Sharp wave-ripple complexes in a reduced model of the hippocampal CA3-CA1 network of the macaque monkey

Sharp wave-ripple complexes observed in the hippocampal CA1 local field potential (LFP) are thought to play a major role in memory reactivation, transfer and consolidation. SPW-Rs are known to result from a complex interplay between local and upstream hippocampal ensembles. However, the key mechanisms that underlie these events remain partly unknown. In this work, we introduce a reduced, but realistic multi-compartmental model of the macaque monkey´s hippocampal CA3-CA1 network. The model consists of two semi-linear layers, each consisting of two-compartmental pyramidal neurons and one-compartmental perisomatic-targeting basket cells. Connections in the network were modeled as AMPA synapses, based on physiological and anatomical data. Notably, while auto-association fibers were prevalent in CA3, CA1 connectivity -inspired by recent findings- implemented a "feedback and reciprocal inhibition", dominated by recurrent inhibition and pyramidal cells-interneurons synapses. SPW-R episodes emerge spontaneously in the CA1 subfield LFP (which is assumed proportional to transmembrane currents across all compartments and medium resistivity): Episodes of short-lived high-frequency oscillations (ripples, 80-180 Hz) on top of a massive dendritic depolarization (< 20 Hz) with visual and quantitative characteristics observed experimentally [1]. Concomitantly, the CA3 subfield LFP presents episodes of quasi-synchronous neuronal bursting in the form of gamma episodes (25-75 Hz). The model reveals a lower bound for the minimal network that may generate SPW-R activity, and predicts a large number of features of in vivo hippocampal recordings in macaque monkeys [1]. Spike-LFP coherence analysis in CA1 displays reliable synchrony of spiking activity in the ripple LFP frequency band, suggesting that modeled SPW-R episodes reflect a genuine network oscillatory regime. Interestingly, interneuronal firing shows coherence increases concomitant with the beginning and the end of the SPW-R event, together with increases over gamma frequencies. The model suggests that activity of both pyramidal neurons and interneurons is critical for the local genesis and dynamics of physiological SPW-R activity. Unlike other models, we found that it is interneuronal silence, not interneuronal firing that triggers these fast oscillatory events, in line with the fact that unbalanced excitability of selected pyramidal cells marks the beginning of single network episodes. Interneuronal silence quickly increases population firing of pyramidal cells. The interneuronal population activity increases with some latency due to the unbalanced excitatory drive, becoming pivotal to pyramidal cell activity, and further pacing pyramidal cells due to interneuronal fast kinetic properties. Our modeled data suggests that this effect is possibly mediated by a silencing-and-rebound-excitation mechanism, maintaining the frequency of the field oscillation bounded to the ripple range. The reduced model suggests a simple mechanism for the occurrence of SPW-Rs, in light of recent experimental evidence. We provide new insights into the dynamics of the hippocampal CA3-CA1 network during ripples, and the relation between neuronal circuits' activity at meso- and microscopic scales. Finally, our model exhibits characteristic cell type-specific activity that might be critical for the emergence of physiological SPW-R activity and therefore, for the formation of hippocampus-dependent memory representations

Modelación del frijol en Latinoamérica: Estado del arte y base de datos para parametrización

Frijol común (Phaseolus vulgaris L.) es la leguminosa de grano para consumo humano de mayor producción en el mundo, y es nativo de las Américas, donde juega un papel importante en la dieta. Los ambientes donde se cultiva el frijol varían desde zonas tropicales hasta alta montaña, con diversos hábitos de crecimiento (arbustivo determinado, arbustivo indeterminado, y voluble), y en sistemas de producción desde los tradicionales hasta los altamente tecnificados. Los esfuerzos en modelaje, por tanto, deben empezar desde identificar el tipo de frijol y el sistema objetivo. El frijol es muy sensible al estrés abiótico, hecho que ha animado el modelaje de su posible respuesta bajo escenarios de cambio climático. Se llevó a cabo una revisión de literatura para identificar quince ejercicios de modelaje ejecutados en América Latina, abarcando estudios de crecimiento (tazas de producción de nudos y área foliar), fenología, y de rendimiento. Los modelos empleados en dichos estudios incluyen EcoCrop, CROPGRO-DRYBEAN (implementado en la plataforma DSSAT), y en un caso cada uno, Maxent y CLIMEX. Se describen cuatro estudios en detalle: en los dos países de mayor producción en el mundo (Brasil y México), y en Centroamérica como región altamente vulnerable al cambio climático. Estos estudios concuerdan que la productividad del frijol podría sufrir serios efectos negativos en el transcurso del Siglo XXI a raíz del cambio climático. Finalmente, se informa sobre un ejercicio reciente de recopilar datos históricos de ensayos de frijol en Latinoamérica para alimentar futuros esfuerzos de modelaje. Common bean (Phaseolus vulgaris L.) is the grain legume of greatest volume of production for direct human consumption, and is native to the Americas where it plays an important role in the diet of consumers. Bean is cultivated in environments from lowland tropical areas to high mountainous zones; with growth habits ranging from determinate bush, to indeterminate bush, to climbing types; and in production systems varying from traditional low input agriculture to highly technified systems. As such, efforts at modelling should focus on a specific plant type and production system. Bean is very sensitive to abiotic stress, a fact that has motivated modelling of its response in light of the dangers of climate change. A review of literature was carried out revealing fifteen studies in Latin America considering different aspects of plant growth (rates of node and leaf area production), phenology, and yield. Models employed include EcoCrop, CROPGRO (a module within the DSSAT cropping system model), and in one instance each, Maxent and CLIMEX. Three studies in particular are detailed: in the two countries of greatest production in the world (Brazil and Mexico), and one study in Central America as a region under direct threat of climate change. These three studies confirm that bean productivity will likely suffer severe negative effects in the course of the 21st century, as a result of climate change. A recent effort has compiled data from historical yield trials in Latin America as a resource for future modelling efforts.JRC.D.5-Food Securit

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis

Heart Rate Variability Dynamics for the Prognosis of Cardiovascular Risk

Statistical, spectral, multi-resolution and non-linear methods were applied to heart rate variability (HRV) series linked with classification schemes for the prognosis of cardiovascular risk. A total of 90 HRV records were analyzed: 45 from healthy subjects and 45 from cardiovascular risk patients. A total of 52 features from all the analysis methods were evaluated using standard two-sample Kolmogorov-Smirnov test (KS-test). The results of the statistical procedure provided input to multi-layer perceptron (MLP) neural networks, radial basis function (RBF) neural networks and support vector machines (SVM) for data classification. These schemes showed high performances with both training and test sets and many combinations of features (with a maximum accuracy of 96.67%). Additionally, there was a strong consideration for breathing frequency as a relevant feature in the HRV analysis

Venezuela's humanitarian crisis, resurgence of vector-borne diseases, and implications for spillover in the region.

In the past 5-10 years, Venezuela has faced a severe economic crisis, precipitated by political instability and declining oil revenue. Public health provision has been affected particularly. In this Review, we assess the impact of Venezuela's health-care crisis on vector-borne diseases, and the spillover into neighbouring countries. Between 2000 and 2015, Venezuela witnessed a 359% increase in malaria cases, followed by a 71% increase in 2017 (411 586 cases) compared with 2016 (240 613). Neighbouring countries, such as Brazil, have reported an escalating trend of imported malaria cases from Venezuela, from 1538 in 2014 to 3129 in 2017. In Venezuela, active Chagas disease transmission has been reported, with seroprevalence in children (<10 years), estimated to be as high as 12·5% in one community tested (n=64). Dengue incidence increased by more than four times between 1990 and 2016. The estimated incidence of chikungunya during its epidemic peak is 6975 cases per 100 000 people and that of Zika virus is 2057 cases per 100 000 people. The re-emergence of many vector-borne diseases represents a public health crisis in Venezuela and has the possibility of severely undermining regional disease elimination efforts. National, regional, and global authorities must take action to address these worsening epidemics and prevent their expansion beyond Venezuelan borders

Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction &gt;0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

The clinical relevance of oliguria in the critically ill patient : Analysis of a large observational database

Funding Information: Marc Leone reports receiving consulting fees from Amomed and Aguettant; lecture fees from MSD, Pfizer, Octapharma, 3 M, Aspen, Orion; travel support from LFB; and grant support from PHRC IR and his institution. JLV is the Editor-in-Chief of Critical Care. The other authors declare that they have no relevant financial interests. Publisher Copyright: © 2020 The Author(s). Copyright: Copyright 2020 Elsevier B.V., All rights reserved.Background: Urine output is widely used as one of the criteria for the diagnosis and staging of acute renal failure, but few studies have specifically assessed the role of oliguria as a marker of acute renal failure or outcomes in general intensive care unit (ICU) patients. Using a large multinational database, we therefore evaluated the occurrence of oliguria (defined as a urine output 16 years) patients in the ICON audit who had a urine output measurement on the day of admission were included. To investigate the association between oliguria and mortality, we used a multilevel analysis. Results: Of the 8292 patients included, 2050 (24.7%) were oliguric during the first 24 h of admission. Patients with oliguria on admission who had at least one additional 24-h urine output recorded during their ICU stay (n = 1349) were divided into three groups: transient - oliguria resolved within 48 h after the admission day (n = 390 [28.9%]), prolonged - oliguria resolved > 48 h after the admission day (n = 141 [10.5%]), and permanent - oliguria persisting for the whole ICU stay or again present at the end of the ICU stay (n = 818 [60.6%]). ICU and hospital mortality rates were higher in patients with oliguria than in those without, except for patients with transient oliguria who had significantly lower mortality rates than non-oliguric patients. In multilevel analysis, the need for RRT was associated with a significantly higher risk of death (OR = 1.51 [95% CI 1.19-1.91], p = 0.001), but the presence of oliguria on admission was not (OR = 1.14 [95% CI 0.97-1.34], p = 0.103). Conclusions: Oliguria is common in ICU patients and may have a relatively benign nature if only transient. The duration of oliguria and need for RRT are associated with worse outcome.publishersversionPeer reviewe

Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis

Supported by F. Hoffmann–La Roche