Interruptions of cART limits CD4 T-cell recovery and increases the risk for opportunistic complications and death

A major goal of antiretroviral therapy (ART) for HIV-1-infected persons is the recovery of CD4 T lymphocytes, resulting in thorough protection against opportunistic complications. Interruptions of ART are still frequent. The long-term effect on CD4 T-cell recovery and clinical events remains unknown.

Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity

Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.

RecNcMIC3-1-R is a microneme- and rhoptry-based chimeric antigen that protects against acute neosporosis and limits cerebral parasite load in the mouse model for Neospora caninum infection

In order to achieve host cell entry, the apicomplexan parasite Neospora caninum relies on the contents of distinct organelles, named micronemes, rhoptries and dense granules, which are secreted at defined timepoints during and after host cell entry. It was shown previously that a vaccine composed of a mixture of three recombinant antigens, corresponding to the two microneme antigens NcMIC1 and NcMIC3 and the rhoptry protein NcROP2, prevented disease and limited cerebral infection and transplacental transmission in mice. In this study, we selected predicted immunogenic domains of each of these proteins and created four different chimeric antigens, with the respective domains incorporated into these chimers in different orders. Following vaccination, mice were challenged intraperitoneally with 2 × 10(6)N. caninum tachzyoites and were then carefully monitored for clinical symptoms during 4 weeks post-infection. Of the four chimeric antigens, only recNcMIC3-1-R provided complete protection against disease with 100% survivors, compared to 40-80% of survivors in the other groups. Serology did not show any clear differences in total IgG, IgG1 and IgG2a levels between the different treatment groups. Vaccination with all four chimeric variants generated an IL-4 biased cytokine expression, which then shifted to an IFN-γ-dominated response following experimental infection. Sera of recNcMIC3-1-R vaccinated mice reacted with each individual recombinant antigen, as well as with three distinct bands in Neospora extracts with similar Mr as NcMIC1, NcMIC3 and NcROP2, and exhibited distinct apical labeling in tachyzoites. These results suggest that recNcMIC3-1-R is an interesting chimeric vaccine candidate and should be followed up in subsequent studies in a fetal infection model.

Wgamma production and limits on anomalous WWgamma couplings in ppbar collisions

We measure the cross section and the difference in rapidities between photons and charged leptons for inclusive W -> lnu+gamma production in egamma and mugamma final states. Using data corresponding to an integrated luminosity of 4.2 fb-1 collected with the D0 detector at the Fermilab Tevatron Collider, the cross section multiplied by the branching fraction for the process ppbar -> Wgamma+X -> lnugamma+X, measured to be 15.8 +/- 0.8 (stat.) +/- 1.2 (syst.) pb, and the distribution of the charge-signed photon-lepton rapidity difference are found to be in agreement with the standard model. These results provide the most stringent limits on anomalous WWgamma couplings for data from hadron colliders: -0.4 < Delta kappa_gamma < 0.4 and -0.08 < lambda_gamma < 0.07 at the 95% C.L.

Chances and limits of method restriction: a detailed analysis of suicide methods in Switzerland

The objective of this study was to estimate the potential of method restriction as a public health strategy in suicide prevention. Data from the Swiss Federal Statistical Office and the Swiss Institutes of Forensic Medicine from 2004 were gathered and categorized into suicide submethods according to accessibility to restriction of means. Of suicides in Switzerland, 39.2% are accessible to method restriction. The highest proportions were found in private weapons (13.2%), army weapons (10.4%), and jumps from hot-spots (4.6%). The presented method permits the estimation of the suicide prevention potential of a country by method restriction and the comparison of restriction potentials between suicide methods. In Switzerland, reduction of firearm suicides has the highest potential to reduce the total number of suicides.

Measurement of W+W- production in pp collisions at √s=7 TeV with the ATLAS detector and limits on anomalous WWZ and WWγ couplings

This paper presents a measurement of the W+W- production cross section in pp collisions at root s = 7 TeV. The leptonic decay channels are analyzed using data corresponding to an integrated luminosity of 4: 6 fb(-1) collected with the ATLAS detector at the Large Hadron Collider. The W+W- production cross section sigma(pp -> W+W- + X) is measured to be 51.9 +/- 2.0(stat) +/- 3.9(syst) +/- 2.0(lumi) pb, compatible with the Standard Model prediction of 44.7(-1.9)(+2.1) pb. A measurement of the normalized fiducial cross section as a function of the leading lepton transverse momentum is also presented. The reconstructed transverse momentum distribution of the leading lepton is used to extract limits on anomalous WWZ and WW gamma couplings.