A Computer Application to Predict Adverse Events in the Short-Term Evolution of Patients With Exacerbation of Chronic Obstructive Pulmonary Disease

Background: Chronic obstructive pulmonary disease (COPD) is a common chronic disease. Exacerbations of COPD (eCOPD) contribute to the worsening of the disease and the patient’s evolution. There are some clinical prediction rules that may help to stratify patients with eCOPD by their risk of poor evolution or adverse events. The translation of these clinical prediction rules into computer applications would allow their implementation in clinical practice. Objective: The goal of this study was to create a computer application to predict various outcomes related to adverse events of short-term evolution in eCOPD patients attending an emergency department (ED) based on valid and reliable clinical prediction rules. Methods: A computer application, Prediction of Evolution of patients with eCOPD (PrEveCOPD), was created to predict 2 outcomes related to adverse events: (1) mortality during hospital admission or within a week after an ED visit and (2) admission to an intensive care unit (ICU) or an intermediate respiratory care unit (IRCU) during the eCOPD episode. The algorithms included in the computer tool were based on clinical prediction rules previously developed and validated within the Investigación en Resultados y Servicios de Salud COPD study. The app was developed for Windows and Android systems, using Visual Studio 2008 and Eclipse, respectively. Results: The PrEveCOPD computer application implements the prediction models previously developed and validated for 2 relevant adverse events in the short-term evolution of patients with eCOPD. The application runs under Windows and Android systems and it can be used locally or remotely as a Web application. Full description of the clinical prediction rules as well as the original references is included on the screen. Input of the predictive variables is controlled for out-of-range and missing values. Language can be switched between English and Spanish. The application is available for downloading and installing on a computer, as a mobile app, or to be used remotely via internet. Conclusions: The PrEveCOPD app shows how clinical prediction rules can be summarized into simple and easy to use tools, which allow for the estimation of the risk of short-term mortality and ICU or IRCU admission for patients with eCOPD. The app can be used on any computer device, including mobile phones or tablets, and it can guide the clinicians to a valid stratification of patients attending the ED with eCOPD.Fondo de Investigación Sanitaria (PI 06\1010, PI06\1017, PI06\714, PI06\0326, PI06\0664) Departamento de Salud del Gobierno Vasco (2012111008) Departamento de Educación, Política Lingüística y Cultura del Gobierno Vasco (IT620-13) Ministerio de Economía y Competitividad del Gobierno Español and FEDER (MTM2013-40941-P and MTM2016-74931-P) the Research Committee of the Hospital Galdakao the thematic networks -REDISSEC (Red de Investigación en Servicios de Salud en Enfermedades Crónicas) - of the Instituto de Salud Carlos III

Serratia marcescens Is Able to Survive and Proliferate in Autophagic-Like Vacuoles inside Non-Phagocytic Cells

Serratia marcescens is an opportunistic human pathogen that represents a growing problem for public health, particularly in hospitalized or immunocompromised patients. However, little is known about factors and mechanisms that contribute to S. marcescens pathogenesis within its host. In this work, we explore the invasion process of this opportunistic pathogen to epithelial cells. We demonstrate that once internalized, Serratia is able not only to persist but also to multiply inside a large membrane-bound compartment. This structure displays autophagic-like features, acquiring LC3 and Rab7, markers described to be recruited throughout the progression of antibacterial autophagy. The majority of the autophagic-like vacuoles in which Serratia resides and proliferates are non-acidic and have no degradative properties, indicating that the bacteria are capable to either delay or prevent fusion with lysosomal compartments, altering the expected progression of autophagosome maturation. In addition, our results demonstrate that Serratia triggers a non-canonical autophagic process before internalization. These findings reveal that S. marcescens is able to manipulate the autophagic traffic, generating a suitable niche for survival and proliferation inside the host cell

Integrated flow cytometry and sequencing to reconstruct evolutionary patterns from dysplasia to acute myeloid leukemia

Clonal evolution in acute myeloid leukemia (AML) originates long before diagnosis and is a dynamic process that may affect survival. However, it remains uninvestigated during routine diagnostic workups. We hypothesized that the mutational status of bone marrow dysplastic cells and leukemic blasts, analyzed at the onset of AML using integrated multidimensional flow cytometry (MFC) immunophenotyping and fluorescence-activated cell sorting (FACS) with next-generation sequencing (NGS), could reconstruct leukemogenesis. Dysplastic cells were detected by MFC in 285 of 348 (82%) newly diagnosed patients with AML. Presence of dysplasia according to MFC and World Health Organization criteria had no prognostic value in older adults. NGS of dysplastic cells and blasts isolated at diagnosis identified 3 evolutionary patterns: stable (n = 12 of 21), branching (n = 4 of 21), and clonal evolution (n = 5 of 21). In patients achieving complete response (CR), integrated MFC and FACS with NGS showed persistent measurable residual disease (MRD) in phenotypically normal cell types, as well as the acquisition of genetic traits associated with treatment resistance. Furthermore, whole-exome sequencing of dysplastic and leukemic cells at diagnosis and of MRD uncovered different clonal involvement in dysplastic myelo-erythropoiesis, leukemic transformation, and chemoresistance. Altogether, we showed that it is possible to reconstruct leukemogenesis in ∼80% of patients with newly diagnosed AML, using techniques other than single-cell multiomics.This work was supported by grants from the Área de Oncología del Instituto de Salud Carlos III, Centro de Investigación Biomédica en Red (CIBER-ONC) (CB16/12/00369, CB16/12/00233, CB16/12/00489, and CB16/12/00284), Instituto de Salud Carlos III/Subdirección General de Investigación Sanitaria (FIS numbers PI16/01661, PI16/00517, and PI19/01518), and the Plan de Investigación de la Universidad de Navarra (PIUNA 2014-18). This work was supported internationally by the Cancer Research UK, FCAECC, and AIRC under the Accelerator Award Program (EDITOR)

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

Anisotropy and chemical composition of ultra-high energy cosmic rays using arrival directions measured by the Pierre Auger Observatory

The Pierre Auger Collaboration has reported evidence for anisotropy in the distribution of arrival directions of the cosmic rays with energies $E>E_{th}=5.5\times 10^{19}$ eV. These show a correlation with the distribution of nearby extragalactic objects, including an apparent excess around the direction of Centaurus A. If the particles responsible for these excesses at $E>E_{th}$ are heavy nuclei with charge $Z$, the proton component of the sources should lead to excesses in the same regions at energies $E/Z$. We here report the lack of anisotropies in these directions at energies above $E_{th}/Z$ (for illustrative values of $Z=6,\ 13,\ 26$). If the anisotropies above $E_{th}$ are due to nuclei with charge $Z$, and under reasonable assumptions about the acceleration process, these observations imply stringent constraints on the allowed proton fraction at the lower energies

Advanced functionality for radio analysis in the Offline software framework of the Pierre Auger Observatory

The advent of the Auger Engineering Radio Array (AERA) necessitates the development of a powerful framework for the analysis of radio measurements of cosmic ray air showers. As AERA performs "radio-hybrid" measurements of air shower radio emission in coincidence with the surface particle detectors and fluorescence telescopes of the Pierre Auger Observatory, the radio analysis functionality had to be incorporated in the existing hybrid analysis solutions for fluoresence and surface detector data. This goal has been achieved in a natural way by extending the existing Auger Offline software framework with radio functionality. In this article, we lay out the design, highlights and features of the radio extension implemented in the Auger Offline framework. Its functionality has achieved a high degree of sophistication and offers advanced features such as vectorial reconstruction of the electric field, advanced signal processing algorithms, a transparent and efficient handling of FFTs, a very detailed simulation of detector effects, and the read-in of multiple data formats including data from various radio simulation codes. The source code of this radio functionality can be made available to interested parties on request.Comment: accepted for publication in NIM A, 13 pages, minor corrections to author list and references in v

Search for First Harmonic Modulation in the Right Ascension Distribution of Cosmic Rays Detected at the Pierre Auger Observatory

We present the results of searches for dipolar-type anisotropies in different energy ranges above $2.5\times 10^{17}$ eV with the surface detector array of the Pierre Auger Observatory, reporting on both the phase and the amplitude measurements of the first harmonic modulation in the right-ascension distribution. Upper limits on the amplitudes are obtained, which provide the most stringent bounds at present, being below 2% at 99% $C.L.$ for EeV energies. We also compare our results to those of previous experiments as well as with some theoretical expectations.Comment: 28 pages, 11 figure

Pantropical modelling of canopy functional traits using Sentinel-2 remote sensing data

Tropical forest ecosystems are undergoing rapid transformation as a result of changing environmental conditions and direct human impacts. However, we cannot adequately understand, monitor or simulate tropical ecosystem responses to environmental changes without capturing the high diversity of plant functional characteristics in the species-rich tropics. Failure to do so can oversimplify our understanding of ecosystems responses to environmental disturbances. Innovative methods and data products are needed to track changes in functional trait composition in tropical forest ecosystems through time and space. This study aimed to track key functional traits by coupling Sentinel-2 derived variables with a unique data set of precisely located in-situ measurements of canopy functional traits collected from 2434 individual trees across the tropics using a standardised methodology. The functional traits and vegetation censuses were collected from 47 field plots in the countries of Australia, Brazil, Peru, Gabon, Ghana, and Malaysia, which span the four tropical continents. The spatial positions of individual trees above 10 cm diameter at breast height (DBH) were mapped and their canopy size and shape recorded. Using geo-located tree canopy size and shape data, community-level trait values were estimated at the same spatial resolution as Sentinel-2 imagery (i.e. 10 m pixels). We then used the Geographic Random Forest (GRF) to model and predict functional traits across our plots. We demonstrate that key plant functional traits can be accurately predicted across the tropicsusing the high spatial and spectral resolution of Sentinel-2 imagery in conjunction with climatic and soil information. Image textural parameters were found to be key components of remote sensing information for predicting functional traits across tropical forests and woody savannas. Leaf thickness (R2 = 0.52) obtained the highest prediction accuracy among the morphological and structural traits and leaf carbon content (R2 = 0.70) and maximum rates of photosynthesis (R2 = 0.67) obtained the highest prediction accuracy for leaf chemistry and photosynthesis related traits, respectively. Overall, the highest prediction accuracy was obtained for leaf chemistry and photosynthetic traits in comparison to morphological and structural traits. Our approach offers new opportunities for mapping, monitoring and understanding biodiversity and ecosystem change in the most species-rich ecosystems on Earth

Analysis of conservation priorities of Iberoamerican cattle based on autosomal microsatellite markers

Articles in International JournalsBackground: Determining the value of livestock breeds is essential to define conservation priorities, manage genetic diversity and allocate funds. Within- and between-breed genetic diversity need to be assessed to preserve the highest intra-specific variability. Information on genetic diversity and risk status is still lacking for many Creole cattle breeds from the Americas, despite their distinct evolutionary trajectories and adaptation to extreme environmental conditions. Methods: A comprehensive genetic analysis of 67 Iberoamerican cattle breeds was carried out with 19 FAOrecommended microsatellites to assess conservation priorities. Contributions to global diversity were investigated using alternative methods, with different weights given to the within- and between-breed components of genetic diversity. Information on Iberoamerican plus 15 worldwide cattle breeds was used to investigate the contribution of geographical breed groups to global genetic diversity. Results: Overall, Creole cattle breeds showed a high level of genetic diversity with the highest level found in breeds admixed with zebu cattle, which were clearly differentiated from all other breeds. Within-breed kinships revealed seven highly inbred Creole breeds for which measures are needed to avoid further genetic erosion. However, if contribution to heterozygosity was the only criterion considered, some of these breeds had the lowest priority for conservation decisions. The Weitzman approach prioritized highly differentiated breeds, such as Guabalá, Romosinuano, Cr. Patagonico, Siboney and Caracú, while kinship-based methods prioritized mainly zebu-related breeds. With the combined approaches, breed ranking depended on the weights given to the within- and between-breed components of diversity. Overall, the Creole groups of breeds were generally assigned a higher priority for conservation than the European groups of breeds. Conclusions: Conservation priorities differed significantly according to the weight given to within- and betweenbreed genetic diversity. Thus, when establishing conservation programs, it is necessary to also take into account other features. Creole cattle and local isolated breeds retain a high level of genetic diversity. The development of sustainable breeding and crossbreeding programs for Creole breeds, and the added value resulting from their products should be taken into consideration to ensure their long-term survival