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Now showing items 17 - 32 of 84

  • Ultrasound detected synovial change and pain response following intra-articular injection of corticosteroid and a placebo in symptomatic osteoarthritic knees: a pilot study

    Hall, Michelle   Doherty, Sally   Courtney, Philip   Latief, Khalid   Zhang, Weiya   Doherty, Michael  

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  • The changing epidemiology of gout

    Roddy, Edward   Zhang, Weiya   Doherty, Michael  

    Gout is one of the most common inflammatory arthritides, which is considered to be a true crystal deposition disorder caused by the formation of monosodium urate crystals in and around joints. A number of epidemiological studies from a diverse range of countries suggest that gout has increased in prevalence and incidence in recent years and that the clinical pattern of gout is becoming more complex. In particular, the greatest increase has been observed in primary gout in older men. Robust epidemiological studies have established risk factors for gout including genetic factors, excess alcohol consumption, purine-rich diet, the metabolic syndrome (obesity hypertension, hyperlipidemia and insulin resistance), use of diuretics and chronic renal failure. Trends in alcohol use, diet, obesity and the metabolic syndrome in the general population might explain changes in the prevalence and incidence of gout in the community. Osteoarthritis, which is thought to predispose patients to monosodium urate crystal deposition in their joints, is becoming more prevalent as a consequence of increased longevity. In hospital settings, widespread diuretic use, increasing prevalence of end-stage renal failure and the success of organ transplant programmes have led to an increase in clinical complexity. Suboptimal management of gout is likely to have contributed to the rise in the prevalence of clinically overt, symptomatic, chronic gout.
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  • Simple Kohler Homogenizers for Image-forming Solar Concentrators

    Winston, Roland   Zhang, Weiya  

    We demonstrate that the Kohler illumination technique can be applied to the image-forming solar concentrators to solve the problem of "hot" spot and to generate the square irradiance pattern. The Kohler homogenizer can be simply a single aspheric lens optimized following a few guidelines. Two examples are given including a Fresnel lens based concentrator and a two-mirror aplanatic system.
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  • Predictors of change in bodily pain in early rheumatoid arthritis: An inception cohort study

    Zhang, Weiya   Mansell, Josephine S.   Kiely, Patrick D. W.   Young, Adam   Walsh, David A.  

    Objective To investigate possible predictors for lack of pain improvement after 1 year of treatment for early rheumatoid arthritis (RA). Methods The Early Rheumatoid Arthritis Network (ERAN) database was used for analysis of baseline and 1-year pain data. The ERAN is a hospital-based inception cohort of 1,189 people. Short Form 36 questionnaire bodily pain scores were used to calculate change in pain at 1 year as the outcome. The proportion of the Disease Activity Score in 28 joints (DAS28) attributable to patient-reported components (joint tenderness and visual analog scale score; DAS28-P) at baseline was derived as a predictor. Predictors of less improvement in pain were investigated using adjusted odds ratios (ORadj) generated by logistic regression, adjusting for 14 additional clinical and demographic covariates. Results Greater pain at baseline was associated with sex, high DAS28, worse mental health, and smoking. Most patients with early RA reported incomplete improvement in bodily pain after 1 year. The DAS28-P index did not significantly change in the patients whose disease remained active. Less improvement in pain was predicted by female sex (ORadj 3.41, 95% confidence interval [95% CI] 1.358.64) and a high DAS28-P index at baseline (ORadj for tertiles 2.09, 95% CI 1.243.55). Other conventional RA risk factors did not predict pain changes. Conclusion The factors most likely to predict less improvement in pain in early RA are female sex and a high DAS28-P index. A high DAS28-P index may reflect greater contributions of noninflammatory factors, such as central sensitization, to pain. Strategies in addition to inflammatory disease suppression may be required to adequately treat pain.
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  • Familial risk of systemic sclerosis and co-aggregation of autoimmune diseases in affected families

    Kuo, Chang-Fu   Luo, Shue-Fen   Yu, Kuang-Hui   See, Lai-Chu   Zhang, Weiya   Doherty, Michael  

    Background: Systemic sclerosis (SSc) is a rare and devastating disease affecting skin and internal organs. Familial aggregation of SSc and co-aggregation with other autoimmune diseases is rarely reported. Methods: We identified 23,658,577 beneficiaries registered with the National Health Insurance database in 2010, 1891 of whom had SSc. We identified 21,009,551 parent-child relationships and 17,168,340 full sibling pairs. The familial risks of SSc and other autoimmune diseases and familial transmission were estimated. Results: The prevalence of SSc in the general population was 0.008 %. There are 3801 individuals had at least one first-degree relative with SSc, among them 3 people had SSc which was equivalent to a prevalence of 0.08 %. The adjusted relative risk (RR) (95 % CI) for SSc was 81.21 (11.40-579.72) for siblings of SSc patients. The familial transmission (genetic plus shared environmental contribution to total phenotypic variance of SSc) was 0.72. However, 84.1 % of patients were expected to be sporadic cases. The RR (95 % CI) in first-degree relatives of SSc patients was 2.64 (1.46-4.75) for rheumatoid arthritis, 6.51 (4.05-10.46) for systemic lupus erythematosus, 2.77 (1.04-7.35) for Sjogren's syndrome, 8.05 (2.03-31.92) for idiopathic inflammatory myositis, and 1.52 (1.15-2.01) for psoriasis. Conclusions: The risks of SSc and other autoimmune diseases are increased in relatives of people with SSc, and family factors explain over two-thirds of the phenotypic variance of the disease. These findings may be useful in counselling families of patients with SSc and for further genetic studies.
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  • MEKK3 coordinates with FBW7 to regulate WDR62 stability and neurogenesis

    Xu, Dan   Yao, Minghui   Wang, Yaqing   Yuan, Ling   Hoeck, Joerg D.   Yu, Jingwen   Liu, Liang   Yeap, Yvonne Y. C.   Zhang, Weiya   Zhang, Feng   Feng, Yinghang   Ma, Tiantian   Wang, Yujie   Ng, Dominic C. H.   Niu, Xiaoyin   Su, Bing   Behrens, Axel   Xu, Zhiheng  

    Mutations of WD repeat domain 62 (WDR62) lead to autosomal recessive primary microcephaly (MCPH), and down-regulation of WDR62 expression causes the loss of neural progenitor cells (NPCs). However, how WDR62 is regulated and hence controls neurogenesis and brain size remains elusive. Here, we demonstrate that mitogen-activated protein kinase kinase kinase 3 (MEKK3) forms a complex with WDR62 to promote c-Jun N-terminal kinase (JNK) signaling synergistically in the control of neurogenesis. The deletion of Mekk3, Wdr62, or Jnk1 resulted in phenocopied defects, including premature NPC differentiation. We further showed that WDR62 protein is positively regulated by MEKK3 and JNK1 in the developing brain and that the defects of wdr62 deficiency can be rescued by the transgenic expression of JNK1. Meanwhile, WDR62 is also negatively regulated by T1053 phosphorylation, leading to the recruitment of F-box and WD repeat domain-containing protein 7 (FBW7) and proteasomal degradation. Our findings demonstrate that the coordinated reciprocal and bidirectional regulation among MEKK3, FBW7, WDR62, and JNK1, is required for fine-tuned JNK signaling for the control of balanced NPC self-renewal and differentiation during cortical development.
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  • Design principles of the first 4x fixed solar concentrator

    Winston, Roland   Zhang, Weiya  

    We discuss the theoretical limits of concentration for stationary solar concentrators allowed by the law of thermodynamics. The principles to design systems that approach the theoretical limits are then presented followed by a few examples; including the first 4x fixed solar concentrator.
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  • Development and validation of self-reported line drawings for assessment of knee malalignment and foot rotation: a cross-sectional comparative study.

    Ingham, Sarah L   Moody, Amanda   Abhishek, Abhishek   Doherty, Sally A   Zhang, Weiya   Doherty, Michael  

    BACKGROUND: For large scale epidemiological studies clinical assessments and radiographs can be impractical and expensive to apply to more than just a sample of the population examined. The study objectives were to develop and validate two novel instruments for self-reported knee malalignment and foot rotation suitable for use in questionnaire studies of knee pain and osteoarthritis.METHODS: Two sets of line drawings were developed using similar methodology. Each instrument consisted of an explanatory question followed by a set of drawings showing straight alignment, then two each at 7.5 degrees angulation and 15 degrees angulation in the varus/valgus (knee) and inward/outward (foot) directions. Forty one participants undertaking a community study completed the instruments on two occasions. Participants were assessed once by a blinded expert clinical observer with demonstrated excellent reproducibility. Validity was assessed by sensitivity, specificity and likelihood ratio (LR) using the observer as the reference standard. Reliability was assessed using weighted kappa (kappa). Knee malalignment was measured on 400 knee radiographs. General linear model was used to assess for the presence of a linear increase in knee alignment angle (measured medially) from self-reported severe varus to mild varus, straight, mild valgus and severe valgus deformity.RESULTS: Observer reproducibility (kappa) was 0.89 and 0.81 for the knee malalignment and foot rotation instruments respectively. Self-reported participant reproducibility was also good for the knee (kappa 0.73) and foot (kappa 0.87) instruments. Validity was excellent for the knee malalignment instrument, with a sensitivity of 0.74 (95%CI 0.54, 0.93) and specificity of 0.97 (95%CI 0.94, 1.00). Similarly the foot rotation instrument was also found to have high sensitivity (0.92, 95%CI 0.83, 1.01) and specificity (0.96, 95%CI 0.93, 1.00). The knee alignment angle increased progressively from self reported severe varus to mild varus, straight, mild valgus and severe valgus knee malalignment (ptrend <0.001).CONCLUSIONS: The two novel instruments appear to provide a valid and reliable assessment of self-reported knee malalignment and foot rotation, and may have a practical use in epidemiological studies.
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  • Self-reported adult footwear and the risks of lower limb osteoarthritis: the GOAL case control study.

    McWilliams, Daniel F   Muthuri, Stella   Muir, Kenneth R   Maciewicz, Rose A   Zhang, Weiya   Doherty, Michael  

    BACKGROUND: Biomechanical factors may play a role in osteoarthritis (OA) development and progression. Previous biomechanical studies have indicated that types of footwear may modulate forces across the knee joint, and high heeled womens' shoes in particular are hypothesised to be detrimental to lower limb joint health. This analysis of data from a case control study investigated persistent users of different adult footwear for risks of knee and hip OA. Our underlying hypotheses were that high heeled, narrow heeled, and hard soled shoe types were putative risk factors for lower limb OA.; METHODS: Data on footwear were initially obtained from participants during the Genetics of Osteoarthritis and Lifestyle (GOAL) hospital-based, case control study using standardised interview-delivered questionnaires. An additional questionnaire was later sent to GOAL study participants to verify findings and to further investigate specific shoe use per decade of life. Persistent users of footwear types (high or narrow heel; sole thickness or hardness) were identified from early adulthood. Participants were grouped into single sex knee OA, hip OA or control groups. Adjusted odds ratios (aOR) and 95% confidence interval (CI) were calculated.; RESULTS: Univariate analysis of persistent users of women's high heeled and narrow heeled shoes during early adulthood showed negative associations with knee OA and hip OA. After logistic regression, persistent narrow heel users were associated with less risk of OA (knee OA aOR 0.59, 95% CI 0.35 - 1.00 and hip aOR: 0.50, 95% CI 0.30 - 0.85), and other analyses were not statistically significant. Further analysis suggested that women with hip OA may have stopped wearing high and narrow heeled footwear to attenuate hip pain in early adulthood. Consistent associations between shoe soles and OA were not found.; CONCLUSIONS: In general, persistent users of high and narrow heeled shoes during early adulthood had a negative association with knee or hip OA. This does not necessarily imply a causal relationship, as changing footwear during early adulthood to modulate index joint pain may provide a possible explanation. Despite the findings of previous biomechanical studies of high heels, we did not find a positive association between women's shoes and lower limb osteoarthritis.=20
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  • Do β-adrenoreceptor blocking drugs associate with reduced risk of symptomatic osteoarthritis and total joint replacement in the general population? A primary care-based, prospective cohort study using the Clinical Practice Research Datalink

    Nakafero, Georgina   Grainge, Matthew   Valdes, Ana   Townsend, Nick   Mallen, Christian   Zhang, Weiya   Doherty, Michael   Mamas, Mamas A   Abhishek, Abhishek  

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  • Optical enhancement for luminescent solar concentrators

    Wang, Chunhua   Winston, Roland   Zhang, Weiya   Pelka, Dave   Carter, Sue  

    A luminescent solar concentrator (LSC) generally is a sheet of highly transparent materials embedded with luminescent materials. Incident sunlight is absorbed by the luminescent materials; and then emitted through down conversion process at longer wavelengths. A large portion of the emitted light is trapped in the sheet and travels to the edges where photovoltaic solar cells are attached. In this study; we investigate the optical enhancement methods for LSCs with different sizes mainly by using optical gel and white diffuser. The largest tested LSC is up to 1.2m in length and with geometrical gain 64. This is; as we know; the largest reported size. It yields electrical gain 3.9 by optical enhancements. And the optical efficiency is still as large as 10%. The study shows that the enhancement by white diffuser is more sensitive to the size of the LSCs than that of the optical gel. Such enhancement drops with the increase of the sizes of LSC; but tends to plateau at certain size.
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  • Familial Aggregation of Systemic Lupus Erythematosus and Coaggregation of Autoimmune Diseases in Affected Families

    Kuo, Chang-Fu   Grainge, Matthew J.   Valdes, Ana M.   See, Lai-Chu   Luo, Shue-Fen   Yu, Kuang-Hui   Zhang, Weiya   Doherty, Michael  

    IMPORTANCE Relatives of patients with systemic lupus erythematosus (SLE) appear to be at higher risk of SLE and other autoimmune diseases, but estimates of individual familial risks are largely unavailable or unreliable. Furthermore, relative contributions of genetic, shared, and unshared environmental factors to SLE susceptibility remain unclear. OBJECTIVE To examine familial aggregation and heritability of SLE and the relative risks (RRs) of other autoimmune diseases in relatives of patients with SLE. DESIGN, SETTING, AND PARTICIPANTS A population-based family study using the Taiwan National Health Insurance Research Database was conducted. Participants included all individuals (N =3D 23 658 577) registered with that database in 2010; of these, 18 283 had SLE. We identified 21 009 551 parent-child relationships, 17 168 340 full sibling pairs, and 342 066 twin pairs. Diagnoses of SLE were ascertained from March 1, 1995, to December 31, 2010, and analysis was conducted between March 1 and August 15, 2014. MAIN OUTCOMES AND MEASURES The prevalence and RRs of SLE and other autoimmune diseases in relatives and spouses of patients with SLE as well as the relative contributions of heritability, shared, and nonshared environmental factors to SLE susceptibility. RESULTS Among the more than 23 million participants, the RRs (95% CIs) for SLE were 315.94 (210.66-473.82) for twins of the patients, 23.68 (20.13-27.84) for siblings, 11.44 (9.74-13.43) for parents, 14.42 (12.45-16.70) for offspring, and 4.44 (2.38-8.30) for spouses without genetic similarity. The accountability for phenotypic variance of SLE was 43.9% for heritability, 25.8% for shared environmental factors, and 30.3% for nonshared environmental factors. The RRs (95% CIs) in individuals with a first-degree relative with SLE were 5.87 (4.89-7.05) for primary Sjgren syndrome, 5.40 (3.37-8.65) for systemic sclerosis, 2.95 (2.04-4.26) formyasthenia gravis, 2.77 (1.45-5.32) for idiopathic inflammatorymyositis, 2.66 (2.28-3.11) for rheumatoid arthritis, 2.58 (1.16-5.72) for multiple sclerosis, 1.68 (1.22-2.32) for type 1 diabetes mellitus, 1.39 (0.66-2.91) for inflammatory bowel diseases, and 0.86 (0.43-1.71) for vasculitis. CONCLUSIONS AND RELEVANCE The individual risks of SLE and other autoimmune diseases were increased in families that included patients with SLE. The heritability of SLE was estimated to be 43.9%. These data should be considered when counseling families with affected members.
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  • Erosive and osteoarthritic structural progression in early rheumatoid arthritis

    McWilliams, Daniel F.   Marshall, Michelle   Jayakumar, Keeranur   Doherty, Sally   Doherty, Michael   Zhang, Weiya   Kiely, Patrick D. W.   Young, Adam   Walsh, David A.  

    Objectives. To investigate factors associated with joint damage in early RA, and how comorbid OA might influence patient assessment and outcomes. Methods. Baseline radiographs of hands and feet from 512 participants in the Early RA Network cohort, and after 3 (+/-1) years, 166 of those participants yielded complete scores for RA [erosions, joint space narrowing (JSN)] and OA [JSN, osteophytes (OST)] using validated atlases. DAS28-P is the proportion of DAS28 attributed to patient-reported factors. Adjusted odds ratios were calculated using logistic regression. Results. OA was common at baseline in early RA (40% hand and 48% foot) and associated with RA radiographic score. Higher baseline RA scores were associated with increasing age and ESR, and lower DAS28-P. OST scores were associated with higher age. DAS28 and patient-reported outcomes improved, whereas RA and OA radiographic scores deteriorated by follow-up. Erosive progression was predicted by higher baseline erosions, female gender, better mental health and lower DAS28-P. Hand OST progression was predicted by baseline OST scores. Inflammatory disease activity was associated with erosive, but not with OA progression. Baseline hand OA predicted worse physical function at follow-up, but radiographic progression did not explain changes in patient-reported outcomes. Conclusion. OA is a common comorbidity that might confound radiographic and clinical assessment, but does not fully explain erosive progression or patient-reported outcomes in early RA. Early RA management should address psychosocial factors and comorbidities, as well as joint inflammation.
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  • The GDF5 rs143383 polymorphism is associated with osteoarthritis of the knee with genome-wide statistical significance RID G-9836-2011

    Valdes, Ana M.   Evangelou, Evangelos   Kerkhof, Hanneke J. M.   Tamm, Agu   Doherty, Sally A.   Kisand, Kalle   Tamm, Ann   Kerna, Irina   Uitterlinden, Andre   Hofman, Albert   Rivadeneira, Fernando   Cooper, Cyrus   Dennison, Elaine M.   Zhang, Weiya   Muir, Kenneth R.   Ioannidis, John P. A.   Wheeler, Margaret   Maciewicz, Rose A.   van Meurs, Joyce B.   Arden, Nigel K.   Spector, Tim D.   Doherty, Michael  

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  • Associations between vitamin D receptor gene polymorphisms and osteoarthritis: an updated meta-analysis

    Zhu, Zhao-Hua   Jin, Xing-zhong   Zhang, Weiya   Chen, Mao   Ye, Dong-Qing   Zhai, Yu   Dong, Fu-Long   Shen, Cai-Liang   Ding, Changhai  

    Objective. Vitamin D receptor (VDR) gene polymorphisms may be associated with the risk of OA, however, evidence for this is controversial. This meta-analysis aims to confirm whether VDR gene polymorphisms are associated with OA. Methods. Meta-analyses on the association between OA and VDR ApaI, BsmI, TaqI and FokI polymorphisms were conducted using allele and homozygote contrast and contrasts in the recessive and dominant models. Stratification analyses by different demographic regions (Europe vs Asian) were also performed and pooled odds ratios (ORs) were obtained using the random effects model if the results were heterogeneous. Results. A total of 13 relevant studies involving OA patients (n = 2104) and controls (n = 2939) were included in the analysis. There were significant associations between VDR ApaI polymorphisms and OA in the Asian population (A vs a: OR = 1.16, 95% CI 1.02, 1.32, P = 0.025; AA vs Aa/aa: OR = 1.36, 95% CI 1.04, 1.77, P = 0.025; AA vs aa: OR = 1.35, 95% CI 1.00, 1.80, P = 0.047), but not in the whole population. There was also a statistically significant association between FokI polymorphism and OA (FF vs Ff/ff: OR = 0.65, 95% CI 0.44, 0.95, P = 0.024); however, this result was derived from only two studies. No significant associations were found between VDR TaqI and BsmI polymorphisms and OA. Conclusion. There are modest but statistically significant associations between VDR ApaI polymorphisms and the susceptibility of OA in the Asian population.
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  • Epidemiology and management of gout in Taiwan: a nationwide population study.

    Kuo, Chang-Fu   Grainge, Matthew J   See, Lai-Chu   Yu, Kuang-Hui   Luo, Shue-Fen   Zhang, Weiya   Doherty, Michael  

    INTRODUCTION: Gout is the most common inflammatory arthritis worldwide and is the only type of chronic arthritis that potentially can be 'cured'. However, data on gout incidence, prevalence and management, assessed at multiple time points in the same population, are sparse, particularly in Asian populations. The aim of this study was to describe trends in the epidemiology of gout in the general population of Taiwan.; METHODS: The National Health Insurance Research Database was used to identify patients with gout and to estimate the prevalence and incidence of gout for each calendar year from 2005 to 2010. The pattern of gout management was also examined.; RESULTS: Of 23,371,362 beneficiaries in 2010, there were 1,458,569 prevalent and 56,595 incident cases of gout, giving a prevalence of 6.24% (95% confidence interval (CI), 6.23% to 6.25%) and an incidence of 2.74 (95% CI, 2.72 to 2.76) per 1,000 person-years. The annual percentage change (APC) of the standardised prevalence was -0.7% (95% CI, -1.7% to 0.3%; P=3D0.14), suggesting that the prevalence of gout was essentially the same throughout the study period. However, The APC of incidence was -13.4 (95% CI, -16.1 to -10.6) between 2005 and 2007 and -2.1 (95% CI, -10.4 to 7.1) between 2007 and 2010. Regions with the highest prevalence and incidence were eastern coastal counties and offshore islets, where indigenous people are clustered. Among prevalent gout cases in 2010, only 22.93% (95% CI, 22.87% to 23.00%) were prescribed urate-lowering treatment (ULT), which remained unchanged between 2005 and 2010 at an APC of 0.0 (95% CI, -3.8 to 4.0). Uricosuric agents were more commonly prescribed than xanthine oxidase inhibitors in Taiwan.; CONCLUSIONS: In Taiwan, 1 in 16 people have gout. Whereas the incidence has decreased recently, the prevalence remains unchanged. Management of gout in Taiwan is poor, with only one in five affected people being treated with ULT.=20
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