Effects of CMB temperature uncertainties on cosmological parameter estimation

We estimate the effect of the experimental uncertainty in the measurement of the temperature of the cosmic microwave background (CMB) on the extraction of cosmological parameters from future CMB surveys. We find that even for an ideal experiment limited only by cosmic variance up to l = 2500 for both the temperature and polarisation measurements, the projected cosmological parameter errors are remarkably robust against the uncertainty of 1 mK in the FIRAS instrument's CMB temperature monopole measurement. The maximum degradation in sensitivity is 20%, for the baryon density estimate, relative to the case in which the monopole is known infinitely well. While this degradation is acceptable, we note that reducing the uncertainty in the current temperature measurement by a factor of five will bring it down to the per cent level. We also estimate the effect of the uncertainty in the dipole temperature measurement. Assuming the overall calibration of the data to be dominated by the dipole error of 0.2% from FIRAS, the sensitivity degradation is insignificant and does not exceed 10% in any parameter direction.Comment: 12 pages, 2 figures, uses iopart.cls, v2: added discussion of CMB dipole uncertainty, version accepted by JCA

Sterile neutrinos with eV masses in cosmology -- how disfavoured exactly?

We study cosmological models that contain sterile neutrinos with eV-range masses as suggested by reactor and short-baseline oscillation data. We confront these models with both precision cosmological data (probing the CMB decoupling epoch) and light-element abundances (probing the BBN epoch). In the minimal LambdaCDM model, such sterile neutrinos are strongly disfavoured by current data because they contribute too much hot dark matter. However, if the cosmological framework is extended to include also additional relativistic degrees of freedom -- beyond the three standard neutrinos and the putative sterile neutrinos, then the hot dark matter constraint on the sterile states is considerably relaxed. A further improvement is achieved by allowing a dark energy equation of state parameter w<-1. While BBN strongly disfavours extra radiation beyond the assumed eV-mass sterile neutrino, this constraint can be circumvented by a small nu_e degeneracy. Any model containing eV-mass sterile neutrinos implies also strong modifications of other cosmological parameters. Notably, the inferred cold dark matter density can shift up by 20 to 75% relative to the standard LambdaCDM value.Comment: 14 pages, 6 figures, v2: minor changes, matches version accepted for publication in JCA

The constraint equations for the Einstein-scalar field system on compact manifolds

We study the constraint equations for the Einstein-scalar field system on compact manifolds. Using the conformal method we reformulate these equations as a determined system of nonlinear partial differential equations. By introducing a new conformal invariant, which is sensitive to the presence of the initial data for the scalar field, we are able to divide the set of free conformal data into subclasses depending on the possible signs for the coefficients of terms in the resulting Einstein-scalar field Lichnerowicz equation. For many of these subclasses we determine whether or not a solution exists. In contrast to other well studied field theories, there are certain cases, depending on the mean curvature and the potential of the scalar field, for which we are unable to resolve the question of existence of a solution. We consider this system in such generality so as to include the vacuum constraint equations with an arbitrary cosmological constant, the Yamabe equation and even (all cases of) the prescribed scalar curvature problem as special cases.Comment: Minor changes, final version. To appear: Classical and Quantum Gravit

Einstein and Yang-Mills theories in hyperbolic form without gauge-fixing

The evolution of physical and gauge degrees of freedom in the Einstein and Yang-Mills theories are separated in a gauge-invariant manner. We show that the equations of motion of these theories can always be written in flux-conservative first-order symmetric hyperbolic form. This dynamical form is ideal for global analysis, analytic approximation methods such as gauge-invariant perturbation theory, and numerical solution.Comment: 12 pages, revtex3.0, no figure

Comparison and relative utility of inequality measurements: as applied to Scotland’s child dental health

This study compared and assessed the utility of tests of inequality on a series of very large population caries datasets. National cross-sectional caries datasets for Scotland’s 5-year-olds in 1993/94 (n = 5,078); 1995/96 (n = 6,240); 1997/98 (n = 6,584); 1999/00 (n = 6,781); 2002/03 (n = 9,747); 2003/04 (n = 10,956); 2005/06 (n = 10,945) and 2007/08 (n = 12,067) were obtained. Outcomes were based on the d3mft metric (i.e. the number of decayed, missing and filled teeth). An area-based deprivation category (DepCat) measured the subjects’ socioeconomic status (SES). Simple absolute and relative inequality, Odds Ratios and the Significant Caries Index (SIC) as advocated by the World Health Organization were calculated. The measures of complex inequality applied to data were: the Slope Index of Inequality (absolute) and a variety of relative inequality tests i.e. Gini coefficient; Relative Index of Inequality; concentration curve; Koolman and Doorslaer’s transformed Concentration Index; Receiver Operator Curve and Population Attributable Risk (PAR). Additional tests used were plots of SIC deciles (SIC10) and a Scottish Caries Inequality Metric (SCIM10). Over the period, mean d3mft improved from 3.1(95%CI 3.0–3.2) to 1.9(95%CI 1.8–1.9) and d3mft = 0% from 41.1(95%CI 39.8–42.3) to 58.3(95%CI 57.8–59.7). Absolute simple and complex inequality decreased. Relative simple and complex inequality remained comparatively stable. Our results support the use of the SII and RII to measure complex absolute and relative SES inequalities alongside additional tests of complex relative inequality such as PAR and Koolman and Doorslaer’s transformed CI. The latter two have clear interpretations which may influence policy makers. Specialised dental metrics (i.e. SIC, SIC10 and SCIM10) permit the exploration of other important inequalities not determined by SES, and could be applied to many other types of disease where ranking of morbidity is possible e.g. obesity. More generally, the approaches described may be applied to study patterns of health inequality affecting worldwide populations

Plasmodium falciparum Resistance to a Lead Benzoxaborole Due to Blocked Compound Activation and Altered Ubiquitination or Sumoylation.

New antimalarial drugs are needed. The benzoxaborole AN13762 showed excellent activity against cultured Plasmodium falciparum, against fresh Ugandan P. falciparum isolates, and in murine malaria models. To gain mechanistic insights, we selected in vitro for P. falciparum isolates resistant to AN13762. In all of 11 independent selections with 100 to 200 nM AN13762, the 50% inhibitory concentration (IC50) increased from 18-118 nM to 180-890 nM, and whole-genome sequencing of resistant parasites demonstrated mutations in prodrug activation and resistance esterase (PfPARE). The introduction of PfPARE mutations led to a similar level of resistance, and recombinant PfPARE hydrolyzed AN13762 to the benzoxaborole AN10248, which has activity similar to that of AN13762 but for which selection of resistance was not readily achieved. Parasites further selected with micromolar concentrations of AN13762 developed higher-level resistance (IC50, 1.9 to 5.0 μM), and sequencing revealed additional mutations in any of 5 genes, 4 of which were associated with ubiquitination/sumoylation enzyme cascades; the introduction of one of these mutations, in SUMO-activating enzyme subunit 2, led to a similar level of resistance. The other gene mutated in highly resistant parasites encodes the P. falciparum cleavage and specificity factor homolog PfCPSF3, previously identified as the antimalarial target of another benzoxaborole. Parasites selected for resistance to AN13762 were cross-resistant with a close analog, AN13956, but not with standard antimalarials, AN10248, or other benzoxaboroles known to have different P. falciparum targets. Thus, AN13762 appears to have a novel mechanism of antimalarial action and multiple mechanisms of resistance, including loss of function of PfPARE preventing activation to AN10248, followed by alterations in ubiquitination/sumoylation pathways or PfCPSF3.IMPORTANCE Benzoxaboroles are under study as potential new drugs to treat malaria. One benzoxaborole, AN13762, has potent activity and promising features, but its mechanisms of action and resistance are unknown. To gain insights into these mechanisms, we cultured malaria parasites with nonlethal concentrations of AN13762 and generated parasites with varied levels of resistance. Parasites with low-level resistance had mutations in PfPARE, which processes AN13762 into an active metabolite; PfPARE mutations prevented this processing. Parasites with high-level resistance had mutations in any of a number of enzymes, mostly those involved in stress responses. Parasites selected for AN13762 resistance were not resistant to other antimalarials, suggesting novel mechanisms of action and resistance for AN13762, a valuable feature for a new class of antimalarial drugs

Identifying factors likely to influence compliance with diagnostic imaging guideline recommendations for spine disorders among chiropractors in North America: a focus group study using the Theoretical Domains Framework

Background: The Theoretical Domains Framework (TDF) was developed to investigate determinants of specific clinical behaviors and inform the design of interventions to change professional behavior. This framework was used to explore the beliefs of chiropractors in an American Provider Network and two Canadian provinces about their adherence to evidence-based recommendations for spine radiography for uncomplicated back pain. The primary objective of the study was to identify chiropractors’ beliefs about managing uncomplicated back pain without xrays and to explore barriers and facilitators to implementing evidence-based recommendations on lumbar spine xrays. A secondary objective was to compare chiropractors in the United States and Canada on their beliefs regarding the use of spine x-rays. Methods: Six focus groups exploring beliefs about managing back pain without x-rays were conducted with a purposive sample. The interview guide was based upon the TDF. Focus groups were digitally recorded, transcribed verbatim, and analyzed by two independent assessors using thematic content analysis based on the TDF. Results: Five domains were identified as likely relevant. Key beliefs within these domains included the following: conflicting comments about the potential consequences of not ordering x-rays (risk of missing a pathology, avoiding adverse treatment effects, risks of litigation, determining the treatment plan, and using x-ray-driven techniques contrasted with perceived benefits of minimizing patient radiation exposure and reducing costs; beliefs about consequences); beliefs regarding professional autonomy, professional credibility, lack of standardization, and agreement with guidelines widely varied (social/professional role & identity); the influence of formal training, colleagues, and patients also appeared to be important factors (social influences); conflicting comments regarding levels of confidence and comfort in managing patients without x-rays (belief about capabilities); and guideline awareness and agreements (knowledge). Conclusions: Chiropractors’ use of diagnostic imaging appears to be influenced by a number of factors. Five key domains may be important considering the presence of conflicting beliefs, evidence of strong beliefs likely to impact the behavior of interest, and high frequency of beliefs. The results will inform the development of a theorybased survey to help identify potential targets for behavioral-change strategies