Some remarks on stability of generalized equations

The paper concerns the computation of the graphical derivative and the regular (Fréchet) coderivative of the solution map to a class of generalized equations, where the multi-valued term amounts to the regular normal cone to a (possibly nonconvex) set given by $C^2$ inequalities. Instead of the Linear Independence qualification condition, standardly used in this context, one assumes a combination of the Mangasarian-Fromovitz and the Constant Rank qualification conditions. On the basis of the obtained generalized derivatives, new optimality conditions for a class of mathematical programs with equilibrium constrains are derived, and a workable characterization of the isolated calmness of the considered solution map is provided

Effectiveness and tolerability of pegylated interferon alfa-2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust Study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community-based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 mu g/kg/wk) and weight. based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91(41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community-based clinical practice. (Ada gastroenterol. belg., 2010, 73, 5-11)

Relationship between ankle brachial index and arterial remodeling in pseudoxanthoma elasticum

ObjectivesPseudoxanthoma elasticum (PXE) is an inherited metabolic disease characterized by elastic fiber fragmentation and calcification in the cutaneous, ophthalmologic, and vascular tissues. Cardiovascular manifestations such as peripheral arterial disease (PAD) are frequent in PXE. Because of the changes in the elastic properties and medial calcification of the arterial wall in PXE, the impact of the arterial remodeling on the ankle brachial index (ABI), a well-established diagnostic method for the detection and follow-up of PAD, remains to be determined in this disease. Methods This was a cross-sectional, comparative, open study, which took place at the PXE Consultation Center, University Hospital of Angers. The subjects were 53 patients (mean age, 49 ± 14 years; 35 females) with PXE clinically proven on the basis of established criteria (skin changes, angioid streaks, and skin biopsy). The ABI at rest, symptoms of intermittent claudication (IC), carotid intima-media thickness (IMT), carotid-femoral pulse wave velocity (c-f PWV), compliance (CC), and β stiffness index were measured in a single-center cohort. Results Forty-five percent of the PXE patients had an ABI ≤0.90, but only one patient had an ABI >1.40. IC was found in 23% of the patients with an ABI ≤0.90. There were no significant differences between the patients with a low and normal ABI in terms of IMT (P = .566) or β stiffness index (P = .194), but differences were significant for c-f PWV (P = .010) and CC (P = .011). Adjusted multivariate linear regression for the Framingham-Laurier score showed that patients with a low ABI had less compliant carotid arteries (B = 0.318, P = .039). Conclusions PAD detected by a low ABI is very frequent in PXE, although with limited prevalence of symptomatic claudication. Unexpectedly, ABI was low in such calcifying PAD and associated with lower CC, independently of atherosclerosis risk factors. These findings demonstrate that PXE represents a unique monogenic model of PAD in which the specific arterial wall remodeling could change the diagnostic value of the ABI to detect PAD

Impact of Bayesian network model structure on the accuracy of medical diagnostic systems

While Bayesian network models may contain a handful of numerical parameters that are important for their quality, several empirical studies have confirmed that overall precision of their probabilities is not crucial. In this paper, we study the impact of the structure of a Bayesian network on the precision of medical diagnostic systems. We show that also the structure is not that important - diagnostic accuracy of several medical diagnostic models changes minimally when we subject their structures to such transformations as arc removal and arc reversal. © 2014 Springer International Publishing

Diabetes mellitus abrogates erythropoietin-induced cardioprotection against ischemic-reperfusion injury by alteration of the RISK/GSK-3β signaling

Recent studies reported cardioprotective effects of erythropoietin (EPO) against ischemia–reperfusion (I/R) injury through activation of the reperfusion injury salvage kinase (RISK) pathway. As RISK has been reported to be impaired in diabetes and insulin resistance syndrome, we examined whether EPO-induced cardioprotection was maintained in rat models of type 1 diabetes and insulin resistance syndrome. Isolated hearts were obtained from three rat cohorts: healthy controls, streptozotocin (STZ)-induced diabetes, and high-fat diet (HFD)-induced insulin resistance syndrome. All hearts underwent 25 min ischemia and 30 min or 120 min reperfusion. They were assigned to receive either no intervention or a single dose of EPO at the onset of reperfusion. In hearts from healthy controls, EPO decreased infarct size (14.36 ± 0.60 and 36.22 ± 4.20% of left ventricle in EPO-treated and untreated hearts, respectively, p < 0.05) and increased phosphorylated forms of Akt, ERK1/2, and their downstream target GSK-3β. In hearts from STZ-induced diabetic rats, EPO did not decrease infarct size (32.05 ± 2.38 and 31.88 ± 1.87% in EPO-treated and untreated diabetic rat hearts, respectively, NS) nor did it increase phosphorylation of Akt, ERK1/2, and GSK-3β. In contrast, in hearts from HFD-induced insulin resistance rats, EPO decreased infarct size (18.66 ± 1.99 and 34.62 ± 3.41% in EPO-treated and untreated HFD rat hearts, respectively, p < 0.05) and increased phosphorylation of Akt, ERK1/2, and GSK-3β. Administration of GSK-3β inhibitor SB216763 was cardioprotective in healthy and diabetic hearts. STZ-induced diabetes abolished EPO-induced cardioprotection against I/R injury through a disruption of upstream signaling of GSK-3β. In conclusion, direct inhibition of GSK-3β may provide an alternative strategy to protect diabetic hearts against I/R injury

The global prevalence of hepatitis D virus infection:systematic review and metaanalysis

Background and Aims There are uncertainties about the epidemic patterns of hepatitis delta virus (HDV) infection and its contribution to the burden of liver disease. We estimated the global prevalence of HDV infection and explored its contribution to the development of cirrhosis and hepatocellular carcinoma (HCC) among hepatitis B surface antigen (HBsAg)-positive people. Methods We searched Pubmed, EMBASE and Scopus for studies reporting on total or IgG anti-HDV among HBsAg-positive people. Anti-HDV prevalence was estimated using a binomial mixed model, weighting for study quality and population size. The population attributable fraction (PAF) of HDV to cirrhosis and HCC among HBsAg-positive people was estimated using random-effects models. Results We included 282 studies, comprising 376 population samples from 95 countries, which together tested 120,293 HBsAg-positive people for anti-HDV. The estimated anti-HDV prevalence was 4.5% (95% CI 3.6, 5.7) among all HBsAg-positive people and 16.4% (14.6, 18.6) among those attending hepatology clinics. Worldwide, 0.16% (0.11, 0.25) of the general population, totalling 12.0 (8.7, 18.7) million people, were estimated to be anti-HDV positive. Prevalence among HBsAg-positive people was highest in Mongolia, the Republic of Moldova and countries in Western and Middle Africa, and was higher in injecting drug users, haemodialysis recipients, men who have sex with men, commercial sex workers, and those with hepatitis C virus or HIV. Among HBsAg-positive people, preliminary PAF estimates of HDV were 18% (10, 26) for cirrhosis and 20% (8, 33) for HCC. Conclusions An estimated 12 million people worldwide have experienced HDV infection, with higher prevalence in certain geographic areas and populations. HDV is a significant contributor to HBV-associated liver disease. More quality data are needed to improve the precisions of burden estimates

Projection methods in conic optimization

There exist efficient algorithms to project a point onto the intersection of a convex cone and an affine subspace. Those conic projections are in turn the work-horse of a range of algorithms in conic optimization, having a variety of applications in science, finance and engineering. This chapter reviews some of these algorithms, emphasizing the so-called regularization algorithms for linear conic optimization, and applications in polynomial optimization. This is a presentation of the material of several recent research articles; we aim here at clarifying the ideas, presenting them in a general framework, and pointing out important techniques

Effectiveness and tolerability of pegylated interferon alfa2b in combination with ribavirin for treatment of chronic hepatitis C: the PegIntrust study

Background and study aims : Large international clinical trials conducted in the past 5 years rapidly improved the treatment of chronic hepatitis C; however, it is unclear whether the advances seen in clinical trials are being paralleled by similar improvements in routine clinical practice. PegIntrust is a Belgian community based trial evaluating the sustained virological response. Patients and Methods : Observational study of 219 patients receiving pegylated interferon alfa-2b (1.5 μg/kg/wk) and weight-based ribavirin (800-1200 mg/day) for 48 weeks. Primary study end point was sustained virological response (SVR), defined as undetectable HCV RNA 6 months after the completion of treatment. Results : In total, 108 patients (49.3 %) had undetectable HCV RNA at the end of therapy, 91 (41.6%) attaining SVR. Of the 111 patients without an end-of-treatment response, 28 were non-responders, and 21 had virological breakthrough. In total, 134 patients attained early virological response (EVR); 88 (65.7%) of those patients attained SVR. In contrast, 82 (96.5 %) of the 85 patients who did not attain EVR also did not attain SVR. Age, fibrosis score and baseline viral load were identified as important predictors of treatment outcome. The most frequently reported serious adverse events resulting in treatment discontinuation were anemia (n = 10), fatigue/asthenia/malaise (n = 6) and fever (n = 3). Conclusion : Our data indicate that treatment of chronic hepatitis C with PEG-IFN alfa-2b plus weight-based ribavirin results in favourable treatment outcomes in a Belgian cohort of patients treated in community- based clinical practice

Using honey to heal diabetic foot ulcers

Diabetic ulcers seem to be arrested in the inflammatory/proliferative stage of the healing process, allowing infection and inflammation to preclude healing. Antibiotic-resistant bacteria have become a major cause of infections, including diabetic foot infections. It is proposed here that the modern developments of an ancient and traditional treatment for wounds, dressing them with honey, provide the solution to the problem of getting diabetic ulcers to move on from the arrested state of healing. Honeys selected to have a high level of antibacterial activity have been shown to be very effective against antibiotic-resistant strains of bacteria in laboratory and clinical studies. The potent anti-inflammatory action of honey is also likely to play an important part in overcoming the impediment to healing that inflammation causes in diabetic ulcers, as is the antioxidant activity of honey. The action of honey in promotion of tissue regeneration through stimulation of angiogenesis and the growth of fibroblasts and epithelial cells, and its insulin-mimetic effect, would also be of benefit in stimulating the healing of diabetic ulcers. The availability of honey-impregnated dressings which conveniently hold honey in place on ulcers has provided a means of rapidly debriding ulcers and removing the bacterial burden so that good healing rates can be achieved with neuropathic ulcers. With ischemic ulcers, where healing cannot occur because of lack of tissue viability, these honey dressings keep the ulcers clean and prevent infection occurring