Viral dynamics of primary viremia and antiretroviral therapy in simian immunodeficiency virus infection

Mathematical modeling of viral replication dynamics, based on sequential measurements of levels of virion-associated RNA in plasma during antiretroviral treatment, has led to fundamental new insights into human immunodeficiency virus type 1 pathogenesis. We took advantage of the simian immunodeficiency virus (SIV)-infected macaque model to perform detailed measurements and mathematical modeling during primary infection and during treatment of established infection with the antiretroviral drug (R)-9-(2-phosphonylmethoxypropyl)adenine (PMPA). The calculated clearance half-life for productively infected cells during resolution of the peak viremia of primary infection was on the order of 1 day, with slightly shorter clearance half-lives calculated during PMPA treatment. Viral reproduction rates upon discontinuation of PMPA treatment after 2 weeks were approximately twofold greater than those obtained just prior to initiation of treatment in the same animals, likely reflecting accumulation of susceptible target cells during treatment. The basic reproductive ratio (R0) for the spread of SIV infection in vivo, which represents the number of productively infected cells derived from each productively infected cell at the beginning of infection, was also estimated. This parameter quantifies the extent to which antiviral therapy or vaccination must limit the initial spread of virus to prevent establishment of chronic disseminated infection. The results thus provide an important guide for efforts to develop vaccines against SIV and, by extension, human immunodeficiency virus.     

Sucralfate attenuates gastric mucosal lesions and increased vascular permeability induced by ischaemia and reperfusion in rats

Recent evidence suggests that oxygen-derived free radicals are involved in mediating gastric microvascular and parenchymal cell injuries induced by ischaemia and reperfusion. Therefore, the effect of the locally acting anti-ulcer drug, sucralfate, was studied on ischaemia and reperfusion (e.g. induced gastric lesions, intraluminal bleeding, changes in vascular permeability and non-protein sulfhydryl levels in the rat stomach). Allopurinol was used as a known standard antioxidant drug. Rats were subjected to 30 min of gastric ischaemia in the presence of 100 mmol/L hydrochloric acid and reperfusion periods of 15, 30 or 60 min duration. The gastric lesions were assessed microscopically under an inverted microscope. The vascular permeability was quantified by measuring the extravasated Evans blue in the stomach. There were significantly greater numbers of gastric lesions, intraluminal bleeding and leakage of Evans blue during all reperfusion periods as compared with those of ischaemia, with maximum effects occurring at 60 min following reperfusion. Pretreatment with sucralfate (31.25-250 mg/kg, p.o.) or allopurinol (12.5-50 mg/kg, i.p.) 30 min before the procedure, dose-dependently reduced the gastric lesions, intraluminal bleeding, and decreased the vascular permeability induced by ischaemia and reperfusion. Furthermore, sucralfate dose-dependently reverses the ischaemia and reperfusion-induced depletion of mucosal non-protein sulfhydryl levels and inhibited the superoxide radical production in both cell-free xanthine-xanthine oxidase and in the stimulated polymorphonuclear cellular systems. These results suggest that the protection produced by sucralfate against gastric injury may be due to its antioxidant effects.     

GaN and AlGaN high-voltage rectifiers grown by metal-organic chemical-vapor deposition

In this paper, we report the study of the electrical characteristics of GaN and AlGaN vertical p-i-n junctions and Schottky rectifiers grown on both sapphire and SiC substrates by metal-organic chemical-vapor deposition. For GaN p-i-n rectifiers grown on SiC with a relatively thin “i” region of 2 μm, a breakdown voltage over 400 V, and forward voltage as low as 4.5 V at 100 A/cm² are exhibited for a 60-μm-diameter device. A GaN Schottky diode with a 2-μm-thick undoped layer exhibits a blocking voltage in excess of ∼230 V at a reverse-leakage current density below 1 mA/cm², and a forward-voltage drop of 3.5 V at a current density of 100 A/cm². It has been found that with the same device structure and process approach, the leakage current of a device grown on a SiC substrate is much lower than a device grown on a sapphire substrate. The use of Mg ion implantation for p-guard rings as planar-edge terminations in mesageometry GaN Schottky rectifiers has also been studied.     

Coronary bypass in vascular patients: a relatively high-risk procedure

A premise of cardiac risk stratification is that the added risk of coronary artery bypass grafting (CABG) is offset by the improved safety of subsequent vascular reconstruction (VR). We questioned if elective CABG is patients with severe peripheral vascular disease (PVD) is a relatively high-risk procedure. A cohort study of 680 elective CABG patients from January 1993 to December 1994 was performed using three mutually exclusive outcomes of complication-free survival, morbidity, and mortality. Patient characteristic, operative, and outcome data were prospectively collected. Retrospective review determined that 58 patients had either a standard indication for or a history of VR. Overall CABG mortality was 2.5%, with statistically similar but relatively higher rates for PVD as compared to non-PVD patients. In contrast, major morbidity occurred at rates 3.6-fold higher in PVD patients (39.7%) than in disease-free patients (16.7%) after adjustment for the effects of patient and operative variables (odds ratio [OR] 3.67, 95% confidence interval [CI] 1.93-6.99). CABG morbidity in the PVD patient was most likely in those patients with aortoiliac (OR 9.51, CI 3.20-28.27) and aortic aneurysmal (OR 5.24, CI 1.28-21.41) disease types. CABG in PVD patients is associated with significant major morbidity. Such morbidity may preclude or alter the timing of subsequent VR.     

The influence of the fabrication process on the buckling of thin-walled steel box sections

Steel box sections are usually fabricated from flat plates which are welded at the corners. The welding process can introduce residual stresses and geometric imperfections into the sections which can influence their strength. For some thin-walled sections, large periodic geometric imperfections have been observed in manufactured sections. Subsequent investigations have indicated that the imperfections are in fact buckling deformations i.e. the box section has buckled due to welding residual stresses prior to any application of external load. The welding procedure and the behaviour of the box sections under load has been modelled using a finite element analysis that accounts for both geometric and material non-linearities. Tests have been carried out on box sections with a range of width to thickness ratios for the plate elements. Modelling has been shown to give good correlation with the test results. The conditions for buckling to take place as a result of the welding process have been established. A design method has been proposed.     

GELYMAC: a Macintosh application for calculating DNA fragment size from gel electrophoresis migration data

A program called GELYMAC takes data on the distances migrated by DNA fragments in a one-dimensional electrophoretic gel and, using a cubic-spline best-fit of marker fragment distance migrated versus molecular size, calculates the molecular sizes of the fragments. Written in the Rascal (Real-time Pascal) programming language, the program runs on the Macintosh family of microcomputers. Rapid entry of marker and experimental fragment migration data is afforded using a scroll bar system adjacent to a graphic representation of a gel. Output includes tabular listing of the data, graphic cartoons of the gel, and the fragment locations and molecular sizes for individual gel lanes, and the calibration curve used in data computations.     

Clinical significance of psychotherapy for unipolar depression: A meta-analytic approach to social comparison.

[Correction Notice: An erratum for this article was reported in Vol 55(3) of Journal of Consulting and Clinical Psychology (see record 2008-10745-001). The data presented in Table 2 were incorrect because a row and a column were inadvertently omitted. The corrected Table 2 appears in the erratum.] This study used meta-analysis to study the clinical significance of psychotherapy for symptoms of unipolar depression. The following questions were addressed: How similar is the posttherapy adjustment of depressed adults to that of nondepressed adults? Is this adjustment maintained at follow-up? What dimensions of treatment, therapists, or design are associated with clinical significance? Using the Beck Depression Inventory (BDI), we calculated composite BDI norms from 28 published studies. Sixty effect sizes (from 31 outcome studies utilizing the BDI) were calculated. The results indicated that psychotherapy produces outcomes that have moderate clinical significance and that are well-maintained at follow-up, that individual therapy is associated with greater clinical significance than group treatment, and that type of therapy is not related to improvement. Alternative approaches for operationalizing clinical significance as the return of individuals to normal levels of functioning are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)