Measurement of an AGN Central Mass on Centiparsec Scales: Results of Long-Term Optical Monitoring of Arp 102B

The optical spectrum of the broad-line radio galaxy Arp 102B has been monitored for more than thirteen years to investigate the nature of the source of its broad, double-peaked hydrogen Balmer emission lines. The shape of the lines varied subtly; there was an interval during which the variation in the ratio of the fluxes of the two peaks appeared to be sinusoidal, with a period of 2.16 years and an amplitude of about 16% of the average value. The variable part of the broad H-alpha line is well fit by a model in which a region of excess emission (a quiescent ``hot spot'') within an accretion disk (fitted to the non-varying portion of the double-peaked line) completes at least two circular orbits and eventually fades. Fits to spectra from epochs when the hot spot is not present allow determination of the disk inclination, while fits for epochs when it is present provide a measurement of the radius of the hot spot's orbit. From these data and the period of variation, we find that the mass within the hot spot's orbit is 2.2 +0.2/-0.7 times 10^8 solar masses, within the range of previous estimates of masses of active galactic nuclei. Because this mass is determined at a relatively small distance (~1000 AU) from the central body, it is extremely difficult to explain without assuming that a supermassive black hole lies within Arp 102B. The lack of any systematic change in the velocity of the blue peak over time yields a lower limit on the combined mass of the two bodies in a binary black hole model like that of Gaskell (1983) of 10^10 solar masses.Comment: 29 pages, including 6 figures; to appear in the Astrophysical Journal 199

Rejection of the Binary Broad-Line Region Interpretation of Double-Peaked Emission Lines in Three Active Galactic Nuclei

It has been suggested that the peculiar double-peaked Balmer lines of certain broad-line radio galaxies come from individual broad-line regions associated with the black holes of a supermassive binary. We continue to search for evidence of the radial velocity variations characteristic of a double-lined spectroscopic binary that are required in such a model. After spectroscopic monitoring of three suitable candidates (Arp 102B, 3C 390.3, and 3C 332) spanning two decades, we find no such long-term systematic changes in radial velocity. A trend noticed by Gaskell in one of the Balmer-line peaks of 3C 390.3 before 1988 did not continue after that year, invalidating his inferred orbital period and mass. Instead, we find lower limits on the plausible orbital periods that would require the assumed supermassive binaries in all three objects to have total masses in excess of 10^10 solar masses. In the case of 3C 390.3 the total binary mass must exceed 10^11 solar masses to satisfy additional observational constraints on the inclination angle. Such large binary black hole masses are difficult to reconcile with other observations and with theory. In addition, there are peculiar properties of the line profiles and flux ratios in these objects that are not explained by ordinary broad-line region cloud models. We therefore doubt that the double-peaked line profiles of the three objects arise in a pair of broad-line regions. Rather, they are much more likely to be intimately associated with a single black hole.Comment: To appear in the Astrophysical Journal. 17 pages, TeX, with postscript figures includede

Practice Coaching model to embed the culture of enhanced recovery: a service evaluation

Poster presented at 'The Future Nurse: enriching people's experience of care' University of Exeter Academy of Nursing, RD&E Hospital, 3rd October 2019

Size-Controlled Hapticity Switching in [Ln(C9H9)(C8H8)][Ln(C_{9}H_{9})(C_{8}H_{8})] Sandwiches

Sandwich complexes of lanthanides have recently attracted a considerable amount of interest due to their applications as Single Molecule Magnet (SMM). Herein, a comprehensive series of heteroleptic lanthanide sandwich complexes ligated by the cyclononatetraenyl (Cnt) and the cyclooctatetraenyl (Cot) ligand [Ln(Cot)(Cnt)] (Ln=Tb, Dy, Er, Ho, Yb, and Lu) is reported. The coordination behavior of the Cnt ligand has been investigated along the series and shows different coordination patterns in the solid-state depending on the size of the corresponding lanthanide ion without altering its overall anisotropy. Besides the characterization in the solid state by single-crystal X-ray diffraction and in solution by $^{1}H$NMR, static magnetic studies and ab initio computational studies were performed

West Africa International Centers of Excellence for Malaria Research: Drug Resistance Patterns to Artemether-Lumefantrine in Senegal, Mali, and The Gambia.

In 2006, artemether-lumefantrine (AL) became the first-line treatment of uncomplicated malaria in Senegal, Mali, and the Gambia. To monitor its efficacy, between August 2011 and November 2014, children with uncomplicated Plasmodium falciparum malaria were treated with AL and followed up for 42 days. A total of 463 subjects were enrolled in three sites (246 in Senegal, 97 in Mali, and 120 in Gambia). No early treatment failure was observed and malaria infection cleared in all patients by day 3. Polymerase chain reaction (PCR)-adjusted adequate clinical and parasitological response (ACPR) was 100% in Mali, and the Gambia, and 98.8% in Senegal. However, without PCR adjustment, ACPR was 89.4% overall; 91.5% in Mali, 98.8% in Senegal, and 64.3% in the Gambia (the lower value in the Gambia attributed to poor compliance of the full antimalarial course). However, pfmdr1 mutations were prevalent in Senegal and a decrease in parasite sensitivity to artesunate and lumefantrine (as measured by ex vivo drug assay) was observed at all sites. Recrudescent parasites did not show Kelch 13 (K13) mutations and AL remains highly efficacious in these west African sites

Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders:Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients

RIPK1 is a master regulator of inflammatory signaling and cell death and increased RIPK1 activity is observed in human diseases, including Alzheimer's disease (AD) and amyotrophic lateral sclerosis (ALS). RIPK1 inhibition has been shown to protect against cell death in a range of preclinical cellular and animal models of diseases. SAR443060 (previously DNL747) is a selective, orally bioavailable, central nervous system (CNS)-penetrant, small-molecule, reversible inhibitor of RIPK1. In three early-stage clinical trials in healthy subjects and patients with AD or ALS (NCT03757325 and NCT03757351), SAR443060 distributed into the cerebrospinal fluid (CSF) after oral administration and demonstrated robust peripheral target engagement as measured by a reduction in phosphorylation of RIPK1 at serine 166 (pRIPK1) in human peripheral blood mononuclear cells compared to baseline. RIPK1 inhibition was generally safe and well-tolerated in healthy volunteers and patients with AD or ALS. Taken together, the distribution into the CSF after oral administration, the peripheral proof-of-mechanism, and the safety profile of RIPK1 inhibition to date, suggest that therapeutic modulation of RIPK1 in the CNS is possible, conferring potential therapeutic promise for AD and ALS, as well as other neurodegenerative conditions. However, SAR443060 development was discontinued due to long-term nonclinical toxicology findings, although these nonclinical toxicology signals were not observed in the short duration dosing in any of the three early-stage clinical trials. The dose-limiting toxicities observed for SAR443060 preclinically have not been reported for other RIPK1-inhibitors, suggesting that these toxicities are compound-specific (related to SAR443060) rather than RIPK1 pathway-specific

Advances and unmet needs in genetic, basic and clinical science in Alport syndrome::report from the 2015 International Workshop on Alport Syndrome

Alport syndrome (AS) is a genetic disease characterized by haematuric glomerulopathy variably associated with hearing loss and anterior lenticonus. It is caused by mutations in the COL4A3, COL4A4 or COL4A5 genes encoding the α3α4α5(IV) collagen heterotrimer. AS is rare, but it accounts for >1% of patients receiving renal replacement therapy. Angiotensin-converting enzyme inhibition slows, but does not stop, the progression to renal failure; therefore, there is an urgent requirement to expand and intensify research towards discovering new therapeutic targets and new therapies. The 2015 International Workshop on Alport Syndrome targeted unmet needs in basic science, genetics and diagnosis, clinical research and current clinical care. In three intensive days, more than 100 international experts including physicians, geneticists, researchers from academia and industry, and patient representatives from all over the world participated in panel discussions and breakout groups. This report summarizes the most important priority areas including (i) understanding the crucial role of podocyte protection and regeneration, (ii) targeting mutations by new molecular techniques for new animal models and potential gene therapy, (iii) creating optimal interaction between nephrologists and geneticists for early diagnosis, (iv) establishing standards for mutation screening and databases, (v) improving widespread accessibility to current standards of clinical care, (vi) improving collaboration with the pharmaceutical/biotech industry to investigate new therapies, (vii) research in hearing loss as a huge unmet need in Alport patients and (viii) the need to evaluate the risk and benefit of novel (including 'repurposing') therapies on an international basis

Pension fund performance and costs: small is beautiful.

Abstract Using the CEM pension fund data set, we document the cost structure and performance of a large sample of US pension funds. To date, self-reporting biases and a deficiency of comprehensive return and cost data have severely hindered pension fund performance studies. The bias-free CEM dataset resolves these issues and provides detailed information on fund-specific returns, benchmarks and costs for all types of pension plans and equity mandates. We find that pension fund cost levels are substantially lower than mutual fund fees. The domestic equity investments of US pension funds tend to generate abnormal returns (after expenses and trading costs) close to zero or slightly positive, contrasting the average underperformance of mutual funds. However, small cap mandates of defined benefit funds have outperformed their benchmarks by about 3% a year. While larger scale brings costs advantages, liquidity limitations seem to allow only smaller funds, and especially small cap mandates, to outperform their benchmarks. JEL Classifications : G23, G11, G14 Acknowledgements Our thanks to Keith Ambachtsheer, CEM Benchmarking Inc. for providing the pension fun