A dominant-negative mutation in the TRESK potassium channel is linked to familial migraine with aura

Migraine with aura is a common, debilitating, recurrent headache disorder associated with transient and reversible focal neurological symptoms. A role has been suggested for the two-pore domain (K2P) potassium channel, TWIK-related spinal cord potassium channel (TRESK, encoded by KCNK18), in pain pathways and general anaesthesia. We therefore examined whether TRESK is involved in migraine by screening the KCNK18 gene in subjects diagnosed with migraine. Here we report a frameshift mutation, F139WfsX24, which segregates perfectly with typical migraine with aura in a large pedigree. We also identified prominent TRESK expression in migraine-salient areas such as the trigeminal ganglion. Functional characterization of this mutation demonstrates that it causes a complete loss of TRESK function and that the mutant subunit suppresses wild-type channel function through a dominant-negative effect, thus explaining the dominant penetrance of this allele. These results therefore support a role for TRESK in the pathogenesis of typical migraine with aura and further support the role of this channel as a potential therapeutic target.

From strategic design to design integration

Within a growing awareness of design as central to the strategic success and the sustained competitive advantage of firms, this paper examines how companies pursue design driven innovation (Verganti, 2008, 2009) and respond to design led innovation initiatives (Matthews & Bucolo 2013). Specifically, this paper reports the findings of a collaborative research project where CEO sponsored senior managers from five multi-national organisations, met regularly over a twelve-month period, to discuss their progress on applying a design led approach in their firms. This longitudinal research project traced the process and progress of change instigated by the senior management representatives, as well as the deeper investigation of the barriers and challenges to re-frame design more strategically in their organisation. Data were collected through workshops and interviews throughout the twelve-month period, regarding the firms’ journeys and also the barriers and challenges firms faced in order to become design led. The findings present a novel set of implications for both designers and management scholars. This paper seeks to contribute to research and practice by investigating the processes and outcomes of a design led innovation program and to propose implications for practice for designers and management.

The effect of polystyrene sodium sulfonate grafting on polyethylene terephthalate artificial ligaments on in vitro mineralisation and in vivo bone tissue integration

This study investigates the impact of polystyrene sodium sulfonate (PolyNaSS) grafting onto the osseo-integration of a polyethylene terephthalate artificial ligament (Ligament Advanced Reinforcement System, LARS™) used for Anterior Cruciate Ligament (ACL). The performance of grafted and non-grafted ligaments was assessed in vitro by culturing human osteoblasts under osteogenic induction and this demonstrated that the surface modification was capable of up-regulating the secretion of ALP and induced higher level of mineralisation as measured 6 weeks post-seeding by Micro-Computed Tomography. Grafted and non-grafted LARS™ were subsequently implanted in an ovine model for ACL reconstruction and the ligament-to-bone interface was evaluated by histology and biomechanical testings 3 and 12 months post-implantation. The grafted ligaments exhibited more frequent direct ligament-to-bone contact and bone formation in the core of the ligament at the later time point than the non-grafted specimens, the grafting also significantly reduced the fibrous encapsulation of the ligament 12 months post-implantation. However, this improved osseo-integration was not translated into a significant increase in the biomechanical pull-out loads. These results provide evidences that PolyNaSS grafting improved the osseo-integration of the artificial ligament within the bone tunnels. This might positively influence the outcome of the surgical reconstructions, as higher ligament stability is believed to limit micro-movement and therefore permits earlier and enhanced healing.

A micro perspective analysis of capability renewal through knowledge integration within product innovation projects

The aim of this paper is examine how firms renew their organisational capabilities based on micro organisational processes. Organisational capability development literature points to firms’ failure in capability renewal process. To overcome this inefficiency, it is proposed to integrate dynamic capability and ambidexterity perspectives by studying knowledge integration within product innovation. In this relation, applying micro perspective in studying technology diffusion within Iranian Auto industry revealed micro co-evolutionary relationships between knowledge integration within product innovation and capability development. Furthermore, based on near decomposability principals, the analysis suggested relationships among modularity of product architecture, modularity of organisational modularity and modularity of industry architecture in downstream and upstream value chain. Based on these micro-macro co evolutionary effects, capability development process underlying successful corporate entrepreneurship may be verified.

On facilitating regional integration and economic development with collaborative technologies in the South Pacific

The current global economic instability and the vulnerability of small island nations are providing the impetus for greater integration between the countries of the South Pacific region. This exercise is critical for their survival in today’s turbulent economic environment. Past efforts of regional integration in the South Pacific have not been very successful. Reasons attributed to this outcome include issues related to damage of sovereignty, and lack of a shared integration infrastructure. Today, the IT resources with collaborative capacities provide the opportunity to develop a shared IT infrastructure to facilitate integration in the South Pacific. In an attempt to develop a model of regional integration with an IT-backed infrastructure, we identify and report on the antecedents of the current stage of regional integration, and the stakeholders’ perceived benefits of an IT resources backed regional integration in the South Pacific. Employing a case study based approach, the study finds that while most stakeholders were positive about the potential of IT-backed regional integration, significant challenges exist that hinder the realisation of this model. The study finds that facilitating IT-backed regional integration requires enabling IT infrastructure, equitable IT development in the region, greater awareness on the potential of the modern IT resources, market liberalisation of the information and telecommunications sector and greater political support for IT initiatives.

Interactions between cars and motorcycles testing underlying concepts through integration of on-road and simulator studies

We conducted on-road and simulator studies to explore the mechanisms underpinning driver-rider crashes. In Study 1 the verbal protocols of 40 drivers and riders were assessed at intersections as part of a 15km on-road route in Melbourne. Network analysis of the verbal transcripts highlighted key differences in the situation awareness of drivers and riders at intersections. In a further study using a driving simulator we examined in car drivers the influence of acute exposure to motorcyclists. In a 15 min simulated drive, 40 drivers saw either no motorcycles or a high number of motorcycles in the surrounding traffic. In a subsequent 45-60 min drive, drivers were asked to detect motorcycles in traffic. The proportion of motorcycles was manipulated so that there was either a high (120) or low (6) number of motorcycles during the drive. Those drivers exposed to a high number of motorcycles were significantly faster at detecting motorcycles. Fundamentally, the incompatible situation awareness at intersections by drivers and riders underpins the conflicts. Study 2 offers some suggestion for a countermeasure here, although more research around schema and exposure training to support safer interactions is needed.

Board age and gender diversity : a test of competing linear and curvilinear predictions

The inconsistent findings of past board diversity research demand a test of competing linear and curvilinear diversity–performance predictions. This research focuses on board age and gender diversity, and presents a positive linear prediction based on resource dependence theory, a negative linear prediction based on social identity theory, and an inverted U-shaped curvilinear prediction based on the integration of resource dependence theory with social identity theory. The predictions were tested using archival data on 288 large organizations listed on the Australian Securities Exchange, with a 1-year time lag between diversity (age and gender) and performance (employee productivity and return on assets). The results indicate a positive linear relationship between gender diversity and employee productivity, a negative linear relationship between age diversity and return on assets, and an inverted U-shaped curvilinear relationship between age diversity and return on assets. The findings provide additional evidence on the business case for board gender diversity and refine the business case for board age diversity.

Fractal dimension of dried foods : a correlation between microstructure and porosity

The quality of dried food is affected by a number of factors including quality of raw material, initial microstructure, and drying conditions. The structure of the food materials goes through deformations due to the simultaneous effect of heat and mass transfer during the drying process. Shrinkage and changes in porosity, microstructure and appearance are some of the most remarkable features that directly influence overall product quality. Porosity and microstructure are the important material properties in relation to the quality attributes of dried foods. Fractal dimension (FD) is a quantitative approach of measuring surface, pore characteristics, and microstructural changes [1]. However, in the field of fractal analysis, there is a lack of research in developing relationship between porosity, shrinkage and microstructure of different solid food materials in different drying process and conditions [2-4]. Establishing a correlation between microstructure and porosity through fractal dimension during convective drying is the main objective of this work.

Inpatients had mostly negative experiences of seclusion during short term treatment in a mental health facility

Design Semi-structured interviews. Setting 2 open, acute care units of a large tertiary mental health facility in Queensland, Australia. Patients 12 patients (58% men) who were 18–52 years of age and were secluded in the previous 7 days (mean duration 3.4 h). Methods Semi-structured, thematically organised interviews were audiotaped and transcribed. Transcripts were checked for errors against the audiotaped versions and were analysed using the process of meaning categorisation. Themes were identified and coded to produce categories. All members of the research team agreed on the final categorisations. These broad categories were further analysed, and themes were used to reflect patients' experiences of seclusion. Main findings 5 recurrent themes emerged. (1) Patients described the use of seclusion. Some patients thought that seclusion was used inappropriately and that the seclusion period was of more benefit to …

Integrating Poverty and Gender into Health Programmes : a Source Book for Health Professionals : Module on Curricular Integration

Over the past two to three decades, our understanding of poverty has broadened from a narrow focus on income and consumption to a multidimensional notion of education, health, social and political 1 participation, personal security and freedom and environmental quality. Thus, it encompasses not just low income, but lack of access to services, resources and skills; vulnerability; insecurity; and voicelessness and powerlessness. Multidimensional poverty is a determinant of health risks, health seeking behaviour, health care access and health outcomes. As analysis of health outcomes becomes more refined, it is increasingly apparent that the impressive gains in health experienced over recent decades are unevenly distributed. Aggregate indicators, whether at the global, regional or national level, often tend to mask striking variations in health outcomes between men and women, rich and poor, both across and within countries...

Curricula Integration

Targeting students’ learning is at the centre of education. In addition, education is promoted as a solution for addressing various issues; consequently educators seek ways in which teachers can meet societal needs and students’ learning needs, and address the overcrowded curriculum. There are debates on the defi nition of curricula integration and its place in education. However, ationalising the value of primary students undertaking curricula-integrated learning can provide motivation for primary teachers to devise and implement curricula-integrated lessons in the classroom. The Applied Learning Experiences highlighted in this chapter provide practical ideas for curricula integration that focus on combining achievement standards from the Australian Curriculum.

Accountancy capstone : enhancing integration and professional identity

Capstone units are generally seen to have three main aims: integrating the program, reflecting on prior learning, and transitioning into the workplace. However, research indicates that most programs do not achieve outcomes in all three areas with Henscheid (2000) revealing that integration is the major goal of many capstone programs. As well, in the accounting education literature there has been little empirical evidence relating to the effectiveness of student learning as a result of implementing a capstone unit. This study reports on the development and implementation of an accountancy capstone unit at the Queensland University of Technology (QUT), which began in 2006. The main features of this capstone unit are: the use of problem-based learning (PBL); integration of the program; the development of a professional identity whereby classes are broken up into groups of a maximum of five students who take on the persona of a professional accounting firm for an entire semester; and the students, acting as professional advisors within that firm, are required to solve a series of unstructured, multi-dimensional accounting problems based on limited given facts. This process is similar to a professional advisor asking a client about the facts relating to the particular problem of the client and then solving the problem. The research was conducted over nine semesters and involved the collection of both quantitative and qualitative data from a student questionnaire. The results indicate that in terms of student perceptions, the capstone unit was very effective in enhancing integration of the program and enhancing professional identity thereby assisting student transition into the professional accounting workplace. Our approach therefore meets two of the three generally accepted aims of a capstone unit. With accounting educators striving to maximise student learning from a finite set of resources, this approach using PBL has resulted in improved learning outcomes for accounting students about to enter the workplace as professionals.

Parametric modelling for the efficient design of daylight strategies with complex geometries

Daylight devices are important components of any climate responsive façade system. But, the evolution of parametric CAD systems and digital fabrication has had an impact on architectural form so that regular forms are shifting to complex geometries. Architectural and engineering integration of daylight devices in envelopes with complex geometries is a challenge in terms of design and performance evaluation. The purpose of this paper is to assess daylight performance of a building with a climatic responsive envelope with complex geometry that integrates shading devices in the façade. The case study is based on the Esplanade buildings in Singapore. Climate-based day-light metrics such as Daylight Availability and Useful Daylight Illuminance are used. DIVA (daylight simulation), and Grasshopper (parametric analysis) plug-ins for Rhinoceros have been employed to examine the range of performance possibilities. Parameters such as dimension, inclination of the device, projected shadows and shape have been changed in order to maximize daylight availability and Useful Daylight Illuminance while minimizing glare probability. While orientation did not have a great impact on the results, aperture of the shading devices did, showing that shading devices with a projection of 1.75 m to 2.00 m performed best, achieving target lighting levels without issues of glare.

International assessments of science learning : their positive and negative contributions to science education

The establishment and continuity of two international comparative assessments of science learning—the IEA’s TIMSS project and the OECD’s PISA project—have meant that there are now high-status reference points for other national and more local approaches to assessing the efficacy of science teaching and learning. Both projects, albeit with very different senses of what the outcome of science learning should be, have contributed positively and negatively to the current state of assessment of school science. The TIMSS project looks back at the science that is commonly included in the curricula of the participating countries. It is thus not about established school science nor about innovations in it. PISA is highly innovative looking, prospectively forward to see how students can use their science learning in everyday life situations. In this chapter some of these positives and negatives are discussed.