Showing papers by "University College Dublin published in 2018"

Analysis of shared heritability in common disorders of the brain

Abstract: Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.

Durable clinical benefit with nivolumab plus ipilimumab in DNA mismatch repair-deficient/microsatellite instability-high metastatic colorectal cancer

Abstract: PurposeNivolumab provides clinical benefit (objective response rate [ORR], 31%; 95% CI, 20.8 to 42.9; disease control rate, 69%; 12-month overall survival [OS], 73%) in previously treated patients with DNA mismatch repair–deficient (dMMR)/microsatellite instability–high (MSI-H) metastatic colorectal cancer (mCRC); nivolumab plus ipilimumab may improve these outcomes. Efficacy and safety results for the nivolumab plus ipilimumab cohort of CheckMate-142, the largest single-study report of an immunotherapy combination in dMMR/MSI-H mCRC, are reported.Patients and MethodsPatients received nivolumab 3 mg/kg plus ipilimumab 1 mg/kg once every 3 weeks (four doses) followed by nivolumab 3 mg/kg once every 2 weeks. Primary end point was investigator-assessed ORR.ResultsOf 119 patients, 76% had received ≥ two prior systemic therapies. At median follow-up of 13.4 months, investigator-assessed ORR was 55% (95% CI, 45.2 to 63.8), and disease control rate for ≥ 12 weeks was 80%. Median duration of response was not reac...

Clustal Omega for making accurate alignments of many protein sequences.

Abstract: Clustal Omega is a widely used package for carrying out multiple sequence alignment. Here, we describe some recent additions to the package and benchmark some alternative ways of making alignments. These benchmarks are based on protein structure comparisons or predictions and include a recently described method based on secondary structure prediction. In general, Clustal Omega is fast enough to make very large alignments and the accuracy of protein alignments is high when compared to alternative packages. The package is freely available as executables or source code from www.clustal.org or can be run on-line from a variety of sites, especially the EBI www.ebi.ac.uk.

Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.

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

Age and Age-Related Diseases: Role of Inflammation Triggers and Cytokines.

Abstract: Cytokine dysregulation is believed to play a key role in the remodeling of the immune system at older age, with evidence pointing to an inability to fine-control systemic inflammation, which seems to be a marker of unsuccessful aging. This reshaping of cytokine expression pattern, with a progressive tendency toward a pro-inflammatory phenotype has been called "inflamm-aging." Despite research there is no clear understanding about the causes of "inflamm-aging" that underpin most major age-related diseases, including atherosclerosis, diabetes, Alzheimer's disease, rheumatoid arthritis, cancer, and aging itself. While inflammation is part of the normal repair response for healing, and essential in keeping us safe from bacterial and viral infections and noxious environmental agents, not all inflammation is good. When inflammation becomes prolonged and persists, it can become damaging and destructive. Several common molecular pathways have been identified that are associated with both aging and low-grade inflammation. The age-related change in redox balance, the increase in age-related senescent cells, the senescence-associated secretory phenotype (SASP) and the decline in effective autophagy that can trigger the inflammasome, suggest that it may be possible to delay age-related diseases and aging itself by suppressing pro-inflammatory molecular mechanisms or improving the timely resolution of inflammation. Conversely there may be learning from molecular or genetic pathways from long-lived cohorts who exemplify good quality aging. Here, we will discuss some of the current ideas and highlight molecular pathways that appear to contribute to the immune imbalance and the cytokine dysregulation, which is associated with "inflammageing" or parainflammation. Evidence of these findings will be drawn from research in cardiovascular disease, cancer, neurological inflammation and rheumatoid arthritis.

Foundations and Challenges of Low-Inertia Systems (Invited Paper)

Abstract: The electric power system is currently undergoing a period of unprecedented changes. Environmental and sustainability concerns lead to replacement of a significant share of conventional fossil fuel-based power plants with renewable energy resources. This transition involves the major challenge of substituting synchronous machines and their well-known dynamics and controllers with power electronics-interfaced generation whose regulation and interaction with the rest of the system is yet to be fully understood. In this article, we review the challenges of such low-inertia power systems, and survey the solutions that have been put forward thus far. We strive to concisely summarize the laid-out scientific foundations as well as the practical experiences of industrial and academic demonstration projects. We touch upon the topics of power system stability, modeling, and control, and we particularly focus on the role of frequency, inertia, as well as control of power converters and from the demand-side.

Gaia Data Release 2. Observations of solar system objects

Abstract: Context. The Gaia spacecraft of the European Space Agency (ESA) has been securing observations of solar system objects (SSOs) since the beginning of its operations. Data Release 2 (DR2) contains the observations of a selected sample of 14,099 SSOs. These asteroids have been already identified and have been numbered by the Minor Planet Center repository. Positions are provided for each Gaia observation at CCD level. As additional information, complementary to astrometry, the apparent brightness of SSOs in the unfiltered G band is also provided for selected observations.Aims. We explain the processing of SSO data, and describe the criteria we used to select the sample published in Gaia DR2. We then explore the data set to assess its quality.Methods. To exploit the main data product for the solar system in Gaia DR2, which is the epoch astrometry of asteroids, it is necessary to take into account the unusual properties of the uncertainty, as the position information is nearly one-dimensional. When this aspect is handled appropriately, an orbit fit can be obtained with post-fit residuals that are overall consistent with the a-priori error model that was used to define individual values of the astrometric uncertainty. The role of both random and systematic errors is described. The distribution of residuals allowed us to identify possible contaminants in the data set (such as stars). Photometry in the G band was compared to computed values from reference asteroid shapes and to the flux registered at the corresponding epochs by the red and blue photometers (RP and BP).Results. The overall astrometric performance is close to the expectations, with an optimal range of brightness G ~ 12 − 17. In this range, the typical transit-level accuracy is well below 1 mas. For fainter asteroids, the growing photon noise deteriorates the performance. Asteroids brighter than G ~ 12 are affected by a lower performance of the processing of their signals. The dramatic improvement brought by Gaia DR2 astrometry of SSOs is demonstrated by comparisons to the archive data and by preliminary tests on the detection of subtle non-gravitational effects.

Gaia Data Release 2. Kinematics of globular clusters and dwarf galaxies around the Milky Way

Abstract: Context. Aims: The goal of this paper is to demonstrate the outstanding quality of the second data release of the Gaia mission and its power for constraining many different aspects of the dynamics of the satellites of the Milky Way. We focus here on determining the proper motions of 75 Galactic globular clusters, nine dwarf spheroidal galaxies, one ultra-faint system, and the Large and Small Magellanic Clouds. Methods: Using data extracted from the Gaia archive, we derived the proper motions and parallaxes for these systems, as well as their uncertainties. We demonstrate that the errors, statistical and systematic, are relatively well understood. We integrated the orbits of these objects in three different Galactic potentials, and characterised their properties. We present the derived proper motions, space velocities, and characteristic orbital parameters in various tables to facilitate their use by the astronomical community. Results: Our limited and straightforward analyses have allowed us for example to (i) determine absolute and very precise proper motions for globular clusters; (ii) detect clear rotation signatures in the proper motions of at least five globular clusters; (iii) show that the satellites of the Milky Way are all on high-inclination orbits, but that they do not share a single plane of motion; (iv) derive a lower limit for the mass of the Milky Way of 9.1-2.6+6.2 × 1011 M⊙ based on the assumption that the Leo I dwarf spheroidal is bound; (v) derive a rotation curve for the Large Magellanic Cloud based solely on proper motions that is competitive with line-of-sight velocity curves, now using many orders of magnitude more sources; and (vi) unveil the dynamical effect of the bar on the motions of stars in the Large Magellanic Cloud. Conclusions: All these results highlight the incredible power of the Gaia astrometric mission, and in particular of its second data release.

Analyzing mixing systems using a new generation of Bayesian tracer mixing models.

Abstract: The ongoing evolution of tracer mixing models has resulted in a confusing array of software tools that differ in terms of data inputs, model assumptions, and associated analytic products. Here we introduce MixSIAR, an inclusive, rich, and flexible Bayesian tracer (e.g., stable isotope) mixing model framework implemented as an open-source R package. Using MixSIAR as a foundation, we provide guidance for the implementation of mixing model analyses. We begin by outlining the practical differences between mixture data error structure formulations and relate these error structures to common mixing model study designs in ecology. Because Bayesian mixing models afford the option to specify informative priors on source proportion contributions, we outline methods for establishing prior distributions and discuss the influence of prior specification on model outputs. We also discuss the options available for source data inputs (raw data versus summary statistics) and provide guidance for combining sources. We then describe a key advantage of MixSIAR over previous mixing model software-the ability to include fixed and random effects as covariates explaining variability in mixture proportions and calculate relative support for multiple models via information criteria. We present a case study of Alligator mississippiensis diet partitioning to demonstrate the power of this approach. Finally, we conclude with a discussion of limitations to mixing model applications. Through MixSIAR, we have consolidated the disparate array of mixing model tools into a single platform, diversified the set of available parameterizations, and provided developers a platform upon which to continue improving mixing model analyses in the future.

Barriers and solutions to online learning in medical education – an integrative review

Abstract: The aim of this study is to review the literature on known barriers and solutions that face educators when developing and implementing online learning programs for medical students and postgraduate trainees. An integrative review was conducted over a three-month period by an inter-institutional research team. The search included ScienceDirect, Scopus, BioMedical, PubMed, Medline (EBSCO & Ovid), ERIC, LISA, EBSCO, Google Scholar, ProQuest A&I, ProQuest UK & Ireland, UL Institutional Repository (IR), UCDIR and the All Aboard Report. Search terms included online learning, medical educators, development, barriers, solutions and digital literacy. The search was carried out by two reviewers. Titles and abstracts were screened independently and reviewed with inclusion/exclusion criteria. A consensus was drawn on which articles were included. Data appraisal was performed using the Critical Appraisal Skills Programme (CASP) Qualitative Research Checklist and NHMRC Appraisal Evidence Matrix. Data extraction was completed using the Cochrane Data Extraction Form and a modified extraction tool. Of the 3101 abstracts identified from the search, ten full-text papers met the inclusion criteria. Data extraction was completed on seven papers of high methodological quality and on three lower quality papers. Findings suggest that the key barriers which affect the development and implementation of online learning in medical education include time constraints, poor technical skills, inadequate infrastructure, absence of institutional strategies and support and negative attitudes of all involved. Solutions to these include improved educator skills, incentives and reward for the time involved with development and delivery of online content, improved institutional strategies and support and positive attitude amongst all those involved in the development and delivery of online content. This review has identified barriers and solutions amongst medical educators to the implementation of online learning in medical education. Results can be used to inform institutional and educator practice in the development of further online learning.

On the Total Energy Efficiency of Cell-Free Massive MIMO

Abstract: We consider the cell-free massive multiple-input multiple-output (MIMO) downlink, where a very large number of distributed multiple-antenna access points (APs) serve many single-antenna users in the same time-frequency resource. A simple (distributed) conjugate beamforming scheme is applied at each AP via the use of local channel state information (CSI). This CSI is acquired through time-division duplex operation and the reception of uplink training signals transmitted by the users. We derive a closed-form expression for the spectral efficiency taking into account the effects of channel estimation errors and power control. This closed-form result enables us to analyze the effects of backhaul power consumption, the number of APs, and the number of antennas per AP on the total energy efficiency, as well as, to design an optimal power allocation algorithm. The optimal power allocation algorithm aims at maximizing the total energy efficiency, subject to a per-user spectral efficiency constraint and a per-AP power constraint. Compared with the equal power control, our proposed power allocation scheme can double the total energy efficiency. Furthermore, we propose AP selections schemes, in which each user chooses a subset of APs, to reduce the power consumption caused by the backhaul links. With our proposed AP selection schemes, the total energy efficiency increases significantly, especially for large numbers of APs. Moreover, under a requirement of good quality-of-service for all users, cell-free massive MIMO outperforms the colocated counterpart in terms of energy efficiency.

The Beaker phenomenon and the genomic transformation of northwest Europe

Abstract: From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.

Identification of heavy-flavour jets with the CMS detector in pp collisions at 13 TeV

Abstract: Many measurements and searches for physics beyond the standard model at the LHC rely on the efficient identification of heavy-flavour jets, i.e. jets originating from bottom or charm quarks. In this paper, the discriminating variables and the algorithms used for heavy-flavour jet identification during the first years of operation of the CMS experiment in proton-proton collisions at a centre-of-mass energy of 13 TeV, are presented. Heavy-flavour jet identification algorithms have been improved compared to those used previously at centre-of-mass energies of 7 and 8 TeV. For jets with transverse momenta in the range expected in simulated events, these new developments result in an efficiency of 68% for the correct identification of a b jet for a probability of 1% of misidentifying a light-flavour jet. The improvement in relative efficiency at this misidentification probability is about 15%, compared to previous CMS algorithms. In addition, for the first time algorithms have been developed to identify jets containing two b hadrons in Lorentz-boosted event topologies, as well as to tag c jets. The large data sample recorded in 2016 at a centre-of-mass energy of 13 TeV has also allowed the development of new methods to measure the efficiency and misidentification probability of heavy-flavour jet identification algorithms. The b jet identification efficiency is measured with a precision of a few per cent at moderate jet transverse momenta (between 30 and 300 GeV) and about 5% at the highest jet transverse momenta (between 500 and 1000 GeV).

The genomic history of southeastern Europe

Abstract: Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to und ...

Group-based multi-trajectory modeling.

Abstract: Identifying and monitoring multiple disease biomarkers and other clinically important factors affecting the course of a disease, behavior or health status is of great clinical relevance. Yet conventional statistical practice generally falls far short of taking full advantage of the information available in multivariate longitudinal data for tracking the course of the outcome of interest. We demonstrate a method called multi-trajectory modeling that is designed to overcome this limitation. The method is a generalization of group-based trajectory modeling. Group-based trajectory modeling is designed to identify clusters of individuals who are following similar trajectories of a single indicator of interest such as post-operative fever or body mass index. Multi-trajectory modeling identifies latent clusters of individuals following similar trajectories across multiple indicators of an outcome of interest (e.g., the health status of chronic kidney disease patients as measured by their eGFR, hemoglobin, blood CO2 levels). Multi-trajectory modeling is an application of finite mixture modeling. We lay out the underlying likelihood function of the multi-trajectory model and demonstrate its use with two examples.

Diabetes UK evidence-based nutrition guidelines for the prevention and management of diabetes.

Abstract: A summary of the latest evidence-based nutrition guidelines for the prevention and management of diabetes is presented. These guidelines are based on existing recommendations last published in 2011, and were formulated by an expert panel of specialist dietitians after a literature review of recent evidence. Recommendations have been made in terms of foods rather than nutrients wherever possible. Guidelines for education and care delivery, prevention of Type 2 diabetes, glycaemic control for Type 1 and Type 2 diabetes, cardiovascular disease risk management, management of diabetes-related complications, other considerations including comorbidities, nutrition support, pregnancy and lactation, eating disorders, micronutrients, food supplements, functional foods, commercial diabetic foods and nutritive and non-nutritive sweeteners are included. The sections on pregnancy and prevention of Type 2 diabetes have been enlarged and the weight management section modified to include considerations of remission of Type 2 diabetes. A section evaluating detailed considerations in ethnic minorities has been included as a new topic. The guidelines were graded using adapted 'GRADE' methodology and, where strong evidence was lacking, grading was not allocated. These 2018 guidelines emphasize a flexible, individualized approach to diabetes management and weight loss and highlight the emerging evidence for remission of Type 2 diabetes. The full guideline document is available at www.diabetes.org.uk/nutrition-guidelines.

3D printing of robotic soft actuators with programmable bioinspired architectures.

Abstract: Soft actuation allows robots to interact safely with humans, other machines, and their surroundings. Full exploitation of the potential of soft actuators has, however, been hindered by the lack of simple manufacturing routes to generate multimaterial parts with intricate shapes and architectures. Here, we report a 3D printing platform for the seamless digital fabrication of pneumatic silicone actuators exhibiting programmable bioinspired architectures and motions. The actuators comprise an elastomeric body whose surface is decorated with reinforcing stripes at a well-defined lead angle. Similar to the fibrous architectures found in muscular hydrostats, the lead angle can be altered to achieve elongation, contraction, or twisting motions. Using a quantitative model based on lamination theory, we establish design principles for the digital fabrication of silicone-based soft actuators whose functional response is programmed within the material's properties and architecture. Exploring such programmability enables 3D printing of a broad range of soft morphing structures.

Performance of the CMS muon detector and muon reconstruction with proton-proton collisions at s=13 TeV

Abstract: The CMS muon detector system, muon reconstruction software, and high-level trigger underwent significant changes in 2013–2014 in preparation for running at higher LHC collision energy and instantaneous luminosity. The performance of the modified system is studied using proton-proton collision data at center-of-mass energy √s=13 TeV, collected at the LHC in 2015 and 2016. The measured performance parameters, including spatial resolution, efficiency, and timing, are found to meet all design specifications and are well reproduced by simulation. Despite the more challenging running conditions, the modified muon system is found to perform as well as, and in many aspects better than, previously. We dedicate this paper to the memory of Prof. Alberto Benvenuti, whose work was fundamental for the CMS muon detector.

Cryo-CMOS Circuits and Systems for Quantum Computing Applications

Abstract: A fault-tolerant quantum computer with millions of quantum bits (qubits) requires massive yet very precise control electronics for the manipulation and readout of individual qubits. CMOS operating at cryogenic temperatures down to 4 K (cryo-CMOS) allows for closer system integration, thus promising a scalable solution to enable future quantum computers. In this paper, a cryogenic control system is proposed, along with the required specifications, for the interface of the classical electronics with the quantum processor. To prove the advantages of such a system, the functionality of key circuit blocks is experimentally demonstrated. The characteristic properties of cryo-CMOS are exploited to design a noise-canceling low-noise amplifier for spin-qubit RF-reflectometry readout and a class-F2,3 digitally controlled oscillator required to manipulate the state of qubits.

Introductory programming: a systematic literature review

Abstract: As computing becomes a mainstream discipline embedded in the school curriculum and acts as an enabler for an increasing range of academic disciplines in higher education, the literature on introductory programming is growing. Although there have been several reviews that focus on specific aspects of introductory programming, there has been no broad overview of the literature exploring recent trends across the breadth of introductory programming. This paper is the report of an ITiCSE working group that conducted a systematic review in order to gain an overview of the introductory programming literature. Partitioning the literature into papers addressing the student, teaching, the curriculum, and assessment, we explore trends, highlight advances in knowledge over the past 15 years, and indicate possible directions for future research.

The role of nitrifier denitrification in the production of nitrous oxide revisited

Abstract: Nitrifier denitrification is the reduction of nitrite (NO2 −) by ammonia-oxidizing bacteria. This process may account for up to 100% of nitrous oxide (N2O) emissions from ammonium (NH4 +) in soils and is more significant than classical denitrification under some conditions. Investigations of nitrifier denitrification have expanded in the last decade but many aspects are still not understood. In this review, we revisit our 2001 paper, present a comprehensive summary of current knowledge concerning nitrifier denitrification, and identify the many research needs. Nitrifier denitrification can be distinguished from other routes of N2O production using isotopic methods: either isotopomer techniques or a combination of 15N and 18O tracers. Our understanding of the regulation and conditions favouring nitrifier denitrification has improved over the last decade as a result of adopting molecular and modelling approaches. Environments low in oxygen, and especially those with fluctuating aerobic-anaerobic conditions, promote N2O production by nitrifier denitrification. Also, large NO2 − concentrations, which often arise following inputs of ammonium or urea, may be linked to changes in aerobicity and high pH and favour nitrifier denitrification. The effects of temperature and carbon contents on nitrifier denitrification are incompletely understood and future research needs include: the study of pathways similar to nitrifier denitrification in archaea and nitrite oxidizers; the effects of interactions among microorganisms and between microorganism and plants; and the regulation and importance of the enzymes involved. A comparison and evaluation of the methods used for differentiating the sources of N2O is urgently needed. Furthermore, results from studies of freshwater and marine environments as well as wastewater treatment, where nitrifier denitrification is also known as nitrous aerobic denitritation (up to N2O) or aerobic denitritation (up to N2), will further advance our understanding.

A universal standard for the validation of blood pressure measuring devices: Association for the Advancement of Medical Instrumentation/European Society of Hypertension/International Organization for Standardization (AAMI/ESH/ISO) Collaboration Statement

Abstract: Copyright © 2018 Wolters Kluwer Health, Inc., and American Heart Association, Inc. This article has been copublished in Hypertension. In the last 30 years, several organizations, such as the US Association for the Advancement of Medical Instrumentation (AAMI), the British Hypertension Society, the European Society of Hypertension (ESH) Working Group on Blood Pressure (BP) Monitoring and the International Organization for Standardization (ISO) have developed protocols for clinical validation of BP measuring devices. However, it is recognized that science, as well as patients, consumers and manufacturers would be best served if all BP measuring devices were assessed for accuracy according to an agreed single validation protocol that had global acceptance. Therefore, an international initiative was taken by AAMI, ESH and ISO experts who agreed to develop a universal standard for device validation. This statement presents the key aspects of a validation procedure, which were agreed by the AAMI, ESH and ISO representatives as the basis for a single universal validation protocol. As soon as the AAMI/ESH/ISO standard is fully developed, this will be regarded as the single universal standard and will replace all other previous standards/protocols.

Biodegradable Plastic Blends Create New Possibilities for End-of-Life Management of Plastics but They Are Not a Panacea for Plastic Pollution

Abstract: Plastic waste pollution is a global environmental problem which could be addressed by biodegradable plastics The latter are blended together to achieve commercially functional properties, but the environmental fate of these blends is unknown We have tested neat polymers, polylactic acid (PLA), polyhydroxybutyrate, polyhydroxyoctanoate, poly(butylene succinate), thermoplastic starch, polycaprolactone (PCL), and blends thereof for biodegradation across seven managed and unmanaged environments PLA is one of the world’s best-selling biodegradable plastics, but it is not home compostable We show here that PLA when blended with PCL becomes home compostable We also demonstrate that the majority of the tested bioplastics and their blends degrade by thermophilic anaerobic digestion with high biogas output, but degradation times are 3–6 times longer than the retention times in commercial plants While some polymers and their blends showed good biodegradation in soil and water, the majority of polymers and thei

Diagnostic criteria of ulcerative Pyoderma Gangrenosum a delphi consensus of international experts

Abstract: Importance Pyoderma gangrenosum is a rare inflammatory skin condition that is difficult to diagnose. Currently, it is a “diagnosis of exclusion,” a definition not compatible with clinical decision making or inclusion for clinical trials. Objective To propose and validate diagnostic criteria for ulcerative pyoderma gangrenosum. Evidence Review Diagnostic criteria were created following a Delphi consensus exercise using the RAND/UCLA Appropriateness Method. The criteria were validated against peer-reviewed established cases of pyoderma gangrenosum and mimickers using k-fold cross-validation with methods of multiple imputation. Findings Delphi exercise yielded 1 major criterion—biopsy of ulcer edge demonstrating neutrophilic infiltrate—and 8 minor criteria: (1) exclusion of infection; (2) pathergy; (3) history of inflammatory bowel disease or inflammatory arthritis; (4) history of papule, pustule, or vesicle ulcerating within 4 days of appearing; (5) peripheral erythema, undermining border, and tenderness at ulceration site; (6) multiple ulcerations, at least 1 on an anterior lower leg; (7) cribriform or “wrinkled paper” scar(s) at healed ulcer sites; and (8) decreased ulcer size within 1 month of initiating immunosuppressive medication(s). Receiver operating characteristic analysis revealed that 4 of 8 minor criteria maximized discrimination, yielding sensitivity and specificity of 86% and 90%, respectively. Conclusions and Relevance This Delphi exercise produced 1 major criterion and 8 minor criteria for the diagnosis of ulcerative pyoderma gangrenosum. The criteria may serve as a guideline for clinicians, allowing for fewer misdiagnoses and improved patient selection for clinical trials.

WUDAPT: An Urban Weather, Climate, and Environmental Modeling Infrastructure for the Anthropocene

Abstract: The World Urban Database and Access Portal Tools (WUDAPT) is an international community-based initiative to acquire and disseminate climate relevant data on the physical geographies of cities for modeling and analysis purposes. The current lacuna of globally consistent information on cities is a major impediment to urban climate science toward informing and developing climate mitigation and adaptation strategies at urban scales. WUDAPT consists of a database and a portal system; its database is structured into a hierarchy representing different levels of detail, and the data are acquired using innovative protocols that utilize crowdsourcing approaches, Geowiki tools, freely accessible data, and building typology archetypes. The base level of information (L0) consists of local climate zone (LCZ) maps of cities; each LCZ category is associated with a range of values for model-relevant surface descriptors (roughness, impervious surface cover, roof area, building heights, etc.). Levels 1 (L1) and 2 (L2) will provide specific intra-urban values for other relevant descriptors at greater precision, such as data morphological forms, material composition data, and energy usage. This article describes the status of the WUDAPT project and demonstrates its potential value using observations and models. As a community-based project, other researchers are encouraged to participate to help create a global urban database of value to urban climate scientists.