Spline-based modelling of trends in the force of HIV infection, with application to the UNAIDS Estimation and Projection Package

Objective: We previously developed a flexible specification of the UNAIDS Estimation and Projection Package (EPP) that relied on splines to generate time-varying values for the force of infection parameter. Here, we test the feasibility of this approach for concentrated HIV/AIDS epidemics with very sparse data and compare two methods for making short-term future projections with the spline-based model. Methods: Penalised B-splines are used to model the average infection risk over time within the EPP 2011 modelling framework, which includes antiretroviral treatment effects and CD4 cell count progression, and is fit to sentinel surveillance prevalence data with a Bayesian algorithm. We compare two approaches for future projections: (1) an informative prior related to equilibrium prevalence and (2) a random walk formulation. Results: The spline-based model produced plausible fits across a range of epidemics, which included 87 subpopulations from 14 countries with concentrated epidemics and 75 subpopulations from 33 countries with generalised epidemics. The equilibrium prior and random walk approaches to future projections yielded similar prevalence estimates, and both performed well in tests of out-of-sample predictive validity for prevalence. In contrast, in some cases the two approaches varied substantially in estimates of incidence, with the random walk formulation avoiding extreme changes in incidence. Conclusions: A spline-based approach to allowing the force of infection parameter to vary over time within EPP 2011 is robust across a diverse array of epidemics, including concentrated ones with limited surveillance data. Future work on the EPP model should consider the impact that different modelling approaches have on estimates of HIV incidence

Risk of miscarriage following amniocentesis or chorionic villus sampling: systematic review of literature and updated meta-analysis

Objectives: To estimate the procedure-related risks of miscarriage after amniocentesis and trans-abdominal chorionic villus sampling (CVS) based on a systematic review of the literature and an updated meta-analysis. Methods: A search of MEDLINE, EMBASE, and The Cochrane Library was carried out to identify studies reporting complications following CVS or amniocentesis. The inclusion criteria for the systematic review were studies reporting results from large controlled studies and those reporting data for pregnancy loss prior to 24 weeks’ gestation. Study authors were contacted when required to identify additional necessary data. Data for cases that had invasive procedure and controls groups were inputted in contingency tables and risk of miscarriage was estimated for each study. Summary statistics based on a fixed and random effects model were calculated after taking into account the weighting for each study included in the systematic review. Procedure-related risk of miscarriage was estimated as a weighted risk difference from the summary statistics for cases and controls. A subgroup analyses according to the similarity risk levels in the invasive testing and control groups was performed. Heterogeneity was assessed using Cochrane’s Q and I2 statistic. Egger Bias was estimated to assess reporting bias in published studies. Summary statistics for procedure-related risk of miscarriage were graphically represented in Forest plots. Results: The electronic search from the databases yielded 2,943 potential citations, from which, we selected 20 controlled studies for inclusion in the systematic review to estimate the procedure-related risk of miscarriage from invasive procedures. There were a total of 580 miscarriages from 63,273 amniocentesis procedures with a weighted risk of pregnancy loss of 0.91% (95%CI: 0.73 to 1.09). In the control group, there were 1,726 miscarriages in 330,469 pregnancies with a loss rate of 0.58% (95CI%: 0.47 to 0.70). The weighted procedure-related risk of miscarriage was 0.30% (95%CI: 0.11 to 0.49, I2=70.1%). There were a total of 163 miscarriages from 13,011 CVS procedures with a risk of pregnancy loss of 1.39% (95%CI: 0.76 to 2.02). In the control group, there were 1,946 miscarriages in 232,680 pregnancies with a loss rate of 1.23% (95CI%: 0.86 to 1.59). The weighted procedure-related risk of miscarriage following CVS was 0.20% (95%CI: -0.12 to 0.52, I2=51.9%). However, when only studies with similar risk profiles between the intervention and control groups were considered, the procedure related risk for amniocentesis became 0.03% (95%CI -0.08 to 0.14, I2=0%) and for CVS -0.38 (95% CI -1.12 to 0.36, I2=0%). Conclusion: The procedure-related risks of miscarriage following amniocentesis and CVS are lower than currently quoted to women. The risk appears to be negligible when these interventions are compared to control groups of the same risk profile

Assessing and adjusting for differences between HIV prevalence estimates derived from national population-based surveys and antenatal care surveillance, with applications for Spectrum 2013

Objective(s): To assess differences between HIV prevalence estimates derived from national population surveys and antenatal care (ANC) surveillance sites and to improve the calibration of ANC-derived estimates in Spectrum 2013 to more appropriately account for differences between these data. Design: Retrospective analysis of national population survey and ANC surveillance data from 25 countries with generalized epidemics in sub-Saharan Africa and 8 countries with concentrated epidemics. Methods: Adult national population survey and ANC surveillance HIV prevalence estimates were compared for all available national population survey data points for the years 1999–2012. For sub-Saharan Africa, a mixed-effects linear regression model determined whether the relationship between national population and ANC estimates was constant across surveys. A new calibration method was developed to incorporate national population survey data directly into the likelihood for HIV prevalence in countries with generalized epidemics. Results were used to develop default rules for adjusting ANC data for countries with no national population surveys. Results: ANC surveillance data typically overestimate population prevalence, although a wide variation, particularly in rural areas, is observed across countries and survey years. The new calibration method yields similar point estimates to previous approaches, but leads to an average 44% increase in the width of 95% uncertainty intervals. Conclusion: Important biases remain in ANC surveillance data for HIV prevalence. The new approach to model-fitting in Spectrum 2013 more appropriately accounts for this bias when producing national estimates in countries with generalized epidemics. In countries with concentrated epidemics, local sex ratios should be used to calibrate ANC surveillance estimates

Photoassociative creation of ultracold heteronuclear 6Li40K* molecules

We investigate the formation of weakly bound, electronically excited, heteronuclear 6Li40K* molecules by single-photon photoassociation in a magneto-optical trap. We performed trap loss spectroscopy within a range of 325 GHz below the Li(2S_(1/2))+K(4P_(3/2)) and Li(2S_(1/2))+K(4P_(1/2)) asymptotic states and observed more than 60 resonances, which we identify as rovibrational levels of 7 of 8 attractive long-range molecular potentials. The long-range dispersion coefficients and rotational constants are derived. We find large molecule formation rates of up to ~3.5x10^7s^(-1), which are shown to be comparable to those for homonuclear 40K_2*. Using a theoretical model we infer decay rates to the deeply bound electronic ground-state vibrational level X^1\Sigma^+(v'=3) of ~5x10^4s^(-1). Our results pave the way for the production of ultracold bosonic ground-state 6Li40K molecules which exhibit a large intrinsic permanent electric dipole moment.Comment: 6 pages, 4 figures, submitted to EP

Measurements and Simulation Studies of Piezoceramics for Acoustic Particle Detection

Calibration sources are an indispensable tool for all detectors. In acoustic particle detection the goal of a calibration source is to mimic neutrino signatures as expected from hadronic cascades. A simple and promising method for the emulation of neutrino signals are piezo ceramics. We will present results of measruements and simulations on these piezo ceramics.Comment: 5 pages, 5 figure

Metastability in spin polarised Fermi gases and quasiparticle decays

We investigate the metastability associated with the first order transition from normal to superfluid phases in the phase diagram of two-component polarised Fermi gases.We begin by detailing the dominant decay processes of single quasiparticles.Having determined the momentum thresholds of each process and calculated their rates, we apply this understanding to a Fermi sea of polarons by linking its metastability to the stability of individual polarons, and predicting a region of metastability for the normal partially polarised phase. In the limit of a single impurity, this region extends from the interaction strength at which a polarised phase of molecules becomes the groundstate, to the one at which the single quasiparticle groundstate changes character from polaronic to molecular. Our argument in terms of a Fermi sea of polarons naturally suggests their use as an experimental probe. We propose experiments to observe the threshold of the predicted region of metastability, the interaction strength at which the quasiparticle groundstate changes character, and the decay rate of polarons

Tests of relativity using a microwave resonator

The frequencies of a cryogenic sapphire oscillator and a hydrogen maser are compared to set new constraints on a possible violation of Lorentz invariance. We determine the variation of the oscillator frequency as a function of its orientation (Michelson-Morley test) and of its velocity (Kennedy-Thorndike test) with respect to a preferred frame candidate. We constrain the corresponding parameters of the Mansouri and Sexl test theory to $\delta - \beta + 1/2 = (1.5\pm 4.2) \times 10^{-9}$ and $\beta - \alpha - 1 = (-3.1\pm 6.9) \times 10^{-7}$ which is equivalent to the best previous result for the former and represents a 30 fold improvement for the latter.Comment: 8 pages, 2 figures, submitted to Physical Review Letters (October 3, 2002

Identification of two distinct structural regions in a human porcine endogenous retrovirus receptor, HuPAR2, contributing to function for viral entry

<p>Abstract</p> <p>Background</p> <p>Of the three subclasses of Porcine Endogenous Retrovirus (PERV), PERV-A is able to infect human cells via one of two receptors, HuPAR1 or HuPAR2. Characterizing the structure-function relationships of the two HuPAR receptors in PERV-A binding and entry is important in understanding receptor-mediated gammaretroviral entry and contributes to evaluating the risk of zoonosis in xenotransplantation.</p> <p>Results</p> <p>Chimeras of the non-permissive murine PAR and the permissive HuPAR2, which scanned the entire molecule, revealed that the first 135 amino acids of HuPAR2 are critical for PERV-A entry. Within this critical region, eighteen single residue differences exist. Site-directed mutagenesis used to map single residues confirmed the previously identified L109 as a binding and infectivity determinant. In addition, we identified seven residues contributing to the efficiency of PERV-A entry without affecting envelope binding, located in multiple predicted structural motifs (intracellular, extracellular and transmembrane). We also show that expression of HuPAR2 in a non-permissive cell line results in an average 11-fold higher infectivity titer for PERV-A compared to equal expression of HuPAR1, although PERV-A envelope binding is similar. Chimeras between HuPAR-1 and -2 revealed that the region spanning amino acids 152–285 is responsible for the increase of HuPAR2. Fine mapping of this region revealed that the increased receptor function required the full sequence rather than one or more specific residues.</p> <p>Conclusion</p> <p>HuPAR2 has two distinct structural regions. In one region, a single residue determines binding; however, in both regions, multiple residues influence receptor function for PERV-A entry.</p