Structuring the Unstructured: Unlocking pharmacokinetic data from journals with Natural Language Processing

The development of a new drug is an increasingly expensive and inefficient process. Many drug candidates are discarded due to pharmacokinetic (PK) complications detected at clinical phases. It is critical to accurately estimate the PK parameters of new drugs before being tested in humans since they will determine their efficacy and safety outcomes. Preclinical predictions of PK parameters are largely based on prior knowledge from other compounds, but much of this potentially valuable data is currently locked in the format of scientific papers. With an ever-increasing amount of scientific literature, automated systems are essential to exploit this resource efficiently. Developing text mining systems that can structure PK literature is critical to improving the drug development pipeline. This thesis studied the development and application of text mining resources to accelerate the curation of PK databases. Specifically, the development of novel corpora and suitable natural language processing architectures in the PK domain were addressed. The work presented focused on machine learning approaches that can model the high diversity of PK studies, parameter mentions, numerical measurements, units, and contextual information reported across the literature. Additionally, architectures and training approaches that could efficiently deal with the scarcity of annotated examples were explored. The chapters of this thesis tackle the development of suitable models and corpora to (1) retrieve PK documents, (2) recognise PK parameter mentions, (3) link PK entities to a knowledge base and (4) extract relations between parameter mentions, estimated measurements, units and other contextual information. Finally, the last chapter of this thesis studied the feasibility of the whole extraction pipeline to accelerate tasks in drug development research. The results from this thesis exhibited the potential of text mining approaches to automatically generate PK databases that can aid researchers in the field and ultimately accelerate the drug development pipeline. Additionally, the thesis presented contributions to biomedical natural language processing by developing suitable architectures and corpora for multiple tasks, tackling novel entities and relations within the PK domain

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Reduced oxygen saturation entropy is associated with poor prognosis in critically ill patients with sepsis

Abstract Recent studies have found that oxygen saturation (SpO2) variability analysis has potential for noninvasive assessment of the functional connectivity of cardiorespiratory control systems during hypoxia. Patients with sepsis have suboptimal tissue oxygenation and impaired organ system connectivity. Our objective with this report was to highlight the potential use for SpO2 variability analysis in predicting intensive care survival in patients with sepsis. MIMIC‐III clinical data of 164 adults meeting Sepsis‐3 criteria and with 30 min of SpO2 and respiratory rate data were analyzed. The complexity of SpO2 signals was measured through various entropy calculations such as sample entropy and multiscale entropy analysis. The sequential organ failure assessment (SOFA) score was calculated to assess the severity of sepsis and multiorgan failure. While the standard deviation of SpO2 signals was comparable in the non‐survivor and survivor groups, non‐survivors had significantly lower SpO2 entropy than those who survived their ICU stay (0.107 ± 0.084 vs. 0.070 ± 0.083, p < 0.05). According to Cox regression analysis, higher SpO2 entropy was a predictor of survival in patients with sepsis. Multivariate analysis also showed that the prognostic value of SpO2 entropy was independent of other covariates such as age, SOFA score, mean SpO2, and ventilation status. When SpO2 entropy was combined with mean SpO2, the composite had a significantly higher performance in prediction of survival. Analysis of SpO2 entropy can predict patient outcome, and when combined with SpO2 mean, can provide improved prognostic information. The prognostic power is on par with the SOFA score. This analysis can easily be incorporated into current ICU practice and has potential for noninvasive assessment of critically ill patients

Impact of Center-related Characteristics and Macroeconomic Factors on the Outcome of Adult Patients With Acute Lymphoblastic Leukemia Treated With Pediatric-inspired Protocols

Altres ajuts: Asociación Española contra el Cáncer (GC16173697BIGA

Human Early Life Exposome (HELIX) study: a European population-based exposome cohort

e021311Purpose Essential to exposome research is the collection of data on many environmental exposures from different domains in the same subjects. The aim of the Human Early Life Exposome (HELIX) study was to measure and describe multiple environmental exposures during early life (pregnancy and childhood) in a prospective cohort and associate these exposures with molecular omics signatures and child health outcomes. Here, we describe recruitment, measurements available and baseline data of the HELIX study populations. Participants The HELIX study represents a collaborative project across six established and ongoing longitudinal population-based birth cohort studies in six European countries (France, Greece, Lithuania, Norway, Spain and the UK). HELIX used a multilevel study design with the entire study population totalling 31 472 mother-child pairs, recruited during pregnancy, in the six existing cohorts (first level); a subcohort of 1301 mother-child pairs where biomarkers, omics signatures and child health outcomes were measured at age 6–11 years (second level) and repeat-sampling panel studies with around 150 children and 150 pregnant women aimed at collecting personal exposure data (third level). Findings to date Cohort data include urban environment, hazardous substances and lifestyle-related exposures for women during pregnancy and their offspring from birth until 6–11 years. Common, standardised protocols were used to collect biological samples, measure exposure biomarkers and omics signatures and assess child health across the six cohorts. Baseline data of the cohort show substantial variation in health outcomes and determinants between the six countries, for example, in family affluence levels, tobacco smoking, physical activity, dietary habits and prevalence of childhood obesity, asthma, allergies and attention deficit hyperactivity disorder. [...]Aplinkotyros katedraVytauto Didžiojo universiteta

The Southern Photometric Local Universe Survey (S-PLUS): improved SEDs, morphologies, and redshifts with 12 optical filters

The Southern Photometric Local Universe Survey (S-PLUS) is imaging similar to 9300 deg(2) of the celestial sphere in 12 optical bands using a dedicated 0.8mrobotic telescope, the T80-South, at the Cerro Tololo Inter-american Observatory, Chile. The telescope is equipped with a 9.2k x 9.2k e2v detector with 10 mu m pixels, resulting in a field of view of 2 deg(2) with a plate scale of 0.55 arcsec pixel-1. The survey consists of four main subfields, which include two non-contiguous fields at high Galactic latitudes (vertical bar b vertical bar > 30 degrees, 8000 deg(2)) and two areas of the Galactic Disc and Bulge (for an additional 1300 deg(2)). S-PLUS uses the Javalambre 12-band magnitude system, which includes the 5 ugriz broad-band filters and 7 narrow-band filters centred on prominent stellar spectral features: the Balmer jump/[OII], Ca H + K, Hd, G band, Mg b triplet, H alpha, and the Ca triplet. S-PLUS delivers accurate photometric redshifts (dz /(1 + z) = 0.02 or better) for galaxies with r < 19.7 AB mag and z < 0.4, thus producing a 3D map of the local Universe over a volume of more than 1 (Gpc/h)(3). The final S-PLUS catalogue will also enable the study of star formation and stellar populations in and around the Milky Way and nearby galaxies, as well as searches for quasars, variable sources, and low-metallicity stars. In this paper we introduce the main characteristics of the survey, illustrated with science verification data highlighting the unique capabilities of S-PLUS. We also present the first public data release of similar to 336 deg(2) of the Stripe 82 area, in 12 bands, to a limiting magnitude of r = 21, available at datalab.noao.edu/splus.© 2019 The Author(s).Published by Oxford University Press on behalf of the Royal Astronomical SocietyThe S-PLUS project, including the T80S robotic telescope and the S-PLUS scientific survey, was founded as a partnership between the Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), the Observatorio Nacional (ON), the Federal University of Sergipe (UFS), and the Federal University of Santa Catarina (UFSC), with important financial and practical contributions from other collaborating institutes in Brazil, Chile (Universidad de La Serena), and Spain (Centro de Estudios de Fisica del Cosmos de Aragon, CEFCA). The members of the collaboration are grateful for the support received from the Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq; grants 312333/2014-5, 306968/2014-2, 142436/2014-3, 459553/2014-3, 400738/2014-7, 302037/2015-2, 312307/2015-2, 300336/2016-0, 304184/2016-0, 304971/2016-2, 401669/2016-5, 308968/2016-6, 309456/2016-9, 421687/2016-9, 150237/2017-0, 311331/2017-3, 304819/2017-4, and 200289/2017-9), FAPESP (grants 2009/54202-8, 2011/51680-6, 2014/07684-5, 2014/11806-9, 2014/13723-3, 2014/18632-6, 2016/17119-9, 2016/12331-0, 2016/21532-9, 2016/21664-2, 2016/23567-4, 2017/01461-2, 2017/23766-0, 2018/02444-7, and 2018/21661-9), the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES; grants 88881.030413/2013-01 and 88881.156185/2017-01), the Fundacao de Amparo a Pesquisa do Estado do Rio de Janeiro (FAPERJ; grants 202.876/2015, 202.835/2016, and 203.186/2016), the Financiadora de Estudos e Projetos (FINEP; grants 1217/13-01.13.0279.00 and 0859/10-01.10.0663.00), the Direccion de Investigacion y Desarrollo de la Universidad de La Serena (DIDULS/ULS; projects PR16143 and PTE16146 and the Programa de Investigadores Asociados), and the Direccion de Postgrado y Postitulo. TCB, VMP, and DDW acknowledge the support from the Physics Frontier Center for the Evolution of the Elements (JINA-CEE) through the US National Science Foundation (grant PHY 14-30152). JLNC is grateful for financial support received from the Southern Office of Aerospace Research and development (SOARD; grants FA9550-15-1-0167 and FA9550-18-1-0018) of the Air Force Office of the Scientific Research International Office of the United States (AFOSR/IO). YJT and RAD acknowledge support from the Spanish National Research Council (CSIC) I-COOP + 2016 program (grant COOPB20263), and the Spanish Ministry of Economy, Industry, and Competitiveness (MINECO; grants AYA2013-48623-C2-1-P and AYA2016-81065-C2-1-P). RAOM acknowledges support from the Direccion General de Asuntos del Personal Academico of the Universidad Nacional Autonoma de Mexico (DGAPA-UNAM) through a post-doctoral fellowship from the Programa de Becas Posdoctorales en la UNAM. This work has made use of data from the Sloan Digital Sky Survey. Funding for the SDSS and SDSS-II has been provided by the Alfred P. Sloan Foundation, the Participating Institutions, the National Science Foundation, the U.S. Department of Enenergy, the National Aeronautics and Space Administration, the Japanese Monbukagakusho, the Max Planck Society, and the Higher Education Funding Council for England. The SDSS Web Site is http://www.sdss.org/.The SDSS is managed by the Astrophysical Research Consortium for the Participating Institutions. The Participating Institutions are the American Museum of Natural History, Astrophysical Institute Potsdam, University of Basel, University of Cambridge, Case Western Reserve University, University of Chicago, Drexel University, Fermilab, the Institute for Advanced Study, the Japan Participation Group, Johns Hopkins University, the Joint Institute for Nuclear Astrophysics, the Kavli Institute for Particle Astrophysics and Cosmology, the Korean Scientist Group, the Chinese Academy of Sciences (LAMOST), Los Alamos National Laboratory, the Max-Planck-Institute for Astronomy (MPIA), the Max-Planck-Institute for Astrophysics (MPA), the New Mexico State University, Ohio State University, University of Pittsburgh, University of Portsmouth, Princeton University, the United States Naval Observatory, and the University of Washington. This publication makes use of data products from the Widefield Infrared Survey Explorer, which is a joint project of the University of California, Los Angeles, and the Jet Propulsion Laboratory/California Institute of Technology, funded by the National Aeronautics and Space Administration. We are grateful for the contributions of CTIO staff in helping in the construction, commissioning, and maintenance of the telescope and camera and we are particularly thankful to the CTIO director, Steve Heathcote, for his support at every phase, without which this project would not have been completed. We thank Cesar Iniguez for making the 2D measurements of the filter transmissions at CEFCA. We warmly thank David Cristobal-Hornillos and his group for helping us to install and run the reduction package JYPE version 0.9.9 in the S-PLUS computer system in Chile. We warmly thank Mariano Moles, Javier Cenarro, Tamara Civera, Sergio Chueca, Javier Hernandez Fuertes, Antonio Marin Franch, Jesus Varella, and Hector Vazquez Ramio -the success of the S-PLUS project relies on the dedication of these and other CEFCA staff members in building OAJ and running J-PLUS and J-PAS. We deeply thank Rene Laporte and INPE, as well as Keith Taylor, for their contributions to the T80S camera

Make EU trade with Brazil sustainable

Brazil, home to one of the planet's last great forests, is currently in trade negotiations with its second largest trading partner, the European Union (EU). We urge the EU to seize this critical opportunity to ensure that Brazil protects human rights and the environment