Bayesian latent trait modeling of migraine symptom data

Definition of disease phenotype is a necessary preliminary to research into genetic causes of a complex disease. Clinical diagnosis of migraine is currently based on diagnostic criteria developed by the International Headache Society. Previously, we examined the natural clustering of these diagnostic symptoms using latent class analysis (LCA) and found that a four-class model was preferred. However, the classes can be ordered such that all symptoms progressively intensify, suggesting that a single continuous variable representing disease severity may provide a better model. Here, we compare two models: item response theory and LCA, each constructed within a Bayesian context. A deviance information criterion is used to assess model fit. We phenotyped our population sample using these models, estimated heritability and conducted genome-wide linkage analysis using Merlin-qtl. LCA with four classes was again preferred. After transformation, phenotypic trait values derived from both models are highly correlated (correlation = 0.99) and consequently results from subsequent genetic analyses were similar. Heritability was estimated at 0.37, while multipoint linkage analysis produced genome-wide significant linkage to chromosome 7q31-q33 and suggestive linkage to chromosomes 1 and 2. We argue that such continuous measures are a powerful tool for identifying genes contributing to migraine susceptibility.

Reciprocity : where art meets the community : action research in response to artistic encounters and relationships

This practice-led research project examines some of the factors and issues facing artists working in the public domain who wish to engage with the community as audience. Using the methodology of action research, the three major creative projects in this study use art as a socio-political tool with the aim of providing an effective vehicle for broadening awareness, understanding forms of social protest and increasing tolerance for diversity. The three projects: Floodline November 7, 2004, Look in, Look out, and The Urban Terrorist Project, dealt with issues of marginalisation of communities, audiences and graffiti artists respectively. The artist/researcher is outlined as both creator and collaborator in the work. Processes included ephemeral elements, such as temporary installation and performance, as well as interactive elements that encouraged direct audience involvement as part of the work. In addition to the roles of creator and collaborator, both of which included audience as well as artist, the presence of an outside entity was evident. Whether local, legal authorities or prevailing attitudes, outside entities had an unavoidable impact on the processes and outcomes of the work. Each project elicited a range of responses from their respective audiences; however, the overarching concept of reciprocity was seen to be the crucial factor in conception, artistic methods and outcomes.

Resolving painful emotional experience during psychodrama

Unresolved painful emotional experiences such as bereavement, trauma and disturbances in core relationships, are common presenting problems for clients of psychodrama or psychotherapy more generally. Emotional pain is experienced as a shattering of the sense of self and disconnection from others and, when unresolved, produces avoidant responses which inhibit the healing process. There is agreement across therapeutic modalities that exposure to emotional experience can increase the efficacy of therapeutic interventions. Moreno proposes that the activation of spontaneity is the primary curative factor in psychodrama and that healing occurs when the protagonist (client) engages with his or her wider social system and develops greater flexibility in response to that system. An extensive case-report literature describes the application of the psychodrama method in healing unresolved painful emotional experiences, but there is limited empirical research to verify the efficacy of the method or to identify the processes that are linked to therapeutic change. The purpose of this current research was to construct a model of protagonist change processes that could extend psychodrama theory, inform practitioners’ therapeutic decisions and contribute to understanding the common factors in therapeutic change. Four studies investigated protagonist processes linked to in-session resolution of painful emotional experiences. Significant therapeutic events were analysed using recordings and transcripts of psychodrama enactments, protagonist and director recall interviews and a range of process and outcome measures. A preliminary study (3 cases) identified four themes that were associated with helpful therapeutic events: enactment, the working alliance with the director and with group members, emotional release or relief and social atom repair. The second study (7 cases) used Comprehensive Process Analysis (CPA) to construct a model of protagonists’ processes linked to in-session resolution. This model was then validated across four more cases in Study 3. Five meta-processes were identified: (i) a readiness to engage in the psychodrama process; (ii) re-experiencing and insight; (iii) activating resourcefulness; (iv) social atom repair with emotional release and (v) integration. Social atom repair with emotional release involved deeply experiencing a wished-for interpersonal experience accompanied by a free flowing release of previously restricted emotion and was most clearly linked to protagonists’ reports of reaching resolution and to post session improvements in interpersonal relationships and sense of self. Acceptance of self in the moment increased protagonists’ capacity to generate new responses within each meta-process and, in resolved cases, there was evidence of spontaneity developing over time. The fourth study tested Greenberg’s allowing and accepting painful emotional experience model as an alternative explanation of protagonist change. The findings of this study suggested that while the process of allowing emotional pain was present in resolved cases, Greenberg’s model was not sufficient to explain the processes that lead to in-session resolution. The protagonist’s readiness to engage and activation of resourcefulness appear to facilitate the transition from problem identification to emotional release. Furthermore, experiencing a reparative relationship was found to be central to the healing process. This research verifies that there can be in-session resolution of painful emotional experience during psychodrama and protagonists’ reports suggest that in-session resolution can heal the damage to the sense of self and the interpersonal disconnection that are associated with unresolved emotional pain. A model of protagonist change processes has been constructed that challenges the view of psychodrama as a primarily cathartic therapy, by locating the therapeutic experience of emotional release within the development of new role relationships. The five meta-processes which are described within the model suggest broad change principles which can assist practitioners to make sense of events as they unfold and guide their clinical decision making in the moment. Each meta-process was linked to specific post-session changes, so that the model can inform the development of therapeutic plans for individual clients and can aid communication for practitioners when a psychodrama intervention is used for a specific therapeutic purpose within a comprehensive program of therapy.

Vitronectin modulates human mesenchymal stem cell response to insulin-like growth factor-I and transforming growth factor beta 1 in a serum-free environment

The use of animal sera for the culture of therapeutically important cells impedes the clinical use of the cells. We sought to characterize the functional response of human mesenchymal stem cells (hMSCs) to specific proteins known to exist in bone tissue with a view to eliminating the requirement of animal sera. Insulin-like growth factor-I (IGF-I), via IGF binding protein-3 or -5 (IGFBP-3 or -5) and transforming growth factor-beta 1 (TGF-beta(1)) are known to associate with the extracellular matrix (ECM) protein vitronectin (VN) and elicit functional responses in a range of cell types in vitro. We found that specific combinations of VN, IGFBP-3 or -5, and IGF-I or TGF-beta(1) could stimulate initial functional responses in hMSCs and that IGF-I or TGF-beta(1) induced hMSC aggregation, but VN concentration modulated this effect. We speculated that the aggregation effect may be due to endogenous protease activity, although we found that neither IGF-I nor TGF-beta(1) affected the functional expression of matrix metalloprotease-2 or -9, two common proteases expressed by hMSCs. In summary, combinations of the ECM and growth factors described herein may form the basis of defined cell culture media supplements, although the effect of endogenous protease expression on the function of such proteins requires investigation.

Eyelid pressure on the cornea

The eyelids play an important role in lubricating and protecting the surface of the eye. Each blink serves to spread fresh tears, remove debris and replenish the smooth optical surface of the eye. Yet little is known about how the eyelids contact the ocular surface and what pressure distribution exists between the eyelids and cornea. As the principal refractive component of the eye, the cornea is a major element of the eye’s optics. The optical properties of the cornea are known to be susceptible to the pressure exerted by the eyelids. Abnormal eyelids, due to disease, have altered pressure on the ocular surface due to changes in the shape, thickness or position of the eyelids. Normal eyelids also cause corneal distortions that are most often noticed when they are resting closer to the corneal centre (for example during reading). There were many reports of monocular diplopia after reading due to corneal distortion, but prior to videokeratoscopes these localised changes could not be measured. This thesis has measured the influence of eyelid pressure on the cornea after short-term near tasks and techniques were developed to quantify eyelid pressure and its distribution. The profile of the wave-like eyelid-induced corneal changes and the refractive effects of these distortions were investigated. Corneal topography changes due to both the upper and lower eyelids were measured for four tasks involving two angles of vertical downward gaze (20° and 40°) and two near work tasks (reading and steady fixation). After examining the depth and shape of the corneal changes, conclusions were reached regarding the magnitude and distribution of upper and lower eyelid pressure for these task conditions. The degree of downward gaze appears to alter the upper eyelid pressure on the cornea, with deeper changes occurring after greater angles of downward gaze. Although the lower eyelid was further from the corneal centre in large angles of downward gaze, its effect on the cornea was greater than that of the upper eyelid. Eyelid tilt, curvature, and position were found to be influential in the magnitude of eyelid-induced corneal changes. Refractively these corneal changes are clinically and optically significant with mean spherical and astigmatic changes of about 0.25 D after only 15 minutes of downward gaze (40° reading and steady fixation conditions). Due to the magnitude of these changes, eyelid pressure in downward gaze offers a possible explanation for some of the day-to-day variation observed in refraction. Considering the magnitude of these changes and previous work on their regression, it is recommended that sustained tasks performed in downward gaze should be avoided for at least 30 minutes before corneal and refractive assessment requiring high accuracy. Novel procedures were developed to use a thin (0.17 mm) tactile piezoresistive pressure sensor mounted on a rigid contact lens to measure eyelid pressure. A hydrostatic calibration system was constructed to convert raw digital output of the sensors to actual pressure units. Conditioning the sensor prior to use regulated the measurement response and sensor output was found to stabilise about 10 seconds after loading. The influences of various external factors on sensor output were studied. While the sensor output drifted slightly over several hours, it was not significant over the measurement time of 30 seconds used for eyelid pressure, as long as the length of the calibration and measurement recordings were matched. The error associated with calibrating at room temperature but measuring at ocular surface temperature led to a very small overestimation of pressure. To optimally position the sensor-contact lens combination under the eyelid margin, an in vivo measurement apparatus was constructed. Using this system, eyelid pressure increases were observed when the upper eyelid was placed on the sensor and a significant increase was apparent when the eyelid pressure was increased by pulling the upper eyelid tighter against the eye. For a group of young adult subjects, upper eyelid pressure was measured using this piezoresistive sensor system. Three models of contact between the eyelid and ocular surface were used to calibrate the pressure readings. The first model assumed contact between the eyelid and pressure sensor over more than the pressure cell width of 1.14 mm. Using thin pressure sensitive carbon paper placed under the eyelid, a contact imprint was measured and this width used for the second model of contact. Lastly as Marx’s line has been implicated as the region of contact with the ocular surface, its width was measured and used as the region of contact for the third model. The mean eyelid pressures calculated using these three models for the group of young subjects were 3.8 ± 0.7 mmHg (whole cell), 8.0 ± 3.4 mmHg (imprint width) and 55 ± 26 mmHg (Marx’s line). The carbon imprints using Pressurex-micro confirmed previous suggestions that a band of the eyelid margin has primary contact with the ocular surface and provided the best estimate of the contact region and hence eyelid pressure. Although it is difficult to directly compare the results with previous eyelid pressure measurement attempts, the eyelid pressure calculated using this model was slightly higher than previous manometer measurements but showed good agreement with the eyelid force estimated using an eyelid tensiometer. The work described in this thesis has shown that the eyelids have a significant influence on corneal shape, even after short-term tasks (15 minutes). Instrumentation was developed using piezoresistive sensors to measure eyelid pressure. Measurements for the upper eyelid combined with estimates of the contact region between the cornea and the eyelid enabled quantification of the upper eyelid pressure for a group of young adult subjects. These techniques will allow further investigation of the interaction between the eyelids and the surface of the eye.

In-vehicle avatars to elicit social response and change driving behaviour

Social and psychological theories have provided a plethora of evidence showing that the physical difficulty to express appropriate social interactions between drivers expresses itself in aggression, selfish driving and anti-social behaviour. Therefore there is a need to improve interactions between drivers and allow clearer collective decision making between them. Personal characteristics and the driving situations play strong roles in driver’s aggression. Our approach is centered around the driving situation as opposed to focusing on personality characteristics. It examines aggression and manipulates contextual variables such as driver’s eye contact exchanges. This paper presents a new unobtrusive in-vehicle system that aims at communicating drivers’ intentions, elicit social responses and increasing mutual awareness. It uses eye gaze as a social cue to affect collective decision making with the view to contribute to safe driving. The authors used a driving simulator to design a case control experiment in which eye gaze movements are conveyed with an avatar. Participants were asked to drive through different types of intersections. An avatar representing the head of the other driver was displayed and driver behaviour was analysed. Significant eye gaze pattern difference where observed when an avatar was displayed. Drivers cautiously refer to the avatar when information is required on the intention of others (e.g. when they do not have the right of way). The majority of participants reported the perception of “being looked at”. The number of glances and time spent gazing at the avatar did not indicate an unsafe distraction by standards of in-vehicle device ergonomic design. Avatars were visually consulted primarily in less demanding driving situations, which underlines their non-distractive nature.

Multi-output buck-boost converter with enhanced dynamic response to load and input voltage changes

This paper presents a new multi-output DC/DC converter topology that has step-up and step-down conversion capabilities. In this topology, several output voltages can be generated which can be used in different applications such as multilevel converters with diode-clamped topology or power supplies with several voltage levels. Steady state and dynamic equations of the proposed multi-output converter have been developed, that can be used for steady state and transient analysis. Two control techniques have been proposed for this topology based on constant and dynamic hysteresis band height control to address different applications. Simulations have been performed for different operating modes and load conditions to verify the proposed topology and its control technique. Additionally, a laboratory prototype is designed and implemented to verify the simulation results.

The strategic mindset of Australian manufacturing managers : some missing links

Manufacturing managers have a measurable mindset (or frame) that structures their response to the manufacturing environment. Most importantly, this frame represents a set of assumptions about the relative prominence of concepts in the manufacturing domains, about the nature of people, and about the sensemaking processes required to understand the nature of the manufacturing environment as seen through the eyes of manufacturing managers. This paper uses work in the area of text analysis and extends the scope of a methodology that has been approached from two different directions by Carley ( Journal of Organizational Behavior , 18 (51), 533-558, 1997) and Gephart ( Journal of Organizational Behavior , 18 (51), 583-622, 1997). This methodology is termed collocate analysis. Based on the analysis of transcripts of interviews of Australian manufacturing managers mind maps of the concepts used by these managers have been constructed. From an analysis of these mind maps it is argued that strategy plays a minor role in their thinking second only to the improvement domain, whereas design and related concepts play a dominant role in their day-to-day thinking.

Journals as Social and Intellectual Fields: A Response

This review is in response to Thinking Collaboratively about Peer-Review Process in Journal Article Publication by Kevin K.Kumashiro. Several authors critique and analyse the reflections of Kevin K. Kumashiro on challenges to publishing ant-oppressive research in educational journals.

Resistance : re-imagining innovation in higher education teaching and learning

The call to innovate is ubiquitous across the Australian educational policy context. The claims of innovative practices and environments that occur frequently in university mission statements, strategic plans and marketing literature suggest that this exhortation to innovate appears to have been taken up enthusiastically by the university sector. Throughout the history of universities, a range of reported deficiencies of higher education have worked to produce a notion of crisis. At present, it would seem that innovation is positioned as the solution to the notion of crisis. This thesis is an inquiry into how the insistence on innovation works to both enable and constrain teaching and learning practices in Australian universities. Alongside the interplay between innovation and crisis is the link between resistance and innovation, a link which remains largely unproblematized in the scholarly literature. This thesis works to locate and unsettle understandings of a relationship between innovation and Australian higher education. The aim of this inquiry is to generate new understandings of what counts as innovation within this context and how innovation is enacted. The thesis draws on a number of postmodernist theorists, whose works have informed firstly the research method, and then the analysis and findings. Firstly, there is an assumption that power is capillary and works through discourse to enact power relations which shape certain truths (Foucault, 1990). Secondly, this research scrutinised language practices which frame the capacity for individuals to act, alongside the language practices which encourage an individual to adopt certain attitudes and actions as one’s own (Foucault, 1988). Thirdly, innovation talk is read in this thesis as an example of needs talk, that is, as a medium through which what is considered domestic, political or economic is made and contested (Fraser, 1989). Fourthly, relationships between and within discourses were identified and analysed beyond cause and effect descriptions, and more productively considered to be in a constant state of becoming (Deleuze, 1987). Finally, the use of ironic research methods assisted in producing alternate configurations of innovation talk which are useful and new (Rorty, 1989). The theoretical assumptions which underpin this thesis inform a document analysis methodology, used to examine how certain texts work to shape the ways in which innovation is constructed. The data consisted of three Federal higher education funding policies selected on the rationale that these documents, as opposed to state or locally based policy and legislation, represent the only shared policy context for all Australian universities. The analysis first provided a modernist reading of the three documents, and this was followed by postmodernist readings of these same policy documents. The modernist reading worked to locate and describe the current truths about innovation. The historical context in which the policy was produced as well as the textual features of the document itself were important to this reading. In the first modernist reading, the binaries involved in producing proper and improper notions of innovation were described and analysed. In the process of the modernist analysis and the subsequent location of binary organisation, a number of conceptual collisions were identified, and these sites of struggle were revisited, through the application of a postmodernist reading. By applying the theories of Rorty (1989) and Fraser (1989) it became possible to not treat these sites as contradictory and requiring resolution, but rather as spaces in which binary tensions are necessary and productive. This postmodernist reading constructed new spaces for refusing and resisting dominant discourses of innovation which value only certain kinds of teaching and learning practices. By exploring a number of ironic language practices found within the policies, this thesis proposes an alternative way of thinking about what counts as innovation and how it happens. The new readings of innovation made possible through the work of this thesis were in response to a suite of enduring, inter-related questions – what counts as innovation?, who or what supports innovation?, how does innovation occur?, and who are the innovators?. The truths presented in response to these questions were treated as the language practices which constitute a dominant discourse of innovation talk. The collisions that occur within these truths were the contested sites which were of most interest for the analysis. The thesis concludes by presenting a theoretical blueprint which works to shift the boundaries of what counts as innovation and how it happens in a manner which is productive, inclusive and powerful. This blueprint forms the foundation upon which a number of recommendations are made for both my own professional practice and broader contexts. In keeping with the conceptual tone of this study, these recommendations are a suite of new questions which focus attention on the boundaries of innovation talk as an attempt to re-configure what is valued about teaching and learning at university.

Brain-derived neurotrophic factor (BDNF) gene : no major impact on antidepressant treatment response

The brain-derived neurotrophic factor (BDNF) has been suggested to play a pivotal role in the aetiology of affective disorders. In order to further clarify the impact of BDNF gene variation on major depression as well as antidepressant treatment response, association of three BDNF polymorphisms [rs7103411, Val66Met (rs6265) and rs7124442] with major depression and antidepressant treatment response was investigated in an overall sample of 268 German patients with major depression and 424 healthy controls. False discovery rate (FDR) was applied to control for multiple testing. Additionally, ten markers in BDNF were tested for association with citalopram outcome in the STAR*D sample. While BDNF was not associated with major depression as a categorical diagnosis, the BDNF rs7124442 TT genotype was significantly related to worse treatment outcome over 6 wk in major depression (p=0.01) particularly in anxious depression (p=0.003) in the German sample. However, BDNF rs7103411 and rs6265 similarly predicted worse treatment response over 6 wk in clinical subtypes of depression such as melancholic depression only (rs7103411: TTresponse in ANOVA models when the remaining SNPs were considered as covariates. The STAR*D analyses did not yield significant results at any of the ten BDNF markers. Our results do not support an association between genetic variation in BDNF and antidepressant treatment response or remission. Post-hoc analyses provide some preliminary support for a potential minor role of genetic variation in BDNF and antidepressant treatment outcome in the context of melancholic depression.