P17-26. Effective design of T-cell driven vaccines applied to the GAIA HIV vaccine: advances in vaccine design based on current preclinical success

Poster Presentatio

The longer your work hours, the worse your relationship? The role of selective optimization with compensation in the associations of working time with relationship satisfaction and self-disclosure in dual-career couples

This two-wave panel study investigates the associations between working time, selective optimization with compensation in private life and relationship outcomes (i.e. relationship satisfaction and self-disclosure) in dual-career couples. We propose that one partner’s selective optimization with compensation in private life either mediates or moderates the association of this partner’s working time and relationship outcomes (i.e. relationship satisfaction and self-disclosure). Moreover, we postulate the crossover (i.e. transmission) of relationship satisfaction and self-disclosure within the couple. To test these hypotheses, we conducted an online study with a time lag of six months, in which 285 dual-career couples took part. We found evidence for selective optimization with compensation in private life as a mediator: working time spent by partners in dual-career couples was associated with selective optimization with compensation in their private life that, in turn, predicted relationship satisfaction and self-disclosure. Results did not support the assumption that one partner’s selective optimization with compensation in private life moderates the association between working time and relationship satisfaction and self-disclosure. Relationship satisfaction, but not self-disclosure, crossed over within the couples. The results challenge the assumption that longer work hours have negative consequences for romantic relationships

Viral Hepatitis and Rapid Diagnostic Test Based Screening for HBsAg in HIV-infected Patients in Rural Tanzania.

\ud \ud Co-infection with hepatitis B virus (HBV) is highly prevalent in people living with HIV in Sub-Saharan Africa. Screening for HBV surface antigen (HBsAg) before initiation of combination antiretroviral therapy (cART) is recommended. However, it is not part of diagnostic routines in HIV programs in many resource-limited countries although patients could benefit from optimized antiretroviral therapy covering both infections. Screening could be facilitated by rapid diagnostic tests for HBsAg. Operating experience with these point of care devices in HIV-positive patients in Sub-Saharan Africa is largely lacking. We determined the prevalence of HBV and Hepatitis C virus (HCV) infection as well as the diagnostic accuracy of the rapid test device Determine HBsAg in an HIV cohort in rural Tanzania. Prospectively collected blood samples from adult, HIV-1 positive and antiretroviral treatment-naïve patients in the Kilombero and Ulanga antiretroviral cohort (KIULARCO) in rural Tanzania were analyzed at the point of care with Determine HBsAg, a reference HBsAg EIA and an anti-HCV EIA. Samples of 272 patients were included. Median age was 38 years (interquartile range [IQR] 32-47), 169/272 (63%) subjects were females and median CD4+ count was 250 cells/µL (IQR 97-439). HBsAg was detected in 25/272 (9.2%, 95% confidence interval [CI] 6.2-13.0%) subjects. Of these, 7/25 (28%) were positive for HBeAg. Sensitivity of Determine HBsAg was rated at 96% (95% CI 82.8-99.6%) and specificity at 100% (95% CI, 98.9-100%). Antibodies to HCV (anti-HCV) were found in 10/272 (3.7%, 95% CI 2.0-6.4%) of patients. This study reports a high prevalence of HBV in HIV-positive patients in a rural Tanzanian setting. The rapid diagnostic test Determine HBsAg is an accurate assay for screening for HBsAg in HIV-1 infected patients at the point of care and may further help to guide cART in Sub-Saharan Africa

Concurrent chemoradiotherapy for squamous cell carcinoma of the anus using a shrinking field radiotherapy technique without a boost

Chemoradiotherapy (CRT) is now widely accepted as the primary treatment modality for squamous cell cancer of the anus. While randomised trials have clearly shown CRT to be more effective than radiotherapy alone, there remains uncertainty over the optimal integration of chemotherapy and radiation. We describe a series of 50 patients treated by a site specialist gastrointestinal nonsurgical oncologist with CRT at a single UK centre. Chemotherapy comprised mitomycin C (MMC) (day 1) and 5-fluorouracil (5-FU) (days 1–4, and 29–32), concurrent with 50 Gy in 25 fractions radiation, using a two-phase shrinking field technique. A radiation boost was not planned. At a median follow-up of 48 months, 11 (22%) of the patients have failed locally, of which three have been surgically salvaged. Nine (18%) have died of anal cancer. These results are comparable with those from large randomised studies, and suggest that a two-phase shrinking field radiotherapy technique with no boost, concurrent with MMC/5-FU chemotherapy, is an effective regimen for this disease. The CRT regimen described here provides the basis for the ‘control arm’ of the current UK-randomised CRT trial in anal cancer (ACT2)

Time for T? Immunoinformatics addresses the challenges of vaccine design for neglected tropical and emerging infectious diseases

Vaccines have been invaluable for global health, saving lives and reducing healthcare costs, while also raising the quality of human life. However, newly emerging infectious diseases (EID) and more well-established tropical disease pathogens present complex challenges to vaccine developers; in particular, neglected tropical diseases, which are most prevalent among the world’s poorest, include many pathogens with large sizes, multistage life cycles and a variety of nonhuman vectors. EID such as MERS-CoV and H7N9 are highly pathogenic for humans. For many of these pathogens, while their genomes are available, immune correlates of protection are currently unknown. These complexities make developing vaccines for EID and neglected tropical diseases all the more difficult. In this review, we describe the implementation of an immunoinformatics-driven approach to systematically search for key determinants of immunity in newly available genome sequence data and design vaccines. This approach holds promise for the development of 21st century vaccines, improving human health everywhere

Background studies for the EDELWEISS dark matter experiment

The EDELWEISS-II collaboration has completed a direct search for WIMP dark matter using cryogenic Ge detectors (400 g each) and 384 kg$\times$days of effective exposure. A cross-section of $4.4 \times 10^{-8}$ pb is excluded at 90% C.L. for a WIMP mass of 85 GeV. The next phase, EDELWEISS-III, aims to probe spin-independent WIMP-nucleon cross-sections down to a few $\times10^{-9}$ pb. We present here the study of gamma and neutron background coming from radioactive decays in the set-up and shielding materials. We have carried out Monte Carlo simulations for the completed EDELWEISS-II setup with GEANT4 and normalised the expected background rates to the measured radioactivity levels (or their upper limits) of all materials and components. The expected gamma-ray event rate in EDELWEISS-II at 20-200 keV agrees with the observed rate of 82 events/kg/day within the uncertainties in the measured concentrations. The calculated neutron rate from radioactivity of 1.0-3.1 events (90% C.L.) at 20-200 keV in the EDELWEISS-II data together with the expected upper limit on the misidentified gamma-ray events ($\le0.9$), surface betas ($\le0.3$), and muon-induced neutrons ($\le0.7$), do not contradict 5 observed events in nuclear recoil band. We have then extended the simulation framework to the EDELWEISS-III configuration with 800 g crystals, better material purity and additional neutron shielding inside the cryostat. The gamma-ray and neutron backgrounds in 24 kg fiducial mass of EDELWEISS-III have been calculated as 14-44 events/kg/day and 0.7-1.4 events per year, respectively. The results of the background studies performed in the present work have helped to select better purity components and improve shielding in EDELWEISS-III to further reduce the expected rate of background events in the next phase of the experiment.Comment: 15 pages, 9 figures, to be published in Astroparticle Physic

Anti-HIV-1 activity of cellulose acetate phthalate: Synergy with soluble CD4 and induction of "dead-end" gp41 six-helix bundles

BACKGROUND: Cellulose acetate phthalate (CAP), a promising candidate microbicide for prevention of sexual transmission of the human immunodeficiency virus type 1 (HIV-1) and other sexually transmitted disease (STD) pathogens, was shown to inactivate HIV-1 and to block the coreceptor binding site on the virus envelope glycoprotein gp120. It did not interfere with virus binding to CD4. Since CD4 is the primary cellular receptor for HIV-1, it was of interest to study CAP binding to HIV-1 complexes with soluble CD4 (sCD4) and its consequences, including changes in the conformation of the envelope glycoprotein gp41 within virus particles. METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to study CAP binding to HIV-1-sCD4 complexes and to detect gp41 six-helix bundles accessible on virus particles using antibodies specific for the α-helical core domain of gp41. RESULTS: 1) Pretreatment of HIV-1 with sCD4 augments subsequent binding of CAP; 2) there is synergism between CAP and sCD4 for inhibition of HIV-1 infection; 3) treatment of HIV-1 with CAP induced the formation of gp41 six-helix bundles. CONCLUSIONS: CAP and sCD4 bind to distinct sites on HIV-1 IIIB and BaL virions and their simultaneous binding has profound effects on virus structure and infectivity. The formation of gp41 six-helical bundles, induced by CAP, is known to render the virus incompetent for fusion with target cells thus preventing infection