Clinical and cost effectiveness of endoscopic bipolar radiofrequency ablation for the treatment of malignant biliary obstruction: a systematic review

BACKGROUND: Early evidence suggests that using radiofrequency ablation as an adjunct to standard care (i.e. endoscopic retrograde cholangiopancreatography with stenting) may improve outcomes in patients with malignant biliary obstruction. OBJECTIVES: To assess the clinical effectiveness, cost-effectiveness and potential risks of endoscopic bipolar radiofrequency ablation for malignant biliary obstruction, and the value of future research. DATA SOURCES: Seven bibliographic databases, three websites and seven trials registers were searched from 2008 until 21 January 2021. REVIEW METHODS: The study inclusion criteria were as follows: patients with biliary obstruction caused by any form of unresectable malignancy; the intervention was reported as an endoscopic biliary radiofrequency ablation to ablate malignant tissue that obstructs the bile or pancreatic ducts, either to fit a stent (primary radiofrequency ablation) or to clear an obstructed stent (secondary radiofrequency ablation); the primary outcomes were survival, quality of life or procedure-related adverse events; and the study design was a controlled study, an observational study or a case report. Risk of bias was assessed using Cochrane tools. The primary analysis was meta-analysis of the hazard ratio of mortality. Subgroup analyses were planned according to the type of probe, the type of stent (i.e. metal or plastic) and cancer type. A de novo Markov model was developed to model cost and quality-of-life outcomes associated with radiofrequency ablation in patients with primary advanced bile duct cancer. Insufficient data were available for pancreatic cancer and secondary bile duct cancer. An NHS and Personal Social Services perspective was adopted for the analysis. A probabilistic analysis was conducted to estimate the incremental cost-effectiveness ratio for radiofrequency ablation and the probability that radiofrequency ablation was cost-effective at different thresholds. The population expected value of perfect information was estimated in total and for the effectiveness parameters. RESULTS: Sixty-eight studies (1742 patients) were included in the systematic review. Four studies (336 participants) were combined in a meta-analysis, which showed that the pooled hazard ratio for mortality following primary radiofrequency ablation compared with a stent-only control was 0.34 (95% confidence interval 0.21 to 0.55). Little evidence relating to the impact on quality of life was found. There was no evidence to suggest an increased risk of cholangitis or pancreatitis, but radiofrequency ablation may be associated with an increase in cholecystitis. The results of the cost-effectiveness analysis were that the costs of radiofrequency ablation was £2659 and radiofrequency ablation produced 0.18 quality-adjusted life-years, which was more than no radiofrequency ablation on average. With an incremental cost-effectiveness ratio of £14,392 per quality-adjusted life-year, radiofrequency ablation was likely to be cost-effective at a threshold of £20,000 per quality-adjusted life-year across most scenario analyses, with moderate uncertainty. The source of the vast majority of decision uncertainty lay in the effect of radiofrequency ablation on stent patency. LIMITATIONS: Only 6 of 18 comparative studies contributed to the survival meta-analysis, and few data were found concerning secondary radiofrequency ablation. The economic model and cost-effectiveness meta-analysis required simplification because of data limitations. Inconsistencies in standard reporting and study design were noted. CONCLUSIONS: Primary radiofrequency ablation increases survival and is likely to be cost-effective. The evidence for the impact of secondary radiofrequency ablation on survival and of quality of life is limited. There was a lack of robust clinical effectiveness data and, therefore, more information is needed for this indication. FUTURE WORK:  Future work investigating radiofrequency ablation must collect quality-of-life data. Highquality randomised controlled trials in secondary radiofrequency ablation are needed, with appropriate outcomes recorded. STUDY REGISTRATION: This study is registered as PROSPERO CRD42020170233. FUNDING:  This project was funded by the National Institute for Health and Care Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 27, No. 7. See the NIHR Journals Library website for further project information

Low-Temperature Fluorocarbonate Mineralization in Lower Devonian Rhynie Chert, UK

Funding: J.G.T.A was partially funded by the Natural Environment Research Council, grant number NE/T003677/1. Acknowledgments: We are grateful to W. Ritchie, J. Johnston, and J. Bowie for skilled technicalsupport. Samples were archived by N.H. Trewin, C.M. Rice and S. Fayers.Peer reviewedPublisher PD

An Exploratory Investigation of Public Perceptions Towards Key Benefits and Concerns from the Future Use of Flying Cars

The imminent introduction of flying cars in the traffic fleet is anticipated to modify the mobility patterns of urban commuters. Flying cars' hybrid operation on the ground and in the air, in conjunction with their (semi-) automated capabilities, may lead to more appealing trip considerations, such as travel time, fuel consumption, or environmental emissions, as well as to the emergence of new sources of concerns for the potential users. In this context, the future adoption of flying cars is directly associated with individuals' perceptions of the benefits and concerns arising from the use of flying cars. This paper aims to identify the perceptual patterns of individuals towards travel time, cost and environmental benefits, as well as towards challenges arising from key flying cars operational characteristics. To that end, grouped random parameters bivariate probit models of individuals' perceptions are estimated using data collected from an online survey of 692 individuals. The statistical analysis shows that a number of socio-demographic, behavioral, and attitudinal characteristics affect respondents' expectations and concerns towards the adoption and implementation of flying cars. Even though individuals' perceptions are anticipated to undergo substantial changes until the introduction of flying cars in the traffic fleet, the findings of this work may shed more light on perceptual nuances with critical effect on public interest about the adoption of flying cars

The K2 Mission: Characterization and Early results

The K2 mission will make use of the Kepler spacecraft and its assets to expand upon Kepler's groundbreaking discoveries in the fields of exoplanets and astrophysics through new and exciting observations. K2 will use an innovative way of operating the spacecraft to observe target fields along the ecliptic for the next 2-3 years. Early science commissioning observations have shown an estimated photometric precision near 400 ppm in a single 30 minute observation, and a 6-hour photometric precision of 80 ppm (both at V=12). The K2 mission offers long-term, simultaneous optical observation of thousands of objects at a precision far better than is achievable from ground-based telescopes. Ecliptic fields will be observed for approximately 75-days enabling a unique exoplanet survey which fills the gaps in duration and sensitivity between the Kepler and TESS missions, and offers pre-launch exoplanet target identification for JWST transit spectroscopy. Astrophysics observations with K2 will include studies of young open clusters, bright stars, galaxies, supernovae, and asteroseismology.Comment: 25 pages, 11 figures, Accepted to PAS

Precision asteroseismology of the pulsating white dwarf GD 1212 using a two-wheel-controlled Kepler spacecraft

We present a preliminary analysis of the cool pulsating white dwarf GD 1212, enabled by more than 11.5 days of space-based photometry obtained during an engineering test of the two-reaction-wheel-controlled Kepler spacecraft. We detect at least 19 independent pulsation modes, ranging from 828.2-1220.8 s, and at least 17 nonlinear combination frequencies of those independent pulsations. Our longest uninterrupted light curve, 9.0 days in length, evidences coherent difference frequencies at periods inaccessible from the ground, up to 14.5 hr, the longest-period signals ever detected in a pulsating white dwarf. These results mark some of the first science to come from a two-wheel-controlled Kepler spacecraft, proving the capability for unprecedented discoveries afforded by extending Kepler observations to the ecliptic.Comment: 8 pages, 4 figures, accepted for publication in The Astrophysical Journa

Trace element geochemistry in the earliest terrestrial ecosystem, the Rhynie Chert

Acknowledgements JGTA is supported by the Natural Environment Research Council (grant NE/T003677/1). Samples were archived at the University of Aberdeen by N.H. Trewin, S.R. Fayers and C.M. Rice. Skilled technical support was provided by J. Johnston, J. Bowie, W. Ritchie and C. Taylor. We are grateful for the comments of two reviewers which improved the manuscript.Peer reviewedPublisher PD

The Absolute Magnitudes of Type Ia Supernovae in the Ultraviolet

We examine the absolute magnitudes and light-curve shapes of 14 nearby(redshift z = 0.004--0.027) Type Ia supernovae (SNe~Ia) observed in the ultraviolet (UV) with the Swift Ultraviolet/Optical Telescope. Colors and absolute magnitudes are calculated using both a standard Milky Way (MW) extinction law and one for the Large Magellanic Cloud that has been modified by circumstellar scattering. We find very different behavior in the near-UV filters (uvw1_rc covering ~2600-3300 A after removing optical light, and u ~3000--4000 A) compared to a mid-UV filter (uvm2 ~2000-2400 A). The uvw1_rc-b colors show a scatter of ~0.3 mag while uvm2-b scatters by nearly 0.9 mag. Similarly, while the scatter in colors between neighboring filters is small in the optical and somewhat larger in the near-UV, the large scatter in the uvm2-uvw1 colors implies significantly larger spectral variability below 2600 A. We find that in the near-UV the absolute magnitudes at peak brightness of normal SNe Ia in our sample are correlated with the optical decay rate with a scatter of 0.4 mag, comparable to that found for the optical in our sample. However, in the mid-UV the scatter is larger, ~1 mag, possibly indicating differences in metallicity. We find no strong correlation between either the UV light-curve shapes or the UV colors and the UV absolute magnitudes. With larger samples, the UV luminosity might be useful as an additional constraint to help determine distance, extinction, and metallicity in order to improve the utility of SNe Ia as standardized candles.Comment: 59 pages, accepted for publication in Ap

An exploratory empirical analysis of willingness to hire and pay for flying taxis and shared flying car services

A new transportation mode that can simultaneously operate on land and in the air, namely the flying cars, is anticipated to penetrate the automobile fleet between 2020 and 2025. Due to their flexible mobility patterns and automated operational characteristics, flying taxi and shared flying car services are expected to expand the existing shared mobility services (such as Uber, Lyft, and similar services) of the urban transportation network. Despite their forthcoming introduction in the shared mobility market, public perceptions and expectations about these services have not been investigated in travel demand literature. This study aims to provide an exploratory analysis of public willingness to hire and pay for flying taxis and shared flying car services, and to identify the determinants of the willingness to hire and pay for such services. Using data collected from an online survey, individuals’ willingness to hire and to pay for flying taxi and shared flying car services are statistically modeled within a correlated grouped random parameters bivariate probit framework. The analysis shows that various socio-demographic characteristics and individuals’ opinions towards the perceived benefits and challenges of flying cars affect public willingness to hire and pay for flying taxi and shared flying car services. Even though the awareness about the operation of flying taxis and shared flying car services is possibly limited in the public sphere, the findings of this study can provide insights into the challenges that policymakers, manufacturing companies, and shared mobility providers will face with the introduction of such flying car services in the transportation networks

Terrestrial Planet Occurrence Rates for the Kepler GK Dwarf Sample

We measure planet occurrence rates using the planet candidates discovered by the Q1-Q16 Kepler pipeline search. This study examines planet occurrence rates for the Kepler GK dwarf target sample for planet radii, 0.75<Rp<2.5 Rearth, and orbital periods, 50<Porb<300 days, with an emphasis on a thorough exploration and identification of the most important sources of systematic uncertainties. Integrating over this parameter space, we measure an occurrence rate of F=0.77 planets per star, with an allowed range of 0.3<F<1.9. The allowed range takes into account both statistical and systematic uncertainties, and values of F beyond the allowed range are significantly in disagreement with our analysis. We generally find higher planet occurrence rates and a steeper increase in planet occurrence rates towards small planets than previous studies of the Kepler GK dwarf sample. Through extrapolation, we find that the one year orbital period terrestrial planet occurrence rate, zeta_1=0.1, with an allowed range of 0.01<zeta_1<2, where zeta_1 is defined as the number of planets per star within 20% of the Rp and Porb of Earth. For G dwarf hosts, the zeta_1 parameter space is a subset of the larger eta_earth parameter space, thus zeta_1 places a lower limit on eta_earth for G dwarf hosts. From our analysis, we identify the leading sources of systematics impacting Kepler occurrence rate determinations as: reliability of the planet candidate sample, planet radii, pipeline completeness, and stellar parameters.Comment: 19 Pages, 17 Figures, Submitted ApJ. Python source to support Kepler pipeline completeness estimates available at http://github.com/christopherburke/KeplerPORTs