The association of HBV core promoter double mutations (A1762T and G1764A) with viral load differs between HBeAg positive and anti-HBe positive individuals: A longitudinal analysis

Background/Aims: Although there have been a few reports regarding the effect of basal core promoter (BCP) double mutations (A1762T and G1764A) on hepatitis B viral loads, the association remains uncertain. We aim to determine the association after controlling for HBeAg - a strong confounding factor.Methods: We selected randomly 190 individuals from a Chinese cohort of 2258 subjects for cross-sectional analysis and 56 of the 190 for longitudinal analysis of viral loads.Results: In multivariable analysis of the cross-sectional data, BCP double mutations are significantly associated with lower viral loads in HBeAg positive subjects but no difference was found in anti-HBe positive subjects. Triple mutations at nucleotide (nt) 1753, 1762 and 1764 and mutations between nt 1809 and 1817, precore stop mutation (nt 1896) and genotype are not associated with viral loads in either HBeAg or anti-HBe positive subjects. Analysis of the longitudinal data yielded similar results to the cross-sectional data. Viral loads differ significantly between individuals infected with wild-type and BCP double mutations prior to HBeAg seroconversion but this difference is lost after seroconversion.Conclusions: BCP double mutations are associated with lower viral loads in HBeAg positive individuals but have no effect on the viral loads of anti-HBe positive individuals. (C) 2008 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved

A prospective study of mortality from cryptococcal meningitis following treatment induction with 1200 mg oral fluconazole in Blantyre, Malawi.

OBJECTIVE: We have previously reported high ten-week mortality from cryptococcal meningitis in Malawian adults following treatment-induction with 800 mg oral fluconazole (57% [33/58]). National guidelines in Malawi and other African countries now advocate an increased induction dose of 1200 mg. We assessed whether this has improved outcomes. DESIGN: This was a prospective observational study of HIV-infected adults with cryptococcal meningitis confirmed by diagnostic lumbar puncture. Treatment was with fluconazole 1200 mg/day for two weeks then 400mg/day for 8 weeks. Mortality within the first 10 weeks was the study end-point, and current results were compared with data from our prior patient cohort who started on fluconazole 800 mg/day. RESULTS: 47 participants received fluconazole monotherapy. Despite a treatment-induction dose of 1200 mg, ten-week mortality remained 55% (26/47). This was no better than our previous study (Hazard Ratio [HR] of death on 1200 mg vs. 800 mg fluconazole: 1.29 (95% CI: 0.77-2.16, p = 0.332)). There was some evidence for improved survival in patients who had repeat lumbar punctures during early therapy to lower intracranial pressure (HR: 0.27 [95% CI: 0.07-1.03, p = 0.055]). CONCLUSION: There remains an urgent need to identify more effective, affordable and deliverable regimens for cryptococcal meningitis

Linear-scaling time-dependent density-functional theory in the linear response formalism

We present an implementation of time-dependent density-functional theory (TDDFT) in the linear response formalism enabling the calculation of low energy optical absorption spectra for large molecules and nanostructures. The method avoids any explicit reference to canonical representations of either occupied or virtual Kohn-Sham states and thus achieves linear-scaling computational effort with system size. In contrast to conventional localised orbital formulations, where a single set of localised functions is used to span the occupied and unoccupied state manifold, we make use of two sets of in situ optimised localised orbitals, one for the occupied and one for the unoccupied space. This double representation approach avoids known problems of spanning the space of unoccupied Kohn-Sham states with a minimal set of localised orbitals optimised for the occupied space, while the in situ optimisation procedure allows for efficient calculations with a minimal number of functions. The method is applied to a number of medium sized organic molecules and a good agreement with traditional TDDFT methods is observed. Furthermore, linear scaling of computational cost with system size is demonstrated on a system of carbon nanotubes

Financing methods for small-scale hardwood plantations in Queensland, Australia

Under Vision 2020, a target was set in 1997 for trebling the plantation area in Australia by the year 2020. Government subsidies and extension for plantation establishment have largely disappeared, hence forestry expansion is highly dependent on access to private finance. In the state of Queensland, plantation expansion has occurred predominantly through managed investment schemes and the joint venture scheme managed by Forestry Plantations Queensland, a government-owned corporation. Most of these plantings are relatively small-scale hardwood plantations, which are designed to replace the hardwood timber from the native forests that will be protected from further logging after 2024 under the South-East Queensland Regional Forestry Agreement. Views on financing methods for forestry expansion in Queensland were investigated through by an email survey of 12 forestry and finance professionals, followed by in-depth personal interviews of the same group of key informants. Some of the issues identified include lack of transparent information, inequitable taxation system between Managed Investment Scheme (MIS) companies and small-scale forest operators, the need for further R&D on all aspects of the industry, the potential impacts of carbon credit schemes on the industry, and the design of a strategic model for forestry investors. Participants took the view that adoption of a strategic alliance model would encourage further investment in small-scale forestry, arguing that this model could protect the interest of all the stakeholders through reducing investment risk and creating competitive advantage. The potential introduction of a carbon trading scheme also attracted interest from investors, who look for recognisable structures that may alleviate the risk of investing in an industry with which they are unfamiliar. The participants considered that further R&D should be the main focus for government participation in small-scale forestry

Trimaximal neutrino mixing from vacuum alignment in A4 and S4 models

Recent T2K results indicate a sizeable reactor angle theta_13 which would rule out exact tri-bimaximal lepton mixing. We study the vacuum alignment of the Altarelli-Feruglio A4 family symmetry model including additional flavons in the 1' and 1" representations and show that it leads to trimaximal mixing in which the second column of the lepton mixing matrix consists of the column vector (1,1,1)^T/sqrt{3}, with a potentially large reactor angle. In order to limit the reactor angle and control the higher order corrections, we propose a renormalisable S4 model in which the 1' and 1" flavons of A4 are unified into a doublet of S4 which is spontaneously broken to A4 by a flavon which enters the neutrino sector at higher order. We study the vacuum alignment in the S4 model and show that it predicts accurate trimaximal mixing with approximate tri-bimaximal mixing, leading to a new mixing sum rule testable in future neutrino experiments. Both A4 and S4 models preserve form dominance and hence predict zero leptogenesis, up to renormalisation group corrections.Comment: 24 pages, 2 figures, version to be published in JHE

What Determines the Shape of an EQ-5D Index Distribution?

Background. EQ-5D-3L index scores in patient and general populations typically have a nonnormal distribution, divided into 2 distinct groups. It is important to understand to what extent this is determined by the way that the EQ-5D-3L index is constructed rather than by the true distribution of ill health. Objective. This paper examines the determinants of the ‘‘2 groups’’ distribution pattern and the extent to which this pattern is attributable either to the EQ-5D-3L classification system used to create health state profiles or to the weights applied to profiles. Methods. Data from the English NHS PROMs program (hip and knee replacements and varicose vein and hernia repairs) and from a study of 2 chronic conditions (asthma and angina) were used to compare the distributions of EQ5D-3L index scores with distributions from which weights have been stripped; profile data decomposed into their constituent dimensions and levels; a condition-specific index; and using weights from different countries, based on both time tradeoff and visual analogue scale. Results. The EQ-5D-3L classification system generates differences between patients with the same condition in respect of dimensions that are mainly observed at level 2 or 3. The weights commonly used to calculate the index exacerbate this grouping by placing a larger weight on level 3 observations, generating a noticeable gap in index scores between the groups. Conclusions. Analyzing EQ-5D profile data enables a better understanding of the resulting distribution of EQ-5D scores. The distinctive shape observed for these distributions is the result of both the classification system and the weights applied to it

Hepatitis B Virus Core Promoter Double Mutations (A1762T, G1764A) Are Associated with Lower Levels of Serum Dihydrolipoyl Dehydrogenase

Published by S. Karger AG, BaselObjectives: The aim of this study was to identify serum proteins with differential concentrations between hepatocellular carcinoma (HCC) patients and HBsAg asymptomatic carriers among individuals infected with hepatitis B virus (HBV) with basal core promoter (BCP) double mutations (A1762T, G1764A). Methods: iTRAQ and liquid chromatography-tandem mass spectrometry were used to identify differentially expressed protein, and an ELISA test was used for the validation test. Results: The total number of proteins identified was 1,125, of which 239 showed statistically significant differences in their expression. The relative concentrations of serum dihydrolipoyl dehydrogenase (DLD), which showed the most significant correlation with liver diseases and infection, were significantly lower in HCC patients than asymptomatic HBsAg carriers and individuals negative for HBsAg. However, only the difference between HCC patients with BCP double mutations and HBsAg-negative individuals could be confirmed by ELISA. Meanwhile, we found that the concentrations of serum DLD in those infected with HBV with BCP double mutations were significantly lower than in individuals with the wild-type BCP. However, the difference in the concentrations of serum DLD between individuals with wild-type BCP and those negative for HBsAg was not significant. Conclusions: HBV with BCP double mutations are associated with lower concentrations of serum DLD

The bright optical afterglow of the nearby gamma-ray burst of 29 March 2003

Many past studies of cosmological gamma-ray bursts (GRBs) have been limited because of the large distance to typical GRBs, resulting in faint afterglows. There has long been a recognition that a nearby GRB would shed light on the origin of these mysterious cosmic explosions, as well as the physics of their fireballs. However, GRBs nearer than z=0.2 are extremely rare, with an estimated rate of localisation of one every decade. Here, we report the discovery of bright optical afterglow emission from GRB 030329. Our prompt dissemination and the brilliance of the afterglow resulted in extensive followup (more than 65 telescopes) from radio through X-ray bands, as well as measurement of the redshift, z=0.169. The gamma-ray and afterglow properties of GRB 030329 are similar to those of cosmological GRBs (after accounting for the small distance), making this the nearest known cosmological GRB. Observations have already securely identified the progenitor as a massive star that exploded as a supernova, and we anticipate futher revelations of the GRB phenomenon from studies of this source.Comment: 13 pages, 4 figures. Original tex

Three dimensional evaluation of posture in standing with the PosturePrint: an intra- and inter-examiner reliability study

Abstract Background Few digitizers can measure the complexity of upright human postural displacements in six degrees of freedom of the head, rib cage, and pelvis. Methods In a University laboratory, three examiners performed delayed repeated postural measurements on forty subjects over two days. Three digital photographs (left lateral, AP, right lateral) of each of 40 volunteer participants were obtained, twice, by three examiners. Examiners placed 13 markers on the subjects before photography and chose 16 points on the photographic images. Using the PosturePrint® internet computer system, head, rib cage, and pelvic postures were calculated as rotations (Rx, Ry, Rz) in degrees and translations (Tx, Tz) in millimeters. For reliability, two different types (liberal = ICC3,1 & conservative = ICC2,1) of inter- and intra-examiner correlation coefficients (ICC) were calculated. Standard error of measurements (SEM) and mean absolute differences within and between observers' measurements were also determined. Results All of the "liberal" ICCs were in the excellent range (> 0.84). For the more "conservative" type ICCs, four Inter-examiner ICCs were in the interval (0.5–0.6), 10 ICCs were in the interval (0.61–0.74), and the remainder were greater than 0.75. SEMs were 2.7° or less for all rotations and 5.9 mm or less for all translations. Mean absolute differences within examiners and between examiners were 3.5° or less for all rotations and 8.4 mm or less for all translations. Conclusion For the PosturePrint® system, the combined inter-examiner and intra-examiner correlation coefficients were in the good (14/44) and excellent (30/44) ranges. SEMs and mean absolute differences within and between examiners' measurements were small. Thus, this posture digitizer is reliable for clinical use