Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: A pilot project of the ENIGMA-DTI working group

The ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium was set up to analyze brain measures and genotypes from multiple sites across the world to improve the power to detect genetic variants that influence the brain. Diffusion tensor imaging (DTI) yields quantitative measures sensitive to brain development and degeneration, and some common genetic variants may be associated with white matter integrity or connectivity. DTI measures, such as the fractional anisotropy (FA) of water diffusion, may be useful for identifying genetic variants that influence brain microstructure. However, genome-wide association studies (GWAS) require large populations to obtain sufficient power to detect and replicate significant effects, motivating a multi-site consortium effort. As part of an ENIGMA-DTI working group, we analyzed high-resolution FA images from multiple imaging sites across North America, Australia, and Europe, to address the challenge of harmonizing imaging data collected at multiple sites. Four hundred images of healthy adults aged 18-85 from four sites were used to create a template and corresponding skeletonized FA image as a common reference space. Using twin and pedigree samples of different ethnicities, we used our common template to evaluate the heritability of tract-derived FA measures. We show that our template is reliable for integrating multiple datasets by combining results through meta-analysis and unifying the data through exploratory mega-analyses. Our results may help prioritize regions of the FA map that are consistently influenced by additive genetic factors for future genetic discovery studies. Protocols and templates are publicly available at (http://enigma.loni.ucla.edu/ongoing/dti-working-group/).

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen’s d=−0.14, % difference=−1.24). This effect was driven by patients with recurrent MDD (Cohen’s d=−0.17, % difference=−1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen’s d=−0.20, % difference=−1.85) and a trend toward smaller amygdala (Cohen’s d=−0.11, % difference=−1.23) and larger lateral ventricles (Cohen’s d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

Quality in group service encounters: A theoretical exploration of the concept of a simultaneous multi‐customer co‐creation process

Purpose The purpose of this paper is to explore the concept of service quality for settings where several customers are involved in the joint creation and consumption of a service. The approach is to provide first insights into the implications of a simultaneous multi‐customer integration on service quality. Design/methodology/approach This conceptual paper undertakes a thorough review of the relevant literature before developing a conceptual model regarding service co‐creation and service quality in customer groups. Findings Group service encounters must be set up carefully to account for the dynamics (social activity) in a customer group and skill set and capabilities (task activity) of each of the individual participants involved in a group service experience. Research limitations/implications Future research should undertake empirical studies to validate and/or modify the suggested model presented in this contribution. Practical implications Managers of service firms should be made aware of the implications and the underlying factors of group services in order to create and manage a group experience successfully. Particular attention should be given to those factors that can be influenced by service providers in managing encounters with multiple customers. Originality/value This article introduces a new conceptual approach for service encounters with groups of customers in a proposed service quality model. In particular, the paper focuses on integrating the impact of customers' co‐creation activities on service quality in a multiple‐actor model.

Aligning and characterising group behaviours using role information

Techniques to align spatio-temporal data for large-scale analysis of human group behaviour have been developed. Application of the techniques to sports databases enable sport team's characteristic styles of play to be discovered and compared for tactical analysis. Applications in surveillance to recognise group activities in real-time for person re-identification from low-resolution video footage have also been developed.

Friends or foes: Group influence effects on moderate drinking behaviors

Drunkenness and the addictive consumption of alcohol remains a key social and public health concern. Advancing beyond traditional individualized prevention approaches, this research explores the role of social influences in determining individual and group influence in moderate-drinking decision-making and participatory actions. A social influence model of intentional moderate drinking actions is conceptualized and validated. Results show group norm as the single social influence predictor of intentions and desire to drink moderately, as opposed to well-known social influence factors (e.g., subjective norm, social identity and drinking contextual effects). Significantly, the peer-group is identified as a key influencer supporting moderate drinking practices, and i-intentions to drink moderately predict group-related we-intentions, which suggests that moderate drinking is a shared goal. These findings advance alcohol prevention research drawing attention to the power of group dynamics to support positive changes in youth drinking behaviors.

The race to patent the SARS virus: The TRIPS agreement and access to essential medicines

This article considers the race to sequence the Severe Acute Respiratory Syndrome virus ('the SARS virus') in light of the debate over patent law and access to essential medicines. Part II evaluates the claims of public research institutions in Canada, the United States, and Hong Kong, and commercial companies, to patent rights in respect of the SARS virus. It highlights the dilemma of ’defensive patenting' - the tension between securing private patent rights and facilitating public disclosure of information and research. Part III considers the race to patent the SARS virus in light of wider policy debates over gene patents. It examines the application of such patent criteria as novelty, inventive step, utility, and secret use. It contends that there is a need to reform the patent system to accommodate the global nature of scientific inquiry, the unique nature of genetics, and the pace of technological change. Part IV examines the role played by the World Trade Organization and the World Health Organization in dealing with patent law and access to essential medicines. The article contends that there is a need to ensure that the patent system is sufficiently flexible and adaptable to accommodate international research efforts on infectious diseases.

A Submission to the Senate Legal and Constitutional Affairs Committee on the Copyright Amendment (Online Infringement) Bill 2015 (Cth)

The film company, Roadshow, the pay television company Foxtel, and Rupert Murdoch’s News Corp and News Limited — as well as copyright industries — have been clamouring for new copyright powers and remedies. In the summer break, the Coalition Government has responded to such entreaties from its industry supporters and donors, with a new package of copyright laws and policies. There has been significant debate over the proposals between the odd couple of Attorney-General George Brandis and the Minister for Communications, Malcolm Turnbull. There has been deep, philosophical differences between the two Ministers over the copyright agenda. The Attorney-General George Brandis has supported a model of copyright maximalism, with strong rights and remedies for the copyright empires in film, television, and publishing. He has shown little empathy for the information technology companies of the digital economy. The Attorney-General has been impatient to press ahead with a copyright regime. The Minister for Communications, Malcolm Turnbull, has been somewhat more circumspect,recognising that there is a need to ensure that copyright laws do not adversely impact upon competition in the digital economy. The final proposal is a somewhat awkward compromise between the discipline-and-punish regime preferred by Brandis, and the responsive regulation model favoured by Turnbull. In his new book, Information Doesn’t Want to Be Free: Laws for the Internet Age, Cory Doctorow has some sage advice for copyright owners: Things that don’t make money: * Complaining about piracy. * Calling your customers thieves. * Treating your customers like thieves. In this context, the push by copyright owners and the Coalition Government to have a copyright crackdown may well be counter-productive to their interests. This submission considers a number of key elements of the Coalition Government’s Copyright Crackdown. Part 1 examines the proposals in respect of the Copyright Amendment (Online Infringement) Bill 2015 (Cth). Part 2 focuses upon the proposed Copyright Code. Part 3 considers the question of safe harbours for intermediaries. Part 4 examines the question of copyright exceptions – particularly looking at the proposal of the Australian Law Reform Commission for the introduction of a defence of fair use. Part 5 highlights the recommendations of the IT Pricing Inquiry and the Harper Competition Policy Review in respect of copyright law, consumer rights, and competition law.

Breast and prostate cancer survivor responses to group exercise and supportive group Psychotherapy

This study qualitatively examined an 8 week group exercise and counseling intervention for breast and prostate cancer survivors. Groups exercised 3 days per week, 50 minutes per session,performing moderate intensity aerobic and resistance training. Groups also underwent 90 minute supportive group psychotherapy sessions once per week. Survivors discussed their experiences in focus groups post intervention. Transcripts were analyzed using interpretative phenomenological analysis. Survivors described how exercise facilitated counseling by creating mutual aid and trust, and counseling helped participants with self-identity, sexuality, and returning to normalcy. When possible, counselors and fitness professionals should create partnerships to optimally support cancer survivors.

Defining anthropometric cut-off levels related to metabolic risk in a group of Sri Lankan children

Background: Body mass index (BMI) is widely used as a measure of adiposity. However, currently used cut-off values are not sensitive in diagnosing obesity in South Asian populations. Aim: To define BMI and waist circumference (WC), cut-off values representing percentage fat mass (%FM) associated with adverse health outcomes. Subjects and methods: A cross-sectional descriptive study of 285 5–14 year old Sri Lankan children (56% boys) was carried out. Fat mass (FM) was assessed using the isotope (D2O) dilution technique based on 2C body composition model. BMI and WC cut-off values were defined based on %FM associated with adverse health outcomes. Results: Sri Lankan children had a low fat free mass index (FFMI) and a high fat mass index (FMI). Individuals with the same BMI had %FM distributed over a wide range. Lean body tissue grew very little with advancing age and weight gain was mainly due to increases in body fat. BMI corresponding to 25% in males and 35% in females at 18 years was 19.2 kg/m2 and 19.7 kg/m2, respectively. WC cut-off values for males and females were 68.4 cm and 70.4 cm, respectively. Conclusion: This chart analysis clearly confirms that Sri Lankan children have a high %FM from a young age. With age, more changes occur in FM than in fat free mass (FFM). Although the newly defined BMI and WC cut-off values appear to be quite low, they are comparable to some recent data obtained in similar populations.

Crowning of dibenzosilole with a naphthalenediimide functional group to prepare an electron acceptor for organic solar cells

A novel, solution-processable non-fullerene electron acceptor 9,9′-(5,5-dioctyl-5H-dibenzo [b,d]silole-3,7-diyl)bis(2,7-dioctyl-4-(octylamino)benzo[lmn][3,8]phenanthroline-1,3,6,8(2H,7H)-tetraone) (B3) based on dibenzosilole and naphthalenediimide building blocks was designed, synthesized, characterized and successfully used in a bulk-heterojunction organic solar cell. B3 displayed excellent solubility, thermal stability and acquired electron energy levels matching with those of archetypal donor polymer poly(3-hexylthiophene). Solution-processable bulk-heterojunction devices afforded 1.16% power conversion efficiency with a high fill factor of 53%. B3 is the first example in the literature using this design principle, where mild donor units at the peripheries of end-capped naphthalenediimide units tune solubility and optical energy levels simultaneously.

Pivotal people, pivotal journeys: Interim report on the impact of a fundraising study tour on CEOs and their organisations

A longitudinal qualitative study was conducted with CEOs of 12 fundraising organisations across Australia to answer the question - how mights a change in the CEO's fundraising knowledge improve fundraising activity and outcomes for their organisation? The CEOs along with the inaugural Australian Grantmaker of the Year, Caitriona Fay from Perpetual and lead researcher Dr Wendy Scaife travelled to San Antonio, Texas, USA to attend the annual Association of Fundraising Professionals (AFP) conference in March 2014. Participants identified five main success factors for such group learning initiatives about fundraising: - Getting away from the day to day business of running the organisation - Informal, social time to debrief and get to know others - Diversity of organisations whereby no one was in direct competition to others - Commitment, openness and willingness of individuals to participate - Group facilitation This research has been supported by the Perpetual Foundation – Trustees Endowment, The Edward Corbould Charitable Trust, and the Samuel and Eileen Gluyas Charitable Trust under the management of Perpetual Trustee Company Ltd.

Group 14 element-based non-centrosymmetric quantum spin hall insulators with large bulk gap

To date, a number of two-dimensional (2D) topological insulators (TIs) have been realized in Group 14 elemental honeycomb lattices, but all are inversionsymmetric. Here, based on first-principles calculations, we predict a new family of 2D inversion-asymmetric TIs with sizeable bulk gaps from 105 meV to 284 meV, in X2–GeSn (X = H, F, Cl, Br, I) monolayers, making them in principle suitable for room-temperature applications. The nontrivial topological characteristics of inverted band orders are identified in pristine X2–GeSn with X = (F, Cl, Br, I), whereas H2–GeSn undergoes a nontrivial band inversion at 8% lattice expansion. Topologically protected edge states are identified in X2–GeSn with X = (F, Cl, Br, I), as well as in strained H2–GeSn. More importantly, the edges of these systems, which exhibit single-Dirac-cone characteristics located exactly in the middle of their bulk band gaps, are ideal for dissipationless transport. Thus, Group 14 elemental honeycomb lattices provide a fascinating playground for the manipulation of quantum states.

Matters Arising: Zhu et al, "A novel gene variation of TNFα associated with ankylosing spondylitis: A reconfirmed study"

In a recently published study1 involving 79 ankylosing spondylitis (AS) patients and 132 unrelated healthy blood donors, Zhu et al report association of a tumour necrosis factor α (TNFα) single nucleotide polymorphism (SNP), rs1799724, with AS.1 I have many concerns with this paper and its conclusions...

HLA class I associations of ankylosing spondylitis in the white population in the United Kingdom

Objective - To investigate the HLA class I associations of ankylosing spondylitis (AS) in the white population, with particular reference to HLA-B27 subtypes. Methods - HLA-B27 and -B60 typing was performed in 284 white patients with AS. Allele frequencies of HLA-B27 and HLA-B60 from 5926 white bone marrow donors were used for comparison. HLA-B27 subtyping was performed by single strand conformation polymorphism (SSCP) in all HLA-B27 positive AS patients, and 154 HLA-B27 positive ethnically matched blood donors. Results - The strong association of HLA-B27 and AS was confirmed (odds ratio (OR) 171, 95% confidence interval (CI) 135 to 218; p < 10-99). The association of HLA-B60 with AS was confirmed in HLA-B27 positive cases (OR 3.6, 95% CI 2.1 to 6.3; p < 5 x 10-5), and a similar association was demonstrated in HLA-B27 negative AS (OR 3.5, 95% CI 1.1 to 11.4; p < 0.05). No significant difference was observed in the frequencies of HLA-B27 allelic subtypes in patients and controls (HLA-B*2702, three of 172 patients v five of 154 controls; HLA-B*2705, 169 of 172 patients v 147 of 154 controls; HkA-B*2708, none of 172 patients v two of 154 controls), and no novel HLA-B27 alleles were detected. Conclusion - HLA-B27 and -B60 are associated with susceptibility to AS, but differences in BLA-B27 subtype do not affect susceptibility to AS in this white population.