Application of Strategic Planning Process with Fleet Level Analysis Methods

The goal of this work is to quantify and characterize the potential system-wide reduction of fuel consumption and corresponding CO2 emissions, resulting from the introduction of N+2 aircraft technologies and concepts into the fleet. Although NASA goals for this timeframe are referenced against a large twin aisle aircraft we consider their application across all vehicle classes of the commercial aircraft fleet, from regional jets to very large aircraft. In this work the authors describe and discuss the formulation and implementation of the fleet assessment by addressing the main analytical components: forecasting, operations allocation, fleet retirement, fleet replacement, and environmental performance modeling

Predicting morbidity by local similarities in multi-scale patient trajectories

[EN] Patient Trajectories (PTs) are a method of representing the temporal evolution of patients. They can include information from different sources and be used in socio-medical or clinical domains. PTs have generally been used to generate and study the most common trajectories in, for instance, the development of a disease. On the other hand, healthcare predictive models generally rely on static snapshots of patient information. Only a few works about prediction in healthcare have been found that use PTs, and therefore benefit from their temporal dimension. All of them, however, have used PTs created from single-source information. Therefore, the use of longitudinal multi-scale data to build PTs and use them to obtain predictions about health conditions is yet to be explored. Our hypothesis is that local similarities on small chunks of PTs can identify similar patients concerning their future morbidities. The objectives of this work are (1) to develop a methodology to identify local similarities between PTs before the occurrence of morbidities to predict these on new query individuals; and (2) to validate this methodology on risk prediction of cardiovascular diseases (CVD) occurrence in patients with diabetes. We have proposed a novel formal definition of PTs based on sequences of longitudinal multi-scale data. Moreover, a dynamic programming methodology to identify local alignments on PTs for predicting future morbidities is proposed. Both the proposed methodology for PT definition and the alignment algorithm are generic to be applied on any clinical domain. We validated this solution for predicting CVD in patients with diabetes and we achieved a precision of 0.33, a recall of 0.72 and a specificity of 0.38. Therefore, the proposed solution in the diabetes use case can result of utmost utility to secondary screening.This work was supported by the CrowdHealth project (COLLECTIVE WISDOM DRIVING PUBLIC HEALTH POLICIES (727560)) and the MTS4up project (DPI2016-80054-R).Carrasco-Ribelles, LA.; Pardo-Más, JR.; Tortajada, S.; Sáez Silvestre, C.; Valdivieso, B.; Garcia-Gomez, JM. (2021). Predicting morbidity by local similarities in multi-scale patient trajectories. Journal of Biomedical Informatics. 120:1-9. https://doi.org/10.1016/j.jbi.2021.103837S1912

Immunosuppressants alter the immune response associated with Glucantime® treatment for Leishmania infantum infection in a mouse model

Background: Immunosuppression is a major risk factor for the development of visceral leishmaniasis (VL). The number of patients receiving immunosuppressant drugs such as TNF antagonist (anti-TNF) and methotrexate (MTX) is increasing. In these patients, VL is more severe, their response to treatment poorer, and they are at higher risk of relapse, a consequence (largely) of the poor and inappropriate immune response they develop. Objectives: To examine the effect of immunosuppressive treatment on the host immune response and thus gain insight into the reduced efficacy of pentavalent antimonials in these patients. Experiments were performed using BALB/c mice immunosuppressed with anti-TNF or MTX, infected with Leishmania infantum promastigotes, and then treated with Glucantime® at clinical doses. Results: Immunosuppression with both agents impeded parasite elimination from the spleen and bone marrow. Low pro-inflammatory cytokine production by CD4+ and CD8+ T cells was detected, along with an increase in PD-1 and IL-10 expression by B and T cells in the immunosuppressed groups after treatment. Conclusion: The immunosuppressed mice were unable to develop specific cellular immunity to the parasite, perhaps explaining the greater risk of VL relapse seen in pharmacologically immunosuppressed human patients.The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This study was funded by the Instituto de Salud Carlos III through ISCIII-AES projects (PI21CIII/00005 and PI22/00009). JCS was supported by a contract from CIBERINFEC (CB21/13/00018).S

Retrospective analysis of cattle poisoning in Argentina (2000-2013)

A retrospective analysis (2000 to 2013) of cattle poisoning caused by toxic plants and other compounds was carried out in the Pampas region of Argentina by the Animal Health Group of INTA-EEA, Balcarce. During this period, 1263 reports of diseases of different etiologies (infectious, parasitic, toxic, metabolic and miscellaneous) were recorded in cattle, by collecting anamnestic, clinical and pathological information. A toxic etiology was diagnosed in 21.1% of these reports. Iatrogenic poisoning caused by ionophores was the most frequently recorded etiology. Consumption of toxic plants (Wedelia glauca, Solanum glaucophyllum, among others), mycotoxins (Claviceps purpurea, Claviceps paspali, Epichloë coenophiala, among others), and plants producing cyanide and nitrates/nitrites were also commonly diagnosed. The high frequency of toxic episodes and the difficulties in their diagnosis by practitioners in our livestock production systems emphasizes the importance of this report.EEA BalcarceFil: García, Juan Agustín. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Canton, German Jose. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Spath, Ernesto Juan. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Odriozola, Ernesto Raul. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; ArgentinaFil: Garcia, Bernardo L. Actividad Privada; ArgentinaFil: Micheloud, Juan Francisco. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Salta; ArgentinaFil: Campero, Carlos Manuel. Instituto Nacional de Tecnología Agropecuaria (INTA). Estación Experimental Agropecuaria Balcarce; Argentin

Analysis of endothelial-to-haematopoietic transition at the single cell level identifies cell cycle regulation as a driver of differentiation

Funder: INTENS EU fp8 consortiumFunder: ERC advanced grant New-CholAbstract: Background: Haematopoietic stem cells (HSCs) first arise during development in the aorta-gonad-mesonephros (AGM) region of the embryo from a population of haemogenic endothelial cells which undergo endothelial-to-haematopoietic transition (EHT). Despite the progress achieved in recent years, the molecular mechanisms driving EHT are still poorly understood, especially in human where the AGM region is not easily accessible. Results: In this study, we take advantage of a human pluripotent stem cell (hPSC) differentiation system and single-cell transcriptomics to recapitulate EHT in vitro and uncover mechanisms by which the haemogenic endothelium generates early haematopoietic cells. We show that most of the endothelial cells reside in a quiescent state and progress to the haematopoietic fate within a defined time window, within which they need to re-enter into the cell cycle. If cell cycle is blocked, haemogenic endothelial cells lose their EHT potential and adopt a non-haemogenic identity. Furthermore, we demonstrate that CDK4/6 and CDK1 play a key role not only in the transition but also in allowing haematopoietic progenitors to establish their full differentiation potential. Conclusion: We propose a direct link between the molecular machineries that control cell cycle progression and EHT

Coal emissions adverse human health effects associated with ultrafine/nano-particles role and resultant engineering controls

There are multiple elements which enable coal geochemistry: (1) boiler and pollution control system design parameters, (2) temperature of flue gas at collection point, (3) feed coal and also other fuels like petroleum coke, tires and biomass geochemistry and (4) fuel feed particle size distribution homogeneity distribution, maintenance of pulverisers, etc. Even though there is a large number of hazardous element pollutants in the coal-processing industry, investigations on micrometer and nanometer-sized particles including their aqueous colloids formation reactions and their behaviour entering the environment are relatively few in numbers. X-ray diffraction (XRD), High Resolution-Transmission Electron microscopy (HR-TEM)/ (Energy Dispersive Spectroscopy) EDS/ (selected-area diffraction pattern) SAED, Field Emission-Scanning Electron Microscopy (FE-SEM)/EDS and granulometric distribution analysis were used as an integrated characterization techniques tool box to determine both geochemistry and nanomineralogy for coal fly ashes (CFAs) from Brazil´s largest coal power plant. Ultrafine/nano-particles size distribution from coal combustion emissions was estimated during the tests. In addition the iron and silicon content was determined as 54.6% of the total 390 different particles observed by electron bean, results aimed that these two particles represent major minerals in the environment particles normally. These data may help in future investigations to asses human health actions related with nano-particles

Capecitabine and irinotecan with bevacizumab 2-weekly for metastatic colorectal cancer: the phase II AVAXIRI study

Background: The optimal sequence of chemotherapeutic agents is not firmly established for the treatment of metastatic colorectal cancer (mCRC). This phase II multi-centre study investigated the efficacy and tolerability of a standard capecitabine plus irinotecan (XELIRI) regimen with bevacizumab in previously untreated patients with mCRC. Methods: Patients received intravenous irinotecan 175 mg/m2 on day 1 and oral capecitabine 1000 mg/m2 (800 mg/m2 for patients >65 years of age) twice daily on days 2–8, followed by a 1-week rest, and bevacizumab 5 mg/kg as an intravenous infusion on day 1 every 2 weeks. Results: Seventy-seven patients were included in the intention-to-treat and safety populations. Progression-free survival at 9 months was 61%. The overall response and disease control rates were 51% and 84%, respectively. Median progression-free and overall survival times were 11.9 and 24.8 months, respectively. 48 patients (62%) had at least one grade 3/4 adverse event, the most common being asthenia, diarrhoea and neutropenia. Quality of life varied little over the study period with mean visual analogue scale general health scores ranging from 71 to 76 over cycles 1–11. Conclusion: Our study found irinotecan and capecitabine administered fortnightly with bevacizumab in patients with mCRC to be an effective and tolerable regimen. Trial registration: clinicaltrials.gov identifier NCT00875771. Trial registration date: 04/02/2009. Keywords: Irinotecan, Capecitabine, Bevacizumab, Metastatic colorectal cancer, Chemotherap

A Day-4 Lille Model Predicts Response to Corticosteroids and Mortality in Severe Alcoholic Hepatitis

OBJECTIVES: Prednisolone therapy increases the risk of infections in patients with severe alcoholic hepatitis (SAH). We evaluated whether the use of the Lille Model at day 4 (LM4) is useful to predict response to prednisolone compared with the classic day 7 (LM7) in order to limit a futile exposure to corticosteroids. METHODS: We performed a retrospective analysis of a large multinational cohort of patients with SAH with Maddrey's discriminant function (DF) ≥32. Response to corticosteroids was assessed with LM4 and LM7, according to the validated cutoff value (CUV>0.45). Receiver operating characteristics (ROC) curves were constructed to determine the optimal CUV for LM4 and to compare accuracy between LM4, LM7, MELD (Model for End-Stage Liver Disease), and ABIC (age, bilirubin, international normalized ratio, and creatinine). Logistic regression models were constructed to predict 28- and 90-day mortality. Cox regression analysis was performed to assess long-term survival. RESULTS: A total of 163 (62.7%) out of 260 patients received corticosteroids. The median DF for the patients treated with corticosteroids was 64.1 (47.9-81.3). Overall 90-day mortality was 35.9%. The median LM4 and LM7 for the patients who received treatment was 0.39 (0.19-0.83) and 0.36 (0.13-0.77). LM4 was a strong independent predictor of 28-day mortality (OR 25.4, (95% confidence interval (CI) 5.1-126.8), P0.45, 28- and 90-day survival was significantly higher for responders (90% and 76%) than non-responders (66% and 40%), P<0.001. Importantly, the area under the ROC curve for predicting mortality for LM4 was similar than the classic LM7 (0.77 vs. 0.75, respectively: P=0.558). CONCLUSIONS: LM4 is as accurate as LM7 in predicting response to corticosteroids, as well as 28- and 90-day mortality. Assessing the efficacy of prednisolone at an earlier time point can avoid a more prolonged futile use of this therapy

Single-cell RNA-sequencing of differentiating iPS cells reveals dynamic genetic effects on gene expression.

Recent developments in stem cell biology have enabled the study of cell fate decisions in early human development that are impossible to study in vivo. However, understanding how development varies across individuals and, in particular, the influence of common genetic variants during this process has not been characterised. Here, we exploit human iPS cell lines from 125 donors, a pooled experimental design, and single-cell RNA-sequencing to study population variation of endoderm differentiation. We identify molecular markers that are predictive of differentiation efficiency of individual lines, and utilise heterogeneity in the genetic background across individuals to map hundreds of expression quantitative trait loci that influence expression dynamically during differentiation and across cellular contexts