Financial interests of patient organisations contributing to technology appraisal at England's National Institute for Health and Care Excellence (NICE): a policy review

Objectives: To investigate the prevalence of financial interests among patient organisations contributing to health technology assessment at the National Institute for Health and Care Excellence (NICE) in England, and the extent to which current disclosure policy ensures decision-making committees are aware of these interests. Design: Policy review using annual accounts, reports and websites of patient organisations, a database of payments declared by pharmaceutical manufacturers (Disclosure UK), other manufacturer declarations, responses from patient organisations, and declarations of interests by nominated representatives of patient organisations. Setting: Appraisals of medicines and treatments for use in the English and Welsh National Health Service. Participants: 53 patient organisations contributing to 41 NICE technology appraisals published in 2015 and 2016, with 117 separate occasions that a patient organisation contributed to the appraisal of a technology. Main outcome measures: (i) Prevalence of specific interests, i.e. funding from manufacturer(s) of a technology under appraisal or competitor products; (ii) Proportion of specific interests of which NICE decision-making committees were aware; (iii) Proportion of specific interests for which disclosure was not required by current NICE policy. Results: 38/53 (71.7%) patient organisations had accepted funding from the manufacturer(s) of a technology or a competitor product in the same or previous year that they had contributed to the appraisal of that technology. Specific interests were 46 present on 92 out of 117 (78.6%) occasions that patient organisations contributed to appraisals in 2015 and 2016. NICE decision-making committees were aware of less than a third of specific interests (36/115, 31.3%). For over half of the specific interests of which committees were unaware (42/79, 53.2%), disclosure by patient organisations was not required by current NICE policy. Conclusions: Specific interests are highly prevalent among patient organisations contributing to health technology assessment. NICE is reviewing its disclosure policy to ensure that decision-making committees are aware of all relevant interests

High-Resolution Mid-Infrared Morphology of Cygnus A

We present subarcsecond resolution mid-infrared images at 10.8 and 18.2 microns of Cygnus A. These images were obtained with the University of Florida mid-IR camera/spectrometer OSCIR at the Keck II 10-m telescope. Our data show extended mid-IR emission primarily to the east of the nucleus with a possible western extension detected after image deconvolution. This extended emission is closely aligned with the bi-conical structure observed at optical and near-IR wavelengths by the HST. This emission is consistent with dust heated from the central engine of Cygnus A. We also marginally detect large-scale low level emission extending > 1.5 kpc from the nucleus which may be caused by in-situ star formation, line emission, and/or PAH contamination within the bandpass of our wide N-band filter.Comment: 20 pages, 8 figures, accepted for publication in the Astrophysical Journa

The Origin of the Silicate Emission Features in the Seyfert 2 Galaxy, NGC 2110

The unified model of active galactic nuclei (AGN) predicts silicate emission features at 10 and 18 microns in type 1 AGN, and such features have now been observed in objects ranging from distant QSOs to nearby LINERs. More surprising, however, is the detection of silicate emission in a few type 2 AGN. By combining Gemini and Spitzer mid-infrared imaging and spectroscopy of NGC 2110, the closest known Seyfert 2 galaxy with silicate emission features, we can constrain the location of the silicate emitting region to within 32 pc of the nucleus. This is the strongest constraint yet on the size of the silicate emitting region in a Seyfert galaxy of any type. While this result is consistent with a narrow line region origin for the emission, comparison with clumpy torus models demonstrates that emission from an edge-on torus can also explain the silicate emission features and 2-20 micron spectral energy distribution of this object. In many of the best-fitting models the torus has only a small number of clouds along the line of sight, and does not extend far above the equatorial plane. Extended silicate-emitting regions may well be present in AGN, but this work establishes that emission from the torus itself is also a viable option for the origin of silicate emission features in active galaxies of both type 1 and type 2.Comment: ApJL, accepte

Silicate absorption in heavily obscured galaxy nuclei

Spectroscopy at 8-13 microns with T-ReCS on Gemini-S is presented for 3 galaxies with substantial silicate absorption features, NGC 3094, NGC 7172 and NGC 5506. In the galaxies with the deepest absorption bands, the silicate profile towards the nuclei is well represented by the emissivity function derived from the circumstellar emission from the red supergiant, mu Cephei which is also representative of the mid-infrared absorption in the diffuse interstellar medium in the Galaxy. There is spectral structure near 11.2 microns in NGC 3094 which may be due to a component of crystalline silicates. In NGC 5506, the depth of the silicate absorption increases from north to south across the nucleus, suggestive of a dusty structure on scales of 10s of parsecs. We discuss the profile of the silicate absorption band towards galaxy nuclei and the relationship between the 9.7 micron silicate and 3.4 micron hydrocarbon absorption bands.Comment: 7 pages, accepted for publication in MNRA

Understanding the 8 micron vs. Pa-alpha relationship on sub-arcsecond scales in Luminous Infrared Galaxies

This work explores in detail the relation between the 8 micron and the Pa-alpha emissions for 122 HII regions identified in a sample of 10 low-z LIRGs with nearly constant metallicity (12 + log (O/H) ~ 8.8). We use Gemini/T-ReCS high-spatial resolution (<~ 0.4" ~ 120 pc for the average distance of 60 Mpc of our sample) mid-infrared imaging (at 8.7 micron or 10.3 micron) together with HST/NICMOS continuum and Pa-alpha images. The LIRG HII regions extend the L_8micron vs. L_Pa-alpha relation found for HII knots in the high-metallicity SINGS galaxies by about two orders of magnitude to higher luminosities. Since the metallicity of the LIRG sample is nearly constant, we can rule out this effect as a cause for the scatter seen in the relationship. In turn, it is attributed to two effects: age and PAH features. The L_8micron/L_Pa-alpha ratio, which varies by a factor of ten for the LIRG HII regions, is reproduced by a model with instantaneous star formation and ages ranging from ~ 4 to 7.5 Myr. The remaining dispersion around the model predictions for a given age is probably due to differential contributions of the PAH features (the 8.6 micron, in our case) to the 8 micron emission from galaxy to galaxy.Comment: 16 pages, 9 figures, accepted for publication in ApJ; paper with full-resolution figures can be found at: http://damir.iem.csic.es/extragalactic

A cyclic peptide inhibitor of HIF-1 heterodimerization that inhibits hypoxia signaling in cancer cells

Hypoxia inducible factor-1 (HIF-1) is a heterodimeric transcription factor that acts as the master regulator of cellular response to reduced oxygen levels, thus playing a key role in the adaptation, survival and progression of tumors. Here we report cyclo-CLLFVY, identified from a library of 3.2 million cyclic hexapeptides using a genetically encoded high-throughput screening platform, as an inhibitor of the HIF-1α/HIF-1β protein-protein interaction in vitro and in cells. The identified compound inhibits HIF-1 dimerization and transcription activity by binding to the PAS-B domain of HIF-1α, reducing HIF-1-mediated hypoxia response signaling in a variety of cell lines, without affecting the function of the closely related HIF-2 isoform. The reported cyclic peptide demonstrates the utility of our high-throughput screening platform for the identification of protein-protein interaction inhibitors, and forms the starting point for the development of HIF-1 targeted cancer therapeutics

The complexity of parsec-scaled dusty tori in AGN

Warm gas and dust surround the innermost regions of active galactic nuclei (AGN). They provide the material for accretion onto the super-massive black hole and they are held responsible for the orientation-dependent obscuration of the central engine. The AGN-heated dust distributions turn out to be very compact with sizes on scales of about a parsec in the mid-infrared. Only infrared interferometry currently provides the necessary angular resolution to directly study the physical properties of this dust. Size estimates for the dust distributions derived from interferometric observations can be used to construct a size--luminosity relation for the dust distributions. The large scatter about this relation suggests significant differences between the dust tori in the individual galaxies, even for nuclei of the same class of objects and with similar luminosities. This questions the simple picture of the same dusty doughnut in all AGN. The Circinus galaxy is the closest Seyfert 2 galaxy. Because its mid-infrared emission is well resolved interferometrically, it is a prime target for detailed studies of its nuclear dust distribution. An extensive new interferometric data set was obtained for this galaxy. It shows that the dust emission comes from a very dense, disk-like structure which is surrounded by a geometrically thick, similarly warm dust distribution as well as significant amounts of warm dust within the ionisation cone.Comment: 8 pages, 3 figures, to appear in the proceedings of the conference "The central kiloparsec in Galactic Nuclei: Astronomy at High Angular Resolution 2011", open access Journal of Physics: Conference Series (JPCS), published by IOP Publishin

The nuclear and extended mid-infrared emission of Seyfert galaxies

We present subarcsecond resolution mid-infrared (MIR) images obtained with 8-10 m-class ground-based telescopes of a complete volume-limited (DL<40 Mpc) sample of 24 Seyfert galaxies selected from the Swift/BAT nine month catalog. We use those MIR images to study the nuclear and circumnuclear emission of the galaxies. Using different methods to classify the MIR morphologies on scales of ~400 pc, we find that the majority of the galaxies (75-83%) are extended or possibly extended and 17-25% are point-like. This extended emission is compact and it has low surface brightness compared with the nuclear emission, and it represents, on average, ~30% of the total MIR emission of the galaxies in the sample. We find that the galaxies whose circumnuclear MIR emission is dominated by star formation show more extended emission (650+-700 pc) than AGN-dominated systems (300+-100 pc). In general, the galaxies with point-like MIR morphologies are face-on or moderately inclined (b/a~0.4-1.0), and we do not find significant differences between the morphologies of Sy1 and Sy2. We used the nuclear and circumnuclear fluxes to investigate their correlation with different AGN and SF activity indicators. We find that the nuclear MIR emission (the inner ~70 pc) is strongly correlated with the X-ray emission (the harder the X-rays the better the correlation) and with the [O IV] lambda 25.89 micron emission line, indicating that it is AGN-dominated. We find the same results, although with more scatter, for the circumnuclear emission, which indicates that the AGN dominates the MIR emission in the inner ~400 pc of the galaxies, with some contribution from star formation.Comment: 27 pages, 12 figures, accepted by MNRA