Self-driving laboratory for accelerated discovery of thin-film materials.

Discovering and optimizing commercially viable materials for clean energy applications typically takes more than a decade. Self-driving laboratories that iteratively design, execute, and learn from materials science experiments in a fully autonomous loop present an opportunity to accelerate this research process. We report here a modular robotic platform driven by a model-based optimization algorithm capable of autonomously optimizing the optical and electronic properties of thin-film materials by modifying the film composition and processing conditions. We demonstrate the power of this platform by using it to maximize the hole mobility of organic hole transport materials commonly used in perovskite solar cells and consumer electronics. This demonstration highlights the possibilities of using autonomous laboratories to discover organic and inorganic materials relevant to materials sciences and clean energy technologies.

The contribution of myostatin (MSTN) and additional modifying genetic loci to race distance aptitude in Thoroughbred horses racing in different geographic regions.

BACKGROUND: Race distance aptitude in Thoroughbred horses is highly heritable and is influenced largely by variation at the myostatin gene (MSTN). OBJECTIVES: In addition to MSTN, we hypothesised that other modifying loci contribute to best race distance. STUDY DESIGN: Using 3006 Thoroughbreds, including 835 'elite' horses, which were >3 years old, had race records and were sampled from Europe/Middle-East, Australia/New Zealand, North America and South Africa, we performed genome-wide association (GWA) tests and separately developed a genomic prediction algorithm to comprehensively catalogue additive genetic variation contributing to best race distance. METHODS: 48,896 single-nucleotide polymorphism (SNP) genotypes were generated from high-density SNP genotyping arrays. Heritability estimates, tests of GWA and genomic prediction models were derived for the phenotypes: average race distance, best race distance for elite, nonelite and all winning horses. RESULTS: Heritability estimates were high ( h m 2  = 0.51, best race distance - elite; h m 2  = 0.42, best race distance - nonelite; h m 2  = 0.40, best race distance - all) and most of the variation was attributed to the MSTN gene. MSTN locus SNPs were the most strongly associated with the trait and included BIEC2-438999 (ECA18:66913090; P = 4.51 × 10-110 , average race distance; P = 2.33 × 10-42 , best race distance - elite). The genomic prediction algorithm enabled the inclusion of variation from all SNPs in a model that partitioned horses into short and long cohorts following assignment of MSTN genotype. Additional genes with minor contributions to best race distance were identified. MAIN LIMITATIONS: The nongenetic influence of owner/trainer decisions on placement of horses in suitable races could not be controlled. CONCLUSIONS: MSTN is the single most important genetic contributor to best race distance in the Thoroughbred. Employment of genetic prediction models will lead to more accurate placing of horses in races that are best suited to their inherited genetic potential for distance aptitude.

Identifying avoidable switchboard delays in England's NHS hospitals: phase one of the national SWITCH project.

BACKGROUND: Inter-hospital communication frequently requires mediation via a switchboard. Identifying and eliminating switchboard inefficiencies may improve patient care. METHODS: All 175 acute hospital switchboards in England were contacted six times. Call contents and duration were recorded. No clinician calls or bleeps were connected. RESULTS: The mean delay before contacting a switchboard operative was 55±46 seconds. 115 hospitals (66%) used automated switchboards; 34 of these (30%) had infection control messages. Robot operators introduced an additional 40 second delay versus humans (mean 70.3±28 versus 29.8±23 seconds, p<0.0001). Multivariate analysis identified robot operators (HR 5.1, p<0.0001) and infection control messages (HR 2.9, p=0.003) as predictors of delays over 60 seconds. CONCLUSIONS: There are significant avoidable delays in contacting switchboard operatives across England. Quality improvement is underway.

EULAR-PReS points to consider for the use of imaging in the diagnosis and management of juvenile idiopathic arthritis in clinical practice.

To develop evidence based points to consider the use of imaging in the diagnosis and management of juvenile idiopathic arthritis (JIA) in clinical practice. The task force comprised a group of paediatric rheumatologists, rheumatologists experienced in imaging, radiologists, methodologists and patients from nine countries. Eleven questions on imaging in JIA were generated using a process of discussion and consensus. Research evidence was searched systematically for each question using MEDLINE, EMBASE and Cochrane CENTRAL. Imaging modalities included were conventional radiography, ultrasound, MRI, CT, scintigraphy and positron emission tomography. The experts used the evidence obtained from the relevant studies to develop a set of points to consider. The level of agreement with each point to consider was assessed using a numerical rating scale. A total of 13 277 references were identified from the search process, from which 204 studies were included in the systematic review. Nine points to consider were produced, taking into account the heterogeneity of JIA, the lack of normative data and consequent difficulty identifying pathology. These encompassed the role of imaging in making a diagnosis of JIA, detecting and monitoring inflammation and damage, predicting outcome and response to treatment, use of guided therapies, progression and remission. Level of agreement for each proposition varied according to the research evidence and expert opinion. Nine points to consider and a related research agenda for the role of imaging in the management of JIA were developed using published evidence and expert opinion.

Decreased tissue factor expression with increased CD11b upregulation on elastin-based biomaterial coatings.

Elastin-like polypeptide (ELP) coatings have been shown to have non-thrombogenic properties both in vitro and in vivo. In this work, we expand our understanding of this phenomenon by investigating the interaction of these coatings with leukocytes. Citrated whole blood was exposed to a shear rate of 300 s-1 for 2 hours at 37 °C on ELP1- and ELP4-coated polyethylene terephthalate (Mylar™) surfaces in a cone and plate device. Scanning electron microscopy and flow cytometry were used to measure leukocyte activation and platelet-leukocyte aggregation in response to the ELP1 and ELP4 coatings on the surface and in the bulk, respectively. Surface analysis showed little leukocyte activity on the surface of uncoated positive controls. Both the tissue factor (TF) expression (indicative of leukocyte activation) and CD61 expression (indicative of platelet-leukocyte aggregates), in the bulk were decreased by 40% and 20%, respectively, with the ELP coating of Mylar™, while a two- to three-fold increase in CD11b upregulation (indicative of leukocyte activation) for ELP1 and ELP4 was determined. Two of three bulk markers indicated that ELP-coated Mylar™ decreased the leukocyte response compared to the uncoated Mylar™, while the third, CD11b, indicated an increase in leukocyte response to the ELP coatings.

Plasma IL-6 levels correlate with clinical and ultrasound measures of arthritis in patients with systemic lupus erythematosus.

OBJECTIVE: The objective of this paper is to elucidate the role of specific cytokines in lupus (SLE) arthritis. METHODS: Fifty SLE and 40 RA patients had an ultrasound (US) scan of their hand as per standardized protocols. US scores were expressed per joint and as a total 'US activity' score, (sum of power Doppler (PD) and grey-scale synovial hypertrophy scores in all joints) and a total erosion score. SLE disease activity was assessed (BILAG and SELENA-SLEDAI). Plasma levels of IL-6, TNF-alpha and BLyS were measured using sandwich ELISA kits (Quantikine kits, R & D). RESULTS: On the basis of the US results SLE patients were divided into three groups: erosive arthritis (n = 20), non-erosive arthritis (n = 18) and those with a normal US scan (n = 12). Across the SLE groups plasma IL-6 levels correlated with CRP (p < 0.001), hand deformity scores (p = 0.005), BILAG musculoskeletal score (p = 0.009), wrist PD score (p = 0.01), the presence of tenosynovitis (p = 0.008) and total US activity score (p < 0.001) (which remained constant when corrected for total BILAG score). Neither TNF-alpha nor BLyS levels correlated with US or clinical measures of lupus arthritis; however, TNF-alpha correlated with total BILAG score (p < 0.001). CONCLUSION: This is the first study to examine levels of specific cytokines in a cohort of SLE patients stratified in terms of joint disease by US, where the most significant finding is that IL-6 levels correlated both with clinical and US measures of arthritis disease activity.

Acute tubular injury is an important component in type I acute antibody-mediated rejection.

BACKGROUND: "Acute tubular necrosis (ATN)-like" changes in type I acute antibody- mediated rejection (AAMR) have been proposed since 2005, but the presence of "ATN-like" injury in AAMR has not well been established. The aim of this study was to confirm the presence of acute tubular injury in type I AAMR, using the specific proximal tubular injury marker, kidney injury molecule-1 (KIM-1). DESIGN: The study included 3 groups of cases, namely, a negative control group (normal nontransplantation renal parenchyma as group 1, n = 11), a positive control group (transplant ATN with negative C4d staining as group 2, n = 12), and study cases (type 1 AAMR as group 3, n = 19). Biopsy specimens from all groups were stained immunohistochemically for KIM-1 (monoclonal antibody) and KIM-1 staining intensity in proximal tubules was graded from 0.5 to 3+. Clinical indices were also correlated and analyzed. RESULTS: Group 1 demonstrated significantly lower serum creatinine levels (1.02 ± 0.10 mg/dL) when compared with both group 2 and group 3. Both groups 2 and 3 showed similar serum creatinine levels (4.02 ± 0.59 mg/dL in group 2 and 3.24 ± 0.34 mg/dL in group 3). The negative control group demonstrated negative proximal tubule staining for KIM-1, whereas both groups 2 and 3 showed positive KIM-1 staining in proximal tubules (intensity ranging from 1+ to 3+ in group 2 and from 0.5 to 3+ in group 3). CONCLUSION: Our results, using KIM-1 immunohistochemistry, demonstrated that acute tubular injury is an important component of type I AAMR.

Hypermobility and musculoskeletal pain in children: a systematic review.

OBJECTIVE: To examine the evidence of an association between hypermobility and musculoskeletal pain in children. METHODS: A systematic review of the literature was performed using the databases PubMed, EMBASE, NHS Evidence, and Medline. Inclusion criteria were observational studies investigating hypermobility and musculoskeletal pain in children. Exclusion criteria were studies conducted on specialist groups (i.e. dancers) or hospital referrals. Pooled odds ratios (ORs) were calculated using random effects models and heterogeneity was tested using χ(2)-tests. Study quality was assessed using the Newcastle-Ottawa Scale for case-control studies. RESULTS: Of the 80 studies identified, 15 met the inclusion criteria and were included in the review. Of these, 13 were included in the statistical analyses. Analysing the data showed that the heterogeneity was too high to allow for interpretation of the meta-analysis (I(2) = 72%). Heterogeneity was much lower when the studies were divided into European (I(2) = 8%) and Afro-Asian subgroups (I(2) = 65%). Sensitivity analysis based on data from studies reporting from European and Afro-Asian regions showed no association in the European studies [OR 1.00, 95% confidence interval (CI) 0.79-1.26] but a marked relationship between hypermobility and joint pain in the Afro-Asian group (OR 2.01, 95% CI 1.45-2.77). Meta-regression showed a highly significant difference between subgroups in both meta-analyses (p < 0.001). CONCLUSION: There seems to be no association between hypermobility and joint pain in Europeans. There does seem to be an association in Afro-Asians; however, there was a high heterogeneity. It is unclear whether this is due to differences in ethnicity, nourishment, climate or study design.

Glomerulitis during acute cellular rejection may be a surrogate marker of vasculitis in renal allografts--better index for diagnosis of vasculitis.

BACKGROUND: The Banff criteria (from 2005 to 2009) use "T cell-mediated rejection" to indicate acute cellular rejection. Vasculitis in smaller arteries is an important diagnostic criterion for moderate and severe T cell-mediated rejection. The renal allograft endothelium is a significant target of inflammatory response-mediated tissue damage. Medium-size arteries (arcuate arteries) are mostly absent in routine allograft biopsies, so identification of vasculitis relies on its identification in small arteries (arterioles to interlobar arteries). Although inflammation in terminal vessels such as the glomerular capillaries has been previously recognized, their role in grading the rejection process is not well characterized. We therefore evaluated the expression of CD3-positive T lymphocytes and CD68-positive macrophages in glomeruli, small arteries, and arcuate arteries of nephrectomy specimens obtained from transplant and renal tumor patients. METHODS: The study group included 21 renal explant subjects with nonreversible moderate to severe T cell-mediated rejection (IIa to III) and/or severe chronic changes. The control group comprised 17 individuals with nephrectomy for renal tumors. In each case, a large renal section from cortex to medulla was stained for CD3 and CD68 by immunohistochemical method. CD3-positive T lymphocytes and CD68-positive macrophages per balanced high-power field were counted in glomeruli, interlobar arteries, and arcuate arteries. RESULTS: In control kidney sections, neither CD3-positive T lymphocytes nor CD68-positive macrophages were noted in glomeruli, interlobar arteries, or arcuate arteries. In the study group, 15/21 showed diffuse C4d positivity. Also in the study group, positive CD3 and CD68 counts in glomeruli were significantly correlated to both interlobar and arcuate artery counts by linear regression analysis. CONCLUSION: We conclude that in renal allograft biopsies, T lymphocytes and macrophages in the glomeruli not only represent a separate entity, "transplant glomerulitis," but also may be a surrogate marker of vasculitis present in larger vascular beds. Comparable amounts of T cells and macrophages imply that "acute cellular rejection" may be a better terminology to reflect the true inflammatory status.

IL7RA polymorphisms and chronic inflammatory arthropathies.

The C allele of a single nucleotide polymorphism (SNP), rs6897932, located in the interleukin-7 receptor alpha chain (IL7RA) was recently found to be associated with multiple sclerosis and Type I diabetes. We analysed 13 SNPs in the IL7RA gene in a combined cohort of patients with chronic inflammatory arthropathies (rheumatoid arthritis and juvenile idiopathic arthritis; 368 patients and 532 unaffected subjects). No significant associations with disease were found with the exception of the non-synonymous SNP rs6897932. This SNP showed modest enrichment of the TT genotype in arthritic patients compared with controls [P = 0.02; OR 1.72 (95% CI 1.08-2.75)]. Our data are suggestive for a role of rs6897932 in predisposition to chronic inflammatory arthropathies.

Impact of coercive tactics on the decision-making of adolescents with intellectual disabilities.

BACKGROUND: High rates of victimization have raised concerns about the ability of adolescents with intellectual disabilities (ID) to avoid and escape from harmful situations and to make decisions in their own best interest. The present study was designed to assess the impact of specific coercive tactics on the decision-making of adolescents with ID. METHOD: Forty-eight adolescents with ID participated in the study. They were asked to respond to a series of brief vignettes depicting equal numbers of situations involving coercion with a lure, coercion with a threat, and no specific coercive tactic. Performance was assessed in terms of independent, prevention-focused decisions, reporting decisions and responses to fact and inference comprehension questions. RESULTS: Overall, participants suggested independent, prevention-focused decisions only about half the time. They were more likely to suggest independent, prevention-focused decisions in situations with no specific coercive tactic or coercion with a lure than in situations involving a threat. However, reporting decisions were more likely in situations involving coercion with a threat than in the other two conditions and both fact and inference comprehension were best in situations involving coercion with a threat. CONCLUSIONS: Results indicated that adolescents with ID are not well-prepared to handle situations on their own that involve coercion, especially coercion with a threat. Because comprehension did not appear to be a key source of the decision-making difficulty in this study, further research is needed to examine all aspects of the decision-making process as a basis for the design of effective interventions.

Preclinical activity of P276-00, a novel small-molecule cyclin-dependent kinase inhibitor in the therapy of multiple myeloma.

Cyclin D dysregulation and overexpression is noted in the majority of multiple myeloma (MM) patients, suggesting its critical role in MM pathogenesis. Here, we sought to identify the effects of targeting cyclin D in MM. We first confirmed cyclin D mRNA overexpression in 42 of 64 (65%) patient plasma cells. Silencing cyclin D1 resulted in >50% apoptotic cell death suggesting its validity as a potential therapeutic target. We next evaluated P276-00, a clinical-grade small-molecule cyclin-dependent kinase inhibitor as a way to target the cyclins. P276-00 resulted in dose-dependent cytotoxicity in MM cells. Cell-cycle analysis confirmed either growth arrest or caspase-dependent apoptosis; this was preceded by inhibition of Rb-1 phosphorylation with associated downregulation of a range of cyclins suggesting a regulatory role of P276-00 in cell-cycle progression through broad activity. Proliferative stimuli such as interleukin-6, insulin-like growth factor-1 and bone-marrow stromal cell adherence induced cyclins; P276-00 overcame these growth, survival and drug resistance signals. Because the cyclins are substrates of proteasome degradation, combination studies with bortezomib resulted in synergism. Finally, in vivo efficacy of P276-00 was confirmed in an MM xenograft model. These studies form the basis of an ongoing phase I study in the treatment of relapsed/refractory MM.

Psychiatric disorder in young adults born very preterm: role of family history.

OBJECTIVE: To investigate whether young adults born very preterm (VPT) (<33 weeks) are at increased risk for psychiatric illness in adulthood and whether a family history of psychiatric disorder further increases this risk. METHODS: We assessed 169 VPT and 101 term born individuals using the Clinical Interview Schedule - Revised. RESULTS: Young adults born VPT had an increased risk for psychiatric disorder compared to controls (OR=3.1, 95% CI=1.1-8.6, p=0.03). Those born VPT who had a history of psychiatric disorder in a first-degree relative, had an increase in risk for psychiatric disorder compared to those born VPT without a family history (OR=5.2, 95% CI=1.8-14.9, p=0.002). CONCLUSION: Individuals born VPT are at increased risk of psychiatric illness in young adulthood compared to controls. In addition, a family history of psychiatric disorder in a first-degree relative may leave young adults born VPT particularly vulnerable to psychiatric illness.

A systematic review of the effectiveness of strategies for reducing fracture risk in children with juvenile idiopathic arthritis with additional data on long-term risk of fracture and cost of disease management.

OBJECTIVES: To review outcome measures and treatment costs in children with juvenile idiopathic arthritis (JIA) and low bone mineral density (BMD) and/or fragility fractures. To review evidence for effectiveness and safety of bisphosphonates and calcium and/or vitamin D in these children. To assess long-term bone health in adults with JIA. DATA SOURCES: Major databases were searched up to July 2005 for effectiveness studies and up to January 2005 for costs. REVIEW METHODS: A structured search strategy was conducted. For the evaluation of long-term bone health, outcome data were derived from two cohorts of adult patients with JIA. As there were few published cost data, an ongoing UK longitudinal study (CAPS) provided background data on the cost of managing JIA. RESULTS: Sixteen studies (78 children with JIA) were included. At baseline, the children had BMD below the expected values for age- and sex-matched children; treatment with bisphosphonates increased BMD with mean percentage increases in spine BMD varying from 4.5 to 19.1%. None of the studies with control groups compared results between the intervention and control groups, they only compared each group with its own baseline. Overall, studies were heterogeneous in design, of variable quality and with no consistency in methods of assessing and reporting outcomes. Hence, data could not be combined or an effect size calculated. A further 43 papers were included in the safety review; side-effects were generally transient. Two studies assessed treatment with calcium and/or vitamin D; BMD was increased from 0.75 to 0.830 g/cm2 after 6 months and BMD Z-score from -2.8 to -2.3 after 6 months and -2.4 after 1 year. There are relatively few long-term studies on the occurrence of low BMD and fragility fractures in children with JIA, with most studies only following children for 1 or 2 years. However, the long- and short-term data indicate that children with JIA have a lower BMD and more fractures than children without JIA. There are very few data on long-term bone health from adults who have JIA, but studies indicate that low BMD persists into adulthood, although adults in remission from JIA may attain the same BMD as healthy adults. From the available data, any predictors of low BMD and fractures in children and adults with JIA remain uncertain. No studies were found that discussed the costs of treating children with JIA and low BMD and/or fragility fractures. In CAPS, 297 of 457 children with JIA attended a 12-month follow-up visit. The mean annual total cost per child in the first year after diagnosis was 1649 pounds (standard deviation 1093 pounds, range 401-6967 pounds). The highest cost component was appointments with paediatric rheumatologists. The study is continuing to accrue and follow up patients and further analyses will be undertaken as the study progresses. CONCLUSIONS: BMD, adjusted for size, should be assessed as the primary outcome in studies of bone health in children with JIA. Quantitative computed tomography could be used where equipment is available as it offers the advantage of measuring volumetric density. Bisphosphonates are a promising treatment for osteoporosis in children with JIA, but the quality of the current evidence is poor. The accurate assessment of outcome is crucial. There are still uncertainties about the use of bisphosphonates in children, including whether the positive effects of treatment continue over time, the length of treatment and the maximal bone mass gain that can be achieved. Adults with JIA may have persistent low BMD compared with an otherwise healthy population together with an increased risk of fracture. There are no studies evaluating the costs of treating children with JIA and low BMD and/or fragility fractures. There are few data evaluating the costs of treating JIA in general. In the first 12 months after diagnosis, children with all JIA disease subtypes consume large, but highly variable, quantities of health service resources, the largest component being the consultant rheumatology appointments. Data from a larger cohort, over a longer period, are required to substantiate these results further. Further research is needed to assess more clearly the role and permit licensing of bisphosphonates for treatment of children, and in particular, longer-term studies.

The MHC2TA-168A/G and +1614G/C polymorphisms and risk for multiple sclerosis or chronic inflammatory arthropathies.

The -168A-G polymorphism has been shown to influence transcription of the MHC2TA gene and has been implicated in several inflammatory/autoimmune disorders. Attempts to reproduce these findings have been inconclusive. We investigated the role of this promoter single nucleotide polymorphism (SNP) in 440 multiple sclerosis (MS), 293 rheumatoid arthritis (RA), 74 juvenile idiopathic arthritis (JIA) patients and 316 healthy controls from Northern Ireland. We also genotyped a non-synonymous SNP in exon 11, +1614G/C. There was no significant difference in the -168G allele frequencies and carriage rates in the separate RA, JIA, or MS collections compared with the control group [odds ratio (OR) = 1.1, 95% confidence intervals (CI) = 0.86-1.44; OR = 1.1, 95% CI = 0.75-1.68; OR = 1.1, 95% CI = 0.84-1.35, respectively]. Assessment of the common phenotype (chronic inflammatory disease; n = 807 vs 316 controls) was negative as well. Carriage of +1614C was protective against JIA (OR = 0.6, 95% CI = 0.3-1.0) and showed a similar trend in RA and MS (OR = 0.7, 95% CI = 0.5-1.0; OR = 0.8, 95% CI = 0.6-1.0, respectively). The common phenotype (chronic inflammatory disease) was also significant (OR = 0.7, 95% CI = 0.6-1.0).

Polymorphisms in the interleukin-4 and IL-4 receptor genes modify risk for chronic inflammatory arthropathies in women.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with polygenic autoimmune background. We analysed the IL-4 +33 C/T and IL-4R Q551R single nucleotide polymorphisms (SNPs) in 294 RA, 72 JIA and 165 controls from Northern Ireland. Analysis of the individual phenotypes (RA or JIA) showed that both the IL-4 +33 TT (P = 0.02; OR: 0.25, 95% CI: 0.07-0.87) and the IL-4R Q551R CC genotypes (P = 0.001; OR: 0.19, 95% CI: 0.06-0.56) were exclusively decreased in female RA patients compared to female controls. Similar non-significant trends were observed in female JIA patients (OR: 0.25, 95% CI: 0.03-2.11 and OR: 0.31, 95% CI: 0.07-1.47, respectively). Analysis of the common phenotype (inflammatory arthropathy; i.e. JIA and RA combined) corroborated the unique association of these polymorphisms with female inflammatory arthropathy (P = 0.013 and 0.002, respectively). This is the first demonstration of sex-specific association of the two foremost genes of the IL-4 signalling cascade with chronic inflammatory arthropathies.

Neurological abnormalities in young adults born preterm.

OBJECTIVE: Individuals born before 33 weeks' gestation (very preterm, VPT) have an increased likelihood of neurological abnormality, impaired cognitive function, and reduced academic performance in childhood. It is currently not known whether neurological signs detected in VPT children persist into adulthood or become attenuated by maturation of the CNS. METHOD: We assessed 153 VPT individuals and 71 term-born controls at 17-18 years old, using a comprehensive neurological examination. This examination divides neurological signs into primary and integrative domains, the former representing the localising signs of classical neurology, and the latter representing signs requiring integration between different neural networks or systems. Integrative signs are sub-divided into three groups: sensory integration, motor confusion, and sequencing. The VPT individuals have been followed up since birth, and neonatal information is available on them, along with the results of neurological assessment at 4 and 8 years of age and neuropsychological assessment at 18 years of age. RESULTS: The total neurology score and primary and integrative scores were significantly increased in VPT young adults compared to term-born controls. Within the integrative domain, sensory integration and motor confusion scores were significantly increased in the VPT group, but sequencing was not significantly different between the VPT and term groups. Integrative neurological abnormalities at 18 were strongly associated with reduced IQ but primary abnormalities were not. CONCLUSIONS: Neurological signs are increased in VPT adults compared to term-born controls, and are strongly associated with reduced neuropsychological function.

The CTLA4+49A/G and CT60 polymorphisms and chronic inflammatory arthropathies in Northern Ireland.

Rheumatoid and juvenile idiopathic arthritis (RA, JIA) are chronic inflammatory arthropathies with an autoimmune background. The cytotoxic T-lymphocyte antigen-4 (CTLA-4) protein plays a key role in the down-regulation of T cell activation. We analyzed the CTLA4 +49A/G and CT60 polymorphisms in cohorts of Northern Irish RA and JIA patients and healthy control subjects using restriction fragment length polymorphism methods. The +49 A allele was increased in RA (61.2%; P=0.02; OR=1.28; 95% C.I.=1.04-1.58) and JIA (61.8%; P=0.14) patients compared to the control population (55.3%). No significant association was observed for the CT60 polymorphism. Haplotype analysis revealed a significantly different distribution of +49 A/G-CT60 haplotypes in RA and JIA patients compared to controls (P value<0.00001 and 0.030 for comparison of RA and JIA patients with controls, respectively). Our results suggest that the CTLA-4 gene is involved in predisposition to inflammatory arthropathies in the Northern Irish population.

Musculoskeletal ultrasound training in rheumatology: the Belfast experience.

OBJECTIVES: Despite the increasing use of musculoskeletal ultrasound (MSUS) as a clinical tool in rheumatology, there is no consensus yet regarding the standards required to achieve a basic level of competence in the use of this imaging technique. A number of sonographers worldwide are developing curricula and standardizing teaching methods in order to improve training in MSUS for rheumatologists. In the meantime, clinicians are devising informal means of training in order to acquire these new skills. Here we describe the informal team approach to MSUS training adopted by a group of rheumatologists from the Regional Rheumatology Centre in Belfast, UK. METHODS: Over a 5-yr period, eight rheumatologists from Musgrave Park Hospital in Belfast used a variety of means to learn the basic skills of MSUS. RESULTS: Seven of the team underwent a formal assessment of their competency in a practical examination devised by an experienced sonographer. All were judged to have attained a basic competency in MSU. CONCLUSIONS: This Belfast experience shows what can be achieved despite the absence of formal MSUS training. Nevertheless, the development of recognized training programmes and international standards of competency are important goals on the way to achieving more widespread acceptance of MSUS as a useful tool in everyday clinical practice.