18 research outputs found

    Interstage Assessment of Remnant Liver Function in ALPPS Using Hepatobiliary Scintigraphy: Prediction of Posthepatectomy Liver Failure and Introduction of the HIBA Index

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    Objective: The aim of this study was to evaluate interstage liver function in associating liver partition and portal vein occlusion for staged hepatectomy (ALPPS) using hepatobiliary scintigraphy (HBS) and whether this may help to predict posthepatectomy liver failure (PHLF). Background: ALPPS remains controversial given the high rate of liver-related mortality after stage 2. HBS combined with single photon emission computed tomography (SPECT) accurately estimates future liver remnant function and may be useful to predict PHLF. Methods: Between 2011 and 2016, 20 of 39 patients (51.3%) underwent SPECT-HBS before ALPPS stage 2 for primary (n = 3) or secondary liver tumors (n = 17) at the Hospital Italiano de Buenos Aires (HIBA). PHLF was defined by the International Study Group of Liver Surgery criteria, 50-50 criteria, or peak bilirubin >7mg/dL. Grade A PHLF was excluded, as it requires no change in clinical management. Receiver-operating characteristic curves were used to determine cutoff for HBS parameters. Results: Interstagely, 3 HBS parameters differed significantly between patients with (n = 4) and without PHLF (n = 16) after stage 2. Among these, the HIBA-index best predicted PHLF, with a cutoff value of 15%. The risk of PHLF in patients with cutoff <15% was 80%, whereas no patient with cutoff ≥15% developed PHLF. Conclusions: Interstage HBS could help to predict clinically significant PHLF after ALPPS stage 2. An HIBA-index cutoff of 15% seemed to give the best diagnostic performance. Although further studies are needed to confirm our findings, the routine application of this noninvasive low-cost examination could facilitate decision-making in institutions performing ALPPS

    Um modelo markoviano-bayesiano de inteligência artificial para avaliação dinâmica do aprendizado: aplicação à logística

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    Tese (doutorado) - Universidade Federal de Santa Catarina, Centro Tecnológico. Programa de Pós-graduação em Engenharia de ProduçãoA tese apresenta o desenvolvimento de um Sistema de Ensino Inteligente (SEI) via Internet, especialmente estruturado para monitorar (mensurar) o desempenho do aluno no tempo e, simular o estilo de avaliação do professor responsável pelo conteúdo, para atender estas finalidades o sistema é alimentado por instruções (definições) do professor a respeito dos conteúdos (informações) a serem inseridos e apresentados. O modelo utilizado pelo sistema usa em conjunto redes probabilísticas (cadeia de Markov e rede de Bayes), apresentando uma estrutura independente do domínio (conteúdo a ser apresentado). A cadeia de Markov armazena o conhecimento do desempenho passado, mesmo que recente (do aluno), podendo pela sua forma acumulativa do conhecimento estimar a previsão futura de desempenho, enquanto a rede de Bayes, de posse de uma evidência (desempenho do aluno) coletada no presente, pode reavaliar evidências passadas ou até inferir possíveis desempenhos, em tarefas, que por ventura possam não ser acessadas o

    Identification of topographic features influencing aerosol observations at high altitude stations

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    High altitude stations are often emphasized as free tropospheric measuring sites but they remain influenced by atmospheric boundary layer (ABL) air masses due to convective transport processes. The local and meso-scale topographical features around the station are involved in the convective boundary layer development and in the formation of thermally induced winds leading to ABL air lifting. The station altitude alone is not a sufficient parameter to characterize the ABL influence. In this study, a topography analysis is performed allowing calculation of a newly defined index called ABL-TopoIndex. The ABL-TopoIndex is constructed in order to correlate with the ABL influence at the high altitude stations and long-term aerosol time series are used to assess its validity. Topography data from the global digital elevation model GTopo30 were used to calculate five parameters for 43 high and 3 middle altitude stations situated on five continents. The geometric mean of these five parameters determines a topography based index called ABL-TopoIndex, which can be used to rank the high altitude stations as a function of the ABL influence. To construct the ABL-TopoIndex, we rely on the criteria that the ABL influence will be low if the station is one of the highest points in the mountainous massif, if there is a large altitude difference between the station and the valleys or high plains, if the slopes around the station are steep, and finally if the inverse drainage basin potentially reflecting the source area for thermally lifted pollutants to reach the site is small. All stations on volcanic islands exhibit a low ABL-TopoIndex, whereas stations in the Himalayas and the Tibetan Plateau have high ABL-TopoIndex values. Spearman's rank correlation between aerosol optical properties and number concentration from 28 stations and the ABL-TopoIndex, the altitude and the latitude are used to validate this topographical approach. Statistically significant (SS) correlations are found between the 5th and 50th percentiles of all aerosol parameters and the ABL-TopoIndex, whereas no SS correlation is found with the station altitude. The diurnal cycles of aerosol parameters seem to be best explained by the station latitude although a SS correlation is found between the amplitude of the diurnal cycles of the absorption coefficient and the ABL-TopoIndex. © 2018 Author(s).The authors gratefully acknowledge the following persons and organizations. – Wolfgang Schwanghart, the programmer of the TopoToolBox for putting his codes as a freeware and for all the kind and always rapid support he offers. – CHC: the Chacaltaya consortium and Laboratory for Atmospheric Physics at UMSA for taking care of the station and collecting the data. Swedish participation was supported by the Swedish Foundation for International Cooperation in Research and Higher Education (STINT) and the Swedish research council FORMAS. – CMN: the European Commission funded ACTRIS, ACTRIS2 EU project and NEXTDATA National project funded by MIUR. – IZO: Global Atmospheric Watch program funded by AEMET and by the project AEROATLAN (CGL2015-66299-P), funded by the Ministry of Economy and Competitiveness of Spain and the European Regional Development Fund (ERDF). – JFJ: International Foundation High Altitude Research Stations Jungfraujoch and Gornergrat (HFSJG) and the Federal Office of Meteorology and Climatology, MeteoSwiss, within the Swiss program of the Global Atmosphere Watch (GAW) of the World Meteorological Organization, funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement no. 654109 (ACTRIS2), and the Swiss State Secretariat for Education, Research and Innovation (SERI) under contract no. 15.0159-1. The opinions expressed and arguments employed herein do not necessarily reflect the official views of the Swiss Government. – LLN: the Taiwan Environmental Protection Administration. – MSA and MSY: MINECO (Spanish Ministry of Economy and Competitiveness), the MAGRAMA (Spanish Ministry of Agriculture, Food and Environment), the Generalitat de Catalunya (AGAUR 2014 SGR33 and the DGQA) and FEDER funds under the PRISMA project (CGL2012-39623-C02/00). This work has received funding from the European Union’s Horizon 2020 research and innovation programme under grant agreement No 654109. Marco Pandolfi is funded by a Ramón y Cajal Fellowship (RYC-2013-14036) awarded by the Spanish Ministry of Economy and Competitiveness.Peer reviewe

    Factores asociados a placa blanda en pacientes con score de calcio igual a cero

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    Background: The coronary artery calcium score is used for risk stratification in asymptomatic patients. Although coronary arterydisease can occur in the absence of coronary artery calcifications, no conditions associated with the presence of soft non-calcifiedplaques have been described in this scenario, beyond the presence of symptoms.Objectives: The aim of this study was to determine the associations between non-calcified plaques and independent variables inpatients with coronary artery calcium score of zero.Methods: Consecutive patients with coronary artery score of zero Agatston units who also underwent computed tomography coronaryangiography were included in the study. Univariate logistic regression analysis was used to find associations. (15) Sensitivity,specificity, positive predictive value (PPV), negative predictive value (NPV), positive likelihood ratio (LH+) and negative likelihoodratio (LH-) were calculated.Results: Among a total of 93 patients, 10% (n = 9) presented non-calcified plaque. A positive exercise stress test was associated withplaques of any degree of severity (OR 6.5; 95% CI, 1.3-33, p = 0.02). This association persisted for non-severe plaques when the positiveexercise stress test was combined with a negative myocardial perfusion SPECT or stress echocardiography for ischemia (OR,12.4; 95% CI 1.5-101, p = 0.02). Sensitivity and specificity of ST-segment depression for non-calcified plaque of any degree of severitywas 44.4% and 86%, respectively, with NPV of 94%, PPV of 25%, LR+ of 3.11 and LR– of 0.65.Conclusions: ST-segment depression could be associated with non-calcified plaques in patients without coronary artery calcifications,even with normal exercise stress myocardial perfusion or wall motion (non-obstructive disease).Introducción: El score de calcio (SC) es una prueba utilizada en la estratificación de riesgo de pacientes asintomáticos. Aunque la enfermedad coronaria puede ocurrir en ausencia de calcificaciones, no se han descripto  afecciones asociadas a la presencia de placa blanda (PB) en este contexto, más allá de la presencia de  síntomas. Objetivos: determinar predictores clínicos de PB y su eventual precisión diagnóstica en pacientes con un SC de cero. Materiales y métodos: Se incluyeron pacientes consecutivos con un SC de 0 Unidades Agatston que se hubieran realizado además una angiotomografía coronaria. Se determinaron predictores a partir de tres modelos de análisis multivariado. Se calculó la sensibilidad, especificidad, VPN, VPP, + LR y - LR. Resultados: Se incluyeron 93 pacientes. El 10% (n = 9) presentaron PB. La ergometría  positiva fue predictor independiente de placas de cualquier severidad (OR 6.5; IC del 95%: 1.3-33, p = 0.02). El poder predictivo persistió para placas no severas cuando se combinó la ergometría con  perfusión miocárdica SPECT o ecocardiograma estrés negativos para isquemia (OR 12.4 IC 95% 1.5 - 101, p = 0.02). La sensibilidad y la especificidad del infradesnivel del ST para placa blanda de cualquier grado de severidad fue 44.4% y 86%, respectivamente. El VPN fue del 94% y el VPP del 25%, + LR fue de 3.11 y -LR fue de 0.65.  Conclusiones: El infradesnivel del ST podría ser predictor de PB en pacientes sin calcificaciones coronarias,  incluso en contexto de  perfusión miocárdica o ecocardiograma estrés normales (enfermedad no obstructiva)

    Rescue of Advanced Pompe Disease in Mice with Hepatic Expression of Secretable Acid α-Glucosidase.

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    Pompe disease is a neuromuscular disorder caused by disease-associated variants in the gene encoding for the lysosomal enzyme acid α-glucosidase (GAA), which converts lysosomal glycogen to glucose. We previously reported full rescue of Pompe disease in symptomatic 4-month-old Gaa knockout (Gaa-/-) mice by adeno-associated virus (AAV) vector-mediated liver gene transfer of an engineered secretable form of GAA (secGAA). Here, we showed that hepatic expression of secGAA rescues the phenotype of 4-month-old Gaa-/- mice at vector doses at which the native form of GAA has little to no therapeutic effect. Based on these results, we then treated severely affected 9-month-old Gaa-/- mice with an AAV vector expressing secGAA and followed the animals for 9 months thereafter. AAV-treated Gaa-/- mice showed complete reversal of the Pompe phenotype, with rescue of glycogen accumulation in most tissues, including the central nervous system, and normalization of muscle strength. Transcriptomic profiling of skeletal muscle showed rescue of most altered pathways, including those involved in mitochondrial defects, a finding supported by structural and biochemical analyses, which also showed restoration of lysosomal function. Together, these results provide insight into the reversibility of advanced Pompe disease in the Gaa-/- mouse model via liver gene transfer of secGAA.This work was supported by Genethon, the French Muscular Dystro-phy Association (AFM), and Spark Therapeutics. It was also sup-ported by the European Union’s Research and Innovation Programunder grant agreement number 667751 (to F.M.), the EuropeanResearch Council Consolidator Grant under grant agreement number617432 (to F.M.), and Marie Skłodowska-Curie Actions-IndividualFellowship (MSCA-IF) grant agreement number 797144 (to U.C.)S

    Long-term trends of black carbon and particle number concentration in the lower free troposphere in Central Europe

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    Background: The implementation of emission mitigation policies in Europe over the last two decades has generally improved the air quality, which resulted in lower aerosol particle mass, particle number, and black carbon mass concentration. However, little is known whether the decreasing particle concentrations at a lower-altitude level can be observed in the free troposphere (FT), an important layer of the atmosphere, where aerosol particles have a longer lifetime and may affect climate dynamics. In this study, we used data from two high-Alpine observatories, Zugspitze-Schneefernerhaus (ZSF) and Jungfraujoch (JFJ), to assess the long-term trends on size-resolved particle number concentrations (PNCs) and equivalent black carbon (eBC) mass concentration separated for undisturbed lower FT conditions and under the influence of air from the planetary boundary layer (PBL) from 2009 to 2018. Results: The FT and PBL-influenced conditions were segregated for both sites. We found that the FT conditions in cold months were more prevalent than in warm months, while the measured aerosol parameters showed different seasonal patterns for the FT and PBL-influenced conditions. The pollutants in the PBL-influenced condition have a higher chance to be transported to high-altitudes due to the mountainous topography, leading to a higher concentration and more distinct seasonal variation, and vice versa. The long-term trends of the measured aerosol parameters were evaluated and the decreased aerosol concentrations were observed for both FT and PBL-influenced conditions. The observed decreasing trends in eBC concentration in the PBL-influenced condition are well consistent with the reported trends in total BC emission in Germany and Switzerland. The decreased concentrations in the FT condition suggest that the background aerosol concentration in the lower FT over Central Europe has correspondingly decreased. The change of back trajectories in the FT condition at ZSF and JFJ was further evaluated to investigate the other possible drivers for the decreasing trends. Conclusions: The background aerosol concentration in the lower FT over Central Europe has significantly decreased during 2009–2018. The implementation of emission mitigation policies is the most decisive factor and the decrease of the regional airmass occurrence over Central Europe also has contributed to the decreasing trends. © 2021, The Author(s)

    Gene therapy with secreted acid alpha-glucosidase rescues Pompe disease in a novel mouse model with early-onset spinal cord and respiratory defects.

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    Pompe disease (PD) is a neuromuscular disorder caused by deficiency of acidalpha-glucosidase (GAA), leading to motor and respiratory dysfunctions. Available Gaa knock-out (KO) mouse models do not accurately mimic PD, particularly its highly impaired respiratory phenotype. Here we developed a new mouse model of PD crossing Gaa KOB6;129 with DBA2/J mice. We subsequently treated Gaa KODBA2/J mice with adeno-associated virus (AAV) vectors expressing a secretable form of GAA (secGAA). Male Gaa KODBA2/J mice present most of the key features of the human disease, including early lethality, severe respiratory impairment, cardiac hypertrophy and muscle weakness. Transcriptome analyses of Gaa KODBA2/J, compared to the parental Gaa KOB6;129 mice, revealed a profoundly impaired gene signature in the spinal cord and a similarly deregulated gene expression in skeletal muscle. Muscle and spinal cord transcriptome changes, biochemical defects, respiratory and muscle function in the Gaa KODBA2/J model were significantly improved upon gene therapy with AAV vectors expressing secGAA. These data show that the genetic background impacts on the severity of respiratory function and neuroglial spinal cord defects in the Gaa KO mouse model of PD. Our findings have implications for PD prognosis and treatment, show novel molecular pathophysiology mechanisms of the disease and provide a unique model to study PD respiratory defects, which majorly affect patients. This work was supported by Genethon, the French Muscular Dystrophy Association (AFM), the European Commission (grant nos. 667751, 617432, and 797144), and Spark Therapeutics.This work was supported by Genethon and the French Muscular Dystrophy Association (AFM, to F.M.). It was also supported by the European Union’s research and innovation program under grant agreement no. 667751 (to F.M.), the European Research Council Consolidator Grant under grant agreement no. 617432 (to F.M.), Marie Skodowska-Curie Actions Individual Fellowship (MSCA-IF) grant agreement no. 797144 (to U.C.), and by Spark Therapeutics under a sponsored research agreement.S

    Characterization and intercomparison of aerosol absorption photometers: Result of two intercomparison workshops

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    Absorption photometers for real time application have been available since the 1980s, but the use of filter-based instruments to derive information on aerosol properties (absorption coefficient and black carbon, BC) is still a matter of debate. Several workshops have been conducted to investigate the performance of individual instruments over the intervening years. Two workshops with large sets of aerosol absorption photometers were conducted in 2005 and 2007. The data from these instruments were corrected using existing methods before further analysis. The inter-comparison shows a large variation between the responses to absorbing aerosol particles for different types of instruments. The unit to unit variability between instruments can be up to 30% for Particle Soot Absorption Photometers (PSAPs) and Aethalometers. Multi Angle Absorption Photometers (MAAPs) showed a variability of less than 5%. Reasons for the high variability were identified to be variations in sample flow and spot size. It was observed that different flow rates influence system performance with respect to response to absorption and instrumental noise. Measurements with non absorbing particles showed that the current corrections of a cross sensitivity to particle scattering are not sufficient. Remaining cross sensitivities were found to be a function of the total particle load on the filter. The large variation between the response to absorbing aerosol particles for different types of instruments indicates that current correction functions for absorption photometers are not adequate. © Author(s) 2011

    Is exposure to pollen a risk factor for moderate and severe asthma exacerbations?

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    Background Limited number of studies have focused on the impact of pollen exposure on asthma. As a part of the EAACI Guidelines on Environment Science, this first systematic review on the relationship of pollen exposure to asthma exacerbations aimed to bridge this knowledge gap in view of implementing recommendations of prevention. Methods We searched electronic iPubMed, Embase, and Web of Science databases using a set of MeSH terms and related synonyms and identified 73 eligible studies that were included for systemic review. When possible, meta-analyses were conducted. Results Overall meta-analysis suggests that outdoor pollen exposure may have an effect on asthma exacerbation but caution is needed due to the low number of studies and their heterogeneity. The strongest associations were found between asthma attacks, asthma-related ED admissions or hospitalizations and an increase of grass pollen concentration in the previous 2 days overall in children aged less than 18 years of age. Tree pollen may increase asthma-related ED visits or admissions lagged up to 7 days overall in individuals younger than 18 years. Rare data show that among subjects under 18 years of age an exposure to grass pollen lagged up to 3 days may lower lung function. Conclusions Further research considering effect modifiers of pollen sensitization, hay fever, asthma, air pollution, green spaces and pre-existing medications is urgently warranted to better evaluate the impacts of pollen on asthma exacerbation. Preventive measures in relation to pollen exposure should be integrated in asthma control as pollen increase continues due to climate change
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