Low specificity of determine HIV1/2 RDT using whole blood in south west Tanzania

Objective: To evaluate the diagnostic performance of two rapid detection tests (RDTs) for HIV 1/2 in plasma and in whole blood samples. Methods: More than 15,000 study subjects above the age of two years participated in two rounds of a cohort study to determine the prevalence of HIV. HIV testing was performed using the Determine HIV 1/2 test (Abbott) in the first (2006/2007) and the HIV 1/2 STAT-PAK Dipstick Assay (Chembio) in the second round (2007/2008) of the survey. Positive results were classified into faint and strong bands depending on the visual appearance of the test strip and confirmed by ELISA and Western blot. Results: The sensitivity and specificity of the Determine RDT were 100% (95% confidence interval = 86.8 to 100%) and 96.8% (95.9 to 97.6%) in whole blood and 100% (99.7 to 100%) and 97.9% (97.6 to 98.1%) in plasma respectively. Specificity was highly dependent on the tested sample type: when using whole blood, 67.1% of positive results were false positive, as opposed to 17.4% in plasma. Test strips with only faint positive bands were more often false positive than strips showing strong bands and were more common in whole blood than in plasma. Evaluation of the STAT-PAK RDT in plasma during the second year resulted in a sensitivity of 99.7% (99.1 to 99.9%) and a specificity of 99.3% (99.1 to 99.4%) with 6.9% of the positive results being false. Conclusions: Our study shows that the Determine HIV 1/2 strip test with its high sensitivity is an excellent tool to screen for HIV infection, but that – at least in our setting – it can not be recommended as a confirmatory test in VCT campaigns where whole blood is used

Classical and quantum: a conflict of interest

We highlight three conflicts between quantum theory and classical general relativity, which make it implausible that a quantum theory of gravity can be arrived at by quantising classical gravity. These conflicts are: quantum nonlocality and space-time structure; the problem of time in quantum theory; and the quantum measurement problem. We explain how these three aspects bear on each other, and how they point towards an underlying noncommutative geometry of space-time.Comment: 15 pages. Published in `Gravity and the quantum' [Essays in honour of Thanu Padmanabhan on the occasion of his sixtieth birthday] Eds. Jasjeet Singh Bagla and Sunu Engineer (Springer, 2017

Spontaneous R-Parity Violation, A4A_4 Flavor Symmetry and Tribimaximal Mixing

We explore the possibility of spontaneous R parity violation in the context of $A_4$ flavor symmetry. Our model contains $SU(3)_c \times SU(2)_L \times U(1)_Y$ singlet matter chiral superfields which are arranged as triplet of $A_4$ and as well as few additional Higgs chiral superfields which are singlet under MSSM gauge group and belong to triplet and singlet representation under the $A_4$ flavor symmetry. R parity is broken spontaneously by the vacuum expectation values of the different sneutrino fields and hence we have neutrino-neutralino as well as neutrino-MSSM gauge singlet higgsino mixings in our model, in addition to the standard model neutrino- gauge singlet neutrino, gaugino-higgsino and higgsino-higgsino mixings. Because all of these mixings we have an extended neutral fermion mass matrix. We explore the low energy neutrino mass matrix for our model and point out that with some specific constraints between the sneutrino vacuum expectation values as well as the MSSM gauge singlet Higgs vacuum expectation values, the low energy neutrino mass matrix will lead to a tribimaximal mixing matrix. We also analyze the potential minimization for our model and show that one can realize a higher vacuum expectation value of the $SU(3)_c \times SU(2)_L \times U(1)_Y$ singlet sneutrino fields even when the other sneutrino vacuum expectation values are extremely small or even zero.Comment: 18 page

The Golden Ratio Prediction for the Solar Angle from a Natural Model with A5 Flavour Symmetry

We formulate a consistent model predicting, in the leading order approximation, maximal atmospheric mixing angle, vanishing reactor angle and tan {\theta}_12 = 1/{\phi} where {\phi} is the Golden Ratio. The model is based on the flavour symmetry A5 \times Z5 \times Z3, spontaneously broken by a set of flavon fields. By minimizing the scalar potential of the theory up to the next-to-leading order in the symmetry breaking parameter, we demonstrate that this mixing pattern is naturally achieved in a finite portion of the parameter space, through the vacuum alignment of the flavon fields. The leading order approximation is stable against higher-order corrections. We also compare our construction to other models based on discrete symmetry groups.Comment: 28 pages, 2 figures. Minor changes, references added. Corrected typos in Appendix A. Version appeared on JHE

Unravelling the genome-wide contributions of specific 2-alkyl-4-quinolones and PqsE to quorum sensing in Pseudomonas aeruginosa

The pqs quorum sensing (QS) system is crucial for Pseudomonas aeruginosa virulence both in vitro and in animal models of infection and is considered an ideal target for the development of anti-virulence agents. However, the precise role played by each individual component of this complex QS circuit in the control of virulence remains to be elucidated. Key components of the pqs QS system are 2-heptyl-4-hydroxyquinoline (HHQ), 2-heptyl-3-hydroxy-4-quinolone (PQS), 2-heptyl-4-hydroxyquinoline N-oxide (HQNO), the transcriptional regulator PqsR and the PQS-effector element PqsE. To define the individual contribution of each of these components to QS-mediated regulation, transcriptomic analyses were performed and validated on engineered P. aeruginosa strains in which the biosynthesis of 2-alkyl 4-quinolones (AQs) and expression of pqsE and pqsR have been uncoupled, facilitating the identification of the genes controlled by individual pqs system components. The results obtained demonstrate that i) the PQS biosynthetic precursor HHQ triggers a PqsR-dependent positive feedback loop that leads to the increased expression of only the pqsABCDE operon, ii) PqsE is involved in the regulation of diverse genes coding for key virulence determinants and biofilm development, iii) PQS promotes AQ biosynthesis, the expression of genes involved in the iron-starvation response and virulence factor production via PqsR-dependent and PqsR-independent pathways, and iv) HQNO does not influence transcription and hence does not function as a QS signal molecule. Overall this work has facilitated identification of the specific regulons controlled by individual pqs system components and uncovered the ability of PQS to contribute to gene regulation independent of both its ability to activate PqsR and to induce the iron-starvation response

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Mixed Mediation of Supersymmetry Breaking with Anomalous U(1) Gauge Symmetry

Models with anomalous U(1) gauge symmetry contain various superfields which can have nonzero supersymmetry breaking auxiliary components providing the origin of soft terms in the visible sector, e.g. the U(1) vector superfield, the modulus or dilaton superfield implementing the Green-Schwarz anomaly cancellation mechanism, U(1)-charged but standard model singlet matter superfield required to cancel the Fayet-Iliopoulos term, and finally the supergravity multiplet. We examine the relative strength between these supersymmetry breaking components in a simple class of models, and find that various different mixed mediations of supersymmetry breaking, involving the modulus, gauge, anomaly and D-term mediations, can be realized depending upon the characteristics of D-flat directions and how those D-flat directions are stabilized with a vanishing cosmological constant. We identify two parameters which represent such properties and thus characterize how the various mediations are mixed. We also discuss the moduli stabilization and soft terms in a variant of KKLT scenario, in which the visible sector K\"ahler modulus is stabilized by the D-term potential of anomalous U(1) gauge symmetry.Comment: 30 pages, 5 figure

New Zealand blackcurrant extract enhances fat oxidation during prolonged cycling in endurance-trained females.

PURPOSE: New Zealand blackcurrant (NZBC) extract has previously been shown to increase fat oxidation during prolonged exercise, but this observation is limited to males. We examined whether NZBC intake also increases fat oxidation during prolonged exercise in females, and whether this was related to greater concentrations of circulating fatty acids. METHODS: In a randomised, crossover, double-blind design, 16 endurance-trained females (age: 28 ± 8 years, BMI: 21.3 ± 2.1 kg·m-2, VO2max: 43.7 ± 1.1 ml·kg-1·min-1) ingested 600 mg·day-1NZBC extract (CurraNZ™) or placebo (600 mg·day-1microcrystalline cellulose) for 7 days. On day 7, participants performed 120 min cycling at 65% VO2max, using online expired air sampling with blood samples collected at baseline and at 15 min intervals throughout exercise for analysis of glucose, NEFA and glycerol. RESULTS: NZBC extract increased mean fat oxidation by 27% during 120 min moderate-intensity cycling compared to placebo (P = 0.042), and mean carbohydrate oxidation tended to be lower (P = 0.063). Pre-exercise, plasma NEFA (P = 0.034) and glycerol (P = 0.051) concentrations were greater following NZBC intake, although there was no difference between conditions in the exercise-induced increase in plasma NEFA and glycerol concentrations (P > 0.05). Mean fat oxidation during exercise was moderately associated with pre-exercise plasma NEFA concentrations (r = 0.45, P = 0.016). CONCLUSIONS: Intake of NZBC extract for 7 days elevated resting concentrations of plasma NEFA and glycerol, indicative of higher lipolytic rates, and this may underpin the observed increase in fat oxidation during prolonged cycling in endurance-trained females

Can psychosocial and socio-demographic questions help identify sexual risk among heterosexually-active women of reproductive age? Evidence from Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3)

Background: Contraceptive advice and supply (CAS) and sexually transmitted infection (STI) testing are increasingly provided in primary care. Most risk assessment tools are based on sexual risk behaviours and socio-demographics, for use online or in specialist services. Combining socio-demographic and psychosocial questions (e.g. religious belief and formative experience) may generate an acceptable tool for targeting women in primary care who would benefit from intervention. We aimed to identify psychosocial and socio-demographic factors associated with reporting key sexual risk behaviours among women in the British general population. Methods: We undertook complex survey analysis of data from 4,911 hetero-sexually active women aged 16-44 years, who participated in Britain’s third National Survey of Sexual Attitudes and Lifestyles (Natsal-3), a national probability sample survey undertaken 2010-2012. We used multivariable regression to examine associations between the available psychosocial and socio-demographic variables in Natsal-3 and reports of 3 key sexual behaviours: a) 2+ partners in the last year (2PP); b) non-use of condoms with 2+ partners in the last year (2PPNC); c) non-use of condoms at first sex with most recent sexual partner (FSNC). We adjusted for key socio-demographic factors: age, ethnicity and socio-economic status (measured by housing tenure). Results: Weekly binge drinking (6+ units on one occasion), and first sex before age 16 were each positively associated with all three sexual behaviours after adjustment. Current relationship status, reporting drug use (ever), younger age and living in rented accommodation were also associated with 2+ partners and 2+partners without condoms after adjustment. Currently being a smoker, older age and respondent ethnicity were associated with FSNC after adjustment for all other variables. Current smoking status, treatment for depression (last year), and living at home with both parents until the age of 14 were each associated with 1 or more of the behaviours. Conclusions: Reported weekly binge drinking, early sexual debut, and age group may help target STI testing and/or CAS among women. Further research is needed to examine the proportion of sexual risk explained by these factors, the acceptability of these questions to women in primary care and the need to customise them for community and other settings

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns