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

HST and Spitzer point source detection and optical extinction in powerful narrow-line radio galaxies

We present the analysis of infrared HST and Spitzer data for a sample of 13 FRII radio galaxies at 0.03<z<0.11 that are classified as narrow-line radio galaxies (NLRG). In the context of the unified schemes for active galactic nuclei (AGN), our direct view of the AGN in NLRG is impeded by a parsec-scale dusty torus structure. Our high resolution infrared observations provide new information about the degree of extinction induced by the torus, and the incidence of obscured AGN in NLRG. We find that the point-like nucleus detection rate increases from 25 per cent at 1.025$\mu$m, to 80 per cent at 2.05$\mu$m, and to 100 per cent at 8.0$\mu$m. This supports the idea that most NLRG host an obscured AGN in their centre. We estimate the extinction from the obscuring structures using X-ray, near-IR and mid-IR data. We find that the optical extinction derived from the 9.7$\mu$m silicate absorption feature is consistently lower than the extinction derived using other techniques. This discrepancy challenges the assumption that all the mid-infrared emission of NLRG is extinguished by a simple screen of dust at larger radii. This disagreement can be explained in terms of either weakening of the silicate absorption feature by (i) thermal mid-IR emission from the narrow-line region, (ii) non-thermal emission from the base of the radio jets, or (iii) by direct warm dust emission that leaks through a clumpy torus without suffering major attenuation.Comment: 18 pages, 7 figures, 8 tables, accepted for publication in MNRA

Transcription factor interactions at the PGK promoter in yeast

Two new transcription factor binding sites have been identified within the phosphoglycerate kinase (PGK) gene promoter in the yeast Saccharomyces cerevisiae. The binding sites are upstream of the previously defined UAS, and are bound in vitro by the multifunctional transcription factors Reb1p and Cpf1p. A deletion of the Reb1p binding site was made from a PGK gene construct on a multicopy plasmid, and also targeted to the chromosomal copy of PGK. Deletions of the Rap1p and Abf1p binding sites in the UAS were also targeted to the chromosome. Analysis of RNA from the chromosomal deletion strains confirmed the central role of Rap1p in the activation of transcription from PGK. Reb1p and Abf1p were also found to be important for transcriptional activation. This is in contrast to results from experiments using multicopy plasmids carrying Reb1p or Abf1p binding site deletions from PGK. In this situation, neither the Reb1p site, nor the Abf1p site, plays a role in transcriptional activation. A role for Cpflp at the PGK promoter was examined using a cpfl null strain of yeast. Northern blot analysis was used to assay transcription from the chromosomal PGK gene in the absence of Cpf1p, and also transcription from a multicopy plasmid carrying the wild type PGK gene in the cpf1- background. In both cases, the absence of Cpf1p was found to have very little effect on the level of transcription. In addition, a role for the potential yATF binding site at the 3' end of the PGK UAS was investigated. Oligonucleotides containing this sequence were inserted upstream of a minimal promoter, and levels of a β-galactosidase reporter were assayed. No activation over the basal level was observed. A deletion of the potential yATF binding site from the UAS was made from a multicopy plasmid construct, and also from the chromosomal locus. Transcription from the deleted constructs was found to be no different from transcription from the wild type gene. Finally, DNA sequences which are able to complement the C-terminus functions of Rap1p were identified. A yeast genomic library was generated downstream of the N-terminus and DNA binding domain of Rap1p. This library was transformed into a rap1ts strain of yeast to look for complementation of the ts phenotype. Transformants which grew at the non-permissive temperature were obtained. Results from the analysis of the DNA sequences in these transformants are presented

Subaru Spectroscopy and Spectral Modeling of Cygnus A

We present high angular resolution ($\sim$0.5$^\prime$$^\prime$) MIR spectra of the powerful radio galaxy, Cygnus A, obtained with the Subaru telescope. The overall shape of the spectra agree with previous high angular resolution MIR observations, as well as previous Spitzer spectra. Our spectra, both on and off nucleus, show a deep silicate absorption feature. The absorption feature can be modeled with a blackbody obscured by cold dust or a clumpy torus. The deep silicate feature is best fit by a simple model of a screened blackbody, suggesting foreground absorption plays a significant, if not dominant role, in shaping the spectrum of Cygnus A. This foreground absorption prevents a clear view of the central engine and surrounding torus, making it difficult to quantify the extent the torus attributes to the obscuration of the central engine, but does not eliminate the need for a torus in Cygnus A

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