Synergistic Model of Cardiac Function with a Heart Assist Device

The breakdown of cardiac self-organization leads to heart diseases and failure, the number one cause of death worldwide. The left ventricular pressure–volume relation plays a key role in the diagnosis and treatment of heart diseases. Lumped-parameter models combined with pressure–volume loop analysis are very effective in simulating clinical scenarios with a view to treatment optimization and outcome prediction. Unfortunately, often invoked in this analysis is the traditional, time-varying elastance concept, in which the ratio of the ventricular pressure to its volume is prescribed by a periodic function of time, instead of being calculated consistently according to the change in feedback mechanisms (e.g., the lack or breakdown of self-organization) in heart diseases. Therefore, the application of the time-varying elastance for the analysis of left ventricular assist device (LVAD)–heart interactions has been questioned. We propose a paradigm shift from the time-varying elastance concept to a synergistic model of cardiac function by integrating the mechanical, electric, and chemical activity on microscale sarcomere and macroscale heart levels and investigating the effect of an axial rotary pump on a failing heart. We show that our synergistic model works better than the time-varying elastance model in reproducing LVAD–heart interactions with sufficient accuracy to describe the left ventricular pressure–volume relation

Modeling and parametric study of end-gas autoignition to allow the realization of ultra-low emissions, high-efficiency heavy-duty spark-ignited natural gas engines

Includes bibliographical references.2022 Fall.Engine knock and misfire are barriers to pathways leading to high-efficiency Spark-Ignited (SI) Natural Gas (NG) engines. The general tendency to knock is highly dependent on engine operating conditions and the fuel reactivity. The problem is further complicated by the low emission limits and the wide range of chemical reactivity in pipeline-quality natural gas. Depending on the region and the source of the natural gas, its reactivity, described by its Methane Number (MN), which is analogous to the Octane Number for liquid SI fuels, can span from 65 to 95. In order to realize diesel-like efficiencies, SI NG engines must be designed to operate at high Brake Mean Effective Pressures (BMEP), near or beyond knock limits, over a wide range of fuel reactivity. This requires a deep understanding of the combustion-engine interactions pertaining to flame propagation and End-Gas Autoignition (EGAI), i.e., the autoignition of the unburned gas (end gas) ahead of the flame front. However, EGAI, if controlled, provides an opportunity to increase SI NG engine efficiency by increasing the combustion rate and the total fraction of burned fuel, mitigating the effects of the slow flame speeds characteristic of natural gas fuels, which generally reduce BMEP and increase unburned hydrocarbon emissions. For this reason, to realize diesel-like efficiencies and ultra-low emissions on SI NG engines, this work proposes the study of the main parameters influencing the modeling and prediction of NG EGAI to allow for its control. In this work, a novel EGAI detection and onset determination method was developed to reliably quantify EGAI for data analysis and engine control. The new method allowed the prediction of EGAI on SI NG engines without the need to use engine- and operating-condition-dependent thresholds and reduced the error in quantifying the fraction of the total energy released by the EGAI event by up to 40%pts. One- and three-dimensional engine models were then developed to study the engine/fuel interactions that lead to NG EGAI and its performance benefits. These models, although having decent agreement with experimental data, showed the need to account for NOx chemistry when predicting NG EGAI due to a consistently later prediction of the EGAI onset (∼1.65 crank-angle degrees) and thus, a new reduced chemical mechanism for real NG fuels was developed containing NOx chemistry. The new reduced mechanism improved the EGAI onset prediction agreement to within ±0.5 crank-angle degrees and decreased simulation time during combustion by nearly 50% when using the further reduced AREIS50NOx chemical mechanism. These models were then used to study the role of NG composition on EGAI, evaluate the engine/fuel interactions leading to NG EGAI, and perform engine optimization while leveraging EGAI to increase thermal efficiency. Piston design optimization combined with a Controlled EGAI (C-EGAI) combustion mode allowed a Heavy-Duty (HD) SI NG engine to operate at diesel-like efficiencies, i.e., Brake Thermal Efficiency (BTE) ≥44%. Experimental and modeling data analysis revealed that earlier and faster heat release increases combustion efficiency by an average of 1% pts, increases work transferred to the piston resulting in a decrease in exhaust losses by 50% depending on the engine operating condition while slightly increasing heat losses. Finally, the simulation results revealed an opportunity to further enhance the BTE (up to 50%) by enabling C-EGAI combustion at leaner conditions, λ=1.4-1.6

Compositional zoning of garnet porphyroblasts from the polymetamorphic Wölz Complex, Eastern Alps

We employ garnet isopleth thermobarometry to derive the P-T conditions of Permian and Cretaceous metamorphism in the Wölz crystalline Complex of the Eastern Alps. The successive growth increments of two distinct growth zones of the garnet porphyroblasts from the Wölz Complex indicate garnet growth in the temperature interval of 540°C to 560°C at pressures of 400 to 500MPa during the Permian and temperatures ranging from 550°C to 570°C at pressures in the range of 700 to 800MPa during the Cretaceous Eo-Alpine event. Based on diffusion modelling of secondary compositional zoning within the outermost portion of the first garnet growth zone constraints on the timing of the Permian and the Eo-Alpine metamorphic events are derived. We infer that the rocks remained in a temperature interval between 570°C and 610°C over about 10 to 20Ma during the Permian, whereas the high temperature stage of the Eo-Alpine event only lasted for about 0.2Ma. Although peak metamorphic temperatures never exceeded 620°C, the prolonged thermal annealing during the Permian produced several 100µm wide alteration halos in the garnet porphyroblasts and partially erased their thermobarometric memory. Short diffusion profiles which evolved around late stage cracks within the first garnet growth zone constrain the crack formation to have occurred during cooling below about 450°C after the Eo-Alpine even

Curing the Sickie: Absence Management in NHS Scotland

Sickness absence is NHS Scotland is a serious problem. The average absence rate has been on a downward trend since 2007 but the rate is still high, creating substantial costs both economically and in terms of service delivery and the health of NHS employees. The results of this study show that sickness absence in NHS Scotland is not a general problem but a problem specific to certain areas of the organisation, most notably Nursing and Midwifery, and is linked to certain variables such as pay, gender and contract type. Management interventions to reduce the levels of sickness absence are in line with best practice and are seeing results. However, this study contends that the interventions are too general in nature and are treating the symptoms of absence rather than the specific causes. The author commends the data collection methods of NHS Scotland but calls for further qualitative research to investigate the true causes of absence in the most affected areas of the organisation

Oligonucléotides amphiphiles et microARNs (mise en place de nanoplateformes à visée diagnostiques et therapeutiques)

De nombreuses études ont montré l'intérêt thérapeutique de molécules dérivant des microARN (inhibiteurs ou analogues) en cancérologie. Cependant avant d'espérer en faire de futurs médicaments, il est indispensable d'élaborer des systèmes permettant leur délivrance préférentielle dans les cellules cancéreuses. Dans ce travail, nous avons développé deux plateformes innovantes basées sur les microARN : la première utilise les propriétés optiques des quantum dots (QD) et est destinée à l'imagerie des microARN ; la seconde repose sur la sérum albumine humaine (SAH) et a une finalité de délivrance ciblée de microARN. La mise en place de ces plateformes a nécessité la synthèse d'une petite chimiothèque de bioconjugués lipidiques dérivés des microARN (inhibiteurs ou analogues), le but étant d'exploiter l'effet hydrophobe pour les fixer à la surface des QD (ancrage hydrophobe dans la paroi lipidique des QD) et de la SAH (interaction avec les sites de liaison aux acides gras). Dans les deux cas, différentes études incluant des caractérisations physico-chimiques (MET, DLS), des expériences in vitro (SPR) et in cellulo (microscopie de fluorescence, criblage fonctionnel, RTqPCR) ont montré la potentialité de ces nouvelles plateformes.Exploitation of gene-silencing is a very promising strategy in human therapeutics. Several engineered small non coding RNAs (inhibitors or mimics) are already in preclinical and clinical trials. However a key impediment to the wider success of these approaches remains the specific delivery of RNA-derived molecules into cancerous cells. This work aimed at developing two innovative microRNA-based plateforms : the first one relying on quantum dots (QD) is dedicated to microRNA imaging and the second one based on human serum albumin (HSA) represents a new targeted delivery system. The implementation of both plateforms required the synthesis of a small library of microRNA derived lipidic bioconjugates (inhibitors or mimics), the aim being to exploit the hydrophobic effect for their loading on QD (hydrophobic anchoring in the hydrophobic QD surface) and on HSA (interaction with fatty acid binding sites). In both cases, different studies including physico-chemical caracterizations (TEM, DLS), in vitro (SPR) and in cellulo experiments (fluorescence microscopy, functional screening, RTqPCR) demonstrated the great promises held by these new plateforms.BORDEAUX2-Bib. électronique (335229905) / SudocSudocFranceF

Simulation neuronaler Aktionspotentiale in Hinblick auf Zellform und Physiologie sowie deren Ableitung mittels extrazellulärer Mikroelektroden

Um die Ursache für unterschiedliche Signalformen bei der extrazellulären Ableitung neuronaler Zellsignale zu ermitteln, wird ein detailliertes Neuronenmodell auf Basis der Finiten-Elemente-Methode entwickelt. Im Zuge einer Simulationsstudie werden die Einflüsse von Zellgeometrie und -elektrophysiologie sowie der Zell-Elektroden-Kopplung auf die resultierenden Signalformen analysiert. Die Ergebnisse zeigen, dass der Verlauf des Elektrodensignals signifikant von der Elektrodenposition abhängig ist und sich ein deutlicher Einfluss der Zell-Elektroden-Kopplung auf die Signalamplitude ergibt.In order to investigate the cause for the variety signal shapes present in extracellular measurements of neuronal activity, a detailed neuron model based on the finite element method is created. In a simulation study the impact of geometrical and electrophysiological properties of the neuron as well as several parameters of the neuron-electrode coupling on the derived signal shape is analyzed. Results show a significant dependence of the signal shape on the position of the recording electrode as well as a noticeable influence of the cell-electrode coupling on the signal amplitude

On the membership of invertible diagonal and scalar matrices

AbstractIn this paper, we consider decidability questions that are related to the membership problem in matrix semigroups. In particular, we consider the membership of a given invertible diagonal matrix in a matrix semigroup and then a scalar matrix, which has a separate geometric interpretation. Both problems have been open for any dimensions and are shown to be undecidable in dimension 4 with integral matrices by a reduction of the Post Correspondence Problem (PCP). Although the idea of PCP reduction is standard for such problems, we suggest a new coding technique to cover the case of diagonal matrices

Altered right portal and umbilical vein doppler parameters in fetal macrosomia resulting from pregestational and gestational diabetic mothers: A prospective case-control study

Objective: To evaluate the blood flow of the umbilical vein and right portal vein in macrosomic fetuses of diabetic mothers and investigate the effect of maternal insulin treatment on these blood flows.Material and Methods: This prospective case-control study was con- ducted between March 2019 and December 2019. Fetuses of the 49 pregestational and gestational diabetic mothers who had an abdominal cir- cumference percentile above 97% were evaluated as macrosomic and formed the study group. The study group was divided into two subgroups: patients treated with insulin and those who did not. In the control group, 48 non-diabetic pregnant women with matched gestatio nal weeks whose fetuses are at the 10-90% percentile were included. Time-averaged maximum blood velocity (TAMXV) values of the right portal vein and the free loop of the umbilical vein were measured.Results: The median right portal vein TAMXV value and umbilical vein TAMXV value were found to be significantly higher in diabetic pregnancies (16.25 cm/s, and 15.28 cm/s, respectively) than in the control group (12.76 cm/s, and 13.38 cm/s, respectively, p<0.001). Umbilical and right portal vein flows were similar in macrosomic fetuses of diabetic mothers who were treated with insulin or those who did not. While umbilical vein flow in macrosomic fetuses increased as the gestational age pro gressed (p=0.028), it was observed steadily in normally growing fetuses. Conclusion: The umbilical and right portal vein flows are higher in macro- somic fetuses of diabetic mothers than in appropriately grown fetuses. Maternal insulin treatment does not affect fetal umbilic al vein and right portal vein blood flow in macrosomic fetuses

STONE TOOL-USE EXPERIMENTS TO DETERMINE THE FUNCTION OF GRINDING STONES AND DENTICULATE SICKLES

Within a broader study of early Chinese agriculture, stone tool-use experiments were undertaken to document usewear on sandstone and tuff implements used to process Quercus acorns, Avena oats and Setaria millet. In other experiments, we examined usewear on denticulate slate sickles used to harvest Quercus acorns, Poaceae grass and Typha reeds. Results support other studies that indicate different patterns of abrasive smoothing, striation formation and polish development together provide a basis for distinguishing some of these tasks. This research is aimed to establish a database for functional analysis of grinding stones and sickles from the early Neolithic Peiligang culture. Controlled experiments are required to identify critical variables (e.g. silica in husks) that affect usewear patterns