The UK NHS Economic Evaluation Database : Economic issues in evaluations of health technology

Objective: The U.K. NHS Economic Evaluation Database (EED) project is commissioned to identify papers on economic evaluations of health technologies and to disseminate their findings to NHS decision makers by means of structured abstracts that are available through a public database and the Cochrane Library. This paper discusses current issues relating to the economic aspects of producing NHS EED abstracts. Methods: A review of NHS EED was undertaken between 1994 and 1999 to determine the methodologies adopted and issues that influence the usefulness of economic evaluations. Methods adopted to improve the quality of NHS EED abstracts are also reported. Results: Eighty-five percent of NHS EED abstracts are cost-effectiveness analyses (CEAs), 9.3% are cost-utility analyses (CUAs), and only 1.4% are cost-benefit analyses (CBAs). Of the total abstracts, 65.9% are based on single studies, 19.5% on reviews, 3.9% on estimates of effectiveness, and 10.7% on combinations of these sources. Models are utilized in 16.7% of CEAs, 60.2% of CUAs, and 20% of CBAs. Analyses of CBA studies reveal a degree of misuse of well-established definitions. NHS EED internal control mechanisms are reported that provide a means of ensuring that abstracts are based on sound academic principles. Conclusions: Most economic evaluations are conducted by means of CEA, followed by CUA, while CBA accounts for an extreme minority of cases. Single studies form the principal source of effectiveness data, although models are widely used, principally in CUA. The structure of NHS EED abstracts provides decision makers with the principal results and an interpretation of the relative strengths and weaknesses of economic evaluations

Acute inhibition of MEK suppresses congenital melanocytic nevus syndrome in a murine model driven by activated NRAS and Wnt signaling

Congenital melanocytic nevus (CMN) syndrome is the association of pigmented melanocytic nevi with extra-cutaneous features, classically melanotic cells within the central nervous system, most frequently caused by a mutation of NRAS codon 61. This condition is currently untreatable and carries a significant risk of melanoma within the skin, brain, or leptomeninges. We have previously proposed a key role for Wnt signaling in the formation of melanocytic nevi, suggesting that activated Wnt signaling may be synergistic with activated NRAS in the pathogenesis of CMN syndrome. Some familial pre-disposition suggests a germ-line contribution to CMN syndrome, as does variability of neurological phenotypes in individuals with similar cutaneous phenotypes. Accordingly, we performed exome sequencing of germ-line DNA from patients with CMN to reveal rare or undescribed Wnt-signaling alterations. A murine model harboring activated NRASQ61K and Wnt signaling in melanocytes exhibited striking features of CMN syndrome, in particular neurological involvement. In the first model of treatment for this condition, these congenital, and previously assumed permanent, features were profoundly suppressed by acute post-natal treatment with a MEK inhibitor. These data suggest that activated NRAS and aberrant Wnt signaling conspire to drive CMN syndrome. Post-natal MEK inhibition is a potential candidate therapy for patients with this debilitating condition

Modeling approach to regime shifts of primary production in shallow coastal ecosystems

Pristine coastal shallow systems are usually dominated by extensive meadows of seagrass species, which are assumed to take advantage of nutrient supply from sediment. An increasing nutrient input is thought to favour phytoplankton, epiphytic microalgae, as well as opportunistic ephemeral macroalgae that coexist with seagrasses. The primary cause of shifts and succession in the macrophyte community is the increase of nutrient load to water; however temperature plays also an important role. A competition model between rooted seagrass (Zostera marina), macroalgae (Ulva sp), and phytoplankton has been developed to analyse the succession of primary producer communities in these systems. Successions of dominance states, with different resilience characteristics, are found when modifying the input of nutrients and the seasonal temperature and light intensity forcing.Comment: 33 pages, including 10 figures. To appear in Ecological Complexit

Current Status of Simulations

As the title suggests, the purpose of this chapter is to review the current status of numerical simulations of black hole accretion disks. This chapter focuses exclusively on global simulations of the accretion process within a few tens of gravitational radii of the black hole. Most of the simulations discussed are performed using general relativistic magnetohydrodynamic (MHD) schemes, although some mention is made of Newtonian radiation MHD simulations and smoothed particle hydrodynamics. The goal is to convey some of the exciting work that has been going on in the past few years and provide some speculation on future directions.Comment: 15 pages, 14 figures, to appear in the proceedings of the ISSI-Bern workshop on "The Physics of Accretion onto Black Holes" (8-12 October 2012

Single-electron transport driven by surface acoustic waves: moving quantum dots versus short barriers

We have investigated the response of the acoustoelectric current driven by a surface-acoustic wave through a quantum point contact in the closed-channel regime. Under proper conditions, the current develops plateaus at integer multiples of ef when the frequency f of the surface-acoustic wave or the gate voltage Vg of the point contact is varied. A pronounced 1.1 MHz beat period of the current indicates that the interference of the surface-acoustic wave with reflected waves matters. This is supported by the results obtained after a second independent beam of surface-acoustic wave was added, traveling in opposite direction. We have found that two sub-intervals can be distinguished within the 1.1 MHz modulation period, where two different sets of plateaus dominate the acoustoelectric-current versus gate-voltage characteristics. In some cases, both types of quantized steps appeared simultaneously, though at different current values, as if they were superposed on each other. Their presence could result from two independent quantization mechanisms for the acoustoelectric current. We point out that short potential barriers determining the properties of our nominally long constrictions could lead to an additional quantization mechanism, independent from those described in the standard model of 'moving quantum dots'.Comment: 25 pages, 12 figures, to be published in a special issue of J. Low Temp. Phys. in honour of Prof. F. Pobel

Supermassive Black Hole Binaries: The Search Continues

Gravitationally bound supermassive black hole binaries (SBHBs) are thought to be a natural product of galactic mergers and growth of the large scale structure in the universe. They however remain observationally elusive, thus raising a question about characteristic observational signatures associated with these systems. In this conference proceeding I discuss current theoretical understanding and latest advances and prospects in observational searches for SBHBs.Comment: 17 pages, 4 figures. To appear in the Proceedings of 2014 Sant Cugat Forum on Astrophysics. Astrophysics and Space Science Proceedings, ed. C.Sopuerta (Berlin: Springer-Verlag

Socioeconomic Disadvantage and Child Morbidity: An Australian Longitudinal Study

While an extensive body of literature has demonstrated an association between socioeconomic status and child mortality, there have been relatively few papers which discuss the impact of socioeconomic inequality on child morbidity. This absence of data is partly attributable to methodological problems (need for large samples, the difficulty of assessing morbidity) and partly to the absence of relevant official health statistics. This paper reports results from the Mater-University of Queensland Study of Pregnancy (MUSP) and its outcomes. The sample comprises 8556 consecutive pregnancies, of which over 90% were followed up to birth. Of those mothers giving birth, approx. 70% of children were successfully given a health assessment five years after the birth (mothers report of the child's health using a set of standard indicators). The results indicate a consistent pattern with the children of the most socioeconomically disadvantaged mothers manifesting the worst health. Thus children living in socioeconomic disadvantage have a higher rate of health service utilisation, more chronic health problems and poorer dental health. The paper discusses some social policies for redressing these inequalities

Phytoplankton in a temperate-zone salt marsh: Net production and exchanges with coastal waters

Phytoplankton production and associated variables were measured in Flax Pond, a 52 ha salt marsh on the north shore of Long Island, New York, from July 1972 to October 1973. Measurements made up to five times per day, once per week, yielded a mean annual net primary production, determined by the 14 C technique, of 20.5 mg C/m 3 /h; daily means were as high as 60.0 mg C/m 3 /h. However, when productivity was calculated for the entire marsh ecosystem, the shallow water in the salt marsh produced only 11.7 g C/m 2 of marsh/year. There was a net flux of phytoplankton from the coastal waters into the marsh; during the summer up to 0.2 g chlorophy 11/m 2 of marsh was carried in with the tides daily and remained in the marsh. Analysis of the productivity data, as well as variables associated with productivity (pH, standing crop, nutrients, extinction coefficient), indicated that the aquatic portion of the marsh behaved more as a net consumer rather than a net producer of phytoplankton.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/46630/1/227_2004_Article_BF00391561.pd

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy