Convergence of Probability Measures. By P. Billingsley. Chichester, Sussex, Wiley, 1968. xii, 253 p. 9 1/4“. 117s.

Convergence of Probability Measures

ContextSerum hepatitis B virus (HBV) DNA level is a marker of viral replication and efficacy of antiviral treatment in individuals with chronic hepatitis B.ObjectiveTo evaluate the relationship between serum HBV DNA level and risk of hepatocellular carcinoma.Design, Setting, and ParticipantsProspective cohort study of 3653 participants (aged 30-65 years), who were seropositive for the hepatitis B surface antigen and seronegative for antibodies against the hepatitis C virus, recruited to a community-based cancer screening program in Taiwan between 1991 and 1992.Main Outcome MeasureIncidence of hepatocellular carcinoma during follow-up examination and by data linkage with the national cancer registry and the death certification systems.ResultsThere were 164 incident cases of hepatocellular carcinoma and 346 deaths during a mean follow-up of 11.4 years and 41 779 person-years of follow-up. The incidence of hepatocellular carcinoma increased with serum HBV DNA level at study entry in a dose-response relationship ranging from 108 per 100 000 person-years for an HBV DNA level of less than 300 copies/mL to 1152 per 100 000 person-years for an HBV DNA level of 1 million copies/mL or greater. The corresponding cumulative incidence rates of hepatocellular carcinoma were 1.3% and 14.9%, respectively. The biological gradient of hepatocellular carcinoma by serum HBV DNA levels remained significant (P<.001) after adjustment for sex, age, cigarette smoking, alcohol consumption, serostatus for the hepatitis B e antigen (HBeAg), serum alanine aminotransferase level, and liver cirrhosis at study entry. The dose-response relationship was most prominent for participants who were seronegative for HBeAg with normal serum alanine aminotransferase levels and no liver cirrhosis at study entry. Participants with persistent elevation of serum HBV DNA level during follow-up had the highest hepatocellular carcinoma risk.ConclusionElevated serum HBV DNA level (≥10 000 copies/mL) is a strong risk predictor of hepatocellular carcinoma independent of HBeAg, serum alanine aminotransferase level, and liver cirrhosis.

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Risk of hepatocellular carcinoma across a biological gradient of serum hepatitis B virus DNA level.

There is increasing concern that most current published research findings are false. The probability that a research claim is true may depend on study power and bias, the number of other studies on the same question, and, importantly, the ratio of true to no relationships among the relationships probed in each scientific field. In this framework, a research finding is less likely to be true when the studies conducted in a field are smaller; when effect sizes are smaller; when there is a greater number and lesser preselection of tested relationships; where there is greater flexibility in designs, definitions, outcomes, and analytical modes; when there is greater financial and other interest and prejudice; and when more teams are involved in a scientific field in chase of statistical significance. Simulations show that for most study designs and settings, it is more likely for a research claim to be false than true. Moreover, for many current scientific fields, claimed research findings may often be simply accurate measures of the prevailing bias. In this essay, I discuss the implications of these problems for the conduct and interpretation of research.

Why most published research findings are false

Background The presence of hepatitis B e antigen (HBeAg) in serum indicates active viral replication in hepatocytes. HBeAg is thus a surrogate marker for the presence of hepatitis B virus DNA. We conducted a prospective study to determine the relation between positivity for hepatitis B surface antigen (HBsAg) and HBeAg and the development of hepatocellular carcinoma. Methods In 1991 and 1992, we enrolled 11,893 men without evidence of hepatocellular carcinoma (age range, 30 to 65 years) from seven townships in Taiwan. Serum samples obtained at the time of enrollment were tested for HBsAg and HBeAg by radioimmunoassay. The diagnosis of hepatocellular carcinoma was ascertained through data linkage with the computerized National Cancer Registry in Taiwan and with death certificates. We performed a multiple regression analysis to determine the relative risk of hepatocellular carcinoma among men who were positive for HBsAg alone or for HBsAg and HBeAg, as compared with those who were negative for both. Results...

Hepatitis B e antigen and the risk of hepatocellular carcinoma.

https://www.cell.com/molecular-cell/pdf/S1097-2765(12)00552-7.pdf

LincRNA-p21 Suppresses Target mRNA Translation

An easy-to-implement global procedure for testing the four assumptions of the linear model is proposed. The test can be viewed as a Neyman smooth test and it only relies on the standardized residual vector. If the global procedure indicates a violation of at least one of the assumptions, the components of the global test statistic can be utilized to gain insights into which assumptions have been violated. The procedure can also be used in conjunction with associated deletion statistics to detect unusual observations. Simulation results are presented indicating the sensitivity of the procedure in detecting model violations under a variety of situations, and its performance is compared with three potential competitors, including a procedure based on the Box-Cox power transformation. The procedure is demonstrated by applying it to a new car mileage data set and a water salinity data set that has been used previously to illustrate model diagnostics.

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Global Validation of Linear Model Assumptions.

The mRNA Binding Proteins HuR and Tristetraprolin Regulate Cyclooxygenase 2 Expression During Colon Carcinogenesis

Resveratrol is a naturally occurring polyphenol that exhibits pleiotropic health beneficial effects, including anti-inflammatory, cardio-protective, and cancer-protective activities. It is recognized as one of the more promising natural molecules in the prevention and treatment of chronic inflammatory and autoimmune disorders. Ulcerative colitis is an idiopathic, chronic inflammatory disease of the colon associated with a high colon cancer risk. Here, we used a dextran sulfate sodium (DSS) mouse model of colitis, which resembles human ulcerative colitis pathology. Resveratrol mixed in food ameliorates DSS-induced colitis in mice in a dose-dependent manner. Resveratrol significantly improves inflammation score, downregulates the percentage of neutrophils in the mesenteric lymph nodes and lamina propria, and modulates CD3(+) T cells that express tumor necrosis factor-alpha and IFN-gamma. Markers of inflammation and inflammatory stress (p53 and p53-phospho-Ser(15)) are also downregulated by resveratrol. Because chronic colitis drives colon cancer risk, we carried out experiments to determine the chemopreventive properties of resveratrol. Tumor incidence is reduced from 80% in mice treated with azoxymethane (AOM) + DSS to 20% in mice treated with AOM + DSS + resveratrol (300 ppm). Tumor multiplicity also decreased with resveratrol treatment. AOM + DSS-treated mice had 2.4 +/- 0.7 tumors per animal compared with AOM + DSS + 300 ppm resveratrol, which had 0.2 +/- 0.13 tumors per animal. The current study indicates that resveratrol is a useful, nontoxic complementary and alternative strategy to abate colitis and potentially colon cancer associated with colitis.

https://cancerpreventionresearch.aacrjournals.org/content/canprevres/3/4/549.full.pdf

Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis

The problem of nonparametric estimation for the distribution function governing the time to occurrence of a recurrent event in the presence of censoring is considered. We derive Nelson–Aalen and Kaplan–Meier-type estimators for the distribution function, and establish their respective finite-sample and asymptotic properties. We allow for random observation periods for each subject under study and explicitly account for the informative sum-quota nature of the data accrual scheme. These allowances complicate technical matters considerably and, in particular, invalidate the direct use of martingale methods. Consistency and weak convergence of our estimators are obtained by extending an approach due to Sellke, who considered a single renewal process (i.e., recurrent events on a single subject) observed over an infinite time period. A useful feature of the present analysis is that strong parallels are drawn to the usual “single-event” setting, providing a natural route toward developing extensions that involve...

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Nonparametric Estimation With Recurrent Event Data

An estimator for the load-share parameters in an equal load-share model is derived based on observing k-component parallel systems of identical components that have a continuous distribution function F (˙) and failure rate r (˙). In an equal load-share model, after the first of k components fails, failure rates for the remaining components change from r (t) to γ1r (t), then to γ2r (t) after the next failure, and so on. On the basis of observations on n independent and identical systems, a semiparametric estimator of the component baseline cumulative hazard function R = –log(1 – F) is presented, and its asymptotic limit process is established to be a Gaussian process. The effect of estimation of the load-share parameters is considered in the derivation of the limiting process. Potential applications can be found in diverse areas, including materials testing, software reliability, and power plant safety assessment.

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Edsel A. Peña

Papers

Global Validation of Linear Model Assumptions.

The mRNA Binding Proteins HuR and Tristetraprolin Regulate Cyclooxygenase 2 Expression During Colon Carcinogenesis

Resveratrol Suppresses Colitis and Colon Cancer Associated with Colitis

Nonparametric Estimation With Recurrent Event Data

Estimating Load-Sharing Properties in a Dynamic Reliability System.