bluuebunny/crossref_metadata_2025 huggingface dataset:
Magnetometry using sodium fluorescence with synchronous modulation of two-photon resonant light fields
Authors: Grewal Raghwinder Singh , Pulido Mauricio , Pati Gour , Tripathi Renu
Published: November 2020

We have demonstrated a technique for remote magnetometry using fluorescence measurements in a sodium cell. This technique utilizes two-photon resonance instead of single-photon resonance to generate magnetic resonances with synchronous modulation of two laser fields. A strong magnetic resonance with its dip matching the Larmor frequency, ΩL, is produced when a magnetic field perpendicular to the laser propagation direction is applied. A magnetic field sensitivity of 45 pT/√Hz is measured at a 35% modulation duty cycle where ΩL resonance has a maximum amplitude. We have discussed ways to further improve the sensitivity closer to the shot-noise limit by making changes to our existing setup. An additional magnetic resonance at 3ΩL is also formed due to two-photon resonance, which can be utilized in determining the magnetic field orientation. We have developed a theoretical model based on density matrix equations to study the magnetic resonances under different conditions and also for validating our experimental observations.
Low temperature atomic layer deposition of GaOxNy thin film on III-GaN:Mg for UV photodetector
Authors: Su Longxing , Chen Sheng-Yu , Zhao Lianqi , Zuo Yuqing , Xie Jin
Published: November 2020

In this work, a UV photodetector was fabricated by constructing a heterojunction between β phase GaOxNy prepared by atomic layer deposition and p-GaN prepared by metal organic chemical vapor deposition. The p-GaN layer shows an extremely sharp absorption characteristic with a cutoff edge of ∼365 nm, while β-GaOxNy shows a broad absorption behavior in the UV region due to its low crystal quality grown at low temperature (200 °C). The β-GaOxNy/GaN photodetector exhibits an obvious rectifying characteristic due to the formation of the type-II heterojunction and shows a high responsivity of 1.46 A/W at a bias voltage of −5 V and a rapid response speed (a rise time of 3.3 ms and a decay time of 6.8 ms). The investigation of the β-GaOxNy/GaN photodetector suggests a simple and effective strategy for next-generation high-performance optoelectronic devices.
Structural integrity, meltability, and variability of thermal properties in the mixed-linker zeolitic imidazolate framework ZIF-62
Authors: Nozari Vahid , Calahoo Courtney , Longley Louis , Bennett Thomas D. , Wondraczek Lothar
Published: November 2020

Metal–organic framework (MOF) glasses have emerged as a new class of melt-quenched glasses; however, so far, all MOF glass production has remained at lab-scale; future applications will require large-scale, commercial production of parent crystalline MOFs. Yet, control of synthetic parameters, such as uniform temperature and mixing, can be challenging, particularly, when scaling-up production of a mixed-linker MOF or a zeolitic imidazolate framework (ZIF). Here, we examine the effect of heterogeneous linker distribution on the thermal properties and melting behavior of ZIF-62. X-ray diffraction (XRD), Raman, and 1H nuclear magnetic resonance spectroscopies revealed little discernable structural difference between samples of ZIF-62 synthesized in our lab and by a commercial supplier. Differential scanning calorimetry and variable temperature/isothermal XRD revealed the samples to have significantly different thermal behavior. Formation of ZIF-zni was identified, which contributed to a dramatic rise in the melting point by around 100 K and also led to the alteration of the macroscopic properties of the final glass. Parameters that might lead to the formation of unexpected phases such as an uneven distribution of linkers were identified, and characterization methods for the detection of unwanted phases are provided. Finally, the need for adequate consideration of linker distribution is stressed when characterizing mixed-linker ZIFs.
Liquid-curtain-based strategy to restrain plume during flushing
Authors: Wu Su-Chen , Guo Meng-Yue , Wang Ji-Xiang , Yao Shuhuai , Chen Jun , Li Yun-yun
Published: November 2020

How to prevent the flushing-induced plume without changing people’s daily habits? Enlightened by thoughts of redesigning the restroom, this article provides a redesigned toilet using liquid-curtain-based strategy and verifies its advantages from the computational fluid dynamics. Two favorable effects are spotted: (1) the liquid curtain can suppress the upward virus particles (only 1% viruses can be lifted out of the toilet) and (2) the flow distribution caused by the liquid curtain can deliver virus particles into the sewage efficiently.
Adoptive cell therapy: Living drugs against cancer
Authors: Laskowski Tamara , Rezvani Katayoun
Published: November 2020

Immunotherapy has made a profound impact in the treatment of cancer in the last decade. Insights from the study of the intricate relationships between immune cells and cancer have led to the clinical development of strategies that redirect the power of the immune system to target and eliminate cancer. Today, immunotherapy represents a rapidly expanding and transformative force comprising multiple modalities.
Function of mammalian M-cones depends on the level of CRALBP in Müller cells
Authors: Kolesnikov Alexander V. , Kiser Philip D. , Palczewski Krzysztof , Kefalov Vladimir J.
Published: November 2020

Cone photoreceptors mediate daytime vision in vertebrates. The rapid and efficient regeneration of their visual pigments following photoactivation is critical for the cones to remain photoresponsive in bright and rapidly changing light conditions. Cone pigment regeneration depends on the recycling of visual chromophore, which takes place via the canonical visual cycle in the retinal pigment epithelium (RPE) and the Müller cell–driven intraretinal visual cycle. The molecular mechanisms that enable the neural retina to regenerate visual chromophore for cones have not been fully elucidated. However, one known component of the two visual cycles is the cellular retinaldehyde-binding protein (CRALBP), which is expressed both in the RPE and in Müller cells. To understand the significance of CRALBP in cone pigment regeneration, we examined the function of cones in mice heterozygous for Rlbp1, the gene encoding CRALBP. We found that CRALBP expression was reduced by ∼50% in both the RPE and retina of Rlbp1+/− mice. Electroretinography (ERG) showed that the dark adaptation of rods and cones is unaltered in Rlbp1+/− mice, indicating a normal RPE visual cycle. However, pharmacologic blockade of the RPE visual cycle revealed suppressed cone dark adaptation in Rlbp1+/− mice in comparison with controls. We conclude that the expression level of CRALPB specifically in the Müller cells modulates the efficiency of the retina visual cycle. Finally, blocking the RPE visual cycle also suppressed further cone dark adaptation in Rlbp1−/− mice, revealing a shunt in the classical RPE visual cycle that bypasses CRALBP and allows partial but unexpectedly rapid cone dark adaptation.
Beam propagation simulations for LISA in the presence of telescope aberrations
Authors: Kenny F , Devaney N
Published: November 2020

Accurate simulation of the propagation of light between the spacecraft of the laser interferometer space antenna (LISA) gravitational wave observatory will be a vital tool in determining the optical design of the telescopes used in the constellation. In this work, we examine the methods available for numerical simulation of this propagation, and consider the effect of an aberrated transmitting telescope (Tx) on the light collected by the receiving telescope (Rx). Propagation software has been developed using direct numerical integration methods, and has been validated by comparison to analytical solutions for particular cases. Zernike modal aberrations up to and including primary spherical have been considered in the Tx, and, in particular, the effects of defocus, astigmatism and coma were examined. It was found that minimization of the even radial order aberrations in Tx resulted in a reduced wavefront error at Rx, while odd aberrations such as coma can displace the maximum irradiance away from the optical axis. Thus careful consideration of the impact of telescope aberrations will be required to minimise detrimental effects on the detection of gravitational waves.
A novel approximate method to calculate the force applied on an elastic half space by a rigid sphere
Authors: Kontomaris S V , Malamou A
Published: November 2020

Assume a rigid sphere that is slightly pushed towards an elastic half space. The applied force on the half space can be easily calculated using the basic theoretical tools provided by the Hertzian contact mechanics theory. It should be noted that the aforementioned analysis is valid under the condition that the deformation depth is significantly smaller compared to the sphere’s radius (h ≪ R). So, a significant question arises; what if the sphere is pushed deeper in the elastic half space (e.g. h > R)? In this paper, the aforementioned question is answered and a relative discussion regarding the application of the results is presented.
A mathematical model for image saturation with an application to the restoration of solar images via adaptive sparse deconvolution
Authors: Guastavino S , Benvenuto F
Published: November 2020

In this paper we introduce a mathematical model of the image saturation phenomenon occurring in a charged coupled device (CCD), and we propose a novel computational method for restoring saturated images acquired by the atmospheric imaging assembly (AIA) telescope. The mathematical model takes into account both primary saturation, when the photon-induced charge reaches the CCD full well capacity, and the blooming effect, when the excess charge flows into adjacent pixels. The restoration of AIA saturated images is then formulated as an inverse problem with a forward operator encoding the standard diffraction of light rays by a convolution, the primary saturation by an upper limit to the number of photons and the blooming effect by the conservation of the photon-induced charge spilled over adjacent pixels. As a result of this theoretical formulation we propose an adaptive ℓ
1 regularized inversion method improving the desaturation capabilities of the existing SE-DESAT method [Guastavino S et al 2019 Astrophys. J.
882 109]. We prove that this method has the consistency estimation property also in the case that a fixed unknown background is considered. We test the adaptive method both in the case of synthetic and real data, comparing the performance with the one of the SE-DESAT method, showing that the proposed method avoids edge effects and artifacts in reconstructions even when the background solar activity is particularly intense.
Roadmap: proton therapy physics and biology
Authors: Paganetti Harald , Beltran Chris , Both Stefan , Dong Lei , Flanz Jacob , Furutani Keith , Grassberger Clemens , Grosshans David R , Knopf Antje-Christin , Langendijk Johannes A , Nystrom Hakan , Parodi Katia , Raaymakers Bas W , Richter Christian , Sawakuchi Gabriel O , Schippers Marco , Shaitelman Simona F , Teo B K Kevin , Unkelbach Jan , Wohlfahrt Patrick , Lomax Tony
Published: November 2020

The treatment of cancer with proton radiation therapy was first suggested in 1946 followed by the first treatments in the 1950s. As of 2020, almost 200 000 patients have been treated with proton beams worldwide and the number of operating proton therapy (PT) facilities will soon reach one hundred. PT has long moved from research institutions into hospital-based facilities that are increasingly being utilized with workflows similar to conventional radiation therapy. While PT has become mainstream and has established itself as a treatment option for many cancers, it is still an area of active research for various reasons: the advanced dose shaping capabilities of PT cause susceptibility to uncertainties, the high degrees of freedom in dose delivery offer room for further improvements, the limited experience and understanding of optimizing pencil beam scanning, and the biological effect difference compared to photon radiation. In addition to these challenges and opportunities currently being investigated, there is an economic aspect because PT treatments are, on average, still more expensive compared to conventional photon based treatment options. This roadmap highlights the current state and future direction in PT categorized into four different themes, ‘improving efficiency’, ‘improving planning and delivery’, ‘improving imaging’, and ‘improving patient selection’.
A multivariable study of deformable image registration evaluation metrics in 4DCT of thoracic cancer patients
Authors: Juan-Cruz Celia , Fast Martin F , Sonke Jan-Jakob
Published: November 2020

Deformable image registration (DIR) accuracy is often validated using manually identified landmarks or known deformations generated using digital or physical phantoms. In daily practice, the application of these approaches is limited since they are time-consuming or require additional equipment. An alternative is the use of metrics automatically derived from the registrations, but their interpretation is not straightforward. In this work we aim to determine the suitability of DIR-derived metrics to validate the accuracy of 4 commonly used DIR algorithms. First, we investigated the DIR accuracy using a landmark-based metric (target registration error (TRE)) and a digital phantom-based metric (known deformation recovery error (KDE)). 4DCT scans of 16 thoracic cancer patients along with corresponding pairwise anatomical landmarks (AL) locations were collected from two public databases. Digital phantoms with known deformations were generated by each DIR algorithm to test all other algorithms and compute KDE. TRE and KDE were evaluated at AL. KDE was additionally quantified in coordinates randomly sampled (RS) inside the lungs. Second, we investigated the associations of 5 DIR-derived metrics (distance discordance metric (DDM), inverse consistency error (ICE), transitivity (TE), spatial (SS) and temporal smoothness (TS)) with DIR accuracy through uni- and multivariable linear regression models. TRE values were found higher compared to KDE values and these varied depending on the phantom used. The algorithm with the best accuracy achieved average values of TRE = 1.1 mm and KDE ranging from 0.3 to 0.8 mm. DDM was the best predictor of DIR accuracy, with moderate correlations (R
2 < 0.61). Poor correlations were obtained at AL for algorithms with better accuracy, which improved when evaluated at RS. Only slight correlation improvement was obtained with a multivariable analysis (R
2 < 0.64). DDM can be a useful metric to identify inaccuracies for different DIR algorithms without employing landmarks or digital phantoms.
Magnetic separation of iron oxide nanoparticles to improve their application for magnetic particle imaging
Authors: Arsalani Soudabeh , Löwa Norbert , Kosch Olaf , Radon Patricia , Baffa Oswaldo , Wiekhorst Frank
Published: November 2020

Magnetic particle imaging (MPI) is a promising medical imaging technique for visualizing the three-dimensional distribution of tracer materials, specifically iron oxide nanoparticles (IONP). The optimization of magnetic nanoparticles (MNP) plays an essential role to improve the image resolution and sensitivity of imaging techniques. Objective. In this work, the optimization of commercial IONP (EMG 700, Ferrotec) coated with anionic surfactants was carried out using magnetic separation (MS) technique, by a low gradient magnetic separation (LGMS) (<15 T m−1) method, to improve their performance as MPI tracers. Approach. The magnetophoretical behavior of the samples in different concentrations ranging from 2 to 120 mmol l−1 was investigated over 24 h of separation. The samples were characterized by dynamic light scattering (DLS), AC susceptibility (ACS), magnetic particle spectroscopy (MPS) and they were imaged in a preclinical MPI scanner, before and after MS. Main results. DLS results showed that by increasing the concentration from 2 to 120 mmol l−1 the hydrodynamic diameter of MNP decrease from 75 to 47 nm and size distribution decrease from 0.19 to 0.11 after 4 min MS. In addition, the MPS results demonstrated the third harmonic amplitude normalized to the iron amount

(

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and harmonic ratio

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of signal increase from 8.38 to 10.59 Am2 kg−1 (Fe) and 24.21–26.60, respectively. Furthermore, the MPI images of the samples after separation showed higher MPI resolution. Significance. Therefore, LGMS can be considered as a valuable method to narrow and control the size distribution of MNP for MPI.
4D deep image prior: dynamic PET image denoising using an unsupervised four-dimensional branch convolutional neural network
Authors: Hashimoto Fumio , Ohba Hiroyuki , Ote Kibo , Kakimoto Akihiro , Tsukada Hideo , Ouchi Yasuomi
Published: November 2020

Although convolutional neural networks (CNNs) demonstrate the superior performance in denoising positron emission tomography (PET) images, a supervised training of the CNN requires a pair of large, high-quality PET image datasets. As an unsupervised learning method, a deep image prior (DIP) has recently been proposed; it can perform denoising with only the target image. In this study, we propose an innovative procedure for the DIP approach with a four-dimensional (4D) branch CNN architecture in end-to-end training to denoise dynamic PET images. Our proposed 4D CNN architecture can be applied to end-to-end dynamic PET image denoising by introducing a feature extractor and a reconstruction branch for each time frame of the dynamic PET image. In the proposed DIP method, it is not necessary to prepare high-quality and large patient-related PET images. Instead, a subject’s own static PET image is used as additional information, dynamic PET images are treated as training labels, and denoised dynamic PET images are obtained from the CNN outputs. Both simulation with [18F]fluoro-2-deoxy-D-glucose (FDG) and preclinical data with [18F]FDG and [11C]raclopride were used to evaluate the proposed framework. The results showed that our 4D DIP framework quantitatively and qualitatively outperformed 3D DIP and other unsupervised denoising methods. The proposed 4D DIP framework thus provides a promising procedure for dynamic PET image denoising.
Design of HL-2A plasma position predictive model based on deep learning
Authors: Yang Bin , Liu Zhenxing , Song Xianmin , Li Xiangwen
Published: November 2020

In tokamak discharge experiments, the plasma position prediction model’s research is to understand the law of plasma motion and verify the correctness of the plasma position controller design. Although Maxwell equations can completely describe plasma movement, obtaining an accurate physical model for predicting plasma behavior is still challenging. This paper describes a deep neural network model that can accurately predict the HL-2A plasma position. That is a hybrid neural network model based on a long short-term memory network. We introduce the topology, training parameter setting, and prediction result analysis of this model in detail. The test results show that a trained deep neural network model has high prediction accuracy for plasma vertical and horizontal displacements.
3D printing and dynamic modeling of a polymer-based bimodal piezoelectric motor
Authors: Li Xiaoniu , Yu De , Cao Teng , Wen Zhiyi , Lu Chunyao , Liu Wei , Zhu Chunling , Wu Dawei
Published: November 2020

Owing to characteristics of single-step fabrication and rapid prototyping, 3D printing have potential applications in processing piezoelectric motors with complex structures. In this paper, a 3D printed resin-based bimodal piezoelectric motor is proposed. Four slots of the motor are designed to reduce the influence of large damping caused by polymer’s viscoelastic and enhance mechanical properties. Considering the viscoelasticity and internal structure of the stator, a dynamic model based on the proposed motor is developed. Furthermore, parameters of these slots are optimized using the Taguchi method. Prototypes are fabricated and experimentally investigated. The results demonstrate that the first longitudinal mode and the second bending mode are 17 765 Hz and 18 006 Hz respectively, which are consistent with the analytical model results. Under the voltage of 300 Vpp, the maximum no-load speed and maximum driving load of the slotted motor are 200 r min−1 and 20 g with a speed of 6 r min−1, respectively. Compared with the motor without slots, the speed and load capacity are increased by 25% and 33%. Therefore, the motor with slots exhibits better mechanical output performance.
Global pattern of historical and future changes in rapid temperature variability
Authors: Xu Zhongfeng , Huang Fang , Liu Qi , Fu Congbin
Published: November 2020

Day-to-day (DTD) temperature variation reflects a rapid weather variability, which significantly affects human health and ecosystems. However, while a few of studies have addressed certain regional variations, no global pattern of rapid temperature variability has yet been investigated. Here, using global daily temperature observation data, we present a study of the worldwide spatial heterogeneity of rapid temperature variability and its long-term trends over the past 60 years. We found a significant decline in northern mid and high latitudes in boreal winter but a significant increase in the Arctic coast, South China and Australia in boreal summer during the study period. Using observational data and Coupled Model Intercomparison Project Phase 5 (CMIP5) multi-model ensemble simulations, we further demonstrate that the human-caused increase in greenhouse gases (GHGs) concentration leads to a significant change in meridional temperature gradient, which in turn results in the observed decline of rapid temperature variability in the mid and high latitudes and the increase in rapid temperature variability in Arctic Coast in summer. In contrast, human-induced increase in GHGs and aerosol accounts for approximately one third and two third of the decline of rapid temperature variability in North China in boreal summer, respectively. However, the increase in summer rapid temperature variability in southern China appears to be primarily associated with the long-term internal climate variability. It is further shown that, based on the CMIP5 multi-model ensemble simulations, the projected rapid temperature variability shows a significant decrease in the high latitudes in winter but a slight increase in tropical zones by the end of this century. These findings clearly reveal an important role of human activities on the historical and future rapid temperature variability.
Detecting the net effect of flooding on infectious diarrheal disease in Anhui Province, China: a quasi-experimental study
Authors: Liao Wenmin , Wu Jiabing , Yang Lianping , Benmarhnia Tarik , Liang Xin-Zhong , Murtugudde Raghu , Sapkota Amir , Ma Wenjun , Zhong Shuang , Huang Cunrui
Published: November 2020

Though a number of studies have shown positive relationships between flooding events and infectious diarrhea, there is a paucity of rigorous evidence regarding the net effect of flooding on diarrhea incidence, controlling for existing pre-trends and meteorological confounders. The study treats the 2016 catastrophic flood event in Anhui Province, China as a natural experiment using a difference-in-differences design with propensity score matching to exclude background variations of diarrhea occurrence and meteorological effects, thus isolating the net effect of flooding on diarrhea. A triple-differences analysis was further deployed to identify the potential effect modifiers, including gender, age, occupation and community health resources. By analyzing 359 580 cases of diarrhea that occurred before, during and after the flooding, we show that the 2016 flood event significantly increased the risk of dysentery (RR: 1.29, 95%CI: 1.15–1.46) in during-flood period, and also increased the risk of all-cause diarrhea (RR: 1.21, 95%CI: 1.17–1.26), typhoidal diarrhea, dysentery, and other infectious diarrhea in post-flood period. Children, males and non-farmers were particularly vulnerable to flooding impacts and the density of health professionals was found to be protective against diarrheal risk in both during-flood (RR: 0.81, 95% CI: 0.72–0.92) and post-flood (RR: 0.83, 95% CI: 0.77–0.88) periods. This study employs quasi-experimental design and provides a better understanding on both acute and sustained effects of flooding on diarrhea, which is important for accurate health impact assessments and developing targeted intervention strategies.
Geometry of efficient Electromagnetic Linear actuators for flapping wing MAVs
Authors: McIvor Blake A , Ogunwa Titilayo T , Chahl Javaan S
Published: November 2020

A constraining factor in the development of flapping wing micro air vehicles (MAVs) is the power density and efficiency of actuators. Piezoelectric and rotary electromagnetic actuators have been shown to have functional power densities but can require mechanically complex transmissions to create flapping motion. Electromagnetic Linear actuators (ELAs) have unique characteristics, allowing them to be controlled and implemented similarly to muscles but demonstrated much lower efficiency. This study presents configurations of ELA consisting of multiple coils and magnets that have the potential to improve efficiency. The use of lightweight conductors in the form of copper clad aluminium (CCA) is explored as a method to improve power density. A numerical method of optimising the geometry and mass distribution of the magnetic and conductive material is presented. The results show the power consumption of these actuators can range between 910-260 W/kg. The inclusion of an additional magnet and coil can improve efficiency by up to 3.5 times over typical flapping wing ELAs.
Transatlantic Noise
Authors: Meer Sarah
Published: November 2020

These three books position themselves within Atlantic studies, but despite significant differences in conceiving that frame, they all, to some extent, conflate the Atlantic world with the US. I suggest that this reflex contraction bears out the regular complaints that the field is prone to Eurocentricism, and dominated by northern, anglophone perspectives. Moreover, as the unequal distribution of academic prestige is reflected in our professional culture and its productions, it is worth attending to the effects of global disparities on writers, journals and scholarly organizations, and their responses to them. For Europeans, studying certain issues on the other side of the Atlantic can be a way to avoid facing them at home; meanwhile, the appearance of an African center for studying the US is hailed as a decolonizing event. Yet both manifest the westward pull of research attention that is so often evident in Atlantic studies, including in these books.

There is an important difference … between exploring one’s worldliness and mistaking oneself for the world. Each of the reviewed texts could be charged … with sailing an American ship under an Atlantic flag.
Encyclopedia of tools for the analysis of miRNA isoforms
Authors: Schmartz Georges Pierre , Kern Fabian , Fehlmann Tobias , Wagner Viktoria , Fromm Bastian , Keller Andreas
Published: November 2020

RNA sequencing data sets rapidly increase in quantity. For microRNAs (miRNAs), frequently dozens to hundreds of billion reads are generated per study. The quantification of annotated miRNAs and the prediction of new miRNAs are leading computational tasks. Now, the increased depth of coverage allows to gain deeper insights into the variability of miRNAs. The analysis of isoforms of miRNAs (isomiRs) is a trending topic, and a range of computational tools for the analysis of isomiRs has been developed. We provide an overview on 27 available computational solutions for the analysis of isomiRs. These include both stand-alone programs (17 tools) and web-based solutions (10 tools) and span a publication time range from 2010 to 2020. Seven of the tools were published in 2019 and 2020, confirming the rising importance of the topic. While most of the analyzed tools work for a broad range of organisms or are completely independent of a reference organism, several tools have been tailored for the analysis of human miRNA data or for plants. While 14 of the tools are general analysis tools of miRNAs, and isomiR analysis is one of their features, the remaining 13 tools have specifically been developed for isomiR analysis. A direct comparison on 20 deep sequencing data sets for selected tools provides insights into the heterogeneity of results. With our work, we provide users a comprehensive overview on the landscape of isomiR analysis tools and in that support the selection of the most appropriate tool for their respective research task.
Evolution of litter size in bats and its influence on longevity and roosting ecology
Authors: Garbino Guilherme Siniciato Terra , Feijó Anderson , Beltrão-Mendes Raone , Da Rocha Patrício Adriano
Published: November 2020

Litter size varies in mammals, with about half of the species producing at least two offspring per gestation (polytocy). In bats, however, the modal litter size is one (monotocy), and polytocy is restricted to family Vespertilionidae. Here, we reconstruct the evolutionary history of polytocy in chiropterans and use phylogenetically informed regressions to investigate its relationship to roost type, longevity and group size. Our phylogenetic reconstructions suggested that production of multiple offspring was the ancestral condition in family Vespertilionidae. The distribution of monotocy/polytocy in Chiroptera was best explained by a minimum of two evolutionary transitions from monotocy to polytocy and by ≥ 18 transitions from polytocy to monotocy. The regression models showed that longevity and roost type explained the variation in litter size, whereas group size did not. Our analyses also revealed a greater diversity of polytocous bats in the Northern Hemisphere, in both temperate and tropical regions. We suggest that the high resource allocation to reproduction in polytocous bats limited their lifespan. The absence of a relationship between polytocy and group size indicates that the benefits of cooperative breeding surpass the costs of intrasexual competition in bats.
Species diversity and biogeography of an ancient frog clade from the Guiana Shield (Anura: Microhylidae:Adelastes,Otophryne,Synapturanus) exhibiting spectacular phenotypic diversification
Authors: Fouquet Antoine , Leblanc Killian , Framit Marlene , Réjaud Alexandre , Rodrigues Miguel T , Castroviejo-Fisher Santiago , Peloso Pedro L V , Prates Ivan , Manzi Sophie , Suescun Uxue , Baroni Sabrina , Moraes Leandro J C L , Recoder Renato , de Souza Sergio Marques , Dal Vecchio Francisco , Camacho Agustín , Ghellere José Mario , Rojas-Runjaic Fernando J M , Gagliardi-Urrutia Giussepe , de Carvalho Vinícius Tadeu , Gordo Marcelo , Menin Marcelo , Kok Philippe J R , Hrbek Tomas , Werneck Fernanda P , Crawford Andrew J , Ron Santiago R , Mueses-Cisneros Jonh Jairo , Rojas Zamora Rommel Roberto , Pavan Dante , Ivo Simões Pedro , Ernst Raffael , Fabre Anne-Claire
Published: November 2020

The outstanding biodiversity of the Guiana Shield has raised many questions about its origins and evolution. Frogs of the genera Adelastes, Otophryne and Synapturanus form an ancient lineage distributed mostly across this region. These genera display strikingly disparate morphologies and life-history traits. Notably, Synapturanus is conspicuously adapted to fossoriality and is the only genus within this group to have dispersed further into Amazonia. Moreover, morphological differences among Synapturanus species suggest different degrees of fossoriality that might be linked to their biogeographical history. Through integrative analysis of genetic, morphometric and acoustic data, we delimited 25 species in this clade, representing a fourfold increase. We found that the entire clade started to diversify ~55 Mya and Synapturanus ~30 Mya. Members of this genus probably dispersed three times out of the Guiana Shield both before and after the Pebas system, a wetland ecosystem occupying most of Western Amazonia during the Miocene. Using a three-dimensional osteological dataset, we characterized a high morphological disparity across the three genera. Within Synapturanus, we further characterized distinct phenotypes that emerged concomitantly with dispersals during the Miocene and possibly represent adaptations to different habitats, such as soils with different physical properties.
Differentiation in the eastern AsianPeriphyllus koelreuteriae(Hemiptera: Aphididae) species complex driven by climate and host plant
Authors: Li Qiang , Lin Xiaolan , Li Junjie , Liu Bing , Huang Xiaolei
Published: November 2020

Divergent adaptation to different ecological conditions is regarded as important for speciation. For phytophagous insects, there is limited empirical evidence on species differentiation driven by climate and host plant. The recent application of molecular data and integrative taxonomic practice may improve our understanding of population divergence and speciation. Periphyllus koelreuteriae aphids feed exclusively on Koelreuteria (Sapindaceae) in temperate and subtropical regions of eastern Asia, and show morphological and phenological variations in different regions. In this study, phylogenetic and haplotype network analyses based on four genes revealed that P. koelreuteriae populations comprised three distinct genetic clades corresponding to climate and host plants, with the populations from subtropical highland regions and on Koelreuteria bipinnata host plants representing the most basal clade. These genetic lineages also showed distinct characteristics in terms of morphology and life cycle. The results indicate that P. koelreuteriae is a species complex with previously unrevealed lineages, whose differentiation may have been driven by climatic difference and host plant.
A benchmark for dose-finding studies with unknown ordering
Authors: Mozgunov Pavel , Paoletti Xavier , Jaki Thomas
Published: November 2020

An important tool to evaluate the performance of a dose-finding design is the nonparametric optimal benchmark that provides an upper bound on the performance of a design under a given scenario. A fundamental assumption of the benchmark is that the investigator can arrange doses in a monotonically increasing toxicity order. While the benchmark can be still applied to combination studies in which not all dose combinations can be ordered, it does not account for the uncertainty in the ordering. In this article, we propose a generalization of the benchmark that accounts for this uncertainty and, as a result, provides a sharper upper bound on the performance. The benchmark assesses how probable the occurrence of each ordering is, given the complete information about each patient. The proposed approach can be applied to trials with an arbitrary number of endpoints with discrete or continuous distributions. We illustrate the utility of the benchmark using recently proposed dose-finding designs for Phase I combination trials with a binary toxicity endpoint and Phase I/II combination trials with binary toxicity and continuous efficacy.
Constituting Child-to-Parent Violence: Lessons from England and Wales
Authors: Holt Amanda , Lewis Sam
Published: November 2020

This paper draws upon the first national study of local responses to child-to-parent violence (CPV) in England and Wales to examine emergent representations of CPV and consider their implications for children and families. Central amongst these is the Government’s depiction of CPV as a form of ‘domestic violence and abuse’. For many individuals and organizations, that term is synonymous with intimate partner violence. We contend that the resulting conflation of (and confusion between) violence by intimate partners, and by children, towards women is producing dominant representations of CPV that may have negative consequences for families. Our research with over 200 practitioners reveals the existence of subjugated knowledges of CPV, however, that provide pockets of resistance to these dominant representations.
Auditory localization should be considered as a sign of minimally conscious state based on multimodal findings
Authors: Carrière Manon , Cassol Helena , Aubinet Charlène , Panda Rajanikant , Thibaut Aurore , Larroque Stephen K , Simon Jessica , Martial Charlotte , Bahri Mohamed A , Chatelle Camille , Martens Géraldine , Chennu Srivas , Laureys Steven , Gosseries Olivia
Published: November 2020

Auditory localization (i.e. turning the head and/or the eyes towards an auditory stimulus) is often part of the clinical evaluation of patients recovering from coma. The objective of this study is to determine whether auditory localization could be considered as a new sign of minimally conscious state, using a multimodal approach. The presence of auditory localization and the clinical outcome at 2 years of follow-up were evaluated in 186 patients with severe brain injury, including 64 with unresponsive wakefulness syndrome, 28 in minimally conscious state minus, 71 in minimally conscious state plus and 23 who emerged from the minimally conscious state. Brain metabolism, functional connectivity and graph theory measures were investigated by means of 18F-fluorodeoxyglucose positron emission tomography, functional MRI and high-density electroencephalography in two subgroups of unresponsive patients, with and without auditory localization. These two subgroups were also compared to a subgroup of patients in minimally conscious state minus. Auditory localization was observed in 13% of unresponsive patients, 46% of patients in minimally conscious state minus, 62% of patients in minimally conscious state plus and 78% of patients who emerged from the minimally conscious state. The probability to observe an auditory localization increased along with the level of consciousness, and the presence of auditory localization could predict the level of consciousness. Patients with auditory localization had higher survival rates (at 2-year follow-up) than those without localization. Differences in brain function were found between unresponsive patients with and without auditory localization. Higher connectivity in unresponsive patients with auditory localization was measured between the fronto-parietal network and secondary visual areas, and in the alpha band electroencephalography network. Moreover, patients in minimally conscious state minus significantly differed from unresponsive patients without auditory localization in terms of brain metabolism and alpha network centrality, whereas no difference was found with unresponsive patients who presented auditory localization. Our multimodal findings suggest differences in brain function between unresponsive patients with and without auditory localization, which support our hypothesis that auditory localization should be considered as a new sign of minimally conscious state. Unresponsive patients showing auditory localization should therefore no longer be considered unresponsive but minimally conscious. This would have crucial consequences on these patients’ lives as it would directly impact the therapeutic orientation or end-of-life decisions usually taken based on the diagnosis.
Frequent neurocognitive deficits after recovery from mild COVID-19
Authors: Woo Marcel S , Malsy Jakob , Pöttgen Jana , Seddiq Zai Susan , Ufer Friederike , Hadjilaou Alexandros , Schmiedel Stefan , Addo Marylyn M , Gerloff Christian , Heesen Christoph , Schulze Zur Wiesch Julian , Friese Manuel A
Published: November 2020

Neuropsychiatric complications associated with coronavirus disease 2019 caused by the Coronavirus SARS-CoV-2 (COVID-19) are increasingly appreciated. While most studies have focussed on severely affected individuals during acute infection, it remains unclear whether mild COVID-19 results in neurocognitive deficits in young patients. Here, we established a screening approach to detect cognitive deficiencies in post-COVID-19 patients. In this cross-sectional study, we recruited 18 mostly young patients 20–105 days (median, 85 days) after recovery from mild to moderate disease who visited our outpatient clinic for post-COVID-19 care. Notably, 14 (78%) patients reported sustained mild cognitive deficits and performed worse in the Modified Telephone Interview for Cognitive Status screening test for mild cognitive impairment compared to 10 age-matched healthy controls. While short-term memory, attention and concentration were particularly affected by COVID-19, screening results did not correlate with hospitalization, treatment, viremia or acute inflammation. Additionally, Modified Telephone Interview for Cognitive Status scores did not correlate with depressed mood or fatigue. In two severely affected patients, we excluded structural or other inflammatory causes by magnetic resonance imaging, serum and cerebrospinal fluid analyses. Together, our results demonstrate that sustained sub-clinical cognitive impairments might be a common complication after recovery from COVID-19 in young adults, regardless of clinical course that were unmasked by our diagnostic approach.
Distribution and prognostic impact of M1 macrophage on esophageal squamous cell carcinoma
Authors: Jiang Chen Hao , Liang Wei Hua , Li Fan Ping , Xie Yu Fang , Yuan Xin , Zhang Hai Jun , Li Man , Li Jiang Fen , Zhang An Zhi , Yang Lan , Liu Chun Xia , Pang Li Juan , Li Feng , Hu Jian Ming
Published: November 2020

Macrophages are a double-edged sword with potential cancer-promoting and anticancer effects. Controversy remains regarding the effect of macrophages, especially M1 macrophages, on tumor promotion and suppression. We aimed to investigate the role of M1 macrophages in the occurrence and progression of esophageal squamous cell carcinoma (ESCC). Analyzing the data in Gene Expression Omnibus database by the CIBERSORT algorithm found that M1 macrophages were one of the important components of many immune cells in ESCCs, and the increase in their number was obviously negatively correlated with tumor T staging. This result was verified by our experimental data: the density of CD68/HLA-DR double-stained M1 macrophages in ESCC tumor nest and tumor stroma was significantly higher than that in cancer-adjacent normal (CAN) tissues. The density of M1 macrophages in ESCC tumor nest was negatively correlated with the patient’s lymph node metastasis and clinical stage (P < 0.05), and the negative tendency was more obvious for M1 macrophages in ESCC tumor stroma (P < 0.001). Exposure to M1 macrophage-conditioned medium inhibited ESCC cell migration and invasion ability significantly (P < 0.05). Moreover, the increased M1 macrophage density in ESCC tumor stroma correlated positively with good prognosis of ESCC. M1 macrophages were involved in inhibiting ESCC cell migration and invasion, which could serve as a good prognostic factor in patients with ESCC.
Actual and Imagined Movements Reveal a Dual Role of the Insular Cortex for Motor Control
Authors: Rousseau Célia , Barbiero Marie , Pozzo Thierry , Papaxanthis Charalambos , White Olivier
Published: November 2020

Movements rely on a mixture of feedforward and feedback mechanisms. With experience, the brain builds internal representations of actions in different contexts. Many factors are taken into account in this process among which is the immutable presence of gravity. Any displacement of a massive body in the gravitational field generates forces and torques that must be predicted and compensated by appropriate motor commands. The insular cortex is a key brain area for graviception. However, no attempt has been made to address whether the same internal representation of gravity is shared between feedforward and feedback mechanisms. Here, participants either mentally simulated (only feedforward) or performed (feedforward and feedback) vertical movements of the hand. We found that the posterior part of the insular cortex was engaged when feedback was processed. The anterior insula, however, was activated only in mental simulation of the action. A psychophysical experiment demonstrates participants’ ability to integrate the effects of gravity. Our results point toward a dual internal representation of gravity within the insula. We discuss the conceptual link between these two dualities.
Desirability of Outcome Ranking for the Management of Antimicrobial Therapy (DOOR MAT): A Framework for Assessing Antibiotic Selection Strategies in the Presence of Drug Resistance
Authors: Wilson Brigid M , Jiang Yunyun , Jump Robin L P , Viau Roberto A , Perez Federico , Bonomo Robert A , Evans Scott R
Published: November 2020

The complexities of antibiotic resistance mean that successful stewardship must consider both the effectiveness of a given antibiotic and the spectrum of that therapy to minimize imposing further selective pressure. To meet this challenge, we propose the Desirability of Outcome Ranking approach for the Management of Antimicrobial Therapy (DOOR MAT), a flexible quantitative framework that evaluates the desirability of antibiotic selection. Herein, we describe the steps required to implement DOOR MAT and present examples to illustrate how the desirability of treatment selection can be evaluated using resistance information. While treatments and the scoring of treatment selections must be adapted to specific clinical settings, the principle of DOOR MAT remains constant: The most desirable antibiotic choice effectively treats the patient while exerting minimal pressure on future resistance.
Tofacitinib for the Treatment of Ulcerative Colitis: Analysis of Infection Rates from the Ulcerative Colitis Clinical Programme
Authors: Winthrop Kevin L , Loftus Edward V , Baumgart Daniel C , Reinisch Walter , Nduaka Chudy I , Lawendy Nervin , Chan Gary , Mundayat Rajiv , Friedman Gary S , Salese Leonardo , Thorpe Andrew J , Su Chinyu
Published: November 2020

Background and Aims

Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of ulcerative colitis. We report integrated analyses of infections in the Phase [P]2 and P3 OCTAVE programmes.

Methods

Three cohorts were analysed: Induction [P2/3 induction studies]; Maintenance [P3 maintenance study]; and Overall [all tofacitinib-treated patients in induction, maintenance, or ongoing, open-label, long-term extension studies; as of May 2019]. Proportions and incidence rates [IRs; unique patients with events/100 patient-years] of serious infections [SIs], herpes zoster [HZ] [non-serious and serious], and opportunistic infections [OIs] are reported [censored at time of event].

Results

In the Induction Cohort [N = 1220], no patients receiving placebo and eight [0.9%] receiving tofacitinib 10 mg twice daily [BID] developed SIs. Maintenance Cohort [N = 592] SI IRs (95% confidence interval [CI]) were 1.94 [0.23–7.00] for placebo and 1.35 [0.16–4.87] and 0.64 [0.02–3.54] for tofacitinib 5 and 10 mg BID, respectively; HZ IRs were 0.97 [0.02–5.42], 2.05 [0.42–6.00], and 6.64 [3.19–12.22], respectively. In the Overall Cohort [N = 1157; 82.9% predominantly received tofacitinib 10 mg BID], SI, HZ, and non-HZ OI IRs were 1.70 [1.24–2.27], 3.48 [2.79–4.30], and 0.15 [0.04–0.38], respectively. No SIs resulted in death.

Conclusions

During induction, SIs were more frequent with tofacitinib versus placebo. SIs were generally infrequent in the Maintenance and Overall Cohorts, with rates comparable between treatment groups. Maintenance Cohort HZ IR was numerically higher with tofacitinib 10 mg BID versus 5 mg BID. Overall Cohort HZ IRs remained stable over time. Non-HZ OIs and viral infections were rare.