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- Manzano-Nunez, Ramiro, et al.
(författare)
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Outcomes and management approaches of resuscitative endovascular balloon occlusion of the aorta based on the income of countries
- 2020
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Ingår i: World Journal of Emergency Surgery. - : Springer Science and Business Media LLC. - 1749-7922. ; 15:57
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Tidskriftsartikel (refereegranskat)abstract
- © 2020 The Author(s). Background: Resuscitative endovascular balloon occlusion of the aorta (REBOA) could provide a survival benefit to severely injured patients as it may improve their initial ability to survive the hemorrhagic shock. Although the evidence supporting the use of REBOA is not conclusive, its use has expanded worldwide. We aim to compare the management approaches and clinical outcomes of trauma patients treated with REBOA according to the countries' income based on the World Bank Country and Lending Groups. Methods: We used data from the AORTA (USA) and the ABOTrauma (multinational) registries. Patients were stratified into two groups: (1) high-income countries (HICs) and (2) low-to-middle income countries (LMICs). Propensity score matching extracted 1:1 matched pairs of subjects who were from an LMIC or a HIC based on age, gender, the presence of pupillary response on admission, impeding hypotension (SBP ≤ 80), trauma mechanism, ISS, the necessity of CPR on arrival, the location of REBOA insertion (emergency room or operating room) and the amount of PRBCs transfused in the first 24 h. Logistic regression (LR) was used to examine the association of LMICs and mortality. Results: A total of 817 trauma patients from 14 countries were included. Blind percutaneous approach and surgical cutdown were the preferred means of femoral cannulation in HICs and LIMCs, respectively. Patients from LMICs had a significantly higher occurrence of MODS and respiratory failure. LR showed no differences in mortality for LMICs when compared to HICs; neither in the non-matched cohort (OR = 0.63; 95% CI: 0.36-1.09; p = 0.1) nor in the matched cohort (OR = 1.45; 95% CI: 0.63-3,33; p = 0.3). Conclusion: There is considerable variation in the management practices of REBOA and the outcomes associated with this intervention between HICs and LMICs. Although we found significant differences in multiorgan and respiratory failure rates, there were no differences in the risk-adjusted odds of mortality between the groups analyzed. Trauma surgeons practicing REBOA around the world should joint efforts to standardize the practice of this endovascular technology worldwide.
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- Bianchi Piccinini, Giulio, 1982, et al.
(författare)
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How Do Drivers Respond to Silent Automation Failures? Driving Simulator Study and Comparison of Computational Driver Braking Models
- 2020
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Ingår i: Human Factors. - Chalmers University of Technology, Gothenburg, Sweden.; Volvo Group Trucks Technology, Gothenburg, Sweden.; Virginia Tech Transportation Institute, Blacksburg, USA.; University of Leeds, UK.; VTI, Gothenburg, Sweden. : SAGE Publications. - 1547-8181 .- 0018-7208. ; 62:7, s. 1212-1229
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Tidskriftsartikel (refereegranskat)abstract
- Objective: This paper aims to describe and test novel computational driver models, predicting drivers’ brake reaction times (BRTs) to different levels of lead vehicle braking, during driving with cruise control (CC) and during silent failures of adaptive cruise control (ACC). Background: Validated computational models predicting BRTs to silent failures of automation are lacking but are important for assessing the safety benefits of automated driving. Method: Two alternative models of driver response to silent ACC failures are proposed: a looming prediction model, assuming that drivers embody a generative model of ACC, and a lower gain model, assuming that drivers’ arousal decreases due to monitoring of the automated system. Predictions of BRTs issued by the models were tested using a driving simulator study. Results: The driving simulator study confirmed the predictions of the models: (a) BRTs were significantly shorter with an increase in kinematic criticality, both during driving with CC and during driving with ACC; (b) BRTs were significantly delayed when driving with ACC compared with driving with CC. However, the predicted BRTs were longer than the ones observed, entailing a fitting of the models to the data from the study. Conclusion: Both the looming prediction model and the lower gain model predict well the BRTs for the ACC driving condition. However, the looming prediction model has the advantage of being able to predict average BRTs using the exact same parameters as the model fitted to the CC driving data. Application: Knowledge resulting from this research can be helpful for assessing the safety benefits of automated driving.
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- Sainas, Stefano, et al.
(författare)
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Targeting Acute Myelogenous Leukemia Using Potent Human Dihydroorotate Dehydrogenase Inhibitors Based on the 2-Hydroxypyrazolo[1,5- a]pyridine Scaffold : SAR of the Aryloxyaryl Moiety
- 2022
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Ingår i: Journal of Medicinal Chemistry. - : American Chemical Society (ACS). - 0022-2623 .- 1520-4804. ; 65:19, s. 12701-12724
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Tidskriftsartikel (refereegranskat)abstract
- In recent years, human dihydroorotate dehydrogenase inhibitors have been associated with acute myelogenous leukemia as well as studied as potent host targeting antivirals. Starting from MEDS433 (IC50 1.2 nM), we kept improving the structure-activity relationship of this class of compounds characterized by 2-hydroxypyrazolo[1,5-a]pyridine scaffold. Using an in silico/crystallography supported design, we identified compound 4 (IC50 7.2 nM), characterized by the presence of a decorated aryloxyaryl moiety that replaced the biphenyl scaffold, with potent inhibition and pro-differentiating abilities on AML THP1 cells (EC50 74 nM), superior to those of brequinar (EC50 249 nM) and boosted when in combination with dipyridamole. Finally, compound 4 has an extremely low cytotoxicity on non-AML cells as well as MEDS433; it has shown a significant antileukemic activity in vivo in a xenograft mouse model of AML.
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