bluuebunny/crossref_metadata_2025 huggingface dataset:
Quasi Two‐, Three‐, and Six‐Day Planetary‐Scale Wave Oscillations in the Upper Atmosphere Observed by TIMED/SABER Over ~17 Years During 2002–2018
Authors: Liu Guiping , England Scott L. , Janches Diego
Published: October 2019

We present for the first time the global climatology of two‐, three‐, and six‐day planetary waves in the upper atmosphere using nearly 17 years of temperature observations by Thermosphere Ionosphere and Mesosphere Electric Dynamics/Sounding of the Atmosphere using Broadband Emission Radiometry (TIMED/SABER) during January 2002–December 2018. The observations span the altitude range ~30–110 km and are continuously available over 50°S–50°N latitudes throughout the time interval. The amplitudes and phases of the oscillations with periods in the ranges of 1.5–2.5, 2.5–3.5, and 5.5–6.5 days, and longitudinal zonal wave numbers of W3 (westward propagating wave number‐3) and E1 (eastward propagating wave number‐1) are determined from the two‐dimensional (2‐D) least squares analysis of the data. The study finds that the two‐day W3 waves can penetrate into the equatorial region, although they are mostly observed at higher latitudes. The three‐ and six‐day E1 waves are trapped at low latitudes, and their amplitudes vary with latitude following a Gaussian function with the maximum centered at the equator and the e‐folding width of 27° and 24° latitudes. In the equatorial region, the monthly mean amplitudes are ~3.8–4.8 K for the three‐day waves, and the two‐ and six‐day waves have relatively smaller amplitudes. The waves have the amplitude maximums around solstices and the minimums close to equinoxes. The peak amplitudes are larger during the solar maximum than during the solar minimum, and superimposed with the quasi two‐year cycle. The vertical wavelengths are approximately 30–40 km, suggesting the propagations to the equatorial upper atmosphere. The climatology revealed could be useful for general circulation models.
Characteristics and Sources of Hourly Trace Elements in Airborne Fine Particles in Urban Beijing, China
Authors: Cui Yang , Ji Dongsheng , Chen Hui , Gao Meng , Maenhaut Willy , He Jun , Wang Yuesi
Published: October 2019

To better investigate the characteristics and sources of trace elements (TEs) in PM2.5 in urban Beijing, a 1‐year hourly observation was continuously made using an online multi‐element analyzer from 1 June 2016 to 31 May 2017. The average concentrations of 14 individual TEs ranged from 1.1 (V) to 900 ng/m3 (K). The occurrence levels of most TEs of interest in Beijing were lower than those in most domestic cities, but higher than those in most foreign countries. The formation of sulfate increased with the concentrations of all studied TEs during autumn and winter. Dust, industry, biomass burning and waste incineration, vehicle emissions, coal combustion, and oil combustion were identified by the positive matrix factorization (PMF) model, which accounted for 36.3%, 10.7%, 27.1%, 13.7%, 7.6%, and 4.6%, respectively, of the total elements. All factors exhibited higher concentrations on weekends than on weekdays. Local vehicular emissions and industry contributed to the loading of TEs, but dust, biomass burning and waste incineration, coal combustion, and oil combustion from neighboring areas appeared to be dominant sources of TEs. Except for dust and industry, the four other sources of TEs were mainly located in the south and southeast areas of the sampling site. The analysis by conditional probability function and potential source contribution function showed that the distribution of the PMF sources of TEs roughly agreed with the location of the main point sources. Overall, this work provides more detailed information on the characteristics of the TEs for the scientific community and modelling work.
Three‐Dimensional Mapping of Lightning‐Produced Ionospheric Reflections
Authors: Malins J. B. , Obenberger K. S. , Taylor G. B. , Dowell J.
Published: October 2019

The powerful high‐frequency/very high frequency radio emissions that occur during lightning flashes can be used as a signal of opportunity to study the bottom side ionosphere. The lightning emission is bright, broad spectrum, and short in duration, providing an ideal signal of opportunity for making ionograms. This study continues previous work in Obenberger et al. (2018), where the direct line of sight signal from lightning can be cross correlated with megahertz frequency radio telescope observations to reveal ionogram traces created from the reflected lightning signals. This process was further developed to automate production of ionograms made from individual lightning flashes over the course of several hours, as well as create new techniques to detect the lightning signal using the all‐sky‐imaging mode. By using the Long Wavelength Array Sevilleta radio telescope as an interferometer, the point of reflection of the lightning signal for each frequency of the ionogram can be located in the ionosphere, instantaneously revealing density gradients within the ionosphere on minute time scales. We also explore the minimum size stations required for the application of this technique, which we found to be at least 32 antennas.
Syntheses, structures, anomalous phase transition and optical properties of two new polymorphic α- and β-LiMoPO6
Authors: Liu Haonan , Wu Hongping , Yu Hongwei , Hu Zhanggui , Wu Yicheng
Published: October 2019

Two new polymorphic α- and β-LiMoPO6 were synthesized, and they exhibit anomalous phase transition caused by the stretching of the [MoO3O3PO]∞ chain.
Expanstines A–D: four unusual isoprenoid epoxycyclohexenones generated byPenicillium expansumYJ-15 fermentation and photopromotion
Authors: Wang Jia-Peng , Shu Yan , Liu Shi-Xi , Hu Jun-Tao , Sun Cheng-Tong , Zhou Hao , Gan Dong , Cai Xue-Yun , Pu Wei , Cai Le , Ding Zhong-Tao
Published: October 2019

Expanstines A–D fromP. expansumYJ-15 were derived under UV and visible light from 4′-oxomacrophoin A (5) and its acetate (6), which plausibly underwent a rare intramolecular photoene reaction and a [2 + 2] Paternò–Büchi photoaddition respectively.
Enantioselective rearrangement of indolyl carbonates catalyzed by chiral DMAP-N-oxides
Authors: Shan Meng , Liang Tao , Zhang Ye-Fei , Xie Ming-Sheng , Qu Gui-Rong , Guo Hai-Ming
Published: October 2019

Bifunctional chiral DMAP-N-oxides, which utilize the oxygen atom as a nucleophilic site, have been reported for the highly enantioselective rearrangement of indolyl carbonates.
Additive manufactured dielectric Gutman lens
Authors: Bjorkqvist O. , Zetterstrom O. , Quevedo‐Teruel O.
Published: October 2019

In this Letter, the design of a 3D printed fully dielectric Gutman lens is presented. The authors demonstrate the feasibility of using highly accessible and cheap additive manufacturing technology to produce a compact and high performing antenna lens. The lens is designed to operate at band and utilises a flat feed surface that approximates the focal sphere. The flat feed surface allows for beam steering that requires only translational movement of the feed. The lens has a measured realised gain of 20 dBi with 3 dB scan loss at . The lens finds applications in systems that require high gain antennas, such as the new generation of satellite and 5G communications and radar technology.
Upper gastrointestinal anatomy detection with multi‐task convolutional neural networks
Authors: Xu Zhang , Tao Yu , Wenfang Zheng , Ne Lin , Zhengxing Huang , Jiquan Liu , Weiling Hu , Huilong Duan , Jianmin Si
Published: October 2019

Esophagogastroduodenoscopy (EGD) has been widely applied for gastrointestinal (GI) examinations. However, there is a lack of mature technology to evaluate the quality of the EGD inspection process. In this Letter, the authors design a multi‐task anatomy detection convolutional neural network (MT‐AD‐CNN) to evaluate the EGD inspection quality by combining the detection task of the upper digestive tract with ten anatomical structures and the classification task of informative video frames. The authors’ model is able to eliminate non‐informative frames of the gastroscopic videos and detect the anatomies in real time. Specifically, a sub‐branch is added to the detection network to classify NBI images, informative and non‐informative images. By doing so, the detected box will be only displayed on the informative frames, which can reduce the false‐positive rate. They can determine the video frames on which each anatomical location is effectively examined, so that they can analyse the diagnosis quality. Their method reaches the performance of 93.74% mean average precision for the detection task and 98.77% accuracy for the classification task. Their model can reflect the detailed circumstance of the gastroscopy examination process, which shows application potential in improving the quality of examinations.
Automatic detection of calcium phosphate deposit plugs at the terminal ends of kidney tubules
Authors: Fernandez Katrina , Korinek Mark , Camp Jon , Lieske John , Holmes David
Published: October 2019

Kidney stones are a common urologic condition with a high amount of recurrence. Recurrence depends on a multitude of factors the incidence of precursors to kidney stones, plugs, and plaques. One method of characterising the stone precursors is endoscopic assessment, though it is manual and time‐consuming. Deep learning has become a popular technique for semantic segmentation because of the high accuracy that has been demonstrated. The present Letter examined the efficacy of deep learning to segment the renal papilla, plaque, and plugs. A U‐Net model with ResNet‐34 encoder was tested; the Letter examined dropout (to avoid overtraining) and two different loss functions (to address the class imbalance problem. The models were then trained in 1666 images and tested on 185 images. The Jaccard‐cross‐entropy loss function was more effective than the focal loss function. The model with the dropout rate 0.4 was found to be more effective due to its generalisability. The model was largely successful at delineating the papilla. The model was able to correctly detect the plaques and plugs; however, small plaques were challenging. Deep learning was found to be applicable for segmentation of an endoscopic image for the papilla, plaque, and plug, with room for improvement.
Two‐ and three‐winding coupled‐inductor‐based high step‐up DC–DC converters for sustainable energy applications
Authors: Eskandarpour Azizkandi Mahmoodreza , Sedaghati Farzad , Shayeghi Hossein , Blaabjerg Frede
Published: October 2019

This study proposes two configurations for a non‐isolated, high step‐up, single‐switch, coupled‐inductor‐based DC–DC converter. A coupled inductor and voltage multiplier cells are used in the presented topologies to obtain a high voltage gain. Also, a passive clamp circuit is applied in the topologies to reduce voltage stress of the main power switch. This leads to utilising a power switch with lower on‐state resistance, which decreases the conduction loss. Several advantages such as low operating duty cycle, high voltage conversion ratio, reduced voltage stress of semiconductors, low turn ratio of the coupled inductor, leakage inductance energy recovery and high efficiency operation make the presented structures appropriate for sustainable energy applications. The operational principle and steady‐state analysis of the suggested topologies in continuous conduction mode are expressed in detail. Also, design procedure and theoretical efficiency of the topologies are presented. Then, the suggested topologies are compared with several similar high step‐up topologies to prove their advantages. Finally, the performance and feasibility of the proposed DC–DC converter configurations are confirmed through experimental measurement results of 29 V input and 435 V/213 W and 480 V/238 W output laboratory prototypes at 50 kHz switching frequency.
Current‐source mode switched‐capacitor power converters with improved current gain capability
Authors: Sun Jin Hong , Cheng Ka Wai Eric
Published: October 2019

A new family of current‐source (CS) mode switched‐capacitor (SC) power converters has been proposed in this study, which imposes an alternative solution for power converters especially for CS systems. The conversion ratio of this type converter is analysed and verified here to have one increased degree of freedom using the switching mode and the capacitor‐tapping mode, which is a good solution to deal with the limitation of duty cycle adjustment. This research improves the CS mode system that is relatively unexplored in previous works and the proposed work fills the research gap by the sides of the well‐established voltage‐source (VS) system. An interesting power conversion ratio formulation is obtained, which can produce the wide range of conversion ratio of VS mode switched‐inductor power converters and CS mode SC power converters in buck, boost and buck–boost versions. In addition, this proposed CS mode SC power converters have high efficiency of power conversion through simulation and prototype experiments verification. These CS mode converters can flexibly supply power directly to the load powered by the CS and successfully replace the VS mode converters operated under the current environment system.
Quantitative assessment of effective regurgitant orifice: impact on risk stratification, and cut-off for severe and torrential tricuspid regurgitation grade
Authors: Peri Yogev , Sadeh Ben , Sherez Chen , Hochstadt Aviram , Biner Simon , Aviram Galit , Ingbir Meirav , Nachmany Ido , Topaz Guy , Flint Nir , Keren Gad , Topilsky Yan
Published: October 2019

Aims 

Asses the added value of quantitative evaluation of tricuspid regurgitation (TR), the proper cut-off value for severe TR and ‘torrential TR’ based on outcome data. The added value of quantitative evaluation of TR, and the cut-off values associated with increased mortality are unknown.

Methods and results

In patients with all-cause TR assessed both qualitatively and quantitatively by proximal iso-velocity surface area method, long-term and 1-year outcome analysis was conducted. Thresholds for excess mortality were assessed using spline curves, receiver-operating characteristic curves, and minimum P-value analysis. The study involved 676 patients with all-cause TR (age 73.9 ± 14 years, male 45%, ejection fraction 52.9 ± 14%). Effective regurgitant orifice (ERO) was strongly associated with decreased survival in unadjusted [hazard ratio (HR) 2.38 (1.79–3.01), P < 0.0001 per 0.1 cm2 increment] and adjusted [2.6 (1.25–5.0), P = 0.01] analyses. Quantitative grading was superior to qualitative grading in prediction of outcome (P < 0.01). The optimal cut-off value for the best separation in survival between groups of patients with severe vs. lesser degree of TR was 0.35 cm2 [P < 0.0001, HR =2.0 (1.5–2.7)]. ERO negatively impacted survival, even when including only the subgroup of patients with severe TR [HR 1.5 (1.01–2.3); P = 0.04]. The optimal threshold corresponding for the best separation for survival between groups of patients with severe vs. ‘torrential’ TR was 0.7 cm2 [P = 0.005, HR =2.6 (1.2–5.1)].

Conclusion 

TR can be severe and even ‘torrential’ and is associated with excess mortality. Quantitative assessment of TR by ERO measurement is a powerful independent predictor of outcome, superior to standard qualitative assessment. The optimal cut-off above which mortality is increased is 0.35 cm2, similar albeit slightly lower than suggested in recent guidelines. Torrential TR >0.7 cm2 is associated with poorer survival compared to patients with severe TR (ERO > 0.4 cm2 and <0.7 cm2).
Matrix-Delivered Autologous Mesenchymal Stem Cell Therapy for Refractory Rectovaginal Crohn’s Fistulas
Authors: Lightner Amy L , Dozois Eric J , Dietz Allan B , Fletcher Joel G , Friton Jessica , Butler Greg , Faubion William A
Published: October 2019

Background

Crohn’s rectovaginal fistulizing disease remains notoriously difficult to treat. A phase I clinical trial to evaluate the safety and feasibility of a novel protocol using a mesenchymal stem cell (MSC)–coated Gore Bio-A fistula plug for the treatment of medically and surgically refractory Crohn’s rectovaginal fistulas was conducted.

Methods

Five patients underwent an autologous subcutaneous adipose tissue harvest via a 2-cm abdominal wall incision at time of exam under anesthesia (EUA) with seton placement. MSCs were isolated, expanded, and impregnated on the plug. After 6 weeks, patients returned to the operating room for placement of the MSC-coated plug. The primary end points were safety and feasibility; the secondary end point was clinical and radiographic healing at 6 months.

Results

Five female patients (median age [range], 49 [38–53] years) with a median disease duration (range) of 23 (7–34) years who were on biologic (n = 5) or combination therapy (n = 3) had successful harvest and expansion of MSCs and delivery of the Gore Bio-A plug. There were no serious adverse events or adverse events related to the MSCs or plug during the 6-month follow-up. At 6 months, 3 patients had complete cessation of drainage, and 2 had >50% reduction in drainage; all had a persistent fistula tract identified on magnetic resonance imaging and EUA at 6 months.

Conclusions

Surgical placement of an autologous adipose-derived MSC-coated fistula plug in diverted patients with Crohn’s rectovaginal fistulas was safe and feasible. All patients had a reduction in the size of their fistula tract, and 3 of 5 had cessation of drainage, but none achieved complete healing.

This was a phase I clinical trial of autologous mesenchymal stem cells on a plug for rectovaginal Crohn’s fistulas.
Intraoperative cell salvage use reduces the rate of perioperative allogenic blood transfusion in patients undergoing periacetabular osteotomy
Authors: van der Merwe Michael , Lightfoot Nicholas J , Munro Jacob T , Boyle Matthew J
Published: October 2019

Blood loss during periacetabular osteotomy (PAO) is variable, with losses ranging from 100 to 3900 ml in published series. Perioperative allogenic blood transfusion is frequently utilized although is associated with significant risk of morbidity. Cell salvage (CS) is a common blood conservation tool; however, evidence supporting its use with PAO is lacking. Our aim was to assess whether CS affects perioperative allogenic blood transfusion rate in patients undergoing PAO. The clinical records of 58 consecutive PAOs in 54 patients (median age 24.7 years, interquartile range 17.8–29.4 years) performed by a single surgeon between 1 January 2016 and 30 April 2018 were reviewed. Autologous blood pre-donation and surgical drains were not used. Due to variable technician availability, CS was intermittently used during the study period. PAOs were allocated into a CS group or no cell salvage group (NCS group), according to whether an intraoperative CS system was used. There was no significant difference in patient age, gender, body mass index, dysplasia severity, regional anesthetic technique, tranexamic acid administration, surgical duration or estimated blood loss (all P > 0.05) between the two groups. The CS group had a lower preoperative hemoglobin compared to the NCS group (median, 13.4 g/dl versus 14.4 g/dl, P = 0.006). The incidence of allogenic blood transfusion was significantly lower in the CS group compared to the NCS group (2.5% versus 33.3% patients transfused, P = 0.003). Multivariate modeling showed CS use to be protective against allogenic blood transfusion (P = 0.003), with an associated 80-fold reduction in the odds of transfusion (odds ratio, 0.01; 95th% CI, 0–0.57). To our knowledge, this is the first study to assess the effect of CS use on allogenic transfusion rate in patients undergoing PAO. Our results demonstrate CS to be a mandatory component of blood conservation for all patients undergoing PAO.
The Resilience Songwriting Program for Adolescent Bereavement: A Mixed Methods Exploratory Study
Authors: Myers-Coffman Katherine , Baker Felicity A , Daly Brian P , Palisano Robert , Bradt Joke
Published: October 2019

Music therapy research with youth who are grieving often reports on a combination of interventions, such as lyric analysis, improvisation, and/or songwriting. Unfortunately, the lack of theoretical transparency in how and why these interventions affect targeted outcomes limits interpretation and application of this important research. In this exploratory study, the authors evaluated the impact of an 8-session, theory-driven group songwriting program on protective factors in adolescent bereavement, and also sought to better understand adolescents' experiences of the program. Using a single-group, pretest-posttest convergent mixed methods design, participants were enrolled from three study sites and included 10 adolescents (five girls and five boys), ages 11–17 years, who self-identified as grieving a loss. Outcomes measured included grief, coping, emotional expression, self-esteem, and meaning making. Qualitative data were captured through in-session journaling and semi-structured interviews. There were no statistically significant improvements for grief, self-esteem, coping, and meaning making. Individual score trends suggested improvements in grief. The majority of the participants reported greater inhibition of emotional expression, and this was statistically significant. Thematic findings revealed that the program offered adolescents a sense of togetherness, a way to safely express grief-related emotions and experiences verbally and nonverbally, and opportunities for strengthening music and coping skills. These findings suggest that engaging in collaborative therapeutic songwriting with grieving peers may decrease levels of grief, enhance creative expression, and provide social support. More research is needed on measuring self-esteem, emotional expression, coping, and meaning making outcomes in ways that are meaningful to adolescents.
An ALMA survey of the SCUBA-2 Cosmology Legacy Survey UKIDSS/UDS field: high-resolution dust continuum morphologies and the link between sub-millimetre galaxies and spheroid formation
Authors: Gullberg B , Smail Ian , Swinbank A M , Dudzevičiūtė U , Stach S M , Thomson A P , Almaini O , Chen C C , Conselice C , Cooke E A , Farrah D , Ivison R J , Maltby D , Michałowski M J , Simpson J M , Scott D , Wardlow J L , Weiss A
Published: October 2019

We present an analysis of the morphology and profiles of the dust continuum emission in 153 bright sub-millimetre galaxies (SMGs) detected with ALMA at signal-to-noise ratios of >8 in high-resolution 0.18 arcsec (∼1 kpc) 870 $\mu$m maps. We measure sizes, shapes, and light profiles for the rest-frame far-infrared emission from these luminous star-forming systems and derive a median effective radius (Re) of 0.10 ± 0.04 arcsec for our sample with a median flux of S870 = 5.6 ± 0.2 mJy. We find that the apparent axial ratio (b/a) distribution of the SMGs peaks at b/a ∼ 0.63 ± 0.02 and is best described by triaxial morphologies, while their emission profiles are best fitted by a Sérsic model with n ≃ 1.0 ± 0.1, similar to exponential discs. This combination of triaxiality and n ∼ 1 Sérsic index are characteristic of bars and we suggest that the bulk of the 870 $\mu$m dust continuum emission in the central ∼2 kpc of these galaxies arises from bar-like structures. As such we caution against using the orientation of shape of the bright dust continuum emission at $\eqsim$ resolution to assess either the orientation of any disc on the sky or tits inclination. By stacking our 870 $\mu$m maps we recover faint extended dust continuum emission on ∼4 kpc scales which contributes 13 ± 1 per cent of the total 870 $\mu$m emission. The scale of this extended emission is similar to that seen for the molecular gas and rest-frame optical light in these systems, suggesting that it represents an extended dust and gas disc at radii larger than the more active bar component. Including this component in our estimated size of the sources we derive a typical effective radius of ≃0.15 ± 0.05 arcsec or 1.2 ± 0.4 kpc. Our results suggest that kpc-scale bars are ubiquitous features of high star-formation rate systems at $z$ ≫ 1, while these systems also contain fainter and more extended gas and stellar envelopes. We suggest that these features, seen some 10–12 Gyr ago, represent the formation phase of the earliest galactic-scale components: stellar bulges.
Spin evolution and feedback of supermassive black holes in cosmological simulations
Authors: Bustamante Sebastian , Springel Volker
Published: October 2019

It is well established that the properties of supermassive black holes (BHs) and their host galaxies are correlated through scaling relations. While hydrodynamical cosmological simulations have begun to account for the coevolution of BHs and galaxies, they typically have neglected the BH spin, even though it may play an important role in modulating the growth and feedback of BHs. Here we introduce a new sub-grid model for the BH spin evolution in the moving-mesh code arepo in order to improve the physical faithfulness of the BH modelling in galaxy formation simulations. We account for several different channels of spin evolution, in particular gas accretion through a Shakura–Sunyaev α-disc, chaotic accretion, and BH mergers. For BH feedback, we extend the IllustrisTNG model, which considers two different BH feedback modes, a thermal quasar mode for high accretion states and a kinetic mode for low Eddington ratios, with a self-consistent accounting of spin-dependent radiative efficiencies and thus feedback strength. We find that BHs with a mass $M_{\mbox{{bh}}}\lesssim 10^{8}\, {\rm M}_{\odot }$ reach high spin values as they typically evolve in the coherent gas accretion regime, in which consecutive accretion episodes are aligned. On the other hand, BHs with a mass $M_{\mbox{{bh}}}\gtrsim 10^{8}\, {\rm M}_{\odot }$ have lower spins as BH mergers become more frequent, and their accretion discs fragment due to self-gravity, inducing chaotic accretion. We also explore the hypothesis that the transition between the quasar and kinetic feedback modes is mediated by the accretion mode of the BH disc itself, i.e. the kinetic feedback mode is activated when the disc enters the self-gravity regime instead of by an ad hoc switch tied to the BH mass. We find excellent agreement between the galaxy and BH populations for this approach and the fiducial TNG model with no spin evolution. Furthermore, our new approach alleviates a tension in the galaxy morphology–colour relation of the original TNG model.
The VMC survey – XXXV. model fitting of LMC Cepheid light curves
Authors: Ragosta Fabio , Marconi Marcella , Molinaro Roberto , Ripepi Vincenzo , Cioni Maria Rosa L , Moretti Maria Ida , Groenewegen Martin A T , Choudhury Samyaday , de Grijs Richard , van Loon Jacco Th , Oliveira Joana M , Ivanov Valentin D , Gonzalez-Fernandez Carlos
Published: October 2019

We present the results of the light curve model fitting technique applied to optical and near-infrared photometric data for a sample of 18 Classical Cepheids (11 fundamentals and 7 first overtones) in the Large Magellanic Cloud (LMC). We use optical photometry from the OGLE III data base and near-infrared photometry obtained by the European Southern Observatory public survey ‘VISTA near-infrared survey of the Magellanic Clouds system’. Iso-periodic non-linear convective model sequences have been computed for each selected Cepheid in order to reproduce the multifilter light-curve amplitudes and shape details. The inferred individual distances provide an intrinsic weighted mean value for the LMC distance modulus of μ0 = 18.56 mag with a standard deviation of 0.13 mag. We derive also the Period–Radius, the Period–Luminosity, and the Period–Wesenheit relations that are consistent with similar relations in the literature. The intrinsic masses and luminosities of the best-fitting models show that all the investigated pulsators are brighter than the predictions of the canonical evolutionary mass–luminosity relation, suggesting a significant efficiency of non-canonical phenomena, such as overshooting, mass-loss, and/or rotation.
Generative deep fields: arbitrarily sized, random synthetic astronomical images through deep learning
Authors: Smith Michael J , Geach James E
Published: October 2019

Generative adversarial networks (GANs) are a class of artificial neural network that can produce realistic, but artificial, images that resemble those in a training set. In typical GAN architectures these images are small, but a variant known as Spatial GANs (SGANs) can generate arbitrarily large images, provided training images exhibit some level of periodicity. Deep extragalactic imaging surveys meet this criteria due to the cosmological tenet of isotropy. Here we train an SGAN to generate images resembling the iconic Hubble Space Telescope eXtreme Deep Field (XDF). We show that the properties of ‘galaxies’ in generated images have a high level of fidelity with galaxies in the real XDF in terms of abundance, morphology, magnitude distributions, and colours. As a demonstration we have generated a 7.6-billion pixel ‘generative deep field’ spanning 1.45 deg. The technique can be generalized to any appropriate imaging training set, offering a new purely data-driven approach for producing realistic mock surveys and synthetic data at scale, in astrophysics and beyond.
Life in the fast lane: a direct view of the dynamics, formation, and evolution of the Milky Way’s bar
Authors: Bovy Jo , Leung Henry W , Hunt Jason A S , Mackereth J Ted , García-Hernández Domingo A , Roman-Lopes Alexandre
Published: October 2019

Studies of the ages, abundances, and motions of individual stars in the Milky Way provide one of the best ways to study the evolution of disc galaxies over cosmic time. The formation of the Milky Way’s barred inner region in particular is a crucial piece of the puzzle of disc galaxy evolution. Using data from APOGEE and Gaia, we present maps of the kinematics, elemental abundances, and age of the Milky Way bulge and disc that show the barred structure of the inner Milky Way in unprecedented detail. The kinematic maps allow a direct, purely kinematic determination of the bar’s pattern speed of $41\pm 3\, \mathrm{km\, s}^{-1}\, \mathrm{kpc}^{-1}$ and of its shape and radial profile. We find the bar’s age, metallicity, and abundance ratios to be the same as those of the oldest stars in the disc that are formed in its turbulent beginnings, while stars in the bulge outside of the bar are younger and more metal-rich. This implies that the bar likely formed ${\approx}8\, \mathrm{Gyr}$ ago, when the decrease in turbulence in the gas disc allowed a thin disc to form that quickly became bar-unstable. The bar’s formation therefore stands as a crucial epoch in the evolution of the Milky Way, a picture that is in line with the evolutionary path that emerges from observations of the gas kinematics in external disc galaxies over the last ${\approx}10\, \mathrm{Gyr}$.
A mechanically-engineered spray to increase brain penetration of chemotherapeutic nanoparticles in the treatment of high-grade gliomas
Authors: McCrorie Phoebe , Taresco Vincenco , Xu Zeyuan , Ritchie Alison , Clarke Phillip , Marlow Maria , Rahman Ruman
Published: October 2019

Design and implementation of innovative local drug delivery systems (DDS) may overcome current limitations in GBM treatment, such as the lack of therapeutic drug concentrations reaching residual GBM cells following surgery.

Here we describe a novel DDS which utilises a bespoke mechanically engineered spray device, designed for safe surgical use, to deliver a mucoadhesive hydrogel containing chemotherapeutic nanoparticles (NPs) into the tumour resection margins. The overall aim is to spray a NP and polymer solution onto the resection cavity and potentially increase penetration of anti-cancer drugs within the 2 cm reoccurrence zone beyond the infiltrative margin.

The mucoadhesive gel of choice, pectin, is currently used in other in vivo applications; however we have repurposed this for the brain. Pectin is biocompatible with GBM and human astrocyte cells in vitro and showed neither toxicity nor inflammation for up to 2 weeks upon orthotopic brain injection. Pectin is biodegradable in artificial CSF and is capable of being sprayed from the engineered device.

A panel of polymeric, oil-based and polymer-coated NPs have been developed and optimised to maximise drug encapsulation of etoposide and olaparib as proof-of-concept for combination drug delivery. Etoposide/olaparib was chosen due to cytotoxicity from 5 GBM cell lines, including primary lines isolated from the invasive tumour margin (Mean IC50 of 1.1 µM and 8.3 µM respectively). The optimal NP/drug formulation (based on drug encapsulation, spray capability and bio-adhesiveness) will ultimately be assessed for tolerability and efficacy using orthotopic allograft and xenograft high-grade glioma models.
Identifying the Zika Virus Target Cell in Malignant Glioma
Authors: Girdler Gemma , Gracia Tannia , Fountain Daniel , Fajardo Jr Ted , Finlay Jack , Hallou Clément , Pollard Steve , Sweeney Trevor , Gergely Fanni , Rowitch David , Bulstrode Harry
Published: October 2019

The Zika Virus epidemic of 2015–2016 was associated with striking failure of forebrain development in infants born to infected mothers, resulting in microcephaly. Studies from numerous labs subsequently confirmed a selective effect of the virus on neural stem cell survival, self-renewal and differentiation. The glioma stem cells which drive glioblastoma and other malignant gliomas depend on neural stem cell transcription programs, so that understanding Zika infection in these cells promises valuable insights into future therapy. We describe here:

1) Study of low passage patient-derived glioblastoma cell lines and normal neural stem cells (CRUK Glioma Cellular Genetics Resource) in adherent culture to address the influence of glioma subtype on infectability

2) Application of genetically modified mCherry reporter Zika Virus strains to address the Zika target cell in glioblastoma.

3) Development of a cerebral organoid model to interrogate the differential effects of the virus on tumour cells and surrounding normal brain.

4) Demonstration of Zika infection on primary patient derived tissue in slice culture format

Using these tools we find that Zika targets a common stem cell population across tumour subtypes and neural stem cell controls, and in embryonic and primary tumour explants, and that infection is influenced by activity of cholesterol biosynthesis pathways.
Using DWI-MRI parameters from multi- B values acquisition and a histogram approach for assessment of early therapeutic response in glioblastoma
Authors: Islam Shah , Morrison Melanie , Orton Matthew , Grech-Sollars Matthew , Waldman Adam
Published: October 2019

Early evaluation of therapeutic response of GBM on imaging is limited by poor biological specificity of clinical MRI. Clinical DWI-MRI models assume diffusion is mono-exponential when derived from only two B-values, although it has been proven diffusion is multiexponential. Purpose: To assess the utility of quantitative diffusion MRI derived from multi B-value acquisitions in the assessment of treatment response. Methods: 13 patients were enrolled into our multicentre study. Imaging was performed pre-RT and mid-RT using a multi B-value acquisition. Histograms within ROIs defined by abnormal FLAIR signal. Changes in histogram percentile profiles were evaluated across the two timepoints and compared with RANO assessment. Results: Following treatment, 5 patients had PD, 4 SD and 4 CR. Patients with PD showed a histogram shift to the left across all models, in keeping with increased cellularity. Parameters DDC and f are the most predictive of PD against RANO assessment, and appear superior to ADC. Reduction in 75th centile (f) and 95th centile (DDC) are the most sensitive histogram metrics for predicting early PD. Discussion: This is the first study to use histogram analysis as a marker of early treatment response in GBM. Results suggest association between early changes in specific diffusion components and subsequent treatment response. Spatially-independent diffusion parameter comparisons provide unbiased sampling of tumour heterogeneity. Conclusion: Our preliminary data suggest differential changes in diffusion parameters early in treatment, and provide proof of principle for multi B-value analysis and spatially-independent longitudinal assessment of diffusion imaging for therapeutic assessment in GBM.
Management Evaluation of Metastasis in the Brain (MEMBRAIN) – A UK & Ireland prospective, multicentre observational study
Authors: Jung Josephine , Tailor Jignesh , Dalton Emma , J Glancz Laurence , Roach Joy , Zakaria Rasheed , P Lammy Simon , Chari Aswin , P Budohoski Karol , J Livermore Laurent , Yu Kenny , D Jenkinson Michael , M Brennan Paul , Brazil Lucy , Bunce Catey , Ashkan Keyoumars , Vergani Francesco
Published: October 2019

Background

Over the recent years an increasing number of patients with brain metastasis are being referred to the neuro-oncology multi-disciplinary team (NMDT). Our aim was to determine if referrals of this group of patients to the NMDT in the UK & Ireland comply with NICE guidelines and to assess referral volume, quality of information provided and its impact on NMDT decision-making.

Methods

Prospective multicentre oberservational study including all adult patients referred with ≥1 cerebral metastasis. Data was collected in neurosurgical units from 11/2017 to 02/2018. Demographics, primary disease, Karnofsky performance status (KPS), imaging and treatment recommendation were entered into an online database.

Results

1049 patients were analysed from 24 neurosurgical units. Median age was 63[range 21–93] years with a median number of 3[range 1–17] referrals per NMDT. The most common primary malignancies were lung (36.5%, n=383), breast (18.5%, n=194) and melanoma (12.0%, n=126). 51.6% (n=541) of the referrals to the NMDT were within the NICE 2006 guidelines, and resulted in specialist intervention being offered in 68.8%. 41.2% (n=197) of patients being referred outside of the NICE 2006 guidelines were offered specialist treatment. NMDT decision-making was influenced by number of metastases, age, KPS, primary disease status and extent of extracranial disease (univariate logistic regression, p<0.0001) as well as metastasis location/histology (p<0.05).

Conclusions

This study confirmed a national change in culture of referral patterns. We identified a delay in NMDT decision-making in ~20%, contributing to increased NMDT workload. New stratification tools may be needed to reflect advancements in diagnostics and treatment modalities.
Chromatin remodelling to facilitate treatment resistance in glioblastoma
Authors: Bruns Alexander-F , Rippaus Nora , Droop Alastair , Al-Jabri Muna , Care Matthew , Jenkinson Michael , Brodbelt Andrew , Chakrabarty Aruna , Ismail Azzam , Short Susan , F Stead Lucy
Published: October 2019

Recent findings from our group, and the wider community, show that standard treatment does not impose an apparent bottleneck on the clonal evolution of adult glioblastoma (GBM), implying a lack of direct therapeutic opportunity. This does not negate the possibility that multiple treatment-resistance mechanisms co-exist in tumours, repeated across patients, making a combination of targeted therapies a potentially effective approach. We investigated whether treatment resistance may be driven by selection of cellular properties conferred above the level of the genome. Differential expression analysis was performed on 23 pairs of primary and recurrent tumours from patients who received standard treatment and had a local recurrence treated by surgery and second line chemotherapy. This revealed a treatment-induced shift in cell states linked to normal neurodevelopment. The latter is orchestrated by cascades of transcription factors. We, therefore, applied a bespoke gene set enrichment analysis to our paired expression data to investigate whether any factors were implicated in co-regulation of the genes that were altered through therapy. This identified a specific chromatin remodelling machinery, instrumental in normal neurogenesis. We validated our results in an independent cohort of 22 paired GBM samples. Our results suggest that the chromatin remodelling machinery is responsible for determining transcriptional hierarchies in GBM, shown elsewhere to have different treatment sensitivities such that their relative abundances are altered through treatment.
Identifying novel molecular differences between WHO grade I and II meningiomas
Authors: Sofela Agbolahan (Boh) , Hanemann Oliver
Published: October 2019

Background

With the increasing emphases on the integrated histo-pheno-genotypical diagnoses of central nervous system (CNS) tumours, there is a pressing need for the identification of biomarkers to aid in the clinical management, diagnosis, prognosis and follow-up of meningiomas too. WHO grade II meningiomas remain a very controversial group of CNS tumours to diagnose/treat, compared to the more prevalent and extensively researched grade I tumours.

Typical clinical scenarios include; the serum diagnosis of conservatively managed tumours, follow-up of surgically managed patients and prognostication, for predicting grade progression. We herein describe the identification of novel biomolecular differences between grade I and II meningiomas.

Aim

To identify biomarkers unique to grade II meningiomas (versus grade I) and describe their potential use in typical clinical scenarios.

Methods

Unbiased global proteomic analyses of four grade I & II primary-meningioma cells were carried out to identify proteins differentially expressed between both grades.

Differential expression and statistical analyses were performed using Perseus and Microsoft Excel.

The significantly differentially expressed proteins were validated by Western blot, IHC and ELISA, using tumour tissue and primary cells.

Results

We identified 3553 proteins commonly expressed in both meningioma grades. Further analysis revealed that 86 of these were significantly differentially up/down-regulated.

Initial validation studies on some of the most promising candidates have confirmed these patterns of expressions between the two tumour grades.

Conclusion

There is a need for the identification of grade II biomarkers. The initial findings of this study have identified novel biomolecular differences between grade I/II meningiomas that can potentially aid in the aforementioned typical clinical scenarios.
Defining the Speech and Language Therapist role in palliative care of neuro-oncology patients: A qualitative research study.
Authors: Evans Rachel , Longo Mirella , Nelson Annmarie
Published: October 2019

Speech and language therapists (SLTs) are experts in the management of swallowing and communication disorders. Although there is increasing recognition of SLTs in palliative care, evidence specifically supporting their role with primary malignant gliomas (PMG) patients is lacking, despite the prevalence of swallowing and communication difficulties in this non-curable disease. This study aimed to explore the contribution of SLT to PMG, as perceived by SLTs themselves and by members of the regional neuro-oncology multidisciplinary team (MDT).

Following ethical approval, semi-structured one-to-one interviews were conducted with ten SLTs working with PMG in outpatients and community settings across South East Wales. In addition, five members of the regional neuro-oncology MDT were interviewed. Thematic analysis was used to analyse the data and to identify and pinpoint salient themes.

The findings indicate that despite lack of professional guidance and previous evidence, SLTs provided evidence to suggest that they contribute beyond swallowing and communication management, to areas such as shared decision-making, key-working, patient advocacy, advanced care planning and support for psychological wellbeing. However, these extended roles are inconsistently recognised by the MDT. Five barriers were identified which hampered SLT contributions: a perceived identity crisis affecting PMG patients, lack of confidence from SLTs, inconsistent MDT integration, reduced resources and strategic direction. The study suggests that SLTs need to promote and educate the MDT in order to achieve routine integration and enhance patient-centred and holistic care. The profession may also benefit from capturing the value of their involvement with PMG to drive service developments.
A service improvement project exploring the extent of need for allied health care professionals within neuro-oncology in Velindre Cancer Centre.
Authors: Evans Rachel , Williams Hayley , Love-Gould Lisa , Tilsley Owen , Powell James , Burke Rhian , Sahar Iqbal Najmus , Johnson Karen , Pearce Siobhan , Williams Rhiannon , Halon Elizabeth , Evans Callum
Published: October 2019

Given the highly complex and holistic needs of neuro-oncology patients, gold standard guidelines recommend that support is best served by a coordinated multi-disciplinary team (MDT) to provide seamless care from diagnosis to end of life (NICE 2018). Allied Healthcare Professionals (AHPs) including occupational therapy (OT), physiotherapy (PT), speech and language therapy (SLT) and dietitians (DT) are recognised as key professions within the MDT. As there is no designated AHP team at Velindre Cancer Centre, input can be reactive and fragmented with limited opportunity for patient education or service developments.

The aim of the project was to scope and evaluate the level of AHP need the neuro-oncology population attending Velindre Cancer Centre. A service improvement grant funded a Band 4 Therapies support worker to conduct the project. The project involved a number of elements including the implementation of a revised neuro-oncology screening tool, strategic effort to improve patient education and self-management and engaging patients and staff to guide future service developments. The mixed methods approach yielded rich quantitative and qualitative data.

The results demonstrated that whilst AHP input was beneficial to patient care, significant unmet needs were highlighted and demands for services exceeded the teams’ capacity. Therefore a designated neuro-oncology therapies team should be a central consideration for future care to enable timely, responsive, equitable and seamless MDT working. Greater AHP resource would also enable greater AHP involvement in research and education to revolutionise care in order to fully meet the needs of this vulnerable and complex patient group.
Ketogenic diets as an adjuvant therapy in glioblastoma (KEATING): A mixed methods randomised feasibility study
Authors: Martin-McGill Kirsty , Cherry Gemma , Marson Anthony , Tudur Smith Catrin , Young Bridget , Jenkinson Michael
Published: October 2019

Background

There is increasing interest in the use of ketogenic diets (KD) as adjuvant therapy for glioblastoma (GBM). Trial aims: i) investigate protocol feasibility; ii) assess patient/carer acceptability; iii) explore the decision-making of patients’ invited to participate in KEATING; and iv) inform phase III trial design.

Methods

Prospective, feasibility study, with embedded qualitative design randomised 12 newly-diagnosed GBM patients to three months of medium chain triglyceride ketogenic diet (MCTKD) or the modified ketogenic diet (MKD) during chemoradiotherapy. Primary outcome was retention; secondary outcomes included recruitment rate, dietary acceptability, progression free survival (PFS) and overall survival (OS). Semi-structured interviews were conducted with a representative sample of patients and relatives (n=15).

Results

Recruitment targets were achieved, but recruitment rate was low (28.6%). Retention was poor; only 4 of 12 completed the three-month diet (MCTKD n=3; MKD n=1). Median duration until discontinuing was 5.2 weeks (0–7 weeks; n=8). Participants made instantaneous decisions without deliberation: relatives supported diet implementation. Decliners made considered decisions factoring diet burden and quality of life. A three-month diet was undesirable to these patients. Median PFS was 11.4 weeks and OS was 67.3 weeks.

Conclusion

Recruitment to a ketogenic-glioblastoma trial is possible. To assess effectiveness in a phase III clinical trial, a six week intervention period is proposed. Future trials should optimise and adequately support the decision-making of patients. The role of relatives should not be underestimated.