The Effect of Wet Pressing on Filler Stratification

Research was conducted to determine the effect of press loading upon filler stratification with the intention of observing the development of a stratified sheet. Press conditions were held constant with the exception of pressure applied to the sheet. The sheet was then split and examined for filler content. The paper tested was highly refined, very moist, and of a heavy basis weight. Results indicated a gradual trend of increased stratification with increased press loading. Filler moved toward the direction that water was leaving the sheet

Cost-Effectiveness Analysis of Alternative Antiviral Strategies for the Treatment of HBeAg-Positive and HBeAg-Negative Chronic Hepatitis B in the United Kingdom

AbstractBackgroundSeven drugs are licensed for the treatment of chronic hepatitis B (CHB) in the United Kingdom. Which initial treatment, secondary therapy, and whether antivirals should be given alone or in combination are questions of considerable uncertainty.ObjectiveThe aim of this model was to undertake a comprehensive economic evaluation of all antiviral treatments for CHB to recommend the most cost-effective therapeutic sequence.MethodsWe developed a probabilistic Markov model to compare the cost-effectiveness of all clinically relevant antiviral treatment sequences for nucleos(t)ide-naive adults with hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative CHB. Relative rates of HBeAg seroconversion and viral suppression were obtained from a network meta-analysis. Data on mortality, antiviral drug resistance, durability of response, adverse events, and costs were obtained from published literature. Results are reported in terms of lifetime costs, quality-adjusted life-years (QALYs), and expected net benefit.ResultsIn the base-case analysis, pegylated interferon alpha-2a (peg-IFN α-2a) followed by tenofovir disoproxil fumarate was most effective and cost-effective in HBeAg-positive patients, with a cost of £7488 per QALY gained compared with no treatment. In HBeAg-negative patients, peg-IFN α-2a followed by entecavir was most effective and cost-effective, with a cost of £6981 per QALY gained. The model was robust to a wide range of sensitivity analyses.ConclusionsPeg-IFN α-2a followed by tenofovir disoproxil fumarate or entecavir is the most effective antiviral treatment strategy for people with both variants of CHB. At a cost of less than £10,000 per QALY gained, these sequences are considered cost-effective in England and Wales. The results of this analysis were used to inform 2013 National Institute for Health and Care Excellence guideline recommendations

The individualized genetic barrier predicts treatment response in a large cohort of HIV-1 infected patients

The success of combination antiretroviral therapy is limited by the evolutionary escape dynamics of HIV-1. We used Isotonic Conjunctive Bayesian Networks (I-CBNs), a class of probabilistic graphical models, to describe this process. We employed partial order constraints among viral resistance mutations, which give rise to a limited set of mutational pathways, and we modeled phenotypic drug resistance as monotonically increasing along any escape pathway. Using this model, the individualized genetic barrier (IGB) to each drug is derived as the probability of the virus not acquiring additional mutations that confer resistance. Drug-specific IGBs were combined to obtain the IGB to an entire regimen, which quantifies the virus' genetic potential for developing drug resistance under combination therapy. The IGB was tested as a predictor of therapeutic outcome using between 2,185 and 2,631 treatment change episodes of subtype B infected patients from the Swiss HIV Cohort Study Database, a large observational cohort. Using logistic regression, significant univariate predictors included most of the 18 drugs and single-drug IGBs, the IGB to the entire regimen, the expert rules-based genotypic susceptibility score (GSS), several individual mutations, and the peak viral load before treatment change. In the multivariate analysis, the only genotype-derived variables that remained significantly associated with virological success were GSS and, with 10-fold stronger association, IGB to regimen. When predicting suppression of viral load below 400 cps/ml, IGB outperformed GSS and also improved GSS-containing predictors significantly, but the difference was not significant for suppression below 50 cps/ml. Thus, the IGB to regimen is a novel data-derived predictor of treatment outcome that has potential to improve the interpretation of genotypic drug resistance tests

The Medicago genome provides insight into the evolution of rhizobial symbioses

Legumes (Fabaceae or Leguminosae) are unique among cultivated plants for their ability to carry out endosymbiotic nitrogen fixation with rhizobial bacteria, a process that takes place in a specialized structure known as the nodule. Legumes belong to one of the two main groups of eurosids, the Fabidae, which includes most species capable of endosymbiotic nitrogen fixation(1). Legumes comprise several evolutionary lineages derived from a common ancestor 60 million years ago (Myr ago). Papilionoids are the largest clade, dating nearly to the origin of legumes and containing most cultivated species(2). Medicago truncatula is a long-established model for the study of legume biology. Here we describe the draft sequence of the M. truncatula euchromatin based on a recently completed BAC assembly supplemented with Illumina shotgun sequence, together capturing similar to 94% of all M. truncatula genes. A whole-genome duplication (WGD) approximately 58 Myr ago had a major role in shaping the M. truncatula genome and thereby contributed to the evolution of endosymbiotic nitrogen fixation. Subsequent to the WGD, the M. truncatula genome experienced higher levels of rearrangement than two other sequenced legumes, Glycine max and Lotus japonicus. M. truncatula is a close relative of alfalfa (Medicago sativa), a widely cultivated crop with limited genomics tools and complex autotetraploid genetics. As such, the M. truncatula genome sequence provides significant opportunities to expand alfalfa's genomic toolbox