Background: Interpretation of simple microarray experiments is usually based on the fold-change of gene expression between a reference and a "treated" sample where the treatment can be of many types from drug exposure to genetic variation. Interpretation of the results usually combines lists of differentially expressed genes with previous knowledge about their biological function. Here we evaluate a method -based on the PageRank algorithm employed by the popular search engine Google -that tries to automate some of this procedure to generate prioritized gene lists by exploiting biological background information.

The prevalence of diabetes in pregnancy is increasing. Pre-existing diabetes is present in 1 in 167 pregnancies in Australia, divided equally between type 1 and type 2 diabetes. Diabetic retinopathy is a leading cause of blindness in women during their childbearing years, and pregnancy increases the short-term risk of diabetic retinopathy progression. We examine the risk factors for progression of diabetic retinopathy during pregnancy including duration of diabetes, baseline level of retinopathy, level of glycaemic control and hypertension. We also examine current screening and management guidelines and their levels of evidence, current treatment options for diabetic retinopathy and avenues for further research.

The algorithm (in Matlab format) is available (see http://www.maths.strath.ac.uk/~aas96106/lock_key.html).

Background A monovalent, parenteral, subunit rotavirus vaccine was well tolerated and immunogenic in adults in the USA and in toddlers and infants in South Africa, but elicited poor responses against heterotypic rotavirus strains. We aimed to evaluate safety and immunogenicity of a trivalent vaccine formulation (P2-VP8-P[4],[6],[8]).Methods A double-blind, randomised, placebo-controlled, dose-escalation, phase 1/2 study was done at three South African research sites. Healthy adults (aged 18-45 years), toddlers (aged 2-3 years), and infants (aged 6-8 weeks, ≥37 weeks' gestation, and without previous receipt of rotavirus vaccination), all without HIV infection, were eligible for enrolment. In the dose-escalation phase, adults and toddlers were randomly assigned in blocks (block size of five) to receive 30 µg or 90 µg of vaccine, or placebo, and infants were randomly assigned in blocks (block size of four) to receive 15 µg, 30 µg, or 90 µg of vaccine, or placebo. In the expanded phase, infants were randomly assigned in a 1:1:1:1 ratio to receive 15 μg, 30 μg, or 90 μg of vaccine, or placebo, in block sizes of four. Participants, parents of participants, and clinical, data, and laboratory staff were masked to treatment assignment. Adults received an intramuscular injection of vaccine or placebo in the deltoid muscle on the day of randomisation (day 0), day 28, and day 56; toddlers received a single injection of vaccine or placebo in the anterolateral thigh on day 0. Infants in both phases received an injection of vaccine or placebo in the anterolateral thigh on days 0, 28, and 56, at approximately 6, 10, and 14 weeks of age. Primary safety endpoints were local and systemic reactions (grade 2 or worse) within 7 days and adverse events and serious adverse events within 28 days after each injection in all participants who received at least one injection. Primary immunogenicity endpoints were analysed in infants in either phase who received all planned injections, had blood samples analysed at the relevant timepoints, and presented no major protocol violations considered to have an effect on the immunogenicity results of the study, and included serum anti-P2-VP8 IgA, IgG, and neutralising antibody geometric mean titres and responses measured 4 weeks after the final injection in vaccine compared with placebo groups. This trial is registered with ClinicalTrials.gov, NCT02646891.

Background: To compare visual and anatomical outcomes between intravitreous bevacizumab (BVB, Avastin) and triamcinolone (TA, Triesence) when administered at the time of cataract surgery in patients with diabetic macular oedema (DME).Design: Prospective, single-masked, randomized clinical trial at The Royal Victorian Eye and Ear Hospital, Melbourne.Participants: Patients with clinically significant cataract and either centre-involving DME or DME treated within the previous 24 months.Methods: Participants were randomized 1:1 to receive intravitreous BVB 1.25 mg or TA 4 mg during cataract surgery, and at subsequent review if required over 6 months.Main Outcome Measures: Change in central macular thickness (CMT) and best corrected visual acuity at 6 months.Results: Forty-one patients (mean age 66.4 years, 73.2% male) were recruited. Visual acuity and CMT were similar between groups at baseline (P > 0.2).After six months, both groups gained vision (mean +21.4 letters in TA group P < 0.0001, +12.5 letters in BVB, P = 0.002), with no significant difference between groups (P = 0.085). In addition, 60.9% of eyes receiving TA achieved a VA of ≥6/12 compared to 73.3% in the BVB group (P = 0.501). However, only TA was associated with a sustained reduction in CMT (À43.8-μm reduction TA vs. +37.3-μm increase BVB, P = 0.006 over 6 months). Following surgery, additional injections were required in 70.6% of participants in the BVB group, compared to 16.7% in the TA group (P < 0.0001). Three patients in the TA group experienced a rise of IOP over 21 mmHg (12.5%) during the 6-month follow-up; BVB had no cases (P = 0.130). There were no cases of endophthalmitis in either group.Conclusions: When administered at the time of cataract surgery in patients with DME, at 6 months both

BackgroundThe study was conducted at a high TB-HIV burden primary health community clinic in Cape Town, South Africa. We describe the management of children under five years of age in household contact with a smear and/or culture-positive adult TB case.MethodsThis study was a record review of routinely-collected programme data.ResultsA total of 1094 adult TB case folders were reviewed. From all identified contacts, 149 children should have received IPT based on local guidelines; in only 2/149 IPT was initiated. Management of child contacts of sputum smear and/or culture-positive compared to sputum-negative TB patients were similar.ConclusionsIPT delivery to children remains an operational challenge, especially in high TB-HIV burden communities. A tool to improve IPT management and targeting sputum smear and/or culture-positive TB child contacts may overcome some of these challenges and should be developed and piloted in such settings.

Background Historical, colonial, and racist policies continue to influence the health of Indigenous people, and they continue to have higher rates of chronic diseases and reduced life expectancy compared with non-Indigenous people. We determined factors accounting for variations in cardiovascular risk factors among First Nations communities in Canada. MethodsMen and women (n=1302) aged 18 years or older from eight First Nations communities participated in a population-based study. Questionnaires, physical measures, blood samples, MRI of preclinical vascular disease, and community audits were collected. In this cross-sectional analysis, the main outcome was the INTERHEART risk score, a measure of cardiovascular risk factor burden. A multivariable model was developed to explain the variations in INTERHEART risk score among communities. The secondary outcome was MRI-detected carotid wall volume, a measure of subclinical atherosclerosis. Findings The mean INTERHEART risk score of all communities was 17•2 (SE 0•2), and more than 85% of individuals had a risk score in the moderate to high risk range. Subclinical atherosclerosis increased significantly across risk score categories (p<0•0001). Socioeconomic advantage (-1•4 score, 95% CI -2•5 to -0•3; p=0•01), trust between neighbours (-0•7, -1•2 to -0•3; p=0•003), higher education level (-1•9, -2•9 to -0•8, p<0•001), and higher social support (-1•1, -2•0 to -0•2; p=0•02) were independently associated with a lower INTERHEART risk score; difficulty accessing routine health care (2•2, 0•3 to 4•1, p=0•02), taking prescription medication (3•5, 2•8 to 4•3; p<0•001), and inability to afford prescription medications (1•5, 0•5 to 2•6; p=0•003) were associated with a higher INTERHEART risk score. Collectively, these factors explained 28% variation in the cardiac risk score among communities. Communities with higher socioeconomic advantage and greater trust, and individuals with higher education and social support, had a lower INTERHEART risk score. Communities with difficulty accessing health care, and individuals taking or unable to afford prescription medications, had a higher INTERHEART risk score. Interpretation Cardiac risk factors are lower in communities with high socioeconomic advantage, greater trust, social support and educational opportunities, and higher where it is difficult to access health care or afford prescription medications. Strategies to optimise the protective factors and reduce barriers to health care in First Nations communities might contribute to improved health and wellbeing.

Clinical presentations of scleritis vary across the Asia-Pacific, particularly in endemic regions for tuberculosis such as India, where it affects younger men with a predominance of nodular and infectious disease.