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Werner Leber

Other affiliations: University of London
Bio: Werner Leber is an academic researcher from Queen Mary University of London. The author has contributed to research in topics: Cluster randomised controlled trial & Population. The author has an hindex of 7, co-authored 19 publications receiving 225 citations. Previous affiliations of Werner Leber include University of London.

Papers
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Journal ArticleDOI
31 May 2015-Trials
TL;DR: An adaptation of the diffusion of innovations model was an effective analytical tool for retrospectively explaining high and low-performing practices in a complex intervention research trial.
Abstract: Complex intervention trials may require health care organisations to implement new service models. In a recent cluster randomised controlled trial, some participating organisations achieved high recruitment, whereas others found it difficult to assimilate the intervention and were low recruiters. We sought to explain this variation and develop a model to inform organisational participation in future complex intervention trials. The trial included 40 general practices in a London borough with high HIV prevalence. The intervention was offering a rapid HIV test as part of the New Patient Health Check. The primary outcome was mean CD4 cell count at diagnosis. The process evaluation consisted of several hundred hours of ethnographic observation, 21 semi-structured interviews and analysis of routine documents (e.g., patient leaflets, clinical protocols) and trial documents (e.g., inclusion criteria, recruitment statistics). Qualitative data were analysed thematically using—and, where necessary, extending—Greenhalgh et al.’s model of diffusion of innovations. Narrative synthesis was used to prepare case studies of four practices representing maximum variety in clinicians’ interest in HIV (assessed by level of serological testing prior to the trial) and performance in the trial (high vs. low recruiters). High-recruiting practices were, in general though not invariably, also innovative practices. They were characterised by strong leadership, good managerial relations, readiness for change, a culture of staff training and available staff time (‘slack resources’). Their front-line staff believed that patients might benefit from the rapid HIV test (‘relative advantage’), were emotionally comfortable administering it (‘compatibility’), skilled in performing it (‘task issues’) and made creative adaptations to embed the test in local working practices (‘reinvention’). Early experience of a positive HIV test (‘observability’) appeared to reinforce staff commitment to recruiting more participants. Low-performing practices typically had less good managerial relations, significant resource constraints, staff discomfort with the test and no positive results early in the trial. An adaptation of the diffusion of innovations model was an effective analytical tool for retrospectively explaining high and low-performing practices in a complex intervention research trial. Whether the model will work prospectively to predict performance (and hence shape the design of future trials) is unknown. ISRCTN Registry number: ISRCTN63473710 . Date assigned: 22 April 2010.

53 citations

Journal ArticleDOI
TL;DR: Promotion of opt-out rapid testing in general practice led to increased rate of diagnosis, and might increase early detection, of HIV, and it is recommended implementation of HIV screening in general practices in areas with high HIV prevalence.

42 citations

Journal ArticleDOI
TL;DR: The unexpected physical attachment of an NCS-like domain to the plasmodial PIP5K might reflect a unique functional link between the calcium and PtdIns(4,5)P(2) pathways allowing modulation of Ptd insurance production in response to changes in intracellular calcium concentrations within the parasite.

39 citations

Journal ArticleDOI
TL;DR: Screening for HIV in primary care is cost-effective and should be promoted, in settings where long-term health-care costs of late-diagnosed patients in high-prevalence regions are much higher (≥60%) than those of patients diagnosed earlier.

39 citations


Cited by
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Journal ArticleDOI
TL;DR: Reading a book as this basics of qualitative research grounded theory procedures and techniques and other references can enrich your life quality.

13,415 citations

Journal ArticleDOI
TL;DR: This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.
Abstract: Phosphoinositides (PIs) make up only a small fraction of cellular phospholipids, yet they control almost all aspects of a cell's life and death. These lipids gained tremendous research interest as plasma membrane signaling molecules when discovered in the 1970s and 1980s. Research in the last 15 years has added a wide range of biological processes regulated by PIs, turning these lipids into one of the most universal signaling entities in eukaryotic cells. PIs control organelle biology by regulating vesicular trafficking, but they also modulate lipid distribution and metabolism via their close relationship with lipid transfer proteins. PIs regulate ion channels, pumps, and transporters and control both endocytic and exocytic processes. The nuclear phosphoinositides have grown from being an epiphenomenon to a research area of its own. As expected from such pleiotropic regulators, derangements of phosphoinositide metabolism are responsible for a number of human diseases ranging from rare genetic disorders to the most common ones such as cancer, obesity, and diabetes. Moreover, it is increasingly evident that a number of infectious agents hijack the PI regulatory systems of host cells for their intracellular movements, replication, and assembly. As a result, PI converting enzymes began to be noticed by pharmaceutical companies as potential therapeutic targets. This review is an attempt to give an overview of this enormous research field focusing on major developments in diverse areas of basic science linked to cellular physiology and disease.

1,239 citations

Journal Article
07 May 2021-Elements
TL;DR: An influenza epidemic simulation model was adapted to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population and the combined intervention was the most effective, reducing the estimated median number of infections.
Abstract: Summary Background Since the coronavirus disease 2019 outbreak began in the Chinese city of Wuhan on Dec 31, 2019, 68 imported cases and 175 locally acquired infections have been reported in Singapore. We aimed to investigate options for early intervention in Singapore should local containment (eg, preventing disease spread through contact tracing efforts) be unsuccessful. Methods We adapted an influenza epidemic simulation model to estimate the likelihood of human-to-human transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in a simulated Singaporean population. Using this model, we estimated the cumulative number of SARS-CoV-2 infections at 80 days, after detection of 100 cases of community transmission, under three infectivity scenarios (basic reproduction number [R0] of 1·5, 2·0, or 2·5) and assuming 7·5% of infections are asymptomatic. We first ran the model assuming no intervention was in place (baseline scenario), and then assessed the effect of four intervention scenarios compared with a baseline scenario on the size and progression of the outbreak for each R0 value. These scenarios included isolation measures for infected individuals and quarantining of family members (hereafter referred to as quarantine); quarantine plus school closure; quarantine plus workplace distancing; and quarantine, school closure, and workplace distancing (hereafter referred to as the combined intervention). We also did sensitivity analyses by altering the asymptomatic fraction of infections (22·7%, 30·0%, 40·0%, and 50·0%) to compare outbreak sizes under the same control measures. Findings For the baseline scenario, when R0 was 1·5, the median cumulative number of infections at day 80 was 279 000 (IQR 245 000–320 000), corresponding to 7·4% (IQR 6·5–8·5) of the resident population of Singapore. The median number of infections increased with higher infectivity: 727 000 cases (670 000–776 000) when R0 was 2·0, corresponding to 19·3% (17·8–20·6) of the Singaporean population, and 1 207 000 cases (1 164 000–1 249 000) when R0 was 2·5, corresponding to 32% (30·9–33·1) of the Singaporean population. Compared with the baseline scenario, the combined intervention was the most effective, reducing the estimated median number of infections by 99·3% (IQR 92·6–99·9) when R0 was 1·5, by 93·0% (81·5–99·7) when R0 was 2·0, and by 78·2% (59·0 −94·4) when R0 was 2·5. Assuming increasing asymptomatic fractions up to 50·0%, up to 277 000 infections were estimated to occur at day 80 with the combined intervention relative to 1800 for the baseline at R0 of 1·5. Interpretation Implementing the combined intervention of quarantining infected individuals and their family members, workplace distancing, and school closure once community transmission has been detected could substantially reduce the number of SARS-CoV-2 infections. We therefore recommend immediate deployment of this strategy if local secondary transmission is confirmed within Singapore. However, quarantine and workplace distancing should be prioritised over school closure because at this early stage, symptomatic children have higher withdrawal rates from school than do symptomatic adults from work. At higher asymptomatic proportions, intervention effectiveness might be substantially reduced requiring the need for effective case management and treatments, and preventive measures such as vaccines. Funding Singapore Ministry of Health, Singapore Population Health Improvement Centre.

317 citations

Journal ArticleDOI
TL;DR: Five potent and broadly anti-HIV neutralizing monoclonal antibodies are able to block infection by two different SHIVs in monkeys and it is determined that titers of roughly 1:100 protected half the animals.
Abstract: It is widely appreciated that effective human vaccines directed against viral pathogens elicit neutralizing antibodies (NAbs). The passive transfer of anti–HIV-1 NAbs conferring sterilizing immunity to macaques has been used to determine the plasma neutralization titers, which must be present at the time of exposure, to prevent acquisition of SIV/HIV chimeric virus (SHIV) infections. We administered five recently isolated potent and broadly acting anti-HIV neutralizing monoclonal antibodies (mAbs) to rhesus macaques and challenged them intrarectally 24 h later with either of two different R5-tropic SHIVs. By combining the results obtained from 60 challenged animals, we determined that the protective neutralization titer in plasma preventing virus infection in 50% of the exposed monkeys was relatively modest (∼1:100) and potentially achievable by vaccination.

291 citations

Journal ArticleDOI
TL;DR: It is clear HIV-specific NAbs drive the evolution of the HIV-1 envelope glycoprotein within an infected individual, and several new potent monoclonal antibodies have been identified, and are beginning to yield important clues into the epitopes common to diverse HIV- 1 strains.
Abstract: Neutralizing antibodies (NAbs) typically play a key role in controlling viral infections and contribute to the protective effect of many successful vaccines. In the case of HIV-1 infection, there is compelling data in experimental animal models that NAbs can prevent HIV-1 acquisition, although there is no similar data in humans and their role in controlling established infection in humans is also limited. It is clear HIV-specific NAbs drive the evolution of the HIV-1 envelope glycoprotein within an infected individual. The virus's ability to evade immune selection may be the main reason HIV-1 NAbs exert limited control during infection. The extraordinary antigenic diversity of HIV-1 also presents formidable challenges to defining NAbs that could provide broad protection against diverse circulating HIV-1 strains. Several new potent monoclonal antibodies (MAbs) have been identified, and are beginning to yield important clues into the epitopes common to diverse HIV-1 strains. In addition, antibodies can also act in concert with effector cells to kill HIV-infected cells; this could provide another mechanism for antibody-mediated control of HIV-1 replication. Understanding the impact of antibodies on HIV-1 transmission and pathogenesis is critical to helping move forward with rational HIV-1 vaccine design.

189 citations