Departures from cost-effectiveness recommendations: The impact of health system constraints on priority setting

The methods and application of cost-effectiveness analysis have reached an advanced stage of development. Many decision makers consider cost-effectiveness analysis to be a valid and feasible approach towards setting health priorities, and it has been extensively applied in evaluating interventions and developing evidence based clinical guidelines. However, the recommendations arising from cost-effectiveness analysis are often not implemented as intended. A fundamental reason for the failure to implement is that CEA assumes a single constraint, in the form of the budget constraint, whilst in reality decision-makers may be faced with numerous other constraints. The objective of this paper is to develop a typology of constraints that may act as barriers to implementation of cost-effectiveness recommendations. Six categories of constraints are considered: the design of the health system; costs of implementing change; system interactions between interventions; uncertainty in estimates of costs and benefits; weak governance; and political constraints. Where possible -and if applicable- for each class of constraint, the paper discusses ways in which these constraints can be taken into account by a decision maker wishing to pursue the principles of cost-effectiveness

High bat (Chiroptera) diversity in the Early Eocene of India

The geographic origin of bats is still unknown, and fossils of earliest bats are rare and poorly diversified, with, maybe, the exception of Europe. The earliest bats are recorded from the Early Eocene of North America, Europe, North Africa and Australia where they seem to appear suddenly and simultaneously. Until now, the oldest record in Asia was from the Middle Eocene. In this paper, we report the discovery of the oldest bat fauna of Asia dating from the Early Eocene of the Cambay Formation at Vastan Lignite Mine in Western India. The fossil taxa are described on the basis of well-preserved fragments of dentaries and lower teeth. The fauna is highly diversified and is represented by seven species belonging to seven genera and at least four families. Two genera and five species are new. Three species exhibit very primitive dental characters, whereas four others indicate more advanced states. Unexpectedly, this fauna presents strong affinities with the European faunas from the French Paris Basin and the German Messel locality. This could result from the limited fossil record of bats in Asia, but could also suggest new palaeobiogeographic scenarios involving the relative position of India during the Early Eocene

Phylogenetic relationships of Pestalotiopsis and allied genera inferred from ribosomal DNA sequences

Publication no. P-2001-0089-MSA,published_or_final_versio

In the face of threat: neural and endocrine correlates of impaired facial emotion recognition in cocaine dependence.

The ability to recognize facial expressions of emotion in others is a cornerstone of human interaction. Selective impairments in the recognition of facial expressions of fear have frequently been reported in chronic cocaine users, but the nature of these impairments remains poorly understood. We used the multivariate method of partial least squares and structural magnetic resonance imaging to identify gray matter brain networks that underlie facial affect processing in both cocaine-dependent (n = 29) and healthy male volunteers (n = 29). We hypothesized that disruptions in neuroendocrine function in cocaine-dependent individuals would explain their impairments in fear recognition by modulating the relationship with the underlying gray matter networks. We found that cocaine-dependent individuals not only exhibited significant impairments in the recognition of fear, but also for facial expressions of anger. Although recognition accuracy of threatening expressions co-varied in all participants with distinctive gray matter networks implicated in fear and anger processing, in cocaine users it was less well predicted by these networks than in controls. The weaker brain-behavior relationships for threat processing were also mediated by distinctly different factors. Fear recognition impairments were influenced by variations in intelligence levels, whereas anger recognition impairments were associated with comorbid opiate dependence and related reduction in testosterone levels. We also observed an inverse relationship between testosterone levels and the duration of crack and opiate use. Our data provide novel insight into the neurobiological basis of abnormal threat processing in cocaine dependence, which may shed light on new opportunities facilitating the psychosocial integration of these patients.This work was funded by a research grant from the Medical Research Council (G0701497) and supported by the infrastructure of the Behavioural and Clinical Neuroscience Institute (which is supported by a joint award from the Medical Research Council and the Wellcome Trust). This study was jointly sponsored by the Cambridge University Hospitals NHS Foundation Trust and the University of Cambridge. KD Ersche, CC Hagan, and PS Jones are supported by the Medical Research Council, and DG Smith by the Cambridge Overseas Trust.This is the final version of the article. It first appeared from NPG via http://dx.doi.org/10.1038/tp.2015.5

A methodology pruning the search space of six compiler transformations by addressing them together as one problem and by exploiting the hardware architecture details

Today’s compilers have a plethora of optimizations-transformations to choose from, and the correct choice, order as well parameters of transformations have a significant/large impact on performance; choosing the correct order and parameters of optimizations has been a long standing problem in compilation research, which until now remains unsolved; the separate sub-problems optimization gives a different schedule/binary for each sub-problem and these schedules cannot coexist, as by refining one degrades the other. Researchers try to solve this problem by using iterative compilation techniques but the search space is so big that it cannot be searched even by using modern supercomputers. Moreover, compiler transformations do not take into account the hardware architecture details and data reuse in an efficient way. In this paper, a new iterative compilation methodology is presented which reduces the search space of six compiler transformations by addressing the above problems; the search space is reduced by many orders of magnitude and thus an efficient solution is now capable to be found. The transformations are the following: loop tiling (including the number of the levels of tiling), loop unroll, register allocation, scalar replacement, loop interchange and data array layouts. The search space is reduced (a) by addressing the aforementioned transformations together as one problem and not separately, (b) by taking into account the custom hardware architecture details (e.g., cache size and associativity) and algorithm characteristics (e.g., data reuse). The proposed methodology has been evaluated over iterative compilation and gcc/icc compilers, on both embedded and general purpose processors; it achieves significant performance gains at many orders of magnitude lower compilation time

Preliminary Limits on the WIMP-Nucleon Cross Section from the Cryogenic Dark Matter Search (CDMS)

We are conducting an experiment to search for WIMPs, or weakly-interacting massive particles, in the galactic halo using terrestrial detectors. This generic class of hypothetical particles, whose properties are similar to those predicted by extensions of the standard model of particle physics, could comprise the cold component of non-baryonic dark matter. We describe our experiment, which is based on cooled germanium and silicon detectors in a shielded low-background cryostat. The detectors achieve a high degree of background rejection through the simultaneous measurement of the energy in phonons and ionization. Using exposures on the order of one kilogram-day from initial runs of our experiment, we have achieved (preliminary) upper limits on the WIMP-nucleon cross section that are comparable to much longer runs of other experiments.Comment: 5 LaTex pages, 5 eps figs, epsf.sty, espcrc2dsa2.sty. Proceedings of TAUP97, Gran Sasso, Italy, 7-11 Sep 1997, Nucl. Phys. Suppl., A. Bottino, A. di Credico and P. Monacelli (eds.). See also http://cfpa.berkeley.ed

The Herschel Exploitation of Local Galaxy Andromeda (HELGA) II: Dust and Gas in Andromeda

We present an analysis of the dust and gas in Andromeda, using Herschel images sampling the entire far-infrared peak. We fit a modified-blackbody model to ~4000 quasi-independent pixels with spatial resolution of ~140pc and find that a variable dust-emissivity index (beta) is required to fit the data. We find no significant long-wavelength excess above this model suggesting there is no cold dust component. We show that the gas-to-dust ratio varies radially, increasing from ~20 in the center to ~70 in the star-forming ring at 10kpc, consistent with the metallicity gradient. In the 10kpc ring the average beta is ~1.9, in good agreement with values determined for the Milky Way (MW). However, in contrast to the MW, we find significant radial variations in beta, which increases from 1.9 at 10kpc to ~2.5 at a radius of 3.1kpc and then decreases to 1.7 in the center. The dust temperature is fairly constant in the 10kpc ring (ranging from 17-20K), but increases strongly in the bulge to ~30K. Within 3.1kpc we find the dust temperature is highly correlated with the 3.6 micron flux, suggesting the general stellar population in the bulge is the dominant source of dust heating there. At larger radii, there is a weak correlation between the star formation rate and dust temperature. We find no evidence for 'dark gas' in M31 in contrast to recent results for the MW. Finally, we obtained an estimate of the CO X-factor by minimising the dispersion in the gas-to-dust ratio, obtaining a value of (1.9+/-0.4)x10^20 cm^-2 [K kms^-1]^-1.Comment: 19 pages, 18 figures. Submitted to ApJ April 2012; Accepted July 201

Mass extinctions and supernova explosions

A nearby supernova (SN) explosion could have negatively influenced life on Earth, maybe even been responsible for mass extinctions. Mass extinction poses a significant extinction of numerous species on Earth, as recorded in the paleontologic, paleoclimatic, and geological record of our planet. Depending on the distance between the Sun and the SN, different types of threats have to be considered, such as ozone depletion on Earth, causing increased exposure to the Sun's ultraviolet radiation, or the direct exposure of lethal x-rays. Another indirect effect is cloud formation, induced by cosmic rays in the atmosphere which result in a drop in the Earth's temperature, causing major glaciations of the Earth. The discovery of highly intensive gamma ray bursts (GRBs), which could be connected to SNe, initiated further discussions on possible life-threatening events in Earth's history. The probability that GRBs hit the Earth is very low. Nevertheless, a past interaction of Earth with GRBs and/or SNe cannot be excluded and might even have been responsible for past extinction events.Comment: Chapter for forthcoming book: Handbook of Supernovae, P. Murdin and A. Alsabeti (eds.), Springer International Publishing (in press

'This is what democracy looks like' : New Labour's blind spot and peripheral vision

New Labour in government since 1997 has been roundly criticized for not possessing a clear, coherent and consistent democratic vision. The absence of such a grand vision has resulted, from this critical perspective, in an absence of 'joined-up' thinking about democracy in an evolving multi-level state. Tensions have been all too apparent between the government's desire to exert central direction - manifested in its most pathological form as 'control freakery' - and its democratising initiatives derived from 'third-way' obsessions with 'decentralising', 'empowering' and 'enabling'. The purpose of this article is to examine why New Labour displayed such apparently impaired democratic vision and why it appeared incapable of conceiving of democratic reform 'in the round'. This article seeks to explain these apparent paradoxes, however, through utilising the notion of 'macular degeneration'. In this analysis, the perceived democratic blind spot of New Labour at Westminster is connected to a democratic peripheral vision, which has envisaged innovative participatory and decentred initiatives in governance beyond Westminster

Comparison of sequencing-based methods to profile DNA methylation and identification of monoallelic epigenetic modifications.

Analysis of DNA methylation patterns relies increasingly on sequencing-based profiling methods. The four most frequently used sequencing-based technologies are the bisulfite-based methods MethylC-seq and reduced representation bisulfite sequencing (RRBS), and the enrichment-based techniques methylated DNA immunoprecipitation sequencing (MeDIP-seq) and methylated DNA binding domain sequencing (MBD-seq). We applied all four methods to biological replicates of human embryonic stem cells to assess their genome-wide CpG coverage, resolution, cost, concordance and the influence of CpG density and genomic context. The methylation levels assessed by the two bisulfite methods were concordant (their difference did not exceed a given threshold) for 82% for CpGs and 99% of the non-CpG cytosines. Using binary methylation calls, the two enrichment methods were 99% concordant and regions assessed by all four methods were 97% concordant. We combined MeDIP-seq with methylation-sensitive restriction enzyme (MRE-seq) sequencing for comprehensive methylome coverage at lower cost. This, along with RNA-seq and ChIP-seq of the ES cells enabled us to detect regions with allele-specific epigenetic states, identifying most known imprinted regions and new loci with monoallelic epigenetic marks and monoallelic expression