Effect of antiretroviral HIV therapy on hepatitis B virus replication and pathogenicity

Coinfections with hepatitis B virus (HBV) and HIV are very frequent. Although HBV is a DNA virus, it replicates via reverse transcription like HIV. Structural similarities between the enzymatic pocket of the HBV DNA polymerase and HIV-1 reverse transcriptase are the basis that certain drugs inhibit both enzymes and thus the replication of both viruses. HBV components increase the pathogenic action of HIV and vice versa directly by certain proteins like HBsAg in the case of HBV and HIV-encoded Tat and Vpr and by disturbing the cytokine balance in affected cells. Antiretroviral therapy is highly beneficial for HIV/HBV-coinfected patients, but carries the risk of drug-induced resistance development and hepatotoxicity. Even with restoration of the immune capacity, signs of hepatic inflammation may develop even after 10 years of treatment

Detection of HIV-1 infection in dried blood spots from a 12-year-old ABO bedside test card

Background and Objectives: We tested dried blood from an ABO bedside test card which had been stored at room temperature for 12 years, to prove that a patient with HIV-1 infection had been infected by blood transfusion. Materials and Methods: Immunoblots for HIV-1 antibodies and threefold PCRs with half-nested primers for the HIV-1 integrase gene were done with eluates from the dried blood spots. Results: HIV-1 antibodies and HIV-1 DNA could be detected in the sample from one unit of blood, but not from the two other units or from the recipient before transfusion. Conclusion: Further studies should be done on the validity of stored dried blood as an alternative to the storage of frozen donor serum for several years for `look-back' studies

Non-perturbative renormalisation for overlap fermions

Using non-perturbative techniques we have found the renormalisation factor, Z, in the RI-MOM scheme for quark bilinear operators in quenched QCD. We worked with overlap fermions using the Luescher-Weisz gauge action. Our calculation was performed at beta=8.45 at a lattice spacing of 1/a=2.1 GeV using a value of rho=1.4. Our results show good agreement between the vector and the axial vector in the zero mass limit. This shows that overlap fermions have good chiral properties. To attempt to improve the discretisation errors in our results we subtracted the O(a^2) terms in one-loop lattice perturbation theory from the Monte Carlo Green functions. In particular we paid attention to the operators for the observable . We found a value for the renormalisation constants Z^msbar_(v_2b) and Z^msbar_(v_2a) just less than 1.9 at mu=1/a=2.1 GeV.Comment: 6 pages, 3 figures, uses PoS style, poster presented at Lattice 2005 (Chiral Fermions), to be published in Proceedings of Scienc

Hearing loss and fluctuating hearing levels in X-linked hypophosphataemic osteomalacia

Abstract Background and objective: X-linked hypophosphataemic osteomalacia is the most common of the genetically determined forms of osteomalacia. The occurrence of hearing loss in X-linked hypophosphataemic osteomalacia has been known since 1984. However, observations on the progression of such hearing loss, and suggestions regarding possible therapy, have not previously been published. Methods: Case report of a patient with X-linked hypophosphataemic osteomalacia and hearing loss, with three years' audiological follow up, description of empirical therapy and literature review. Results: The patient presented with fluctuating hearing. An audiogram showed mild to severe sensorineural hearing loss mainly in the low and high frequencies. A temporary improvement of 20-40dB after steroid therapy was observed. Four weeks later, hearing had deteriorated again, mainly in the low frequencies. After one year of fluctuating hearing levels, stabilisation occurred. Conclusions: In X-linked hypophosphataemic osteomalacia, hearing loss occurs predominantly in the low and high frequencies. The hearing loss type and progression pattern point to an endolymphatic hydrops as the pathogenetic mechanism. Steroid therapy may be of some benefi

A lattice determination of g_A and <x> from overlap fermions

We present results for the nucleon's axial charge g_A and the first moment of the unpolarized parton distribution function from a simulation of quenched overlap fermions.Comment: Talk presented at Lattice2004(chiral), 4 pages, 4 figure

Sabotage in Contests: A Survey

A contest is a situation in which individuals expend irretrievable resources to win valuable prize(s). ‘Sabotage’ is a deliberate and costly act of damaging a rival’s' likelihood of winning the contest. Sabotage can be observed in, e.g., sports, war, promotion tournaments, political or marketing campaigns. In this article, we provide a model and various perspectives on such sabotage activities and review the economics literature analyzing the act of sabotage in contests. We discuss the theories and evidence highlighting the means of sabotage, why sabotage occurs, and the effects of sabotage on individual players and on overall welfare, along with possible mechanisms to reduce sabotage. We note that most sabotage activities are aimed at the ablest player, the possibility of sabotage reduces productive effort exerted by the players, and sabotage may lessen the effectiveness of public policies, such as affirmative action, or information revelation in contests. We discuss various policies that a designer may employ to counteract sabotage activities. We conclude by pointing out some areas of future research

Monte Carlo simulations and field transformation: the scalar case

We describe a new method in lattice field theory to compute observables at various values of the parameters lambda_i in the action S[phi,lambda_i]. Firstly one performs a single simulation of a ``reference action'' S[phi^r, lambda_i^r] with fixed lambda_i^r. Then the phi^r-configurations are transformed into those of a field phi distributed according to S[phi,lambda_i], apart from a ``remainder action'' which enters as a \break weight. In this way we measure the observables at values of lambda_i different from lambda_i^r. We study the performance of the algorithm in the case of the simplest renormalizable model, namely the phi^4 scalar theory on a four dimensional lattice and compare the method with the ``histogram'' technique of which it is a generalization.Comment: Latex, 23 pgs, 8 eps-figures include

Where the electroweak phase transition ends

We give a more precise characterisation of the end of the electroweak phase transition in the framework of the effective 3d SU(2)--Higgs lattice model than has been given before. The model has now been simulated at gauge couplings beta_G=12 and 16 for Higgs masses M_H^*=70, 74, 76 and 80 GeV up to lattices 96^3 and the data have been used for reweighting. The breakdown of finite volume scaling of the Lee-Yang zeroes indicates the change from a first order transition to a crossover at lambda_3/g_3^2=0.102(2) in rough agreement with results of Karsch et al (hep-lat/9608087) at \beta_G=9 and smaller lattices. The infinite volume extrapolation of the discontinuity Delta /g_3^2 turns out to be zero at lambda_3/g_3^2=0.107(2) being an upper limit. We comment on the limitations of the second method.Comment: RevTeX, 19 pages, 11 figures, 2 tables; additional MC-data near the endpoint considere

Feasibility, drug safety, and effectiveness of etiological treatment programs for Chagas disease in Honduras, Guatemala, and Bolivia: 10-year experience of Médecins Sans Frontières

BACKGROUND: Chagas disease (American trypanosomiasis) is a zoonotic or anthropozoonotic disease caused by the parasite Trypanosoma cruzi. Predominantly affecting populations in poor areas of Latin America, medical care for this neglected disease is often lacking. Médecins Sans Frontières/Doctors Without Borders (MSF) has provided diagnostic and treatment services for Chagas disease since 1999. This report describes 10 years of field experience in four MSF programs in Honduras, Guatemala, and Bolivia, focusing on feasibility protocols, safety of drug therapy, and treatment effectiveness. METHODOLOGY: From 1999 to 2008, MSF provided free diagnosis, etiological treatment, and follow-up care for patients <18 years of age seropositive for T. cruzi in Yoro, Honduras (1999-2002); Olopa, Guatemala (2003-2006); Entre Ríos, Bolivia (2002-2006); and Sucre, Bolivia (2005-2008). Essential program components guaranteeing feasibility of implementation were information, education, and communication (IEC) at the community and family level; vector control; health staff training; screening and diagnosis; treatment and compliance, including family-based strategies for early detection of adverse events; and logistics. Chagas disease diagnosis was confirmed by testing blood samples using two different diagnostic tests. T. cruzi-positive patients were treated with benznidazole as first-line treatment, with appropriate counseling, consent, and active participation from parents or guardians for daily administration of the drug, early detection of adverse events, and treatment withdrawal, when necessary. Weekly follow-up was conducted, with adverse events recorded to assess drug safety. Evaluations of serological conversion were carried out to measure treatment effectiveness. Vector control, entomological surveillance, and health education activities were carried out in all projects with close interaction with national and regional programs. RESULTS: Total numbers of children and adolescents tested for T. cruzi in Yoro, Olopa, Entre Ríos, and Sucre were 24,471, 8,927, 7,613, and 19,400, respectively. Of these, 232 (0.9%), 124 (1.4%), 1,475 (19.4%), and 1,145 (5.9%) patients, respectively, were diagnosed as seropositive. Patients were treated with benznidazole, and early findings of seroconversion varied widely between the Central and South American programs: 87.1% and 58.1% at 18 months post-treatment in Yoro and Olopa, respectively; 5.4% by up to 60 months in Entre Ríos; and 0% at an average of 18 months in Sucre. Benznidazole-related adverse events were observed in 50.2% and 50.8% of all patients treated in Yoro and Olopa, respectively, and 25.6% and 37.9% of patients in Entre Ríos and Sucre, respectively. Most adverse events were mild and manageable. No deaths occurred in the treatment population. CONCLUSIONS: These results demonstrate the feasibility of implementing Chagas disease diagnosis and treatment programs in resource-limited settings, including remote rural areas, while addressing the limitations associated with drug-related adverse events. The variability in apparent treatment effectiveness may reflect differences in patient and parasite populations, and illustrates the limitations of current treatments and measures of efficacy. New treatments with improved safety profiles, pediatric formulations of existing and new drugs, and a faster, reliable test of cure are all urgently needed