Adefovir Dipivoxil for the Treatment of Hepatitis B e Antigen–Positive Chronic Hepatitis B

BACKGROUND In preclinical and phase 2 studies, adefovir dipivoxil demonstrated potent activity against hepatitis B virus (HBV), including lamivudine-resistant strains. METHODS We randomly assigned 515 patients with chronic hepatitis B who were positive for hepatitis B e antigen (HBeAg) to receive 10 mg of adefovir dipivoxil (172 patients), 30 mg of adefovir dipivoxil (173), or placebo (170) daily for 48 weeks. The primary end point was histologic improvement in the 10-mg group as compared with the placebo group. RESULTS After 48 weeks of treatment, significantly more patients who received 10 mg or 30 mg of adefovir dipivoxil per day than who received placebo had histologic improvement (53 percent [P CONCLUSIONS In patients with HBeAg-positive chronic hepatitis B, 48 weeks of 10 mg or 30 mg of adefovir dipivoxil per day resulted in histologic liver improvement, reduced serum HBV DNA and alanine aminotransferase levels, and increased the rates of HBeAg seroconversion. The 10-mg dose has a favorable risk–benefit profile for long-term treatment. No adefovir-associated resistance mutations were identified in the HBV DNA polymerase gene

Interferon Alfa-2b Alone or in Combination with Ribavirin as Initial Treatment for Chronic Hepatitis C

BACKGROUND Only 15 to 20 percent of patients with chronic hepatitis C have a sustained virologic response to interferon therapy. We compared the efficacy and safety of recombinant interferon alfa-2b alone with those of a combination of interferon alfa-2b and ribavirin for the initial treatment of patients with chronic hepatitis C. METHODS We randomly assigned 912 patients with chronic hepatitis C to receive standard-dose interferon alfa-2b alone or in combination with ribavirin (1000 or 1200 mg orally per day, depending on body weight) for 24 or 48 weeks. Efficacy was assessed by measurements of serum hepatitis C virus (HCV) RNA and serum aminotransferases and by liver biopsy. RESULTS The rate of sustained virologic response (defined as an undetectable serum HCV RNA level 24 weeks after treatment was completed) was higher among patients who received combination therapy for either 24 weeks (70 of 228 patients, 31 percent) or 48 weeks (87 of 228 patients, 38 percent) than among patients who received interferon alone for either 24 weeks (13 of 231 patients, 6 percent) or 48 weeks (29 of 225 patients, 13 percent) (P CONCLUSIONS In patients with chronic hepatitis C, initial therapy with interferon and ribavirin was more effective than treatment with interferon alone

Box spline prewavelets of small support

The purpose of this paper is the construction of bi- and trivariate prewavelets from box-spline spaces, \ie\ piecewise polynomials of fixed degree on a uniform mesh. They have especially small support and form Riesz bases of the wavelet spaces, so they are stable. In particular, the supports achieved are smaller than those of the prewavelets due to Riemenschneider and Shen in a recent, similar constructio

Reconciliation Revisited: Handling Multiple Optima when Reconciling with Duplication, Transfer, and Loss

Phylogenetic tree reconciliation is a powerful approach for inferring evolutionary events like gene duplication, horizontal gene transfer, and gene loss, which are fundamental to our understanding of molecular evolution. While duplication–loss (DL) reconciliation leads to a unique maximum-parsimony solution, duplication-transfer-loss (DTL) reconciliation yields a multitude of optimal solutions, making it difficult to infer the true evolutionary history of the gene family. This problem is further exacerbated by the fact that different event cost assignments yield different sets of optimal reconciliations. Here, we present an effective, efficient, and scalable method for dealing with these fundamental problems in DTL reconciliation. Our approach works by sampling the space of optimal reconciliations uniformly at random and aggregating the results. We show that even gene trees with only a few dozen genes often have millions of optimal reconciliations and present an algorithm to efficiently sample the space of optimal reconciliations uniformly at random in O(mn[superscript 2]) time per sample, where m and n denote the number of genes and species, respectively. We use these samples to understand how different optimal reconciliations vary in their node mappings and event assignments and to investigate the impact of varying event costs. We apply our method to a biological dataset of approximately 4700 gene trees from 100 taxa and observe that 93% of event assignments and 73% of mappings remain consistent across different multiple optima. Our analysis represents the first systematic investigation of the space of optimal DTL reconciliations and has many important implications for the study of gene family evolution.National Science Foundation (U.S.) (CAREER Award 0644282)National Institutes of Health (U.S.) (Grant RC2 HG005639)National Science Foundation (U.S.). Assembling the Tree of Life (Program) (Grant 0936234

Calibration of Super-Kamiokande Using an Electron Linac

In order to calibrate the Super-Kamiokande experiment for solar neutrino measurements, a linear accelerator (LINAC) for electrons was installed at the detector. LINAC data were taken at various positions in the detector volume, tracking the detector response in the variables relevant to solar neutrino analysis. In particular, the absolute energy scale is now known with less than 1 percent uncertainty.Comment: 24 pages, 16 figures, Submitted to NIM

Measurement of a small atmospheric νμ/νe\nu_\mu/\nu_e ratio

From an exposure of 25.5~kiloton-years of the Super-Kamiokande detector, 900 muon-like and 983 electron-like single-ring atmospheric neutrino interactions were detected with momentum $p_e > 100$ MeV/$c$, $p_\mu > 200$ MeV/$c$, and with visible energy less than 1.33 GeV. Using a detailed Monte Carlo simulation, the ratio $(\mu/e)_{DATA}/(\mu/e)_{MC}$ was measured to be $0.61 \pm 0.03(stat.) \pm 0.05(sys.)$, consistent with previous results from the Kamiokande, IMB and Soudan-2 experiments, and smaller than expected from theoretical models of atmospheric neutrino production.Comment: 14 pages with 5 figure

Measurement of radon concentrations at Super-Kamiokande

Radioactivity from radon is a major background for observing solar neutrinos at Super-Kamiokande. In this paper, we describe the measurement of radon concentrations at Super-Kamiokande, the method of radon reduction, and the radon monitoring system. The measurement shows that the current low-energy event rate between 5.0 MeV and 6.5 MeV implies a radon concentration in the Super-Kamiokande water of less than 1.4 mBq/m$^3$.Comment: 11 pages, 4 figure

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education