Next-Generation Dengue Vaccines: Novel Strategies Currently Under Development

Dengue has become the most important arboviral infection worldwide with more than 30 million cases of dengue fever estimated to occur each year. The need for a dengue vaccine is great and several live attenuated dengue candidate vaccines are proceeding through clinical evaluation. The need to induce a balanced immune response against all four DENV serotypes with a single vaccine has been a challenge for dengue vaccine developers. A live attenuated DENV chimeric vaccine produced by Sanofi Pasteur has recently entered Phase III evaluation in numerous dengue-endemic regions of the world. Viral interference between serotypes contained in live vaccines has required up to three doses of the vaccine be given over a 12-month period of time. For this reason, novel DENV candidate vaccines are being developed with the goal of achieving a protective immune response with an immunization schedule that can be given over the course of a few months. These next-generation candidates include DNA vaccines, recombinant adenovirus vectored vaccines, alphavirus replicons, and sub-unit protein vaccines. Several of these novel candidates will be discussed

Polycyclic aromatic hydrocarbons in residential dust: sources of variability.

BackgroundThere is interest in using residential dust to estimate human exposure to environmental contaminants.ObjectivesWe aimed to characterize the sources of variability for polycyclic aromatic hydrocarbons (PAHs) in residential dust and provide guidance for investigators who plan to use residential dust to assess exposure to PAHs.MethodsWe collected repeat dust samples from 293 households in the Northern California Childhood Leukemia Study during two sampling rounds (from 2001 through 2007 and during 2010) using household vacuum cleaners, and measured 12 PAHs using gas chromatography-mass spectrometry. We used a random- and a mixed-effects model for each PAH to apportion observed variance into four components and to identify sources of variability.ResultsMedian concentrations for individual PAHs ranged from 10 to 190 ng/g of dust. For each PAH, total variance was apportioned into regional variability (1-9%), intraregional between-household variability (24-48%), within-household variability over time (41-57%), and within-sample analytical variability (2-33%). Regional differences in PAH dust levels were associated with estimated ambient air concentrations of PAH. Intraregional differences between households were associated with the residential construction date and the smoking habits of residents. For some PAHs, a decreasing time trend explained a modest fraction of the within-household variability; however, most of the within-household variability was unaccounted for by our mixed-effects models. Within-household differences between sampling rounds were largest when the interval between dust sample collections was at least 6 years in duration.ConclusionsOur findings indicate that it may be feasible to use residential dust for retrospective assessment of PAH exposures in studies of health effects

Product and other fine structure in polynomial resolutions of mapping spaces

Let Map_T(K,X) denote the mapping space of continuous based functions between two based spaces K and X. If K is a fixed finite complex, Greg Arone has recently given an explicit model for the Goodwillie tower of the functor sending a space X to the suspension spectrum \Sigma^\infty Map_T(K,X). Applying a generalized homology theory h_* to this tower yields a spectral sequence, and this will converge strongly to h_*(Map_T(K,X)) under suitable conditions, e.g. if h_* is connective and X is at least dim K connected. Even when the convergence is more problematic, it appears the spectral sequence can still shed considerable light on h_*(Map_T(K,X)). Similar comments hold when a cohomology theory is applied. In this paper we study how various important natural constructions on mapping spaces induce extra structure on the towers. This leads to useful interesting additional structure in the associated spectral sequences. For example, the diagonal on Map_T(K,X) induces a `diagonal' on the associated tower. After applying any cohomology theory with products h^*, the resulting spectral sequence is then a spectral sequence of differential graded algebras. The product on the E_\infty -term corresponds to the cup product in h^*(Map_T(K,X)) in the usual way, and the product on the E_1-term is described in terms of group theoretic transfers. We use explicit equivariant S-duality maps to show that, when K is the sphere S^n, our constructions at the fiber level have descriptions in terms of the Boardman-Vogt little n-cubes spaces. We are then able to identify, in a computationally useful way, the Goodwillie tower of the functor from spectra to spectra sending a spectrum X to \Sigma ^\infty \Omega ^\infty X.Comment: Published by Algebraic and Geometric Topology at http://www.maths.warwick.ac.uk/agt/AGTVol2/agt-2-28.abs.htm

Poor choices: the limits of competitive markets in the provision of essential services to low-income consumers

A major study of the problems faced by the poor in the market for seven essential services in the UK - energy, food, housing, water, telecoms, transport, and financial services. Together these represent 60% of spending by the poorest 30% of households

Skin color preferences in a Malaysian Chinese population

Facial skin color influences the perceived health and attractiveness of Caucasian faces, and has been proposed as a valid cue to aspects of physiological health. Similar preferences for skin color have previously been found in African participants, while different preferences have been found among mainland Chinese participants. Here, we asked Malaysian Chinese participants (ethnic Chinese living in an Asian country with high levels of exposure to Western culture) to manipulate the skin color of Malaysian Chinese, Caucasian, and African faces to make them “look as healthy as possible.” Participants chose to increase skin yellowness to a greater extent than to increase skin redness to optimize healthy appearance. The slight reduction in skin lightness chosen was not statistically significant after correction for multiple comparisons. While broadly in line with the preferences of Caucasian and African participants from previous studies, this differs from mainland Chinese participants. There may be a role for culture in skin color preferences, though methodological differences mean that further research is necessary to identify the cause of these differences in preferences

Helping chronically ill or disabled people into work: what can we learn from international comparative analyses?

This project has added to knowledge in five main areas: It has mapped the range and types of policies and interventions that have been implemented in Canada, Denmark, Norway, Sweden and the UK that may influence employment chances for chronically ill and disabled people. By doing so it has added to understanding about what has actually been tried in each country and what might be considered in others. It has refined a typology of the focussed interventions that have been identified, based on the underlying programme logic of the intervention, which aids strategic thinking about national efforts to help chronically ill and disabled people into work. It has produced systematic reviews of the impact of the focussed interventions on the employment chances of chronically ill and disabled people and demonstrated the use of the typology in helping to interpret the results of the evaluations. The project’s empirical analyses of individual-level data have identified how chronically ill people from different socio-economic groups have fared in the labour markets of the five countries over the past two decades. It has then tested these findings against hypotheses about the impact of macro-level labour market policies on chronically ill people to provide insights into the influence of the policy context. The project has contributed to methodological development in evidence synthesis and the evaluation of natural policy experiments. By studying a small number of countries in great depth, we gained greater understanding of the policies and interventions that have been tried in these countries to help chronically ill and disabled people into work, against the backdrop of the wider labour market and macro-economic trends in those countries. We then integrated evidence from the wider policy context into the findings of systematic reviews of effectiveness of interventions, to advance interpretation of the natural policy experiments that have been implemented in these countries

Pseudoangiomatous Stromal Hyperplasia: A Case Report

Pseudoangiomatous stromal hyperplasia (PASH) is a rare benign proliferating breast condition. It was first reported in 1986 when Vuitch, Rosen, and Erlandson described nine cases of benign well-circumscribed, breast masses that simulated vascular lesions consisting of mammary stromal proliferations (Vuitch et al. (1986)). Since then there have been few reported cases of PASH in the literature (Taira et al. (2005)). We describe a large PASH, mimicking inflammatory carcinoma in a young lady that was excised with excellent cosmetic results