Commissioning for health improvement following the 2012 health and social care reforms in England: what has changed?

Background: The wide-ranging program of reforms brought about by the Health and Social Care Act (2012) in England fundamentally changed the operation of the public health system, moving responsibility for the commissioning and delivery of services from the National Health Service to locally elected councils and a new national public health agency. This paper explores the ways in which the reforms have altered public health commissioning. Methods: We conducted multi-methods research over 33 months, incorporating national surveys of Directors of Public Health and local council elected members at two time-points, and in-depth case studies in five purposively selected geographical areas. Results: Public health commissioning responsibilities have changed and become more fragmented, being split amongst a range of different organisations, most of which were newly created in 2013. There is much change in the way public health commissioning is done, in who is doing it, and in what is commissioned, since the reforms. There is wider consultation on decisions in the local council setting than in the NHS, and elected members now have a strong influence on public health prioritisation. There is more (and different) scrutiny being applied to public health contracts, and most councils have embarked on wide-ranging changes to the health improvement services they commission. Public health money is being used in different ways as councils are adapting to increasing financial constraint. Conclusions: Our findings suggest that, while some of the intended opportunities to improve population health and create a more joined-up system with clearer leadership have been achieved, fragmentation, dispersed decision-making and uncertainties regarding funding remain significant challenges. There have been profound changes in commissioning processes, with consequences for what health improvement services are ultimately commissioned. Time (and further research) will tell if any of these changes lead to improved population health outcomes and reduced health inequalities, but many of the opportunities brought about by the reforms are threatened by the continued flux in the system

Current Industrial Practices in Assessing CYP450 Enzyme Induction: Preclinical and Clinical

Induction of drug metabolizing enzymes, such as the cytochromes P450 (CYP) is known to cause drug-drug interactions due to increased elimination of co-administered drugs. This increased elimination may lead to significant reduction or complete loss of efficacy of the co-administered drug. Due to the significance of such drug interactions, many pharmaceutical companies employ screening and characterization models which predict CYP enzyme induction to avoid or attenuate the potential for drug interactions with new drug candidates. The most common mechanism of CYP induction is transcriptional gene activation. Activation is mediated by nuclear receptors, such as AhR, CAR, and PXR that function as transcription factors. Early high throughput screening models utilize these nuclear hormone receptors in ligand binding or cell-based transactivation/reporter assays. In addition, immortalized hepatocyte cell lines can be used to assess enzyme induction of specific drug metabolizing enzymes. Cultured primary human hepatocytes, the best established in vitro model for predicting enzyme induction and most accepted by regulatory agencies, is the predominant assay used to evaluate induction of a wide variety of drug metabolizing enzymes. These in vitro models are able to appropriately predict enzyme induction in patients when compared to clinical drug-drug interactions. Finally, transgenic animal models and the cynomolgus monkey have also been shown to recapitulate human enzyme induction and may be appropriate in vivo animal models for predicting human drug interactions

Reversible femtosecond pulse lengthening using prism pairs and a focusing element

This paper experimentally examines the use of prism pairs and focusing elements to reversibly lengthen the duration of femtosecond pulses by means of spatial dispersion of the different frequency components of an ultrashort optical pulse in a direction transverse to the direction of propagation.1 Unlike techniques based on a linear pulse chirp, this approach has the advantage of not favoring one part of the pulse spectrum over another in a nonlinear amplifier medium. The temporal lengthening described here, from the order of 50 fs to the order of 500 fs, is expected to have significant consequences because key mechanisms in amplifier media, such as spectral hole burning, have time constants of the order of 100 fs or less. The prism pairs also provide other useful features, such as a group velocity dispersion correction that can be adjusted from negative through positive values, low insertion loss, and easily adjusted spectral filtering. A comparison of the experimentally measured pulse broadening and its analytically calculated value for the experimental conditions shows good agreement between experiment and theory.2 We will also discuss amplifier designs that take advantage of this pulse lengthening technique.</jats:p

Colliding pulse mode-locked lasers: intracavity evolution of pulse chirp and intensity

To obtain minimal pulse widths in colliding pulse mode-locked (CPM) lasers it is essential that the intracavity elements, both active and passive, be chosen to control pulse chirp and the time dependence of the gain and absorption. To date, the analyses of CPM lasers have dealt largely with the steady-state output and in a few cases the evolution of that output. In contrast we consider the details of the intracavity pulse evolution.</jats:p

Retina-like Adaptive Thresholding in a Nonlinear Joint Transform Correlator

Joint transform correlators, now made practical by the availability of many electrically- and optically- addressed spatial light modulators (SLM) and convenient coherent light sources, have been shown to be effective at both optical pattern recognition (OPR) [1] and tracking [2].</jats:p