Is IP-10 a Better Biomarker for Active and Latent Tuberculosis in Children than IFNγ?

Background: The blood based interferon-gamma release assays (IGRA) for the diagnosis of tuberculosis do not discriminate between active TB disease and latent TB infection (LTBI). The search for distinguishing biomarkers therefore continues, as the accurate diagnosis of tuberculosis is particularly challenging in children. IFN-c-inducible protein 10 (IP-10/CXCL10) has recently been evaluated as a marker for active TB in adults with promising results. Aim: To investigate this new biomarker for active TB and LTBI in paediatrics. Method: We measured IP-10 levels using ELISA in supernatants of whole blood samples stimulated with TB-specificantigens and negative control antigen. Results: IP-10 is produced in high levels following mycobacterial antigen stimulation in active TB (n = 17) and LTBI (n = 16) compared to controls (n = 16) and to IFN-c. The baseline levels of IP-10 are increased in active TB and in LTBI, but there is no significant difference of stimulated levels of IP-10 between active TB and LTBI. Conclusions: IP-10 is a biomarker for tuberculosis in children. However like IFNc, IP-10 also does not distinguish between active TB and LTBI

Deformation-related volcanism in the Pacific Ocean linked to the Hawaiian-Emperor bend

Ocean islands, seamounts and volcanic ridges are thought to form above mantle plumes. Yet, this mechanism cannot explain many volcanic features on the Pacific Ocean floor and some might instead be caused by cracks in the oceanic crust linked to the reorganization of plate motions. A distinctive bend in the Hawaiian–Emperor volcanic chain has been linked to changes in the direction of motion of the Pacific Plate, movement of the Hawaiian plume, or a combination of both. However, these links are uncertain because there is no independent record that precisely dates tectonic events that affected the Pacific Plate. Here we analyse the geochemical characteristics of lava samples collected from the Musicians Ridges, lines of volcanic seamounts formed close to the Hawaiian–Emperor bend. We find that the geochemical signature of these lavas is unlike typical ocean island basalts and instead resembles mid-ocean ridge basalts. We infer that the seamounts are unrelated to mantle plume activity and instead formed in an extensional setting, due to deformation of the Pacific Plate. 40Ar/39Ar dating reveals that the Musicians Ridges formed during two time windows that bracket the time of formation of the Hawaiian–Emperor bend, 53–52 and 48–47 million years ago. We conclude that the Hawaiian–Emperor bend was formed by plate–mantle reorganization, potentially triggered by a series of subduction events at the Pacific Plate margins

A second generation human haplotype map of over 3.1 million SNPs

We describe the Phase II HapMap, which characterizes over 3.1 million human single nucleotide polymorphisms (SNPs) genotyped in 270 individuals from four geographically diverse populations and includes 25-35% of common SNP variation in the populations surveyed. The map is estimated to capture untyped common variation with an average maximum r(2) of between 0.9 and 0.96 depending on population. We demonstrate that the current generation of commercial genome-wide genotyping products captures common Phase II SNPs with an average maximum r(2) of up to 0.8 in African and up to 0.95 in non-African populations, and that potential gains in power in association studies can be obtained through imputation. These data also reveal novel aspects of the structure of linkage disequilibrium. We show that 10-30% of pairs of individuals within a population share at least one region of extended genetic identity arising from recent ancestry and that up to 1% of all common variants are untaggable, primarily because they lie within recombination hotspots. We show that recombination rates vary systematically around genes and between genes of different function. Finally, we demonstrate increased differentiation at non-synonymous, compared to synonymous, SNPs, resulting from systematic differences in the strength or efficacy of natural selection between populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62863/1/nature06258.pd

Long Lamai community ICT4D E‐commerce system modelling: an agent oriented role‐based approach

This paper presents the post‐mortem report upon completion of the Long Lamai e‐commerce development project. Some weaknesses with regards to the current software modelling approach are identified and an alternative role‐based approach is proposed. We argue that the existing software modelling technique is not suitable for modelling, making it difficult to establish a good contract between stakeholders causing delays in the project delivery. The role‐based approach is able to explicitly highlight the responsibilities among stakeholders, while also forming the contract agreement among them leading towards sustainable ICT4D

Evaluation of appendicitis risk prediction models in adults with suspected appendicitis

Background Appendicitis is the most common general surgical emergency worldwide, but its diagnosis remains challenging. The aim of this study was to determine whether existing risk prediction models can reliably identify patients presenting to hospital in the UK with acute right iliac fossa (RIF) pain who are at low risk of appendicitis. Methods A systematic search was completed to identify all existing appendicitis risk prediction models. Models were validated using UK data from an international prospective cohort study that captured consecutive patients aged 16–45 years presenting to hospital with acute RIF in March to June 2017. The main outcome was best achievable model specificity (proportion of patients who did not have appendicitis correctly classified as low risk) whilst maintaining a failure rate below 5 per cent (proportion of patients identified as low risk who actually had appendicitis). Results Some 5345 patients across 154 UK hospitals were identified, of which two‐thirds (3613 of 5345, 67·6 per cent) were women. Women were more than twice as likely to undergo surgery with removal of a histologically normal appendix (272 of 964, 28·2 per cent) than men (120 of 993, 12·1 per cent) (relative risk 2·33, 95 per cent c.i. 1·92 to 2·84; P < 0·001). Of 15 validated risk prediction models, the Adult Appendicitis Score performed best (cut‐off score 8 or less, specificity 63·1 per cent, failure rate 3·7 per cent). The Appendicitis Inflammatory Response Score performed best for men (cut‐off score 2 or less, specificity 24·7 per cent, failure rate 2·4 per cent). Conclusion Women in the UK had a disproportionate risk of admission without surgical intervention and had high rates of normal appendicectomy. Risk prediction models to support shared decision‐making by identifying adults in the UK at low risk of appendicitis were identified