Clinical insights into the interaction of childhood tuberculosis and HIV in the Western Cape

No Abstract

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Observation of associated near-side and away-side long-range correlations in √sNN=5.02 TeV proton-lead collisions with the ATLAS detector

Two-particle correlations in relative azimuthal angle (Δϕ) and pseudorapidity (Δη) are measured in √sNN=5.02  TeV p+Pb collisions using the ATLAS detector at the LHC. The measurements are performed using approximately 1  μb-1 of data as a function of transverse momentum (pT) and the transverse energy (ΣETPb) summed over 3.1<η<4.9 in the direction of the Pb beam. The correlation function, constructed from charged particles, exhibits a long-range (2<|Δη|<5) “near-side” (Δϕ∼0) correlation that grows rapidly with increasing ΣETPb. A long-range “away-side” (Δϕ∼π) correlation, obtained by subtracting the expected contributions from recoiling dijets and other sources estimated using events with small ΣETPb, is found to match the near-side correlation in magnitude, shape (in Δη and Δϕ) and ΣETPb dependence. The resultant Δϕ correlation is approximately symmetric about π/2, and is consistent with a dominant cos⁡2Δϕ modulation for all ΣETPb ranges and particle pT

Validation of the SF-36 in patients with endometriosis.

OBJECTIVES: Endometriosis presents with significant pain as the most common symptom. Generic health measures can allow comparisons across diseases or populations. However, the Medical Outcomes Study Short Form 36 (SF-36) has not been validated for this disease. The goal of this study was to validate the SF-36 (version 2) for endometriosis. METHODS: Using data from two clinical trials (N = 252 and 198) of treatment for endometriosis, a full complement of psychometric analyses was performed. Additional instruments included a pain visual analog scale (VAS); a physician-completed questionnaire based on patient interview (modified Biberoglu and Behrman--B&B); clinical global impression of change (CGI-C); and patient satisfaction with treatment. RESULTS: Bodily pain (BP) and the Physical Component Summary Score (PCS) were correlated with the pain VAS at baseline and over time and the B&B at baseline and end of study. In addition, those who had the greatest change in BP and PCS also reported the greatest change on CGI-C and patient satisfaction with treatment. Other subscales showed smaller, but significant, correlations with change in the pain VAS, CGI-C, and patient satisfaction with treatment. CONCLUSIONS: The SF-36--particularly BP and the PCS--appears to be a valid and responsive measure for endometriosis and its treatment

TB or not TB?

Object: The aim of the study was to identify diagnoses that are confused with pulmonary tuberculosis in children. Design: Prospective, investigative clinical study. Setting: Tertiary care teaching hospital and an urban tuberculosis clinic in an area with a very high incidence of pulmonary tuberculosis (&gt; 800 new cases/100 ODD/year). Patients: Children suspected of having tuberculosis, children followed up for pulmonary infiltrates with eosinophilia and children with congenital pulmonjiry anomalies were investigated. Intervention(s): None. Outcome measure: Pulmonary tuberculosis was diagnosed using modified World Health Organisation criteria and the diagnoses of those children not suffering from pulmonary tuberculosis were analysed. Results: Of the 354 children initially suspected of suffering from tuberculosis 71 (20%) were found to be suffering from other pulmonary disease, viz. pneumonia or bronchopneumonia (29%), bronchopneumonia with Wheezing (18%), and asthma with lobar or segmental collapse (12%). Of 14 children suffering from pulmonary infiltrates with peripheral eosinophilia 6 (43%) were initially incorrectly diagnosed and treated for tuberculosis. Of 54 children with congenital pulmonary anomalies, 8 (15%) were treated for tuberculosis before the correct diagnosis was made. Congenital anomalies most often confused with tuberculosis were unilateral lung hypoplasia, bronchogenic cyst and tracheal bronchus with an anomalous lobe. Conclusions: The criteria for diagnosing tuberculosis in children is complicated in areas with a high incidence of tuberculosis and poor socio-economic circumstances where many children presenting with conditions other than tuberculosis will be in contact with an adult case of pulmonary tuberculosis. The commonest conditions confused with tuberculosis are pneumonia, bronchopneumonia and asthma. Pulmonary infiltrates with  peripheral eosinophilia and congenital lung abnormalities should be considered especially if the children have an atypical clinical picture or do not respond to tuberculosis treatment.S Afr Med J 1995; 85: 658-66

Search for R-parity-violating supersymmetry in events with four or more leptons in sqrt(s) =7 TeV pp collisions with the ATLAS detector

A search for new phenomena in final states with four or more leptons (electrons or muons) is presented. The analysis is based on 4.7 fb−1 of $\sqrt{s}=7\;\mathrm{TeV}$ proton-proton collisions delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in two signal regions: one that requires moderate values of missing transverse momentum and another that requires large effective mass. The results are interpreted in a simplified model of R-parity-violating supersymmetry in which a 95% CL exclusion region is set for charged wino masses up to 540 GeV. In an R-parity-violating MSUGRA/CMSSM model, values of m 1/2 up to 820 GeV are excluded for 10 < tan β < 40

SIVagm Infection in Wild African Green Monkeys from South Africa: Epidemiology, Natural History, and Evolutionary Considerations

Pathogenesis studies of SIV infection have not been performed to date in wild monkeys due to difficulty in collecting and storing samples on site and the lack of analytical reagents covering the extensive SIV diversity. We performed a large scale study of molecular epidemiology and natural history of SIVagm infection in 225 free-ranging AGMs from multiple locations in South Africa. SIV prevalence (established by sequencing pol, env, and gag) varied dramatically between infant/juvenile (7%) and adult animals (68%) (p<0.0001), and between adult females (78%) and males (57%). Phylogenetic analyses revealed an extensive genetic diversity, including frequent recombination events. Some AGMs harbored epidemiologically linked viruses. Viruses infecting AGMs in the Free State, which are separated from those on the coastal side by the Drakensberg Mountains, formed a separate cluster in the phylogenetic trees; this observation supports a long standing presence of SIV in AGMs, at least from the time of their speciation to their Plio-Pleistocene migration. Specific primers/probes were synthesized based on the pol sequence data and viral loads (VLs) were quantified. VLs were of 104-106 RNA copies/ml, in the range of those observed in experimentally-infected monkeys, validating the experimental approaches in natural hosts. VLs were significantly higher (107-108 RNA copies/ml) in 10 AGMs diagnosed as acutely infected based on SIV seronegativity (Fiebig II), which suggests a very active transmission of SIVagm in the wild. Neither cytokine levels (as biomarkers of immune activation) nor sCD14 levels (a biomarker of microbial translocation) were different between SIV-infected and SIV-uninfected monkeys. This complex algorithm combining sequencing and phylogeny, VL quantification, serology, and testing of surrogate markers of microbial translocation and immune activation permits a systematic investigation of the epidemiology, viral diversity and natural history of SIV infection in wild African natural hosts. © 2013 Ma et al

The Cognitive Ecology of the Internet

In this chapter, we analyze the relationships between the Internet and its users in terms of situated cognition theory. We first argue that the Internet is a new kind of cognitive ecology, providing almost constant access to a vast amount of digital information that is increasingly more integrated into our cognitive routines. We then briefly introduce situated cognition theory and its species of embedded, embodied, extended, distributed and collective cognition. Having thus set the stage, we begin by taking an embedded cognition view and analyze how the Internet aids certain cognitive tasks. After that, we conceptualize how the Internet enables new kinds of embodied interaction, extends certain aspects of our embodiment, and examine how wearable technologies that monitor physiological, behavioral and contextual states transform the embodied self. On the basis of the degree of cognitive integration between a user and Internet resource, we then look at how and when the Internet extends our cognitive processes. We end this chapter with a discussion of distributed and collective cognition as facilitated by the Internet

The Bandim TBscore – reliability, further development, and evaluation of potential uses

Background: The tuberculosis (TB) case detection rate has stagnated at 60% due to disorganized case finding and insensitivity of sputum smear microscopy. Of the identified TB cases, 4% die while being treated, monitored with tools that insufficiently predict failure/mortality. Objective: To explore the TBscore, a recently proposed clinical severity measure for pulmonary TB (PTB) patients, and to refine, validate, and investigate its place in case finding. Design: The TBscore's inter-observer agreement was assessed and compared to the Karnofsky Performance Score (KPS) (paper I). The TBscore's variables underlying constructs were assessed, sorting out unrelated items, proposing a more easily assessable TBscoreII, which was validated internally and externally (paper II). Finally, TBscore and TBscoreII's place in PTB-screening was examined in paper III. Results: The inter-observer variability when grading PTB patients into severity classes was moderate for both TBscore (κ W=0.52, 95% CI 0.46–0.56) and KPS (κ W=0.49, 95% CI 0.33–0.65). KPS was influenced by HIV status, whereas TBscore was unaffected by it. In paper II, proposed TBscoreII was validated internally, in Guinea-Bissau, and externally, in Ethiopia. In both settings, a failure to bring down the score by ≥25% from baseline to 2 months of treatment predicted subsequent failure (p=0.007). Finally, in paper III, TBscore and TBscoreII were assessed in health-care-seeking adults and found to be higher in PTB-diagnosed patients, 4.9 (95% CI 4.6–5.2) and 3.9 (95% CI 3.8–4.0), respectively, versus patients not diagnosed with PTB, 3.0 (95% CI 2.7–3.2) and 2.4 (95% CI 2.3–2.5), respectively. Had we referred only patients with cough >2 weeks to sputum smear, we would have missed 32.1% of the smear confirmed cases in our cohort. A TBscoreII>=2 missed 8.6%. Conclusions: TBscore and TBscoreII are useful monitoring tools for PTB patients on treatment, as they could fill the void which currently exists in risk grading of patients. They may also have a role in PTB screening; however, this requires our findings to be repeated elsewhere