capitalist) areas of law have been swift to embrace free software, or at least incorporate it into its own tenets. One area in particular is that of competition (antitrust) law, which itself has long been in theoretical conflict with intellectual property, due to the restriction on competition inherent in the grant of ‘monopoly’ rights by copyrights, patents and trademarks. This contribution will examine how competition law has approached free software by examining instances in which courts have had to deal with such initiatives, for instance in the Oracle Sun Systems merger, and the implications that these decisions have on free software initiatives. The presence or absence of corporate involvement in initiatives will be an important factor in this investigation, with it being posited that true instances of ‘commons-based peer production’ can still subvert the capitalist system, including perplexing its laws beyond intellectual property.