Gründung eines Heimatvereins in Londorf

Recent cases of successful control of human immunodeficiency virus (HIV) by bone marrow transplant in combination with suppressive antiretroviral therapy (ART) and very early initiation of ART have provided proof of concept that HIV infection might now be cured. Current efforts focusing on gene therapy, boosting HIV-specific immunity, reducing inflammation and activation of latency have all been the subject of recent excellent reviews. We now propose an additional avenue of research towards a cure for HIV: targeting HIV apoptosis regulatory pathways. The central enigma of HIV disease is that HIV infection kills most of the CD4 T cells that it infects, but those cells that are spared subsequently become a latent reservoir for HIV against which current medications are ineffective. We propose that if strategies could be devised which would favor the death of all cells which HIV infects, or if all latently infected cells that release HIV would succumb to viral-induced cytotoxicity, then these approaches combined with effective ART to prevent spreading infection, would together result in a cure for HIV. This premise is supported by observations in other viral systems where the relationship between productive infection, apoptosis resistance, and the development of latency or persistence has been established. Therefore we propose that research focused at understanding the mechanisms by which HIV induces apoptosis of infected cells, and ways that some cells escape the pro-apoptotic effects of productive HIV infection are critical to devising novel and rational approaches to cure HIV infection

Making it real: exploring the potential of Augmented Reality for teaching primary school science

The use of Augmented Reality (AR) in formal education could prove a key component in future learning environments that are richly populated with a blend of hardware and software applications. However, relatively little is known about the potential of this technology to support teaching and learning with groups of young children in the classroom. Analysis of teacher-child dialogue in a comparative study between use of an AR virtual mirror interface and more traditional science teaching methods for 10-year-old children, revealed that the children using AR were less engaged than those using traditional resources. We suggest four design requirements that need to be considered if AR is to be successfully adopted into classroom practice. These requirements are: flexible content that teachers can adapt to the needs of their children, guided exploration so learning opportunities can be maximised, in a limited time, and attention to the needs of institutional and curricular requirements

SUPPORT Tools for evidence-informed health Policymaking (STP) 12: Finding and using research evidence about resource use and costs

This article is part of a series written for people responsible for making decisions about health policies and programmes and for those who support these decision makers

A Large Scale Double Beta and Dark Matter Experiment: GENIUS

The recent results from the HEIDELBERG-MOSCOW experiment have demonstrated the large potential of double beta decay to search for new physics beyond the Standard Model. To increase by a major step the present sensitivity for double beta decay and dark matter search much bigger source strengths and much lower backgrounds are needed than used in experiments under operation at present or under construction. We present here a study of a project proposed recently, which would operate one ton of 'naked' enriched GErmanium-detectors in liquid NItrogen as shielding in an Underground Setup (GENIUS). It improves the sensitivity to neutrino masses to 0.01 eV. A ten ton version would probe neutrino masses even down to 10^-3 eV. The first version would allow to test the atmospheric neutrino problem, the second at least part of the solar neutrino problem. Both versions would allow in addition significant contributions to testing several classes of GUT models. These are especially tests of R-parity breaking supersymmetry models, leptoquark masses and mechanism and right-handed W-boson masses comparable to LHC. The second issue of the experiment is the search for dark matter in the universe. The entire MSSM parameter space for prediction of neutralinos as dark matter particles could be covered already in a first step of the full experiment - with the same purity requirements but using only 100 kg of 76Ge or even of natural Ge - making the experiment competitive to LHC in the search for supersymmetry. The layout of the proposed experiment is discussed and the shielding and purity requirements are studied using GEANT Monte Carlo simulations. As a demonstration of the feasibility of the experiment first results of operating a 'naked' Ge detector in liquid nitrogen are presented.Comment: 22 pages, 12 figures, see also http://pluto.mpi-hd.mpg.de/~betalit/genius.htm

HIV research in Australia: linking basic research findings with clinical and public health outcomes

Despite a population of only 20 million and sustained low prevalence of HIV infection in Australia, Australian researchers have provided many substantial original findings to the fields of HIV pathogenesis, treatment and prevention. More recently, Australian clinicians and scientists have turned their attention to assisting other countries in developing effective responses, particularly within the Asia-Pacific region. It is therefore fitting that the 4th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention will be held in Sydney in July 2007. The meeting is expected to attract over 5000 participants and will have a dynamic and innovative programme within the three major themes of HIV basic science, clinical research and biomedical prevention

Multi-stakeholder consensus on a target product profile for an HIV cure

Developing a cure for HIV is a global priority. Target product profiles are a tool commonly used throughout the drug development process to align interested parties around a clear set of goals or requirements for a potential product. Three distinct therapeutic modalities (combination therapies, ex-vivo gene therapy, and in-vivo gene therapy) for a target product profile for an HIV cure were identified. Using a process of expert face-to-face consultation and an online Delphi consultation, we found a high degree of agreement regarding the criteria for the optimum target product profile. Although the minimum attributes for a cure were debated, the broad consensus was that an acceptable cure need not be as safe and effective as optimally delivered antiretroviral therapy. An intervention that successfully cured a reasonable fraction of adults would be sufficient to advance to the clinic. These target product profiles will require further discussion and ongoing revisions as the field matures

The case for an HIV cure and how to get there

In light of the increasing global burden of new HIV infections, growing financial requirements, and shifting funding landscape, the global health community must accelerate the development and delivery of an HIV cure to complement existing prevention modalities. An effective curative intervention could prevent new infections, overcome the limitations of antiretroviral treatment, combat stigma and discrimination, and provide a sustainable financial solution for pandemic control. We propose steps to plan for an HIV cure now, including defining a target product profile and establishing the HIV Cure Africa Acceleration Partnership (HCAAP), a multidisciplinary public-private partnership that will catalyse and promote HIV cure research through diverse stakeholder engagement. HCAAP will convene stakeholders, including people living with HIV, at an early stage to accelerate the design, social acceptability, and rapid adoption of HIV-cure products

Neurotoxicity with high dose disulfiram and vorinostat used for HIV latency reversal

OBJECTIVE: To examine whether administering both vorinostat and disulfiram to people with HIV (PWH) on antiretroviral therapy (ART) is safe and can enhance HIV latency reversal. DESIGN: Vorinostat and disulfiram, can increase HIV transcription in people with HIV (PWH) on antiretroviral therapy (ART). Together these agents may lead to significant HIV latency reversal. METHODS: Virologically suppressed PWH on ART received disulfiram 2000 mg daily for 28 days and vorinostat 400 mg daily on days 8-10 and 22-24. The primary endpoint was plasma HIV RNA on day 11 relative to baseline using a single copy assay. Assessments included cell-associated (CA) unspliced (US) RNA as a marker of latency reversal, HIV DNA in CD4+ T-cells, plasma HIV RNA and plasma concentrations of ART, vorinostat and disulfiram. RESULTS: The first two participants (P1 and P2) experienced grade 3 neurotoxicity leading to trial suspension. After 24 days, P1 presented with confusion, lethargy, and ataxia having stopped disulfiram and ART. Symptoms resolved by day 29. After 11 days, P2 presented with paranoia, emotional lability, lethargy, ataxia and study drugs were ceased. Symptoms resolved by day 23. CA-US RNA increased by 1.4- and 1.3-fold for P1 and P2 respectively. Plasma HIV RNA was detectable from day 8-37 (peak 81 copies/mL) for P2 but was not increased in P1 Antiretroviral levels were therapeutic and neuronal injury markers were elevated in P1. CONCLUSIONS: The combination of prolonged high dose disulfiram and vorinostat was not safe in PWH on ART and should not be pursued despite evidence of latency reversal