Short-scale effects on model boundary-layer spots

This theoretical work, on the spot in an otherwise laminar boundary layer, concerns the initial-value problem for three-dimensional inviscid disturbances covering a wide range of scales. The study asks whether or not comparatively short scales can have a substantial impact on the spot spreading rate, as well as on other important features including the spot structure. It is found that such scales act to reduce the spread angle to approximately 11°, close to the experimental observations for transitional/turbulent spots, as opposed to the angle of 19.47° for waves near or behind the spot trailing edge. The scales emerge from coupling uniform shear flow directly with the local uniform stream and then analysing large-time features. The leading edge and trailing edge of the spot are also examined in detail, along with other structural properties. It is concluded that nonlinearity and short-scale effects probably combine to restrict the global spread angle as above, while viscous sublayer bursting among other things completes the spot structure. Related work on nonlinear, trailing-edge and leading-edge behaviours and comparisons with experiments are also discussed

On effects of increasing amplitude in a boundary-layer spot

The boundary-layer spots involved here come from large-time theory and related computations on the Euler equations to cover the majority of the global properties of the spot disturbances, which are nonlinear, three-dimensional, and transitional rather than turbulent. The amplitude levels investigated are higher than those examined in detail previously and produce a new near-wall momentum contribution in the mean flow, initially close to the wingtips of the spot. This enables the amplitude levels in the analysis to be raised successively, a process which gradually causes the wing-tip region to spread inwards. The process is accompanied by subtle increases in the induced phase variations. Among other things the work finds the details of how nonlinear effects grow from the wing-tips to eventually alter the entire trailing edge, and then the centre of the spot, in a strongly nonlinear fashion. Comparisons with earlier suggestions and with experiments are described at the end

Shrinking the Malaria Map: A Prospectus on Malaria Elimination

The Prospectus provides detailed and informed practical means of achieving and sustaining zero transmission. It is designed as a road map, providing direction and options from which to choose an appropriate path. The Prospectus reviews the operational, technical, and financial feasibility for those working on the front lines and outlines the tools that can be considered for an elimination program. The 10 chapters of the Prospectus were written by 33 contributing authors. The Prospectus is divided into two sections: Section 1 - Eliminating Malaria, comprises four chapters covering the strategic components important to the periods before, during, and after an elimination program. Section 2 - Tools for the Job, comprises six chapters that outline basic information about how interventions in an elimination program will be different from those in a control setting. A companion document, A Guide on Malaria Elimination for Policy Makers, is provided for those countries or agencies whose responsibility is primarily to make the policy decisions on whether to pursue or support a malaria elimination strategy

Lifting multi-blade flows with interaction

Planar flow past multiple successive blades and wakes is studied for nearly aligned configurations with normal non-symmetry inducing lift. The typical blade lies relatively near the centreline of the oncoming wake from the preceding blade. The central motion over a wide parameter range is in condensed periodic boundary layers and wakes with fixed displacement, buried within surrounding incident shear flow. This is accompanied, however, by streamwise jumps in the pressure, velocity and mass flux, across the leading edge of each blade, a new and surprising feature which is supported by the combination of incident shears and a solid surface and which is related to the normal flow through the multi-blade system. The leading-edge jumps are required in order to satisfy the equi-pressure condition at the trailing edge. Computational results include separating flows and show the lift and drag, and these are followed by a short-blade analysis which captures the main flow properties explicitly. The results agree qualitatively with experiments and direct simulations for rotor blade flows. The jump feature also extends for example to a single blade immersed in the relatively large wake of an upstream blade

Increasing value and reducing waste by optimizing the development of complex interventions: Enriching the development phase of the Medical Research Council (MRC) Framework

This is the final version of the article. Available from Elsevier via the DOI in this record.Background In recent years there has been much emphasis on ‘research waste’ caused by poor question selection, insufficient attention to previous research results, and avoidable weakness in research design, conduct and analysis. Little attention has been paid to the effect of inadequate development of interventions before proceeding to a full clinical trial. Objective We therefore propose to enrich the development phase of the MRC Framework by adding crucial elements to improve the likelihood of success and enhance the fit with clinical practice Methods Based on existing intervention development guidance and synthesis, a comprehensive iterative intervention development approach is proposed. Examples from published reports are presented to illustrate the methodology that can be applied within each element to enhance the intervention design. Results A comprehensive iterative approach is presented by combining the elements of the MRC Framework development phase with essential elements from existing guidance including: problem identification, the systematic identification of evidence, identification or development of theory, determination of needs, the examination of current practice and context, modelling the process and expected outcomes leading to final element: the intervention design. All elements are drawn from existing models to provide intervention developers with a greater chance of producing an intervention that is well adopted, effective and fitted to the context. Conclusion This comprehensive approach of developing interventions will strengthen the internal and external validity, minimize research waste and add value to health care research. In complex interventions in health care research, flaws in the development process immediately impact the chances of success. Knowledge regarding the causal mechanisms and interactions within the intended clinical context is needed to develop interventions that fit daily practice and are beneficial for the end-user

Adenoviral gene transfer of PLD1-D4 enhances insulin sensitivity in mice by disrupting phospholipase D1 interaction with PED/PEA-15.

Over-expression of phosphoprotein enriched in diabetes/phosphoprotein enriched in astrocytes (PED/PEA-15) causes insulin resistance by interacting with the D4 domain of phospholipase D1 (PLD1). Indeed, the disruption of this association restores insulin sensitivity in cultured cells over-expressing PED/PEA-15. Whether the displacement of PLD1 from PED/PEA-15 improves insulin sensitivity in vivo has not been explored yet. In this work we show that treatment with a recombinant adenoviral vector containing the human D4 cDNA (Ad-D4) restores normal glucose homeostasis in transgenic mice overexpressing PED/PEA-15 (Tg ped/pea-15) by improving both insulin sensitivity and secretion. In skeletal muscle of these mice, D4 over-expression inhibited PED/PEA-15-PLD1 interaction, decreased Protein Kinase C alpha activation and restored insulin induced Protein Kinase C zeta activation, leading to amelioration of insulin-dependent glucose uptake. Interestingly, Ad-D4 administration improved insulin sensitivity also in high-fat diet treated obese C57Bl/6 mice. We conclude that PED/PEA-15-PLD1 interaction may represent a novel target for interventions aiming at improving glucose tolerance

Nets, Spray or Both? The Effectiveness of Insecticide-Treated Nets and Indoor Residual Spraying in Reducing Malaria Morbidity and Child Mortality in sub-Saharan Africa.

Malaria control programmes currently face the challenge of maintaining, as well as accelerating, the progress made against malaria with fewer resources and uncertain funding. There is a critical need to determine what combination of malaria interventions confers the greatest protection against malaria morbidity and child mortality under routine conditions. This study assesses intervention effectiveness experienced by children under the age of five exposed to both insecticide-treated nets (ITNs) and indoor residual spraying (IRS), as compared to each intervention alone, based on nationally representative survey data collected from 17 countries in sub-Saharan Africa. Living in households with both ITNs and IRS was associated with a significant risk reduction against parasitaemia in medium and high transmission areas, 53% (95% CI 37% to 67%) and 31% (95% CI 11% to 47%) respectively. For medium transmission areas, an additional 36% (95% CI 7% to 53%) protection was garnered by having both interventions compared with exposure to only ITNs or only IRS. Having both ITNs and IRS was not significantly more protective against parasitaemia than either intervention alone in low and high malaria transmission areas. In rural and urban areas, exposure to both interventions provided significant protection against parasitaemia, 57% (95% CI 48% to 65%) and 39% (95% CI 10% to 61%) respectively; however, this effect was not significantly greater than having a singular intervention. Statistically, risk for all-cause child mortality was not significantly reduced by having both ITNs and IRS, and no additional protectiveness was detected for having dual intervention coverage over a singular intervention. These findings suggest that greater reductions in malaria morbidity and health gains for children may be achieved with ITNs and IRS combined beyond the protection offered by IRS or ITNs alone

Eliminating Malaria Vectors.

Malaria vectors which predominantly feed indoors upon humans have been locally eliminated from several settings with insecticide treated nets (ITNs), indoor residual spraying or larval source management. Recent dramatic declines of An. gambiae in east Africa with imperfect ITN coverage suggest mosquito populations can rapidly collapse when forced below realistically achievable, non-zero thresholds of density and supporting resource availability. Here we explain why insecticide-based mosquito elimination strategies are feasible, desirable and can be extended to a wider variety of species by expanding the vector control arsenal to cover a broader spectrum of the resources they need to survive. The greatest advantage of eliminating mosquitoes, rather than merely controlling them, is that this precludes local selection for behavioural or physiological resistance traits. The greatest challenges are therefore to achieve high biological coverage of targeted resources rapidly enough to prevent local emergence of resistance and to then continually exclude, monitor for and respond to re-invasion from external populations