Comparing Proxy, Adolescent, and Adult Assessments of Functional Ability in Adolescents With Juvenile Idiopathic Arthritis.

Objective: In pediatric research, investigators rely on proxy reports of outcome, such as the proxy-completed Childhood Health Assessment Questionnaire (C-HAQ), to assess function in juvenile idiopathic arthritis (JIA). As children mature, they may self-complete the adult HAQ or the unvalidated adolescent-specific C-HAQ. It is unclear how these measures compare and whether they are directly interchangeable.

Brief Report: The Genetic Profile of Rheumatoid Factor-Positive Polyarticular Juvenile Idiopathic Arthritis Resembles That of Adult Rheumatoid Arthritis.

Objective: Juvenile idiopathic arthritis (JIA) comprises 7 heterogeneous categories of chronic childhood arthritides. Approximately 5% of children with JIA have rheumatoid factor (RF)-positive arthritis, which phenotypically resembles adult rheumatoid arthritis (RA). Our objective was to compare and contrast the genetics of RF-positive polyarticular JIA with those of RA and selected other JIA categories, to more fully understand the pathophysiologic relationships of inflammatory arthropathies.

Novel Blood Pressure Locus and Gene Discovery Using Genome-Wide Association Study and Expression Data Sets From Blood and the Kidney.

Elevated blood pressure is a major risk factor for cardiovascular disease and has a substantial genetic contribution. Genetic variation influencing blood pressure has the potential to identify new pharmacological targets for the treatment of hypertension. To discover additional novel blood pressure loci, we used 1000 Genomes Project-based imputation in 150 134 European ancestry individuals and sought significant evidence for independent replication in a further 228 245 individuals.

Quantifying Digital Ulcers in Systemic Sclerosis: Reliability of Computer-Assisted Planimetry in Measuring Lesion Size.

Objective: Digital ulcers are a major problem in patients with systemic sclerosis (SSc), causing severe pain and impairment of hand function. In addition, digital ulcers heal slowly and sometimes become infected, which can lead to gangrene and necessitate amputation if appropriate intervention is not taken. A reliable, objective method for assessing digital ulcer healing or progression is needed in both the clinical and research arenas.

Preliminary support for a brief psychological intervention to improve first-time hearing aid use among adults.

Objectives: Suboptimal hearing aid use extorts significant social, health, and economic costs. The aims of this study were to (1) test the novel hypothesis that the threat associated with being diagnosed with hearing loss could be ameliorated with a self-affirmation manipulation and (2) gauge the feasibility of deploying the manipulation in routine clinical practice.

Design: Parallel groups randomized controlled trial with 10-week follow-up.

Twenty-Year Outcome and Association Between Early Treatment and Mortality and Disability in an Inception Cohort of Patients With Rheumatoid Arthritis: Results From the Norfolk Arthritis Register.

Objective: To describe the outcome in patients with rheumatoid arthritis (RA) over 20 years from symptom onset, and to assess the association between early treatment (with disease-modifying antirheumatic drugs/steroids) and mortality and disability during follow-up.

Methods: Patients recruited to the Norfolk Arthritis Register (NOAR) between 1990 and 1994 who met the 2010 American College of Rheumatology/European League Against Rheumatism RA criteria at baseline were included in this analysis. Demographic and clinical variables were collected at baseline and at years 1-3, 5, 7, 10, 15, and 20.

HLA-DRB1 Amino Acid Positions 11/13, 71, and 74 Are Associated With Inflammation Level, Disease Activity, and the Health Assessment Questionnaire Score in Patients With Inflammatory Polyarthritis.

Objective: Rheumatoid arthritis (RA) susceptibility HLA-DRB1 haplotypes based on amino acid positions 11/13, 71, and 74 predict radiographic damage. The mechanism of action is unknown, but it may be mediated by inflammation. We undertook this study to systematically investigate the effect of these amino acids on nonradiographic measures of disease activity/outcomes.

Tartrate-Resistant Acid Phosphatase Deficiency in the Predisposition to Systemic Lupus Erythematosus.

Objective: Mutations in the ACP5 gene, which encodes tartrate-resistant acid phosphatase (TRAP), cause the immuno-osseous disorder spondyloenchondrodysplasia, which includes as disease features systemic lupus erythematosus (SLE) and a type I interferon (IFN) signature. Our aims were to identify TRAP substrates, determine the consequences of TRAP deficiency in immune cells, and assess whether ACP5 mutations are enriched in sporadic cases of SLE.

Methods: Interaction between TRAP and its binding partners was tested by a yeast 2-hybrid screening, confocal microscopy, and immunoprecipitation/Western blotting.

Age and Smoking Related Changes in Metal Ion Levels in Human Lens: Implications for Cataract Formation.

Age-related cataract formation is the primary cause of blindness worldwide and although treatable by surgical removal of the lens the majority of sufferers have neither the finances nor access to the medical facilities required. Therefore, a better understanding of the pathogenesis of cataract may identify new therapeutic targets to prevent or slow its progression. Cataract incidence is strongly correlated with age and cigarette smoking, factors that are often associated with accumulation of metal ions in other tissues.

Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations.

Ulcerative colitis and Crohn's disease are the two main forms of inflammatory bowel disease (IBD). Here we report the first trans-ancestry association study of IBD, with genome-wide or Immunochip genotype data from an extended cohort of 86,640 European individuals and Immunochip data from 9,846 individuals of East Asian, Indian or Iranian descent. We implicate 38 loci in IBD risk for the first time.

Boosting drug named entity recognition using an aggregate classifier.

Objective: Drug named entity recognition (NER) is a critical step for complex biomedical NLP tasks such as the extraction of pharmacogenomic, pharmacodynamic and pharmacokinetic parameters. Large quantities of high quality training data are almost always a prerequisite for employing supervised machine-learning techniques to achieve high classification performance. However, the human labour needed to produce and maintain such resources is a significant limitation.

Mutations of human NARS2, encoding the mitochondrial asparaginyl-tRNA synthetase, cause nonsyndromic deafness and Leigh syndrome.

Here we demonstrate association of variants in the mitochondrial asparaginyl-tRNA synthetase NARS2 with human hearing loss and Leigh syndrome. A homozygous missense mutation ([c.637G>T; p.

Role of Factor H and Related Proteins in Regulating Complement Activation in the Macula, and Relevance to Age-Related Macular Degeneration.

The recent revolution in age-related macular degeneration (AMD) genetics has demonstrated that genetic alterations affecting the alternative pathway of the complement cascade have a major influence on AMD risk. One of the two most important genetic loci is on chromosome 1 and contains genes encoding complement factor H (FH) and the factor H related proteins (FHR proteins). In macular tissue, especially Bruch's membrane, relatively high levels of a truncated splice variant of FH called factor H-like protein 1 (FHL-1) are present.

Complementing the Sugar Code: Role of GAGs and Sialic Acid in Complement Regulation.

Sugar molecules play a vital role on both microbial and mammalian cells, where they are involved in cellular communication, govern microbial virulence, and modulate host immunity and inflammatory responses. The complement cascade, as part of a host's innate immune system, is a potent weapon against invading bacteria but has to be tightly regulated to prevent inappropriate attack and damage to host tissues. A number of complement regulators, such as factor H and properdin, interact with sugar molecules, such as glycosaminoglycans (GAGs) and sialic acid, on host and pathogen membranes and direct the appropriate complement response by either promoting the binding of complement activators or inhibitors.

Dysmorphology services: a snapshot of current practices and a vision for the future.

Dysmorphology concerns the recognition and management of rare, multiple anomaly syndromes. Genomic technologies and software for gestalt recognition will re-shape dysmorphology services. In order to reflect on a model of the service in the post-genomic era, we compared the utility of dysmorphology consultations in two Mediterranean cities, Athens, Greece and Afula, Israel (MDS), the Manchester Centre for Genomic Medicine, a UK service with dysmorphology expertise (UKDS) and the DYSCERNE, digital service (DDS).

Compound heterozygosity of low-frequency promoter deletions and rare loss-of-function mutations in TXNL4A causes Burn-McKeown syndrome.

Mutations in components of the major spliceosome have been described in disorders with craniofacial anomalies, e.g., Nager syndrome and mandibulofacial dysostosis type Guion-Almeida.

Identification of factor H-like protein 1 as the predominant complement regulator in Bruch's membrane: implications for age-related macular degeneration.

The tight regulation of innate immunity on extracellular matrix (ECM) is a vital part of immune homeostasis throughout the human body, and disruption to this regulation in the eye is thought to contribute directly to the progression of age-related macular degeneration (AMD). The plasma complement regulator factor H (FH) is thought to be the main regulator that protects ECM against damaging complement activation. However, in the present study we demonstrate that a truncated form of FH, called FH-like protein 1 (FHL-1), is the main regulatory protein in the layer of ECM under human retina, called Bruch's membrane.

Age-dependent changes in heparan sulfate in human Bruch's membrane: implications for age-related macular degeneration.

Purpose: Heparan sulfate (HS) has been implicated in age-related macular degeneration (AMD), since it is the major binding partner for complement factor H (CFH) in human Bruch's membrane (BrM), and CFH has a central role in inhibiting complement activation on extracellular matrices. The aim was to investigate potential aging changes in HS quantity and composition in human BrM.

Methods: Postmortem human ocular tissue was obtained from donors without known retinal disease.

Numerical compression schemes for proteomics mass spectrometry data.

The open XML format mzML, used for representation of MS data, is pivotal for the development of platform-independent MS analysis software. Although conversion from vendor formats to mzML must take place on a platform on which the vendor libraries are available (i.e.

The cost-effectiveness of a pharmacogenetic test: a trial-based evaluation of TPMT genotyping for azathioprine.

Background: Thiopurine-methyl transferase (TPMT) testing prior to the prescription of azathioprine in autoimmune diseases is one of the few examples of a pharmacogenetic test that has made the transition from research into clinical practice. TPMT testing could lead to improved prescribing of azathioprine resulting in a reduction in adverse drug reactions as well as an improvement in effectiveness. When allocating scarce resources robust evidence on cost-effectiveness is required.

Maternal residential proximity to major roads in north west England and adverse pregnancy outcomes.

Objective: To investigate the effects of maternal residential proximity to major roads on adverse pregnancy outcomes.

Methods: Major road networks in North West England were linked to the maternal residence of 190,909 births (2004 to 2008). Distance between the residence and the nearest major road was calculated and dichotomized at 200 m.

A comparison of population air pollution exposure estimation techniques with personal exposure estimates in a pregnant cohort.

There is increasing evidence of the harmful effects for mother and fetus of maternal exposure to air pollutants. Most studies use large retrospective birth outcome datasets and make a best estimate of personal exposure (PE) during pregnancy periods. We compared estimates of personal NOx and NO2 exposure of pregnant women in the North West of England with exposure estimates derived using different modelling techniques.

Cancer risk in Lynch Syndrome.

Lynch Syndrome, or hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant cancer predisposition syndrome caused by inactivating mutations in DNA mismatch repair genes. It accounts for 2-4 % of all incident colorectal cancers. Mutation carriers are at risk of early onset colorectal cancer, endometrial cancer, and a spectrum of other tumours.