A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.

INCREASED SARCOLEMMAL PERMEABILITY AS AN EARLY EVENT IN EXPERIMENTAL SEPTIC CARDIOMYOPATHY: A POTENTIAL ROLE FOR OXIDATIVE DAMAGE TO LIPIDS AND PROTEINS

This study describes increased sarcolemmal permeability and myofilamentar damage that occur together with lipid peroxidation and protein nitration in the myocardium in severe sepsis induced by cecal ligation and puncture. Male C57BL/6 mice were submitted to moderate and severe septic injury and sham operation. Using light and laser confocal microscopy, diffuse foci of myocytolysis associated with focal disruption of the actin/myosin contractile apparatus could be seen in hearts with severe septic injury. The myocardial expressions of the sarcomeric proteins myosin and actin were downregulated by both severe and moderate injuries. The detection of albumin staining in the cytoplasm of myocytes to evaluate sarcolemmal permeability provided evidence of severe and mild injury of the plasma membrane in hearts with severe and moderate septic injury, respectively. The administration of a superoxide scavenger caused marked reduction of sarcolemmal permeability, indicating the involvement of free radicals in its genesis. On electron microscopy, these changes were seen to correspond to spread blocks of a few myocytes with fragmentation and dissolution of myofibrils, intracellular edema, and, occasionally, rupture of the sarcolemma. In addition, oxidative damage to lipids, using anti-4-hydroxynonenal, an indicator of oxidative stress and disruption of plasma membrane lipids, and to proteins, using antinitrotyrosine, a stable biomarker of peroxynitrite-mediated protein nitration, was demonstrated. These findings make plausible the hypothesis that increased sarcolemmal permeability might be a primary event in myocardial injury in severe sepsis possibly due to oxidative damage to lipids and proteins that could precede phenotypic changes that characterize a septic cardiomyopathy.

Effect of Gender on Swallow Event Duration Assessed by Videofluoroscopy

There are data suggesting that women swallow liquids at a lower flow rate and ingest smaller volumes in each swallow than men. Our objective in this work was to compare swallowing in asymptomatic men and women by videofluoroscopy. We studied 18 men [age = 33-77 years, mean = 61 (10) years] and 12 women [age = 29-72 years, mean = 53 (15) years] who swallowed in duplicate 5 and 10 ml of liquid and paste barium boluses. None of the volunteers had dysphagia, neurologic diseases, or oral, pharyngeal, or esophageal diseases. The videofluoroscopic examination showed that for the 5-ml bolus, women had a longer oropharyngeal transit [liquid: men, 0.63 (0.21) s, women, 0.88 (0.39) s; paste: men, 0.64 (0.35) s, women, 0.94 (0.58) s], longer oral transit [liquid: men, 0.41 (0.21) s, women, 0.59 (0.35) s; paste: men, 0.39 (0.28) s, women, 0.59 (0.42) s], and longer pharyngeal clearance [liquid: men, 0.36 (0.11) s, women, 0.45 (0.16) s; paste: men, 0.42 (0.25) s, women, 0.56 (0.27) s] compared with men (p < 0.05). We conclude that there are differences in swallowing between men and women, with women having a longer oropharyngeal transit than men for a 5-ml bolus.