Conditioned increase of locomotor activity induced by haloperidol

Dopamine antagonist drugs have profound effects on locomotor activity. In particular, the administration of the D2 antagonist haloperidol produces a state that is similar to catalepsy. In order to confirm whether the modulation of the dopaminergic activity produced by haloperidol was repeatedly paired with the presence of distinctive contextual cues that served as a Conditioned Stimulus. Paradoxically, the results revealed a dose-dependent increase n locomotor activity following conditioning with dopamine antagonist (Experiments 1) that was susceptible of extinction when the conditioned stimulus was presented repeatedly by itself after conditioning (Experiment 2). These data are interpreted from an associative perspective, considering them as a result of a classical conditioning process.Ministerio de Economía, Industria y Competitividad PSI2015-64 965-

Bearing signal separation enhancement with application to helicopter transmission system

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Bearing vibration signal separation is essential for fault detection of gearboxes, especially where the vibration is nonstationary, susceptible to background noise, and subjected to an arduous transmission path from the source to the receiver. This paper presents a methodology for improving fault detection via a series of vibration signal processing techniques, including signal separation, synchronous averaging (SA), spectral kurtosis (SK), and envelope analysis. These techniques have been tested on experimentally obtained vibration data acquired from the transmission system of a CS-29 Category A helicopter gearbox operating under different bearing damage conditions. Results showed successful enhancement of bearing fault detection on the second planetary stage of the gearbo

Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying

The main aim of this work was to evaluate the effect of high-intensity ultrasound (US) on the drying kinetics of orange peel as well as its influence on the microstructural changes induced during drying. Convective drying kinetics of orange peel slabs were carried out at a relative humidity of 26.5±0.9%, 40 °C and 1 m/s with (AIR+US) and without (AIR) ultrasound application. In order to identify the US effect on water transport, drying kinetics were analyzed by taking the diffusion theory into account. Fresh, AIR and AIR+US dried samples were analyzed using Cryo-Scanning Electron Microscopy. Results showed that the drying kinetics of orange peel were significantly improved by US application, which involved a significant (p<0.05) improvement of mass transfer coefficient and effective moisture diffusivity. The effects on mass transfer properties were confirmed with microstructural observations. In the cuticle surface of flavedo, the pores were obstructed by the spread of the waxy components, this fact evidencing US effects on the air solid interfaces. Furthermore, the cells of the albedo were disrupted by US, as it created large intercellular air spaces facilitating water transfer through the tissue.The authors would like to acknowledge the financial support of MICINN and CEE (European Regional Development Fund) from projects Ref. DPI2009-14549-C04-04, PSE-060000-2009-003, and FP6-2004-FOOD-23140 HIGHQ RTE.García Pérez, JV.; Ortuño Cases, C.; Puig Gómez, CA.; Cárcel Carrión, JA.; Pérez Munuera, IM. (2012). Enhancement of Water Transport and Microstructural Changes Induced by High-Intesity Ultrasound Application on Orange Peel Drying. Food and Bioprocess Technology. 5(6):2256-2265. https://doi.org/10.1007/s11947-011-0645-0S2256226556Alandes, L., Perez-Munuera, I., Llorca, E., Quiles, A., & Hernando, I. (2009). 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Food Research International, 36(1), 35–41.Chau, C., Sheu, F., Huang, Y., & Su, L. (2005). Improvement in intestinal function and health by the peel fibre derived from Citrus sinensis L cv Liucheng. Journal of the Science of Food & Agriculture, 85(7), 1211–1216.Crank J. (1975). The Mathematics of diffusion. Oxford (2nd ed.), UK: Clarendon Press.Cruz, R. M. S., Vieira, M. C., Fonseca, S. C., Silva, C. L. M. (2010). Impact of thermal blanching and thermosonication treatments on watercress (Nasturtium officinale) quality: thermosonication process optimization and microstructure evaluation. Food and Bioprocess Technology. doi: 10.1007/s11947-009-0220-0 , in press.Delgado, A. E., Zheng, L., & Sun, D.-W. (2010). Influence of ultrasound on freezing rate of immersion-frozen apples. Food and Bioprocess Technology, 2(3), 263–270.FAOSTAT (2010). FAO Statistical Databases. Food and Agriculture of the United Nations. Available at: http://faostat.fao.org/site/291/default.aspx . Accessed 15 January 2010.Fernandes, F. A. N., Gallao, M. I., & Rodrigues, S. (2008a). Effect of osmotic dehydration and ultrasound pre-treatment on cell structure: Melon dehydration. Food Science and Technology, 41(4), 604–610.Fernandes, F. A. N., Oliveira, F. I. P., & Rodrigues, S. (2008b). Use of ultrasound for dehydration of papayas. Food and Bioprocess Technology, 1(4), 339–345.Gabaldon-Leyva, C. A., Quintero-Ramos, A., Barnard, J., Balandrán-Quintana, R., Talamás-Abbud, R., & Jiménez-Castro, J. (2007). Effect of ultrasound on the mass transfer and physical changes in brine bell pepper at different temperatures. Journal of Food Engineering, 81(2), 374–379.Gallego-Juárez, J. A. (1998). Some applications of air-borne power ultrasound to food processing. In M. J. W., Povey, T. J. Mason (Eds.), Ultrasound in Food Processing. UK: London, Chapman & Hall.Gallego-Juárez, J. A., Rodríguez-Corral, G., Gálvez-Moraleda, J. C., & Yang, T. S. (1999). A new high intensity ultrasonic technology for food dehydration. Drying Technology, 17(3), 597–608.Garau, M. C., Simal, S., Femenia, A., & Rosselló, C. (2006). Drying of orange skin: drying kinetics modelling and functional properties. Journal of Food Engineering, 75(2), 288–295.Garau, M. C., Simal, S., Rossello, C., & Femenia, A. (2007). Effect of air-drying temperature on physico-chemical properties of dietary fibre and antioxidant capacity of orange (Citrus aurantium v. Canoneta) by-products. Food Chemistry, 104(3), 1014–1024.Garcia-Perez, J. V., Cárcel, J. A., De la Fuente, S., & Riera, E. (2006). Ultrasonic drying of foodstuff in a fluidized bed. Parametric study. Ultrasonics, 44, 539–543.Garcia-Perez, J. V., Cárcel, J. A., Benedito, J., & Mulet, A. (2007). Power ultrasound mass transfer enhancement in food drying. Food and Bioproducts Proccessing, 85(3), 247–254.Guiné, R. P. F., Henrriques, F., Barroca, M. J. (2010). Mass transfer coefficients for the drying of pumpkin (Cucurbita moschata) and dried product quality. Food and Bioprocess Technology. doi: 10.1007/s11947-009-0275 , in press.Khalloufi, S., Almeida-Rivera, C., & Bongers, P. (2009). A theoretical model and its experimental validation to predict the porosity as a function of shrinkage and collapse phenomena during drying. Food Research International, 42(8), 1122–1130.Larrauri, J. A., Rupérez, P., Bravo, L., & Saura-Calixto, F. (1996). High dietary fibre powders from orange and lime peels: associated polyphenols and antioxidant capacity. Food Research International, 29(8), 757–762.Mujumdar, A. S., & Law, C. L. (2010). Drying technology: trends and applications in postharvest processing. Food and Bioprocess Technology, 3(6), 843–852.Mulet, A., Blasco, M., García-Reverter, J., & Garcia-Perez, J. V. (2005). Drying kinetics of Curcuma longa rhizomes. Journal of Food Science, 7(5), 318–323.Oliveira, F. I. P., Gallao, M. I., Rodrigues, S., Fernandes, F.A.N. (2010). Dehydration of malay apple (Syzygium malaccense L.) using ultrasound as a pretreatment. Food and Bioprocess Technology. doi: 10.1007/s11947-010-0351-3 , in press.Ortuño, C., Perez-Munuera, I., Puig, A., Riera, E., & Garcia-Perez, J.V. (2010). Influence of power ultrasound application on mass transport and microstructure of orange peel during hot air drying. Physics Procedia, 3, 153–159.Perry, R. H. & Chilton, C. H. (1973). Chemical Engineers’ Handbook. McGraw Hill (5th ed.), New York, US.Ruiz-López, I. I., Castillo-Zamudio, R. I., Salgado-Cervantes, M. A., Rodríguez-Jimenes, G. C., & García-Alvarado, M. A. (2010). Mass transfer modelling during osmotic dehydration of hexahedral pineapple slices in limited volume solutions. Food and Bioprocess Technology, 3(3), 427–433.Salvador, A., Salvador, L., Besada, C., Larrea, V., Hernando, I., & Perez-Munuera, I. (2008). Reduced effectiveness of the treatment for removing astringency in persimmon fruit when stored at 15 °C: Physiological and microstructural study. Postharvest Biology and Technology, 49(3), 340–347.Sanchez, E. S., Simal, S., Femenía, A., Benedito, J., & Roselló, C. (2001). Effect of acoustic brining on lipolysis and on sensory characteristics of Mahon cheese. Journal of Food Science, 66(6), 892–896.Sanchez, E. S., Simal, S., Femenía, A., Llul, P., & Roselló, C. (2001). Proteolysis of Mahon cheese as affected by acoustic-assited brining. European Food Research and Technology, 212(2), 147–152.Sharma, A., & Gupta, M. N. (2006). Ultrasonic pre-irradiation effect upon aqueous enzymatic oil extraction from almond and apricot seeds. Ultrasonics Sonochemistry, 13(6), 529–534.Simal, S., Rosello, C., & Mulet, A. (1998). Modelling of air drying in regular shaped bodies. Trends in Chemical Engineering, 4(4), 171–180.Simal, S., Femenia, A., & Garcia-Pascual, P. (2003). Simulation of the drying curves of a meat-based product: effect of the external resistance to mass transfer. Journal of Food Engineering, 58(2), 193–199.Singh, R. P., & Heldman, D. R. (2001). Introduction to Food Engineering. Academic Press (3rd ed.): San Diego.Toma, M., Vinatoru, M., Paniwnyk, L., & Mason, T. J. (2001). Investigation of the effects of ultrasound on vegetal tissues during solvent extraction. Ultrasonics Sonochemistry, 8(2), 137–142

Planetary bearing defect detection in a commercial helicopter main gearbox with vibration and acoustic emission

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Helicopter gearboxes significantly differ from other transmission types and exhibit unique behaviors that reduce the effectiveness of traditional fault diagnostics methods. In addition, due to lack of redundancy, helicopter transmission failure can lead to catastrophic accidents. Bearing faults in helicopter gearboxes are difficult to discriminate due to the low signal to noise ratio (SNR) in the presence of gear vibration. In addition, the vibration response from the planet gear bearings must be transmitted via a time-varying path through the ring gear to externally mounted accelerometers, which cause yet further bearing vibration signal suppression. This research programme has resulted in the successful proof of concept of a broadband wireless transmission sensor that incorporates power scavenging whilst operating within a helicopter gearbox. In addition, this paper investigates the application of signal separation techniques in detection of bearing faults within the epicyclic module of a large helicopter (CS-29) main gearbox using vibration and Acoustic Emissions (AE). It compares their effectiveness for various operating conditions. Three signal processing techniques including an adaptive filter, spectral kurtosis and envelope analysis, were combined for this investigation. In addition, this research discusses the feasibility of using AE for helicopter gearbox monitoring

Characterization of a medium size Xe/TMA TPC instrumented with microbulk Micromegas, using low-energy gamma-rays

NEXT-MM is a general-purpose high pressure (10 bar, ~ 25 l active volume) Xenon-based TPC, read out in charge mode with an 0.8 cm × 0.8 cm-segmented 700 cm2 plane (1152 ch) of the latest microbulk-Micromegas technology. It has been recently commissioned at University of Zaragoza as part of the R&D of the NEXT 0νββ experiment, although the experiment's first stage is currently being built based on a SiPM/PMT-readout concept relying on electroluminescence. Around 2 million events were collected during the last months, stemming from the low energy γ-rays emitted by a 241Am source when interacting with the Xenon gas (Eγ = 26, 30, 59.5 keV). The localized nature of such events around atmospheric pressure, the long drift times, as well as the possibility to determine their production time from the associated α particle in coincidence, allow the extraction of primordial properties of the TPC filling gas, namely the drift velocity, diffusion and attachment coefficients. In this work we focus on the little explored combination of Xe and trimethylamine (TMA) for which, in particular, such properties are largely unknown. This gas mixture offers potential advantages over pure Xenon when aimed at Rare Event Searches, mainly due to its Penning characteristics, wave-length shifting properties and reduced diffusion, and it is being actively investigated by our collaboration. The chamber is currently operated at 2.7 bar, as an intermediate step towards the envisaged 10 bar. We report here its performance as well as a first implementation of the calibration procedures that have allowed the extension of the previously reported energy resolution to the whole readout plane (10.6% FWHM@30 keV)

Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives

[EN] We introduce a simulation framework for the transport of high and low energy electrons in xenon-based optical time projection chambers (OTPCs). The simulation relies on elementary cross sections (electron-atom and electron-molecule) and incorporates, in order to compute the gas scintillation, the reaction/quenching rates (atom-atom and atom-molecule) of the first 41 excited states of xenon and the relevant associated excimers, together with their radiative cascade. The results compare positively with observations made in pure xenon and its mixtures with CO2 and CF4 in a range of pressures from 0.1 to 10 bar. This work sheds some light on the elementary processes responsible for the primary and secondary xenon-scintillation mechanisms in the presence of additives, that are of interest to the OTPC technology.DGD is supported by the Ramon y Cajal program (Spain) under contract number RYC-2015-18820. The authors want to acknowledge the RD51 collaboration for encouragement and support during the elaboration of this work, and in particular discussions with F. Resnati, A. Milov, V. Peskov, M. Suzuki and A. F. Borghesani. The NEXT Collaboration acknowledges support from the following agencies and institutions: the European Research Council (ERC) under the Advanced Grant 339787-NEXT; the Ministerio de Economia y Competitividad of Spain under grants FIS2014-53371-C04 and the Severo Ochoa Program SEV-2014-0398; the GVA of Spain under grant PROM-ETEO/2016/120; the Portuguese FCT and FEDER through the program COMPETE, project PTDC/FIS-NUC/2525/2014 and UID/FIS/04559/2013; the U.S. Department of Energy under contracts number DE-AC02-07CH11359 (Fermi National Accelerator Laboratory) and DE-FG02-13ER42020 (Texas A& and the University of Texas at Arlington.Azevedo, C.; Gonzalez-Diaz, D.; Biagi, SF.; Oliveira, CAB.; Henriques, CAO.; Escada, J.; Monrabal, F.... (2018). Microscopic simulation of xenon-based optical TPCs in the presence of molecular additives. Nuclear Instruments and Methods in Physics Research Section A Accelerators Spectrometers Detectors and Associated Equipment. 877:157-172. https://doi.org/10.1016/j.nima.2017.08.049S15717287

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570