Two novel mutations and a previously unreported intronic polymorphism in the NOTCH3 gene

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disease of small vessel caused by mutations in the NOTCH3 gene (NCBI Gene ID: 4854) located on chromosome 19p13.1. NOTCH3 consists of 33 exons which encode a protein of 2321 amino acids. Exons 3 and 4 were found to be mutation hotspots, containing more than 65% of all CADASIL mutations. We performed direct sequencing on an ABI 3130 Genetic Analyser to screen for mutations and polymorphisms on 300 patients who were clinically suspected to have CADASIL. First, exons 3 and 4 were screened in NOTCH3 and if there were no variations found, then extended CADASIL testing (exons 2, 11, 18 and 19) was offered to patients. Here we report two novel non-synonymous mutations identified in the NOTCH3 gene. The first mutation, located in exon 4 was found in a 49-year-old female and causes an alanine to valine amino acid change at position 202 (605C > T). The second mutation, located in exon 11, was found in a 66-year-old female and causes a cysteine to arginine amino acid change at position 579 (1735T > C). We also report a 46-year-old male with a known polymorphism Thr101Thr (rs3815188) and an unreported polymorphism NM_000435.2:c.679+60G>A observed in intron 4 of the NOTCH3 gene. Although Ala202Ala (rs1043994) is a common polymorphism in the NOTCH3 gene, our reported novel mutation (Ala202Val) causes an amino acid change at the same locus. Our other reported mutation (Cys579Arg) correlates well with other known mutations in NOTCH3, as the majority of the CADASIL-associated mutations in NOTCH3 generally occur in the EGF-like (epidermal growth factor-like) repeat domain, causing a change in the number of cysteine residues. The intronic polymorphism NM_000435.2:c.679+60G>A lies close to the intron–exon boundary and may affect the splicing mechanism in the NOTCH3 gene.

Supporting collaboration in large-scale multi-user workspaces

CubIT is a multi-user, large-scale presentation and collaboration framework installed at the Queensland University of Technology’s (QUT) Cube facility, an interactive facility made up 48 multi-touch screens and very large projected display screens. The CubIT system allows users to upload, interact with and share their own content on the Cube’s display surfaces. This paper outlines the collaborative features of CubIT which are implemented via three user interfaces, a large-screen multi-touch interface, a mobile phone and tablet application and a web-based content management system. Each of these applications plays a different role and supports different interaction mechanisms supporting a wide range of collaborative features including multi-user shared workspaces, drag and drop upload and sharing between users, session management and dynamic state control between different parts of the system.

Isolation of bioactive compounds that relate to the anti-platelet activity of Cymbopogon ambiguus

Infusions and decoctions of Cymbopogon ambiguus have been used traditionally in Australia for the treatment of headache, chest infections and muscle cramps. The aim of the present study was to screen and identify bioactive compounds from C. ambiguus that could explain this plant's anti-headache activity. A dichloromethane extract of C. ambiguus was identified as having activity in adenosine-diphosphate-induced human platelet aggregation and serotonin-release inhibition bioassays. Subsequent fractionation of this extract led to the isolation of four phenylpropenoids, eugenol, elemicin, Eugenol methylether and trans-isoelemicin. While both Eugenol and elemicin exhibited dose-dependent inhibition of ADP-induced human platelet serotonin release, only eugenol displayed potent inhibitory activity with an IC(50) value of 46.6 microM, in comparison to aspirin, with an IC(50) value of 46.1 microM. These findings provide evidence to support the therapeutic efficacy of C. ambiguus in the non-conventional treatment of Headache and Inflammatory conditions.

Home-based activity program for older people with depressive symptoms: DeLLITE–A randomized controlled trial

PURPOSE We wanted to assess the effectiveness of a home-based physical activity program, the Depression in Late Life Intervention Trial of Exercise (DeLLITE), in improving function, quality of life, and mood in older people with depressive symptoms. METHODS We undertook a randomized controlled trial involving 193 people aged 75 years and older with depressive symptoms at enrollment who were recruited from primary health care practices in Auckland, New Zealand. Participants received either an individualized physical activity program or social visits to control for the contact time of the activity intervention delivered over 6 months. Primary outcome measures were function, a short physical performance battery comprising balance and mobility, and the Nottingham Extended Activities of Daily Living scale. Secondary outcome measures were quality of life, the Medical Outcomes Study 36-item short form, mood, Geriatric Depression Scale (GDS-15), physical activity, Auckland Heart Study Physical Activity Questionnaire, and self-report of falls. Repeated measures analyses tested the differential impact on outcomes over 12 months’ follow-up. RESULTS The mean age of the participants was 81 years, and 59% were women. All participants scored in the at–risk category on the depression screen, 53% had a Diagnostic and Statistical Manual of Mental Disorders or International Classification of Diseases, Tenth Revision diagnosis of major depression or scored more than 4 on the GDS-15 at baseline, indicating moderate or severe depression. Almost all participants, 187 (97%), completed the trial. Overall there were no differences in the impact of the 2 interventions on outcomes. Mood and mental health related quality of life improved for both groups. CONCLUSION he DeLLITE activity program improved mood and quality of life for older people with depressive symptoms as much as the effect of social visits. Future social and activity interventions should be tested against a true usual care control.

A genetic analysis of serotonergic biosynthetic and metabolic enzymes in migraine using a DNA pooling approach

Migraine is a common debilitating primary headache disorder with significant mental, physical and social health implications. The brain neurotransmitter 5-hydroxytryptamine (5-HT; serotonin) is involved in nociceptive pathways and has been implicated in the pathophysiology of migraine. With few genetic studies investigating biosynthetic and metabolic enzymes governing the rate of 5-HT activity and their relationship to migraine, it was the objective of this study to assess genetic variants within the human tryptophan hydroxylase (TPH), amino acid decarboxylase (AADC) and monoamine oxidase A (MAOA) genes in migraine susceptibility. This objective was undertaken using a high-throughput DNA pooling experimental design, which proved to be a very accurate, sensitive and specific method of estimating allele frequencies for single nucleotide polymorphism, insertion deletion and variable number tandem repeat loci. Application of DNA pooling to a wide array of genetic loci provides greater scope in the assessment of population-based genetic association study designs. Despite the application of this high-throughput genotyping method, negative results from the two-stage DNA pooling design used to screen loci within the TPH, AADC and MAOA genes did not support their role in migraine susceptibility.

Preparing for performance capture #1

This video article articulates two exercises that have been developed to respond to the need for preparedness in the growing field of Performance Capture. The first is called Walking Through (Delbridge 2013), where the actor navigates a series of objects that exist in screen space through a developed sense of the existing physical particularities of the studio and an interaction with a screen (or feedback loop). The second exercise is called The Donut (Delbridge 2013), where the performer continues to navigate screen space but this time does so through the literal stepping through of a Torus in the virtual – again with nothing but the studio infrastructure and the screen as a guide. Notions of Motion Captured performance infer the existence of an interface that combines performer with system, separating (or intervening in) the space between performance and the screen. It is precisely the effect and provided opportunity of the intermediary device on the practice, craft and preparedness of the actor as they navigate the connection between 3D screen space and the physical properties of the studio that is examined here. Defining the scope of current practice for the contemporary actor is a key construct of this challenge, with the most appropriate definition revolving around the provision of a required mixture of performance and content for live, mediated, framed and variously captured formats. One of these particular formats is Performance Capture. The exercises presented here are two from a series, developed over a three year study that contribute to our understanding of the potential for a training regimen to be developed for the rigors of Performance Capture.

The impact of interface modality on police officers' visual behaviour when using an in-vehicle system

Background Standard operating procedures state that police officers should not drive while interacting with their mobile data terminal (MDT) which provides in-vehicle information essential to police work. Such interactions do however occur in practice and represent a potential source of driver distraction. The MDT comprises visual output with manual input via touch screen and keyboard. This study investigated the potential for alternative input and output methods to mitigate driver distraction with specific focus on eye movements. Method Nineteen experienced drivers of police vehicles (one female) from the NSW Police Force completed four simulated urban drives. Three drives included a concurrent secondary task: imitation licence plate search using an emulated MDT. Three different interface methods were examined: Visual-Manual, Visual-Voice, and Audio-Voice (“Visual” and “Audio” = output modality; “Manual” and “Voice” = input modality). During each drive, eye movements were recorded using FaceLAB™ (Seeing Machines Ltd, Canberra, ACT). Gaze direction and glances on the MDT were assessed. Results The Visual-Voice and Visual-Manual interfaces resulted in a significantly greater number of glances towards the MDT than Audio-Voice or Baseline. The Visual-Manual and Visual-Voice interfaces resulted in significantly more glances to the display than Audio-Voice or Baseline. For longer duration glances (>2s and 1-2s) the Visual-Manual interface resulted in significantly more fixations than Baseline or Audio-Voice. The short duration glances (<1s) were significantly greater for both Visual-Voice and Visual-Manual compared with Baseline and Audio-Voice. There were no significant differences between Baseline and Audio-Voice. Conclusion An Audio-Voice interface has the greatest potential to decrease visual distraction to police drivers. However, it is acknowledged that an audio output may have limitations for information presentation compared with visual output. The Visual-Voice interface offers an environment where the capacity to present information is sustained, whilst distraction to the driver is reduced (compared to Visual-Manual) by enabling adaptation of fixation behaviour.

Cone signals and activity in myopia and emmetropia

Myopia (short-sightedness) is a common ocular disorder of children and young adults. Studies primarily using animal models have shown that the retina controls eye growth and the outer retina is likely to have a key role. One theory is that the proportion of L (long-wavelength-sensitive) and M (medium-wavelength-sensitive) cones is related to myopia development; with a high L/M cone ratio predisposing individuals to myopia. However, not all dichromats (persons with red-green colour vision deficiency) with extreme L/M cone ratios have high refractive errors. We predict that the L/M cone ratio will vary in individuals with normal trichromatic colour vision but not show a systematic difference simply due to refractive error. The aim of this study was to determine if L/M cone ratios in the central 30° are different between myopic and emmetropic young, colour normal adults. Information about L/M cone ratios was determined using the multifocal visual evoked potential (mfVEP). The mfVEP can be used to measure the response of visual cortex to different visual stimuli. The visual stimuli were generated and measurements performed using the Visual Evoked Response Imaging System (VERIS 5.1). The mfVEP was measured when the L and M cone systems were separately stimulated using the method of silent substitution. The method of silent substitution alters the output of three primary lights, each with physically different spectral distributions to control the excitation of one or more photoreceptor classes without changing the excitation of the unmodulated photoreceptor classes. The stimulus was a dartboard array subtending 30° horizontally and 30° vertically on a calibrated LCD screen. The m-sequence of the stimulus was 215-1. The N1-P1 amplitude ratio of the mfVEP was used to estimate the L/M cone ratio. Data were collected for 30 young adults (22 to 33 years of age), consisting of 10 emmetropes (+0.3±0.4 D) and 20 myopes (–3.4±1.7 D). The stimulus and analysis techniques were confirmed using responses of two dichromats. For the entire participant group, the estimated central L/M cone ratios ranged from 0.56 to 1.80 in the central 3°-13° diameter ring and from 0.94 to 1.91 in the more peripheral 13°-30° diameter ring. Within 3°-13°, the mean L/M cone ratio of the emmetropic group was 1.20±0.33 and the mean was similar, 1.20±0.26, for the myopic group. For the 13°-30° ring, the mean L/M cone ratio of the emmetropic group was 1.48±0.27 and it was slightly lower in the myopic group, 1.30±0.27. Independent-samples t-test indicated no significant difference between the L/M cone ratios of the emmetropic and myopic group for either the central 3°-13° ring (p=0.986) or the more peripheral 13°-30° ring (p=0.108). The similar distributions of estimated L/M cone ratios in the sample of emmetropes and myopes indicates that there is likely to be no association between the L/M cone ratio and refractive error in humans.

The function and mechanisms of action of ghrelin and obestatin in ovarian cancer

In this study, we have demonstrated that the preproghrelin derived hormones, ghrelin and obestatin, may play a role in ovarian cancer. Ghrelin and obestatin stimulated an increase in cell migration in ovarian cancer cell lines and may play a role in cancer progression. Ovarian cancer is the leading cause of death among gynaecological cancers and is the sixth most common cause of cancer-related deaths in women in developed countries. As ovarian cancer is difficult to diagnose at a low tumour grade, two thirds of ovarian cancers are not diagnosed until the late stages of cancer development resulting in a poor prognosis for the patient. As a result, current treatment methods are limited and not ideal. There is an urgent need for improved diagnostic markers, as well better therapeutic approaches and adjunctive therapies for this disease. Ghrelin has a number of important physiological effects, including roles in appetite regulation and the stimulation of growth hormone release. It is also involved in regulating the immune, cardiovascular and reproductive systems and regulates sleep, memory and anxiety, and energy metabolism. Over the last decade, the ghrelin axis, (which includes the hormones ghrelin and obestatin and their receptors), has been implicated in the pathogenesis of many human diseases and it may t may also play an important role in the development of cancer. Ghrelin is a 28 amino acid peptide hormone that exists in two forms. Acyl ghrelin (usually referred to as ghrelin), has a unique n-octanoic acid post-translational modification (which is catalysed by ghrelin O-acyltransferase, GOAT), and desacyl ghrelin, which is a non-octanoylated form. Octanoylated ghrelin acts through the growth hormone secretagogue receptor type 1a (GHSR1a). GHSR1b, an alternatively spliced isoform of GHSR, is C-terminally truncated and does not bind ghrelin. Ghrelin has been implicated in the pathophysiology of a number of diseases Obestatin is a 23 amino acid, C-terminally amidated peptide which is derived from preproghrelin. Although GPR39 was originally thought to be the obestatin receptor this has been disproven, and its receptor remains unknown. Obestatin may have as diverse range of roles as ghrelin. Obestatin improves memory, inhibits thirst and anxiety, increases pancreatic juice secretion and has cardioprotective effects. Obestatin also has been shown to regulate cell proliferation, differentiation and apoptosis in some cell types. Prior to this study, little was known regarding the functions and mechanisms of action ghrelin and obestatin in ovarian cancer. In this study it was demonstrated that the full length ghrelin, GHSR1b and GOAT mRNA transcripts were expressed in all of the ovarian-derived cell lines examined (SKOV3, OV-MZ-6 and hOSE 17.1), however, these cell lines did not express GHSR1a. Ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for ghrelin, obestatin, and GOAT, but not GHSR1a, or GHSR1b. No correlations between cancer grade and the level of expression of these transcripts were observed. This study demonstrated for the first time that both ghrelin and obestatin increase cell migration in ovarian cancer cell lines. Treatment with ghrelin (for 72 hours) significantly increased cell migration in the SKOV3 and OV-MZ-6 ovarian cancer cell lines. Ghrelin (100 nM) stimulated cell migration in the SKOV3 (2.64 +/- 1.08 fold, p <0.05) and OV-MZ-6 (1.65 +/- 0.31 fold, p <0.05) ovarian cancer cell lines, but not in the representative normal cell line hOSE 17.1. This increase in migration was not accompanied by an increase in cell invasion through Matrigel. In contrast to other cancer types, ghrelin had no effect on proliferation. Ghrelin treatment (10nM) significantly decreased attachment of the SKOV3 ovarian cancer cell line to collagen IV (24.7 +/- 10.0 %, p <0.05), however, there were no changes in attachment to the other extracellular matrix molecules (ECM) tested (fibronectin, vitronectin and collagen I), and there were no changes in attachment to any of the ECM molecules in the OV-MZ-6 or hOSE 17.1 cell lines. It is, therefore, unclear if ghrelin plays a role in cell attachment in ovarian cancer. As ghrelin has previously been demonstrated to signal through the ERK1/2 pathway in cancer, we investigated ERK1/2 signalling in ovarian cancer cell lines. In the SKOV3 ovarian cancer cell line, a reduction in ERK1/2 phosphorylation (0.58 fold +/- 0.23, p <0.05) in response to 100 nM ghrelin treatment was observed, while no significant change in ERK1/2 signalling was seen in the OV-MZ-6 cell line with treatment. This suggests that this pathway is unlikely to be involved in mediating the increased migration seen in the ovarian cancer cell lines with ghrelin treatment. In this study ovarian cancer tissue of varying stages and normal ovarian tissue expressed the coding region for obestatin, however, no correlation between cancer grade and level of obestatin transcript expression was observed. In the ovarian-derived cell lines studied (SKOV3, OV-MZ-6 and hOSE 17.1) it was demonstrated that the full length preproghrelin mRNA transcripts were expressed in all cell lines, suggesting they have the ability to produce mature obestatin. This is the first study to demonstrate that obestatin stimulates cell migration and cell invasion. Obestatin induced a significant increase in migration in the SKOV3 ovarian cancer cell line with 10 nM (2.80 +/- 0.52 fold, p <0.05) and 100 nM treatments (3.12 +/- 0.68 fold, p <0.05) and in the OV-MZ-6 cancer cell line with 10 nM (2.04 +/- 0.10 fold, p <0.01) and 100 nM treatments (2.00 +/- 0.37 fold, p <0.05). Obestatin treatment did no affect cell migration in the hOSE 17.1normal ovarian epithelial cell line. Obestatin treatment (100 nM) also stimulated a significant increase in cell invasion in the OV-MZ-6 ovarian cancer cell line (1.45 fold +/- 0.13, p <0.05) and in the hOSE17.1 normal ovarian cell line cells (1.40 fold +/- 0.04 and 1.55 fold +/- 0.05 respectively, p <0.01) with 10 nM and 100 nM treatments. Obestatin treatment did not stimulate cell invasion in the SKOV3 ovarian cancer cell line. This lack of obestatin-stimulated invasion in the SKOV3 cell line may be a cell line specific result. In this study, obestatin did not stimulate cell proliferation in the ovarian cell lines and it has previously been shown to have no effect on cell proliferation in the BON-1 pancreatic neuroendocrine and GC rat somatotroph tumour cell lines. In contrast, obestatin has been shown to affect cell proliferation in gastric and thyroid cancer cell lines, and in some normal cell lines. Obestatin also had no effect on attachment of any of the cell lines to any of the ECM components tested (fibronectin, vitronectin, collagen I and collagen IV). The mechanism of action of obestatin was investigated further using a two dimensional-difference in gel electrophoresis (2D-DIGE) proteomic approach. After treatment with obestating (0, 10 and 100 nM), SKOV3 ovarian cancer and hOSE 17.1 normal ovarian cell lines were collected and 2D-DIGE analysis and mass spectrometry were performed to identify proteins that were differentially expressed in response to treatment. Twenty-six differentially expressed proteins were identified and analysed using Ingenuity Pathway Analysis (IPA). This linked 16 of these proteins in a network. The analysis suggested that the ERK1/2 MAPK pathway was a major mediator of obestatin action. ERK1/2 has previously been shown to be associated with obestatin-stimulated cell proliferation and with the anti-apoptotic effects of obestatin. Activation of the ERK1/2 signalling pathway by obestatin was, therefore, investigated in the SKOV3 and OV-MZ-6 ovarian cancer cell lines using anti-active antibodies and Western immunoblots. Obestatin treatment significantly decreased ERK1/2 phosphorylation at higher obestatin concentrations in both the SKOV3 (100 nM and 1000 nM) and OV-MZ-6 (1000 nM) cell lines compared to the untreated controls. Currently, very little is known about obestatin signalling in cancer. This thesis has demonstrated for the first time that the ghrelin axis may play a role in ovarian cancer migration. Ghrelin and obestatin increased cell migration in ovarian cancer cell lines, indicating that they may be a useful target for therapies that reduce ovarian cancer progression. Further studies investigating the role of the ghrelin axis using in vivo ovarian cancer metastasis models are warranted.

Exploring new and emerging models for nonlinear performative works

This dissertation seeks to define and classify potential forms of Nonlinear structure and explore the possibilities they afford for the creation of new musical works. It provides the first comprehensive framework for the discussion of Nonlinear structure in musical works and provides a detailed overview of the rise of nonlinearity in music during the 20th century. Nonlinear events are shown to emerge through significant parametrical discontinuity at the boundaries between regions of relatively strong internal cohesion. The dissertation situates Nonlinear structures in relation to linear structures and unstructured sonic phenomena and provides a means of evaluating Nonlinearity in a musical structure through the consideration of the degree to which the structure is integrated, contingent, compressible and determinate as a whole. It is proposed that Nonlinearity can be classified as a three dimensional space described by three continuums: the temporal continuum, encompassing sequential and multilinear forms of organization, the narrative continuum encompassing processual, game structure and developmental narrative forms and the referential continuum encompassing stylistic allusion, adaptation and quotation. The use of spectrograms of recorded musical works is proposed as a means of evaluating Nonlinearity in a musical work through the visual representation of parametrical divergence in pitch, duration, timbre and dynamic over time. Spectral and structural analysis of repertoire works is undertaken as part of an exploration of musical nonlinearity and the compositional and performative features that characterize it. The contribution of cultural, ideological, scientific and technological shifts to the emergence of Nonlinearity in music is discussed and a range of compositional factors that contributed to the emergence of musical Nonlinearity is examined. The evolution of notational innovations from the mobile score to the screen score is plotted and a novel framework for the discussion of these forms of musical transmission is proposed. A computer coordinated performative model is discussed, in which a computer synchronises screening of notational information, provides temporal coordination of the performers through click-tracks or similar methods and synchronises the audio processing and synthesized elements of the work. It is proposed that such a model constitutes a highly effective means of realizing complex Nonlinear structures. A creative folio comprising 29 original works that explore nonlinearity is presented, discussed and categorised utilising the proposed classifications. Spectrograms of these works are employed where appropriate to illustrate the instantiation of parametrically divergent substructures and examples of structural openness through multiple versioning.

Assessment of police subjective workload and preference for using a voice-based interface during simulated driving

Police in-vehicle systems include a visual output mobile data terminal (MDT) with manual input via touch screen and keyboard. This study investigated the potential for voice-based input and output modalities for reducing subjective workload of police officers while driving. Nineteen experienced drivers of police vehicles (one female) from New South Wales (NSW) Police completed four simulated urban drives. Three drives included a concurrent secondary task: an imitation licence number search using an emulated MDT. Three different interface output-input modalities were examined: Visual-Manual, Visual-Voice, and Audio-Voice. Following each drive, participants rated their subjective workload using the NASA - Raw Task Load Index and completed questions on acceptability. A questionnaire on interface preferences was completed by participants at the end of their session. Engaging in secondary tasks while driving significantly increased subjective workload. The Visual-Manual interface resulted in higher time demand than either of the voice-based interfaces and greater physical demand than the Audio-Voice interface. The Visual-Voice and Audio-Voice interfaces were rated easier to use and more useful than the Visual-Manual interface, although not significantly different from each other. Findings largely echoed those deriving from the analysis of the objective driving performance data. It is acknowledged that under standard procedures, officers should not drive while performing tasks concurrently with certain invehicle policing systems; however, in practice this sometimes occurs. Taking action now to develop voice-based technology for police in-vehicle systems has potential to realise visions for potentially safer and more efficient vehicle-based police work.

Acquiring search expertise : learning experiences and threshold concepts

Expert searchers engage with information as information brokers, researchers, reference librarians, information architects, faculty who teach advanced search, and in a variety of other information-intensive professions. Their experiences are characterized by a profound understanding of information concepts and skills and they have an agile ability to apply this knowledge to interacting with and having an impact on the information environment. This study explored the learning experiences of searchers to understand the acquisition of search expertise. The research question was: What can be learned about becoming an expert searcher from the learning experiences of proficient novice searchers and highly experienced searchers? The key objectives were: (1) to explore the existence of threshold concepts in search expertise; (2) to improve our understanding of how search expertise is acquired and how novice searchers, intent on becoming experts, can learn to search in more expertlike ways. The participant sample drew from two population groups: (1) highly experienced searchers with a minimum of 20 years of relevant professional experience, including LIS faculty who teach advanced search, information brokers, and search engine developers (11 subjects); and (2) MLIS students who had completed coursework in information retrieval and online searching and demonstrated exceptional ability (9 subjects). Using these two groups allowed a nuanced understanding of the experience of learning to search in expertlike ways, with data from those who search at a very high level as well as those who may be actively developing expertise. The study used semi-structured interviews, search tasks with think-aloud narratives, and talk-after protocols. Searches were screen-captured with simultaneous audio-recording of the think-aloud narrative. Data were coded and analyzed using NVivo9 and manually. Grounded theory allowed categories and themes to emerge from the data. Categories represented conceptual knowledge and attributes of expert searchers. In accord with grounded theory method, once theoretical saturation was achieved, during the final stage of analysis the data were viewed through lenses of existing theoretical frameworks. For this study, threshold concept theory (Meyer & Land, 2003) was used to explore which concepts might be threshold concepts. Threshold concepts have been used to explore transformative learning portals in subjects ranging from economics to mathematics. A threshold concept has five defining characteristics: transformative (causing a shift in perception), irreversible (unlikely to be forgotten), integrative (unifying separate concepts), troublesome (initially counter-intuitive), and may be bounded. Themes that emerged provided evidence of four concepts which had the characteristics of threshold concepts. These were: information environment: the total information environment is perceived and understood; information structures: content, index structures, and retrieval algorithms are understood; information vocabularies: fluency in search behaviors related to language, including natural language, controlled vocabulary, and finesse using proximity, truncation, and other language-based tools. The fourth threshold concept was concept fusion, the integration of the other three threshold concepts and further defined by three properties: visioning (anticipating next moves), being light on one's 'search feet' (dancing property), and profound ontological shift (identity as searcher). In addition to the threshold concepts, findings were reported that were not concept-based, including praxes and traits of expert searchers. A model of search expertise is proposed with the four threshold concepts at its core that also integrates the traits and praxes elicited from the study, attributes which are likewise long recognized in LIS research as present in professional searchers. The research provides a deeper understanding of the transformative learning experiences involved in the acquisition of search expertise. It adds to our understanding of search expertise in the context of today's information environment and has implications for teaching advanced search, for research more broadly within library and information science, and for methodologies used to explore threshold concepts.

Genetic susceptibility to complex traits : moving towards informed analysis of whole-genome screens

Susceptibility to complex traits, by definition, involves aetiological polymorphisms at multiple genetic loci combined with variable contributions by environmental factors. However, the approaches taken to identifying genetic loci implicated in susceptibility to complex traits frequently overlooks the compounding contribution of multiple loci in favour of highlighting a single gene solely responsible for predisposition. It is only in a small minority of cases that this has resulted in clear disease heritability associated with polymorphisms in a single gene. More often, this approach has led to an accumulation of single-gene associations with minor contributions to disease susceptibility. As the genomic era advances and genome-wide screens become higher in resolution and throughput, the need for simultaneous consideration of multiple loci is becoming more important. With special reference to non-Hodgkin’s lymphoma (NHL), this chapter will overview the current progress made in elucidating genetic polymorphisms associated with disease susceptibility. We also present novel data from a high-resolution single nucleotide polymorphism (SNP) microarray screen for susceptibility loci that are involved in NHL. Using an ‘informed approach’, the findings are highlighted within the context of cellular pathways, and provide insight and new ideas for methods of analysis for genome-wide screens for susceptibility.

The art of being a fan : complicity and criticality in contemporary art and fandom

This practice-led research project aims to use contemporary art processes and concepts of fandom to construct a space for the critical and creative exploration of the relationship between them. Much of the discourse addressing the intersection of these spaces over the last three decades tends to treat art and fan studies as separate areas of critical and theoretical research. There has also been very little consideration of the critical interface that art practice and fandom share in their engagement with one another – or how the artist as fan might creatively exploit this relationship. Approaching these issues through a practice-led methodology that combines studio based explorations and traditional modes of research, the project aims to demonstrate how my 'fannish' engagements with popular culture can generate new responses to, and understandings of, the relationship between fandom, affect and visual art. The research acts as a performative and creative investigation of fandom as I document the complicit tendencies that arise out of my affective relationship with pop cultural artefacts. It does this through appropriating and reconfiguring content from film, television and print media, to create digital video installations aimed at engendering new experiences and critical interpretations of screen culture. This approach promotes new possibilities for creative engagements with art and popular culture, and these are framed through the lens of what I term the digital-bricoleur. The research will be primarily contextualised by examining other artists' practices as well as selected theoretical frameworks that traverse my investigative terrain. The key artists that are discussed include Douglas Gordon, Candice Brietz, Pierre Huyghe, Paul Pfieffer, and Jennifer and Kevin McCoy. The theoretical developments of the project are drawn from a pluralistic range of ideas ranging from Johanna Drucker's discussion of critical complicity in contemporary art, Matt Hills' discussion of subjectivity in fandom and academia, Nicolas Bourriaud's discussion of Postproduction art practices, and Jacques Rancière's ideas about aesthetics and politics. The methodology and artworks developed over the course of this project will also demonstrate how digital-bricolage leads to new understandings of the relationships between contemporary art and entertainment. The research aims to exploit these apparently contradictory positions to generate a productive site for rethinking the relationship between the creative and critical possibilities of art and fandom. The outcomes of the research consists of a body of artworks – 75% – that demonstrate new contributions to knowledge, and an exegetical component – 25% – that acts to reflect on, analyse and critically contextualise the practice-led findings.

Vote with your feet : hyperlocal polling for urban screens

Vote with Your Feet is a hyperlocal polling tool for urban screens that lets users express their opinion on current affairs. Similar to vox populi interviews on TV, it is meant to reflect the mindset of the community and its diversity. It shows one Yes/No question at a time and lets the user vote by stepping with their foot on one of two physical buttons. By not only displaying the local but also national results (taken from newspaper polls or TV news), it creates a sense of place and can spark offline conversations as well as making people think about their own opinion. As a tangible media installation that bridges physical and digital urban layers, the project empowers citizens and facilitates a bottom-up approach in terms of stimulating opinions and decision making (rather than broadcasting or automating). In a second iteration of the design, we want to encourage users to submit their own questions.