Showing papers by "Queen's University Belfast published in 2019"

European Consensus Guidelines on the Management of Respiratory Distress Syndrome - 2019 Update.

Abstract: As management of respiratory distress syndrome (RDS) advances, clinicians must continually revise their current practice. We report the fourth update of “European Guidelines for the Management of RDS” by a European panel of experienced neonatologists and an expert perinatal obstetrician based on available literature up to the end of 2018. Optimising outcome for babies with RDS includes prediction of risk of preterm delivery, need for appropriate maternal transfer to a perinatal centre and timely use of antenatal steroids. Delivery room management has become more evidence-based, and protocols for lung protection including initiation of CPAP and titration of oxygen should be implemented immediately after birth. Surfactant replacement therapy is a crucial part of management of RDS, and newer protocols for its use recommend early administration and avoidance of mechanical ventilation. Methods of maintaining babies on non-invasive respiratory support have been further developed and may cause less distress and reduce chronic lung disease. As technology for delivering mechanical ventilation improves, the risk of causing lung injury should decrease, although minimising time spent on mechanical ventilation using caffeine and, if necessary, postnatal steroids are also important considerations. Protocols for optimising general care of infants with RDS are also essential with good temperature control, careful fluid and nutritional management, maintenance of perfusion and judicious use of antibiotics all being important determinants of best outcome.

Polygenic Risk Scores for Prediction of Breast Cancer and Breast Cancer Subtypes

Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.

Progress in cancer survival, mortality, and incidence in seven high-income countries 1995–2014 (ICBP SURVMARK-2): a population-based study

Abstract: Summary Background Population-based cancer survival estimates provide valuable insights into the effectiveness of cancer services and can reflect the prospects of cure. As part of the second phase of the International Cancer Benchmarking Partnership (ICBP), the Cancer Survival in High-Income Countries (SURVMARK-2) project aims to provide a comprehensive overview of cancer survival across seven high-income countries and a comparative assessment of corresponding incidence and mortality trends. Methods In this longitudinal, population-based study, we collected patient-level data on 3·9 million patients with cancer from population-based cancer registries in 21 jurisdictions in seven countries (Australia, Canada, Denmark, Ireland, New Zealand, Norway, and the UK) for seven sites of cancer (oesophagus, stomach, colon, rectum, pancreas, lung, and ovary) diagnosed between 1995 and 2014, and followed up until Dec 31, 2015. We calculated age-standardised net survival at 1 year and 5 years after diagnosis by site, age group, and period of diagnosis. We mapped changes in incidence and mortality to changes in survival to assess progress in cancer control. Findings In 19 eligible jurisdictions, 3 764 543 cases of cancer were eligible for inclusion in the study. In the 19 included jurisdictions, over 1995–2014, 1-year and 5-year net survival increased in each country across almost all cancer types, with, for example, 5-year rectal cancer survival increasing more than 13 percentage points in Denmark, Ireland, and the UK. For 2010–14, survival was generally higher in Australia, Canada, and Norway than in New Zealand, Denmark, Ireland, and the UK. Over the study period, larger survival improvements were observed for patients younger than 75 years at diagnosis than those aged 75 years and older, and notably for cancers with a poor prognosis (ie, oesophagus, stomach, pancreas, and lung). Progress in cancer control (ie, increased survival, decreased mortality and incidence) over the study period was evident for stomach, colon, lung (in males), and ovarian cancer. Interpretation The joint evaluation of trends in incidence, mortality, and survival indicated progress in four of the seven studied cancers. Cancer survival continues to increase across high-income countries; however, international disparities persist. While truly valid comparisons require differences in registration practice, classification, and coding to be minimal, stage of disease at diagnosis, timely access to effective treatment, and the extent of comorbidity are likely the main determinants of patient outcomes. Future studies are needed to assess the impact of these factors to further our understanding of international disparities in cancer survival. Funding Canadian Partnership Against Cancer; Cancer Council Victoria; Cancer Institute New South Wales; Cancer Research UK; Danish Cancer Society; National Cancer Registry Ireland; The Cancer Society of New Zealand; National Health Service England; Norwegian Cancer Society; Public Health Agency Northern Ireland, on behalf of the Northern Ireland Cancer Registry; The Scottish Government; Western Australia Department of Health; and Wales Cancer Network.

Promoting transparency and reproducibility in enhanced molecular simulations

Abstract: The PLUMED consortium unifies developers and contributors to PLUMED, an open-source library for enhanced- sampling, free-energy calculations and the analysis of molecular dynamics simulations. Here, we outline our efforts to promote transparency and reproducibility by disseminating protocols for enhanced-sampling molecular simulations.

Soil nematode abundance and functional group composition at a global scale

Abstract: Soil organisms are a crucial part of the terrestrial biosphere. Despite their importance for ecosystem functioning, few quantitative, spatially explicit models of the active belowground community currently exist. In particular, nematodes are the most abundant animals on Earth, filling all trophic levels in the soil food web. Here we use 6,759 georeferenced samples to generate a mechanistic understanding of the patterns of the global abundance of nematodes in the soil and the composition of their functional groups. The resulting maps show that 4.4 ± 0.64 × 1020 nematodes (with a total biomass of approximately 0.3 gigatonnes) inhabit surface soils across the world, with higher abundances in sub-Arctic regions (38% of total) than in temperate (24%) or tropical (21%) regions. Regional variations in these global trends also provide insights into local patterns of soil fertility and functioning. These high-resolution models provide the first steps towards representing soil ecological processes in global biogeochemical models and will enable the prediction of elemental cycling under current and future climate scenarios.

Data-driven health estimation and lifetime prediction of lithium-ion batteries: A review

Abstract: Accurate health estimation and lifetime prediction of lithium-ion batteries are crucial for durable electric vehicles. Early detection of inadequate performance facilitates timely maintenance of battery systems. This reduces operational costs and prevents accidents and malfunctions. Recent advancements in “Big Data” analytics and related statistical/computational tools raised interest in data-driven battery health estimation. Here, we will review these in view of their feasibility and cost-effectiveness in dealing with battery health in real-world applications. We categorise these methods according to their underlying models/algorithms and discuss their advantages and limitations. In the final section we focus on challenges of real-time battery health management and discuss potential next-generation techniques. We are confident that this review will inform commercial technology choices and academic research agendas alike, thus boosting progress in data-driven battery health estimation and prediction on all technology readiness levels.

Clinical practice update on heart failure 2019: pharmacotherapy, procedures, devices and patient management. An expert consensus meeting report of the Heart Failure Association of the European Society of Cardiology

Abstract: The European Society of Cardiology (ESC) has published a series of guidelines on heart failure (HF) over the last 25 years, most recently in 2016. Given the amount of new information that has become available since then, the Heart Failure Association (HFA) of the ESC recognized the need to review and summarise recent developments in a consensus document. Here we report from the HFA workshop that was held in January 2019 in Frankfurt, Germany. This expert consensus report is neither a guideline update nor a position statement, but rather a summary and consensus view in the form of consensus recommendations. The report describes how these guidance statements are supported by evidence, it makes some practical comments, and it highlights new research areas and how progress might change the clinical management of HF. We have avoided re-interpretation of information already considered in the 2016 ESC/HFA guidelines. Specific new recommendations have been made based on the evidence from major trials published since 2016, including sodium-glucose co-transporter 2 inhibitors in type 2 diabetes mellitus, MitraClip for functional mitral regurgitation, atrial fibrillation ablation in HF, tafamidis in cardiac transthyretin amyloidosis, rivaroxaban in HF, implantable cardioverter-defibrillators in non-ischaemic HF, and telemedicine for HF. In addition, new trial evidence from smaller trials and updated meta-analyses have given us the chance to provide refined recommendations in selected other areas. Further, new trial evidence is due in many of these areas and others over the next 2 years, in time for the planned 2021 ESC guidelines on the diagnosis and treatment of acute and chronic heart failure.

Vascular dysfunction-The disregarded partner of Alzheimer's disease

Abstract: Increasing evidence recognizes Alzheimer's disease (AD) as a multifactorial and heterogeneous disease with multiple contributors to its pathophysiology, including vascular dysfunction. The recently updated AD Research Framework put forth by the National Institute on Aging-Alzheimer's Association describes a biomarker-based pathologic definition of AD focused on amyloid, tau, and neuronal injury. In response to this article, here we first discussed evidence that vascular dysfunction is an important early event in AD pathophysiology. Next, we examined various imaging sequences that could be easily implemented to evaluate different types of vascular dysfunction associated with, and/or contributing to, AD pathophysiology, including changes in blood-brain barrier integrity and cerebral blood flow. Vascular imaging biomarkers of small vessel disease of the brain, which is responsible for >50% of dementia worldwide, including AD, are already established, well characterized, and easy to recognize. We suggest that these vascular biomarkers should be incorporated into the AD Research Framework to gain a better understanding of AD pathophysiology and aid in treatment efforts.

The Formation of Human Populations in South and Central Asia

Abstract: By sequencing 523 ancient humans, we show that the primary source of ancestry in modern South Asians is a prehistoric genetic gradient between people related to early hunter-gatherers of Iran and Southeast Asia. After the Indus Valley Civilization's decline, its people mixed with individuals in the southeast to form one of the two main ancestral populations of South Asia, whose direct descendants live in southern India. Simultaneously, they mixed with descendants of Steppe pastoralists who, starting around 4000 years ago, spread via Central Asia to form the other main ancestral population. The Steppe ancestry in South Asia has the same profile as that in Bronze Age Eastern Europe, tracking a movement of people that affected both regions and that likely spread the distinctive features shared between Indo-Iranian and Balto-Slavic languages.

A brief review on key technologies in the battery management system of electric vehicles

Abstract: Batteries have been widely applied in many high-power applications, such as electric vehicles (EVs) and hybrid electric vehicles, where a suitable battery management system (BMS) is vital in ensuring safe and reliable operation of batteries. This paper aims to give a brief review on several key technologies of BMS, including battery modelling, state estimation and battery charging. First, popular battery types used in EVs are surveyed, followed by the introduction of key technologies used in BMS. Various battery models, including the electric model, thermal model and coupled electro-thermal model are reviewed. Then, battery state estimations for the state of charge, state of health and internal temperature are comprehensively surveyed. Finally, several key and traditional battery charging approaches with associated optimization methods are discussed.

Ubiquitous cell-free Massive MIMO communications

Abstract: Since the first cellular networks were trialled in the 1970s, we have witnessed an incredible wireless revolution. From 1G to 4G, the massive traffic growth has been managed by a combination of wider bandwidths, refined radio interfaces, and network densification, namely increasing the number of antennas per site. Due its cost-efficiency, the latter has contributed the most. Massive MIMO (multiple-input multiple-output) is a key 5G technology that uses massive antenna arrays to provide a very high beamforming gain and spatially multiplexing of users and hence increases the spectral and energy efficiency (see references herein). It constitutes a centralized solution to densify a network, and its performance is limited by the inter-cell interference inherent in its cell-centric design. Conversely, ubiquitous cell-free Massive MIMO refers to a distributed Massive MIMO system implementing coherent user-centric transmission to overcome the inter-cell interference limitation in cellular networks and provide additional macro-diversity. These features, combined with the system scalability inherent in the Massive MIMO design, distinguish ubiquitous cell-free Massive MIMO from prior coordinated distributed wireless systems. In this article, we investigate the enormous potential of this promising technology while addressing practical deployment issues to deal with the increased back/front-hauling overhead deriving from the signal co-processing.

A Multimodal Deep Learning Method for Android Malware Detection Using Various Features

Abstract: With the widespread use of smartphones, the number of malware has been increasing exponentially. Among smart devices, android devices are the most targeted devices by malware because of their high popularity. This paper proposes a novel framework for android malware detection. Our framework uses various kinds of features to reflect the properties of android applications from various aspects, and the features are refined using our existence-based or similarity-based feature extraction method for effective feature representation on malware detection. Besides, a multimodal deep learning method is proposed to be used as a malware detection model. This paper is the first study of the multimodal deep learning to be used in the android malware detection. With our detection model, it was possible to maximize the benefits of encompassing multiple feature types. To evaluate the performance, we carried out various experiments with a total of 41 260 samples. We compared the accuracy of our model with that of other deep neural network models. Furthermore, we evaluated our framework in various aspects including the efficiency in model updates, the usefulness of diverse features, and our feature representation method. In addition, we compared the performance of our framework with those of other existing methods including deep learning-based methods.

CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans.

Abstract: Glycolipids (such as glycoglycerolipids, glycosphingolipids, and glycosylphosphatidylinositol) and lipoglycans (such as lipopolysaccharides (LPS), lipooligosaccharides (LOS), mycobacterial lipoarabinomannan, and mycoplasma lipoglycans) are typically found on the surface of cell membranes and play crucial roles in various cellular functions. Characterizing their structure and dynamics at the molecular level is essential to understand their biological roles, but systematic generation of glycolipid and lipoglycan structures is challenging because of great variations in lipid structures and glycan sequences (i.e., carbohydrate types and their linkages). To facilitate the generation of all-atom glycolipid/LPS/LOS structures, we have developed Glycolipid Modeler and LPS Modeler in CHARMM-GUI ( http://www.charmm-gui.org ), a web-based interface that simplifies building of complex biological simulation systems. In addition, we have incorporated these modules into Membrane Builder so that users can readily build a complex symmetric or asymmetric biological membrane system with various glycolipids and LPS/LOS. These tools are expected to be useful in innovative and novel glycolipid/LPS/LOS modeling and simulation research by easing tedious and intricate steps in modeling complex biological systems and shall provide insight into structures, dynamics, and underlying mechanisms of complex glycolipid-/LPS-/LOS-containing biological membrane systems.

Intensity-modulated fractionated radiotherapy versus stereotactic body radiotherapy for prostate cancer (PACE-B): acute toxicity findings from an international, randomised, open-label, phase 3, non-inferiority trial.

Abstract: Summary Background Localised prostate cancer is commonly treated with external-beam radiotherapy. Moderate hypofractionation has been shown to be non-inferior to conventional fractionation. Ultra-hypofractionated stereotactic body radiotherapy would allow shorter treatment courses but could increase acute toxicity compared with conventionally fractionated or moderately hypofractionated radiotherapy. We report the acute toxicity findings from a randomised trial of standard-of-care conventionally fractionated or moderately hypofractionated radiotherapy versus five-fraction stereotactic body radiotherapy for low-risk to intermediate-risk localised prostate cancer. Methods PACE is an international, phase 3, open-label, randomised, non-inferiority trial. In PACE-B, eligible men aged 18 years and older, with WHO performance status 0–2, low-risk or intermediate-risk prostate adenocarcinoma (Gleason 4 + 3 excluded), and scheduled to receive radiotherapy were recruited from 37 centres in three countries (UK, Ireland, and Canada). Participants were randomly allocated (1:1) by computerised central randomisation with permuted blocks (size four and six), stratified by centre and risk group, to conventionally fractionated or moderately hypofractionated radiotherapy (78 Gy in 39 fractions over 7·8 weeks or 62 Gy in 20 fractions over 4 weeks, respectively) or stereotactic body radiotherapy (36·25 Gy in five fractions over 1–2 weeks). Neither participants nor investigators were masked to allocation. Androgen deprivation was not permitted. The primary endpoint of PACE-B is freedom from biochemical or clinical failure. The coprimary outcomes for this acute toxicity substudy were worst grade 2 or more severe Radiation Therapy Oncology Group (RTOG) gastrointestinal or genitourinary toxic effects score up to 12 weeks after radiotherapy. Analysis was per protocol. This study is registered with ClinicalTrials.gov , NCT01584258 . PACE-B recruitment is complete and follow-up is ongoing. Findings Between Aug 7, 2012, and Jan 4, 2018, we randomly assigned 874 men to conventionally fractionated or moderately hypofractionated radiotherapy (n=441) or stereotactic body radiotherapy (n=433). 432 (98%) of 441 patients allocated to conventionally fractionated or moderately hypofractionated radiotherapy and 415 (96%) of 433 patients allocated to stereotactic body radiotherapy received at least one fraction of allocated treatment. Worst acute RTOG gastrointestinal toxic effect proportions were as follows: grade 2 or more severe toxic events in 53 (12%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 43 (10%) of 415 patients in the stereotactic body radiotherapy group (difference −1·9 percentage points, 95% CI −6·2 to 2·4; p=0·38). Worst acute RTOG genitourinary toxicity proportions were as follows: grade 2 or worse toxicity in 118 (27%) of 432 patients in the conventionally fractionated or moderately hypofractionated radiotherapy group versus 96 (23%) of 415 patients in the stereotactic body radiotherapy group (difference −4·2 percentage points, 95% CI −10·0 to 1·7; p=0·16). No treatment-related deaths occurred. Interpretation Previous evidence (from the HYPO-RT-PC trial) suggested higher patient-reported toxicity with ultrahypofractionation. By contrast, our results suggest that substantially shortening treatment courses with stereotactic body radiotherapy does not increase either gastrointestinal or genitourinary acute toxicity. Funding Accuray and National Institute of Health Research.

Guidelines on the management of acute respiratory distress syndrome

Abstract: The Faculty of Intensive Care Medicine and Intensive Care Society Guideline Development Group have used GRADE methodology to make the following recommendations for the management of adult patients with acute respiratory distress syndrome (ARDS). The British Thoracic Society supports the recommendations in this guideline. Where mechanical ventilation is required, the use of low tidal volumes (<6 ml/kg ideal body weight) and airway pressures (plateau pressure <30 cmH2O) was recommended. For patients with moderate/severe ARDS (PF ratio<20 kPa), prone positioning was recommended for at least 12 hours per day. By contrast, high frequency oscillation was not recommended and it was suggested that inhaled nitric oxide is not used. The use of a conservative fluid management strategy was suggested for all patients, whereas mechanical ventilation with high positive end-expiratory pressure and the use of the neuromuscular blocking agent cisatracurium for 48 hours was suggested for patients with ARDS with ratio of arterial oxygen partial pressure to fractional inspired oxygen (PF) ratios less than or equal to 27 and 20 kPa, respectively. Extracorporeal membrane oxygenation was suggested as an adjunct to protective mechanical ventilation for patients with very severe ARDS. In the absence of adequate evidence, research recommendations were made for the use of corticosteroids and extracorporeal carbon dioxide removal.

Trends and cyclical variation in the incidence of childhood type 1 diabetes in 26 European centres in the 25 year period 1989-2013: a multicentre prospective registration study.

Abstract: Against a background of a near-universally increasing incidence of childhood type 1 diabetes, recent reports from some countries suggest a slowing in this increase. Occasional reports also describe cyclical variations in incidence, with periodicities of between 4 and 6 years. Age/sex-standardised incidence rates for the 0- to 14-year-old age group are reported for 26 European centres (representing 22 countries) that have registered newly diagnosed individuals in geographically defined regions for up to 25 years during the period 1989–2013. Poisson regression was used to estimate rates of increase and test for cyclical patterns. Joinpoint regression software was used to fit segmented log-linear relationships to incidence trends. Significant increases in incidence were noted in all but two small centres, with a maximum rate of increase of 6.6% per annum in a Polish centre. Several centres in high-incidence countries showed reducing rates of increase in more recent years. Despite this, a pooled analysis across all centres revealed a 3.4% (95% CI 2.8%, 3.9%) per annum increase in incidence rate, although there was some suggestion of a reduced rate of increase in the 2004–2008 period. Rates of increase were similar in boys and girls in the 0- to 4-year-old age group (3.7% and 3.7% per annum, respectively) and in the 5- to 9-year-old age group (3.4% and 3.7% per annum, respectively), but were higher in boys than girls in the 10- to 14-year-old age group (3.3% and 2.6% per annum, respectively). Significant 4 year periodicity was detected in four centres, with three centres showing that the most recent peak in fitted rates occurred in 2012. Despite reductions in the rate of increase in some high-risk countries, the pooled estimate across centres continues to show a 3.4% increase per annum in incidence rate, suggesting a doubling in incidence rate within approximately 20 years in Europe. Although four centres showed support for a cyclical pattern of incidence with a 4 year periodicity, no plausible explanation for this can be given.

British Thoracic Society Guideline for bronchiectasis in adults

Abstract: ### How should the diagnosis of bronchiectasis be determined? #### Recommendations – Imaging #### Good practice points CT imaging protocol CT features of bronchiectasis General ### In whom should the diagnosis of bronchiectasis be suspected? #### Recommendations

Using Blockchain for Electronic Health Records

Abstract: Blockchain have been an interesting research area for a long time and the benefits it provides have been used by a number of various industries. Similarly, the healthcare sector stands to benefit immensely from the blockchain technology due to security, privacy, confidentiality and decentralization. Nevertheless, the Electronic Health Record (EHR) systems face problems regarding data security, integrity and management. In this paper, we discuss how the blockchain technology can be used to transform the EHR systems and could be a solution of these issues. We present a framework that could be used for the implementation of blockchain technology in healthcare sector for EHR. The aim of our proposed framework is firstly to implement blockchain technology for EHR and secondly to provide secure storage of electronic records by defining granular access rules for the users of the proposed framework. Moreover, this framework also discusses the scalability problem faced by the blockchain technology in general via use of off-chain storage of the records. This framework provides the EHR system with the benefits of having a scalable, secure and integral blockchain-based solution.

Klebsiella pneumoniae infection biology: living to counteract host defences.

Abstract: Klebsiella species cause a wide range of diseases including pneumonia, urinary tract infections (UTIs), bloodstream infections and sepsis. These infections are particularly a problem among neonates, elderly and immunocompromised individuals. Klebsiella is also responsible for a significant number of community-acquired infections. A defining feature of these infections is their morbidity and mortality, and the Klebsiella strains associated with them are considered hypervirulent. The increasing isolation of multidrug-resistant strains has significantly narrowed, or in some settings completely removed, the therapeutic options for the treatment of Klebsiella infections. Not surprisingly, this pathogen has then been singled out as an 'urgent threat to human health' by several organisations. This review summarises the tremendous progress that has been made to uncover the sophisticated immune evasion strategies of K. pneumoniae. The co-evolution of Klebsiella in response to the challenge of an activated immune has made Klebsiella a formidable pathogen exploiting stealth strategies and actively suppressing innate immune defences to overcome host responses to survive in the tissues. A better understanding of Klebsiella immune evasion strategies in the context of the host-pathogen interactions is pivotal to develop new therapeutics, which can be based on antagonising the anti-immune strategies of this pathogen.

High thermal conductivity of high-quality monolayer boron nitride and its thermal expansion.

Abstract: Heat management has become more and more critical, especially in miniaturized modern devices, so the exploration of highly thermally conductive materials with electrical insulation is of great importance. Here, we report that high-quality one-atom-thin hexagonal boron nitride (BN) has a thermal conductivity (κ) of 751 W/mK at room temperature, the second largest κ per unit weight among all semiconductors and insulators. The κ of atomically thin BN decreases with increased thickness. Our molecular dynamic simulations accurately reproduce this trend, and the density functional theory (DFT) calculations reveal the main scattering mechanism. The thermal expansion coefficients of monolayer to trilayer BN at 300 to 400 K are also experimentally measured for the first time. Owing to its wide bandgap, high thermal conductivity, outstanding strength, good flexibility, and excellent thermal and chemical stability, atomically thin BN is a strong candidate for heat dissipation applications, especially in the next generation of flexible electronic devices.

Many-body perturbation theory calculations using the yambo code.

Abstract: yambo is an open source project aimed at studying excited state properties of condensed matter systems from first principles using many-body methods. As input, yambo requires ground state electronic structure data as computed by density functional theory codes such as Quantum ESPRESSO and Abinit. yambo's capabilities include the calculation of linear response quantities (both independent-particle and including electron-hole interactions), quasi-particle corrections based on the GW formalism, optical absorption, and other spectroscopic quantities. Here we describe recent developments ranging from the inclusion of important but oft-neglected physical effects such as electron-phonon interactions to the implementation of a real-time propagation scheme for simulating linear and non-linear optical properties. Improvements to numerical algorithms and the user interface are outlined. Particular emphasis is given to the new and efficient parallel structure that makes it possible to exploit modern high performance computing architectures. Finally, we demonstrate the possibility to automate workflows by interfacing with the yambopy and AiiDA software tools.

Spatially resolved steady-state negative capacitance.

Abstract: Negative capacitance is a newly discovered state of ferroelectric materials that holds promise for electronics applications by exploiting a region of thermodynamic space that is normally not accessible1–14. Although existing reports of negative capacitance substantiate the importance of this phenomenon, they have focused on its macroscale manifestation. These manifestations demonstrate possible uses of steady-state negative capacitance—for example, enhancing the capacitance of a ferroelectric–dielectric heterostructure4,7,14 or improving the subthreshold swing of a transistor8–12. Yet they constitute only indirect measurements of the local state of negative capacitance in which the ferroelectric resides. Spatial mapping of this phenomenon would help its understanding at a microscopic scale and also help to achieve optimal design of devices with potential technological applications. Here we demonstrate a direct measurement of steady-state negative capacitance in a ferroelectric–dielectric heterostructure. We use electron microscopy complemented by phase-field and first-principles-based (second-principles) simulations in SrTiO3/PbTiO3 superlattices to directly determine, with atomic resolution, the local regions in the ferroelectric material where a state of negative capacitance is stabilized. Simultaneous vector mapping of atomic displacements (related to a complex pattern in the polarization field), in conjunction with reconstruction of the local electric field, identify the negative capacitance regions as those with higher energy density and larger polarizability: the domain walls where the polarization is suppressed. Imaging steady-state negative capacitance in SrTiO3/PbTiO3 superlattices with atomic resolution provides solid microscale support for this phenomenon.

Integrating Genomics into Healthcare: A Global Responsibility

Abstract: Genomic sequencing is rapidly transitioning into clinical practice, and implementation into healthcare systems has been supported by substantial government investment, totaling over US$4 billion, in at least 14 countries. These national genomic-medicine initiatives are driving transformative change under real-life conditions while simultaneously addressing barriers to implementation and gathering evidence for wider adoption. We review the diversity of approaches and current progress made by national genomic-medicine initiatives in the UK, France, Australia, and US and provide a roadmap for sharing strategies, standards, and data internationally to accelerate implementation.

Taxonomy of the order Mononegavirales: update 2019.

Abstract: In February 2019, following the annual taxon ratification vote, the order Mononegavirales was amended by the addition of four new subfamilies and 12 new genera and the creation of 28 novel species. This article presents the updated taxonomy of the order Mononegavirales as now accepted by the International Committee on Taxonomy of Viruses (ICTV).

Ranked List Loss for Deep Metric Learning

Abstract: The objective of deep metric learning (DML) is to learn embeddings that can capture semantic similarity information among data points. Existing pairwise or tripletwise loss functions used in DML are known to suffer from slow convergence due to a large proportion of trivial pairs or triplets as the model improves. To improve this, rankingmotivated structured losses are proposed recently to incorporate multiple examples and exploit the structured information among them. They converge faster and achieve state-of-the-art performance. In this work, we present two limitations of existing ranking-motivated structured losses and propose a novel ranked list loss to solve both of them. First, given a query, only a fraction of data points is incorporated to build the similarity structure. Consequently, some useful examples are ignored and the structure is less informative. To address this, we propose to build a setbased similarity structure by exploiting all instances in the gallery. The samples are split into a positive set and a negative set. Our objective is to make the query closer to the positive set than to the negative set by a margin. Second, previous methods aim to pull positive pairs as close as possible in the embedding space. As a result, the intraclass data distribution might be dropped. In contrast, we propose to learn a hypersphere for each class in order to preserve the similarity structure inside it. Our extensive experiments show that the proposed method achieves state-of-the-art performance on three widely used benchmarks.