Reforming the cancer drug fund focus on drugs that might be shown to be cost effective

The Cancer Drug Fund was originally conceived as a temporary measure, until value based pricing for drugs was introduced, to give NHS cancer patients access to drugs not approved by NICE. Spending on these drugs rose from less than the £50m (€63m; $79m) budgeted for the first year in 2010-11 to well over £200m in 2013-14, and the budget for the scheme—now extended for a further two years—will reach £280m by 2016.1 The recent changes to the fund recognise the impossibility, within any sensible budget limit, of providing all the new cancer drugs that offer possible benefit to patients. More radical changes are needed to the working of the fund, given the failure to introduce value based pricing, so that it deals with the underlying problem of inadequate information on the effectiveness and cost effectiveness of new cancer drugs when used in the NHS

Progress and challenges in modelling country-level HIV/AIDS epidemics: the UNAIDS Estimation and Projection Package 2007

The UNAIDS Estimation and Projection Package (EPP) was developed to aid in country-level estimation and short-term projection of HIV/AIDS epidemics. This paper describes advances reflected in the most recent update of this tool (EPP 2007), and identifies key issues that remain to be addressed in future versions. The major change to EPP 2007 is the addition of uncertainty estimation for generalised epidemics using the technique of Bayesian melding, but many additional changes have been made to improve the user interface and efficiency of the package. This paper describes the interface for uncertainty analysis, changes to the user interface for calibration procedures and other user interface changes to improve EPP’s utility in different settings. While formal uncertainty assessment remains an unresolved challenge in low-level and concentrated epidemics, the Bayesian melding approach has been applied to provide analysts in these settings with a visual depiction of the range of models that may be consistent with their data. In fitting the model to countries with longer-running epidemics in sub-Saharan Africa, a number of limitations have been identified in the current model with respect to accommodating behaviour change and accurately replicating certain observed epidemic patterns. This paper discusses these issues along with their implications for future changes to EPP and to the underlying UNAIDS Reference Group model

Flat Tree-level Inflationary Potentials in Light of CMB and LSS Data

We use cosmic microwave background and large scale structure data to test a broad and physically well-motivated class of inflationary models: those with flat tree-level potentials (typical in supersymmetry). The non-trivial features of the potential arise from radiative corrections which give a simple logarithmic dependence on the inflaton field, making the models very predictive. We also consider a modified scenario with new physics beyond a certain high-energy cut-off showing up as non-renormalizable operators (NRO) in the inflaton field. We find that both kinds of models fit remarkably well CMB and LSS data, with very few free parameters. Besides, a large part of these models naturally predict a reasonable number of e-folds. A robust feature of these scenarios is the smallness of tensor perturbations (r < 10^{-3}). The NRO case can give a sizeable running of the spectral index while achieving a sufficient number of e-folds. We use Bayesian model comparison tools to assess the relative performance of the models. We believe that these scenarios can be considered as a standard physical class of inflationary models, on a similar footing with monomial potentials.Comment: 42 LaTeX pages, 8 figure

The SWAP EUV Imaging Telescope Part I: Instrument Overview and Pre-Flight Testing

The Sun Watcher with Active Pixels and Image Processing (SWAP) is an EUV solar telescope on board ESA's Project for Onboard Autonomy 2 (PROBA2) mission launched on 2 November 2009. SWAP has a spectral bandpass centered on 17.4 nm and provides images of the low solar corona over a 54x54 arcmin field-of-view with 3.2 arcsec pixels and an imaging cadence of about two minutes. SWAP is designed to monitor all space-weather-relevant events and features in the low solar corona. Given the limited resources of the PROBA2 microsatellite, the SWAP telescope is designed with various innovative technologies, including an off-axis optical design and a CMOS-APS detector. This article provides reference documentation for users of the SWAP image data.Comment: 26 pages, 9 figures, 1 movi

Carotid Revascularization and Its Effect on Cognitive Function: A Prospective Nonrandomized Multicenter Clinical Study

© 2020 The Author(s) Background: There is conflicting data on the effect of carotid revascularization on cognitive function. Objective: To examine cerebral blood flow and cognitive function after carotid revascularization. Methods: Patients with unilateral, asymptomatic hemodynamically significant carotid artery stenosis (80% by computed tomography angiography or magnetic resonance angiography) were eligible. Cerebral blood flow was measured preoperatively and 1 month postoperatively using quantitative phase contrast magnetic resonance angiography. Preoperative flow impairment was defined as ipsilateral flow at least 20% less than contralateral flow (ie, an ipsilateral and/or contralateral flow ratio ≤0.8). Significant improvement in blood flow was defined as at least a 0.15 increase in flow ratio from pre- to postoperative. A control group was managed medically. Four cognitive domains were assessed at baseline, 1 month, and 6-12 months postoperatively. Results: Seventy-five patients were enrolled at 6 sites; 53 carotid endarterectomy, 11 carotid artery stenting, and 11 medical management only controls. Preoperative Trails B scores were similar between groups. Revascularization was associated with significant improvement in executive function (Trials B) while no improvement was observed in controls (P = .007). Of patients with improvement in middle cerebral artery (MCA) flow, 90% had improved Trails B scores compared to 46.5% of patients without MCA flow improvement (P = .01). Greater absolute improvement in mean Trails B scores was observed in patients with MCA flow improvement compared to those without (48 seconds versus 24.7 seconds, P = .001). Conclusions: In a cohort of patient with asymptomatic carotid stenosis, improvement in MCA flow following carotid revascularization is associated with improvement in executive functioning

Development of severe colitis is associated with lung inflammation and pathology

Inflammatory bowel diseases (IBD) such as Crohn’s disease and ulcerative colitis are chronic relapsing diseases that affect the gastrointestinal tract, most commonly the colon. A link between the gut and the lung is suggested since patients with IBD have an increased susceptibility for chronic inflammatory lung disease. Furthermore, in the absence of overt lung disease, IBD patients have worsened lung function and more leukocytes in sputum than healthy individuals, highlighting a conduit between the gut and lung in disease. To study the gut-lung axis in the context of IBD, we used TCRδ-/- mice, which are highly susceptible to dextran sulfate sodium (DSS) due to the importance of γδ T cells in maintenance of barrier integrity. After induction of experimental colitis using DSS, the lungs of TCRδ-/- mice exhibited signs of inflammation and mild emphysema, which was not observed in DSS-treated C57BL/6 mice. Damage to the lung tissue was accompanied by a large expansion of neutrophils in the lung parenchyma and an increase in alveolar macrophages in the lung wash. Gene expression analyses showed a significant increase in Csf3, Cxcl2, Tnfa, and Il17a in lung tissue in keeping with neutrophil infiltration. Expression of genes encoding reactive oxygen species enzymes and elastolytic enzymes were enhanced in the lungs of both C57BL/6 and TCRδ-/- mice with colitis. Similarly, surfactant gene expression was also enhanced, which may represent a protective mechanism. These data demonstrate that severe colitis in a susceptible genetic background is sufficient to induce lung inflammation and tissue damage, providing the research community with an important tool for the development of novel therapeutics aimed at reducing co-morbidities in IBD patients

Constraints on CDM cosmology from galaxy power spectrum, CMB and SNIa evolution

We examine the constraints that can be obtained on standard cold dark matter models from the most currently used data set: CMB anisotropies, type Ia supernovae and the SDSS luminous red galaxies. We also examine how these constraints are widened when the equation of state parameter $w$ and the curvature parameter $\Omega_k$ are left as free parameters. For the $\Lambda$CDM model, our 'vanilla' model, cosmological parameters are tightly constrained and consistent with current estimates from various methods. When the dark energy parameter $w$ is free we find that the constraints remain mostly unchanged, i.e. changes are smaller than the 1 sigma uncertainties. Similarly, relaxing the assumption of a flat universe leads to nearly identical constraints on the dark energy density parameter of the universe $\Omega_\Lambda$, baryon density of the universe $\Omega_b$, the optical depth $\tau$, the index of the power spectrum of primordial fluctuations $n_S$, with most one sigma uncertainties better than 5%. More significant changes appear on other parameters: while preferred values are almost unchanged, uncertainties for the physical dark matter density $\Omega_ch^2$, Hubble constant $H_0$ and $\sigma_8$ are typically twice as large. We found that different methodological approaches on large scale structure estimates lead to appreciable differences in preferred values and uncertainty widths. We also found that possible evolution in SNIa intrinsic luminosity does not alter these constraints by much, except for $w$, for which the uncertainty is twice as large. At the same time, this possible evolution is severely constrained. We conclude that systematic uncertainties for some estimated quantities are similar or larger than statistical ones.Comment: Revised version, 9 pages, 8 figures, accepted for publication in A&