bluuebunny/crossref_metadata_2025_split huggingface dataset:
PP189 Filling In The Blanks: Is RWE From MAAs Used In NICE Decision Making?
Authors: Liu Lok Wan , Hall Adam , Macaulay Richard , Walsh Sean 
Published: December 2019

IntroductionThe National Institute for Health and Care Excellence (NICE) may recommend temporary funding through managed access agreements (MAAs) for oncology drugs (via the Cancer Drugs Fund [CDF]) and highly specialized therapies for rare diseases. MAAs allow for the collection of evidence to address key areas of clinical uncertainty, while providing access of medicines to patients, prior to re-appraisal by NICE. Observational data and other real-world evidence (RWE) are crucial requirements for all MAAs and herein we examine the extent these data are being used to inform HTA decisions at re-appraisal.MethodsExisting MAAs entered into between the National Health Service (NHS) England and manufacturers as of 30 October 2018 were identified; for drug:indication pairings with NICE re-appraisals, all information was reviewed and the key data extracted.ResultsOf the twenty-two MAAs identified, only two drug:indication pairings have been subsequently re-appraised by NICE: BV(brentuximab vedotin):non-Hodgkin lymphoma (’recommended’) and pembrolizumab:relapsed or refractory classical Hodgkin lymphoma (’recommended’). Data from a retrospective questionnaire regarding the proportion of patients that received curative stem cell transplant (SCT) post-BV (from patients who received BV in the old CDF) were accepted to provide sufficient evidence on the post-BV SCT rate by NICE. Meanwhile, for pembrolizumab, long-term survival benefit was the key clinical uncertainty; the primary data collection source was updated phase III randomized controlled trial data. At re-appraisal no reference was made to the observational data component; more mature survival data reduced uncertainty over survival benefits and were sufficient to support a positive NICE recommendation.ConclusionsOf the twenty-two MAAs to date, only two drugs have been re-appraised thus far, with both receiving positive NICE recommendations. Observational data were successfully used to address key clinical uncertainties regarding subsequent real-world treatment patterns for BV, but observational data were not referred to in the NICE recommendation for pembrolizumab. The re-appraisal of more drugs in the future will clarify the importance being placed on observational data collection requested by NICE for existing MAAs.
VP33 Pharmacoeconomic Submission Requirements: Africa Compared With England
Authors: Marsh Sophia , Truter Ilse 
Published: December 2019

IntroductionThe South African Pharmacoeconomic Submissions Guideline (SAPG) is currently voluntary for medicines in the private health sector but may become mandatory and more widely used under the proposed National Health Insurance system. To make recommendations on evidence generation and areas where the SAPG could be strengthened, the study compared the SAPG requirements with other African pharmacoeconomic guidelines and the National Institute for Health and Care Excellence Methods Guide (NICE MG).MethodsThe World Health Organisation, International Network of Agencies for Health Technology Assessment (INAHTA), HTA International, and the International Society for Pharmacoeconomics and Outcomes Research websites were consulted, and email requests sent to named individuals from retrieved source material. The European Network for HTA Core Model® (version 3.0) (the Model®) provided the evaluation and comparison framework, using three criteria: completely, partly or not completely requiring the same or similar information as the Model®.ResultsOf the forty-five countries identified, only Egypt had a publicly available pharmacoeconomic guideline (Egyptian Pharmacoeconomic Guideline (EPG)). The guidelines varied considerably in their intended audience, size and content. All three guidelines’ primary focus was the cost and economic evaluation, and health problem and current use domains. Safety, organisational, ethical and legal aspects were poorly covered by the SAPG and EPG guidelines (less than thirty percent of issues in each domain completely / partly covered). The SAPG completely or partly required the same or similar information in the Model® for thirty-nine percent of total issues, the EPG thirty-three percent and the NICE MG sixty-six percentConclusionsThe SAPG was not as comprehensive as the NICE MG and poorly covered some key aspects of HTAs, suggesting that the SAPG could be developed to be more informative for decision-makers. Evidence generation should focus on describing the health problem the technology is targeting and on evidence that can be synthesized into cost-effectiveness analyses.
High mass X-ray binaries as progenitors of gravitational wave sources
Authors: Klencki Jakub , Nelemans Gijs 
Published: December 2019

AbstractX-ray binaries with black hole (BH) accretors and massive star donors at short orbital periods of a few days can evolve into close binary BH (BBH) systems that merge within the Hubble time. From an observational point of view, upon the Roche-lobe overflow such systems will most likely appear as ultra-luminous X-ray sources (ULXs). To study this connection, we compute the mass transfer phase in systems with BH accretors and massive star donors (M > 15 Mʘ) at various orbital separations and metallicities. In the case of core-hydrogen and core-helium burning donors (cases A and C of mass transfer) we find the typical duration of super-Eddington mass transfer of up to 106 and 105 yr, with rates of 10−6 and 10−5Mʘ yr-1, respectively. Given that roughly 0.5 ULXs are found per unit of star formation rate, we estimate the rate of BBH mergers from stable mass transfer evolution to be at most 10 Gpc−3 yr−1.
Formation of the SMC WO+O binary AB8
Authors: Wang Chen , Langer Norbert , Gräfener Götz , Marchant Pablo 
Published: December 2019

AbstractWolf-Rayet (WR) stars are stripped stellar cores that form through strong stellar wind or binary mass transfer. It is proposed that binary evolution plays a vital role in the formation of WR stars in low metallicity environments due to the metallicity dependance of stellar winds. However observations indicate a similar binary fraction of WR stars in the Small Magellanic Cloud (SMC) compared to the Milky Way. There are twelve WR stars in the SMC and five of them are members of binary systems. One of them (SMC AB8) harbors a WO type star. In this work we explore possible formation channels of this binary. We use the MESA code to compute large grids of binary evolution models, and then use least square fitting to compare our models with the observations. In order to reproduce the key properties of SMC AB8, we require efficient semiconvection to produce a sufficiently large convective core, as well as a longer He-burning lifetime. We also need a high mass loss rate during the WN stage to assist the removal of the outer envelope. In this way, we can reproduce the observed properties of AB8, except for the surface carbon to oxygen ratio, which requires further investigation.
On the origin of Supergiant Fast X-ray Transients
Authors: Hubrig Swetlana , Sidoli Lara , Postnov Konstantin A. , Schöller Markus , Kholtygin Alexander F. , Järvinen Silva P. 
Published: December 2019

Abstract. A fraction of high-mass X-ray binaries are supergiant fast X-ray transients. These systems have on average low X-ray luminosities, but display short flares during which their X-ray luminosity rises by a few orders of magnitude. The leading model for the physics governing this X-ray behaviour suggests that the winds of the donor OB supergiants are magnetized. In agreement with this model, the first spectropolarimetric observations of the SFXT IGR J11215-5952 using the FORS 2 instrument at the Very Large Telescope indicate the presence of a kG longitudinal magnetic field. Based on these results, it seems possible that the key difference between supergiant fast X-ray transients and other high-mass X-ray binaries are the properties of the supergiant’s stellar wind and the physics of the wind’s interaction with the neutron star magnetosphere.
Analytical solution for magnetized thin accretion disk in comparison with numerical simulations
Authors: Čemeljić Miljenko , Parthasarathy Varadarajan , Kluźniak Włodek 
Published: December 2019

AbstractWe obtained equations for a thin magnetic accretion disk, using the method of asymptotic approximation. They cannot be solved analytically-without solutions for a magnetic field in the magnetosphere between the star and the disk, only a set of general conditions on the solutions can be derived. To compare the analytical results with numerical solutions, we find expressions for physical quantities in the disk, using our results from resistive and viscous star-disk magnetospheric interaction simulations.
Optical interferometry of High-Mass X-ray Binaries: Resolving wind, disk and jet outflows at sub-milliarcsecond scale
Authors: Waisberg Idel , Dexter Jason , Petrucci P.-O. , Dubus Guillaume , Perraut Karine ,   GRAVITY Collaboration
Published: December 2019

AbstractBecause of their small angular size < 1 mas, spatial information on High-mass X-ray binaries (HMXB) has typically been inferred from photometry or spectroscopy. Optical interferometry offers the possibility to spatially resolve such systems, but has been traditionally limited to bright targets or low spectral resolution. The VLTI instrument GRAVITY, working in the near-infrared K band, achieves unprecedented precision in differential interferometric quantities at high spectral resolution, allowing to study HMXBs through the lens of optical interferometry for the first time. We present GRAVITY observations on two X-ray binaries: the microquasar SS 433 and the supergiant HMXB BP Cru. The former is the only known steady super-Eddington accretor in the Galaxy and is in a unique stage of binary evolution, with probable ties to at least part of the ULX population. With GRAVITY, we resolve its massive winds and optical baryonic jets for the first time, finding evidence for powerful equatorial outflows and photoionization as the main heating process along the jets. BP Cru harbors an X-ray pulsar accreting from the wind of its early-blue hypergiant companion Wray 977. The GRAVITY observations resolve the inner parts of the stellar wind and allow probing the influence of the orbiting pulsar on the circumstellar environment.
The dark side of supergiant High-Mass X-ray Binaries
Authors: Chaty Sylvain , Fortin Francis , García Federico , Fogantini Federico 
Published: December 2019

Abstract. High Mass X-ray Binaries (HMXB) have been revealed by a wealth of multi-wavelength observations, from X-ray to optical and infrared domain. After describing the 3 different kinds of HMXB, we focus on 3 HMXB hosting supergiant stars: IGR J16320-4751, IGR J16465-4507 and IGR J16318-4848, respectively called “The Good”, “The Bad” and “The Ugly”. We review in these proceedings what the observations of these sources have brought to light concerning our knowledge of HMXB, and what part still remains in the dark side. Many questions are still pending, related to accretion processes, stellar wind properties in these massive and active stars, and the overall evolution due to transfer of mass and angular momentum between the companion star and the compact object. Future observations should be able to answer these questions, which constitute the dark side of HMXB.
High-Mass X-ray Binaries: progenitors of double compact objects
Authors: van den Heuvel Edward P. J. 
Published: December 2019

AbstractA summary is given of the present state of our knowledge of High-Mass X-ray Binaries (HMXBs), their formation and expected future evolution. Among the HMXB-systems that contain neutron stars, only those that have orbital periods upwards of one year will survive the Common-Envelope (CE) evolution that follows the HMXB phase. These systems may produce close double neutron stars with eccentric orbits. The HMXBs that contain black holes do not necessarily evolve into a CE phase. Systems with relatively short orbital periods will evolve by stable Roche-lobe overflow to short-period Wolf-Rayet (WR) X-ray binaries containing a black hole. Two other ways for the formation of WR X-ray binaries with black holes are identified: CE-evolution of wide HMXBs and homogeneous evolution of very close systems. In all three cases, the final product of the WR X-ray binary will be a double black hole or a black hole neutron star binary.
Different generations of HMXBs: clues about their formation efficiency from Magellanic Clouds studies
Authors: Antoniou Vallia , Zezas Andreas , Drake Jeremy J. , Badenes Carles , Haberl Frank , Hong Jaesub , Plucinsky Paul P. ,   the SMC XVP Collaboration Team
Published: December 2019

AbstractNearby star-forming galaxies offer a unique environment to study the populations of young (<100 Myr) accreting binaries. These systems are tracers of past populations of massive stars that heavily affect their immediate environment and parent galaxies. Using a Chandra X-ray Visionary program, we investigate the young neutron-star binary population in the low metallicity of the Small Magellanic Cloud (SMC) by reaching quiescent X-ray luminosity levels (~few times 1032 erg/s). We present the first measurement of the formation efficiency of high-mass X-ray binaries (HMXBs) as a function of the age of their parent stellar populations by using 3 indicators: the number ratio of HMXBs to OB stars, to the SFR, and to the stellar mass produced during the specific star-formation burst they are associated with. In all cases, we find that the HMXB formation efficiency increases as a function of time up to ~40–60 Myr, and then gradually decreases.
On the nature of the 35-day cycle in the X-ray binary Her X-1/HZ Her
Authors: Shakura N. , Kolesnikov D. , Postnov K. , Volkov I. , Bikmaev I. , Irsmambetova T. , Staubert R. , Wilms J. , Irtuganov E. , Shurygin P. , Golysheva P. , Shugarov S. , Nikolenko I. , Trunkovsky E. , Schonherr G. , Schwope A. , Klochkov D. 
Published: December 2019

AbstractThe X-ray binary Her X-1 consists of an accreting neutron star and the optical companion HZ Her. The 35-day X-ray variability of this system is known since its discovery in 1972 by the UHURU satellite and is believed to be caused by forced precession of the warped accretion disk tilted to the orbital plane. We argue that the observed features of the optical variability of HZ Her can be explained by free precession of the neutron star with a period close to that of the forced disk precession. The model parameters include a) the intensity (power) of the stream of matter flowing out of the optical star; b) the X-ray luminosity of the neutron star; c) the optical flux of the accretion disk; d) the X-ray irradiation pattern on the donor star; e) the tilt of the inner and outer edge of the accretion disk. A possible synchronization mechanism based on the coupling between the neutron star free precession and the dynamical action of non-stationary gas streams is discussed shortly.
The young Be-star binary Circinus X-1
Authors: Schulz Norbert S. , Kallman Timothy E. , Heinz Sebastian , Sell Paul , Jonker Peter , Brandt William N. 
Published: December 2019

AbstractCir X-1 is a young X-ray binary exhibiting X-ray flux changes of four orders of magnitude over several decades. It has been observed many times since the launch of the Chandra X-ray Observatory with high energy transmission grating spectrometer and each time the source gave us a vastly different look. At its very lowest X-ray flux we found a single 1.7 keV blackbody spectrum with an emission radius of 0.5 km. Since the neutron star in Cir X-1 is only few thousand years old we identify this as emission from an accretion column since at this youth the neutron star is assumed to be highly magnetized. At an X-ray flux of 1.8×10−11 erg cm−2 s−1 this implies a moderate magnetic field of a few times of 1011 G. The photoionized X-ray emission line properties at this low flux are consistent with B5-type companion wind. We suggest that Cir X-1 is a very young Be-star binary.
Evolution of the Global Carbon Cycle and Climate Regulation on Earth
Authors: Isson T. T. , Planavsky N. J. , Coogan L. A. , Stewart E. M. , Ague J. J. , Bolton E. W. , Zhang S. , McKenzie N. R. , Kump L. R. 
Published: December 2019

AbstractThe existence of stabilizing feedbacks within Earth's climate system is generally thought to be necessary for the persistence of liquid water and life. Over the course of Earth's history, Earth's atmospheric composition appears to have adjusted to the gradual increase in solar luminosity, resulting in persistently habitable surface temperatures. With limited exceptions, the Earth system has been observed to recover rapidly from pulsed climatic perturbations. Carbon dioxide (CO2) regulation via negative feedbacks within the coupled global carbon‐silica cycles are classically viewed as the main processes giving rise to climate stability on Earth. Here we review the long‐term global carbon cycle budget, and how the processes modulating Earth's climate system have evolved over time. Specifically, we focus on the relative roles that shifts in carbon sources and sinks have played in driving long‐term changes in atmospheric pCO2. We make the case that marine processes are an important component of the canonical silicate weathering feedback, and have played a much more important role in pCO2 regulation than traditionally imagined. Notably, geochemical evidence indicate that the weathering of marine sediments and off‐axis basalt alteration act as major carbon sinks. However, this sink was potentially dampened during Earth's early history when oceans had higher levels of dissolved silicon (Si), iron (Fe), and magnesium (Mg), and instead likely fostered more extensive carbon recycling within the ocean‐atmosphere system via reverse weathering—that in turn acted to elevate ocean‐atmosphere CO2 levels.
Effect of Fluid Viscosity on Fault Reactivation and Coseismic Weakening
Authors: Cornelio C. , Passelègue F. X. , Spagnuolo E. , Di Toro G. , Violay M. 
Published: December 2019

AbstractHigh‐viscosity fluids are often used during hydraulic fracking operations in georeservoirs. Here we performed dedicated experiments to study the influence of fluid viscosity on fault reactivation and associated induced earthquakes. Experiments were conducted in the rotary‐shear machine Slow to HIgh Velocity Apparatus on experimental fault of Westerly granite saturated by fluids with increasing viscosity (at room temperature) from 0.1 mPa s (water) to 1.2 Pa s (99% glycerol). Fault reactivation was triggered at constant effective normal stress by increasing the shear stress acting on the fault. Our results showed that independent of the viscosity, fault reactivation followed a Coulomb‐failure criterion. Instead, fluid viscosity affected the fault weakening mechanism: flash heating was the dominant weakening mechanism in room humidity and water‐saturated conditions, whereas the presence of more viscous fluids favored the activation of elasto‐hydrodynamic lubrication. Independent of the weakening mechanism, the breakdown work Wb dissipated during seismic faulting increased with slip U following a power law (Wb ∝ U 1.25) in agreement with seismological estimates of natural and induced earthquakes.
A novel microscale selective laser sintering (μ-SLS) process for the fabrication of microelectronic parts
Authors: Roy Nilabh K. , Behera Dipankar , Dibua Obehi G. , Foong Chee S. , Cullinan Michael A. 
Published: December 2019

AbstractOne of the biggest challenges in microscale additive manufacturing is the production of three-dimensional, microscale metal parts with a high enough throughput to be relevant for commercial applications. This paper presents a new microscale additive manufacturing process called microscale selective laser sintering (μ-SLS) that can produce true 3D metal parts with sub-5 μm resolution and a throughput of greater than 60 mm3/hour. In μ-SLS, a layer of metal nanoparticle ink is first coated onto a substrate using a slot die coating system. The ink is then dried to produce a uniform nanoparticle layer. Next, the substrate is precisely positioned under an optical subsystem using a set of coarse and fine nanopositioning stages. In the optical subsystem, laser light that has been patterned using a digital micromirror array is used to heat and sinter the nanoparticles into the desired patterns. This set of steps is then repeated to build up each layer of the 3D part in the μ-SLS system. Overall, this new technology offers the potential to overcome many of the current limitations in microscale additive manufacturing of metals and become an important process in microelectronics packaging applications.
Layered material platform for surface plasmon resonance biosensing
Authors: Wu F. , Thomas P. A. , Kravets V. G. , Arola H. O. , Soikkeli M. , Iljin K. , Kim G. , Kim M. , Shin H. S. , Andreeva D. V. , Neumann C. , Küllmer M. , Turchanin A. , De Fazio D. , Balci O. , Babenko V. , Luo B. , Goykhman I. , Hofmann S. , Ferrari A. C. , Novoselov K. S. , Grigorenko A. N. 
Published: December 2019

AbstractPlasmonic biosensing has emerged as the most sensitive label-free technique to detect various molecular species in solutions and has already proved crucial in drug discovery, food safety and studies of bio-reactions. This technique relies on surface plasmon resonances in ~50 nm metallic films and the possibility to functionalize the surface of the metal in order to achieve selectivity. At the same time, most metals corrode in bio-solutions, which reduces the quality factor and darkness of plasmonic resonances and thus the sensitivity. Furthermore, functionalization itself might have a detrimental effect on the quality of the surface, also reducing sensitivity. Here we demonstrate that the use of graphene and other layered materials for passivation and functionalization broadens the range of metals which can be used for plasmonic biosensing and increases the sensitivity by 3-4 orders of magnitude, as it guarantees stability of a metal in liquid and preserves the plasmonic resonances under biofunctionalization. We use this approach to detect low molecular weight HT-2 toxins (crucial for food safety), achieving phase sensitivity~0.5 fg/mL, three orders of magnitude higher than previously reported. This proves that layered materials provide a new platform for surface plasmon resonance biosensing, paving the way for compact biosensors for point of care testing.
Structured Back Focal Plane Interferometry (SBFPI)
Authors: Upadhya Avinash , Zheng Yujie , Li Li , Lee Woei Ming 
Published: December 2019

AbstractBack focal plane interferometry (BFPI) is one of the most straightforward and powerful methods for achieving sub-nanometer particle tracking precision at high speed (MHz). BFPI faces technical challenges that prohibit tunable expansion of linear detection range with minimal loss to sensitivity, while maintaining robustness against optical aberrations. In this paper, we devise a tunable BFPI combining a structured beam (conical wavefront) and structured detection (annular quadrant photodiode). This technique, which we termed Structured Back Focal Plane Interferometry (SBFPI), possesses three key novelties namely: extended tracking range, low loss in sensitivity, and resilience to spatial aberrations. Most importantly, the conical wavefront beam preserves the axial Gouy phase shift and lateral beam waist that can then be harnessed in a conventional BFPI system. Through a series of experimental results, we were able to tune detection sensitivity and detection range over the SBFPI parameter space. We also identified a figure of merit based on the experimental optimum that allows us to identify optimal SBPFI configurations that balance both range and sensitivity. In addition, we also studied the resilience of SBFPI against asymmetric spatial aberrations (astigmatism of up to 0.8 λ) along the lateral directions. The simplicity and elegance of SBFPI will accelerate its dissemination to many associated fields in optical detection, interferometry and force spectroscopy.