Exploring the interdependencies of research funders in the UK

Investment in medical research is vital to the continuing improvement of the UK's health and wealth. It is through research that we expand our understanding of disease and develop new treatments for patients. Medical research charities currently contribute over £1 billion annually to medical research in the UK, of which over £350 million is provided by Cancer Research UK. Many charities, including Cancer Research UK, receive no government funding for their research activity. Cancer Research UK is engaged in a programme of work in order to better understand the medical research funding environment and demonstrate the importance of sustained investment. A key part of that is the Office of Health Economics‟ (OHE) 2011 report “Exploring the interdependency between public and charitable medical research”. This study found that there are substantial benefits, both financial and qualitative, from the existence of a variety of funders and that reductions in the level of government financial support for medical research are likely to have broader negative effects. This contributed to other evidence which found that the activities and funding of the charity, public and private sectors respectively are complementary, i.e. mutually reinforcing, rather than duplicative or merely substituting for one another. “Exploring the interdependencies of research funders in the UK” by the Office of Health Economics (OHE) and SPRU: Science and Technology Policy Research at the University of Sussex, represents a continued effort to build the evidence base around the funding of medical research. This report uncovers the extent to which funders of cancer research are interdependent, nationally and internationally. Key figures show that two thirds of publications acknowledging external support have relied on multiple funders, while just under half benefited from overseas funding, and almost a fifth are also supported by industry. In addition the analysis shows that the general public would not want tax funding of cancer research to be reduced, but would not donate enough to charities to compensate for any such reduction

Why does Low-Luminosity AGN Fueling Remain an Unsolved Problem?

Despite many years of effort, observational studies have not found a strong correlation between the presence of any proposed fueling mechanism and low-luminosity AGN. After a discussion of the mass requirements for fueling, I summarize this observational work and provide a number of hypotheses for why the nature of AGN fueling has remained unresolved. In particular, I stress the potential importance of the increasing number of candidate fueling mechanisms with decreasing mass accretion rate, the relevant spatial scales for different fueling mechanisms, and the lifetime of an individual episode of nuclear accretion. The episodic AGN lifetime is a particularly relevant complication if it is comparable to or shorter than the time that the responsible fueling mechanisms are observationally detectable. I conclude with a number of relatively accessible areas for future investigation.Comment: 7 pages, 2 figures. Invited review to appear in "The Interplay among Black Holes, Stars and ISM in Galactic Nuclei," Proc. IAU 222 (Gramado, Brazil), eds. Th. Storchi Bergmann, L.C. Ho, H.R. Schmit

Phenotypic and Genotypic Characteristics of Methicillin-Resistant Staphylococcus aureus (MRSA) Related to Persistent Endovascular Infection.

Persistent methicillin-resistant Staphylococcus aureus (MRSA) bacteremia (PB) represents an important subset of S. aureus infection and correlates with poor clinical outcomes. MRSA isolates from patients with PB differ significantly from those of resolving bacteremia (RB) with regard to several in vitro phenotypic and genotypic profiles. For instance, PB strains exhibit less susceptibility to cationic host defense peptides and vancomycin (VAN) killing under in vivo-like conditions, greater damage to endothelial cells, thicker biofilm formation, altered growth rates, early activation of many global virulence regulons (e.g., sigB, sarA, sae and agr) and higher expression of purine biosynthesis genes (e.g., purF) than RB strains. Importantly, PB strains are significantly more resistant to VAN treatment in experimental infective endocarditis as compared to RB strains, despite similar VAN minimum inhibitory concentrations (MICs) in vitro. Here, we review relevant phenotypic and genotypic characteristics related to the PB outcome. These and future insights may improve our understanding of the specific mechanism(s) contributing to the PB outcome, and aid in the development of novel therapeutic and preventative measures against this life-threatening infection

Predicting sinusoidal obstruction syndrome after allogeneic stem cell transplantation with the EASIX biomarker panel

No biomarker panel is established for prediction of sinusoidal obstruction syndrome/veno-occlusive disease (SOS/VOD), a major complication of allogeneic stem cell transplantation (alloSCT). We compared the potential of the Endothelial Activation and Stress Index (EASIX), based on lactate dehydrogenase, creatinine, and thrombocytes, with that of the SOS/VOD CIBMTR clinical risk score to predict SOS/VOD in two independent cohorts. In a third cohort, we studied the impact of endothelium-active prophylaxis with pravastatin and ursodeoxycholic acid (UDA) on SOS/VOD risk. The cumulative incidence of SOS/VOD within 28 days after alloSCT in the training cohort (Berlin, 2013-2015, n=446) and in the validation cohort (Heidelberg, 2002-2009, n=380) was 9.6% and 8.4%, respectively. In both cohorts, EASIX assessed at the day of alloSCT (EASIX-d0) was significantly associated with SOS/VOD incidence (p<0.0001), overall survival (OS) and non-relapse mortality (NRM). In contrast, the CIBMTR score showed no statistically significant association with SOS/VOD incidence, and did not predict OS and NRM. In patients receiving pravastatin/UDA, the cumulative incidence of SOS/VOD was significantly lower at 1.7% (p<0.0001, Heidelberg, 2010-2015, n=359) than in the two cohorts not receiving pravastatin/UDA. The protective effect was most pronounced in patients with high EASIX-d0. The cumulative SOS/VOD incidence in the highest EASIX-d0 quartiles were 18.1% and 16.8% in both cohorts without endothelial prophylaxis as compared to 2.2% in patients with pravastatin/UDA prophylaxis (p<0.0001). EASIX-d0 is the first validated biomarker for defining a subpopulation of alloSCT recipients at high risk for SOS/VOD. Statin/UDA endothelial prophylaxis could constitute a prophylactic measure for patients at increased SOS/VOD risk

GRB Progenitors and Observational Criteria

Phenomenologically, two classes of GRBs (long/soft vs. short/hard) are identified based on their gamma-ray properties. The boundary between the two classes is vague. Multi-wavelength observations lead to identification of two types of GRB progenitor: one related to massive stars (Type II), and another related to compact stars (Type I). Evidence suggests that the majority of long GRBs belong to Type II, while at least the majority of nearby short GRBs belong to Type I. Nonetheless, counter examples do exist. Both long-duration Type I and short-duration Type II GRBs have been observed. In this talk, I review the complications in GRB classification and efforts in diagnosing GRB progenitor based on multiple observational criteria. In particular, I raise the caution to readily accept that all short/hard GRBs detected by BATSE are due to compact star mergers. Finally, I propose to introduce "amplitude" as the third dimension (besides "duration" and "hardness") to quantify burst properties, and point out that the "tip-of-iceberg" effect may introduce confusion in defining the physical category of GRBs, especially for low-amplitude, high-redshift GRBs.Comment: Invited talk at IAU Symposium 279: "Death of Massive Stars: Supernovae and Gamma-Ray Bursts". To appear in the Proceedings IAU Symposium 279, (eds. P. Roming, N. Kawai, E. Pian). 8 page

A massive exoplanet candidate around KOI-13: Independent confirmation by ellipsoidal variations

We present an analysis of the KOI-13.01 candidate exoplanet system included in the September 2011 Kepler data release. The host star is a known and relatively bright $(m_{\rm KP} = 9.95)$ visual binary with a separation significantly smaller (0.8 arcsec) than the size of a Kepler pixel (4 arcsec per pixel). The Kepler light curve shows both primary and secondary eclipses, as well as significant out-of-eclipse light curve variations. We confirm that the transit occurs round the brighter of the two stars. We model the relative contributions from (i) thermal emission from the companion, (ii) planetary reflected light, (iii) Doppler beaming, and (iv) ellipsoidal variations in the host-star arising from the tidal distortion of the host star by its companion. Our analysis, based on the light curve alone, enables us to constrain the mass of the KOI-13.01 companion to be $M_{\rm C} = 8.3 \pm 1.25M_{\rm J}$ and thus demonstrates that the transiting companion is a planet (rather than a brown dwarf which was recently proposed by \cite{b7}). The high temperature of the host star (Spectral Type A5-7V, $T_{\rm eff} = 8511-8020$ K), combined with the proximity of its companion KOI-13.01, may make it one of the hottest exoplanets known, with a detectable thermal contribution to the light curve even in the Kepler optical passband. However, the single passband of the Kepler light curve does not enable us to unambiguously distinguish between the thermal and reflected components of the planetary emission. Infrared observations may help to break the degeneracy, while radial velocity follow-up with $\sigma \sim$ 100 m s$^{-1}$ precision should confirm the mass of the planet.Comment: 7 pages, 5 figure

Bootstrapping Real-world Deployment of Future Internet Architectures

The past decade has seen many proposals for future Internet architectures. Most of these proposals require substantial changes to the current networking infrastructure and end-user devices, resulting in a failure to move from theory to real-world deployment. This paper describes one possible strategy for bootstrapping the initial deployment of future Internet architectures by focusing on providing high availability as an incentive for early adopters. Through large-scale simulation and real-world implementation, we show that with only a small number of adopting ISPs, customers can obtain high availability guarantees. We discuss design, implementation, and evaluation of an availability device that allows customers to bridge into the future Internet architecture without modifications to their existing infrastructure