bluuebunny/crossref_metadata_2025 huggingface dataset:
Does One Dose Really Fit All? On the Monitoring of Direct Oral Anticoagulants: A Review of the Literature
Authors: Moner-Banet Thomas , Alberio Lorenzo , Bart Pierre-Alexandre
Published: May 2020

Background There is an increasing amount of literature on direct oral anticoagulant (DOAC) laboratory monitoring. The aims of the present review were to evaluate published data on monitoring DOACs, to provide clinical guidance on how to interpret results, and to summarize why, when, and how to monitor DOACs.

Methods The publications screened for this review were obtained through a PubMed search for articles published in English or French before April 2019 that had the following as their main themes: DOAC monitoring, DOAC exposure–effect relationship, DOAC drug interactions, and pharmacokinetics and pharmacodynamics of DOACs.

Results DOACs show important inter- and intrapersonal concentration variability and a significant exposure–effect relationship. Concentrations out of the expected range have been shown to lead to an increased adverse event rate and a lower efficacy. No definitive therapeutic range exists for DOACs except for dabigatran for which trough levels of 40 to 200 ng/mL seem to be the consensus. Indications to monitor include suspected drug accumulation in special patient populations, suspected drug failure, and acute situations such as hemorrhagic or thrombotic events.

Conclusion There is a likely benefit to monitor DOACs in order to improve their safety and efficacy but randomized controlled trials are required to determine the therapeutic range of these drugs and evaluate whether DOAC monitoring can improve outcomes in a clinical setting.
Flickering of cardiac state before the onset and termination of atrial fibrillation
Authors: Lan Boon Leong , Liew Yew Wai , Toda Mikito , Kamsani Suraya Hani
Published: May 2020

Complex dynamical systems can shift abruptly from a stable state to an alternative stable state at a tipping point. Before the critical transition, the system either slows down in its recovery rate or flickers between the basins of attraction of the alternative stable states. Whether the heart critically slows down or flickers before it transitions into and out of paroxysmal atrial fibrillation (PAF) is still an open question. To address this issue, we propose a novel definition of cardiac states based on beat-to-beat (RR) interval fluctuations derived from electrocardiogram data. Our results show the cardiac state flickers before PAF onset and termination. Prior to onset, flickering is due to a “tug-of-war” between the sinus node (the natural pacemaker) and atrial ectopic focus/foci (abnormal pacemakers), or the pacing by the latter interspersed among the pacing by the former. It may also be due to an abnormal autonomic modulation of the sinus node. This abnormal modulation may be the sole cause of flickering prior to termination since atrial ectopic beats are absent. Flickering of the cardiac state could potentially be used as part of an early warning or screening system for PAF and guide the development of new methods to prevent or terminate PAF. The method we have developed to define system states and use them to detect flickering can be adapted to study critical transition in other complex systems.
Relativistic plasma physics in supercritical fields
Authors: Zhang P. , Bulanov S. S. , Seipt D. , Arefiev A. V. , Thomas A. G. R.
Published: May 2020

Since the invention of chirped pulse amplification, which was recognized by a Nobel Prize in physics in 2018, there has been a continuing increase in available laser intensity. Combined with advances in our understanding of the kinetics of relativistic plasma, studies of laser–plasma interactions are entering a new regime where the physics of relativistic plasmas is strongly affected by strong-field quantum electrodynamics (QED) processes, including hard photon emission and electron–positron (e−–e+) pair production. This coupling of quantum emission processes and relativistic collective particle dynamics can result in dramatically new plasma physics phenomena, such as the generation of dense e−–e+ pair plasma from near vacuum, complete laser energy absorption by QED processes, or the stopping of an ultra-relativistic electron beam, which could penetrate a cm of lead, by a hair's breadth of laser light. In addition to being of fundamental interest, it is crucial to study this new regime to understand the next generation of ultra-high intensity laser-matter experiments and their resulting applications, such as high energy ion, electron, positron, and photon sources for fundamental physics studies, medical radiotherapy, and next generation radiography for homeland security and industry.
Defect limitations in Cu2ZnSn(S, Se)4 solar cells utilizing an In2S3 buffer layer
Authors: Campbell Stephen , Qu Yongtao , Gibbon James , Edwards Holly J. , Dhanak Vin R. , Tiwari Devendra , Barrioz Vincent , Beattie Neil S. , Zoppi Guillaume
Published: May 2020

Alternative n-type buffer layer such as In2S3 has been proposed as a Cd-free alternative in kesterite Cu2ZnSn(S,Se)4 (CZTSSe) solar cells. In this study, optical and electronic characterization techniques together with device analysis and simulation were used to assess nanoparticle-based CZTSSe absorbers and solar cells with CdS and In2S3 buffers. Photoluminescence spectroscopy indicated that CZTSSe absorbers with In2S3 buffer had a lower density of detrimental non-radiative defects and a higher concentration of copper vacancies VCu+, responsible for p-type conductivity in CZTSSe, in comparison to the absorber with CdS buffer. Capacitance–voltage (C–V) measurements revealed that the In2S3 buffer-based CZTSSe devices had a three times higher apparent doping density and a consequently narrower space charge region than devices with a CdS layer. This resulted in poorer collection of photo-generated charge carriers in the near-IR region despite a more favorable band alignment as determined by x-ray photoelectron and inverse photoelectron spectroscopy. The presence of interfacial defect states in In2S3 devices as determined by C–V and biased quantum efficiency measurements is also responsible for the loss in open-circuit voltage compared with reference devices with CdS.
Temporal differential elastic wave computational metamaterials
Authors: Lv Zengyao , Ding Yuanshuai , Pei Yongmao
Published: May 2020

Computational metamaterials have enabled the realization of real-time mathematical operations in spatial and time domains. Here, we present the design and experimental demonstration of time-domain differential operations based on an elastic wave computational metamaterial. For generality and universality, the linearity and the product rule for the wave-based differentiation are also verified, as well as the functionality of cascaded differentiators. We expect that acoustic computational metamaterials will enable new capabilities in signal acquisition and processing and network computing and drive new applications of the sound wave.
Strain-promoted perpendicular magnetic anisotropy in Co–Rh alloys
Authors: Aksu P. , Deger C. , Yavuz I. , Yildiz F.
Published: May 2020

We report on a comprehensive experimental, numerical, and computational investigation on the concentration dependence of the structural/magnetic properties of Co–Rh alloy films. A sizable perpendicular magnetic anisotropy is achieved by controlling the lattice strain via the Co content. Within the 30–40% range of Co concentrations, an experimental effective magnetic anisotropy on the order of 100 kJ/m3 and a computational uniaxial magnetic anisotropy energy of 567 μeV/atom have been observed. First-principles calculations revealed that the lattice strain promotes a strong d-orbital degeneracy near the Fermi level for 40% of Co concentration, leading to an enhanced magnetic anisotropy energy.
Perspectives on high resolution microvascular imaging with contrast ultrasound
Authors: Kierski Thomas M. , Dayton Paul A.
Published: May 2020

Recent developments in contrast enhanced ultrasound have demonstrated a potential to visualize small blood vessels in vivo, unlike anything possible with traditional grayscale ultrasound. This Perspective article introduces microvascular imaging strategies and their underlying technology.
Superdiffusive transport of energy in one-dimensional metals
Authors: Bulchandani Vir B. , Karrasch Christoph , Moore Joel E.
Published: May 2020

Metals in one spatial dimension are described at the lowest energy scales by the Luttinger liquid theory. It is well understood that this free theory, and even interacting integrable models, can support ballistic transport of conserved quantities including energy. In contrast, realistic one-dimensional metals, even without disorder, contain integrability-breaking interactions that are expected to lead to thermalization and conventional diffusive linear response. We argue that the expansion of energy when such a nonintegrable Luttinger liquid is locally heated above its ground state shows superdiffusive behavior (i.e., spreading of energy that is intermediate between diffusion and ballistic propagation), by combining an analytical anomalous diffusion model with numerical matrix-product–state calculations on a specific perturbed spinless fermion chain. Different metals will have different scaling exponents and shapes in their energy spreading, but the superdiffusive behavior is stable and should be visible in time-resolved experiments.
The multi-faceted mechano-bactericidal mechanism of nanostructured surfaces
Authors: Ivanova Elena P. , Linklater Denver P. , Werner Marco , Baulin Vladimir A. , Xu XiuMei , Vrancken Nandi , Rubanov Sergey , Hanssen Eric , Wandiyanto Jason , Truong Vi Khanh , Elbourne Aaron , Maclaughlin Shane , Juodkazis Saulius , Crawford Russell J.
Published: May 2020

Significance

The bactericidal action delivered by rigid nanopillar arrays stems from the mechanical rupture of the bacterial cell membrane; however, the precise mechanism may be unique to the individual nanopillar geometries. In this study, we demonstrate that the bactericidal action of highly ordered, high-aspect-ratio nanopillar arrays may be associated with the relative flexibility of the individual nanopillars and the mechanical energy stored within the nanopillars. We propose that the lateral stretching of the cell membrane and interactions at the cell edge are induced by elastic pillar deformations that occur during bacterial adhesion. The results obtained in this study provide insight into a previously unknown category of mechano-bactericidal mechanism, highlighting another facet to the mechano-bactericidal action of nanostructured surfaces.
Imperfect transparency and camouflage in glass frogs
Authors: Barnett James B. , Michalis Constantine , Anderson Hannah M. , McEwen Brendan L. , Yeager Justin , Pruitt Jonathan N. , Scott-Samuel Nicholas E. , Cuthill Innes C.
Published: May 2020

Camouflage patterns prevent detection and/or recognition by matching the background, disrupting edges, or mimicking particular background features. In variable habitats, however, a single pattern cannot match all available sites all of the time, and efficacy may therefore be reduced. Active color change provides an alternative where coloration can be altered to match local conditions, but again efficacy may be limited by the speed of change and range of patterns available. Transparency, on the other hand, creates high-fidelity camouflage that changes instantaneously to match any substrate but is potentially compromised in terrestrial environments where image distortion may be more obvious than in water. Glass frogs are one example of terrestrial transparency and are well known for their transparent ventral skin through which their bones, intestines, and beating hearts can be seen. However, sparse dorsal pigmentation means that these frogs are better described as translucent. To investigate whether this imperfect transparency acts as camouflage, we used in situ behavioral trials, visual modeling, and laboratory psychophysics. We found that the perceived luminance of the frogs changed depending on the immediate background, lowering detectability and increasing survival when compared to opaque frogs. Moreover, this change was greatest for the legs, which surround the body at rest and create a diffuse transition from background to frog luminance rather than a sharp, highly salient edge. This passive change in luminance, without significant modification of hue, suggests a camouflage strategy, “edge diffusion,” distinct from both transparency and active color change.
Orbital-use fees could more than quadruple the value of the space industry
Authors: Rao Akhil , Burgess Matthew G. , Kaffine Daniel
Published: May 2020

The space industry’s rapid recent growth represents the latest tragedy of the commons. Satellites launched into orbit contribute to—and risk damage from—a growing buildup of space debris and other satellites. Collision risk from this orbital congestion is costly to satellite operators. Technological and managerial solutions—such as active debris removal or end-of-life satellite deorbit guidelines—are currently being explored by regulatory authorities. However, none of these approaches address the underlying incentive problem: satellite operators do not account for costs they impose on each other via collision risk. Here, we show that an internationally harmonized orbital-use fee can correct these incentives and substantially increase the value of the space industry. We construct and analyze a coupled physical–economic model of commercial launches and debris accumulation in low-Earth orbit. Similar to carbon taxes, our model projects an optimal fee that rises at a rate of 14% per year, equal to roughly $235,000 per satellite-year in 2040. The long-run value of the satellite industry would more than quadruple by 2040—increasing from around $600 billion under business as usual to around $3 trillion. In contrast, we project that purely technological solutions are unlikely to fully address the problem of orbital congestion. Indeed, we find debris removal sometimes worsens economic damages from congestion by increasing launch incentives. In other sectors, addressing the tragedy of the commons has often been a game of catch-up with substantial social costs. The infant space industry can avert these costs before they escalate.
Quantum critical phenomena in a compressible displacive ferroelectric
Authors: Coak Matthew J. , Haines Charles R. S. , Liu Cheng , Rowley Stephen E. , Lonzarich Gilbert G. , Saxena Siddharth S.
Published: May 2020

The dielectric and magnetic polarizations of quantum paraelectrics and paramagnetic materials have in many cases been found to initially increase with increasing thermal disorder and hence, exhibit peaks as a function of temperature. A quantitative description of these examples of “order-by-disorder” phenomena has remained elusive in nearly ferromagnetic metals and in dielectrics on the border of displacive ferroelectric transitions. Here, we present an experimental study of the evolution of the dielectric susceptibility peak as a function of pressure in the nearly ferroelectric material, strontium titanate, which reveals that the peak position collapses toward absolute zero as the ferroelectric quantum critical point is approached. We show that this behavior can be described in detail without the use of adjustable parameters in terms of the Larkin–Khmelnitskii–Shneerson–Rechester (LKSR) theory, first introduced nearly 50 y ago, of the hybridization of polar and acoustic modes in quantum paraelectrics, in contrast to alternative models that have been proposed. Our study allows us to construct a detailed temperature–pressure phase diagram of a material on the border of a ferroelectric quantum critical point comprising ferroelectric, quantum critical paraelectric, and hybridized polar-acoustic regimes. Furthermore, at the lowest temperatures, below the susceptibility maximum, we observe a regime characterized by a linear temperature dependence of the inverse susceptibility that differs sharply from the quartic temperature dependence predicted by the LKSR theory. We find that this non-LKSR low-temperature regime cannot be accounted for in terms of any detailed model reported in the literature, and its interpretation poses an empirical and conceptual challenge.
Factors affecting L2 phonological awareness in Chinese-Dutch preschoolers
Authors: Yuan Han , Segers Eliane , Verhoeven Ludo
Published: May 2020

The present study compared the relationship between Dutch phonological awareness (rhyme awareness, initial phoneme
isolation), Dutch speech decoding and Dutch receptive vocabulary in two groups in different linguistic environments: 30 Mandarin
Chinese-Dutch bilingual children and 24 monolingual Dutch peers. Chinese vocabulary and phonological awareness were taken into account in
the bilingual group. Bilingual children scored below their Dutch monolingual counterparts on all Dutch tasks. In the bilingual group, Dutch
rhyme awareness was predicted by Dutch speech decoding, both directly, and indirectly via Dutch receptive vocabulary. When adding Chinese
proficiency to the model, Chinese rhyme awareness was found to mediate the relationship between Dutch speech decoding and Dutch rhyme
awareness. It can thus be concluded that second language (L2) phonological awareness in Chinese-Dutch kindergartners is affected by their L2
speech and vocabulary level, on the one hand, and their level of phonological awareness in the first language (L1).
Peasants, dispossession and resistance in Egypt: an analysis of protest movements and organisations before and after the 2011 uprising
Authors: de Lellis Francesco
Published: May 2020

The livelihoods of Egypt’s agrarian working classes have been under attack for at least 30 years by policies dispossessing them of natural and economic resources. This process accelerated in the mid 1990s when a domestic land grab took place, eradicating tenure rights for poor tenants. Rural Egypt was part of the 2011 revolutionary process, although heavily marginalised in narratives about the ‘Spring’. Land occupations, farmers’ protests and unionisation were part of the revolutionary landscape, in direct continuity with previous struggles, but also showing signs of rupture and innovation. Reactions from below against dispossession have been variegated and developing, but their determinants remain largely unaddressed. The article retraces the trajectories of these struggles, pointing at the crucial role that the peasants’ allies (leftist civic activism, NGOs and political parties) have played in enhancing and/or undermining agrarian movements at particular historical conjunctures.
Energy-reduced beta radiation fields from90Sr/90Y for the BSS 2
Authors: Behrens R.
Published: May 2020

For decades, the irradiation facility for beta radiation, the Beta Secondary Standard BSS 2 developed at PTB, has been in worldwide use to irradiate dosemeters, detectors and other devices with calibrated beta sources. In this work two energy-reduced radiation fields based on the90Sr/90Y source are described. Their electron and photon particle spectra are made available as data files. In addition, angular distributions and the depth dose profiles are given. The spectra were determined using the Monte Carlo particle transport code EGSnrc/BEAMnrc and are provided in the supplementary data.
Preliminary study of nitrite content in South Sulawesi uncleaned edible bird nest
Authors: Yusuf B , Farahmida P , Jamaluddin A W , Amir M N , Maulany R I , Sari D K
Published: May 2020

Edible bird nest is a nest made from saliva of swiftlet (Aerodramus fuciphagus). In term of food safety, nitrite is one of chemical hazards that should be checked in edible bird nest (EBN) which can affect human health. Occurance of nitrite in edible bird nest is determined from its level in uncleaned EBN and cleaning process. This preliminary study was aimed to check level of nitrite in edible bird nest taken from swiftlet houses in South Sulawesi. The nitrite analysis using spectrophotometer showed that nitrite content is varied among swiftlet houses ranged from 4.7 µg/g to 164.4 µg/g. This result showed that most EBN sample in uncleaned South Sulawesi edible bird nest is below the limit of nitrite content regulated by Indonesian government which is 125 µg/g. This finding also indicates that good farming practice should be introduced into swiftlet farmers.
Extraction of thermally stable cellulose nanocrystals in short processing time from waste newspaper by conventional acid hydrolysis
Authors: Van-Pham Dan-Thuy , Pham Thi Yen Nhu , Tran Minh Chien , Nguyen Chanh-Nghiem , Tran-Cong-Miyata Qui
Published: May 2020

Motivated by many exclusive and useful features of cellulose nanocrystals (CNC) and the underutilized resource of waste newspaper, this study aimed to extract CNC from waste newspapers by means of alkali and bleaching treatments followed by acid hydrolysis. The morphological structure of the obtained CNC was analysed by optical microscopy, scanning electron microscopy (SEM), and transmission electron microscopy (TEM) methods. The remarkable removal of surface contamination and the reduction in fiber diameter during alkali and bleaching treatment were observed and the nano-dimension of the extracted CNC was revealed with the average diameter of 12.3 ± 2.8 nm. Characterization of the extracted CNC showed a high whiteness index of 80%, and high transparency of about 80% of the light at 600 nm calculated for a 0.02 mm thick nanocellulose film. Fourier transform infrared spectroscopy (FTIR) indicated that lignin, hemicellulose and other coloring agents were successfully removed. A comparably high crystallinity index of 80.15% was calculated from x-ray diffraction data. Thermogravimetric analysis showed that the product had a typical maximum thermal degradation at 300 °C. The analysis results indicated the successful extraction of good CNC from waste newspaper with the shortest processing time ever reported for acid hydrolysis with conventional alkali and bleaching pretreatment. The findings also strongly support for further research of nanocomposites reinforced by CNC produced from waste newspaper.
The COVID-19 rehabilitation pandemic
Authors: De Biase Sarah , Cook Laura , Skelton Dawn A , Witham Miles , ten Hove Ruth
Published: May 2020

The coronavirus disease 2019 (COVID-19) pandemic and the response to the pandemic are combining to produce a tidal wave of need for rehabilitation. Rehabilitation will be needed for survivors of COVID-19, many of whom are older, with underlying health problems. In addition, rehabilitation will be needed for those who have become deconditioned as a result of movement restrictions, social isolation, and inability to access healthcare for pre-existing or new non-COVID-19 illnesses. Delivering rehabilitation in the same way as before the pandemic will not be practical, nor will this approach meet the likely scale of need for rehabilitation. This commentary reviews the likely rehabilitation needs of older people both with and without COVID-19 and discusses how strategies to deliver effective rehabilitation at scale can be designed and implemented in a world living with COVID-19.
Filtering Tort Accidents
Authors: De Mot Jef , Depoorter Ben , Miceli Thomas J
Published: May 2020

Conventional wisdom in the economic analysis of tort law holds that legal errors distort incentives, causing behavior to depart from the optimum. If potential injurers know that courts err, they may engage in less or more than optimal precaution. This article revisits the effect of judicial error on the incentives of potential injurers by identifying a heretofore-neglected filtering effect of uncertainty in settings of imperfect judicial decision-making. We show that when courts make errors in the application of the liability standards, uncertainty about erroneous decision-making filters out the most harmful torts but leaves unaffected less harmful accidents. Our insight applies to various procedural and institutional aspects of legal adjudication, including the randomization of case assignment, the strength of precedent, and the use of standards versus rules.
VI—Panpsychism and Free Will: A Case Study in Liberal Naturalism
Authors: Goff Philip
Published: May 2020

There has been a resurgence of interest in panpsychism in contemporary philosophy of mind. According to its supporters, panpsychism offers an attractive solution to the mind–body problem, avoiding the deep difficulties associated with the more conventional options of dualism and materialism. There has been little focus, however, on whether panpsychism can help with philosophical problems pertaining to free will. In this paper I will argue (a) that it is coherent and consistent with observation to postulate a kind of libertarian agent causation at the micro-level, and (b) that if one if believes in libertarian agent causation at the macro-level, there are significant advantages in also postulating its existence at the micro-level.
Using deep neural networks and biological subwords to detect protein S-sulfenylation sites
Authors: Do Duyen Thi , Le Thanh Quynh Trang , Le Nguyen Quoc Khanh
Published: May 2020

Protein S-sulfenylation is one kind of crucial post-translational modifications (PTMs) in which the hydroxyl group covalently binds to the thiol of cysteine. Some recent studies have shown that this modification plays an important role in signaling transduction, transcriptional regulation and apoptosis. To date, the dynamic of sulfenic acids in proteins remains unclear because of its fleeting nature. Identifying S-sulfenylation sites, therefore, could be the key to decipher its mysterious structures and functions, which are important in cell biology and diseases. However, due to the lack of effective methods, scientists in this field tend to be limited in merely a handful of some wet lab techniques that are time-consuming and not cost-effective. Thus, this motivated us to develop an in silico model for detecting S-sulfenylation sites only from protein sequence information. In this study, protein sequences served as natural language sentences comprising biological subwords. The deep neural network was consequentially employed to perform classification. The performance statistics within the independent dataset including sensitivity, specificity, accuracy, Matthews correlation coefficient and area under the curve rates achieved 85.71%, 69.47%, 77.09%, 0.5554 and 0.833, respectively. Our results suggested that the proposed method (fastSulf-DNN) achieved excellent performance in predicting S-sulfenylation sites compared to other well-known tools on a benchmark dataset.
Unnecessary Antibiotic Prescribing in US Ambulatory Care Settings, 2010–2015
Authors: Hersh Adam L , King Laura M , Shapiro Daniel J , Hicks Lauri A , Fleming-Dutra Katherine E
Published: May 2020

The proportion of antibiotic prescriptions prescribed in US physician offices and emergency departments that were unnecessary decreased slightly, from 30% in 2010–2011 to 28% in 2014–2015. However, a greater decrease occurred in children: 32% in 2010–2011 to 19% in 2014–2015. Unnecessary prescribing in adults did not change during this period.
Evidence for height and immune function trade-offs among preadolescents in a high pathogen population
Authors: Garcia Angela R , Blackwell Aaron D , Trumble Benjamin C , Stieglitz Jonathan , Kaplan Hillard , Gurven Michael D
Published: May 2020

Background

In an energy-limited environment, caloric investments in one characteristic should trade-off with investments in other characteristics. In high pathogen ecologies, biasing energy allocation towards immune function over growth would be predicted, given strong selective pressures against early-life mortality.

Methodology

In the present study, we use flow cytometry to examine trade-offs between adaptive immune function (T cell subsets, B cells), innate immune function (natural killer cells), adaptive to innate ratio and height-for-age z scores (HAZ) among young children (N = 344; aged 2 months–8 years) in the Bolivian Amazon, using maternal BMI and child weight-for-height z scores (WHZ) as proxies for energetic status.

Results

Markers of adaptive immune function negatively associate with child HAZ, a pattern most significant in preadolescents (3+ years). In children under three, maternal BMI appears to buffer immune and HAZ associations, while child energetic status (WHZ) moderates relationships in an unexpected direction: HAZ and immune associations are greater in preadolescents with higher WHZ. Children with low WHZ maintain similar levels of adaptive immune function, but are shorter compared to high WHZ peers.

Conclusions

Reduced investment in growth in favor of immunity may be necessary for survival in high pathogen contexts, even under energetic constraints. Further, genetic and environmental factors are important considerations for understanding variation in height within this population. These findings prompt consideration of whether there may be a threshold of investment into adaptive immunity required for survival in high pathogen environments, and thus question the universal relevance of height as a marker of health.

Lay Summary

Adaptive immune function is negatively associated with child height in this high pathogen environment. Further, low weight-for-height children are shorter but maintain similar immune levels. Findings question the relevance of height as a universal health marker, given that costs and benefits of height versus immunity may be calibrated to local ecology.
Machine learning does not improve upon traditional regression in predicting outcomes in atrial fibrillation: an analysis of the ORBIT-AF and GARFIELD-AF registries
Authors: Loring Zak , Mehrotra Suchit , Piccini Jonathan P , Camm John , Carlson David , Fonarow Gregg C , Fox Keith A A , Peterson Eric D , Pieper Karen , Kakkar Ajay K
Published: May 2020

Aims

Prediction models for outcomes in atrial fibrillation (AF) are used to guide treatment. While regression models have been the analytic standard for prediction modelling, machine learning (ML) has been promoted as a potentially superior methodology. We compared the performance of ML and regression models in predicting outcomes in AF patients.

Methods and results

The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation (ORBIT-AF) and Global Anticoagulant Registry in the FIELD (GARFIELD-AF) are population-based registries that include 74 792 AF patients. Models were generated from potential predictors using stepwise logistic regression (STEP), random forests (RF), gradient boosting (GB), and two neural networks (NNs). Discriminatory power was highest for death [STEP area under the curve (AUC) = 0.80 in ORBIT-AF, 0.75 in GARFIELD-AF] and lowest for stroke in all models (STEP AUC = 0.67 in ORBIT-AF, 0.66 in GARFIELD-AF). The discriminatory power of the ML models was similar or lower than the STEP models for most outcomes. The GB model had a higher AUC than STEP for death in GARFIELD-AF (0.76 vs. 0.75), but only nominally, and both performed similarly in ORBIT-AF. The multilayer NN had the lowest discriminatory power for all outcomes. The calibration of the STEP modelswere more aligned with the observed events for all outcomes. In the cross-registry models, the discriminatory power of the ML models was similar or lower than the STEP for most cases.

Conclusion

When developed from two large, community-based AF registries, ML techniques did not improve prediction modelling of death, major bleeding, or stroke.
Reproductive system infections in women: lower genital tract syndromes
Authors: Brunham Robert C , Paavonen Jorma
Published: May 2020

Gynecological and obstetrical infectious diseases are an important component of women's health. A system approach to gynecological and obstetrical infection helps unify and classify microbial etiology and pathogenesis within a clinical anatomical framework of lower and upper genital tract syndromes. The reproductive system of women includes the vulva, vagina, cervix, uterus, fallopian tubes and ovaries. During pregnancy, additional tissues include the chorioamnion and placenta together with the fetus and amniotic fluid. We review in two parts reproductive system infection syndromes in women using selected research results to illustrate the clinical utility of the system approach in terms of diagnosis, treatment and prevention. We conclude that a reproductive system perspective will lead to improvements in understanding, management and prevention of these diseases.
Meta-Analysis on Mediated Contact and Prejudice
Authors: Banas John A , Bessarabova Elena , Massey Zachary B
Published: May 2020

This paper presents a meta-analysis of 79 cases (N = 21,857) testing the effectiveness of mediated intergroup contact on prejudice. Positive mediated contact decreased (r = −.23; 95% CI, −.29 to −.17), whereas negative mediated contact increased prejudicial attitudes (r = .31; 95% CI, .24 to .38) and intergroup anxiety and empathy were both significant mediators of these relationships. Furthermore, the data revealed no significant differences between parasocial and vicarious effects, positive and negative mediated-contact effects, or the effects of the duration of mediated-contact stimulus exposure on prejudice. However, the data did reveal experiments to have stronger effects than survey research. These and other results are discussed along with implications, limitations, and future research directions.
Epigenetic Responses to Temperature and Climate
Authors: McCaw Beth A , Stevenson Tyler J , Lancaster Lesley T
Published: May 2020

Synopsis

Epigenetics represents a widely accepted set of mechanisms by which organisms respond to the environment by regulating phenotypic plasticity and life history transitions. Understanding the effects of environmental control on phenotypes and fitness, via epigenetic mechanisms, is essential for understanding the ability of organisms to rapidly adapt to environmental change. This review highlights the significance of environmental temperature on epigenetic control of phenotypic variation, with the aim of furthering our understanding of how epigenetics might help or hinder species’ adaptation to climate change. It outlines how epigenetic modifications, including DNA methylation and histone/chromatin modification, (1) respond to temperature and regulate thermal stress responses in different kingdoms of life, (2) regulate temperature-dependent expression of key developmental processes, sex determination, and seasonal phenotypes, (3) facilitate transgenerational epigenetic inheritance of thermal adaptation, (4) adapt populations to local and global climate gradients, and finally (5) facilitate in biological invasions across climate regions. Although the evidence points towards a conserved role of epigenetics in responding to temperature change, there appears to be an element of temperature- and species-specificity in the specific effects of temperature change on epigenetic modifications and resulting phenotypic responses. The review identifies areas of future research in epigenetic responses to environmental temperature change.
Technical note: Relationship between placentome location and gene expression in bovine pregnancy
Authors: Picking Elizabeth M , Trubenbach Levi A , Bazer Fuller W , Sawyer Jason E , Wickersham Tryon A , Satterfield M Carey
Published: May 2020

A novel, non-terminal surgical procedure to remove a single placentome from the pregnant ewe for gene expression and histological analyses was recently developed in our laboratory. This technique allows for evaluation of nutritional insults on placental development at more than one stage of gestation using a single animal. Early attempts to develop a similar technique in cattle were met with complications due to inaccessibility of the gravid uterine horn because of its location and mass. One alternative is to collect a placentome from the contralateral uterine horn; however, the question remains as to whether gene expression varies among placentomes based on location relative to the fetus. Pregnant heifers were maintained on forage during early gestation and later moved into pens with a Calan gate system (American Calan, Northwood, NH). On gestational day (GD) 158, five heifers were assigned to receive a hay-based diet formulated to meet 100% of NRC requirements, and five heifers were fed 70% of NRC requirements until necropsy on GD244. At necropsy, a single representative placentome was selected for analysis from the antimesometrial side: (1) of the gravid uterine horn central to the amnion, (2) over the allantois immediately adjacent to the amnion, (3) in the tip of the gravid uterine horn, and (4) in the tip of the contralateral uterine horn. Mean placentome weight was greater (P < 0.05) for locations central to the amnion and allantois compared to locations within the tips of the ipsilateral and contralateral horns, respectively. Gene expression for angiogenic factors (FGF2, ODC1, VEGFA, and FLT1), nutrient transporters (SLC7A1 and SLC2A1), and factors associated with hormone action (ESR1, IGF1, IGFBP3, CSH1, and PAG1) were unaffected (P > 0.05) by dietary treatment or location of the placentome. Results indicate that location of the placentome in relation to the fetus does not impact gene expression, enhancing the efficacy of nonterminal methodologies for sampling gene expression in placentomes.
Lung adenocarcinoma in a patient with Li–Fraumeni syndrome bearing a novel germ-line mutation, TP53R333Vfs*12
Authors: Takahashi Shodai , Shimazu Kazuhiro , Kodama Koya , Fukuda Koji , Yoshida Taichi , Taguchi Daiki , Takahashi Tsutomu , Nanjyo Hiroshi , Shibata Hiroyuki
Published: May 2020

Germline mutations of TP53 are responsible for Li–Fraumeni syndrome in its 60–80%. We found a novel germline mutation, TP53: c.997del:p.R333Vfs*12 (NM_000546.6, GRCh, 17:7670713..7670713). The proband is a 40-year-old female, who was suffered from osteosarcoma in her right forearm at her age of 11. She was also suffered from lung adenocarcinoma in her right upper lobe and bone metastasis in her right scapula at her age of 37. She was treated with gefitinib, an epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) because of EGFR mutation (L747-S752 del). Her bone metastasis became resistant after 1-year treatment. Bone metastasis had an additional EGFR mutation (T790M). The secondary treatment with osimertinib, an another EGFR-TKI, can successfully control the tumors for over 2 years. This TP53 mutation (R333Vfs*12) was first found in lung adenocarcinomas. The therapeutic effect of osimertinib for this triple mutant lung adenocarcinoma is better than the previous report.
A PSF-based Approach to TESS High quality data Of Stellar clusters (PATHOS) – II. Search for exoplanets in open clusters of the Southern ecliptic hemisphere and their frequency
Authors: Nardiello D , Piotto G , Deleuil M , Malavolta L , Montalto M , Bedin L R , Borsato L , Granata V , Libralato M , Manthopoulou E E
Published: May 2020

The scope of the project ‘A PSF-based Approach to TESS High Quality data Of Stellar clusters’ (PATHOS) is the extraction and analysis of high-precision light curves of stars in stellar clusters and young associations for the identification of candidate exoplanets and variable stars. The cutting-edge tools used in this project allow us to measure the real flux of stars in dense fields, minimizing the effects due to contamination by neighbour sources. We extracted about 200 000 light curves of stars in 645 open clusters located in the Southern ecliptic hemisphere and observed by TESS during the first year of its mission. We searched for transiting signals and we found 33 objects of interest, 11 of which are strong candidate exoplanets. Because of the limited SNR, we did not find any Earth or super-Earth. We identified two Neptune-size planets orbiting stars with $R_{\star }\lt 1.5\, \mathrm{\it R}_{\odot }$, implying a frequency $f_{\star }=1.34 \pm 0.95\, {{\ \rm per\ cent}}$, consistent with the frequency around field stars. The seven Jupiter candidates around stars with $R_{\star }\lt \, 1.5\, \mathrm{\it R}_{\odot }$ imply a frequency $f_{\star }=0.19\pm 0.07\, {{\ \rm per\ cent}}$, which is smaller than in the field. A more complete estimate of the survey completeness and false positive rate is needed to confirm these results. Light curves used in this work will be made available to the astronomical community on the Mikulski Archive for Space Telescope under the project PATHOS.
The evidence for a spatially flat Universe
Authors: Efstathiou George , Gratton Steven
Published: May 2020

We use a new and statistically powerful Planck likelihood to show that the Planck temperature and polarization spectra are consistent with a spatially flat Universe, in contrast to recent claims in the literature. When combined with other astrophysical data, particularly geometrical measurements of baryon acoustic oscillations, our likelihood constrains the Universe to be spatially flat to extremely high precision. We deduce a curvature density parameter ΩK = 0.0004 ± 0.0018 in good agreement with the 2018 results of the Planck team. In the context of inflationary cosmology, the observations offer strong support for models of inflation with a large number of e-foldings and disfavour models of incomplete inflation.
Effects of Prior Influenza Exposure on Immunogenicity of Influenza Vaccine
Authors: Cao Jia-Qian , Jin Peng-Fei , Zeng Zhao-Zhun , Zhang Li , Meng Fan-Yue , Chu Kai , Wang Yuan-Yuan , Li Jing-Xin , Zhu Feng-Cai
Published: May 2020

Background

To investigate effects of prior influenza exposure on vaccine-elicited humor immune responses to circulating influenza variants.

Method

We randomly selected 360 participants in previous clinical trials stratified by age. Blood samples before and 28 days after vaccination were collected and tested by hemagglutination-inhibition tests against both vaccine strains and circulating variants during the 2015–2016 influenza seasons in China. The antigenic map was plotted and antigenic distance was calculated.

Results

Subjects with H1-priming had higher cross-reactive antibodies titers against A/JiangsuTinghu/11019/2015(H3N2) compared with subjects with B-priming did (Padjusted=0.038). Subjects with H1-priming also had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.036). Nevertheless, subjects with no H1 and B-priming had higher cross-reactive antibodies titers against A/Jiangsu Qinhuai/11059/2015(H3N2) than subjects with both H1 and B priming did (Padjusted=0.012). Antigenic distance was well-matched with serological results. Besides, age-specific differences in human post-vaccination responses against the identical circulating strain was noted. And children had most cross-reactive response to both H3N2 and B-yamagata subtypes.

Conclusion

Our results suggest that prior exposure to H1 or B influenza virus may influence cross-reactivity of H3-specific post-vaccination responses and consequently could influence the vaccine effectiveness. Our findings also support that there are age-specific differences in human post-vaccination responses.
0092 A Daytime Nap Restores Hippocampal Function and Improves Declarative Learning
Authors: Ong J , Lau T , Lee X , van Rijn E , Chee M W
Published: May 2020

Introduction

Daytime naps have been shown to improve learning outcomes. One theory underlying enhanced encoding following a nap is via the synaptic downscaling of neurons potentiated during wake - a process facilitated by slow oscillations. In this study, we sought to investigate neural mechanisms underlying enhanced encoding following a nap compared to a waking period using a combination of PSG and fMRI methods.

Methods

40 healthy undergraduates (M=23.3y, SD=2.96y; 10 males) who slept normally the previous night encoded word pair lists across 2 runs in an MRI scanner at 1PM and 4.30PM. In between encoding sessions, participants either stayed awake and watched a documentary (Wake group; N=20), or napped for 90-min while undergoing polysomnography (Nap group; N=20). Approximately 40min after each encoding session, memory of these word lists were assessed in a cued-recall fashion. Performance in each session was measured by percentage of correct responses.

Results

There were no baseline differences in encoding performance. However, a Session x Group interaction effect (p<0.001) was observed whereby performance significantly improved only in the Nap group in the second encoding session (Nap:20±19% vs. Wake:-1±13%). Concurrent to this, fMRI analyses revealed a Session x Run x Group interaction effect in the hippocampus (p=0.002) whereby hippocampal activation during encoding of the word lists increased only in the Nap group. In addition, although there was no association between degree of performance improvement in the nap group with duration of sleep or the various sleep stages (N1,N2,N3,REM), spindle count (12-15Hz) in the Nap group correlated significantly with both performance improvement (rs=0.46) and increase in hippocampal activation (rs=0.46).

Conclusion

These results confirm the benefit of a nap on encoding processes. Hippocampal activation also increased following the nap, which could indicate renewed hippocampal capacity to store new information. While we hypothesized that slow wave sleep would aid in this transfer, we instead found a relationship between spindle count and both degree of performance improvement and increase in hippocampal activation. The interplay between NREM sleep oscillations, hippocampal downscaling and encoding performance could be more complex than originally thought.

Support

National Medical Research Council, Singapore (NMRC/STaR/015/2013) and the Far East Organization.
0103 Novel Prebiotic Enhances Sleep-Wake Cycle and Memory Consolidation in 5xFAD Mice
Authors: Shimomura K
Published: May 2020

Introduction

Prior studies have shown that the gut microbiomes of Alzheimer’s Disease (AD) patients differ from unaffected individuals. Sleep and circadian rhythm disturbances are common in AD and often precede dementia symptoms. Gut microbiome alterations have also been observed in models of circadian disruption. Therefore, we hypothesized that altering the gut microbiome could improve sleep/circadian rhythms and cognition in an AD mouse model.

Methods

Mice were given a dietary polysaccharide, Modified Resistant Maltodextrin (MRM), as a 1% solution in the drinking water beginning at 2 months of age. 5xFAD and wild-type (WT) littermates were tested. Sleep-wake was recorded by EEG/EMG, memory consolidation was tested by the Object-Location Memory test, and beta amyloid deposition in the brain was assayed (dot blot). Composition of the gut microbiota was determined from amplicon sequencing of the 16s ribosomal RNA gene from fecal DNA.

Results

MRM treatment reduced dark (active)-phase sleep and the phase scattering of REM sleep in 5xFAD mice, indices of circadian consolidation. 6-month-old 5xFAD mice given plain water exhibited no 24hr retention of object location memory. However, MRM-treated 5xFAD mice demonstrated 24-hour memory, even at 12 months of age. Both improved memory and increased consolidation of sleep were also observed in WT mice. Two unclassified species of bacteria from the family Tannerellaceae were significantly increased in MRM-treated 5xFAD and WT mice. At 12 months of age, synaptic and neuronal loss become prominent in this AD model. However, the level of beta amyloid deposition in the brain was not significantly different between MRM and water control groups.

Conclusion

MRM treatment altered the gut microbiome, improved circadian timing of sleep and memory retention, but did not impact beta amyloid deposition in 5xFAD mice. Because these effects were also present in WT mice, MRM-induced microbiome changes may affect sleep and cognition independently from beta amyloid.

Support

Northwestern University Feinberg School of Medicine Center for Circadian and Sleep Medicine