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Importance Randomized clinical trials (RCTs) of therapeutic-dose heparin in patients hospitalized with COVID-19 produced conflicting results, possibly due to heterogeneity of treatment effect (HTE) across individuals. Better understanding of HTE could facilitate individualized clinical decision-making. Objective To evaluate HTE of therapeutic-dose heparin for patients hospitalized for COVID-19 and to compare approaches to assessing HTE. Design, Setting, and Participants Exploratory analysis of a multiplatform adaptive RCT of therapeutic-dose heparin vs usual care pharmacologic thromboprophylaxis in 3320 patients hospitalized for COVID-19 enrolled in North America, South America, Europe, Asia, and Australia between April 2020 and January 2021. Heterogeneity of treatment effect was assessed 3 ways: using (1) conventional subgroup analyses of baseline characteristics, (2) a multivariable outcome prediction model (risk-based approach), and (3) a multivariable causal forest model (effect-based approach). Analyses primarily used bayesian statistics, consistent with the original trial. Exposures Participants were randomized to therapeutic-dose heparin or usual care pharmacologic thromboprophylaxis. Main Outcomes and Measures Organ support–free days, assigning a value of −1 to those who died in the hospital and the number of days free of cardiovascular or respiratory organ support up to day 21 for those who survived to hospital discharge; and hospital survival. Results Baseline demographic characteristics were similar between patients randomized to therapeutic-dose heparin or usual care (median age, 60 years; 38% female; 32% known non-White race; 45% Hispanic). In the overall multiplatform RCT population, therapeutic-dose heparin was not associated with an increase in organ support–free days (median value for the posterior distribution of the OR, 1.05; 95% credible interval, 0.91-1.22). In conventional subgroup analyses, the effect of therapeutic-dose heparin on organ support–free days differed between patients requiring organ support at baseline or not (median OR, 0.85 vs 1.30; posterior probability of difference in OR, 99.8%), between females and males (median OR, 0.87 vs 1.16; posterior probability of difference in OR, 96.4%), and between patients with lower body mass index (BMI 90% for all comparisons). In risk-based analysis, patients at lowest risk of poor outcome had the highest propensity for benefit from heparin (lowest risk decile: posterior probability of OR >1, 92%) while those at highest risk were most likely to be harmed (highest risk decile: posterior probability of OR

The inherent complexity of critical production systems, coupled with policies to preserve people's safety and health, environmental management, and the facilities themselves, and stricter laws regarding the occurrence of accidents, are the motivation to the design of Safety Control Systems that leads the mitigation functionality. According to experts, the concept of Safety Instrumented Systems (SIS) is a solution to these types of issues. They strongly recommend layers of risk reduction based on hierarchical control systems in order to manage risks, preventing or mitigating faults, or to lead the process to a safe state. Additionally some of the safety standards such as IEC 61508, IEC 61511, among others, guide different activities related Safety Life Cycle design of SIS. The IEC 61508 suggests layers of critical fault prevention and critical fault mitigation. In the context of mitigation control system, the standard provides a recommendation of activities to mitigate critical faults, by proposing control levels of mitigation. This paper proposes a method to implement the mitigation layer based on the risk analysis of the plant and the consequences of faults of its critical components. The control architecture, based on distributed and hierarchical control systems in a collaborative way, will make use of the techniques of risk analysis raised and mitigation actions, based on the knowledge of an expert, implemented by fuzzy logic. The mitigation layer therefore seeks to reduce the inherent risk in a process, and besides proposing the mitigation layer, this work aims to a further reduction of process risk on proposing an anticipatory mitigation action through temporal analysis of the evolution of the parameter used to measure the effect of the occurrence of a critical fault.

One of the most important recent improvements in cardiology is the use of ventricular assist devices (VADs) to help patients with severe heart diseases, especially when they are indicated to heart transplantation. The Institute Dante Pazzanese of Cardiology has been developing an implantable centrifugal blood pump that will be able to help a sick human heart to keep blood flow and pressure at physiological levels. This device will be used as a totally or partially implantable VAD. Therefore, an improvement on device performance is important for the betterment of the level of interaction with patient's behavior or conditions. But some failures may occur if the device's pumping control does not follow the changes in patient's behavior or conditions. The VAD control system must consider tolerance to faults and have a dynamic adaptation according to patient's cardiovascular system changes, and also must attend to changes in patient conditions, behavior, or comportments. This work proposes an application of the mechatronic approach to this class of devices based on advanced techniques for control, instrumentation, and automation to define a method for developing a hierarchical supervisory control system that is able to perform VAD control dynamically, automatically, and securely. For this methodology, we used concepts based on Bayesian network for patients' diagnoses, Petri nets to generate a VAD control algorithm, and Safety Instrumented Systems to ensure VAD system security. Applying these concepts, a VAD control system is being built for method effectiveness confirmation.

OBJETIVO: Avaliar os diferentes métodos de quantificação de insuficiência mitral (IM) ao ecocardiograma transesofágico (ETE) em pacientes com suspeita clínica de disfunção de prótese mitral. MÉTODOS: Foram estudados 15 pacientes, divididos em dois grupos, conforme a presença ou não de IM expressiva (grau importante) ao cateterismo cardíaco (Cate). A IM foi quantificada ao ETE pelos seguintes métodos, habitualmente empregados para IM de valvas nativas: avaliação subjetiva do jato regurgitante ao mapeamento de fluxo a cores, avaliação objetiva com base na área absoluta do jato regurgitante e na sua área relativa (área do jato/área do átrio esquerdo (AE)), e avaliação baseada na presença de fluxo sistólico reverso em veia pulmonar. RESULTADOS: A IM foi predominantemente de origem transprotética (14 pacientes) e de distribuição excêntrica (11 pacientes). Observou-se concordância estatisticamente significante (p7cm²) e relativa (área de jato >35% da área do AE) não mostraram concordância significante com o Cate, com nítida subestimação ao ETE pela área relativa. Houve, porém, concordância significante, quando considerado como IM expressiva, jato cuja área relativa foi >30% da área do AE. CONCLUSÃO: O ETE identificou adequadamente as IM protéticas angiograficamente expressivas, particularmente pelos métodos subjetivo e de fluxo sistólico reverso em veia pulmonar. É necessário cautela na utilização de critérios baseados na área do jato regurgitante, em virtude da subestimação da área na presença de jato excêntrico, freqüente em disfunção de prótese mitral.PURPOSE: To evaluate the different methods for grading mitral regurgitation (MR) by transesophageal echocardiography (TEE) in patients with clinical suspicion of mitral prosthesis dysfunction. METHODS: Cardiac catheterization (Cath) was performed in 15 patients for grading the severity of prosthetic MR, divided in two groups based on the presence or absence of severe MR. Prosthetic MR was quantified by TEE using methods commonly used for MR of native valves: subjective assessment by color Doppler, objective assessment based on absolute jet area and on its relative area (jet area/left atrial area) and assessment based on the presence of systolic flow reversal in pulmonary vein. RESULTS: Prosthetic MR was mostly transprosthetic (14 patients) and eccentric (11 patients). There was significant correlation (p7cm²) and relative (jet area >35% of left atrial area) jet areas did not reveal significant correlation with the angiographic grade and showed clear underestimation by TEE when the last method was used. However, there was good correlation (p30% were considered as cut point. CONCLUSION: TEE correctly identified angiographic severe mitral prosthesis regurgitation, mainly by the presence of systolic flow reversal in pulmonary vein and subjective assessment. The estimation of severity of the prosthetic MR by absolute or relative jet area seems to be limited and should be used with caution due to eccentricity of the regurgitant jet, frequently seen in mitral prosthesis dysfunction.

Numerical calculations were used to assess the probable microscopic distribution of the electric field along or close to the actual Si-SiO 3 interface of a metal oxide semiconductor (MOS) capacitor biased into accumulation. Silicon wafers were oxidized to 20 nm at 1150°C by rapid thermal oxidation, according to two different thermal recipes in order to yield different Si-SiO 2 interface roughnesses. After oxide removal, typical atomic force microscopy (AFM) line scans of the silicon surface were exported into the MEDICI program as a description of the Si-SiO 2 , interface in order to calculate the electric field distribution within the oxide layer of a bidimensional MOS capacitor biased into accumulation. This distribution was found to be highly inhomogeneous even for relatively smooth Si-SiO 2 interfaces, displaying strong local electric field enhancements, the spatial distribution of which will be called electronic roughness in this work. Simple local oxide thinning at the position of the protrusions cannot account for these field enhancements, thus indicating that the shape of the protrusion is dictating the electronic roughness. The electronic roughness could be correlated with electric breakdown characteristics of actual MOS capacitors prepared on these wafers.

This paper proposes a switched-capacitor converter to drive power light emitting diodes (LEDs). In contrast to conventional constant dc current drivers, the current pulse is provided by this switched-capacitor LED driver. In the present driver, the capacitor is charged and discharged through of the output circuit and the current flow direction is controlled by switch. Based on the charge control analysis, the effects of switching devices on the proposed converter are discriminated and evaluated. The experimental results demonstrated the technical feasibility of using the proposed converter for LEDs.

Endophytic fungi, isolated from a number of different species of tropical plants, were investigated for lipid biodiesel precursor production. The extracts produced from liquid cultures of these fungi were subjected to acid-catalyzed transesterification reactions with methanol producing methyl esters and then analyzed through chromatographic (GC—FID) and spectrometric techniques (MS, NMR 1 H). The European Standard Method, EN 14103, was used for the quantification of methyl esters extracted from the fungi of the species and genera studied. Xylariaceous fungi exhibited the highest concentrations of methyl esters (91%), and hence may be a promising source for biofuel.

One of the most important recent improvements in cardiology is the use of ventricular assist devices (VADs) to help patients with severe heart diseases, especially when they are indicated to heart transplantation. The Institute Dante Pazzanese of Cardiology has been developing an implantable centrifugal blood pump that will be able to help a sick human heart to keep blood flow and pressure at physiological levels. This device will be used as a totally or partially implantable VAD. Therefore, an improvement on device performance is important for the betterment of the level of interaction with patient's behavior or conditions. But some failures may occur if the device's pumping control does not follow the changes in patient's behavior or conditions. The VAD control system must consider tolerance to faults and have a dynamic adaptation according to patient's cardiovascular system changes, and also must attend to changes in patient conditions, behavior, or comportments. This work proposes an application of the mechatronic approach to this class of devices based on advanced techniques for control, instrumentation, and automation to define a method for developing a hierarchical supervisory control system that is able to perform VAD control dynamically, automatically, and securely. For this methodology, we used concepts based on Bayesian network for patients' diagnoses, Petri nets to generate a VAD control algorithm, and Safety Instrumented Systems to ensure VAD system security. Applying these concepts, a VAD control system is being built for method effectiveness confirmation.

Part 12: Fault-Tolerant Systems; International audience; When a patient have severe heart diseases, Ventricular Assist Device (VAD) implantation may be necessary. However, the improvement of the interaction between the device and the patient’s behavior is crucial. Currently, the control of these pumps does not follow changes in patient behavior and the devices are no safe. Therefore, if VAD has no faults tolerance and no dynamic behavior according to the cardiovascular system performance, there is a serious limitation on expected results. This research investigates a mechatronic approach for this class of devices based on advanced techniques for control, instrumentation and automation to define a method for developing a hierarchical supervisory control system to control a VAD dynamically and securely. To apply this method, concepts based on Petri nets and Safety Instrumented Systems are used. This innovation reduces the interventions and unnecessary drugs, enabling a reduction of deposable material and patient hospitalization, and contributes to sustainability concept.

Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina UNIFESP, EPM SciELO

OBJECTIVE: To describe a new more efficient method of endocardial cardiac stimulation, which produces a narrower QRS without using the coronary sinus or cardiac veins. METHODS: We studied 5 patients with severe dilated cardiomyopathy, chronic atrial fibrillation and AV block, who underwent definitive endocardial pacemaker implantation, with 2 leads, in the RV, one in the apex and the other in the interventricular septum (sub pulmonary), connected, respectively, to ventricular and atrial bicameral pacemaker outputs. Using Doppler echocardiography, we compared, in the same patient, conventional (VVI), high septal ("AAI") and bifocal ("DDT" with AV interval ~ 0) stimulation. RESULTS: The RV bifocal stimulation had the best results with an increase in ejection fraction and cardiac output and reduction in QRS duration, mitral regurgitation and in the left atrium area (p

OBJETIVO: Avaliar os diferentes métodos de quantificação de insuficiência mitral (IM) ao ecocardiograma transesofágico (ETE) em pacientes com suspeita clínica de disfunção de prótese mitral. MÉTODOS: Foram estudados 15 pacientes, divididos em dois grupos, conforme a presença ou não de IM expressiva (grau importante) ao cateterismo cardíaco (Cate). A IM foi quantificada ao ETE pelos seguintes métodos, habitualmente empregados para IM de valvas nativas: avaliação subjetiva do jato regurgitante ao mapeamento de fluxo a cores, avaliação objetiva com base na área absoluta do jato regurgitante e na sua área relativa (área do jato/área do átrio esquerdo (AE)), e avaliação baseada na presença de fluxo sistólico reverso em veia pulmonar. RESULTADOS: A IM foi predominantemente de origem transprotética (14 pacientes) e de distribuição excêntrica (11 pacientes). Observou-se concordância estatisticamente significante (p7cm²) e relativa (área de jato >35% da área do AE) não mostraram concordância significante com o Cate, com nítida subestimação ao ETE pela área relativa. Houve, porém, concordância significante, quando considerado como IM expressiva, jato cuja área relativa foi >30% da área do AE. CONCLUSÃO: O ETE identificou adequadamente as IM protéticas angiograficamente expressivas, particularmente pelos métodos subjetivo e de fluxo sistólico reverso em veia pulmonar. É necessário cautela na utilização de critérios baseados na área do jato regurgitante, em virtude da subestimação da área na presença de jato excêntrico, freqüente em disfunção de prótese mitral. PURPOSE: To evaluate the different methods for grading mitral regurgitation (MR) by transesophageal echocardiography (TEE) in patients with clinical suspicion of mitral prosthesis dysfunction. METHODS: Cardiac catheterization (Cath) was performed in 15 patients for grading the severity of prosthetic MR, divided in two groups based on the presence or absence of severe MR. Prosthetic MR was quantified by TEE using methods commonly used for MR of native valves: subjective assessment by color Doppler, objective assessment based on absolute jet area and on its relative area (jet area/left atrial area) and assessment based on the presence of systolic flow reversal in pulmonary vein. RESULTS: Prosthetic MR was mostly transprosthetic (14 patients) and eccentric (11 patients). There was significant correlation (p7cm²) and relative (jet area >35% of left atrial area) jet areas did not reveal significant correlation with the angiographic grade and showed clear underestimation by TEE when the last method was used. However, there was good correlation (p30% were considered as cut point. CONCLUSION: TEE correctly identified angiographic severe mitral prosthesis regurgitation, mainly by the presence of systolic flow reversal in pulmonary vein and subjective assessment. The estimation of severity of the prosthetic MR by absolute or relative jet area seems to be limited and should be used with caution due to eccentricity of the regurgitant jet, frequently seen in mitral prosthesis dysfunction.

OBJETIVO: Avaliação não invasiva das respostas cardiopulmonares ao exercício a curto e longo prazo após valvotomia mitral por cateter balão. MÉTODOS: Estudaram-se 9 pacientes do sexo feminino, 35±9 anos, com estenose mitral, tipo funcional II ou III, em uso de digitálicos e diuréticos, através de teste ergoespirométrico, eletrocardiograma e ecocardiograma, antes e após valvotomia em fase precoce (3 a 5 dias) e tardia (8 a 12 meses). RESULTADOS: Os pacientes evoluíram para tipo funcional II (44%) ou I (56%), na fase tardia. Houve redução da freqüência cardíaca de repouso (87±11bpm vs 85±7bpm vs 75±9bpm) e elevação do número de estágios (4±1 estágios vs 5±2 estágios vs 6±1 estágios); a capacidade aeróbia máxima aumentou apenas na fase tardia (16±3mL/kg/min vs 18±4mL/kg/min vs 22±7mL/kg/min). O limiar anaeróbio, a ventilação pulmonar e o equivalente ventilatório do O2 permaneceram inalterados. Nas cargas submáximas de exercício ocorreu redução da freqüência cardíaca (estágio I: 124±18bpm vs 112±13bpm vs 87±15bpm), consumo de O2 (estágio I: 10±2mL/kg/min vs 8±2mL/kg/min vs 8±mL/kg/min) e ventilação pulmonar, nas fases precoce e tardia. A área valvar mitral mostrou reduções na fase tardia (0,94cm² vs 1,66cm² vs 1,20cm² ). CONCLUSÃO: Apesar da tendência à reestenose parcial, houve melhora no tipo funcional e no desempenho cardiopulmonar com diminuição da sobrecarga circulatória no exercício submáximo. PURPOSE: To evaluate the early and late cardiorespiratory responses after balloon mitral valvuloplasty. METHODS: Nine female patients aged 35±9 years, with mitral stenosis, in class II or III (NYHA) underwent upright ergoespirometric test, resting electrocardiogram and echocardiogram before, 3 to 5 days (early evaluation) and 8 to 12 months (late evaluation) after mitral valvuloplasty. All patients were treated with digitalis and diuretics. RESULTS: During late evaluation, 44% patients were in class II and 56% were in class I (NYHA). The resting heart rate decreased (87±11bpm vs 85±7bpm vs 75±9bpm) and the number of steps increased (4±1 steps vs 5±2 steps vs 6±1 steps); the peak oxygen uptake improved only in the late evaluation (16±3mL/kg/min vs 18±4mL/kg/min vs 22±7mL/kg/min). The anaerobic threshold, minute ventilation (VE) and ventilatory equivalent for oxygen showed no change. The heart rate (1st step: 124±18bpm vs 112±13bpm vs 87±15bpm), O2 uptake (1st step: 10±2mL/kg/min vs 8±2mL/kg/min vs 8±2mL/kg/min) and VE decreased during submaximal exercise in early and late phases. The mitral valve area decreased in the late evaluation (0.94cm² vs 1.66cm² vs 1.20cm²). CONCLUSION: Although partial restenosis tended to occur in these patients, they improved the functional class and cardiorespiratory performance and cardiocirculatory load during submaximal exercise.

The occurrence of all-trans (-)-14,15-epoxygeranyl-geraniol in Pterodon pubescens Benth. is established, and its prophylactic activity against infection by Schitsosma mansoni demonstrated. Two other diterpenes present in the oil are inactive.

Recent studies show the designs of automated systems are becoming increasingly complex to meet the global competitive market. Additionally, organizations have focused on policies to achieve people’s safety and health, environmental management system, and controlling of risks, based on standards. In this context, any industrial system in the event of a fault that is not diagnosed and treated correctly could be considered to pose a serious risk to people’s health, to the environment and to the industrial equipment. According to experts, the concept of Safety Instrumented Systems (SIS) is a practical solution to these types of issues. They strongly recommend layers for risk reduction based on control systems organized hierarchically in order to manage risks, preventing or mitigating faults, or to bringing the process to a safe state. Additionally, the concept of Risk and Hazard Control can be applied to accomplish the required functionalities. It is based on problem solving components and considers a cooperative way to find a control solution. In this context, the software architecture can be based on a service-oriented architecture (SOA) approach. This paper initially proposes a new architecture for design of safety control systems for critical systems, based on Safety Supervisory Control Architecture, in accordance with standards IEC 61508 and IEC 61511. Furthermore, a method is also proposed for design the control layer of risk prevention within Safety Supervisory Control Architecture.