Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART): Study protocol for a randomized controlled trial

Background: Acute respiratory distress syndrome (ARDS) is associated with high in-hospital mortality. Alveolar recruitment followed by ventilation at optimal titrated PEEP may reduce ventilator-induced lung injury and improve oxygenation in patients with ARDS, but the effects on mortality and other clinical outcomes remain unknown. This article reports the rationale, study design, and analysis plan of the Alveolar Recruitment for ARDS Trial (ART). Methods/Design: ART is a pragmatic, multicenter, randomized (concealed), controlled trial, which aims to determine if maximum stepwise alveolar recruitment associated with PEEP titration is able to increase 28-day survival in patients with ARDS compared to conventional treatment (ARDSNet strategy). We will enroll adult patients with ARDS of less than 72 h duration. The intervention group will receive an alveolar recruitment maneuver, with stepwise increases of PEEP achieving 45 cmH(2)O and peak pressure of 60 cmH2O, followed by ventilation with optimal PEEP titrated according to the static compliance of the respiratory system. In the control group, mechanical ventilation will follow a conventional protocol (ARDSNet). In both groups, we will use controlled volume mode with low tidal volumes (4 to 6 mL/kg of predicted body weight) and targeting plateau pressure <= 30 cmH2O. The primary outcome is 28-day survival, and the secondary outcomes are: length of ICU stay; length of hospital stay; pneumothorax requiring chest tube during first 7 days; barotrauma during first 7 days; mechanical ventilation-free days from days 1 to 28; ICU, in-hospital, and 6-month survival. ART is an event-guided trial planned to last until 520 events (deaths within 28 days) are observed. These events allow detection of a hazard ratio of 0.75, with 90% power and two-tailed type I error of 5%. All analysis will follow the intention-to-treat principle. Discussion: If the ART strategy with maximum recruitment and PEEP titration improves 28-day survival, this will represent a notable advance to the care of ARDS patients. Conversely, if the ART strategy is similar or inferior to the current evidence-based strategy (ARDSNet), this should also change current practice as many institutions routinely employ recruitment maneuvers and set PEEP levels according to some titration method.Hospital do Coracao (HCor) as part of the Program 'Hospitais de Excelencia a Servico do SUS (PROADI-SUS)'Brazilian Ministry of Healt

Large Eddy Simulation of Turbulent Reacting Flows With Radiative Heat Transfer

Combustion is the most common method of energy conversion constituting about 85 % of the primary energy consumption. However, combustion is responsible for emissions of CO, NOx , CO2 , soot and others pollutants. Hence, having the expected increase of the global energy demand in mind as well as the challenge of a global reduction in the greenhouse gases emissions and the current difficulties in developing renewable energy sources for a foreseeable future, combustion science will continue being a very important topic and a very active field of technology. Moreover, since the parameters involved in combustion systems are affected by heat transfer, the understanding and development of mathematical models for analyses of heat transfer is crucial. Studying such flows is not a straightforward task because of the high nonlinear interaction among the involving processes, which include chemical kinetics, turbulence and thermal radiation. In this context, Large Eddy Simulation (LES) is an outstanding approach and has become a common model to deal with such complex flows. In this approach, the instantaneous form of the governing equations are filtered. As a consequence of the filter procedure, unclosed terms appear that correspond to effects of Turbulence-Chemistry Interactions (TCI) and Turbulence Radiation Interactions (TRI). The importance of the TCI has long been recognized and it is a very active research topic in the combustion community. Furthermore, the relevance of TRI has been gaining recognition but just a few LES studies considered their effects of TRI. This thesis deals with the simulation of turbulent flames by taking into account radiative heat transfer. The focus of this work is on the development and application of a radiation solver for computing turbulent reacting flows. In this study, the role of the TRI in the context of LES is analyzed for two important and widely investigated configurations: Sandia flame D and bluff-body stabilized non-premixed flame. The radiation solver was implemented by considering the complete radiative transfer equation, including the emission, absorption and scattering terms. The finite volume method, which is a variation of the Discrete Ordinates Method (DOM), was applied to discretize this equation. To account for the spectral behavior of the combustion gases involved, the Weighted Sum of Gray Gases (WSGG) method is used. To include thermal radiation in the LES framework, the filtered radiative source term should be computed. The contribution of the resolved scales can be explicitly calculated, whereas the terms involving the subgrid-scale contributions are unclosed and require approximations. The Optically Thin Fluctuation Assumption (OTFA) is applied for approximating the filtered absorption term and the Eulerian Stochastic Field (ESF) method is employed for representing the emission TRI. Following, the importance of considering the subgrid-scale contributions is analyzed. For this aim, simulations are performed by considering and neglecting these contributions. The Sandia flame D, bluff-body flame and their corresponding four times scaled flames are the configurations studied here for analyzing the TRI. The scaled flames are additionally investigated in order to have a more pronounced radiation effect. For all cases, the difference between the radiative source term computed by accounting and neglecting the subgrid-scale contribution is not significant, which indicates that considering these terms is not important in the context of LES. Additionally, the radiative source term is computed with the mean fields of temperature and species concentrations to show the difference to Reynolds Averaged Navier-Stokes equations (RANS), since this procedure corresponds to compute the radiative source term in a RANS framework. As expected, the results for this case presented a significant difference to the remaining procedures, which demonstrates that considering the subgrid-scale contributions are relevant for RANS simulations

Mathematical Modeling and Computational Simulation of two-phase ows with Insoluble Surfactant

When it comes to two-phase ows, it is inevitable to talk about surfactants. Surfactants are surface-active agents that may be present in systems, as impurities, or deliberately added to the mixture to control interfacial physical efects. Surfactants are widely used in many engineering applications; for instance, they are used to generate emulsions, to handle drops and bubbles in microchannels, or to stabilize droplets suspended in an immiscible medium, they are also used in the process of water purification, etc. The main functions of surfactants are to reduce surface tension and prevent coalescence. The presence of these active agents can critically afect the dynamics of interfacial two-phase ows. Surfactants adhered to the interface result in a decrease, in a non-uniform way, of the surface tension; which makes the capillary force non-linear and introduces the Marangoni force. By using the front-tracking method and adaptive meshes locally refined, this work aims to study the efect of insoluble surfactant in interfacial two-dimensional ows. Since the surfactant is assumed to be insoluble, there is no net mass transport between the interface and the bulk uid. Therefore, the transport of surfactant is only done on the interface and for that, the transport equation for the surfactant concentration is solved in the Lagrangian mesh. This equation was implemented in the AMR2D code developed by Villar (2007). In the first step, the numerical code was validated by an analitical expression developed to calculate the drag coeficient for two-dimensional bubbles, then, the analytical and numerical results were compared. The implementation of surfactant concentration equation was verified through convergence analysis. It was simulated one and two bubbles immersed in a shear ow seeking to make a comparison between clean and contaminated interfaces. For that, it was evaluated the efects of surfactant on the dynamics of these ows. Moreover, for the case of two bubbles, the efects of surfactant in the interaction between bubbles were also investigated. After that, it was demonstrated the presence of the Marangoni efect in contaminated ows through a test in which the interface moves only because of the Marangoni force. Finally, a study of moving contact lines is presented. This study is about the modeling of the contact point, where there is the interaction of the three phases present in the ow and, in this context, the surfactant acts by modifying the value of contact angle. This is also a problem of great industrial interest. It appears in the processes of wetting, coating and many biological applications and it has been in the focus of study by many researchers for several decades.Conselho Nacional de Desenvolvimento Científico e TecnológicoMestre em Engenharia MecânicaQuando se trata de escoamentos bifásicos, torna-se inevitável falar de surfactantes. Surfactantes são agentes ativos de superfície que podem estar presentes em sistemas, tanto na forma de impurezas quanto na forma de substâncias químicas adicionadas propositalmente _a misturas para controlar efeitos físicos interfaciais. Os surfactantes são amplamente usados em numerosas aplica _c~oes de engenharia, como por exemplo, eles são usados na produção de emulsões, ou para manipular bolhas e gotas em microcanais, para estabilizar gotas suspensas em um meio imiscível, também usados no processo de purificação de _água, etc. As funções principais do surfactante são diminuir a tensão superficial e prevenir a coalescência. A presença destes agentes ativos pode afetar criticamente a dinâmica interfacial dos escoamentos bifásicos. Surfactantes aderidos _a interface resultam em uma diminuição não uniforme de tensão superficial, isso torna a força de capilaridade não linear a introduz a força de Marangoni. Utilizando o método Front-Tracking e malhas adaptativas refinadas localmente, o presente trabalho tem como objetivo estudar o efeito de surfactantes insolúveis em escoamentos interfaciais bidimensionais. O surfactante dito insolúvel _e aquele que se mantém na interface e não há uxo de massa de surfactante entre a interface e o ruido ambiente. Portanto, o transporte de surfactante _e feito somente sobre a interface e para tal, a equação de transporte para a concentração de surfactante _e resolvida na malha lagrangiana. As implementações foram feitas no código AMR2D desenvolvido por Villar (2007). Num primeiro momento, fez-se a validação do código numérico através de uma expressão desenvolvida para o cálculo do coeficiente de arrasto para bolhas bidimensionais, onde são comparados os resultados numérico e analítico. Fez-se também a verificação das implementações feitas, sobre a equação de surfactante, por intermédio da análise de convergência por referência de malha. Buscando fazer a comparação entre interface limpa e contaminada, simulou-se uma e duas bolhas imersas em um escoamento cisalhante com o interesse de verificar os efeitos do surfactante na dinâmica desses escoamentos e para o caso de duas bolhas, investigar também os efeitos do surfactante na interaçãao entre as bolhas. Em seguida, fez-se um teste para evidenciar a presença do efeito Marangoni em escoamentos contaminados. Neste teste, a interface se movimenta devido somente à força de Marangoni. Por último, apresenta-se um estudo de problemas de linhas de contato dinâmicas. Este estudo trata-se da modelagem do ponto triplo de contato, onde se tem a interação das três fases presentes no escoamento e, neste contexto, o surfactante presente age modificando o valor do ângulo de contato. Este também é um problema de grande importância industrial. Ele aparece em processos de umedecimento, revestimento e em muitas aplicações biológicas e tem sido objeto de estudo de muitos pesquisadores desde várias décadas

Study of a Rock-Ramp Fish Pass with Staggered Emergent Square Obstacles

A rock-ramp fish passage with square obstacles was experimentally and numerically studied in this work with the objective of investigating in detail the hydraulic behind such fishways and to evaluate the importance of the shape of the obstacles. The LES and VOF methods were used for the simulations, and for the measurements, shadowgraphy and ADV were applied. Two different validations were successfully performed. In the first one, the experimental and numerical results of a chosen case were compared in detail. In the second validation, the focus was given to the stage-discharge. Following the validation, a numerical study was carried out to point out the differences in the flow characteristics from a configuration with square and circular obstacles. The discharge was nearly the same for both configurations, which implies different water depths. The results showed a lower velocity field, lower turbulent kinetic energy, and lower lateral fluctuations for the configuration with square blocks, which indicated a better passability for this geometry. However, it also presented a higher water depth, which led to a less attractive discharge. The differences in the flow generated in the two configurations indicated that the shape is an important modifiable parameter to be considered in the design process

Effects of balanced solution on short-term outcomes in traumatic brain injury patients: a secondary analysis of the BaSICS randomized trial

Objective: To describe the effects of balanced solution use on the short-term outcomes of patients with traumatic brain injury enrolled in BaSICS trial. Methods: Patients were randomized to receive either 0.9% saline or balanced solution during their intensive care unit stay. The primary endpoint was 90-day mortality, and the secondary outcomes were days alive and free of intensive care unit stay at 28 days. The primary endpoint was assessed using Bayesian logistic regression. The secondary endpoint was assessed using a Bayesian zero-inflated beta binomial regression. Results: We included 483 patients (236 in the 0.9% saline arm and 247 in the balanced solution arm). A total of 338 patients (70%) with a Glasgow coma scale score ≤ 12 were enrolled. The overall probability that balanced solutions were associated with higher 90-day mortality was 0.98 (OR 1.48; 95%CrI 1.04 - 2.09); this mortality increment was particularly noticeable in patients with a Glasgow coma scale score below 6 at enrollment (probability of harm of 0.99). Balanced solutions were associated with -1.64 days alive and free of intensive care unit at 28 days (95%CrI -3.32 - 0.00) with a probability of harm of 0.97. Conclusion: There was a high probability that balanced solutions were associated with high 90-day mortality and fewer days alive and free of intensive care units at 28 days

Plano de análise estatística para o estudo Balanced Solution versus Saline in Intensive Care Study (BaSICS)

OBJECTIVE: To report the statistical analysis plan (first version) for the Balanced Solutions versus Saline in Intensive Care Study (BaSICS). METHODS: BaSICS is a multicenter factorial randomized controlled trial that will assess the effects of Plasma-Lyte 148 versus 0.9% saline as the fluid of choice in critically ill patients, as well as the effects of a slow (333mL/h) versus rapid (999mL/h) infusion speed during fluid challenges, on important patient outcomes. The fluid type will be blinded for investigators, patients and the analyses. No blinding will be possible for the infusion speed for the investigators, but all analyses will be kept blinded during the analysis procedure. RESULTS: BaSICS will have 90-day mortality as its primary endpoint, which will be tested using mixed-effects Cox proportional hazard models, considering sites as a random variable (frailty models) adjusted for age, organ dysfunction and admission type. Important secondary endpoints include renal replacement therapy up to 90 days, acute renal failure, organ dysfunction at days 3 and 7, and mechanical ventilation-free days within 28 days. CONCLUSION: This manuscript provides details on the first version of the statistical analysis plan for the BaSICS trial and will guide the study's analysis when follow-up is finished

Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults A Secondary Exploratory Analysis of the BaSICS Clinical Trial

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission. Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type. Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model. Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66–10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56–1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50–0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65–0.97; probability of benefit, 0.97). Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment. Clinical trial registered with www.clinicaltrials.gov (NCT 02875873)