bluuebunny/crossref_metadata_2025 huggingface dataset:
Enhanced third-harmonic generation from layered graphene/insulator disks array
Authors: Liu Jian-Qiang , Fang Jiang-Nan , Wang Dian Yuan , Chen San , He Meng-Dong
Published: October 2020

The non-linear responses of optical materials offer useful mechanisms for optical switching, novel optical sources, and harmonic frequency conversion. However, the non-linear response of traditional materials is usually extremely weak and requires high input power for excitation. In this study, we theoretically propose a scheme for enhancing the third harmonic generation (THG) efficiency and output power of layered graphene disks array by introducing a plasmonic antibonding state with enhanced oscillation strength due to plasmonic coupling. We verify that, the THG efficiency of a double-layer stacked graphene/SiO2 disk structure under relatively low input intensity can be significantly enhanced more than one order of magnitude with appropriate design, as compared with monolayer patterned graphene nanostructure. We also demonstrate that the THG efficiency can be further improved by optimizing the geometry parameters such as spacer distance and Fermi energy. Our results offer an effective mechanism for significantly improving THG efficiency in the mid-infrared and terahertz ranges, thereby paving the way for new frequency converters and modulators in optical communication and signal processing.
Coherent terahertz emission from free-electron-driven Fabry–Pérot resonators with coupled grooves
Authors: Liu Weihao , Zhang Liwen , Yu Zijia , Liu Yucheng , Li Weiwei , Jia Qika , Sun Baogen , Xu Hongliang , Liu Wenxin
Published: October 2020

Fabry–Pérot (FP) resonators with metallic subwavelength grooves or holes, which have been extensively applied in optical region, have recently attracted increasing interest for terahertz wave generation and manipulation. However, the practices of such resonators in the terahertz region are greatly restricted by the low energy-capacity and by the difficulty of manufacturing high-aspect-ratio grooves/holes. Here we illustrate a kind of terahertz FP resonator formed by a cluster of coupled grooves with low-aspect-ratio, which has much higher energy-capacity, higher quality-factor and is much easier to fabricate than one formed by a single uncoupled-groove. Using free-electron beams to excite an array of such FP resonators, coherent terahertz emission can be achieved, the intensity of which is more than an order of magnitude higher than that from an array of uncoupled-grooves, affording a promising way for high-power and coherent terahertz wave generation.
Thermal interface materials with graphene fillers: review of the state of the art and outlook for future applications
Authors: Lewis Jacob S , Perrier Timothy , Barani Zahra , Kargar Fariborz , Balandin Alexander A
Published: October 2020

We review the current state-of-the-art graphene-enhanced thermal interface materials for the management of heat in the next generation of electronics. Increased integration densities, speed and power of electronic and optoelectronic devices require thermal interface materials with substantially higher thermal conductivity, improved reliability, and lower cost. Graphene has emerged as a promising filler material that can meet the demands of future high-speed and high-powered electronics. This review describes the use of graphene as a filler in curing and non-curing polymer matrices. Special attention is given to strategies for achieving the thermal percolation threshold with its corresponding characteristic increase in the overall thermal conductivity. Many applications require high thermal conductivity of composites, while simultaneously preserving electrical insulation. A hybrid filler approach, using graphene and boron nitride, is presented as a possible technology providing for the independent control of electrical and thermal conduction. The reliability and lifespan performance of thermal interface materials is an important consideration towards the determination of appropriate practical applications. The present review addresses these issues in detail, demonstrating the promise of graphene-enhanced thermal interface materials compared to alternative technologies.
Design of a head coil for high resolution mouse brain perfusion imaging using magnetic particle imaging
Authors: Graeser Matthias , Ludewig Peter , Szwargulski Patryk , Foerger Fynn , Liebing Tom , Forkert Nils D , Thieben Florian , Magnus Tim , Knopp Tobias
Published: October 2020

Magnetic particle imaging (MPI) is a novel and versatile imaging modality developing toward human application. When up-scaling to human size, the sensitivity of the systems naturally drops as the coil sensitivity depends on the bore diameter. Thus, new methods to push the sensitivity limit further have to be investigated to cope for this loss. In this paper a dedicated surface coil for mice is developed, improving the sensitivity in cerebral imaging applications. Similar to magnetic resonance imaging the developed surface coil improves the sensitivity due to the closer vicinity to the region of interest. With the developed surface coil presented in this work, it is possible to image tracer samples containing only 896 pg

Fe

  and detect even small vessels and anatomical structures within a wild type mouse model. As current sensitivity measures require a tracer system a new method for determining a sensitivity measure without this requirement is presented and verified to enable comparison between MPI receiver systems.
A model of heat pulse induced limit-cycle-oscillations in the edge of magnetically confined plasmas
Authors: Li Xiaobo , Guo Zhibin , Zhao Kaijun
Published: October 2020

Limit-cycle-oscillation (LCO) is a ubiquitous feature in low to high confinement mode transition. We propose a double-source (heat and turbulence) prey-predator model of heat pulse induced LCOs in the edge plasmas. It is shown that the development of the radial electric field is a combined process of turbulent thermal and momentum transports. The causality relation between the turbulence intensity and the radial electric field reverses during the transport channel transfer. A numerical study reveals that the appearance of LCOs can be explained as a transition from a ‘forced’ oscillation to an ‘intrinsic’ oscillation of the edge plasmas. It is also found that there exists a critical equilibrium pressure gradient, above which the transient LCOs become stationary ones, i.e. a steady I-phase may be sustained.
Spatial-temporal aspects of continuous EEG-based neurorobotic control
Authors: Suma Daniel , Meng Jianjun , Edelman Bradley Jay , He Bin
Published: October 2020

Objective. The goal of this work is to identify the spatio-temporal facets of state-of-the-art electroencephalography (EEG)-based continuous neurorobotics that need to be addressed, prior to deployment in practical applications at home and in the clinic. Approach. Nine healthy human subjects participated in five sessions of one-dimensional (1D) horizontal (LR), 1D vertical (UD) and two-dimensional (2D) neural tracking from EEG. Users controlled a robotic arm and virtual cursor to continuously track a Gaussian random motion target using EEG sensorimotor rhythm modulation via motor imagery (MI) commands. Continuous control quality was analyzed in the temporal and spatial domains separately. Main results. Axis-specific errors during 2D tasks were significantly larger than during 1D counterparts. Fatigue rates were larger for control tasks with higher cognitive demand (LR, left- and right-hand MI) compared to those with lower cognitive demand (UD, both hands MI and rest). Additionally robotic arm and virtual cursor control exhibited equal tracking error during all tasks. However, further spatial error analysis of 2D control revealed a significant reduction in tracking quality that was dependent on the visual interference of the physical device. In fact, robotic arm performance was significantly greater than that of virtual cursor control when the users’ sightlines were not obstructed. Significance. This work emphasizes the need for practical interfaces to be designed around real-world tasks of increased complexity. Here, the dependence of control quality on cognitive task demand emphasizes the need for decoders that facilitate the translation of 1D task mastery to 2D control. When device footprint was accounted for, the introduction of a physical robotic arm improved control quality, likely due to increased user engagement. In general, this work demonstrates the need to consider both the physical footprint of devices, the complexity of training tasks, and the synergy of control strategies during the development of neurorobotic control.
Stationary plasma configurations in a toroidal trap with D-shaped cross section in the two-fluid MHD approximation (Morozov–Soloviev equations)
Authors: Savelyev V V
Published: October 2020

In 1974, A.I. Morozov and L.S. Soloviev derived a general set of hydrodynamic equations for two-component ideal plasma under the stationary flow conditions, as applied to the plasma acceleration problems. Under the conditions of axial symmetry, the authors managed to reduce this very complex system to a more simple form by introducing three functions of the flux (the magnetic field flux, electron flux and ion flux). This situation is reminiscent of the one that develops when obtaining the Grad–Shafranov equation: the problem of static plasma equilibrium is reduced to solving one second-order equation for the magnetic field flux function. The rest condition for the two-component plasma is usually interpreted as the condition of vanishing the mass-average plasma velocity. This condition coincides with the condition of ion immobility up to a value of the order of the electron to ion mass ratio. In this work, the Morozov–Soloviev equations will be used for the first time to study the stationary plasma configurations in the toroidal magnetic trap with the D-shaped cross section. The geometric parameters of the trap correspond to those of the two currently operating tokamaks: the JET and the JT60U.
Common Methods for Handling Missing Data in Marginal Structural Models: What Works and Why
Authors: Leyrat Clémence , Carpenter James R , Bailly Sébastien , Williamson Elizabeth J
Published: October 2020

Marginal structural models (MSMs) are commonly used to estimate causal intervention effects in longitudinal nonrandomized studies. A common challenge when using MSMs to analyze observational studies is incomplete confounder data, where a poorly informed analysis method will lead to biased estimates of intervention effects. Despite a number of approaches described in the literature for handling missing data in MSMs, there is little guidance on what works in practice and why. We reviewed existing missing-data methods for MSMs and discussed the plausibility of their underlying assumptions. We also performed realistic simulations to quantify the bias of 5 methods used in practice: complete-case analysis, last observation carried forward, the missingness pattern approach, multiple imputation, and inverse-probability-of-missingness weighting. We considered 3 mechanisms for nonmonotone missing data encountered in research based on electronic health record data. Further illustration of the strengths and limitations of these analysis methods is provided through an application using a cohort of persons with sleep apnea: the research database of the French Observatoire Sommeil de la Fédération de Pneumologie. We recommend careful consideration of 1) the reasons for missingness, 2) whether missingness modifies the existing relationships among observed data, and 3) the scientific context and data source, to inform the choice of the appropriate method(s) for handling partially observed confounders in MSMs.
Progesterone receptor membrane components: key regulators of fetal membrane integrity
Authors: Lozovyy Violetta , Richardson Lauren , Saade George , Menon Ramkumar
Published: October 2020

Pro-pregnancy hormone progesterone (P4) helps to maintain a quiescent status of uterine tissues during gestation. However, P4’s functional role in maintaining fetal membrane (amniochorion) integrity remains unclear. P4 functions through its membrane receptors (progesterone receptor membrane components (PGRMCs)) as fetal membrane cells lack nuclear receptors. This study screened the differential expression of PGRMCs in the fetal membranes and tested P4–PGRMC interactions under normal and oxidative stress (OS) conditions expected that can disrupt P4–PGRMC interactions impacting fetal membrane stability resulting in parturition. Human fetal membranes were collected from term and preterm deliveries (N = 5). Immunohistochemistry and western blot localized and determined differential expression of P4 receptors. Primary amnion epithelial, mesenchymal (AMCs), and chorion cell were treated with P4 alone or co-treated (P4 + OS induced by cigarette smoke extract (CSE)). Proximity ligation assay (PLA) documented P4–receptor binding, whereas P4 enzyme-linked immunosorbent assay documented culture supernatant levels. Immunohistology confirmed lack of nuclear progesterone receptors; however, confirmed expressions of PGRMC 1 and 2. Term labor (P = 0.01) and preterm rupture (P = 0.01) are associated with significant downregulation of PGRMC2. OS-induced differential downregulation of PGRMCs in both amnion and chorion cells (all P < 0.05) and downregulates P4 release (AMCs; P = 0.01). The PLA showed preferential receptor–ligand binding in amnion and chorion cells. Co-treatment of P4 + CSE did not reverse CSE-induced effects. In conclusion, P4–PGRMCs interaction maintains fetal membranes’ functional integrity throughout pregnancy. Increased OS reduces endogenous P4 production and cell type-dependent downregulation of PGRMCs. These changes can lead to fetal membrane-specific “functional progesterone withdrawal,” contributing to the dysfunctional fetal membrane status seen at term and preterm conditions.
Hydroxychloroquine as Pre-exposure Prophylaxis for Coronavirus Disease 2019 (COVID-19) in Healthcare Workers: A Randomized Trial
Authors: Rajasingham Radha , Bangdiwala Ananta S , Nicol Melanie R , Skipper Caleb P , Pastick Katelyn A , Axelrod Margaret L , Pullen Matthew F , Nascene Alanna A , Williams Darlisha A , Engen Nicole W , Okafor Elizabeth C , Rini Brian I , Mayer Ingrid A , McDonald Emily G , Lee Todd C , Li Peter , MacKenzie Lauren J , Balko Justin M , Dunlop Stephen J , Hullsiek Katherine H , Boulware David R , Lofgren Sarah M ,   COVID PREP team, Abassi Mahsa , Balster Andrew , Collins Lindsey B , Drobot Glen , Krakower Douglas S , Lother Sylvain A , MacKay Dylan S , Meyer-Mueller Cameron , Selinsky Stephen , Solvason Dayna , Zarychanski Ryan , Zash Rebecca
Published: October 2020

Background

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a rapidly emerging virus causing the ongoing coronavirus disease 2019 (COVID-19) pandemic with no known effective prophylaxis. We investigated whether hydroxychloroquine could prevent SARS-CoV-2 in healthcare workers at high risk of exposure.

Methods

We conducted a randomized, double-blind, placebo-controlled clinical trial of healthcare workers with ongoing exposure to persons with SARS-CoV-2, including those working in emergency departments, intensive care units, COVID-19 hospital wards, and first responders. Participants across the United States and in the Canadian province of Manitoba were randomized to hydroxychloroquine loading dose then 400 mg once or twice weekly for 12 weeks. The primary endpoint was confirmed or probable COVID-19–compatible illness. We measured hydroxychloroquine whole-blood concentrations.

Results

We enrolled 1483 healthcare workers, of whom 79% reported performing aerosol-generating procedures. The incidence of COVID-19 (laboratory-confirmed or symptomatic compatible illness) was 0.27 events/person-year with once-weekly and 0.28 events/person-year with twice-weekly hydroxychloroquine compared with 0.38 events/person-year with placebo. For once-weekly hydroxychloroquine prophylaxis, the hazard ratio was .72 (95% CI, .44–1.16; P = .18) and for twice-weekly was .74 (95% CI, .46–1.19; P = .22) compared with placebo. Median hydroxychloroquine concentrations in whole blood were 98 ng/mL (IQR, 82–120) with once-weekly and 200 ng/mL (IQR, 159–258) with twice-weekly dosing. Hydroxychloroquine concentrations did not differ between participants who developed COVID-19–compatible illness (154 ng/mL) versus participants without COVID-19 (133 ng/mL; P = .08).

Conclusions

Pre-exposure prophylaxis with hydroxychloroquine once or twice weekly did not significantly reduce laboratory-confirmed COVID-19 or COVID-19–compatible illness among healthcare workers.

Clinical Trials Registration

Clinicaltrials.gov NCT04328467.
KiMoSys 2.0: an upgraded database for submitting, storing and accessing experimental data for kinetic modeling
Authors: Mochão Hugo , Barahona Pedro , Costa Rafael S
Published: October 2020

The KiMoSys (https://kimosys.org), launched in 2014, is a public repository of published experimental data, which contains concentration data of metabolites, protein abundances and flux data. It offers a web-based interface and upload facility to share data, making it accessible in structured formats, while also integrating associated kinetic models related to the data. In addition, it also supplies tools to simplify the construction process of ODE (Ordinary Differential Equations)-based models of metabolic networks. In this release, we present an update of KiMoSys with new data and several new features, including (i) an improved web interface, (ii) a new multi-filter mechanism, (iii) introduction of data visualization tools, (iv) the addition of downloadable data in machine-readable formats, (v) an improved data submission tool, (vi) the integration of a kinetic model simulation environment and (vii) the introduction of a unique persistent identifier system. We believe that this new version will improve its role as a valuable resource for the systems biology community.

Database URL:  www.kimosys.org
Evidence for an Age-Related Positivity Effect in Metacognitive Judgments
Authors: Sanders Edie C , Berry Jane M
Published: October 2020

Objectives

If older adults (OAs) are focused on emotionally meaningful goals in late life, they should demonstrate memory biases for positive stimuli over neutral and negative stimuli and, arguably, these cognitive biases should be reflected in their metacognitive judgments of learning (JOLs). To address this question, we examined age differences in metacognitive monitoring of emotionally valenced stimuli.

Method

Younger adults (YAs) and OAs (N = 85) studied positive, neutral, and negative words and made immediate JOLs, followed by a 2-alternative forced choice (2AFC) recognition memory task.

Results

Analyses of JOLs revealed evidence for a positivity effect in metacognitive judgments for OAs and an emotional salience effect in YAs. YAs recognized more words than OAs, but valence did not affect number of words recognized and did not moderate age differences in memory (p = .055). Memory monitoring as measured by resolution accuracy was equivalent in YAs and OAs. Positive affect was higher and negative affect was lower in OAs relative to YAs, lending additional evidence to the emergence of a positive orientation in older adulthood.

Discussion

These results provide intriguing and novel support for the positivity effect in the domain of metacognitive aging, adding to what is known in memory, attention, and emotion domains. Our findings fall squarely within socioemotional and metacognitive theoretical frameworks from which they were derived. We discuss research directions that might identify mechanisms by which affective states and stimuli interact to produce metacognitive outcomes in late life.
Vagueness of Patent Claim Language, Claim Construction and Patent Infringement – What a Mess!
Authors: Chakroun Nefissa
Published: October 2020

The claim drafting process, which is inherently related to inventions, is not exempt from difficulties. Prominent among these is vagueness, which can often be the chief characteristic of patent claims. This paper argues that such ambiguities may hamper the development and teaching functions of patent documents and can also distort infringement systems. It addresses legal issues related to patent claim construction, including the use of intrinsic or extrinsic evidence to clarify an ambiguous or vague claim. Confusion surrounding the use of expert testimony for determining the meaning of a claim is also highlighted. Largely based on the US law, the paper suggests ways to reduce claim ambiguity, such as the use of claim charts. Emphasis is placed on the clarity of the claims’ wording, because this acts as a safeguard against any infringement risk. In brief, constructing patent claims remains largely an unsettled and uncertain area of patent law. What really matters is the clarity of the claim language because definiteness, preciseness, conciseness and exactness are major guarantees of a patent’s validity.
An egalitarian society? Widening inequalities in premature mortality from non-communicable diseases in Australia, 2006–16
Authors: Adair Tim , Lopez Alan D
Published: October 2020

Background

The recent slowdown in life expectancy increase in Australia has occurred concurrently with widening socioeconomic and geographical inequalities in all-cause mortality risk. We analysed whether, and to what extent, mortality inequalities among specific non-communicable diseases (NCDs) in Australia at ages 35–74 years widened during 2006–16.

Methods

Registered deaths that occurred during 2006–16 in Australia were analysed. Inequalities were measured by area socioeconomic quintile [ranging from Q1 (lowest) to Q5 (highest)] and remoteness (major cities, inner regional, outer regional/remote/very remote). Age-standardized death rates (ASDR) for 35–74 years were calculated and smoothed over time.

Results

NCD mortality inequalities by area socioeconomic quintile widened; the ratio of Q1 to Q5 ASDR for males increased from 1.96 [95% confidence interval (CI) 1.91–2.01] in 2011 to 2.08 (2.03–2.13) in 2016, and for females from 1.78 (1.73–1.84) to 1.96 (1.90–2.02). Moreover, Q1 NCD ASDRs did not clearly decline from 2011 to 2016. CVD mortality inequalities were wider than for all NCDs. There were particularly large increases in smoking-related mortality inequalities. In 2016, mortality inequalities were especially high for chronic respiratory diseases, alcohol-related causes and diabetes. NCD mortality rates outside major cities were higher than within major cities, and these differences widened during 2006–16. Higher mortality rates in inner regional areas than in major cities were explained by socioeconomic factors.

Conclusions

Widening of inequalities in premature mortality rates is a major public health issue in Australia in the context of slowing mortality decline. Inequalities are partly explained by major risk factors for CVDs and NCDs: being overweight or obese, lack of exercise, poor diet and smoking. There is a need for urgent policy responses that consider socioeconomic disadvantage.
Travellers returning from the island of Zanzibar colonized with MDREscherichia colistrains: assessing the impact of local people and other sources
Authors: Moser Aline I , Kuenzli Esther , Büdel Thomas , Campos-Madueno Edgar I , Bernasconi Odette J , DeCrom-Beer Susan , Jakopp Barbara , Mohammed Ali Haji , Hassan Nadir Khatib , Fehr Jan , Zinsstag Jakob , Hatz Christoph , Endimiani Andrea
Published: October 2020

Objectives

Many travellers to low-income countries return home colonized at the intestinal level with extended-spectrum cephalosporin-resistant (ESC-R) and/or colistin-resistant (CST-R) Escherichia coli (Ec) strains. However, nothing is known about the local sources responsible for the transmission of these pathogens to the travellers.

Methods

We compared the ESC-R- and CST-R-Ec strains found in the pre- (n = 23) and post-trip (n = 37) rectal swabs of 37 travellers from Switzerland to Zanzibar with those (i) contemporarily isolated from local people, poultry, retailed chicken meat (n = 31), and (ii) from other sources studied in the recent past (n = 47). WGS and core-genome analyses were implemented.

Results

Twenty-four travellers returned colonized with ESC-R- (n = 29) and/or CST-R- (n = 8) Ec strains. Almost all ESC-R-Ec were CTX-M-15 producers and belonged to heterogeneous STs/core-genome STs (cgSTs), while mcr-positive strains were not found. Based on the strains’ STs/cgSTs, only 20 subjects were colonized with ESC-R- and/or CST-R-Ec that were not present in their gut before the journey. Single nucleotide variant (SNV) analysis showed that three of these 20 travellers carried ESC-R-Ec (ST3489, ST3580, ST361) identical (0–20 SNVs) to those found in local people, chicken meat, or poultry. Three further subjects carried ESC-R-Ec (ST394, ST648, ST5173) identical or highly related (15–55 SNVs) to those previously reported in local people, fish, or water.

Conclusions

This is the first known study comparing the ESC-R- and/or CST-R-Ec strains obtained from travellers and local sources using solid molecular methods. We showed that for at least one-third of the returning travellers the acquired antibiotic-resistant Ec had a corresponding strain among resident people, food, animal and/or environmental sources.
Turkish Court of Appeal finds likelihood of confusion based on a common weak element
Authors: Doğan Alkan Güldeniz , C¸ıtak Ayşenur
Published: October 2020

Yıldız Holding Anonim Şirketi v İbrahim Aslanyavrusu (2020) 11th Chamber of Turkish Court of Appeals Merit No: 2019/3006 E., No: 2020/841 K., 03 February 2020
The Anatomy and Physiology of Teaming in Cancer Care Delivery: A Conceptual Framework
Authors: Verhoeven Dana C , Chollette Veronica , Lazzara Elizabeth H , Shuffler Marissa L , Osarogiagbon Raymond U , Weaver Sallie J
Published: October 2020

Care coordination challenges for patients with cancer continue to grow as expanding treatment options, multimodality treatment regimens, and an aging population with comorbid conditions intensify demands for multidisciplinary cancer care. Effective teamwork is a critical yet understudied cornerstone of coordinated cancer care delivery. For example, comprehensive lung cancer care involves a clinical “team of teams”—or clinical multiteam system (MTS)—coordinating decisions and care across specialties, providers, and settings. The teamwork processes within and between these teams lay the foundation for coordinated care. Although the need to work as a team and coordinate across disciplinary, organizational, and geographic boundaries increases, evidence identifying and improving the teamwork processes underlying care coordination and delivery among the multiple teams involved remains sparse. This commentary synthesizes MTS structure characteristics and teamwork processes into a conceptual framework called the cancer MTS framework to advance future cancer care delivery research addressing evidence gaps in care coordination. Included constructs were identified from published frameworks, discussions at the 2016 National Cancer Institute-American Society of Clinical Oncology Teams in Cancer Care Workshop, and expert input. A case example in lung cancer provided practical grounding for framework refinement. The cancer MTS framework identifies team structure variables and teamwork processes affecting cancer care delivery, related outcomes, and contextual variables hypothesized to influence coordination within and between the multiple clinical teams involved. We discuss how the framework might be used to identify care delivery research gaps, develop hypothesis-driven research examining clinical team functioning, and support conceptual coherence across studies examining teamwork and care coordination and their impact on cancer outcomes.
Subtyping Cutaneous Melanoma Matters
Authors: El Sharouni Mary-Ann , van Diest Paul Johannes , Witkamp Arjen Joost , Sigurdsson Vigfús , van Gils Carla Henrica
Published: October 2020

Background

Our aim was to investigate the role of melanoma subtype on survival and focus on the effects stratified by Breslow thickness and ulceration status.

Methods

Patients with cutaneous melanoma stage I, II, or III diagnosed between 2000 and 2014 were derived from the Dutch Nationwide Pathology Registry and overall survival data from the Netherlands Cancer Registry. Patients were followed until 2018. Using multivariable Cox proportional hazards models, hazard ratios were calculated for each melanoma subtype, per Breslow thickness category and ulceration status, and adjusted for age, sex, stage, and localization.

Results

A total of 48 361 patients were included: 79.3% had superficial spreading melanoma (SSM), 14.6% nodular melanoma (NM), 5.2% lentigo maligna melanoma, and 0.9% acral lentiginous melanoma (ALM). In the total patient group, using SSM as the reference category, adjusted hazard ratios were 1.06 (95% confidence interval [CI] = 1.01 to 1.12) for NM, 1.02 (95% CI = 0.93 to 1.13) for lentigo maligna melanoma, and 1.26 (95% = CI 1.06 to 1.50) for ALM. Among patients with 1.0 mm or less Breslow thickness and no ulceration, NM showed a twofold increased risk (hazard ratio = 1.96, 95% CI = 1.58 to 2.45) compared with SSM. Compared with 1.0 mm or less SSM without ulceration, the hazard ratio for 1.0 mm or less SSM with ulceration was 1.94 (95% CI = 1.55 to 2.44), and the hazard ratio for 1.0 mm or less NM with ulceration was 3.46 (95% CI = 2.17 to 5.50). NM patients with tumors greater than 1.0 mm did not show worse survival than SSM patients with tumors greater than 1.0 mm.

Conclusions

In this large nationwide study, ALM patients showed worse survival than SSM patients. Among patients with melanomas that were thin (1.0 mm or less), NM subtype patients also showed worse survival than SSM patients.
Investigating the growing population of massive quiescent galaxies at cosmic noon
Authors: Sherman Sydney , Jogee Shardha , Florez Jonathan , Stevans Matthew L , Kawinwanichakij Lalitwadee , Wold Isak , Finkelstein Steven L , Papovich Casey , Ciardullo Robin , Gronwall Caryl , Cora Sofía A , Hough Tomás , Vega-Martínez Cristian A
Published: October 2020

We explore the build-up of quiescent galaxies using a sample of 28 469 massive (M⋆ ≥ 1011 M⊙) galaxies at redshifts 1.5 < $z$ < 3.0, drawn from a 17.5 deg2 area (0.33 Gpc3 comoving volume at these redshifts). This allows for a robust study of the quiescent fraction as a function of mass at 1.5 < $z$ < 3.0 with a sample ∼40 times larger at log(M⋆/$\rm M_{\odot })\ge 11.5$ than previous studies. We derive the quiescent fraction using three methods: specific star formation rate, distance from the main sequence, and UVJ colour–colour selection. All three methods give similar values at 1.5 < $z$ < 2.0, however the results differ by up to a factor of 2 at 2.0 < $z$ < 3.0. At redshifts 1.5 < $z$ < 3.0, the quiescent fraction increases as a function of stellar mass. By $z$ = 2, only 3.3 Gyr after the big bang, the universe has quenched ∼25 per cent of M⋆ = 1011 M⊙ galaxies and ∼45 per cent of M⋆ = 1012 M⊙ galaxies. We discuss physical mechanisms across a range of epochs and environments that could explain our results. We compare our results with predictions from hydrodynamical simulations SIMBA and IllustrisTNG and semi-analytic models (SAMs) SAG, SAGE, and Galacticus. The quiescent fraction from IllustrisTNG is higher than our empirical result by a factor of 2–5, while those from SIMBA and the three SAMs are lower by a factor of 1.5–10 at 1.5 < $z$ < 3.0.
A smoothed particle hydrodynamics algorithm for multigrain dust with separate sets of particles
Authors: Mentiplay Daniel , Price Daniel J , Pinte Christophe , Laibe Guillaume
Published: October 2020

We present a method for simulating the dynamics of a mixture of gas and multiple species of large Stokes number dust grains, typical of evolved protoplanetary discs and debris discs. The method improves upon earlier methods, in which only a single grain size could be represented, by capturing the differential backreaction of multiple dust species on the gas. This effect is greater for large dust-to-gas ratios that may be expected in the later stages of the protoplanetary disc life. We benchmark the method against analytic solutions for linear waves, drag, and shocks in dust–gas mixtures, and radial drift in a protoplanetary disc showing that the method is robust and accurate.
Eigenspectra: a framework for identifying spectra from 3D eclipse mapping
Authors: Mansfield Megan , Schlawin Everett , Lustig-Yaeger Jacob , Adams Arthur D , Rauscher Emily , Arcangeli Jacob , Feng Y Katherina , Gupta Prashansa , Keating Dylan , Stevenson Kevin B , Beatty Thomas G
Published: October 2020

Planetary atmospheres are inherently 3D objects that can have strong gradients in latitude, longitude, and altitude. Secondary eclipse mapping is a powerful way to map the 3D distribution of the atmosphere, but the data can have large correlations and errors in the presence of photon and instrument noise. We develop a technique to mitigate the large uncertainties of eclipse maps by identifying a small number of dominant spectra to make them more tractable for individual analysis via atmospheric retrieval. We use the eigencurves method to infer a multiwavelength map of a planet from spectroscopic secondary eclipse light curves. We then apply a clustering algorithm to the planet map to identify several regions with similar emergent spectra. We combine the similar spectra together to construct an ‘eigenspectrum’ for each distinct region on the planetary map. We demonstrate how this approach could be used to isolate hot from cold regions and/or regions with different chemical compositions in observations of hot Jupiters with the James Webb Space Telescope (JWST). We find that our method struggles to identify sharp edges in maps with sudden discontinuities, but generally can be used as a first step before a more physically motivated modelling approach to determine the primary features observed on the planet.
On the origin of low escape fractions of ionizing radiation from massive star-forming galaxies at high redshift
Authors: Yoo Taehwa , Kimm Taysun , Rosdahl Joakim
Published: October 2020

The physical origin of low escape fractions of ionizing radiation derived from massive star-forming galaxies at z ∼ 3–4 is not well understood. We perform idealized disc galaxy simulations to understand how galactic properties such as metallicity and gas mass affect the escape of Lyman continuum (LyC) photons using radiation-hydrodynamic simulations with strong stellar feedback. We find that the luminosity-weighted escape fraction from a metal-poor (Z = 0.002) galaxy embedded in a halo of mass $M_{\rm h}\simeq 10^{11}\, \mathrm{M}_\odot$ is $\left\langle {f_{\rm esc}^{\rm 3D}}\right\rangle \simeq 10\, {{\ \rm per\ cent}}$. Roughly half of the LyC photons are absorbed within scales of 100 pc, and the other half is absorbed in the ISM ($\lesssim 2\, {\rm kpc}$). When the metallicity of the gas is increased to Z = 0.02, the escape fraction is significantly reduced to $\left\langle {f_{\rm esc}^{\rm 3D}}\right\rangle \simeq 1{{\ \rm per\ cent}}$ because young stars are enshrouded by their birth clouds for a longer time. In contrast, increasing the gas mass by a factor of 5 leads to $\left\langle {f_{\rm esc}^{\rm 3D}}\right\rangle \simeq 5\, {{\ \rm per\ cent}}$ because LyC photons are only moderately absorbed by the thicker disc. Our experiments suggest that high metallicity is likely more responsible for the low escape fractions observed in massive star-forming galaxies, supporting the scenario in which the escape fraction is decreasing with increasing halo mass. Finally, negligible correlation is observed between the escape fraction and surface density of star formation or galactic outflow rates.
Birth sites of young stellar associations and recent star formation in a flocculent corrugated disc
Authors: Quillen Alice C , Pettitt Alex R , Chakrabarti Sukanya , Zhang Yifan , Gagné Jonathan , Minchev Ivan
Published: October 2020

With backwards orbit integration, we estimate birth locations of young stellar associations and moving groups identified in the solar neighbourhood that are younger than 70 Myr. The birth locations of most of these stellar associations are at a smaller galactocentric radius than the Sun, implying that their stars moved radially outwards after birth. Exceptions to this rule are the Argus and Octans associations, which formed outside the Sun’s galactocentric radius. Variations in birth heights of the stellar associations suggest that they were born in a filamentary and corrugated disc of molecular clouds, similar to that inferred from the current filamentary molecular cloud distribution and dust extinction maps. Multiple spiral arm features with different but near corotation pattern speeds and at different heights could account for the stellar association birth sites. We find that the young stellar associations are located in between peaks in the radial/tangential (UV) stellar velocity distribution for stars in the solar neighbourhood. This would be expected if they were born in a spiral arm, which perturbs stellar orbits that cross it. In contrast, stellar associations seem to be located near peaks in the vertical phase-space distribution, suggesting that the gas in which stellar associations are born moves vertically together with the low-velocity dispersion disc stars.
Characterizing dynamical states of Galactic open clusters with Gaia DR2
Authors: Angelo M S , Corradi W J B , Santos J F C , Maia F F S , Ferreira F A
Published: October 2020

In this work, we investigate the dynamical properties of 38 Galactic open clusters: 34 of them are located at low Galactic latitudes (|b| < 10°) and are projected against dense stellar fields; the other four comparison objects present clearer contrasts with the field population. We determine structural and time-related parameters that are associated with the clusters’ dynamical evolution: core (rc), tidal (rt), and half-mass (rhm) radii, ages (t), and crossing times (tcr). We have also incorporated results for 27 previously studied clusters, creating a sample of 65, spanning the age and Galactocentric distance (RG) ranges $7.0 \lt \textrm {log}\, t \lt 9.7$ and 6 < RG (kpc) < 13. We employ a uniform analysis method which incorporates photometric and astrometric data from the Gaia DR2 catalogue. Member stars are identified by employing a decontamination algorithm which operates on the 3D astrometric space of parallax and proper motion and attributes membership likelihoods for stars in the cluster region. Our results show that internal relaxation causes rc to correlate negatively with the dynamical ratio τdyn = t/tcr. This implies that dynamically older systems tend to be more centrally concentrated. The more concentrated ones tend to present smaller rhm/rt ratios, which means that they are less subject to tidal disruption. The analysis of coeval groups at compatible RG suggests that the inner structure of clusters is reasonably insensitive to variations in the external tidal field. Additionally, our results confirm, on average, an increase in rt for regions with less-intense Galactic gravitational fields.
Global H i asymmetries in IllustrisTNG: a diversity of physical processes disturb the cold gas in galaxies
Authors: Watts Adam B , Power Chris , Catinella Barbara , Cortese Luca , Stevens Adam R H
Published: October 2020

Observations of the cold neutral atomic hydrogen (H i) in and around disc galaxies have revealed that spatial and kinematic asymmetries are common place, and are reflected in the global H i spectra. We use the TNG100 box from the IllustrisTNG suite of cosmological simulations to study the conditions under which these asymmetries may arise in current theoretical galaxy formation models. We find that more than 50 per cent of the sample has at least a 10 per cent difference in integrated flux between the high- and low-velocity half of the spectrum, thus the typical TNG100 galaxy has an H i profile that is not fully symmetric. We find that satellite galaxies are a more asymmetric population than centrals, consistent with observational results. Using halo mass as a proxy for environment, this trend appears to be driven by the satellite population within the virial radius of haloes more massive than 1013 M⊙, typical of medium/large groups. We show that, while the excess of H i asymmetry in group satellites is likely driven by ram pressure, the bulk of the asymmetric H i profiles observed in TNG100 are driven by physical processes able to affect both the central and satellite populations. Our results highlight how asymmetries are not driven solely by environment, and multiple physical processes can produce the same asymmetric shape in global H i spectra.
Enzymatic synthesis of hypermodified DNA polymers for sequence-specific display of four different hydrophobic groups
Authors: Ondruš Marek , Sýkorová Veronika , Bednárová Lucie , Pohl Radek , Hocek Michal
Published: October 2020

A set of modified 2′-deoxyribonucleoside triphosphates (dNTPs) bearing a linear or branched alkane, indole or phenyl group linked through ethynyl or alkyl spacer were synthesized and used as substrates for polymerase synthesis of hypermodified DNA by primer extension (PEX). Using the alkyl-linked dNTPs, the polymerase synthesized up to 22-mer fully modified oligonucleotide (ON), whereas using the ethynyl-linked dNTPs, the enzyme was able to synthesize even long sequences of >100 modified nucleotides in a row. In PCR, the combinations of all four modified dNTPs showed only linear amplification. Asymmetric PCR or PEX with separation or digestion of the template strand can be used for synthesis of hypermodified single-stranded ONs, which are monodispersed polymers displaying four different substituents on DNA backbone in sequence-specific manner. The fully modified ONs hybridized with complementary strands and modified DNA duplexes were found to exist in B-type conformation (B- or C-DNA) according to CD spectral analysis. The modified DNA can be replicated with high fidelity to natural DNA through PCR and sequenced. Therefore, this approach has a promising potential in generation and selection of hypermodified aptamers and other functional polymers.
Brain metastasis detection using machine learning: a systematic review and meta-analysis
Authors: Cho Se Jin , Sunwoo Leonard , Baik Sung Hyun , Bae Yun Jung , Choi Byung Se , Kim Jae Hyoung
Published: October 2020

Background

Accurate detection of brain metastasis (BM) is important for cancer patients. We aimed to systematically review the performance and quality of machine-learning-based BM detection on MRI in the relevant literature.

Methods

A systematic literature search was performed for relevant studies reported before April 27, 2020. We assessed the quality of the studies using modified tailored questionnaires of the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) criteria and the Checklist for Artificial Intelligence in Medical Imaging (CLAIM). Pooled detectability was calculated using an inverse-variance weighting model.

Results

A total of 12 studies were included, which showed a clear transition from classical machine learning (cML) to deep learning (DL) after 2018. The studies on DL used a larger sample size than those on cML. The cML and DL groups also differed in the composition of the dataset, and technical details such as data augmentation. The pooled proportions of detectability of BM were 88.7% (95% CI, 84–93%) and 90.1% (95% CI, 84–95%) in the cML and DL groups, respectively. The false-positive rate per person was lower in the DL group than the cML group (10 vs 135, P < 0.001). In the patient selection domain of QUADAS-2, three studies (25%) were designated as high risk due to non-consecutive enrollment and arbitrary exclusion of nodules.

Conclusion

A comparable detectability of BM with a low false-positive rate per person was found in the DL group compared with the cML group. Improvements are required in terms of quality and study design.
Population-based estimates of survival among elderly patients with brain metastases
Authors: Lamba Nayan , Kearney Rachel Brigell , Catalano Paul J , Hassett Michael J , Wen Patrick Y , Haas-Kogan Daphne A , Aizer Ayal A
Published: October 2020

Background

Prognostic estimates for patients with brain metastases (BM) stem from younger, healthier patients enrolled in clinical trials or databases from academic centers. We characterized population-level prognosis in elderly patients with BM.

Methods

Using Surveillance, Epidemiology, and End Results (SEER)–Medicare data, we identified 9882 patients ≥65 years old with BM secondary to lung, breast, skin, kidney, esophageal, colorectal, and ovarian primaries between 2014 and 2016. Survival was assessed by primary site and evaluated with Cox regression.

Results

In total, 2765 versus 7117 patients were diagnosed with BM at primary cancer diagnosis (synchronous BM, median survival = 2.9 mo) versus thereafter (metachronous BM, median survival = 3.4 mo), respectively. Median survival for all primary sites was ≤4 months, except ovarian cancer (7.5 mo). Patients with non-small-cell lung cancer (NSCLC) receiving epidermal growth factor receptor (EGFR)– or anaplastic lymphoma kinase (ALK)–based therapy for synchronous BM displayed notably better median survival at 12.5 and 20.1 months, respectively, versus 2.8 months exhibited by other patients with NSCLC; survival estimates in melanoma patients based on receipt of BRAF/MEK therapy versus not were 6.7 and 2.8 months, respectively. On multivariable regression, older age, greater comorbidity, and type of managing hospital were associated with poorer survival; female sex, higher median household income, and use of brain-directed stereotactic radiation, neurosurgical resection, or systemic therapy (versus brain-directed non-stereotactic radiation) were associated with improved survival (all P < 0.05).

Conclusions

Elderly patients with BM have a poorer prognosis than suggested by prior algorithms. If prognosis is driven by systemic and not intracranial disease, brain-directed therapy with potential for significant toxicity should be utilized cautiously.
The long noncoding RNA lnc-HLX-2-7 is oncogenic in Group 3 medulloblastomas
Authors: Katsushima Keisuke , Lee Bongyong , Kunhiraman Haritha , Zhong Cuncong , Murad Rabi , Yin Jun , Liu Ben , Garancher Alexandra , Gonzalez-Gomez Ignacio , Monforte Hector L , Stapleton Stacie , Vibhakar Rajeev , Bettegowda Chetan , Wechsler-Reya Robert J , Jallo George , Raabe Eric , Eberhart Charles G , Perera Ranjan J
Published: October 2020

Background

Medulloblastoma (MB) is an aggressive brain tumor that predominantly affects children. Recent high-throughput sequencing studies suggest that the noncoding RNA genome, in particular long noncoding RNAs (lncRNAs), contributes to MB subgrouping. Here we report the identification of a novel lncRNA, lnc-HLX-2-7, as a potential molecular marker and therapeutic target in Group 3 MBs.

Methods

Publicly available RNA sequencing (RNA-seq) data from 175 MB patients were interrogated to identify lncRNAs that differentiate between MB subgroups. After characterizing a subset of differentially expressed lncRNAs in vitro and in vivo, lnc-HLX-2-7 was deleted by CRISPR/Cas9 in the MB cell line. Intracranial injected tumors were further characterized by bulk and single-cell RNA-seq.

Results

Lnc-HLX-2-7 is highly upregulated in Group 3 MB cell lines, patient-derived xenografts, and primary MBs compared with other MB subgroups as assessed by quantitative real-time, RNA-seq, and RNA fluorescence in situ hybridization. Depletion of lnc-HLX-2-7 significantly reduced cell proliferation and 3D colony formation and induced apoptosis. Lnc-HLX-2-7–deleted cells injected into mouse cerebellums produced smaller tumors than those derived from parental cells. Pathway analysis revealed that lnc-HLX-2-7 modulated oxidative phosphorylation, mitochondrial dysfunction, and sirtuin signaling pathways. The MYC oncogene regulated lnc-HLX-2-7, and the small-molecule bromodomain and extraterminal domain family‒bromodomain 4 inhibitor Jun Qi 1 (JQ1) reduced lnc-HLX-2-7 expression.

Conclusions

Lnc-HLX-2-7 is oncogenic in MB and represents a promising novel molecular marker and a potential therapeutic target in Group 3 MBs.