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/).

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability.

Identification of common variants associated with human hippocampal and intracranial volumes

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease and is reduced in schizophrenia, major depression and mesial temporal lobe epilepsy. Whereas many brain imaging phenotypes are highly heritable, identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 × 10 -16) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 × 10 -12). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 × 10 -7).

The ENIGMA Consortium: Large-scale collaborative analyses of neuroimaging and genetic data

The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.

Distribution Revolution: Conversations about the Digital Future of Film and Television

Distribution Revolution is a collection of interviews with leading film and TV professionals concerning the many ways that digital delivery systems are transforming the entertainment business. These interviews provide lively insider accounts from studio executives, distribution professionals, and creative talent of the tumultuous transformation of film and TV in the digital era. The first section features interviews with top executives at major Hollywood studios, providing a window into the big-picture concerns of media conglomerates with respect to changing business models, revenue streams, and audience behaviors. The second focuses on innovative enterprises that are providing path-breaking models for new modes of content creation, curation, and distribution—creatively meshing the strategies and practices of Hollywood and Silicon Valley. And the final section offers insights from creative talent whose professional practices, compensation, and everyday working conditions have been transformed over the past ten years. Taken together, these interviews demonstrate that virtually every aspect of the film and television businesses is being affected by the digital distribution revolution, a revolution that has likely just begun. Interviewees include: • Gary Newman, Chairman, 20th Century Fox Television • Kelly Summers, Former Vice President, Global Business Development and New Media Strategy, Walt Disney Studios • Thomas Gewecke, Chief Digital Officer and Executive Vice President, Strategy and Business Development, Warner Bros. Entertainment • Ted Sarandos, Chief Content Officer, Netflix • Felicia D. Henderson, Writer-Producer, Soul Food, Gossip Girl • Dick Wolf, Executive Producer and Creator, Law & Order

Biomonitoring of polycyclic aromatic hydrocarbons exposure in small groups of residents in Brisbane, Australia and Hanoi, Vietnam, and those travelling between the two cities

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with adverse health outcomes. Concentrations of urinary PAH metabolites (OH-PAHs) provide an integrated measure of human exposure to PAHs but measurement of urinary OH-PAHs has not been done in Australia and rarely in Vietnam, where air pollution is of concern. In this study, we assessed exposure to PAHs in 16 participants living in Brisbane, Australia and Hanoi, Vietnam, with 4 participants travelling between the two cities during the monitoring period. A total of 312 first morning urine samples were collected over 10 weeks and were analysed for nine OH-PAHs. Concentrations of the urinary OH-PAHs were 2–10 times higher in participants from Hanoi than those from Brisbane. For example, the median concentrations of 1-hydroxypyrene were 292 pg/mL in Hanoi, compared to 64 pg/mL in Brisbane. For participants travelling from Brisbane to Hanoi and back, differences in exposure to PAHs in these two cities resulted in corresponding changes of urinary OH-PAH concentrations, demonstrating that the more polluted environment in Hanoi was likely the source for higher PAH exposure there.

Generating benefits and negotiating tensions through an international doctoral forum: A sociological analysis

Workshops and seminars are widely-used forms of doctoral training. However, research with a particular focus on these forms of doctoral training is sporadic in the literature. There is no, if any, such research concerning the international context and participants’ own voices. Mindful of these lacunae in the literature, we write the current paper as a group of participants in one of a series of doctoral forums co-organised annually by Beijing Normal University, China and Queensland University of Technology, Australia. The paper voices our own experiences of participation in the doctoral forum. Data were drawn from reflections, journals, and group discussions of all 12 student and academic participants. These qualitative data were organised and analysed through Bourdieu’s notions of capital and field. Findings indicate that the doctoral forum created enabling and challenging social fields where participants accrued and exchanged various forms of capital and negotiated transient and complex power relations. In this respect, the sociological framework used provides a distinctive theoretical tool to conceptualise and analyse the benefits and tensions of participation in the doctoral forum. Knowledge built and lessons learned through our paper will provide implications and recommendations for future planning of, and participation in, the doctoral forum series and similar activities elsewhere.

Letter: Brain natriuretic peptide is a potentially useful screening tool for the detection of cardiovascular disease in patients with rheumatoid arthritis

Patients with rheumatoid arthritis (RA) have a significantly higher risk of coronary heart disease, despite being less likely to report symptoms of angina, and are more likely to experience unrecognised myocardial infarction and sudden cardiac death than non-RA controls.1 Furthermore, left ventricular diastolic dysfunction has been described in up to 40% of patients with RA.2...

Delay tolerant routing protocols for energy-neutral animal tracking

This paper investigates communication protocols for relaying sensor data from animal tracking applications back to base stations. While Delay Tolerant Networks (DTNs) are well suited to such challenging environments, most existing protocols do not consider the available energy that is particularly important when tracking devices can harvest energy. This limits both the network lifetime and delivery probability in energy-constrained applications to the point when routing performance becomes worse than using no routing at all. Our work shows that substantial improvement in data yields can be achieved through simple yet efficient energy-aware strategies. Conceptually, there is need for balancing the energy spent on sensing, data mulling, and delivery of direct packets to destination. We use empirical traces collected in a flying fox (fruit bat) tracking project and show that simple threshold-based energy-aware strategies yield up to 20% higher delivery rates. Furthermore, these results generalize well for a wide range of operating conditions.

Crossing international boundaries through doctoral partnerships: Learnings from a Chinese-Australian forum

International forums for doctoral students offer a fertile context for developing strategic partner-ships between higher education institutions, as well as for building the intercultural capacity of early career academics. However, there is limited research investigating the benefits of international doctoral forum partnerships. This paper presents learnings from a recent international doctoral forum held in Beijing, China and attended by doctoral students and academics from Beijing Normal University (China) and Queensland University of Technology (Australia). Drawing on qualitative case study method and a model of boundary crossing mechanisms, we identify the beneficial outcomes of the forum. We describe how the forum arose from a strong ongoing partnership between the Education Faculties of Beijing Normal University and Queensland University of Technology. We then identify how, at the institutional and individual level, international doctoral forum participants can be challenged and benefit in four areas: collaboration, intercultural capacity, academic enhancement and program development. Implications for engaging successfully in international doctoral forum partnerships are also discussed.

The positioning of palliative care in acute care: A multiperspective qualitative study in the context of metastatic melanoma

Objective: The positioning and meaning of palliative care within the healthcare system lacks clarity which adds a level of complexity to the process of transition to palliative care. This study explores the transition to the palliative care process in the acute care context of metastatic melanoma. Method: A theoretical framework drawing on interpretive and critical traditions informs this research. The pragmatism of symbolic interactionism and the critical theory of Habermas brought a broad orientation to the research. Integration of the theoretical framework and grounded-theory methods facilitated data generation and analysis of 29 interviews with patients, family carers, and healthcare professionals. Results: The key analytical findings depict a scope of palliative care that was uncertain for users of the system and for those working within the system. Becoming “palliative” is not a defined event; nor is there unanimity around referral to a palliative care service. As such, ambiguity and tension contribute to the difficulties involved in negotiating the transition to palliative care. Significance of Results: Our findings point to uncertainty around the scopes of practice in the transition to palliative care. The challenge in the transition process lies in achieving greater coherency of care within an increasingly specialized healthcare system. The findings may not only inform those within a metastatic melanoma context but may contribute more broadly to palliative practices within the acute care setting.

Some remarks on the symplectic pairing on the moduli space of representations of the fundamental group of surfaces

This work grew out of an attempt to understand a conjectural remark made by Professor Kyoji Saito to the author about a possible link between the Fox-calculus description of the symplectic structure on the moduli space of representations of the fundamental group of surfaces into a Lie group and pairs of mutually dual sets of generators of the fundamental group. In fact in his paper [3] , Prof. Kyoji Saito gives an explicit description of the system of dual generators of the fundamental group.

Factors influencing sustainability of health service innovation: Emergency nurse practitioner services

Introduction: Emergency department nurse practitioner services are one of the most frequently implemented service delivery models in Australian hospitals. This research examined factors influencing sustainability of this innovative service delivery model and offers some recommendations for future service integration. Background Many health service innovations have been implemented in an attempt to meet the growing demand for efficient, cost effective health care however, sustainability of many of these innovations has not been evaluated and is poorly understood. Aim The aim of the research was to identify factors that influence sustainability of emergency department nurse practitioner services and to operationalise a theoretical framework for evaluating innovation sustainability. Methodology The research used case study methodology. The case was emergency nurse practitioner services, and units of analysis were emergency department staff, emergency nurse practitioners and documents relating to nurse practitioner services. The data collection methods included, survey, one-on-one interviews, document analysis and telephone survey. Results This research shows that emergency nurse practitioner services partially comply with the factors of sustainability as described in the Sustainability of Innovation theoretical framework: Political, Organisational, Workforce, Financial and Innovation specific factors. Where services do not entirely meet the factors the existing benefits of the service may outweigh the barriers and other means of working around shortfalls are also implemented by staff to ensure patient safety. Conclusion The rapidly expanding emergency nurse practitioner service has been examined using case study methodology to find that certain factors may be threatening the sustainability of this health service innovation. Potentially an innovation may be sustained when only some factors are met in the short term, however, long term sustainability may be challenged if factors are not addressed and supported.