bluuebunny/crossref_metadata_2025 huggingface dataset:
VP16 A NICE Way To Manage Managed Access: Case Study In Muscular Dystrophy
Authors: Kent Emma , Paling Thomas
Published: December 2019

Introduction

Managed access arrangements (MAAs) represent a way of enabling patient access to promising treatments while collecting real world data to inform future health technology evaluations (HTE) and commissioning decisions. In July 2016, the National Institute for Health and Care Excellence (NICE) recommended Ataluren for treating Duchenne Muscular Dystrophy within a MAA. NICE is uniquely placed to oversee the implementation and monitoring of this MAA in collaboration with multiple stakeholders to ensure the final outputs meet the needs of a future HTE.

Methods

NICE assembled an Ataluren Managed Access Oversight Committee (MAOC) consisting of representatives from the manufacturer, patient organisations, commissioning body and treatment centres. This group were to meet every six months under the chairmanship of NICE with the primary function of reviewing the progress of data collection and identifying operational challenges in implementing the terms of the arrangement.

Results

The Ataluren MAOC has convened four times since the MAA commenced and these discussions identified a number of important actions. Data completeness was a concern and prompted stakeholders to collaborate on implementing measures to circumvent this, to ensure data quality for future HTE. Lack of awareness and understanding of the MAA in the patient community was highlighted and resulted in the production of lay information. A review of the statistical analysis plan resulted in the need for an agreement amendment. To ensure an audit trail and appropriate critique, NICE produced an amendment process to define and justify amendments made during the agreement term.

Conclusions

MAOC meetings play an important role in monitoring the progress of MAAs and have ensured that implementation issues are identified promptly and resolved with input from key stakeholders. This process allows NICE to coordinate the work of stakeholders to facilitate the success of the MAA, and will be adopted in future NICE MAAs in ultra-rare diseases.
VP23 Assessing The Effectiveness Of A Medical Device With Limited Evidence
Authors: Macmillan Thomas , Chalkidou Anastasia , Goddard Kate
Published: December 2019

Introduction

SecurAcath (Interrad Medical), a catheter securement device designed for central venous catheters, was assessed by the National Institute for Health and Care Excellence (NICE) in 2017 resulting in Medical Technology Guidance 34 (MTG34). Due to the limited number and quality of published evidence, novel methods were used to deliver a report that allowed a recommendation on adoption to be made.

Methods

KiTEC, an external assessment centre for NICE, independently evaluated the manufacturers submission of clinical and economic evidence. The submission was characterised by a lack of strong clinical evidence, comprising just one randomized clinical trial (RCT) and a small number of non-comparative observational studies, some of which were available as conference abstracts or poster presentations. KiTEC ran a meta-analysis of these studies along with data on the comparators, securement with sutures and securement with StatLock (Bard Access Systems). Due to the lack of comparative studies, KiTEC pooled data on five outcomes (migration, dislodgement, catheter-related infection, CRBSI, unplanned removals/reinsertions) and calculated relative risks for each. KiTEC revised the manufacturer's cost model, changing a number of parameters and assumptions. The decision to recommend SecurAcath for use in the National Health Service (NHS) was also supported by qualitative evidence from expert clinicians who had used the SecurAcath in practice.

Results

KiTEC's meta-analysis showed non-inferiority for SecurAcath over the comparators. The limited information in the studies made it impossible to ascertain study heterogeneity in the meta-analysis. KiTEC's economic analyses showed that SecurAcath could be cost saving in some scenarios, but not for short indwell times (≤5 days). However, clinical expert opinion was overwhelmingly positive and this qualitative evidence was viewed alongside the less conclusive clinical and cost-effectiveness evidence. SecurAcath was recommended to be used in the NHS, with annual savings estimated to be a minimum of GBP 4.2m.

Conclusions

In cases where there is a lack of published evidence, unpublished material and expert clinical opinion can be used to bolster the case for the adoption of medical devices.
VP34 Impact Of Adverse Events On Reimbursement Recommendations
Authors: Inumerable Riza Veronica , Farinella Michelle , Rubinstein Judith , Sharma Kriti
Published: December 2019

Introduction

European agencies evaluate the adverse events (AEs) of asthma drugs in studies. The impact of these evaluations on reimbursement decisions remains unclear.

Methods

Adult asthma evaluations were accessed from initial regulatory decision by the European Medicines Agency (EMA) through reimbursement evaluations. Omalizumab and reslizumab were chosen for the comparison of an older with a newer asthma drug. A timeline was then constructed to evaluate the effect of AEs on reimbursement recommendations. Evaluations from the United Kingdom (NICE) were not used because their documents are not as complete or in depth, including those from Sweden (TLV) and Germany (IQWIG).

Results

Omalizumab was first approved as add-on therapy to improve asthma control in October 2005. Of the 6 decisions made between 2006 and 2012, safety information was found in 4 of them, all from 2006 and evaluated by either Scotland (SMC) or France (HAS). These desicions all received either a ‘Do not recommend’ or a ‘Recommend with restrictions’ decision. Reslizumab was first approved as add-on therapy for patients with severe eosinophilic asthma in August 2016. Of the 9 decisions made in 2017, safety information was found in 5 decisions evaluated by IQWiG, Germany (G-BA), HAS, or SMC, which gave them a Do not recommend, Recommend with restrictions, or Recommend decision. Of the Do not recommend decisions, both the omalizumab and reslizumab safety evaluations mentioned common AEs (worsening asthma) and less common AEs (malignant tumors). Of the Recommend with restrictions decisions, the same AEs were seen. Only reslizumab had Recommended decisions. In the safety evaluation, there were no specific AEs named.

Conclusions

The impact of AEs on reimbursement decisions could not be detected when comparing omalizumab and reslizumab reviews, as other factors may contribute to the decisions. Further research should be conducted to explore this issue.
VP61 Rapid HTA Of The CarbonCool Full Body Suit For Exertional Heat Injuries
Authors: Pwee Keng Ho
Published: December 2019

Introduction

The CarbonCool full body suit is a portable, non-invasive core body cooling system for use by first responders and clinicians for targeted temperature management and heat stroke treatment. It uses pads made of a highly thermal conductive carbon-based cooling medium to absorb heat from the body. Our department was requested to review the effectiveness of the suit and whether it might be used in place of a Body Cooling Unit (BCU).

Methods

A rapid review was carried out on the technology. The PICO elements were: Population- Emergency department patients with exertional heat injury; Intervention- CarbonCool full body suit; Comparator- Body Cooling Unit; Outcomes- Adverse effects, clinical outcomes (survival, neurological status), physical measures (rate of cooling). The NHS Centre for Reviews & Dissemination databases, Cochrane Database of Systematic Reviews, PubMed (MEDLINE) and the US National Guidelines Clearinghouse were searched for systematic reviews, HTA reports and clinical practice guidelines. The importer was contacted to provide supporting studies for their product.

Results

No publications were found on CarbonCool products. The importer provided the unpublished abstract of a retrospective cohort study of 124 post-cardiac arrest patients requiring targeted temperature management. The importer advised that a trial on pre-hospital heat stroke was pending. The full body suit is not intended as a replacement for body cooling units. Three clinical practice guidelines on management of heat injuries did not mention such cooling systems, but did recommend ice packs as a treatment option.

Conclusions

The CarbonCool Full Body Suit is not intended as a replacement for a Body Cooling Unit. No published studies were found showing effectiveness for managing exertional heat injuries. A trial on pre-hospital heat stroke was pending. Guidelines on managing heat injuries do not mention the use of the technology. It was recommended to await results of pending trials, or to use it only under research.
VP77 Extrapolating ICERs At Different Discount Rates
Authors: Teljeur Conor , Ryan Máirín
Published: December 2019

Introduction

Applicability of incremental cost-effectiveness ratios from another jurisdiction is often affected by a different local discount rate, creating uncertainty about the ICER using the local discount rate. The ICER is sometimes reported at additional discount rates in the sensitivity analysis. We aimed to investigate the extent to which an ICER can be predicted at a given non-differential discount rate if estimates are available for at least two discount rates.

Methods

We used six previously published economic models representing analyses with a range of time horizons and ICERs calculated at discount rates from 1% to 8%. A simulation exercise was applied whereby the ICER at a discount rate selected from the range 2% to 5% was calculated based on ICERs provided at two or three randomly selected discount rates. With two discount rates a linear model was used to predict the ICER at the selected rate. For three discount rates an exponential model was used. Error between the predicted and actual ICER was calculated as the absolute difference divided by the actual ICER.

Results

For four of the models, ICERs could be well predicted by a linear model (i.e., with two points), with average errors of less than 5%. For the final two models the error was substantial with a linear model but substantially improved to under 15% with an exponential model (i.e., with three data points). The two models with a poor fit to a linear model assessed childhood vaccination programmes over a lifetime horizon.

Conclusions

For studies with a relatively short time-horizon, or where the majority of costs and benefits accrue in the short-term, a simple linear extrapolation can facilitate calculation of the ICER at a discount rate other than those reported. With longer time horizons, a third data point facilitates more reliably extrapolation of ICERs at desired discount rates.
High-mass X-ray binaries: Evolutionary population synthesis modeling
Authors: Zuo Zhao-yu
Published: December 2019

Using an evolutionary population synthesis code, we modeled the universal, featureless X-ray luminosity function of high-mass X-ray binaries (HMXBs) in star-forming galaxies. We put constraints on the natal kicks, super-Eddington accretion factor, as well as common envelope prescriptions usually adopted (i.e., the αCE formalism and the γ algorithm), and presented the detailed properties of HMXBs under different models, which may be investigated further by future high-resolution X-ray and optical observations.
The black hole spin in coalescing binary black holes and high-mass X-ray binaries
Authors: Qin Y. , Fragos T. , Meynet G. , Marchant P. , Kalogera V. , Andrews J. , Sørensen M. , Song H. F.
Published: December 2019

The six LIGO detections of merging black holes (BHs) allowed to infer slow spin values for the two pre-merging BHs. The three cases where the spins of the BHs can be determined in high-mass X-ray binaries (HMXBs) show that those BHs have high spin values. We discuss here scenarios explaining these differences in spin properties in these two classes of object.
Massive star winds and HMXB donors
Authors: Sander Andreas A. C.
Published: December 2019

Understanding the complex behavior of High Mass X-ray binaries (HMXBs) is not possible without detailed information about their donor stars. While crucial, this turns out to be a challenge on multiple fronts. First, multi-wavelength spectroscopy is vital. As such systems can be highly absorbed, this is often already hard to accomplish. Secondly, even if the spectroscopic data is available, the determination of reliable stellar parameters requires sophisticated model atmospheres that accurately describe the outermost layers and the wind of the donor star.

For early-type donors, the stellar wind is radiatively driven and there is a smooth transition between the outermost layers of the star and the wind. The intricate non-LTE conditions in the winds of hot stars complicate the situation even further, as proper model atmospheres need to account for a multitude of physics to accurately provide stellar and wind parameters. The latter are especially crucial for the so-called “wind-fed” HXMBs, where the captured wind of the supergiant donor is the only source for the material accreted by the compact object.

In this review I will briefly address the different approaches for treating stellar winds in the analysis of HMXBs. The fundamentals of stellar atmosphere modeling will be discussed, also addressing the limitations of modern models. Examples from recent analysis results for particular HMXBs will be outlined. Furthermore, the path for the next generation of stellar atmosphere models will be outlined, where models can be used not only for measurement purposes, but also to make predictions and provide a laboratory for theoretical conclusions. Stellar atmospheres are a key tool in understanding HMXBs, e.g. by providing insights about the accretion of stellar winds onto the compact object, or by placing the studied systems in the correct evolutionary context in order to identify potential gravitational wave (GW) progenitors.
Investigating High Mass X-ray Binaries at hard X-rays with INTEGRAL
Authors: Sidoli Lara , Paizis Adamantia
Published: December 2019

The INTEGRAL archive developed at INAF-IASF Milano with the available public observations from late 2002 to 2016 is investigated to extract the X-ray properties of 58 High Mass X-ray Binaries (HMXBs). This sample consists of sources hosting either a Be star (Be/XRBs) or an early-type supergiant companion (SgHMXBs), including the Supergiant Fast X-ray Transients (SFXTs). INTEGRAL light curves (sampled at 2 ks) are used to build their hard X-ray luminosity distributions, returning the source duty cycles, the range of variability of the X-ray luminosity and the time spent in each luminosity state. The phenomenology observed with INTEGRAL, together with the source variability at soft X-rays taken from the literature, allows us to obtain a quantitative overview of the main sub-classes of massive binaries in accretion (Be/XRBs, SgHMXBs and SFXTs). Although some criteria can be derived to distinguish them, some SgHMXBs exist with intermediate properties, bridging together persistent SgHMXBs and SFXTs.
Rapid evolution of the relativistic jet system SS 433
Authors: Goranskij V. P. , Barsukova E. A. , Burenkov A. N. , Valeev A. F. , Trushkin S. A. , Volkov I. M. , Esipov V. F. , Irsmambetova T. R. , Zharova A. V.
Published: December 2019

. We analyzed a 40-year set of multicolor photometry and a 15-year set of synoptic monitoring of SS 433 along with fragmentary spectral and radio data. This system contains a neutron star and an A3–A7 I giant. The system is found to be either close, in contact, or it has a common envelope from time to time. The A-type giant is now in transition to the dynamical mass transfer.
X-ray binaries with neutron stars at different accretion stages
Authors: Postnov Konstantin A. , Kuranov Alexander G. , Yungelson Lev R.
Published: December 2019

. Different accretion regimes onto magnetized NSs in HMXBs are considered: wind-fed supersonic (Bondi) regime at high accretion rates  g s-1, subsonic settling regime at lower  and supercritical disc accretion during Roche lobe overflow. In wind-fed stage, NSs in HMXBs reach equilibrium spin periods P* proportional to binary orbital period Pb. At supercritical accretion stage, the system may appear as a pulsating ULX. Population synthesis of Galactic HMXBs using standard assumptions on the binary evolution and NS formation is presented. Comparison of the model P* – Pb (the Corbet diagram), P* – Lx and Pb – Lx distributions with those for the observed HMXBs (including Be X-ray binaries) and pulsating ULXs suggests the importance of the reduction of P* in non-circular orbits, explaining the location of Be X-ray binaries in the model Corbet diagram, and the universal parameters of pulsating ULXs depending only on the NS magnetic fields.
Numerical models of VHE emission by magnetic reconnection in X-ray binaries: GRMHD simulations and Monte Carlo cosmic-ray emission
Authors: Rodríguez-Ramírez J. C. , de Gouveia Dal Pino E. M. , Alves Batista R.
Published: December 2019

Galactic microquasars have been detected at very-high-energies (VHE) (> 100 GeV) and the particle acceleration mechanisms that produce this emission are not yet well-understood. Here we investigate a hadronic emission scenario where cosmic-rays (CRs) are accelerated in magnetic reconnection events by the turbulent, advected-dominated accretion flow (ADAF) believed to be present in the hard state of black hole binaries. We present Monte Carlo simulations of CR emission plus γ-γ and inverse Compton cascades, injecting CRs with a total energy consistent with the magnetic energy of the plasma. The background gas density, magnetic, and photon fields where CRs propagate and interact are modelled with general relativistic (GR), magneto-hydrodynamical simulations together with GR radiative transfer calculations. Our approach is applied to the microquasar Cygnus X-1, where we show a model configuration consistent with the VHE upper limits provided by MAGIC collaboration.
Firm detection of 7-year X-ray periodicity from X Persei
Authors: Nakajima Motoki , Negoro Hitoshi , Mihara Tatehiro , Sugizaki Mutsumi , Yatabe Fumiaki , Makishima Kazuo
Published: December 2019

We report on the detection of long-term X-ray periodicity from the Be/X-ray binary pulsar X Persei. Based on over 23 years of X-ray data observed using RXTE/ASM, Swift/BAT and MAXI/GSC, we confirmed that X Persei exhibits quasi-periodic X-ray flares with a period of ∼7 years. The recurrence timescale corresponds to approximately 10 times its binary orbital period of 250 days. Spectral and hardness ratio changes were not detected along with long-term periodic activity. If we interpret the observed 7 year periodicity of X-ray band flux as a superorbital modulation, then this would be the first observation among the Be/X-ray binaries.
Superstrong magnetic fields of neutron stars in Be X-ray binaries
Authors: Shi ChangSheng , Zhang ShuangNan , Li XiangDong
Published: December 2019

A few Be X-ray binaries might constitute a group of special sources because the neutron stars in them may have superstrong magnetic fields. Generally, the neutron stars have long spin periods and some emission lines are shown from the B type star, which is attributed to an equatorial disc. We re-build new dimensionless torque models and obtain the superstrong magnetic fields of the neutron stars in the Be X-ray binaries in Large Magellanic Cloud, Small Magellanic Cloud and Milky Way when the compressed magnetosphere is considered. Although our conclusions are obtained when the disk accretion mode is considered, the results may be applied the Be X-ray binaries with wind accretion mode. SXP1323 and 4U 2206+54, in which the magnetic fields of the NSs may be close to the maximum ‘virial’ value, are the best objects to explore superstrong magnetic field.
Accretion simulations of Eta Carinae and implications to massive binaries
Authors: Kashi Amit
Published: December 2019

Using high resolution 3D hydrodynamical simulations we quantify the amount of mass accreted onto the secondary star of the binary system η Carinae during periastron passage on its highly eccentric orbit. The accreted mass is responsible for the spectroscopic event occurring every orbit close to periastron passage, during which many lines vary and the x-ray emission associated with the destruction wind collision structure declines. The system is mainly known for its giant eruptions that occurred in the nineteenth century. The high mass model of the system, M1=170M⊙ and M2=80M⊙, gives Macc≍ 3×10−6M⊙ compatible with the amount required for explaining the reduction in secondary ionization photons during the spectroscopic event, and also matches its observed duration. As accretion occurs now, it surely occurred during the giant eruptions. This implies that mass transfer can have a huge influence on the evolution of massive stars.
On the nature of the X-ray outbursts in Be/X-ray binaries
Authors: Yan Jingzhi , Liu Wei , Zhang Peng , Liu Qingzhong
Published: December 2019

Be/X-ray binaries are a major subclass of high mass X-ray binaries. Two different X-ray outbursts are displayed in the X-ray light curves of such systems. It is generally believed that the X-ray outbursts are connected with the neutron star periastron passage of the circumstellar disk around the Be star. The optical emission of the Be star should be very important to understand the X-ray emission of the compact object. We have monitored several Be/X-ray binaries photometrically and spectroscopically in the optical band. The relationship between the optical emission and X-ray activity is described, which is very useful to explain the X-ray outbursts in Be/X-ray binaries.
Collaborative Modeling With Fine‐Resolution Data Enhances Flood Awareness, Minimizes Differences in Flood Perception, and Produces Actionable Flood Maps
Authors: Sanders Brett F. , Schubert Jochen E. , Goodrich Kristen A. , Houston Douglas , Feldman David L. , Basolo Victoria , Luke Adam , Boudreau Dani , Karlin Beth , Cheung Wing , Contreras Santina , Reyes Abigail , Eguiarte Ana , Serrano Kimberly , Allaire Maura , Moftakhari Hamed , AghaKouchak Amir , Matthew Richard A.
Published: December 2019

Existing needs to manage flood risk in the United States are underserved by available flood hazard information. This contributes to an alarming escalation of flood impacts amounting to hundreds of billions of dollars per year and countless disrupted lives and affected communities. Making information about flood hazards useful for the range of decisions that dictate the consequences of flooding poses many challenges. Here, we describe collaborative flood modeling, whereby researchers and end‐users at two coastal sites co‐develop fine‐resolution flood hazard models and maps responsive to decision‐making needs. We find, first of all, that resident perception and awareness of flooding are enhanced more by fine‐resolution depth contour maps than Federal Emergency Management Agency (FEMA) flood hazard classification maps and that viewing fine‐resolution depth contour maps helps to minimize differences in flood perception across subgroups within the community, generating a shared understanding. We also find that collaborative flood modeling supports the engagement of a wide range of end‐users in contemplating the risks of flooding and provides strong evidence that the co‐produced knowledge can be readily adopted and applied for Flood Risk Management (FRM). Overall, collaborative flood modeling advances FRM by providing multiple points of entry for diverse groups of end‐users to contemplate the spatial extent, intensity, timing, chance, and consequences of flooding, thus enabling the web of decision‐making related to flooding to be better informed with the best available science. This transdisciplinary approach emphasizes vulnerability reduction and is complementary to FEMA Flood Insurance Rate Maps used for flood insurance administration.
Bifurcated Region 2 Field‐Aligned Currents Associated With Substorms
Authors: Sangha H. , Milan S. E. , Carter J. A. , Fogg A. R. , Anderson B. J. , Korth H. , Paxton L. J.
Published: December 2019

We analyze the magnetosphere‐ionosphere field‐aligned currents associated with substorms using the Active Magnetosphere and Planetary Electrodynamics Response Experiment. We report a new phenomenon related to substorm onset: the development of a second pair of R2 field‐aligned currents located equatorward of the preexisting R1/R2 currents, especially in the dusk sector. The appearance of such events favors the summer hemisphere, suggesting that ionospheric conductance modulates this phenomenon. During ongoing geomagnetic activity, the events have a quasiperiodicity of approximately 1 hr. We suggest that this phenomenon is related to subauroral polarization streams, which are strong westward flows in the dusk sector midlatitude ionosphere. This paper proposes a new mechanism that describes the formation of these current bifurcations: Consecutive particle injections into the inner magnetosphere during disturbed geomagnetic conditions cause separate partial ring currents to form, leading to the presence of distinct R2 current systems, all flowing into the R1 current.
Radial Evolution of Coronal Mass Ejections Between MESSENGER, Venus Express, STEREO, and L1: Catalog and Analysis
Authors: Salman T. M. , Winslow R. M. , Lugaz N.
Published: December 2019

Our knowledge of the properties of coronal mass ejections (CMEs) in the inner heliosphere is constrained by the relative lack of plasma observations between the Sun and 1 AU. In this work, we present a comprehensive catalog of 47 CMEs measured in situ measurements by two or more radially aligned spacecraft (MESSENGER, Venus Express, STEREO, Wind/ACE). We estimate the CME impact speeds at Mercury and Venus using a drag‐based model and present an average propagation profile of CMEs (speed and deceleration/acceleration) in the inner heliosphere. We find that CME deceleration continues past Mercury's orbit but most of the deceleration occurs between the Sun and Mercury. We examine the exponential decrease of the maximum magnetic field strength in the CME with heliocentric distance using two approaches: a modified statistical method and analysis from individual conjunction events. Findings from both the approaches are on average consistent with previous studies but show significant event‐to‐event variability. We also find the expansion of the CME sheath to be well fit by a linear function. However, we observe the average sheath duration and its increase to be fairly independent of the initial CME speed, contradicting commonly held knowledge that slower CMEs drive larger sheaths. We also present an analysis of the 3 November 2011 CME observed in longitudinal conjunction between MESSENGER, Venus Express, and STEREO‐B focusing on the expansion of the CME and its correlation with the exponential falloff of the maximum magnetic field strength in the ejecta.
Identifying Radiation Belt Electron Source and Loss Processes by Assimilating Spacecraft Data in a Three‐Dimensional Diffusion Model
Authors: Cervantes S. , Shprits Y. Y. , Aseev N. A. , Drozdov A. Y. , Castillo A. , Stolle C.
Published: December 2019

Data assimilation aims to blend incomplete and inaccurate data with physics‐based dynamical models. In the Earth's radiation belts, it is used to reconstruct electron phase space density, and it has become an increasingly important tool in validating our current understanding of radiation belt dynamics, identifying new physical processes, and predicting the near‐Earth hazardous radiation environment. In this study, we perform reanalysis of the sparse measurements from four spacecraft using the three‐dimensional Versatile Electron Radiation Belt diffusion model and a split‐operator Kalman filter over a 6‐month period from 1 October 2012 to 1 April 2013. In comparison to previous works, our 3‐D model accounts for more physical processes, namely, mixed pitch angle‐energy diffusion, scattering by Electromagnetic Ion Cyclotron waves, and magnetopause shadowing. We describe how data assimilation, by means of the innovation vector, can be used to account for missing physics in the model. We use this method to identify the radial distances from the Earth and the geomagnetic conditions where our model is inconsistent with the measured phase space density for different values of the invariants
and
. As a result, the Kalman filter adjusts the predictions in order to match the observations, and we interpret this as evidence of where and when additional source or loss processes are active. The current work demonstrates that 3‐D data assimilation provides a comprehensive picture of the radiation belt electrons and is a crucial step toward performing reanalysis using measurements from ongoing and future missions.
Numerical Modeling of Mantle Flow Beneath Madagascar to Constrain Upper Mantle Rheology Beneath Continental Regions
Authors: Rajaonarison T. A. , Stamps D. S. , Fishwick S. , Brune S. , Glerum A. , Hu J.
Published: December 2019

Over the past few decades, azimuthal seismic anisotropy measurements have been widely used proxy to study past and present‐day deformation of the lithosphere and to characterize convection in the mantle. Beneath continental regions, distinguishing between shallow and deep sources of anisotropy remains difficult due to poor depth constraints of measurements and a lack of regional‐scale geodynamic modeling. Here, we constrain the sources of seismic anisotropy beneath Madagascar where a complex pattern cannot be explained by a single process such as absolute plate motion, global mantle flow, or geology. We test the hypotheses that either Edge‐Driven Convection (EDC) or mantle flow derived from mantle wind interactions with lithospheric topography is the dominant source of anisotropy beneath Madagascar. We, therefore, simulate two sets of mantle convection models using regional‐scale 3‐D computational modeling. We then calculate Lattice Preferred Orientation that develops along pathlines of the mantle flow models and use them to calculate synthetic splitting parameters. Comparison of predicted with observed seismic anisotropy shows a good fit in northern and southern Madagascar for the EDC model, but the mantle wind case only fits well in northern Madagascar. This result suggests the dominant control of the measured anisotropy may be from EDC, but the role of localized fossil anisotropy in narrow shear zones cannot be ruled out in southern Madagascar. Our results suggest that the asthenosphere beneath northern and southern Madagascar is dominated by dislocation creep. Dislocation creep rheology may be dominant in the upper asthenosphere beneath other regions of continental lithosphere.
Multispecies Assessment of Factors Influencing Regional CO2 and CH4 Enhancements During the Winter 2017 ACT‐America Campaign
Authors: Baier Bianca C. , Sweeney Colm , Choi Yonghoon , Davis Kenneth J. , DiGangi Joshua P. , Feng Sha , Fried Alan , Halliday Hannah , Higgs Jack , Lauvaux Thomas , Miller Benjamin R. , Montzka Stephen A. , Newberger Timothy , Nowak John B. , Patra Prabir , Richter Dirk , Walega James , Weibring Petter
Published: December 2019

Diagnosing carbon dioxide (CO2) and methane (CH4) fluxes at subcontinental scales is complicated by sparse observations, limited knowledge of prior fluxes and their uncertainties, and background and transport errors. Multispecies measurements in flasks sampled during the wintertime ACT‐America campaign were used for background characterization and source apportionment of regional anthropogenic CO2 and CH4 fluxes when ecosystem CO2 exchange is likely to be least active. Continental background trace gas mole fractions for regional enhancements are defined using samples from the upper troposphere and assessed using model products. Trace gas enhancements taken from flask samples in the lower troposphere with background levels subtracted out are then interpreted to inform CO2 and CH4 enhancement variability in the eastern United States. Strong correlations between CO2 and CH4 enhancements in the Midwestern and Mid‐Atlantic United States indicated colocated anthropogenic sources. Oil and natural gas influence was also broadly observed throughout the entire observational domain. In the Midwestern United States, agricultural influence on CO2 and CH4 enhancement variability was evident during above‐average wintertime temperatures. Weaker correlations between CO2 and anthropogenic tracer enhancements in the Southeastern United States indicated potentially nonnegligible wintertime ecosystem CO2 exchange, with biogenic tracers indicating more active surface processing than other regions. These whole‐air flask samples illuminated significant regional CO2 and CH4 sources or sinks during Atmospheric Carbon and Transport‐America (ACT‐America) and can provide additional information for informing regional inverse modeling efforts.
Exploring Oxidation in the Remote Free Troposphere: Insights From Atmospheric Tomography (ATom)
Authors: Brune W. H. , Miller D. O. , Thames A. B. , Allen H. M. , Apel E. C. , Blake D. R. , Bui T. P. , Commane R. , Crounse J. D. , Daube B. C. , Diskin G. S. , DiGangi J. P. , Elkins J. W. , Hall S. R. , Hanisco T. F. , Hannun R. A. , Hintsa E. J. , Hornbrook R. S. , Kim M. J. , McKain K. , Moore F. L. , Neuman J. A. , Nicely J. M. , Peischl J. , Ryerson T. B. , St. Clair J. M. , Sweeney C. , Teng A. P. , Thompson C. , Ullmann K. , Veres P. R. , Wennberg P. O. , Wolfe G. M.
Published: December 2019

Earth's atmosphere oxidizes the greenhouse gas methane and other gases, thus determining their lifetimes and oxidation products. Much of this oxidation occurs in the remote, relatively clean free troposphere above the planetary boundary layer, where the oxidation chemistry is thought to be much simpler and better understood than it is in urban regions or forests. The NASA airborne Atmospheric Tomography study (ATom) was designed to produce cross sections of the detailed atmospheric composition in the remote atmosphere over the Pacific and Atlantic Oceans during four seasons. As part of the extensive ATom data set, measurements of the atmosphere's primary oxidant, hydroxyl (OH), and hydroperoxyl (HO2) are compared to a photochemical box model to test the oxidation chemistry. Generally, observed and modeled median OH and HO2 agree to within combined uncertainties at the 2σ confidence level, which is ~±40%. For some seasons, this agreement is within ~±20% below 6‐km altitude. While this test finds no significant differences, OH observations increasingly exceeded modeled values at altitudes above 8 km, becoming ~35% greater, which is near the combined uncertainties. Measurement uncertainty and possible unknown measurement errors complicate tests for unknown chemistry or incorrect reaction rate coefficients that would substantially affect the OH and HO2 abundances. Future analysis of detailed comparisons may yield additional discrepancies that are masked in the median values.
Fate of Organic Carbon Burial in Modern Sediment Within Yangtze River Estuary
Authors: Sun Xueshi , Fan Dejiang , Liao Huijie , Tian Yuan
Published: December 2019

Large river‐dominated margins play a potential key role in regulating global carbon cycle and budget due to high terrestrial organic carbon (Corg) inputs and sediment accumulation rates. Here bulk elements (Corg and TN), isotopic compositions (δ13Corg and δ15N), radioisotope 210Pb, sedimentary grain size, pH, Eh, and physicochemical properties were analyzed on samples from the Yangtze River Estuary to determine the mechanism involved in transporting sedimentary Corg offshore. In addition, nine box‐cores were analyzed to further reveal the potential effects of the declining sediment load on the modern depositional pattern of Corg. The statistical analyses indicate that the hydrodynamically driven sediment composition exerts a significant control on the transport, mobilization, and accumulation of sedimentary Corg from the river to the estuary, with respect to the redistribution of fine‐grained sediments. Furthermore, X‐radiographs and 210Pb indicate that reworked environment dominates carbon burial in the Yangtze proximal deposit, while a stable sedimentary environment of Corg (3.50–5.58 g cm−2 year−1) is observed in the Yangtze distal mud. Notably, the enhanced erosional inputs that contain terrestrial plant debris (mainly the coarse fractions) have tended to become important sources for Corg. Although reworked sediments in the Yangtze River Estuary are frequently exposed to oxygen during physical and biological processes, there appears to be a high potential for long‐term sedimentary Corg storage, due to its association with sediment particles (mainly the clay fractions) that provide physical protection against its degradation.
Some Experiments in Extreme‐Value Statistical Modeling of Magnetic Superstorm Intensities
Authors: Love Jeffrey J.
Published: December 2019

In support of projects for forecasting and mitigating the deleterious effects of extreme space weather storms, an examination is made of the intensities of magnetic superstorms recorded in the
index time series (1957–2016). Modified peak‐over‐threshold and solar cycle, block‐maximum samplings of the
time series are performed to obtain compilations of storm maximum
intensity values. Lognormal, upper limit lognormal, generalized Pareto, and generalized extreme‐value model distributions are fitted to the
data using a maximum‐likelihood algorithm. All four candidate models provide good representations of the data. Comparisons of the statistical significance and goodness of fits of the various models give no clear indication as to which model is best. The statistical models are used to extrapolate to extreme‐value intensities, such as would be expected (on average) to occur once per century. An upper limit lognormal fit to peak‐over‐threshold
data above a superstorm threshold of 283 nT gives a 100‐year extrapolated intensity of 542 nT and a 68% confidence interval (obtained by bootstrap resampling) of [466, 583] nT. A generalized extreme‐value distribution fit to solar cycle, block‐maximum
data gives a nine‐solar cycle (approximately 100‐year) extrapolated intensity of 591 nT. The
data are found to be insufficient for providing usefully accurate estimates of a statistically theoretical upper limit for magnetic storm intensity. Secular change in storm intensities is noted, as is a need for improved estimates of pre‐1957 magnetic storm intensities.
Ultrafast electrical switching of nanostructured metadevice with dual-frequency liquid crystal
Authors: Kowerdziej Rafał , Wróbel Jerzy , Kula Przemysław
Published: December 2019

Shortening of switching times of various soft-matter-based tunable metamaterials is one of the key challenges to improve the functionality of modern active devices. Here we show an effective strategy in the evolution of soft-matter-based tunable metamaterials that makes possible acceleration of both on and off switching processes by using a dual-frequency liquid crystal mixture. The frequency-convertible dielectric anisotropy of the dual-frequency mixture enabled us to create a fast-response in-plane switching metasurface at the nanoscale, which could be tuned by an electrical signal with different frequencies. The results clearly show that the resonance of the metamaterial can be continuously and reversibly controlled within a wavelength range of 100 nm as the applied frequency is inverted between 1 kHz and 40 kHz, with a total response time (τ = τON + τOFF) of 1.89 ms. Furthermore, experimental characteristics of the hybrid metamaterial are in great agreement with numerical calculations, which allow us to anticipate active epsilon-near-zero behavior of the metadevice. This work indicates the future development direction of liquid-crystal-based active plasmonic systems.
An Efficient Intestinal Organoid System of Direct Sorting to Evaluate Stem Cell Competition in Vitro
Authors: Fujimichi Yuki , Otsuka Kensuke , Tomita Masanori , Iwasaki Toshiyasu
Published: December 2019

Stem cell competition could shed light on the tissue-based quality control mechanism that prevents carcinogenesis. To quantitatively evaluate stem cell competition in vitro, we developed a two-color intestinal organoid forming system. First, we improved a protocol of culturing organoids from intestinal leucine-rich-repeat containing G-protein-coupled receptor 5 (Lgr5)- enhanced green fluorescent protein (EGFP)high stem cells directly sorted on Matrigel without embedding. The organoid-forming potential (OFP) was 25% of Lgr5-EGFPhigh cells sorted at one cell per well. Using this culture protocol with lineage tracing, we established a two-color organoid culture system by mixing stem cells expressing different fluorescent colors. To analyze stem cell competition, two-color organoids were formed by mixing X-ray-irradiated and non-irradiated intestinal stem cells. In the two-color organoids, irradiated stem cells exhibited a growth disadvantage, although the OFP of irradiated cells alone did not decrease significantly from that of non-irradiated cells. These results suggest that stem cell competition can be evaluated quantitively in vitro using our new system.
Characterization and functional roles of paternal RNAs in 2–4 cell bovine embryos
Authors: Gross Nicole , Strillacci Maria Giuseppina , Peñagaricano Francisco , Khatib Hasan
Published: December 2019

Embryos utilize oocyte-donated RNAs until they become capable of producing RNAs through embryonic genome activation (EGA). The sperm’s influence over pre-EGA RNA content of embryos remains unknown. Recent studies have revealed that sperm donate non-genomic components upon fertilization. Thus, sperm may also contribute to RNA presence in pre-EGA embryos. The first objective of this study was to investigate whether male fertility status is associated with the RNAs present in the bovine embryo prior to EGA. A total of 65 RNAs were found to be differentially expressed between 2–4 cell bovine embryos derived from high and low fertility sires. Expression patterns were confirmed for protein phosphatase 1 regulatory subunit 36 (PPP1R36) and ataxin 2 like (ATXN2L) in three new biological replicates. The knockdown of ATXN2L led to a 22.9% increase in blastocyst development. The second objective of this study was to characterize the parental origin of RNAs present in pre-EGA embryos. Results revealed 472 sperm-derived RNAs, 2575 oocyte-derived RNAs, 2675 RNAs derived from both sperm and oocytes, and 663 embryo-exclusive RNAs. This study uncovers an association of male fertility with developmentally impactful RNAs in 2–4 cell embryos. This study also provides an initial characterization of paternally-contributed RNAs to pre-EGA embryos. Furthermore, a subset of 2–4 cell embryo-specific RNAs was identified.
Inflammation as a predictor of acute kidney injury and mediator of higher mortality after acute kidney injury in non-cardiac surgery
Authors: Murashima Miho , Nishimoto Masatoshi , Kokubu Maiko , Hamano Takayuki , Matsui Masaru , Eriguchi Masahiro , Samejima Ken-ichi , Akai Yasuhiro , Tsuruya Kazuhiko
Published: December 2019

This retrospective cohort study examined the roles of inflammation in acute kidney injury (AKI). Serum albumin and C-reactive protein (CRP) were used as markers of inflammation. Adults who underwent non–cardiac surgery from 2007 to 2011 were included. Exclusion criteria were urological surgery, obstetric surgery, missing data, and pre-operative dialysis. Subjects were followed until the end of 2015 or loss to follow-up. Associations between pre–operative albumin or CRP and post-operative AKI or association between AKI and mortality were examined by logistic or Cox regression, respectively. Mediation analyses were performed using albumin and CRP as mediators. Among 4,538 subjects, 272 developed AKI. Pre-operative albumin was independently associated with AKI (odds ratio [95% confidence interval (CI)]: 0.63 [0.48–0.83]). During a median follow-up of 4.5 years, 649 died. AKI was significantly associated with mortality (hazard ratio [HR] [95% CI]: 1.58 [1.22–2.04]). Further adjustment for pre-operative albumin and CRP attenuated the association (HR [95% CI]: 1.28 [0.99–1.67]). The proportions explained by mediating effects of lnCRP and albumin were 29.3% and 39.2% and mediation effects were statistically significant. In conclusion, inflammation is a predictor of AKI and a mediator of mortality after AKI. Interventions targeting inflammation might improve outcomes of AKI.
Gestational exposure to the cannabinoid WIN 55,212-2 and its effect on the innate intestinal immune response
Authors: Hernández-Cervantes Rosalía , Pérez-Torres Armando , Prospéro-García Óscar , Morales Montor Jorge
Published: December 2019

The consequences of marijuana consumption during pregnancy and its effects on the function of the immune system have been little studied. Marijuana is one of the most consumed recreational drugs among pregnant women, and it is known that gestational exposure to marijuana can have serious effects on the offspring after birth. In this study, we challenged the immune system of Wistar rats by infecting them with the parasitic nematode Trichinella spiralis. A treatment group of these animals was prenatally exposed to the cannabinoid WIN 55,212-2; a control group was not exposed. At 5 days of infection, the treated animals were less effective in eliminating intestinal parasites; moreover, this effect was correlated with a deficiency in mucus production, lower recruitment of eosinophils in the duodenum, and a reduced percentage of Tγδ and NK cells. In conclusion, the gestational administration of the synthetic cannabinoid WIN 55,212-2 induces lasting changes to the function of the immune system against infection with T. spiralis in male Wistar rats, making them more susceptible to infection.
Hyperuniform disordered waveguides and devices for near infrared silicon photonics
Authors: Milošević Milan M. , Man Weining , Nahal Geev , Steinhardt Paul J. , Torquato Salvatore , Chaikin Paul M. , Amoah Timothy , Yu Bowen , Mullen Ruth Ann , Florescu Marian
Published: December 2019

We introduce a hyperuniform-disordered platform for the realization of near-infrared photonic devices on a silicon-on-insulator platform, demonstrating the functionality of these structures in a flexible silicon photonics integrated circuit platform unconstrained by crystalline symmetries. The designs proposed advantageously leverage the large, complete, and isotropic photonic band gaps provided by hyperuniform disordered structures. An integrated design for a compact, sub-volt, sub-fJ/bit, hyperuniform-clad, electrically controlled resonant optical modulator suitable for fabrication in the silicon photonics ecosystem is presented along with simulation results. We also report results for passive device elements, including waveguides and resonators, which are seamlessly integrated with conventional silicon-on-insulator strip waveguides and vertical couplers. We show that the hyperuniform-disordered platform enables improved compactness, enhanced energy efficiency, and better temperature stability compared to the silicon photonics devices based on rib and strip waveguides.