2,892 research outputs found

    Human Colon Carcinoma Cells Expressing CMVpp65 Antigen: An IN-VIVO Model for Adoptive Immunotherapy Of CMV Disease

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    Evolution of surface gravity waves over a submarine canyon

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    The effects of a submarine canyon on the propagation of ocean surface waves are examined with a three-dimensional coupled-mode model for wave propagation over steep topography. Whereas the classical geometrical optics approximation predicts an abrupt transition from complete transmission at small incidence angles to no transmission at large angles, the full model predicts a more gradual transition with partial reflection/transmission that is sensitive to the canyon geometry and controlled by evanescent modes for small incidence angles and relatively short waves. Model results for large incidence angles are compared with data from directional wave buoys deployed around the rim and over Scripps Canyon, near San Diego, California, during the Nearshore Canyon Experiment (NCEX). Wave heights are observed to decay across the canyon by about a factor 5 over a distance shorter than a wavelength. Yet, a spectral refraction model predicts an even larger reduction by about a factor 10, because low frequency components cannot cross the canyon in the geometrical optics approximation. The coupled-mode model yields accurate results over and behind the canyon. These results show that although most of the wave energy is refractively trapped on the offshore rim of the canyon, a small fraction of the wave energy 'tunnels' across the canyon. Simplifications of the model that reduce it to the standard and modified mild slope equations also yield good results, indicating that evanescent modes and high order bottom slope effects are of minor importance for the energy transformation of waves propagating across depth contours at large oblique angles

    Service delivery interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review.

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    BackgroundVoluntary medical male circumcision (VMMC) remains an essential component of combination HIV prevention services, particularly in priority countries in sub-Saharan Africa. As VMMC programs seek to maximize impact and efficiency, and to support World Health Organization guidance, specific uptake-enhancing strategies are critical to identify.MethodsWe systematically reviewed the literature to evaluate the impact of service delivery interventions (e.g., facility layout, service co-location, mobile outreach) on VMMC uptake among adolescent and adult men. For the main effectiveness review, we searched for publications or conference abstracts that measured VMMC uptake or uptake of HIV testing or risk reduction counselling within VMMC services. We synthesized data by coding categories and outcomes. We also reviewed studies assessing acceptability, values/preferences, costs, and feasibility.ResultsFour randomized controlled trials and five observational studies were included in the effectiveness review. Studies took place in South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. They assessed a range of service delivery innovations, including community-, school-, and facility-based interventions. Overall, interventions increased VMMC uptake; some successfully improved uptake among age-specific subpopulations, but urban-rural stratification showed no clear trends. Interventions that increased adult men's uptake included mobile services (compared to static facilities), home-based testing with active referral follow-up, and facility-based HIV testing with enhanced comprehensive sexual education. Six acceptability studies suggested interventions were generally perceived to help men choose to get circumcised. Eleven cost studies suggested interventions create economies-of-scale and efficiencies. Three studies suggested such interventions were feasible, improving facility preparedness, service quality and quantity, and efficiencies.ConclusionsInnovative changes in male-centered VMMC services can improve adult men's and adolescent boys' VMMC uptake. Limited evidence on interventions that enhance access and acceptability show promising results, but evidence gaps persist due to inconsistent intervention definition and delivery, due in part to contextual relevance and limited age disaggregation

    Economic compensation interventions to increase uptake of voluntary medical male circumcision for HIV prevention: A systematic review and meta-analysis.

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    BackgroundEconomic compensation interventions may help support higher voluntary medical male circumcision (VMMC) coverage in priority sub-Saharan African countries. To inform World Health Organization guidelines, we conducted a systematic review of economic compensation interventions to increase VMMC uptake.MethodsEconomic compensation interventions were defined as providing money or in-kind compensation, reimbursement for associated costs (e.g. travel, lost wages), or lottery entry. We searched five electronic databases and four scientific conferences for studies examining the impact of such interventions on VMMC uptake, HIV testing and safer-sex/risk-reduction counseling uptake within VMMC, community expectations about compensation, and potential coercion. We screened citations, extracted data, and assessed risk of bias in duplicate. We conducted random-effects meta-analysis. We also reviewed studies examining acceptability, values/preferences, costs, and feasibility.ResultsOf 2484 citations identified, five randomized controlled trials (RCTs) and three non-randomized controlled trials met our eligibility criteria. Studies took place in Kenya, Malawi, South Africa, Tanzania, Uganda, Zambia, and Zimbabwe. Meta-analysis of four RCTs showed significant impact of any economic compensation on VMMC uptake (relative risk: 5.23, 95% CI: 3.13 to 8.76). RCTs of food/transport vouchers and conditional cash transfers generally showed increases in VMMC uptake, but lotteries, subsidized VMMC, and receiving a gift appeared somewhat less effective. Three non-randomized trials showed mixed impact. Six additional studies suggested economic compensation interventions were generally acceptable, valued for addressing key barriers, and motivating to men. However, some participants felt they were insufficiently motivating or necessary; one study suggested they might raise community suspicions. One study from South Africa found a program cost of US91peradditionalcircumcisionandUS91 per additional circumcision and US450-$1350 per HIV infection averted.ConclusionsEconomic compensation interventions, particularly transport/food vouchers, positively impacted VMMC uptake among adult men and were generally acceptable to potential clients. Carefully selected economic interventions may be a useful targeted strategy to enhance VMMC coverage

    Communication in cross-cultural consultations in primary care in Europe: the case for improvement. The rationale for the RESTORE FP 7 project

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    The purpose of this paper is to substantiate the importance of research about barriers and levers to the implementation of supports for cross-cultural communication in primary care settings in Europe. After an overview of migrant health issues, with the focus on communication in cross-cultural consultations in primary care and the importance of language barriers, we highlight the fact that there are serious problems in routine practice that persist over time and across different European settings. Language and cultural barriers hamper communication in consultations between doctors and migrants, with a range of negative effects including poorer compliance and a greater propensity to access emergency services. It is well established that there is a need for skilled interpreters and for professionals who are culturally competent to address this problem. A range of professional guidelines and training initiatives exist that support the communication in cross-cultural consultations in primary care. However, these are commonly not implemented in daily practice. It is as yet unknown why professionals do not accept or implement these guidelines and interventions, or under what circumstances they would do so. A new study involving six European countries, RESTORE (REsearch into implementation STrategies to support patients of different ORigins and language background in a variety of European primary care settings), aims to address these gaps in knowledge. It uses a unique combination of a contemporary social theory, normalisation process theory (NPT) and participatory learning and action (PLA) research. This should enhance understanding of the levers and barriers to implementation, as well as providing stakeholders, with the opportunity to generate creative solutions to problems experienced with the implementation of such interventions

    Learning Representations that Support Extrapolation

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    Extrapolation -- the ability to make inferences that go beyond the scope of one's experiences -- is a hallmark of human intelligence. By contrast, the generalization exhibited by contemporary neural network algorithms is largely limited to interpolation between data points in their training corpora. In this paper, we consider the challenge of learning representations that support extrapolation. We introduce a novel visual analogy benchmark that allows the graded evaluation of extrapolation as a function of distance from the convex domain defined by the training data. We also introduce a simple technique, temporal context normalization, that encourages representations that emphasize the relations between objects. We find that this technique enables a significant improvement in the ability to extrapolate, considerably outperforming a number of competitive techniques.Comment: ICML 202

    P450 gene duplication and divergence led to the evolution of dual novel functions and insecticide cross-resistance in the brown planthopper Nilaparvata lugens

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    The sustainable control of many highly damaging insect crop pests and disease vectors is threatened by the evolution of insecticide resistance. As a consequence, strategies have been developed that aim to prevent or delay resistance development by rotating or mixing insecticides with different modes of action (MoA). However, these approaches can be compromised by the emergence of mechanisms that confer cross-resistance to insecticides with different MoA. Despite the applied importance of cross-resistance, its evolutionary underpinnings remain poorly understood. Here we reveal how a single gene evolved the capacity to detoxify two structurally unrelated insecticides with different MoA. Using transgenic approaches we demonstrate that a specific variant of the cytochrome P450 CYP6ER1, previously shown to confer resistance to the neonicotinoid imidacloprid in the brown planthopper, N. lugens, also confers cross-resistance to the phenylpyrazole ethiprole. CYP6ER1 is duplicated in resistant strains, and we show that while the acquisition of mutations in two encoded substrate recognition sites (SRS) of one of the parologs led to resistance to imidacloprid, a different set of mutations, outside of known SRS, are primarily responsible for resistance to ethiprole. Epistatic interactions between these mutations and their genetic background suggest that the evolution of dual resistance from the same gene copy involved functional trade-offs in respect to CYP6ER1 catalytic activity for ethiprole versus imidacloprid. Surprisingly, the mutations leading to ethiprole and imidacloprid resistance do not confer the ability to detoxify the insecticide fipronil, another phenylpyrazole with close structural similarity to ethiprole. Taken together, these findings reveal how gene duplication and divergence can lead to the evolution of multiple novel functions from a single gene. From an applied perspective they also demonstrate how cross-resistance to structurally unrelated insecticides can evolve, and illustrate the difficulty in predicting cross-resistance profiles mediated by metabolic mechanisms
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