Association study of genes related to bone formation and resorption and the extent of radiographic change in ankylosing spondylitis

Objective: To identify genetic associations with severity of radiographic damage in ankylosing spondylitis (AS). Method: We studied 1537 AS cases of European descent; all fulfilled the modified New York Criteria. Radiographic severity was assessed from digitised lateral radiographs of the cervical and lumbar spine using the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS). A two-phase genotyping design was used. In phase 1, 498 single nucleotide polymorphisms (SNPs) were genotyped in 688 cases; these were selected to capture >90% of the common haplotypic variation in the exons, exon-intron boundaries, and 5 kb flanking DNA in the 5' and 3' UTR of 74 genes involved in anabolic or catabolic bone pathways. In phase 2, 15 SNPs exhibiting p<0.05 were genotyped in a further cohort of 830 AS cases; results were analysed both separately and in combination with the discovery phase data. Association was tested by contingency tables after separating the samples into 'mild' and 'severe' groups, defined as the bottom and top 40% by mSASSS, adjusted for gender and disease duration. Results: Experiment-wise association was observed with the SNP rs8092336 (combined OR 0.32, p=1.2×10-5), which lies within RANK (receptor activator of NF?B), a gene involved in osteoclastogenesis, and in the interaction between T cells and dendritic cells. Association was also found with the SNP rs1236913 in PTGS1 (prostaglandin-endoperoxide synthase 1, cyclooxygenase 1), giving an OR of 0.53 (p=2.6×10-3). There was no observed association between radiographic severity and HLA-B*27. Conclusions: These findings support roles for bone resorption and prostaglandins pathways in the osteoproliferative changes in AS.

Whole blood transcriptional profiling in ankylosing spondylitis identifies novel candidate genes that might contribute to the inflammatory and tissue-destructive disease aspects

Introduction: A number of genetic-association studies have identified genes contributing to ankylosing spondylitis (AS) susceptibility but such approaches provide little information as to the gene activity changes occurring during the disease process. Transcriptional profiling generates a 'snapshot' of the sampled cells' activity and thus can provide insights into the molecular processes driving the disease process. We undertook a whole-genome microarray approach to identify candidate genes associated with AS and validated these gene-expression changes in a larger sample cohort. Methods: A total of 18 active AS patients, classified according to the New York criteria, and 18 gender- and age-matched controls were profiled using Illumina HT-12 whole-genome expression BeadChips which carry cDNAs for 48,000 genes and transcripts. Class comparison analysis identified a number of differentially expressed candidate genes. These candidate genes were then validated in a larger cohort using qPCR-based TaqMan low density arrays (TLDAs). Results: A total of 239 probes corresponding to 221 genes were identified as being significantly different between patients and controls with a P-value <0.0005 (80% confidence level of false discovery rate). Forty-seven genes were then selected for validation studies, using the TLDAs. Thirteen of these genes were validated in the second patient cohort with 12 downregulated 1.3- to 2-fold and only 1 upregulated (1.6-fold). Among a number of identified genes with well-documented inflammatory roles we also validated genes that might be of great interest to the understanding of AS progression such as SPOCK2 (osteonectin) and EP300, which modulate cartilage and bone metabolism. Conclusions: We have validated a gene expression signature for AS from whole blood and identified strong candidate genes that may play roles in both the inflammatory and joint destruction aspects of the disease.

Revisiting the CO oxidation reaction on various Au/TiO2catalysts: Roles of the surface OH groups and the reaction mechanism

This work aims to understand the influence of TiO2 surface structure in Au/TiO2 catalysts on CO oxidation. Au nanoparticles (3 wt%) in the range of 4 to 8 nm were loaded onto four kinds of TiO2 surfaces, which had different surface structures and were synthesized by calcining hydrogen titanate nanotubes at various temperatures and in different atmospheres. The Au catalyst supported on anatase nanorods exhibited the highest activity in CO oxidation at 30 °C among all the five Au/TiO2 catalysts including the reference catalyst of Au/TiO2-P25. X-ray photoelectron spectroscopy (XPS) and infrared emission spectra (IES) results indicate that the anatase nanorods have the most active surface on which water molecules can be strongly adsorbed and OH groups can be formed readily. Theoretical calculation indicates that the surface OH can facilitate the O2 adsorption on the anatase surface. Such active surface features are conducive to the O2 activation and CO oxidation

Effect of age, gender and mannose-binding lectin (MBL) status on the inflammatory profile in peripheral blood plasma of Australian blood donors

Transfusion of blood components has been associated with poor patient outcomes and, an overall increase in morbidity and mortality. Differences in the blood components arising from donor health, age and immune status may impact on outcomes of transfusion and transfusion-related immune modulation in recipients. The aim of this study was to investigate differences in inflammatory profile in donors and association with parameters including age, gender and deficiency status of pattern recognition molecule mannose-binding lectin (MBL). MBL level was determined by ELISA. Serum levels of interleukin (IL)-1α, IL-1β, IL-6, IL-8, IL-10, IL-12, tumour necrosis factor (TNF)-α, macrophage inflammatory protein (MIP)-1α, monocyte chemoattractant protein (MCP)-1, interferon (IFN)-α, and IFN-γ were examined by cytometric bead array (CBA). C-reactive protein (CRP) and rheumatoid factor (RF) were examined by immunoturbidimetry. This study demonstrated age was a parameter associated with the immune profile of blood donors, with significant increases in MCP-1 (p < 0.05) and RF (p < 0.05) and decreases in IL-1α evident in the older donors (61–76 years). Significant gender-associated differences in MCP-1, IL-12 and CRP plasma levels in the blood donor cohort were also reported. There was no significant difference in the level of any inflammatory markers studied according to MBL status. This study demonstrated that age and gender are associated with inflammatory profile in donors. These differences may be a factor impacting on outcomes of transfusion.

The effects of high temperature on cardiovascular admissions in the most populous tropical city in Vietnam

This study examined the short-term effects of temperature on cardiovascular hospital admissions (CHA) in the largest tropical city in Southern Vietnam. We applied Poisson time-series regression models with Distributed Lag Non-Linear Model (DLNM) to examine the temperature-CHA association while adjusting for seasonal and long-term trends, day of the week, holidays, and humidity. The threshold temperature and added effects of heat waves were also evaluated. The exposure-response curve of temperature-CHA reveals a J-shape relationship with a threshold temperature of 29.6 °C. The delayed effects temperature-CHA lasted for a week (0–5 days). The overall risk of CHA increased 12.9% (RR, 1.129; 95%CI, 0.972–1.311) during heatwave events, which were defined as temperature ≥ the 99th percentile for ≥2 consecutive days. The modification roles of gender and age were inconsistent and non-significant in this study. An additional prevention program that reduces the risk of cardiovascular disease in relation to high temperatures should be developed.

Adolescent sexual behavioral intentions measurement: A gender approach in the Colombian Caribbean region [Medición de la Intención en la Actividad Sexual en Adolescentes: una Aproximación de Acuerdo al Género del Caribe Colombiano]

The study of 1777 male and female adolescent students of 11-19 years in the Colombian Caribbean had two objectives: development and validation of two reproductive health intention scales and analyze gender differences. The pilot of the scale consisted of 8 items and was reduced to 6, to check the reliability and validity using factor analysis and principal components with VARIMAX rotation yielded two factors: Intention and Intention Risk Protection, explained between 69.4% and 70% respectively. In the male Protection Intent (M = 3.87 and SD = 1.29) and risk (M = 2.56 and SD = 1.18) obtained an alpha between 0.74 and 0.86, and in Protection of Intent to female (M = 3.49 and SD = 1.35) and risk (M = 1.50 and SD = 0.89) ranged between 0.78 and 086. In conclusion, the reliability and structural stability are adequate and there are gender differences in the scales.

Site and gender specificity of inheritance of bone mineral density

Differences in genetic control of BMD by skeletal sites and genders were examined by complex segregation analysis in 816 members of 147 families with probands with extreme low BMD. Spine BMD correlated more strongly in male-male comparisons and hip BMD in female-female comparisons, consistent with gender- and site-specificity of BMD heritability. Introduction: Evidence from studies in animals and humans suggests that the genetic control of bone mineral density (BMD) may differ at different skeletal sites and between genders. This question has important implications for the design and interpretation of genetic studies of osteoporosis. Methods: We examined the genetic profile of 147 families with 816 individuals recruited through probands with extreme low BMD (T-score < −2.5, Z-score < −2.0). Complex segregation analysis was performed using the Pedigree Analysis Package. BMD was measured by DXA at both lumbar spine (L1-L4) and femoral neck. Results: Complex segregation analysis excluded purely monogenic and environmental models of segregation of lumbar spine and femoral neck BMD in these families. Pure polygenic models were excluded at the lumbar spine when menopausal status was considered as a covariate, but not at the femoral neck. Mendelian models with a residual polygenic component were not excluded. These models were consistent with the presence of a rare Mendelian genotype of prevalence 3–19 %, causing high BMD at the hip and spine in these families, with additional polygenic effects. Total heritability range at the lumbar spine was 61–67 % and at the femoral neck was 44–67 %. Significant differences in correlation of femoral neck and lumbar spine BMD were observed between male and female relative pairs, with male-male comparisons exhibiting stronger lumbar spine BMD correlation than femoral neck, and female-female comparisons having greater femoral neck BMD correlation than lumbar spine. These findings remained true for parent-offspring correlations when menopausal status was taken into account. The recurrence risk ratio for siblings of probands of a Z-score < −2.0 was 5.4 at the lumbar spine and 5.9 at the femoral neck. Conclusions: These findings support gender- and site-specificity of the inheritance of BMD. These results should be considered in the design and interpretation of genetic studies of osteoporosis.

Older adults and driving reduction: Is the gender gap narrowing?

This study investigated driving reduction in a diverse sample of 229 male and female older drivers aged 70 years and above in Queensland, Australia. The study sought to determine whether differences existed between male and female older drivers in regard to driving patterns, and to identify factors that were predictive of driving reduction in female versus male older drivers. Participants provided information on their health, self-reported driving patterns, driving perceptions, alternative transport options, and feedback. Overall, females were more likely to avoid challenging situations but less likely to reduce their driving when compared to males. Self-rated health and driving confidence were significant predictors for driving reduction among females. For males, driving importance was the only significant predictor for driving reduction in this sample. This study indicates the need for longitudinal research on the process of driving reduction and whether the planning process for driving cessation differ between females and males.

Roles of forced nicotine exposure and Comt gene disruption in the development of addiction-related behavioural and neurochemical changes in mice

Activation of midbrain dopamine systems is thought to be critically involved in the addictive properties of abused substances. Drugs of abuse increase dopamine release in the nucleus accumbens and dorsal striatum, which are the target areas of mesolimbic and nigrostriatal dopamine pathways, respectively. Dopamine release in the nucleus accumbens is thought to mediate the attribution of incentive salience to rewards, and dorsal striatal dopamine release is involved in habit formation. In addition, changes in the function of prefrontal cortex (PFC), the target area of mesocortical dopamine pathway, may skew information processing and memory formation such that the addict pays an abnormal amount of attention to drug-related cues. In this study, we wanted to explore how long-term forced oral nicotine exposure or the lack of catechol-O-methyltransferase (COMT), one of the dopamine metabolizing enzymes, would affect the functioning of these pathways. We also wanted to find out how the forced nicotine exposure or the lack of COMT would affect the consumption of nicotine, alcohol, or cocaine. First, we studied the effect of forced chronic nicotine exposure on the sensitivity of dopamine D2-like autoreceptors in microdialysis and locomotor activity experiments. We found that the sensitivity of these receptors was unchanged after forced oral nicotine exposure, although an increase in the sensitivity was observed in mice treated with intermittent nicotine injections twice daily for 10 days. Thus, the effect of nicotine treatment on dopamine autoreceptor sensitivity depends on the route, frequency, and time course of drug administration. Second, we investigated whether the forced oral nicotine exposure would affect the reinforcing properties of nicotine injections. The chronic nicotine exposure did not significantly affect the development of conditioned place preference to nicotine. In the intravenous self-administration paradigm, however, the nicotine-exposed animals self-administered nicotine at a lower unit dose than the control animals, indicating that their sensitivity to the reinforcing effects of nicotine was enhanced. Next, we wanted to study whether the Comt gene knock-out animals would be a suitable model to study alcohol and cocaine consumption or addiction. Although previous work had shown male Comt knock-out mice to be less sensitive to the locomotor-activating effects of cocaine, the present study found that the lack of COMT did not affect the consumption of cocaine solutions or the development of cocaine-induced place preference. However, the present work did find that male Comt knock-out mice, but not female knock-out mice, consumed ethanol more avidly than their wild-type littermates. This finding suggests that COMT may be one of the factors, albeit not a primary one, contributing to the risk of alcoholism. Last, we explored the effect of COMT deficiency on dorsal striatal, accumbal, and prefrontal cortical dopamine metabolism under no-net-flux conditions and under levodopa load in freely-moving mice. The lack of COMT did not affect the extracellular dopamine concentrations under baseline conditions in any of the brain areas studied. In the prefrontal cortex, the dopamine levels remained high for a prolonged time after levodopa treatment in male, but not female, Comt knock-out mice. COMT deficiency induced accumulation of 3,4-dihydroxyphenylacetic acid, which increased further under levodopa load. Homovanillic acid was not detectable in Comt knock-out animals either under baseline conditions or after levodopa treatment. Taken together, the present results show that although forced chronic oral nicotine exposure affects the reinforcing properties of self-administered nicotine, it is not an addiction model itself. COMT seems to play a minor role in dopamine metabolism and in the development of addiction under baseline conditions, indicating that dopamine function in the brain is well-protected from perturbation. However, the role of COMT becomes more important when the dopaminergic system is challenged, such as by pharmacological manipulation.

Podiatry scope of practice: The role of gender in identification as a specialist

Background Ensuring efficient and effective delivery of health care to an aging population has been a major driver for a review of the health workforce in Australia. As part of this review a new National Registration and Accreditation Scheme (NRAS) has evolved with one goal being to improve workforce flexibility. With increased flexibility there have been discussions about the role specialist scopes of practice plays. This study explored the role of gender and other work related characteristics in relation to contemporary scope of podiatry practice and specialisation in Australia. Methods A cross sectional survey was administered through an on-line survey tool on behalf of the Australasian Podiatry Council. Descriptive data was collected over a three-week period. Queensland University of Technology Human Research Ethics approval was sought and confirmed exemption from review, exemption number 1400000791. Results Of the podiatrists participating in this survey (n=218), they were predominately female (66%), early career (34%, 0-9 years) and work in private practices (78%) in multi-podiatrists centres (41%). Relationship between clinical activities performed and “self-perception” of performing a “specialist role” was significant for practitioners who undertook treatment of specific patient groups. The largest area of interest was biomechanics (n=65), followed closely by diabetes (n=61), a third area identified was paediatrics (n=26). Self-perception of specialist status was compared with gender, years of experience, location, primary work environment and clinical practice. When practitioners are asked to categorise themselves to be either “generalist” or “specialist/ generalist with a special interest” podiatrist, male gender was identified as being the only factor which would predict perception of status; 64% males identified as specialist, as opposed to 49% of female survey respondents (Chi square, df = 1, P = 0.044). Self-perception of specialist status was not explained by years of experience, location, working in rural versus urban environment, state worked in, or part-time/full-time work status. Conclusions In conclusion; gender, work environment plus area of interest form a complex relationship, which appear to influence both perception and reality of service provision. Incorporation of specialisation activity (surgical podiatry along with endorsement for use of scheduled medicines) will have lasting impact on the scope of the podiatry profession in Australia. To meet community expectation and maintain high standards, the addition of new subspecialties may be indicated.

A Literary Turn : Rethinking the Roles of Generalization and Theory in Anglo-American Moral Philosophy

This work investigates the role of narrative literature in late-20th century and contemporary Anglo-American moral philosophy. It aims to show the trend of reading narrative literature for purposes of moral philosophy from the 1970 s and early 80 s to the present day as a part of a larger movement in Anglo-American moral philosophy, and to present a view of its significance for moral philosophy overall. Chapter 1 provides some preliminaries concerning the view of narrative literature which my discussion builds on. In chapter 2 I give an outline of how narrative literature is considered in contemporary Anglo-American moral philosophy, and connect this use to the broad trend of neo-Aristotelian ethics in this context. In chapter 3 I connect the use of literature to the idea of the non-generalizability of moral perception and judgment, which is central to the neo-Aristotelian trend, as well as to a range of moral particularisms and anti-theoretical positions of late 20th century and contemporary ethics. The joint task of chapters 2 and 3 is to situate the trend of reading narrative literature for the purposes of moral philosophy in the present context of moral philosophy. In the following two chapters, 4 and 5, I move on from the particularizing power of narrative literature, which is emphasized by neo-Aristotelians and particularists alike, to a broader under-standing of the intellectual potential of narrative literature. In chapter 4 I argue that narrative literature has its own forms of generalization which are enriching for our understanding of the workings of ethical generalizations in philosophy. In chapter 5 I discuss Iris Murdoch s and Martha Nussbaum s respective ways of combining ethical generality and particularity in a philosophical framework where both systematic moral theory and narrative literature are taken seriously. In chapter 6 I analyse the controversy between contemporary anti-theoretical conceptions of ethics and Nussbaum s refutation of these. I present my suggestion for how the significance of the ethics/literature discussion for moral philosophy can be understood if one wants to overcome the limitations of both Nussbaum s theory-centred, equilibrium-seeking perspective, and the anti-theorists repudiation of theory. I call my position the inclusive approach .

Rauta ja Ristilukki : Vilho Helasen salapoliisiromaanisarja

Vilho Helanen (1899 1952) was a right-wing opinion leader in interwar Finland. But following the Second World War, the political situation in the country changed dramatically, and Helanen lost his job as well as his influential social station. He began to write detective fiction, and between 1946 and 1952 published seven novels (one had already been published in 1941). The novels protagonist is Kaarlo Rauta, a lawyer who acts as a private investigator. This doctoral dissertation analyzes the Rauta series from three different points of view. It investigates the extent to which the author s life and his strong political background appears in the series. The study also situates the series within Finnish society during and after the war. Finally, the study examines the Rauta series in terms of the genre conventions of detective fiction, that is, the study compares the Rauta series with other Finnish crime fiction and international crime fiction written during the 1940s. The Iron and The Cross Spider uses the term citizenship education when analyzing how Helanen implicitly continued his political teaching when writing crime fiction. The series includes a didactic register, which instructs the middle class in appropriate behaviour and manners, and the social roles entailed by gender. A special area of focus in this didacticism are norms of correct masculinity and femininity. The study devotes specific attention to the status of character in the series. The masculine detective and his beautiful wife are prominent, as is the fictive community and the tensions that criss-cross it. After the war, the Rauta series takes on a positive tone. Men can earn their place in society by fighting at the front, and after the war a homosocial bond exists between all the former soldiers. Women are shut out of the war experience. The detective hero has served in the war, but he is physically and psychologically untouched by it. The community is threatened by artists and immoral bohemians, but not the working class. Artists have affairs outside of marriage and abnormal sexual habits. The members of the upper class are also described as immoral in the series. Sadistic sexuality is often characteristic of the criminals, who are mostly femme fatales in the fashion of hard-boiled detective stories and film noir. Also, strong feelings have a negative connotation in the series, and showing them is forbidden behaviour. Men become criminals when they are insufficiently masculine or when they have not carried out their duty by fighting in the war. Helanen portrayed the communists, his political opponents from the 1930s, as criminals in his post-war series, but they were not openly represented as Russians or communists. Instead, Helanen used the cross spider as their symbol, a symbol which the readers of the time would recognize.

Close Encounters of the Continuum: Speaking (to), Performing and Experiencing Gender In Janet Cardiff’s Whispering Room

This 'project' investigates Janet Cardiff's Whispering Room. It examines how Cardiff deconstructs the privileging of the visual over all other corporeal senses in her work, the Whispering Room. Using sound as a fulcrum, Cardiff explores the links between subjects, collective narratives, memories, experiences and performances. Janet Cardiff destabilizes time and space and fractures the continuum through the use of sound. My 'project' celebrates sound as a transgressive medium — sound not as a gendered medium but as a vehicle in which to speak (to) gender. It explores how sound can destabilize notions of perception and reception and question art and museal practices. In the process this 'project' reveals the complexity of interpreting and representing art as an object. My aim is to reflect the very intertextual and expressionist collage that Cardiff has created in Whispering Room in my own text. Cardiff solicits the viewer's intimacy and participation. Whispering Room is a physical yet metonymic space in which Cardiff creates a place for performatvity, experience, memory, desire and speech, thus she opens up a space for the utterance and performance of the viewer. Viewers construct and create meaning/s for themselves within this mnemonic space by digging up their own memories, desires and reveries. The strength of Cardiff's work is that it relies on a viewer to perform, a body to trigger the pseudo-spectacle and a voice to interrupt the whispers. One might ask of Whispering Room where the illusionistic space begins and where the physical space ends. This 'project' investigates how in Whispering Room there is no one experience but many experiences.

A PCR assay for gender assignment in dugong (Dugong dugon) and West Indian manatee (Trichechus manatus)

Gender assignment for some aquatic mammals in the field is difficult. Molecular sexing from tissue biopsies is possible as males are heterogametic. Here we describe a multiplex PCR assay that amplifies the male specific SRY gene and differentiates ZFX and ZFY gametologues in two sirenian species, dugong (Dugong dugon) and West Indian manatee (Trichechus manatus). The assay was validated with animals of known gender and proved accurate and robust to experimental failure.

Women in leadership: An analysis of the gender pay gap in ASX-listed firms

This study provides evidence that after several decades of fighting for equal pay for equal work, an unexplained gender pay gap remains amongst senior executives in ASX-listed firms. After controlling for a large suite of personal, occupational and firm observables, we find female senior executives receive, on average, 22.58 percent less in base salary for the period 2002–2013. When executives are awarded performance-based pay, females receive on average 16.47 percent less in cash bonus and 18.21 percent less in long-term incentives than males. The results are robust to using firm fixed effects and propensity-score matching. Blinder–Oaxaca decomposition results show that the mean pay gap cannot be attributed to gender differences in attributes, including job titles. Instead, the results point to differences in returns on firm-specific variables, in particular firm risk.