Association of variants in MMEL1 and CTLA4 with rheumatoid arthritis in the Han Chinese population

Background: The genome-wide association study era has made great progress in identifying susceptibility genes and genetic loci for rheumatoid arthritis (RA) in populations of White European ancestry. However, few studies have tried to dissect disease aetiopathogenesis in other ethnic populations. Objective: To investigate these associations in the Han Chinese population. Methods: Haplotypes from the HapMap database Chinese population were used to select tag-single-nucleotide polymorphisms (SNPs) (r2 =0.8) across 19 distinct RA genomic regions. A two phase case-control association study was performed, with 169 SNPs genotyped in phase I (n=571 cases, n=880 controls), and 64 SNPs achieving p<0.2 in the first phase being genotyped in phase II (n=464 cases, n=822 controls). Association statistics were calculated using permutation tests both unadjusted and adjusted for the number of markers studied. Results: Robust association was detected for MMEL1 and CTLA4 , and modest association was identified for another six loci: PADI4 , STAT4 , PRDM1 , CDK6 , TRAF1-C5 and KIF5A-PIP4K2C. All three markers genotyped in MMEL1 demonstrated association, with peak signal for rs3890745 (p=2.6×10 -5unadjusted, p=0.003 adjusted, OR=0.79). For CTLA4 , significance was detected for three of five variants showing association, with peak association for marker rs12992492 (p=4.3×10-5 unadjusted, p=0.0021 adjusted, OR=0.77). Lack of association of common variants in PTPN22 with RA in Han Chinese was confirmed. Conclusion: This study identifies MMEL1 and CTLA4 as RA susceptibility genes, provides suggestive evidence of association for a further six loci in the Han Chinese population and confirms lack of PTPN22 association in Asian populations. It also confirms the value of multiethnic population studies to help dissect disease aetiopathogenesis.

Association of STAT3 and TNFRSF1A with ankylosing spondylitis in Han Chinese

Objectives: Recent association studies by the Australo-Anglo-American Spondyloarthritis Consortium (TASC) in Caucasian European populations from Australia, North America and the UK have identified a number of genes as being associated with ankylosing spondylitis (AS). A candidate gene study in a Han Chinese population was performed based on these findings to identify associated genes in this population. Methods: A case-control study was performed in a Han Chinese population of patients with AS (n=775) and controls (n=1587) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The cases and controls were genotyped for 115 single nucleotide polymorphisms (SNPs) tagging IL23R, ERAP1, STAT3, JAK2, TNFRSF1A and TRADD, as well as other confirmation SNPs from the TASC study, using the Sequenom iPlex and the ABI OpenArray platforms. Statistical analysis of genotyped SNPs was performed using the Cochran - Armitage test for trend and meta-analysis was performed using METAL. SNPs in AS-associated genes in this study were then imputed using MaCH, and association with AS tested by logistic regression. Results: SNPs in TNFRSF1A (rs4149577, p=8.2×10-4), STAT3 (rs2293152, p=0.0015; rs1053005, p=0.017) and ERAP1 (rs27038, p=0.0091; rs27037, p=0.0092) were significantly associated with AS in Han Chinese. Association was also observed between AS and the intergenic region 2p15 (rs10865331, p=0.023). The lack of association between AS and IL23R in Han Chinese was confirmed (all SNPs p>0.1). Conclusions: The study results demonstrate for the first time that genetic polymorphisms in STAT3, TNFRSF1A and 2p15 are associated with AS in Han Chinese, suggesting common pathogenic mechanisms for the disease in Chinese and Caucasian European populations. Furthermore, previous findings demonstrating that ERAP1, but not IL23R, is associated with AS in Chinese patients were confirmed.

High-throughput sequencing of IL23R reveals a low-frequency, nonsynonymous single-nucleotide polymorphism that is associated with ankylosing spondylitis in a Han Chinese population

Objective Ankylosing spondylitis (AS) is a highly heritable common inflammatory arthritis that targets the spine and sacroiliac joints of the pelvis, causing pain and stiffness and leading eventually to joint fusion. Although previous studies have shown a strong association of IL23R with AS in white Europeans, similar studies in East Asian populations have shown no association with common variants of IL23R, suggesting either that IL23R variants have no role or that rare genetic variants contribute. The present study was undertaken to screen IL23R to identify rare variants associated with AS in Han Chinese. Methods A 170-kb region containing IL23R and its flanking regions was sequenced in 50 patients with AS and 50 ethnically matched healthy control subjects from a Han Chinese population. In addition, the 30-kb region of peak association in white Europeans was sequenced in 650 patients with AS and 1,300 healthy controls. Validation genotyping was undertaken in 846 patients with AS and 1,308 healthy controls. Results We identified 1,047 variants, of which 729 were not found in the dbSNP genomic build 130. Several potentially functional rare variants in IL23R were identified, including one nonsynonomous single-nucleotide polymorphism (nsSNP), Gly149Arg (position 67421184 GA on chromosome 1). Validation genotyping showed that the Gly149Arg variant was associated with AS (odds ratio 0.61, P = 0.0054). Conclusion This is the first study to implicate rare IL23R variants in the pathogenesis of AS. The results identified a low-frequency nsSNP with predicted loss-of-function effects that was protectively associated with AS in Han Chinese, suggesting that decreased function of the interleukin-23 (IL-23) receptor protects against AS. These findings further support the notion that IL-23 signaling has an important role in the pathogenesis of AS.

Association of ERAP1, but not IL23R, with ankylosing spondylitis in a Han Chinese population

Objective The results of a recent genome-wide association study have shown that ERAP1 and IL23R are associated with ankylosing spondylitis (AS) in Caucasian populations from North America and the UK. Based on these findings, we undertook the current study to investigate whether single-nucleotide polymorphisms (SNPs) covering the genes ERAP1 and IL23R are associated with AS in a Han Chinese population. Methods A case-control study was performed in Han Chinese patients with AS (n = 527) and controls (n = 945) from Shanghai and Nanjing. All patients met the modified New York criteria for AS. The Sequenom iPlex platform was used to genotype cases and controls for 21 tag SNPs covering IL23R and 38 tag SNPs covering ERAP1. Statistical analysis was performed using the Cochran-Armitage test for trend. Results Multiple SNPs in ERAP1 were significantly associated with AS (for rs27980, P = 0.0048; for rs7711564, P = 0.0081). However, no association was observed between IL23R and AS (for all SNPs, P > 0.1). The nonsynonymous SNP in IL23R, rs11209026, widely thought to be the primary AS-associated SNP in IL23R in Europeans, was found not to be polymorphic in Chinese. Conclusion Our results demonstrate that genetic polymorphisms in ERAP1 are associated with AS in Han Chinese, suggesting a common pathogenic mechanism for the disease in Chinese and Caucasian populations, and that IL23R is not associated with AS in Chinese, indicating a difference in the mechanism of disease pathogenesis between Chinese and Caucasian populations. This may result from the fact that rs11209026, the nonsynonymous SNP in IL23R, is not polymorphic in Chinese patients, providing further evidence that rs11209026 is the key polymorphism associated with AS (and likely inflammatory bowel disease and psoriasis) in this gene.

Novel risk loci for rheumatoid arthritis in Han Chinese and congruence with risk variants in Europeans

Objective To investigate differences in genetic risk factors for rheumatoid arthritis (RA) in Han Chinese as compared with Europeans. Methods A genome-wide association study was conducted in China with 952 patients and 943 controls, and 32 variants were followed up in 2,132 patients and 2,553 controls. A transpopulation meta-analysis with results from a large European RA study was also performed to compare the genetic architecture across the 2 ethnic remote populations. Results Three non-major histocompatibility complex (non-MHC) loci were identified at the genome-wide significance level, the effect sizes of which were larger in anti-citrullinated protein antibody (ACPA)-positive patients than in ACPA-negative patients. These included 2 novel variants, rs12617656, located in an intron of DPP4 (odds ratio [OR] 1.56, P = 1.6 × 10 -21), and rs12379034, located in the coding region of CDK5RAP2 (OR 1.49, P = 1.1 × 10-16), as well as a variant at the known CCR6 locus, rs1854853 (OR 0.71, P = 6.5 × 10-15). The analysis of ACPA-positive patients versus ACPA-negative patients revealed that rs12617656 at the DPP4 locus showed a strong interaction effect with ACPAs (P = 5.3 × 10-18), and such an interaction was also observed for rs7748270 at the MHC locus (P = 5.9 × 10-8). The transpopulation meta-analysis showed genome-wide overlap and enrichment in association signals across the 2 populations, as confirmed by prediction analysis. Conclusion This study has expanded the list of alleles that confer risk of RA, provided new insight into the pathogenesis of RA, and added empirical evidence to the emerging polygenic nature of complex trait variation driven by common genetic variants. Copyright © 2014 by the American College of Rheumatology.

Introduction to "Learning Chinese as a Heritage Language : An Australia Perspective"

The book grapples with the complex entanglement of identity construction, language choice, cultural heritage, and social orders. Specifically, the book investigates how Chinese Australians negotiate their Chineseness and capitalise on resources through learning Chinese as a heritage language in Australia and beyond. Though the book is concerned with Chinese Australians, knowledge built and lessons learned can provide insight into other multicultural settings where people of Chinese descent are becoming increasingly prominent in representing the cultural and linguistic diversity of the society, and more recently, in contributing to the economic dynamics of the society. In addition, the focus on the potholes and distractions as well as the benefits and gains of heritage language learning is not restricted to Chinese diaspora, but relevant to ethnic minority individuals and communities elsewhere.

Using the factors that have a positive impact on the retention of low socioeconomic students to prepare accelerated enrolled nurses for the science units of a nursing degree : a practice report

At a campus in a low socioeconomic (SES) area, our University allows enrolled nurses entry into the second year of a Bachelor of Nursing, but attrition is high. Using the factors, described by Yorke and Thomas (2003) to have a positive impact on the attrition of low SES students, we developed strategies to prepare the enrolled nurses for the pharmacology and bioscience units of a nursing degree with the aim of reducing their attrition. As a strategy, the introduction of review lectures of anatomy, physiology and microbiology, was associated with significantly reduced attrition rates. The subsequent introduction of a formative website activity of some basic concepts in bioscience and pharmacology, and a workshop addressing study skills and online resources, were associated with a further reduction in attrition rates of enrolled nursing students in a Bachelor of Nursing.

Using collaboration and technology to enhance Vietnamese students' English language writing skills

This action research study investigated face-to-face and wiki technology collaboration to enhance students' English writing skills in a second language (L2) class in Vietnam. The thesis is underpinned by socio-cultural theory and argues that collaborative learning using wikis led to an enhancement in L2 writing skills. The findings show that collaborating via wikis challenged traditional L2 writing pedagogy in the following ways: increased student autonomy; understanding formative feedback; and awareness of process writing, genre and audiences. This study contributes practical knowledge about affordances and constraints of collaborative writing using wikis in Vietnam and other countries where traditional pedagogies are prevalent.

Exploring female university students' beliefs about binge eating

Binge eating (BE) among female university students is rising in prevalence and few studies have considered the role of social cognitive processes in decisions to engage in BE. This study adopted a theory of planned behavior (TPB) belief-based approach to examine the beliefs that underpin female university students' intentions to BE. Participants (N = 250) completed self-report questionnaires assessing BE intentions and the TPB behavioral (advantages and disadvantages of BE), normative (important others approving/disapproving of BE), and control (barriers toward and motivators for BE) belief measures. For analyses, participants were grouped based on a median split of the overall intention score into those with higher and lower intentions to binge eat. Differences in the TPB beliefs about BE between these two groups were then assessed. Female students with higher intentions to binge eat differed significantly in their endorsement of the likely beliefs related to BE, compared to female students with lower intentions to binge eat. The results suggest that interventions to decrease BE in the female student population should reduce the associated advantages (e.g., stress relief and feelings of comfort), enhance perceptions of disapproval for BE from important others (e.g., partner and friends), provide education about the health implications to strengthen the perceived barriers discouraging BE, and suggest healthy alternatives to overcome the factors (e.g., being alone and boredom) motivating BE

Experiences of countertransference: Reports of clinical psychology students

While historically linked with psychoanalysis, countertransference is recognised as an important component of the experience of therapists, regardless of the therapeutic modality. This study considers the implications of this for the training of psychologists. Fifty-five clinical psychology trainees from four university training programmes completed an anonymous questionnaire that collected written reports of countertransference experiences, ratings of confidence in managing these responses, and supervision in this regard. The reports were analysed using a process of thematic analysis. Several themes emerged including a desire to protect or rescue clients, feeling criticised or controlled by clients, feeling helpless, and feeling disengaged. Trainees varied in their reports of awareness of countertransference and the regularity of supervision in this regard. The majority reported a lack of confidence in managing their responses, and all reported interest in learning about countertransference. The implications for reflective practice in postgraduate psychology training are discussed.

Impact of temperature on mortality in three major Chinese cities

To study the relation between temperature and mortality by estimating the temperature-related mortality in Beijing, Shanghai, and Guangzhou. METHODS: Data of daily mortality, weather and air pollution in the three cities were collected. A distributed lag nonlinear model was established and used in analyzing the effects of temperature on mortality. Current and future net temperature-related mortality was estimated. RESULTS: The association between temperature and mortality was J-shaped, with an increased death risk of both hot and cold temperature in these cities. The effects of cold temperature on health lasted longer than those of hot temperature. The projected temperature-related mortality increased with the decreased cold-related mortality. The mortality was higher in Guangzhou than in Beijing and Shanghai. CONCLUSION: The impact of temperature on health varies in the 3 cities of China, which may have implications for climate policy making in China.

Grant application: QUT Learning and Teaching scheme 2012 Cracking the Code - A checklist to complement CRAs for first year Justice students.

Widening participation brings with it increasing diversity, increased variation in the level of academic preparedness (Clarke, 2011; Nelson, Clarke, & Kift 2010). Cultural capital coupled with negotiating the academic culture creates an environment based on many assumptions about academic writing and university culture. Variations in staff and student expectations relating to the teaching and learning experience is captured in a range of national and institutional data (AUSSE, CEQ, LEX). Nationally, AUSSE data (2009) indicates that communication, writing, speaking and analytic skills, staff expectations are quite a bit higher than students. The research team noted a recognisable shift in the changing cohort of students and their understanding and engagement with feedback and CRAs, as well as variations in teaching staff and student expectations. The current reality of tutor and student roles is that: - Students self select when/how they access lectures and tutorials. - Shorter tutorial times result in reduced opportunity to develop rapport with students. - CRAs are not always used consistently by staff (different marking styles and levels of feedback). - Marking is not always undertaken by the student’s tutor/lecturer. - Student support services might be recommended to students once a poor grade has been given. Students can perceive this as remedial and a further sense of failure. - CRA sheet has a mark /grade attached to it. Stigma attached to low mark. Hard to focus on the CRA feedback with a poor mark etched next to it. - Limited opportunities for sessionals to access professional development to assist with engaging students and feedback. - FYE resources exist, however academic time is a factor in exploring and embedding these resources. Feedback is another area with differing expectations and understandings. Sadler (2009) contends that students are not equipped to decode the statements properly. For students to be able to apply feedback, they need to understand the meaning of the feedback statement. They also need to identify, the particular aspects of their work that need attention. The proposed Checklist/guide would be one page and submitted with each assessment piece thereby providing an interface to engage students and tutors in managing first year understandings and expectations around CRAs, feedback, and academic practice.

Motivation and behavioural patterns of students accessing a peer-facilitated support for learning program

This paper describes the development and use of personas, a Human Computer Interaction (HCI) research methodology, within the STIMulate peer learning program, in order to better understand student behaviour patterns and motivations. STIMulate is a support for learning program at the Queensland University of Technology (QUT) in Brisbane, Australia. The program provides assistance in mathematics, science and information technology (IT) for course work students. A STIMulate space is provided for students to study and obtain one-on-one assistance from Peer Learning Facilitators (PLFs), who are experienced students that have excelled in relevant subject areas. This paper describes personas – archetypal users - that represent the motivations and behavioural patterns of students that utilise STIMulate (particularly the IT stream). The personas were developed based on interviews with PLFs, and subsequently validated by a PLF focus group. Seven different personas were developed. The personas enable us to better understand the characteristics of the students utilising the STIMulate program. The research provides a clearer picture of visiting student motivations and behavioural patterns. This has helped us identify gaps in the services provided, and be more aware of our assumptions about students. The personas have been deployed in PLF training programs, to help PLFs provide a better service to the students. The research findings suggest further study on the resonances between some students and PLFs, which we would like to better elicit.