Showing papers by "University of Manchester published in 2018"
Clotilde Théry1, Kenneth W. Witwer2, Elena Aikawa3, María José Alcaraz4 +414 more•Institutions (209)
TL;DR: The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities, and a checklist is provided with summaries of key points.
Abstract: The last decade has seen a sharp increase in the number of scientific publications describing physiological and pathological functions of extracellular vesicles (EVs), a collective term covering various subtypes of cell-released, membranous structures, called exosomes, microvesicles, microparticles, ectosomes, oncosomes, apoptotic bodies, and many other names. However, specific issues arise when working with these entities, whose size and amount often make them difficult to obtain as relatively pure preparations, and to characterize properly. The International Society for Extracellular Vesicles (ISEV) proposed Minimal Information for Studies of Extracellular Vesicles (“MISEV”) guidelines for the field in 2014. We now update these “MISEV2014” guidelines based on evolution of the collective knowledge in the last four years. An important point to consider is that ascribing a specific function to EVs in general, or to subtypes of EVs, requires reporting of specific information beyond mere description of function in a crude, potentially contaminated, and heterogeneous preparation. For example, claims that exosomes are endowed with exquisite and specific activities remain difficult to support experimentally, given our still limited knowledge of their specific molecular machineries of biogenesis and release, as compared with other biophysically similar EVs. The MISEV2018 guidelines include tables and outlines of suggested protocols and steps to follow to document specific EV-associated functional activities. Finally, a checklist is provided with summaries of key points.
5,988 citations
TL;DR: In this paper, the cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies were presented, with good consistency with the standard spatially-flat 6-parameter CDM cosmology having a power-law spectrum of adiabatic scalar perturbations from polarization, temperature, and lensing separately and in combination.
Abstract: We present cosmological parameter results from the final full-mission Planck measurements of the CMB anisotropies. We find good consistency with the standard spatially-flat 6-parameter $\Lambda$CDM cosmology having a power-law spectrum of adiabatic scalar perturbations (denoted "base $\Lambda$CDM" in this paper), from polarization, temperature, and lensing, separately and in combination. A combined analysis gives dark matter density $\Omega_c h^2 = 0.120\pm 0.001$, baryon density $\Omega_b h^2 = 0.0224\pm 0.0001$, scalar spectral index $n_s = 0.965\pm 0.004$, and optical depth $\tau = 0.054\pm 0.007$ (in this abstract we quote $68\,\%$ confidence regions on measured parameters and $95\,\%$ on upper limits). The angular acoustic scale is measured to $0.03\,\%$ precision, with $100\theta_*=1.0411\pm 0.0003$. These results are only weakly dependent on the cosmological model and remain stable, with somewhat increased errors, in many commonly considered extensions. Assuming the base-$\Lambda$CDM cosmology, the inferred late-Universe parameters are: Hubble constant $H_0 = (67.4\pm 0.5)$km/s/Mpc; matter density parameter $\Omega_m = 0.315\pm 0.007$; and matter fluctuation amplitude $\sigma_8 = 0.811\pm 0.006$. We find no compelling evidence for extensions to the base-$\Lambda$CDM model. Combining with BAO we constrain the effective extra relativistic degrees of freedom to be $N_{\rm eff} = 2.99\pm 0.17$, and the neutrino mass is tightly constrained to $\sum m_
u< 0.12$eV. The CMB spectra continue to prefer higher lensing amplitudes than predicted in base -$\Lambda$CDM at over $2\,\sigma$, which pulls some parameters that affect the lensing amplitude away from the base-$\Lambda$CDM model; however, this is not supported by the lensing reconstruction or (in models that also change the background geometry) BAO data. (Abridged)
3,077 citations
TL;DR: Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by Mol probity's unique all‐atom clashscore.
Abstract: This paper describes the current update on macromolecular model validation services that are provided at the MolProbity website, emphasizing changes and additions since the previous review in 2010. There have been many infrastructure improvements, including rewrite of previous Java utilities to now use existing or newly written Python utilities in the open-source CCTBX portion of the Phenix software system. This improves long-term maintainability and enhances the thorough integration of MolProbity-style validation within Phenix. There is now a complete MolProbity mirror site at http://molprobity.manchester.ac.uk. GitHub serves our open-source code, reference datasets, and the resulting multi-dimensional distributions that define most validation criteria. Coordinate output after Asn/Gln/His "flip" correction is now more idealized, since the post-refinement step has apparently often been skipped in the past. Two distinct sets of heavy-atom-to-hydrogen distances and accompanying van der Waals radii have been researched and improved in accuracy, one for the electron-cloud-center positions suitable for X-ray crystallography and one for nuclear positions. New validations include messages at input about problem-causing format irregularities, updates of Ramachandran and rotamer criteria from the million quality-filtered residues in a new reference dataset, the CaBLAM Cα-CO virtual-angle analysis of backbone and secondary structure for cryoEM or low-resolution X-ray, and flagging of the very rare cis-nonProline and twisted peptides which have recently been greatly overused. Due to wide application of MolProbity validation and corrections by the research community, in Phenix, and at the worldwide Protein Data Bank, newly deposited structures have continued to improve greatly as measured by MolProbity's unique all-atom clashscore.
2,355 citations
TL;DR: Durvalumab therapy resulted in significantly longer overall survival than placebo, and no new safety signals were identified.
Abstract: BACKGROUND:
An earlier analysis in this phase 3 trial showed that durvalumab significantly prolonged progression-free survival, as compared with placebo, among patients with stage III, unresectable non-small-cell lung cancer (NSCLC) who did not have disease progression after concurrent chemoradiotherapy. Here we report the results for the second primary end point of overall survival.
METHODS:
We randomly assigned patients, in a 2:1 ratio, to receive durvalumab intravenously, at a dose of 10 mg per kilogram of body weight, or matching placebo every 2 weeks for up to 12 months. Randomization occurred 1 to 42 days after the patients had received chemoradiotherapy and was stratified according to age, sex, and smoking history. The primary end points were progression-free survival (as assessed by blinded independent central review) and overall survival. Secondary end points included the time to death or distant metastasis, the time to second progression, and safety.
RESULTS:
Of the 713 patients who underwent randomization, 709 received the assigned intervention (473 patients received durvalumab and 236 received placebo). As of March 22, 2018, the median follow-up was 25.2 months. The 24-month overall survival rate was 66.3% (95% confidence interval [CI], 61.7 to 70.4) in the durvalumab group, as compared with 55.6% (95% CI, 48.9 to 61.8) in the placebo group (two-sided P=0.005). Durvalumab significantly prolonged overall survival, as compared with placebo (stratified hazard ratio for death, 0.68; 99.73% CI, 0.47 to 0.997; P=0.0025). Updated analyses regarding progression-free survival were similar to those previously reported, with a median duration of 17.2 months in the durvalumab group and 5.6 months in the placebo group (stratified hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.63). The median time to death or distant metastasis was 28.3 months in the durvalumab group and 16.2 months in the placebo group (stratified hazard ratio, 0.53; 95% CI, 0.41 to 0.68). A total of 30.5% of the patients in the durvalumab group and 26.1% of those in the placebo group had grade 3 or 4 adverse events of any cause; 15.4% and 9.8% of the patients, respectively, discontinued the trial regimen because of adverse events.
CONCLUSIONS:
Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461 .).
1,881 citations
TL;DR: Different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L 1 overexpression, neoantigens, and genetic and epigenetic signatures are discussed, which could improve the efficacy of this promising new cancer therapy.
Abstract: Cancer growth and progression are associated with immune suppression. Cancer cells have the ability to activate different immune checkpoint pathways that harbor immunosuppressive functions. Monoclonal antibodies that target immune checkpoints provided an immense breakthrough in cancer therapeutics. Among the immune checkpoint inhibitors, PD-1/PD-L1 and CTLA-4 inhibitors showed promising therapeutic outcomes, and some have been approved for certain cancer treatments, while others are under clinical trials. Recent reports have shown that patients with various malignancies benefit from immune checkpoint inhibitor treatment. However, mainstream initiation of immune checkpoint therapy to treat cancers is obstructed by the low response rate and immune-related adverse events in some cancer patients. This has given rise to the need for developing sets of biomarkers that predict the response to immune checkpoint blockade and immune-related adverse events. In this review, we discuss different predictive biomarkers for anti-PD-1/PD-L1 and anti-CTLA-4 inhibitors, including immune cells, PD-L1 overexpression, neoantigens, and genetic and epigenetic signatures. Potential approaches for further developing highly reliable predictive biomarkers should facilitate patient selection for and decision-making related to immune checkpoint inhibitor-based therapies.
1,296 citations
TL;DR: This study narrows down the immense number of bacterial taxa to a “most wanted” list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving the understanding of soil microbes and their contributions to ecosystem functioning.
Abstract: The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a “most wanted” list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.
1,204 citations
TL;DR: A dysprosium compound is reported that manifests magnetic hysteresis at temperatures up to 80 kelvin, which overcomes an essential barrier toward the development of nanomagnet devices that function at practical temperatures.
Abstract: Single-molecule magnets (SMMs) containing only one metal center may represent the lower size limit for molecule-based magnetic information storage materials. Their current drawback is that all SMMs require liquid-helium cooling to show magnetic memory effects. We now report a chemical strategy to access the dysprosium metallocene cation [(CpiPr5)Dy(Cp*)]+ (CpiPr5 = penta-iso-propylcyclopentadienyl, Cp* = pentamethylcyclopentadienyl), which displays magnetic hysteresis above liquid-nitrogen temperatures. An effective energy barrier to reversal of the magnetization of Ueff = 1,541 cm–1 is also measured. The magnetic blocking temperature of TB = 80 K for this cation overcomes an essential barrier towards the development of nanomagnet devices that function at practical temperatures.
1,198 citations
TL;DR: A cellular and molecular checkpoint for intratumoral cDC1 recruitment is revealed that is targeted by tumor-derived PGE2 for immune evasion and that could be exploited for cancer therapy.
991 citations
TL;DR: It is suggested that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost.
Abstract: Objective To update the "Testosterone Therapy in Men With Androgen Deficiency Syndromes" guideline published in 2010. Participants The participants include an Endocrine Society-appointed task force of 10 medical content experts and a clinical practice guideline methodologist. Evidence This evidence-based guideline was developed using the Grading of Recommendations, Assessment, Development, and Evaluation approach to describe the strength of recommendations and the quality of evidence. The task force commissioned two systematic reviews and used the best available evidence from other published systematic reviews and individual studies. Consensus process One group meeting, several conference calls, and e-mail communications facilitated consensus development. Endocrine Society committees and members and the cosponsoring organization were invited to review and comment on preliminary drafts of the guideline. Conclusions We recommend making a diagnosis of hypogonadism only in men with symptoms and signs consistent with testosterone (T) deficiency and unequivocally and consistently low serum T concentrations. We recommend measuring fasting morning total T concentrations using an accurate and reliable assay as the initial diagnostic test. We recommend confirming the diagnosis by repeating the measurement of morning fasting total T concentrations. In men whose total T is near the lower limit of normal or who have a condition that alters sex hormone-binding globulin, we recommend obtaining a free T concentration using either equilibrium dialysis or estimating it using an accurate formula. In men determined to have androgen deficiency, we recommend additional diagnostic evaluation to ascertain the cause of androgen deficiency. We recommend T therapy for men with symptomatic T deficiency to induce and maintain secondary sex characteristics and correct symptoms of hypogonadism after discussing the potential benefits and risks of therapy and of monitoring therapy and involving the patient in decision making. We recommend against starting T therapy in patients who are planning fertility in the near term or have any of the following conditions: breast or prostate cancer, a palpable prostate nodule or induration, prostate-specific antigen level > 4 ng/mL, prostate-specific antigen > 3 ng/mL in men at increased risk of prostate cancer (e.g., African Americans and men with a first-degree relative with diagnosed prostate cancer) without further urological evaluation, elevated hematocrit, untreated severe obstructive sleep apnea, severe lower urinary tract symptoms, uncontrolled heart failure, myocardial infarction or stroke within the last 6 months, or thrombophilia. We suggest that when clinicians institute T therapy, they aim at achieving T concentrations in the mid-normal range during treatment with any of the approved formulations, taking into consideration patient preference, pharmacokinetics, formulation-specific adverse effects, treatment burden, and cost. Clinicians should monitor men receiving T therapy using a standardized plan that includes: evaluating symptoms, adverse effects, and compliance; measuring serum T and hematocrit concentrations; and evaluating prostate cancer risk during the first year after initiating T therapy.
907 citations
TL;DR: The basic physical principles and properties of plasmonic surface lattice resonances are described: the width and quality of the resonances, singularities of the light phase, electric field enhancement, etc.
Abstract: When metal nanoparticles are arranged in an ordered array, they may scatter light to produce diffracted waves. If one of the diffracted waves then propagates in the plane of the array, it may couple the localized plasmon resonances associated with individual nanoparticles together, leading to an exciting phenomenon, the drastic narrowing of plasmon resonances, down to 1–2 nm in spectral width. This presents a dramatic improvement compared to a typical single particle resonance line width of >80 nm. The very high quality factors of these diffractively coupled plasmon resonances, often referred to as plasmonic surface lattice resonances, and related effects have made this topic a very active and exciting field for fundamental research, and increasingly, these resonances have been investigated for their potential in the development of practical devices for communications, optoelectronics, photovoltaics, data storage, biosensing, and other applications. In the present review article, we describe the basic phy...
828 citations
TL;DR: It is shown in grassland mesocosms that drought promotes destabilising properties in soil bacterial, but not fungal, co-occurrence networks, and that changes in bacterial communities link more strongly to soil functioning during recovery than do changes in fungal communities.
Abstract: Soil microbial communities play a crucial role in ecosystem functioning, but it is unknown how co-occurrence networks within these communities respond to disturbances such as climate extremes This represents an important knowledge gap because changes in microbial networks could have implications for their functioning and vulnerability to future disturbances Here, we show in grassland mesocosms that drought promotes destabilising properties in soil bacterial, but not fungal, co-occurrence networks, and that changes in bacterial communities link more strongly to soil functioning during recovery than do changes in fungal communities Moreover, we reveal that drought has a prolonged effect on bacterial communities and their co-occurrence networks via changes in vegetation composition and resultant reductions in soil moisture Our results provide new insight in the mechanisms through which drought alters soil microbial communities with potential long-term consequences, including future plant community composition and the ability of aboveground and belowground communities to withstand future disturbances
VU University Amsterdam1, Erasmus University Rotterdam2, Karolinska Institutet3, Charité4, Virginia Commonwealth University5, South London and Maudsley NHS Foundation Trust6, QIMR Berghofer Medical Research Institute7, King's College London8, University of Southern Denmark9, University of California, Riverside10, University of Southern California11, University of Minnesota12, University of Queensland13, University College London14, Johns Hopkins University15, University of California, Los Angeles16, University of Crete17, Veterans Health Administration18, Icahn School of Medicine at Mount Sinai19, Harvard University20, Yale University21, Haukeland University Hospital22, Trinity College, Dublin23, University of Edinburgh24, North Shore-LIJ Health System25, Hofstra University26, National Institutes of Health27, University of Bergen28, Oslo University Hospital29, National University of Ireland, Galway30, University of Helsinki31, University of Oslo32, Martin Luther University of Halle-Wittenberg33, Duke University34, National and Kapodistrian University of Athens35, Mental Health Research Institute36, University of Colorado Boulder37, Imperial College London38, University of Manchester39, Wellcome Trust40, Manchester Academic Health Science Centre41, Stanford University42, University of Oregon43, University of Toronto44, University of Michigan45, Erasmus University Medical Center46, Broad Institute47, University of North Carolina at Chapel Hill48
TL;DR: A large-scale genetic association study of intelligence identifies 190 new loci and implicates 939 new genes related to neurogenesis, neuron differentiation and synaptic structure, a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
Abstract: Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
The Royal Marsden NHS Foundation Trust1, University of Birmingham2, University College London3, University of Salford4, University of Manchester5, Guy's and St Thomas' NHS Foundation Trust6, St James's University Hospital7, Kantonsspital St. Gallen8, Beatson West of Scotland Cancer Centre9, Clatterbridge Cancer Centre NHS Foundation Trust10, Cardiff University11, University of Wolverhampton12, University of Glasgow13, University Hospitals Birmingham NHS Foundation Trust14, Queen Alexandra Hospital15, University of London16, Gloucestershire Hospitals NHS Foundation Trust17, Royal Surrey County Hospital18, Queen's University Belfast19, East Lancashire Hospitals NHS Trust20, Freeman Hospital21, Singleton Hospital22, Royal Devon and Exeter Hospital23, Telford24
TL;DR: Radiotherapy to the prostate did not improve overall survival for unselected patients with newly diagnosed metastatic prostate cancer, and the benefit would be greatest in patients with a low metastatic burden.
TL;DR: A comprehensive survey of the original birth, the most recent development, and the future research directions of non-orthogonal multiple access, along with a range of challenging open problems that should be solved for NOMA.
Abstract: In the fifth generation (5G) of wireless communication systems, hitherto unprecedented requirements are expected to be satisfied. As one of the promising techniques of addressing these challenges, non-orthogonal multiple access (NOMA) has been actively investigated in recent years. In contrast to the family of conventional orthogonal multiple access (OMA) schemes, the key distinguishing feature of NOMA is to support a higher number of users than the number of orthogonal resource slots with the aid of non-orthogonal resource allocation. This may be realized by the sophisticated inter-user interference cancellation at the cost of an increased receiver complexity. In this paper, we provide a comprehensive survey of the original birth, the most recent development, and the future research directions of NOMA. Specifically, the basic principle of NOMA will be introduced at first, with the comparison between NOMA and OMA especially from the perspective of information theory. Then, the prominent NOMA schemes are discussed by dividing them into two categories, namely, power-domain and code-domain NOMA. Their design principles and key features will be discussed in detail, and a systematic comparison of these NOMA schemes will be summarized in terms of their spectral efficiency, system performance, receiver complexity, etc. Finally, we will highlight a range of challenging open problems that should be solved for NOMA, along with corresponding opportunities and future research trends to address these challenges.
Evangelos Evangelou1, Evangelos Evangelou2, Helen R. Warren3, Helen R. Warren4 +338 more•Institutions (93)
TL;DR: In this article, the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry was conducted.
Abstract: High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future
TL;DR: The Hospital Frailty Risk Score provides hospitals and health systems with a low-cost, systematic way to screen for frailty and identify a group of patients who are at greater risk of adverse outcomes and for whom a frailty-attuned approach might be useful.
TL;DR: This dataset has the largest series of patients with rectal cancer treated with a W&W approach, consisting of approximately 50% data from previous cohort series and 50% unpublished data.
Fredrick R. Schumacher1, Ali Amin Al Olama2, Sonja I. Berndt3, Sara Benlloch2 +204 more•Institutions (79)
TL;DR: A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology of PrCa1.
Abstract: Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10−9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55–2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04–6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1. A large meta-analysis combining genome-wide and custom high-density genotyping array data identifies 63 new susceptibility loci for prostate cancer, enhancing fine-mapping efforts and providing insights into the underlying biology.
TL;DR: A critical look at the status of composites for developing high-strength, low-density, high-conductivity materials with nanotubes or graphene is presented, pointing out the challenges and opportunities that exist in the field.
Abstract: Composite materials with carbon nanotube and graphene additives have long been considered as exciting prospects among nanotechnology applications. However, after nearly two decades of work in the area, questions remain about the practical impact of nanotube and graphene composites. This uncertainty stems from factors that include poor load transfer, interfacial engineering, dispersion, and viscosity-related issues that lead to processing challenges in such nanocomposites. Moreover, there has been little effort to identify selection rules for the use of nanotubes or graphene in composite matrices for specific applications. This review is a critical look at the status of composites for developing high-strength, low-density, high-conductivity materials with nanotubes or graphene. An outlook of the different approaches that can lead to practically useful nanotube and graphene composites is presented, pointing out the challenges and opportunities that exist in the field.
TL;DR: This paper proposes the use of deep learning approaches for breast ultrasound lesion detection and investigates three different methods: a Patch-based LeNet, a U-Net, and a transfer learning approach with a pretrained FCN-AlexNet.
Abstract: Breast lesion detection using ultrasound imaging is considered an important step of computer-aided diagnosis systems. Over the past decade, researchers have demonstrated the possibilities to automate the initial lesion detection. However, the lack of a common dataset impedes research when comparing the performance of such algorithms. This paper proposes the use of deep learning approaches for breast ultrasound lesion detection and investigates three different methods: a Patch-based LeNet, a U-Net, and a transfer learning approach with a pretrained FCN-AlexNet. Their performance is compared against four state-of-the-art lesion detection algorithms (i.e., Radial Gradient Index, Multifractal Filtering, Rule-based Region Ranking, and Deformable Part Models). In addition, this paper compares and contrasts two conventional ultrasound image datasets acquired from two different ultrasound systems. Dataset A comprises 306 (60 malignant and 246 benign) images and Dataset B comprises 163 (53 malignant and 110 benign) images. To overcome the lack of public datasets in this domain, Dataset B will be made available for research purposes. The results demonstrate an overall improvement by the deep learning approaches when assessed on both datasets in terms of True Positive Fraction, False Positives per image, and F-measure.
TL;DR: The first public data release of the DES DR1 dataset is described in this paper, consisting of reduced single-epoch images, co-add images, and co-added source catalogs, and associated products and services.
Abstract: We describe the first public data release of the Dark Energy Survey, DES DR1, consisting of reduced single-epoch images, co-added images, co-added source catalogs, and associated products and services assembled over the first 3 yr of DES science operations. DES DR1 is based on optical/near-infrared imaging from 345 distinct nights (2013 August to 2016 February) by the Dark Energy Camera mounted on the 4 m Blanco telescope at the Cerro Tololo InterAmerican Observatory in Chile. We release data from the DES wide-area survey covering similar to 5000 deg(2) of the southern Galactic cap in five broad photometric bands, grizY. DES DR1 has a median delivered point-spread function of g = 1.12, r = 0.96, i = 0.88, z = 0.84, and Y = 0.'' 90 FWHM, a photometric precision of <1% in all bands, and an astrometric precision of 151 mas. The median co-added catalog depth for a 1.'' 95 diameter aperture at signal-to-noise ratio (S/N) = 10 is g = 24.33, r = 24.08, i = 23.44, z = 22.69, and Y = 21.44 mag. DES DR1 includes nearly 400 million distinct astronomical objects detected in similar to 10,000 co-add tiles of size 0.534 deg(2) produced from similar to 39,000 individual exposures. Benchmark galaxy and stellar samples contain similar to 310 million and similar to 80 million objects, respectively, following a basic object quality selection. These data are accessible through a range of interfaces, including query web clients, image cutout servers, jupyter notebooks, and an interactive co-add image visualization tool. DES DR1 constitutes the largest photometric data set to date at the achieved depth and photometric precision.
TL;DR: In this paper, the authors report catchmentwide patterns of microplastic contamination, classified by type, size and density, in channel bed sediments at 40 sites across urban, suburban and rural river catchments in northwest England.
Abstract: Microplastic contamination of the oceans is one of the world’s most pressing environmental concerns. The terrestrial component of the global microplastic budget is not well understood because sources, stores and fluxes are poorly quantified. We report catchment-wide patterns of microplastic contamination, classified by type, size and density, in channel bed sediments at 40 sites across urban, suburban and rural river catchments in northwest England. Microplastic contamination was pervasive on all river channel beds. We found multiple urban contamination hotspots with a maximum microplastic concentration of approximately 517,000 particles m−2. After a period of severe flooding in winter 2015/16, all sites were resampled. Microplastic concentrations had fallen at 28 sites and 18 saw a decrease of one order of magnitude. The flooding exported approximately 70% of the microplastic load stored on these river beds (equivalent to 0.85 ± 0.27 tonnes or 43 ± 14 billion particles) and eradicated microbead contamination at 7 sites. We conclude that microplastic contamination is efficiently flushed from river catchments during flooding.
TL;DR: A comprehensive review of a large number of empirical studies exploring leadership and workplace creativity and innovation is presented in this paper, where the main effects of leadership on creativity and creativity and the variables assumed to moderate these effects are discussed.
Abstract: Leadership is a key predictor of employee, team, and organizational creativity and innovation. Research in this area holds great promise for the development of intriguing theory and impactful policy implications, but only if empirical studies are conducted rigorously. In the current paper, we report a comprehensive review of a large number of empirical studies (N = 195) exploring leadership and workplace creativity and innovation. Using this article cache, we conducted a number of systematic analyses and built narrative arguments documenting observed trends in five areas. First, we review and offer improved definitions of creativity and innovation. Second, we conduct a systematic review of the main effects of leadership upon creativity and innovation and the variables assumed to moderate these effects. Third, we conduct a systematic review of mediating variables. Fourth, we examine whether the study designs commonly employed are suitable to estimate the causal models central to the field. Fifth, we conduct a critical review of the creativity and innovation measures used, noting that most are sub-optimal. Within these sections, we present a number of taxonomies that organize extant research, highlight understudied areas, and serve as a guide for future variable selection. We conclude by highlighting key suggestions for future research that we hope will reorient the field and improve the rigour of future research such that we can build more reliable and useful theories and policy recommendations.
TL;DR: Capacitance measurements reveal a low dielectric constant for atomically thin layers of water next to solid surfaces and reveal the presence of an interfacial layer with vanishingly small polarization such that its out-of-plane ε is only ~2, while the electrically dead layer is found to be two to three molecules thick.
Abstract: The dielectric constant of interfacial water has been predicted to be smaller than that of bulk water (= 80) because the rotational freedom of water dipoles is expected to decrease near surfaces, yet experimental evidence is lacking. We report local capacitance measurements for water confined between two atomically-flat walls separated by various distances down to 1 nm. Our experiments reveal the presence of an interfacial layer with vanishingly small polarization such that its out-of-plane dielectric constant is only approximately 2. The electrically dead layer is found to be two to three molecules thick. These results provide much needed feedback for theories describing water-mediated surface interactions and behavior of interfacial water, and show a way to investigate the dielectric properties of other fluids and solids under extreme confinement.
TL;DR: A mechanism map for predicting the evolution of melt features, changes in melt track morphology from a continuous hemi-cylindrical track to disconnected beads with decreasing linear energy density and improved molten pool wetting with increasing laser power is developed.
Abstract: The laser–matter interaction and solidification phenomena associated with laser additive manufacturing (LAM) remain unclear, slowing its process development and optimisation. Here, through in situ and operando high-speed synchrotron X-ray imaging, we reveal the underlying physical phenomena during the deposition of the first and second layer melt tracks. We show that the laser-induced gas/vapour jet promotes the formation of melt tracks and denuded zones via spattering (at a velocity of 1 m s−1). We also uncover mechanisms of pore migration by Marangoni-driven flow (recirculating at a velocity of 0.4 m s−1), pore dissolution and dispersion by laser re-melting. We develop a mechanism map for predicting the evolution of melt features, changes in melt track morphology from a continuous hemi-cylindrical track to disconnected beads with decreasing linear energy density and improved molten pool wetting with increasing laser power. Our results clarify aspects of the physics behind LAM, which are critical for its development. Additive manufacturing of metals is now widely available, but the interaction of the metal powder with the laser remains unclear. Here, the authors use X-rays to image melt features and pore behaviour during laser melting of powders.
University of Würzburg1, University of Pennsylvania2, Pohang University of Science and Technology3, University of Manchester4, Dresden University of Technology5, Stanford University6, Utrecht University7, Saga University8, Vienna University of Technology9, Tsinghua University10, Drexel University11, University of Tokyo12, Wake Forest Institute for Regenerative Medicine13, University of Otago14
TL;DR: A simple but general definition of bioinks is proposed, and its distinction from biomaterial inks is clarified, to briefly summarize the historic evolution of this term within the field of biofabrication.
Abstract: Biofabrication aims to fabricate biologically functional products through bioprinting or bioassembly (Groll et al 2016 Biofabrication 8 013001). In biofabrication processes, cells are positioned at defined coordinates in three-dimensional space using automated and computer controlled techniques (Moroni et al 2018 Trends Biotechnol. 36 384-402), usually with the aid of biomaterials that are either (i) directly processed with the cells as suspensions/dispersions, (ii) deposited simultaneously in a separate printing process, or (iii) used as a transient support material. Materials that are suited for biofabrication are often referred to as bioinks and have become an important area of research within the field. In view of this special issue on bioinks, we aim herein to briefly summarize the historic evolution of this term within the field of biofabrication. Furthermore, we propose a simple but general definition of bioinks, and clarify its distinction from biomaterial inks.
TL;DR: This tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported.
Abstract: Quality assurance (QA) and quality control (QC) are two quality management processes that are integral to the success of metabolomics including their application for the acquisition of high quality data in any high-throughput analytical chemistry laboratory. QA defines all the planned and systematic activities implemented before samples are collected, to provide confidence that a subsequent analytical process will fulfil predetermined requirements for quality. QC can be defined as the operational techniques and activities used to measure and report these quality requirements after data acquisition. This tutorial review will guide the reader through the use of system suitability and QC samples, why these samples should be applied and how the quality of data can be reported. System suitability samples are applied to assess the operation and lack of contamination of the analytical platform prior to sample analysis. Isotopically-labelled internal standards are applied to assess system stability for each sample analysed. Pooled QC samples are applied to condition the analytical platform, perform intra-study reproducibility measurements (QC) and to correct mathematically for systematic errors. Standard reference materials and long-term reference QC samples are applied for inter-study and inter-laboratory assessment of data.
TL;DR: A new cascade control structure, based on a fixed-time distributed observer, is developed to achieve the fixed- time consensus tracking control for high-order integrator multiagent systems subject to matched external disturbances.
Abstract: This paper addresses the fixed-time leader–follower consensus problem for high-order integrator multiagent systems subject to matched external disturbances. A new cascade control structure, based on a fixed-time distributed observer, is developed to achieve the fixed-time consensus tracking control. A simulation example is included to show the efficacy and the performance of the proposed control structure with respect to different initial conditions.
TL;DR: Interestingly, mutations predominantly in the N-terminal motor domain of KIF5A are causative for two neurodegenerative diseases: hereditary spastic paraplegia and Charcot-Marie-Tooth type 2.
Technical University of Berlin1, Jadavpur University2, Carnegie Mellon University3, University of Leeds4, Eni5, University of Manchester6, International Institute of Minnesota7, University of Oxford8, Yale University9, Centre for Policy Research10, Central European University11, Princeton University12
TL;DR: In this article, a transdisciplinary approach is proposed to identify demand-side climate solutions, investigate their mitigation potential, detail policy measures and assess their implications for well-being, and propose a trans-disciplinary approach to identify and analyse demand side climate solutions.
Abstract: Research on climate change mitigation tends to focus on supply-side technology solutions A better understanding of demand-side solutions is missing We propose a transdisciplinary approach to identify demand-side climate solutions, investigate their mitigation potential, detail policy measures and assess their implications for well-being