Chromosome I linkage studies in Charcot-Marie-Tooth neuropathy type I

Charcot-Marie-Tooth neuropathy type 1 (CMT1) is an autosomal dominant disorder of peripheral nerve. The gene for CMT1 was originally localized to chromosome 1 by linkage to the Duffy blood group, but it has since been shown that not all CMT1 pedigrees show this linkage. We report here the results of linkage studies using five chromosome 1 markers - Duffy (Fy), antithrombin III (AT3), renin (REN), β-nerve growth factor (NGFB), and salivary amylase (AMY1) - in 16 CMT1 pedigrees. The total lod scores exclude close linkage of CMT1 to any of these markers. However, individual families show probable linkage of CMT1 to Duffy, AT3, and/or AMY1. No linkage was indicated with REN or NGFB. These results indicate that possible location of a CMT1 gene between the AMY1 and AT3 loci at p21 and q23, respectively, on chromosome 1 and support the theory that there is at least one other CMT1 gene.

The duration of Chlamydia muridarum genital tract infection and associated chronic pathological changes are reduced in IL-17 knockout mice but protection is not increased further by immunization

IL-17 is believed to be important for protection against extracellular pathogens, where clearance is dependent on neutrophil recruitment and local activation of epithelial cell defences. However, the role of IL-17 in protection against intracellular pathogens such as Chlamydia is less clear. We have compared (i) the course of natural genital tract C. muridarum infection, (ii) the development of oviduct pathology and (iii) the development of vaccine-induced immunity against infection in wild type (WT) BALB/c and IL-17 knockout mice (IL-17-/-) to determine if IL-17-mediated immunity is implicated in the development of infection-induced pathology and/or protection. Both the magnitude and duration of genital infection was significantly reduced in IL-17-/- mice compared to BALB/c. Similarly, hydrosalpinx was also greatly reduced in IL-17-/- mice and this correlated with reduced neutrophil and macrophage infiltration of oviduct tissues. Matrix metalloproteinase (MMP) 9 and MMP2 were increased in WT oviducts compared to IL-17-/- animals at day 7 post-infection. In contrast, oviducts from IL-17-/- mice contained higher MMP9 and MMP2 at day 21. Infection also elicited higher levels of Chlamydia-neutralizing antibody in serum of IL-17-/- mice than WT mice. Following intranasal immunization with C. muridarum Major Outer Membrane Protein (MOMP) and cholera toxin plus CpG adjuvants, significantly higher levels of chlamydial MOMP-specific IgG and IgA were found in serum and vaginal washes of IL-17-/- mice. T cell proliferation and IFNγ production by splenocytes was greater in WT animals following in vitro re-stimulation, however vaccination was only effective at reducing infection in WT, not IL-17-/- mice. Intranasal or transcutaneous immunization protected WT but not IL-17-/- mice against hydrosalpinx development. Our data show that in the absence of IL-17, the severity of C. muridarum genital infection and associated oviduct pathology are significantly attenuated, however neither infection or pathology can be reduced further by vaccination protocols that effectively protect WT mice.

Diurnal rhythm and effects of feeding, exercise and recombinant equine growth hormone on serum insulin concentrations in the horse

Reasons for performing the study As growth hormone increases lean body mass, it could be a therapy for obese horses. However, growth hormone use induces hyperinsulinaemia in some species, so further investigation is warranted. Objectives To investigate the effects of feeding, exercise and growth hormone therapy on basal insulin concentrations in healthy horses. Study design In vivo experimental study. Methods Blood samples were obtained every 30 min from 12 geldings over 24 h, to establish basal serum insulin concentrations, before they underwent a 3-week exercise programme. Horses were allocated into 2 groups and exercised for another 4 weeks. Group A received daily i.m. injections of recombinant equine growth hormone; 5 mg/day for 5 days, then 12.5 mg/day for 16 days. Blood samples were taken daily before feeding. Insulin vs. time area under curve of Groups A and B were compared using a Student's unpaired t test. Results Horses demonstrated insulin peaks within 2 h of feeding of 577 ± 108.3 pmol/l at 09.30 h and 342.4 ± 75.7 pmol/l at 17.30 h, despite receiving the same meal. The nadir was between midnight and 07.30 h. Exercise had no effect on basal insulin concentrations prior to equine growth hormone administrations. The equine growth hormone injections increased serum insulin concentrations (P = 0.01) within Group A, from 44.4 ± 15.3 pmol/l initially to 320.9 ± 238.2 pmol/l by Day 12. Exogenous growth hormone caused variable hyperinsulinaemia, which was alleviated once equine growth hormone administration ceased. Conclusions Single serum samples taken prior to the morning meal provide basal insulin concentrations. Exercise did not change basal insulin concentrations. However, equine growth hormone injections increased basal insulin concentrations, which were not ameliorated by exercise. Potential relevance This therapy is not recommended to address obesity in insulin-resistant equids.

Prediction of muscular architecture of the rectus femoris and vastus lateralis from EMG during isometric contractions in soccer players

Objectives The purpose of the study was to establish regression equations that could be used to predict muscle thickness and pennation angle at different intensities from electromyography (EMG) based measures of muscle activation during isometric contractions. Design Cross-sectional study. Methods Simultaneous ultrasonography and EMG were used to measure pennation angle, muscle thickness and muscle activity of the rectus femoris and vastus lateralis muscles, respectively, during graded isometric knee extension contractions performed on a Cybex dynamometer. Data form fifteen male soccer players were collected in increments of approximately 25% intensity of the maximum voluntary contraction (MVC) ranging from rest to MVC. Results There was a significant correlation (P < 0.05) between ultrasound predictors and EMG measures for the muscle thickness of rectus femoris with an R2 value of 0.68. There was no significant correlation (P > 0.05) between ultrasound pennation angle for the vastus lateralis predictors for EMG muscle activity with an R2 value of 0.40. Conclusions The regression equations can be used to characterise muscle thickness more accurately and to determine how it changes with contraction intensity, this provides improved estimates of muscle force when using musculoskeletal models.

The health effects of temperature : current estimates, future projections, and adaptation strategies

Climate change is expected to be one of the biggest global health threats in the 21st century. In response to changes in climate and associated extreme events, public health adaptation has become imperative. This thesis examined several key issues in this emerging research field. The thesis aimed to identify the climate-health (particularly temperature-health) relationships, then develop quantitative models that can be used to project future health impacts of climate change, and therefore help formulate adaptation strategies for dealing with climate-related health risks and reducing vulnerability. The research questions addressed by this thesis were: (1) What are the barriers to public health adaptation to climate change? What are the research priorities in this emerging field? (2) What models and frameworks can be used to project future temperature-related mortality under different climate change scenarios? (3) What is the actual burden of temperature-related mortality? What are the impacts of climate change on future burden of disease? and (4) Can we develop public health adaptation strategies to manage the health effects of temperature in response to climate change? Using a literature review, I discussed how public health organisations should implement and manage the process of planned adaptation. This review showed that public health adaptation can operate at two levels: building adaptive capacity and implementing adaptation actions. However, there are constraints and barriers to adaptation arising from uncertainty, cost, technologic limits, institutional arrangements, deficits of social capital, and individual perception of risks. The opportunities for planning and implementing public health adaptation are reliant on effective strategies to overcome likely barriers. I proposed that high priorities should be given to multidisciplinary research on the assessment of potential health effects of climate change, projections of future health impacts under different climate and socio-economic scenarios, identification of health cobenefits of climate change policies, and evaluation of cost-effective public health adaptation options. Heat-related mortality is the most direct and highly-significant potential climate change impact on human health. I thus conducted a systematic review of research and methods for projecting future heat-related mortality under different climate change scenarios. The review showed that climate change is likely to result in a substantial increase in heatrelated mortality. Projecting heat-related mortality requires understanding of historical temperature-mortality relationships, and consideration of future changes in climate, population and acclimatisation. Further research is needed to provide a stronger theoretical framework for mortality projections, including a better understanding of socioeconomic development, adaptation strategies, land-use patterns, air pollution and mortality displacement. Most previous studies were designed to examine temperature-related excess deaths or mortality risks. However, if most temperature-related deaths occur in the very elderly who had only a short life expectancy, then the burden of temperature on mortality would have less public health importance. To guide policy decisions and resource allocation, it is desirable to know the actual burden of temperature-related mortality. To achieve this, I used years of life lost to provide a new measure of health effects of temperature. I conducted a time-series analysis to estimate years of life lost associated with changes in season and temperature in Brisbane, Australia. I also projected the future temperaturerelated years of life lost attributable to climate change. This study showed that the association between temperature and years of life lost was U-shaped, with increased years of life lost on cold and hot days. The temperature-related years of life lost will worsen greatly if future climate change goes beyond a 2 °C increase and without any adaptation to higher temperatures. The excess mortality during prolonged extreme temperatures is often greater than the predicted using smoothed temperature-mortality association. This is because sustained period of extreme temperatures produce an extra effect beyond that predicted by daily temperatures. To better estimate the burden of extreme temperatures, I estimated their effects on years of life lost due to cardiovascular disease using data from Brisbane, Australia. The results showed that the association between daily mean temperature and years of life lost due to cardiovascular disease was U-shaped, with the lowest years of life lost at 24 °C (the 75th percentile of daily mean temperature in Brisbane), rising progressively as temperatures become hotter or colder. There were significant added effects of heat waves, but no added effects of cold spells. Finally, public health adaptation to hot weather is necessary and pressing. I discussed how to manage the health effects of temperature, especially with the context of climate change. Strategies to minimise the health effects of high temperatures and climate change can fall into two categories: reducing the heat exposure and managing the health effects of high temperatures. However, policy decisions need information on specific adaptations, together with their expected costs and benefits. Therefore, more research is needed to evaluate cost-effective adaptation options. In summary, this thesis adds to the large body of literature on the impacts of temperature and climate change on human health. It improves our understanding of the temperaturehealth relationship, and how this relationship will change as temperatures increase. Although the research is limited to one city, which restricts the generalisability of the findings, the methods and approaches developed in this thesis will be useful to other researchers studying temperature-health relationships and climate change impacts. The results may be helpful for decision-makers who develop public health adaptation strategies to minimise the health effects of extreme temperatures and climate change.

Writing the oriental woman : an examination of the representation of Japanese women in contemporary Australian crime fiction

This study considers the challenges in representing women from other cultures in the crime fiction genre. The study is presented in two parts; an exegesis and a creative practice component consisting of a full length crime fiction novel, Batafurai. The exegesis examines the historical period of a section of the novel—post-war Japan—and how the area of research known as Occupation Studies provides an insight into the conditions of women during this period. The exegesis also examines selected postcolonial theory and its exposition of representations of the 'other' as a western construct designed to serve Eurocentric ends. The genre of crime fiction is reviewed, also, to determine how characters purportedly representing Oriental cultures are constricted by established stereotypes. Two case studies are examined to investigate whether these stereotypes are still apparent in contemporary Australian crime fiction. Finally, I discuss my own novel, Batafurai, to review how I represented people of Asian background, and whether my attempts to resist stereotype were successful. My conclusion illustrates how novels written in the crime fiction genre are reliant on strategies that are action-focused, rather than character-based, and thus often use easily recognizable types to quickly establish frameworks for their stories. As a sub-set of popular fiction, crime fiction has a tendency to replicate rather than challenge established stereotypes. Where it does challenge stereotypes, it reflects a territory that popular culture has already visited, such as the 'female', 'black' or 'gay' detective. Crime fiction also has, as one of its central concerns, an interest in examining and reinforcing the notion of societal order. It repeatedly demonstrates that crime either does not pay or should not pay. One of the ways it does this is to contrast what is 'good', known and understood with what is 'bad', unknown, foreign or beyond our normal comprehension. In western culture, the east has traditionally been employed as the site of difference, and has been constantly used as a setting of contrast, excitement or fear. Crime fiction conforms to this pattern, using the east to add a richness and depth to what otherwise might become a 'dry' tale. However, when used in such a way, what is variously eastern, 'other' or Oriental can never be paramount, always falling to secondary side of the binary opposites (good/evil, known/unknown, redeemed/doomed) at work. In an age of globalisation, the challenge for contemporary writers of popular fiction is to be responsive to an audience that demands respect for all cultures. Writers must demonstrate that they are sensitive to such concerns and can skillfully manage the tensions caused by the need to deliver work that operates within the parameters of the genre, and the desire to avoid offence to any cultural or ethnic group. In my work, my strategy to manage these tensions has been to create a back-story for my characters of Asian background, developing them above mere genre types, and to situate them with credibility in time and place through appropriate historical research.

Cervical auscultation in the diagnosis of oropharyngeal aspiration in children : a study protocol for a randomised controlled trial

Background Oropharyngeal aspiration (OPA) can lead to recurrent respiratory illnesses and chronic lung disease in children. Current clinical feeding evaluations performed by speech pathologists have poor reliability in detecting OPA when compared to radiological procedures such as the modified barium swallow (MBS). Improved ability to diagnose OPA accurately via clinical evaluation potentially reduces reliance on expensive, less readily available radiological procedures. Our study investigates the utility of adding cervical auscultation (CA), a technique of listening to swallowing sounds, in improving the diagnostic accuracy of a clinical evaluation for the detection of OPA. Methods We plan an open, unblinded, randomised controlled trial at a paediatric tertiary teaching hospital. Two hundred and sixteen children fulfilling the inclusion criteria will be randomised to one of the two clinical assessment techniques for the clinical detection of OPA: (1) clinical feeding evaluation only (CFE) group or (2) clinical feeding evaluation with cervical auscultation (CFE + CA) group. All children will then undergo an MBS to determine radiologically assessed OPA. The primary outcome is the presence or absence of OPA, as determined on MBS using the Penetration-Aspiration Scale. Our main objective is to determine the sensitivity, specificity, negative and positive predictive values of ‘CFE + CA��� versus ‘CFE’ only compared to MBS-identified OPA. Discussion Early detection and appropriate management of OPA is important to prevent chronic pulmonary disease and poor growth in children. As the reliability of CFE to detect OPA is low, a technique that can improve the diagnostic accuracy of the CFE will help minimise consequences to the paediatric respiratory system. Cervical auscultation is a technique that has previously been documented as a clinical adjunct to the CFE; however, no published RCTs addressing the reliability of this technique in children exist. Our study will be the first to establish the utility of CA in assessing and diagnosing OPA risk in young children.

Through-focus performance with multifocal contact lenses : effect of binocularity, pupil diameter and inherent ocular aberrations

Purpose to evaluate the effects of the wearer’s pupil size and spherical aberration on visual performance with centre-near, aspheric multifocal contact lenses (MFCLs). The advantage of binocular over monocular vision was also investigated. Methods Twelve young volunteers, with an average age of 27±5 years, participated in the study. LogMAR Visual Acuity (VA) was measured under cycloplegia for a range of defocus levels (from +3.0 to -3.0D, in 0.5D steps) with no correction and with three aspheric MFCLs (Air Optix Aqua Multifocal, Ciba Vision, Duluth, GA, US) with a centre-near design, providing correction for “Low”, “Med” and “High” near demands. Measurements were performed for all combinations of the following conditions: i) artificial pupils of 6mm and 3mm diameter, ii) binocular and monocular (dominant eye) vision. Depth-of-focus (DOF) was calculated from the VA vs. defocus curves. Ocular aberrations under cycloplegia were measured using iTrace. Results VA at -3.0D defocus (simulating near performance) was statistically higher for the 3mm than for the 6mm pupil (p=0.006), and for binocular rather than for monocular vision (p<0.001). Similarly, DOF was better for the 3mm pupil (p=0.002) and for binocular viewing conditions (p<0.001, ANOVA). Both VA at –3.0D defocus and DOF increased as the “addition” of the MFCL correction increased. Finally, with the centre-near MFCLs a linear correlation was found between VA at –3.0D defocus and the wearer’s ocular spherical aberration (R2=0.20 p<0.001 for 6mm data), with the eyes exhibiting the higher positive spherical aberration experiencing lower VAs. By contrast, no correlation was found between VA and spherical aberration at 0.00D defocus (distance vision). Conclusions Both near VA and depth-of-focus improve with these MFCLs, with the effects being more pronounced for small pupils and binocular than for monocular vision. Coupling of the wearer’s ocular spherical aberration with the aberration profiles provided by MFCLs affects their functionality.

Epigenetic regulation of glucose transporters in non-small cell lung cancer

Due to their inherently hypoxic environment, cancer cells often resort to glycolysis, or the anaerobic breakdown of glucose to form ATP to provide for their energy needs, known as the Warburg effect. At the same time, overexpression of the insulin receptor in non-small cell lung cancer (NSCLC) is associated with an increased risk of metastasis and decreased survival. The uptake of glucose into cells is carried out via glucose transporters or GLUTs. Of these, GLUT-4 is essential for insulin-stimulated glucose uptake. Following treatment with the epigenetic targeting agents histone deacetylase inhibitors (HDACi), GLUT-3 and GLUT-4 expression were found to be induced in NSCLC cell lines, with minimal responses in transformed normal human bronchial epithelial cells (HBECs). Similar results for GLUT-4 were observed in cells derived from liver, muscle, kidney and pre-adipocytes. Bioinformatic analysis of the promoter for GLUT-4 indicates that it may also be regulated by several chromatin binding factors or complexes including CTCF, SP1 and SMYD3. Chromatin immunoprecipitation studies demonstrate that the promoter for GLUT-4 is dynamically remodeled in response to HDACi. Overall, these results may have value within the clinical setting as (a) it may be possible to use this to enhance fluorodeoxyglucose (18F) positron emission tomography (FDG-PET) imaging sensitivity; (b) it may be possible to target NSCLC through the use of HDACi and insulin mediated uptake of the metabolic targeting drugs such as 2-deoxyglucose (2-DG); or (c) enhance or sensitize NSCLC to chemotherapy. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

The role of epigenetics in resistance to cisplatin chemotherapy in lung cancer

Non-small cell lung cancer (NSCLC) is the most common cause of cancer related death in the world. Cisplatin and carboplatin are the most commonly used cytotoxic chemotherapeutic agents to treat the disease. These agents, usually combined with drugs such as gemcitabine or pemetrexed, induce objective tumor responses in only 20-30% of patients. Aberrant epigenetic regulation of gene expression is a frequent event in NSCLC. In this article we review the emerging evidence that epigenetics and the cellular machinery involved with this type of regulation may be key elements in the development of cisplatin resistance in NSCLC. © 2011 by the authors; licensee MDPI, Basel, Switzerland.

Networked masculinities and social networking sites : a call for the analysis of men and contemporary digital media

It is of course recognised that technology can be gendered and implicated in gender relations. However, it continues to be the case that men’s experiences with technology are underexplored and the situation is even more problematic where digital media is concerned. Over the past 30 years we have witnessed a dramatic rise in the pervasiveness of digital media across many parts of the world and as associated with wide ranging aspects of our lives. This rise has been fuelled over the last decade by the emergence of Web 2.0 and particularly Social Networking Sites (SNS). Given this context, I believe it is necessary for us to undertake more work to understand men’s engagements with digital media, the implications this might have for masculinities and the analysis of gender relations more generally. To begin to unpack this area, I engage theorizations of the properties of digital media networks and integrate this with the masculinity studies field. Using this framework, I suggest we need to consider the rise in what I call networked masculinities – those masculinities (co)produced and reproduced with digitally networked publics. Through this analysis I discuss themes related to digital mediators, relationships, play and leisure, work and commerce, and ethics. I conclude that as masculinities can be, and are being, complicated and given agency by advancing notions and practices of connectivity, mobility, classification and convergence, those engaged with masculinity studies and digital media have much to contribute.

Theatre-arts pedagogy for social justice : case study of the area youth foundation in Jamaica

In this paper I describe and analyse the socio-educational significance of a theatre arts approach to learning for young adults in Jamaica, implemented by the Area Youth Foundation (AYF). Briefly outlining the genesis and development of the AYF, I provide snapshots of the experiences and destinations of some of its young participants. The paper discusses AYF workshops to show how the pedagogy was shaped by the expressive arts and based on the critical praxis approach systematized by Paulo Freire in adult education and Augusto Boal in theatre. Based on interviews with AYF’s leader and some of the learners, I discuss how the foundation’s motto, “Youth Empowerment Through the Arts,” is played out in workshops and creative productions that are simultaneously learner-driven and teacher-guided, with the powerful impact of inspiring politically thoughtful creativity and skills in youths from less-privileged communities.

Large-scale analysis of formations in soccer

Due to the demand for better and deeper analysis in sports, organizations (both professional teams and broadcasters) are looking to use spatiotemporal data in the form of player tracking information to obtain an advantage over their competitors. However, due to the large volume of data, its unstructured nature, and lack of associated team activity labels (e.g. strategic/tactical), effective and efficient strategies to deal with such data have yet to be deployed. A bottleneck restricting such solutions is the lack of a suitable representation (i.e. ordering of players) which is immune to the potentially infinite number of possible permutations of player orderings, in addition to the high dimensionality of temporal signal (e.g. a game of soccer last for 90 mins). Leveraging a recent method which utilizes a "role-representation", as well as a feature reduction strategy that uses a spatiotemporal bilinear basis model to form a compact spatiotemporal representation. Using this representation, we find the most likely formation patterns of a team associated with match events across nearly 14 hours of continuous player and ball tracking data in soccer. Additionally, we show that we can accurately segment a match into distinct game phases and detect highlights. (i.e. shots, corners, free-kicks, etc) completely automatically using a decision-tree formulation.

Exploring schema-driven differences in situation awareness between road users : an on-road study of driver, cyclist and motorcyclist situation awareness

Collisions between different road users make a substantial contribution to road trauma. Although evidence suggests that different road users interpret the same road situations differently, it is not clear how road users' situation awareness differs, nor is it clear which differences might lead to conflicts. This article presents the findings from an on-road study conducted to examine driver, motorcyclist and cyclist situation awareness in different road environments. The findings suggest that, in addition to minor differences in the structure of different road users' situation awareness (i.e. amount of information and how it is integrated), the actual content of situation awareness in terms of road user schemata, the resulting interaction with the world and the information underpinning situation awareness is markedly different. Further examination indicates that the differences are likely to be compatible along arterial roads, shopping strips and at roundabouts, but that they may create conflicts between different road users at intersections. Interventions designed to support compatible situation awareness and behaviour between different road users are discussed. Practitioner Summary: Incompatible situation awareness plays a key role in collisions between different road users (e.g. drivers and motorcyclists). This on-road study examined situation awareness in drivers, motorcyclists and cyclists, identifying the key differences and potential conflicts that arise. The findings are used to propose interventions designed to enhance the compatibility of situation awareness between road users.

Ruptured relations : guerrilla theatre, time & Pranksterish disability performance practice

Guerrilla theatre tends, by its very definition, to pop up unpredictably – it interrupts what people might see as the proper or typical flow of time, place and space. The subversive tenor of such work means that questions about ‘what has happened’ tend to the decidedly less polite form of ‘WTF’ as passersby struggle to make sense of, and move on from, moments in which accustomed narratives of action and interaction no longer apply. In this paper I examine examples of guerrilla theatre by performers with disabilities in terms of these ruptures in time, and the way they prompt reflection, reconfigure relations, or recede into traditional relations again - focusing particularly on comedian Laurence Clark. Many performers with disabilities – Bill Shannon, Katherine Araniello, Aaron Williamson, Ju Gosling, and others – find guerrilla-style interventions in public places apposite to their aesthetic and political agendas. They prompt passersby to reflect on their relationship to people with disabilities. They can be recorded for later dissection and display, teaching people something about the way social performers, social spectators and society as a whole deal with disability. In this paper, as I unpack Clark's work, I note that the embarrassment that characterises these encounters can be a flag of an ethical process taking place for passersby. Caught between two moments in which time, roles and relationships suddenly fail to flow along the smooth routes of socially determined habits, passersbys’ frowns, gasps and giggles flag difficulties dealing with questions about their attitude to disabled people they do not now know how to answer. I consider the productivity, politics and performerly ethics of drawing passersby into such a process – a chaotic, challenging interstitial time in which a passersbys choices become fodder for public consumption – in such a wholly public way.