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.

Matrix metalloproteinase localisation by in situ-RT-PCR in archival human breast biopsy material

Utilising archival human breast cancer biopsy material we examined the stromal/epithelial interactions of several matrix metalloproteinases (MMPs) using in situ-RT-PCR (IS-RT-PCR). In breast cancer, the stromal/epithelial interactions that occur, and the site of production of these proteases, are central to understanding their role in invasive and metastatic processes. We examined MT1-MMP (MMP-14, membrane type-1-MMP), MMP-1 (interstitial collagenase) and MMP-3 (stromelysin-1) for their localisation profile in progressive breast cancer biopsy material (poorly differentiated invasive breast carcinoma (PDIBC), invasive breast carcinomas (IBC) and lymph node metastases (LNM)). Expression of MT1-MMP, MMP-1 and MMP-3 was observed in both the tumour epithelial and surrounding stromal cells in most tissue sections examined. MT1-MMP expression was predominantly localised to the tumour component in the pre-invasive lesions. MMP-1 gene expression was relatively well distributed between both tissue compartments, while MMP-3 demonstrated highest expression levels in the stromal tissue surrounding the epithelial tumour cells. The results demonstrate the ability to distinguish compartmental gene expression profiles using IS-RT-PCR. Further, we suggest a role for MT1-MMP in early tumour progression, expression of MMP-1 during metastasis and focal expression pattern of MMP-3 in areas of expansion. These expression profiles may provide markers for early breast cancer diagnoses and present potential therapeutic targets.

Distributed low-power image processing in wireless sensor networks for intelligent video surveillance applications

Distributed Wireless Smart Camera (DWSC) network is a special type of Wireless Sensor Network (WSN) that processes captured images in a distributed manner. While image processing on DWSCs sees a great potential for growth, with its applications possessing a vast practical application domain such as security surveillance and health care, it suffers from tremendous constraints. In addition to the limitations of conventional WSNs, image processing on DWSCs requires more computational power, bandwidth and energy that presents significant challenges for large scale deployments. This dissertation has developed a number of algorithms that are highly scalable, portable, energy efficient and performance efficient, with considerations of practical constraints imposed by the hardware and the nature of WSN. More specifically, these algorithms tackle the problems of multi-object tracking and localisation in distributed wireless smart camera net- works and optimal camera configuration determination. Addressing the first problem of multi-object tracking and localisation requires solving a large array of sub-problems. The sub-problems that are discussed in this dissertation are calibration of internal parameters, multi-camera calibration for localisation and object handover for tracking. These topics have been covered extensively in computer vision literatures, however new algorithms must be invented to accommodate the various constraints introduced and required by the DWSC platform. A technique has been developed for the automatic calibration of low-cost cameras which are assumed to be restricted in their freedom of movement to either pan or tilt movements. Camera internal parameters, including focal length, principal point, lens distortion parameter and the angle and axis of rotation, can be recovered from a minimum set of two images of the camera, provided that the axis of rotation between the two images goes through the camera's optical centre and is parallel to either the vertical (panning) or horizontal (tilting) axis of the image. For object localisation, a novel approach has been developed for the calibration of a network of non-overlapping DWSCs in terms of their ground plane homographies, which can then be used for localising objects. In the proposed approach, a robot travels through the camera network while updating its position in a global coordinate frame, which it broadcasts to the cameras. The cameras use this, along with the image plane location of the robot, to compute a mapping from their image planes to the global coordinate frame. This is combined with an occupancy map generated by the robot during the mapping process to localised objects moving within the network. In addition, to deal with the problem of object handover between DWSCs of non-overlapping fields of view, a highly-scalable, distributed protocol has been designed. Cameras that follow the proposed protocol transmit object descriptions to a selected set of neighbours that are determined using a predictive forwarding strategy. The received descriptions are then matched at the subsequent camera on the object's path using a probability maximisation process with locally generated descriptions. The second problem of camera placement emerges naturally when these pervasive devices are put into real use. The locations, orientations, lens types etc. of the cameras must be chosen in a way that the utility of the network is maximised (e.g. maximum coverage) while user requirements are met. To deal with this, a statistical formulation of the problem of determining optimal camera configurations has been introduced and a Trans-Dimensional Simulated Annealing (TDSA) algorithm has been proposed to effectively solve the problem.

Identification of TFG (TRK-fused gene) as a putative metastatic melanoma tumor suppressor gene

High density SNP arrays can be used to identify DNA copy number changes in tumors such as homozygous deletions of tumor suppressor genes and focal amplifications of oncogenes. Illumina Human CNV370 Bead chip arrays were used to assess the genome for unbalanced chromosomal events occurring in 39 cell lines derived from stage III metastatic melanomas. A number of genes previously recognized to have an important role in the development and progression of melanoma were identified including homozygous deletions of CDKN2A (13 of 39 samples), CDKN2B (10 of 39), PTEN (3 of 39), PTPRD (3 of 39), TP53 (1 of 39), and amplifications of CCND1 (2 of 39), MITF (2 of 39), MDM2 (1 of 39), and NRAS (1 of 39). In addition, a number of focal homozygous deletions potentially targeting novel melanoma tumor suppressor genes were identified. Because of their likely functional significance for melanoma progression, FAS, CH25H, BMPR1A, ACTA2, and TFG were investigated in a larger cohort of melanomas through sequencing. Nonsynonymous mutations were identified in BMPR1A (1 of 43), ACTA2 (3 of 43), and TFG (5 of 103). A number of potentially important mutation events occurred in TFG including the identification of a mini mutation ‘‘hotspot’’ at amino acid residue 380 (P380S and P380L) and the presence of multiple mutations in two melanomas. Mutations in TFG may have important clinical relevance for current therapeutic strategies to treat metastatic melanoma.

Environmental sustainability of urban road transport : an integrated analysis for life cycle emission impact

Despite of significant contributions of urban road transport to global economy and society, it is one of the largest sources of local and global emission impact. In order to address the environmental concerns of urban road transport it is imperative to achieve a holistic understanding of contributory factors causing emissions which requires a complete look onto its whole life cycle. Previous studies were mainly based on segmental views which mostly studied environmental impacts of individual transport modes and very few considered impacts other than operational phase. This study develops an integrated life cycle inventory model for urban road transport emissions from a holistic modal perspective. Singapore case was used to demonstrate the model. Results show that total life cycle greenhouse gas emission from Singapore’s road transport sector is 7.8 million tons per year. The total amount of criteria air pollutants are also estimated in this study.

2 Hour game jam at SLQ Garage Gamer - Live performance with crowd participation

The 2 hour game jam was performed as part of the State Library of Queensland 'Garage Gamer' series of events, summer 2013, at the SLQ exhibition. An aspect of the exhibition was the series of 'Level Up' game nights. We hosted the first of these - under the auspices of brIGDA, Game On. It was a party - but the focal point of the event was a live streamed 2 hour game jam. Game jams have become popular amongst the game development and design community in recent years, particularly with the growth of the Global Game Jam, a yearly event which brings thousands of game makers together across different sites in different countries. Other established jams take place on-line, for example the Ludum Dare challenge which as been running since 2002. Other challenges follow the same model in more intimate circumstances and it is now common to find institutions and groups holding their own small local game making jams. There are variations around the format, some jams are more competitive than others for example, but a common aspect is the creation of an intense creative crucible centred around team work and ‘accelerated game development’. Works (games) produced during these intense events often display more experimental qualities than those undertaken as commercial projects. In part this is because the typical jam is started with a conceptual design brief, perhaps a single word, or in the case of the specific game jam described in this paper, three words. Teams have to envision the challenge key word/s as a game design using whatever skills and technologies they can and produce a finished working game in the time given. Game jams thus provide design researchers with extraordinary fodder and recent years have also seen a number of projects which seek to illuminate the design process as seen in these events. For example, Gaydos, Harris and Martinez discuss the opportunity of the jam to expose students to principles of design process and design spaces (2011). Rouse muses on the game jam ‘as radical practice’ and a ‘corrective to game creation as it is normally practiced’. His observations about his own experience in a jam emphasise the same artistic endeavour forefronted earlier, where the experience is about creation that is divorced from the instrumental motivations of commercial game design (Rouse 2011) and where the focus is on process over product. Other participants remark on the social milieu of the event as a critical factor and the collaborative opportunity as a rich site to engage participants in design processes (Shin et al, 2012). Shin et al are particularly interested in the notion of the site of the process and the ramifications of participants being in the same location. They applaud the more localized event where there is an emphasis on local participation and collaboration. For other commentators, it is specifically the social experience in the place of the jam is the most important aspect (See Keogh 2011), not the material site but rather the physical embodied experience of ‘being there’ and being part of the event. Participants talk about game jams they have attended in a similar manner to those observations made by Dourish where the experience is layered on top of the physical space of the event (Dourish 2006). It is as if the event has taken on qualities of place where we find echoes of Tuan’s description of a particular site having an aura of history that makes it a very different place, redolent and evocative (Tuan 1977). The 2 hour game jam held during the SLQ Garage Gamer program was all about social experience.

Concealing their communication : exploring psychosocial predictors of young drivers’ intentions and engagement in concealed texting

Making a conscious effort to hide the fact that you are texting while driving (i.e., concealed texting) is a deliberate and risky behaviour involving attention diverted away from the road. As the most frequent users of text messaging services and mobile phones while driving, young people appear at heightened risk of crashing from engaging in this behaviour. This study investigated the phenomenon of concealed texting while driving, and utilised an extended Theory of Planned Behaviour (TPB) including the additional predictors of moral norm, mobile phone involvement, and anticipated regret to predict young drivers’ intentions and subsequent behaviour. Participants (n = 171) were aged 17 to 25 years, owned a mobile phone, and had a current driver’s licence. Participants completed a questionnaire measuring their intention to conceal texting while driving, and a follow-up questionnaire a week later to report their behavioural engagement. The results of hierarchical multiple regression analyses showed overall support for the predictive utility of the TPB with the standard constructs accounting for 69% of variance in drivers’ intentions, and the extended predictors contributing an additional 6% of variance in intentions over and above the standard constructs. Attitude, subjective norm, PBC, moral norm, and mobile phone involvement emerged as significant predictors of intentions; and intention was the only significant predictor of drivers’ self-reported behaviour. These constructs can provide insight into key focal points for countermeasures including advertising and other public education strategies aimed at influencing young drivers to reconsider their engagement in this risky behaviour.

Flexibility in change practices and job outcomes for nurses : exploring the role of subjective fit

Aims To integrate existing theoretical perspectives on change management, subjective fit and occupational stress to better understand the effects of change on employee adjustment. Background Although subjective fit with organizational goals and objectives has been shown to have positive effects on employee adjustment, its role in the organizational change–occupational stress context is not understood. This represents a caveat in research when considering the notion that those who feel that they fit with the organization's goals may be better equipped to reconcile and deal with change. Design A cross-sectional survey of nurses from public and non-profit sector hospitals was conducted. Method Data were collected from 252 public and non-profit sector nurses via online surveys. Data were collected from June–October in 2010. Structural equation modelling was used to test the direct and indirect effects among the focal variables. Results The results showed that public and non-profit nurses experience flexibility-limiting and flexibility-promoting change initiatives and that these are differentially related to the perception of administrative stressors and adjustment with these relationships directly and indirectly influenced by perceptions of subjective fit. Flexibility-limiting change initiatives led to lower levels of subjective fit, higher levels of administrative stressors and less favourable adjustment. On the other hand, flexibility-promoting change practices led to higher levels of subjective fit, lower levels of administrative stressors and ultimately better adjustment. Conclusion The results further the theoretical understanding of the role of subjective fit in organizational change and occupational stress theories.

In vitro assessment of surface congruency and integration of chondrocytes at adjacent edges of micro-fabricated clefts on cartilage

Osteochondral grafts are common treatment options for joint focal defects due to their excellent functionality. However, the difficulty is matching the topography of host and graft(s) surfaces flush to one another. Incongruence could lead to disintegration particularly when the gap reaches subchondoral region. The aim of this study is therefore to investigate cell response to gap geometry when forming cartilage-cartilage bridge at the interface. The question is what would be the characteristics of such a gap if the cells could bridge across to fuse the edges? To answer this, osteochondral plugs devoid of host cells were prepared through enzymatic decellularization and artificial clefts of different sizes were created on the cartilage surface using laser ablation. High density pellets of heterologous chondrocytes were seeded on the defects and cultured with chondrogenic differentiation media for 35 days. The results showed that the behavior of chondrocytes was a function of gap topography. Depending on the distance of the edges two types of responses were generated. Resident cells surrounding distant edges demonstrated superficial attachment to one side whereas clefts of 150 to 250 µm width experienced cell migration and anchorage across the interface. The infiltration of chondrocytes into the gaps provided extra space for their proliferation and laying matrix; as the result faster filling of the initial void space was observed. On the other hand, distant and fit edges created an incomplete healing response due to the limited ability of differentiated chondrocytes to migrate and incorporate within the interface. It seems that the initial condition of the defects and the curvature profile of the adjacent edges were the prime determinants of the quality of repair; however, further studies to reveal the underlying mechanisms of cells adapting to and modifying the new environment would be of particular interest.

Fine tuning of elasticity via crosslinking collagen-based materials to mediate mechanotransduction and stability using corona treatment

The common goal of tissue engineering is to develop substitutes that can closely mimic the structure of extracellular matrix (ECM). However, similarly important is the intensive material properties which have often been overlooked, in particular, for soft tissues that are not to bear load assumingly. The mechanostructural properties determine not only the structural stability of biomaterials but also their physiological functionality by directing cellular activity and regulating cell fate decision. The aim here is to emphasize that cells could sense intensive material properties like elasticity and reside, proliferate, migrate and differentiate accordinglyno matter if the construct is from a natural source like cartilage, skin etc. or of synthetic one. Meanwhile, the very objective of this work is to provide a tunable scheme for manipulating the elasticity of collagen-based constructs to be used to demonstrate how to engineer cell behavior and regulate mechanotransduction. Articular cartilage was chosen as it represents one of the most complex hierarchical arrangements of collagen meshwork in both connective tissues and ECM-like biomaterials. Corona discharge treatment was used to produce constructs with varying density of crosslinked collagen and stiffness accordingly. The results demonstrated that elastic modulus increased up to 33% for samples treated up to one minute as crosslink density was found to increase with exposure time. According to the thermal analysis, longer exposure to corona increased crosslink density as the denaturation enthalpy increased. However the spectroscopy results suggested that despite the stabilization of the collagen structure the integrity of the triple helical structure remained intact. The in vitro superficial culture of heterologous chondrocytes also determined that the corona treatment can modulate migration with increased focal adhesion of cells due to enhanced stiffness, without cytotoxicity effects, and providing the basis for reinforcing three-dimensional collagen-based biomaterials in order to direct cell function and mediate mechanotransduction.

The Sessional Academic Success (SAS) project

The Sessional Academic Success (SAS) project is a sustainable, distributed model for supporting sessional staff at QUT. Developed by the Learning and Teaching Unit. SAS complements our Sessional Academic Program (SAP): a sequence of formal academic development workshops explained in complementary nomination. SAS recognises that while these programs are very well received and a crucial aspect of preparing and advancing sessional teachers, they are necessarily encapsulated in the moment of their delivery and are generic, as they address all faculties (with their varied cultures, processes and pedagogies). The SAS project extends this formal, centrally offered activity into local, ‘just in time’, ongoing support within schools. It takes a distributed leadership approach. Experienced sessional academics are recruited and employed as Sessional Academic Success Advisors (SASAs). They provide sessional staff in their schools with contextually specific, needs based, peer-to-peer development opportunities; one-on-one advice on classroom management and strategies for success; and help to trouble-shoot challenges. The SASAs are trained by the Learning and Teaching Unit co-ordinator, and ongoing support is provided centrally and by school-based co-ordinators. This team approach situates the SASAs at the centre of an organisation map (see diagram of support relationships below). The SAS project aims to support sessional staff in their professional development by: • Offering contextual, needs-based support at school level by harnessing local expertise; • Providing further development opportunities that are local and focal; SAS aims to retain Sessional Staff by: • Responding to self-nominated requests for support and ‘just in time’, safe and reliable advice in times of need; • Building sessional staff confidence through help with dealing with challenges from a trusted peer; • Building a supportive academic community for sessional staff, which helps them feel a part of faculty life, and a community of teaching practice. SAS aims to support sessional staff in the development of academic teaching careers by: • Recognising the capacity of experienced sessional staff to support their peers in ways that are unique, valuable and valued and providing the agency to do so; • Providing career advancement and leadership opportunities for sessional staff. SAS takes unique approaches within each school using strategies such as: • Welcomes and schools orientation by SASAs; • Regular check ins; face-to-face advice and online support; • Compiling local resources to complement university wide resources. • Sessional-to-sessional ‘just in time’ training (eg. assessment and marking when marking commences); • Peer feedback and mentoring (the opportunities to sit in more experiences sessionals’ classes; • Sessional staff awards (nominated by students); • Communities of practice to discuss topics and issues with a view to (and support for) publishing on learning and teaching. In these ways, SASAs complement support offered by unit coordinators, administrators, and the Learning and Teaching Unit. Pairing senior and ‘understudy’ advisors ensures a line of succession, sustainability and continuity. A pilot program commenced in 2012 involving three schools (Psychology and Social Work; Electrical Engineering and Computer Science; Media, Entertainment and Creative Arts). It will be expanded across schools in 2013.

Results using Trabecular Metal™ augments in combination with acetabular impaction bone grafting in deficient acetabula

We examined whether the use of trabecular metal wedges to fill segmental defects is an effective method of socket reconstruction when used in combination with impaction grafting and implantation of a cemented socket. Fifteen hips in 14 patients underwent impaction grafting in combination with a TM wedge with a minimum of 2 years follow-up. All patients had their defects assessed using the Paprosky classification. Patients were reviewed with x-rays and migration of the implant was measured. Outcome scores were also collected. Mean follow-up was 39 months (25-83). The mean age at surgery was 67.8 (49-85) years. Seven of the patients had previously undergone impaction grafting with the use of a stainless steel rim mesh to constrain the graft. None of the patients had failed either clinically or radiologically.

Physical activity promotion as a school priority : what do parents think?

The demands and responsibilities placed on schools in contemporary education systems are vast. However, with growing obesity levels and physical inactivity, the prevention of chronic disease has focused on youth populations, with schools playing the focal educative asset in this strategy. Parents play a decisive role in their child’s educational setting, and as fee and tax payers, are ultimately a consumer. Parents (82 males and 208 females) of secondary school children were recruited from three private (n=151) and two government schools (n=150) in Brisbane, Australia. The mean (standard deviation) age was 44.57 (6.21) years. Participants responded to a series of questions about physical activity at their child’s school, in addition to completing the International Physical Activity Questionnaire. Data were analysed using descriptive statistics, frequency distributions and logistic regressions. Parents were deemed sufficiently physically active if they participated in at least 150 minutes of moderate-to-vigorous physical activity per week. Overall, 83 (59.7%) parents from private and 60 (50.8%) parents from government schools were deemed sufficiently physically active. Concerning whether physical activity promotion should be a priority at their child’s school, 111 (73.5%) parents from private schools either agreed or strongly agreed, as opposed to 97 (64.7%) parents from government schools. Logistic regressions indicated that the concept of physical activity promotion being prioritised at schools was dependent on whether the child attended a private school (OR =1.34, z = 2.30, p = 0.02), and whether the participant was sufficiently active (OR =.71, z = -2.48, p = 0.01). Physical activity promotion within schools may provide substantial future benefits on a population scale. The demands on schools may need to be addressed to meet the needs of students and the desires of their parents.

Cortisol shifts financial risk preferences

Risk taking is central to human activity. Consequently, it lies at the focal point of behavioral sciences such as neuroscience, economics, and finance. Many influential models from these sciences assume that financial risk preferences form a stable trait. Is this assumption justified and, if not, what causes the appetite for risk to fluctuate? We have previously found that traders experience a sustained increase in the stress hormone cortisol when the amount of uncertainty, in the form of market volatility, increases. Here we ask whether these elevated cortisol levels shift risk preferences. Using a double-blind, placebo-controlled, cross-over protocol we raised cortisol levels in volunteers over eight days to the same extent previously observed in traders. We then tested for the utility and probability weighting functions underlying their risk taking, and found that participants became more risk averse. We also observed that the weighting of probabilities became more distorted among men relative to women. These results suggest that risk preferences are highly dynamic. Specifically, the stress response calibrates risk taking to our circumstances, reducing it in times of prolonged uncertainty, such as a financial crisis. Physiology-induced shifts in risk preferences may thus be an under-appreciated cause of market instability.

Recasting the theory of mosquito-borne pathogen transmission dynamics and control

Mosquito-borne diseases pose some of the greatest challenges in public health, especially in tropical and sub-tropical regions of theworld. Efforts to control these diseases have been underpinned by a theoretical framework developed for malaria by Ross and Macdonald, including models, metrics for measuring transmission, and theory of control that identifies key vulnerabilities in the transmission cycle. That framework, especially Macdonald’s formula for R0 and its entomological derivative, vectorial capacity, are nowused to study dynamics and design interventions for many mosquito-borne diseases. A systematic review of 388 models published between 1970 and 2010 found that the vast majority adopted the Ross–Macdonald assumption of homogeneous transmission in a well-mixed population. Studies comparing models and data question these assumptions and point to the capacity to model heterogeneous, focal transmission as the most important but relatively unexplored component in current theory. Fine-scale heterogeneity causes transmission dynamics to be nonlinear, and poses problems for modeling, epidemiology and measurement. Novel mathematical approaches show how heterogeneity arises from the biology and the landscape on which the processes of mosquito biting and pathogen transmission unfold. Emerging theory focuses attention on the ecological and social context formosquito blood feeding, themovement of both hosts and mosquitoes, and the relevant spatial scales for measuring transmission and for modeling dynamics and control.