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Phosphatidylserine (PtdS) is classified as a glycerophospholipid and a primary anionic phospholipid and is particularly abundant in the inner leaflet of the plasma membrane in neural tissues. It is synthesized from phosphatidylcholine or phosphatidylethanolamine by exchanging the base head group with serine, and this reaction is catalyzed by PtdS synthase-1 and PtdS synthase-2 located in the endoplasmic reticulum. PtdS exposure on the outside surface of the cell is essential for eliminating apoptotic cells and initiating the blood clotting cascade. It is also a precursor of phosphatidylethanolamine, produced by PtdS decarboxylase in bacteria, yeast, and mammalian cells. Furthermore, PtdS acts as a cofactor for several necessary enzymes that participate in signaling pathways. Beyond these functions, several studies indicate that PtdS plays a role in various cerebral functions, including activating membrane signaling pathways, neuroinflammation, neurotransmission, and synaptic refinement associated with the central nervous system (CNS). This review discusses the occurrence of PtdS in nature and biosynthesis via enzymes and genes in plants, yeast, prokaryotes, mammalian cells, and the brain, and enzymatic synthesis through phospholipase D (PLD). Furthermore, we discuss metabolism, its role in the CNS, the fortification of foods, and supplementation for improving some memory functions, the results of which remain unclear. PtdS can be a potentially beneficial addition to foods for kids, seniors, athletes, and others, especially with the rising consumer trend favoring functional foods over conventional pills and capsules. Clinical studies have shown that PtdS is safe and well tolerated by patients.
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BACKGROUND: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the USA. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. METHODS: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 h of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 h will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient-reported quality of life measures. DISCUSSION: In vitro and in vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. TRIAL REGISTRATION: ClinicalTrials.gov NCT04217551. Registered on 30 December 2019.
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Coma , Hipotermia Inducida , Estudios Multicéntricos como Asunto , Paro Cardíaco Extrahospitalario , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Hipotermia Inducida/métodos , Hipotermia Inducida/efectos adversos , Paro Cardíaco Extrahospitalario/terapia , Paro Cardíaco Extrahospitalario/fisiopatología , Coma/terapia , Coma/etiología , Coma/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Recuperación de la Función , Neuroprotección , Estados Unidos , Investigación sobre la Eficacia ComparativaRESUMEN
Background: Cardiac arrest is a common and devastating emergency of both the heart and brain. More than 380,000 patients suffer out-of-hospital cardiac arrest annually in the United States. Induced cooling of comatose patients markedly improved neurological and functional outcomes in pivotal randomized clinical trials, but the optimal duration of therapeutic hypothermia has not yet been established. Methods: This study is a multi-center randomized, response-adaptive, duration (dose) finding, comparative effectiveness clinical trial with blinded outcome assessment. We investigate two populations of adult comatose survivors of cardiac arrest to ascertain the shortest duration of cooling that provides the maximum treatment effect. The design is based on a statistical model of response as defined by the primary endpoint, a weighted 90-day mRS (modified Rankin Scale, a measure of neurologic disability), across the treatment arms. Subjects will initially be equally randomized between 12, 24, and 48 hours of therapeutic cooling. After the first 200 subjects have been randomized, additional treatment arms between 12 and 48 hours will be opened and patients will be allocated, within each initial cardiac rhythm type (shockable or non-shockable), by response adaptive randomization. As the trial continues, shorter and longer duration arms may be opened. A maximum sample size of 1800 subjects is proposed. Secondary objectives are to characterize: the overall safety and adverse events associated with duration of cooling, the effect on neuropsychological outcomes, and the effect on patient reported quality of life measures. Discussion: In-vitro and in-vivo studies have shown the neuroprotective effects of therapeutic hypothermia for cardiac arrest. We hypothesize that longer durations of cooling may improve either the proportion of patients that attain a good neurological recovery or may result in better recovery among the proportion already categorized as having a good outcome. If the treatment effect of cooling is increasing across duration, for at least some set of durations, then this provides evidence of the efficacy of cooling itself versus normothermia, even in the absence of a normothermia control arm, confirming previous RCTs for OHCA survivors of shockable rhythms and provides the first prospective controlled evidence of efficacy in those without initial shockable rhythms. Trial registration: ClinicalTrials.gov (NCT04217551, 2019-12-30).
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BACKGROUND AND OBJECTIVES: Postoperative seizures are a common complication after surgical drainage of nonacute chronic subdural hematomas (SDHs). The literature increasingly supports the use of prophylactic antiepileptic drugs for craniotomy, a procedure that is often associated with larger collections and worse clinical status at admission. This study aimed to compare the incidence of postoperative seizures in patients treated with burr-hole drainage and those treated with craniotomy through propensity score matching (PSM). METHODS: A retrospective cohort analysis was conducted on patients with surgical drainage of nonacute SDHs (burr-holes and craniotomies) between January 2017 to December 2021 at 2 academic institutions in the United States. PSM was performed by controlling for age, subdural thickness, subacute component, and preoperative Glasgow Coma Scale. Seizure rates and accompanying abnormalities on electroencephalographic tracing were evaluated postmatching. RESULTS: A total of 467 patients with 510 nonacute SDHs underwent 474 procedures, with 242 burr-hole evacuations (51.0%) and 232 craniotomies (49.0%). PSM resulted in 62 matched pairs. After matching, univariate analysis revealed that burr-hole evacuations exhibited lower rates of seizures (1.6% vs 11.3%; P = .03) and abnormal electroencephalographic findings (0.0% vs 4.8%; P = .03) compared with craniotomies. No significant differences were observed in postoperative Glasgow Coma Scale (P = .77) and length of hospital stay (P = .61). CONCLUSION: Burr-hole evacuation demonstrated significantly lower seizure rates than craniotomy using a propensity score-matched analysis controlling for significant variables.
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Medium and long-chain triacylglycerol (MLCT) rich in n-3 polyunsaturated fatty acids (PUFAs) were obtained in three-hour interesterification of fish oil with medium-chain triacylglycerol (MCTs), using lipase bio-imprinted with surfactant as a catalyst. Initially, for bio-imprinted lipase preparation, the interesterification reaction conditions were optimized, resulting in a lipase with 1.47 times higher catalytic activity compared to control (non-bio-imprinted). Afterwards, the reaction conditions for MLCT synthesis were optimized, using bio-imprinted lipase as a catalyst. The reaction reached equilibrium within first three hours at 70 °C temperature, 4 wt% lipase load, and molar ratio of substrate 1:1.5. Under these conditions, final product contained 18.52% MCT, 56.65% MLCT, and 24.83% long-chain triacylglycerol (LCT). To reduce the MCT content, a solvent extraction process was performed, yielding 2.42% MCT, 56.19% MLCT, and 41.39% LCT. The obtained structured lipids (SLs), enriched in n-3 PUFAs, offer significant health benefits, enhanced bioavailability, with potential applications in functional foods and nutraceuticals.
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Ácidos Grasos Omega-3 , Aceites de Pescado , Lipasa , Triglicéridos , Lipasa/química , Lipasa/metabolismo , Triglicéridos/química , Ácidos Grasos Omega-3/química , Esterificación , Aceites de Pescado/química , Biocatálisis , Enzimas Inmovilizadas/química , Proteínas Fúngicas/químicaRESUMEN
The study presents a new parameter free adaptive exponentially weighted moving average (AEWMA) control chart tailored for monitoring process dispersion, utilizing an adaptive approach for determining the smoothing constant. This chart is crafted to adeptly detect shifts within anticipated ranges in process dispersion by dynamically computing the smoothing constant. To assess its effectiveness, the chart's performance is measured through concise run-length profiles generated from Monte Carlo simulations. A notable aspect is the incorporation of an unbiased estimator in computing the smoothing constant through the suggested function, thereby improving the chart's capability to identify different levels of increasing and decreasing shifts in process dispersion. The comparison with an established adaptive EWMA-S2 dispersion chart highlights the considerable efficiency of the proposed chart in addressing diverse magnitudes of process dispersion shifts. Additionally, the study includes an application to a real-life dataset, showcasing the practicality and user-friendly nature of the proposed chart in real-world situations.
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The Max-Mixed EWMA Exponentially Weighted Moving Average (MM EWMA) control chart is a statistical process control technique used for joint monitoring of the mean and variance of a process. This control chart is designed to detect small and moderate shifts in the mean and variance of a process by comparing the maximum of two statistics, one based on the mean and the other on the variance. In this paper, we propose a new MM EWMA control chart. The proposed chart is compared with existing control charts using simulation studies, and the results show that the chart performs better in detecting small and moderate shifts in both the mean and variance. The proposed chart can be helpful in quality control applications, where joint monitoring of mean and variance is necessary to ensure a product's or process's quality. The real-life application of the proposed control chart on yogurt packing in a cup data set shows the outperformance of the MM EWMA control chart. Both simulations & real-life application results demonstrate the better performance of the proposed chart in detecting smaller shifts during the production process.
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In the current study, we demonstrate the use of a quality framework to review the process for improving the quality and safety of the patient in the health care department. The researchers paid attention to assessing the performance of the health care service, where the data is usually heterogeneous to patient's health conditions. In our study, the support vector machine (SVM) regression model is used to handle the challenge of adjusting the risk factors attached to the patients. Further, the design of exponentially weighted moving average (EWMA) control charts is proposed based on the residuals obtained through SVM regression model. Analyzing real cardiac surgery patient data, we employed the SVM method to gauge patient condition. The resulting SVM-EWMA chart, fashioned via SVM modeling, revealed superior shift detection capabilities and demonstrated enhanced efficacy compared to the risk-adjusted EWMA control chart.
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Procedimientos Quirúrgicos Cardíacos , Máquina de Vectores de Soporte , Humanos , Procedimientos Quirúrgicos Cardíacos/métodos , Factores de Riesgo , Ajuste de Riesgo/métodosRESUMEN
This article introduces an adaptive approach within the Bayesian Max-EWMA control chart framework. Various Bayesian loss functions were used to jointly monitor process deviations from the mean and variance of normally distributed processes. Our study proposes the mechanism of using a function-based adaptive method that picks self-adjusting weights incorporated in Bayesian Max-EWMA for the estimation of mean and variance. This adaptive mechanism significantly enhances the effectiveness and sensitivity of the Max-EWMA chart in detecting process shifts in both the mean and dispersion. The Monte Carlo simulation technique was used to calculate the run-length profiles of different combinations. A comparative performance analysis with an existing chart demonstrates its effectiveness. A practical example from the hard-bake process in semiconductor manufacturing is presented for practical context and illustration of the chart settings and performance. The empirical results showcase the superior performance of the Adaptive Bayesian Max-EWMA control chart in identifying out-of-control signals. The chart's ability to jointly monitor the mean and variance of a process, its adaptive nature, and its Bayesian framework make it a useful and effective control chart.
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The simultaneous monitoring of both the process mean and dispersion has gained considerable attention in statistical process control, especially when the process follows the normal distribution. This paper introduces a novel Bayesian adaptive maximum exponentially weighted moving average (Max-EWMA) control chart, designed to jointly monitor the mean and dispersion of a non-normal process. This is achieved through the utilization of the inverse response function, particularly suitable for processes conforming to a Weibull distribution. To assess the effectiveness of the proposed control chart, we employed the average run length (ARL) and the standard deviation of run length (SDRL). Subsequently, we compared the performance of our proposed control chart with that of an existing Max-EWMA control chart. Our findings suggest that the proposed control chart demonstrates a higher level of sensitivity in detecting out-of-control signals. Finally, to illustrate the effectiveness of our Bayesian Max-EWMA control chart under various Loss Functions (LFs) for a Weibull process, we present a practical case study focusing on the hard-bake process in the semiconductor manufacturing industry. This case study highlights the adaptability of the chart to different scenarios. Our results provide compelling evidence of the exceptional performance of the suggested control chart in rapidly detecting out-of-control signals during the hard-bake process, thereby significantly contributing to the improvement of process monitoring and quality control.
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This paper aims to introduce a novel family of probability distributions by the well-known method of the T-X family of distributions. The proposed family is called a "Novel Generalized Exponent Power X Family" of distributions. A three-parameters special sub-model of the proposed method is derived and named a "Novel Generalized Exponent Power Weibull" distribution (NGEP-Wei for short). For the proposed family, some statistical properties are derived including the hazard rate function, moments, moment generating function, order statistics, residual life, and reverse residual life. The well-known method of estimation, the maximum likelihood estimation method is used for estimating the model parameters. Besides, a comprehensive Monte Carlo simulation study is conducted to assess the efficacy of this estimation method. Finally, the model selection criterion such as Akaike information criterion (AINC), the correct information criterion (CINC), the Bayesian information criterion (BINC), the Hannan-Quinn information criterion (HQINC), the Cramer-von-Misses (CRMI), and the ANDA (Anderson-Darling) are used for comparison purpose. The comparison of the NGEP-Wei with other rival distributions is made by Two COVID-19 data sets. In terms of performance, we show that the proposed method outperforms the other competing methods included in this study.
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COVID-19 , Humanos , Teorema de Bayes , México/epidemiología , COVID-19/epidemiología , Simulación por Computador , CanadáRESUMEN
The simultaneous monitoring of both process mean and dispersion, particularly in normal processes, has garnered significant attention within the field. In this article, we present a new Bayesian Max-EWMA control chart that is intended to track a non-normal process mean and dispersion simultaneously. This is accomplished through the utilization of the inverse response function, especially in cases where the procedure follows a Weibull distribution. We used the average run length (ARL) and the standard deviation of run length (SDRL) to assess the efficacy of our suggested control chart. Next, we contrast our suggested control chart's performance with an already-existing Max-EWMA control chart. Our results show that compared to the control chart under consideration, the proposed control chart exhibits a higher degree of sensitivity. Finally, we present a useful case study centered around the hard-bake process in the semiconductor manufacturing sector to demonstrate the performance of our Bayesian Max-EWMA control chart under different Loss Functions (LFs) for a Weibull process. The case study highlights how flexible the chart is to various situations. Our results offer strong proof of the outstanding ability of the Bayesian Max-EWMA control chart to quickly identify out-of-control signals during the hard-bake procedure. This in turn significantly contributes to the enhancement of process monitoring and quality control.
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The use of extracorporeal membrane oxygenation (ECMO) to support patients with cardiac arrest, cardiogenic shock, and acute respiratory distress syndrome is rising worldwide.1 While ECMO may save the lives of some of our sickest patients, the outlook of ECMO survivorship remains uncertain. Defining longer-term functional and neuropsychiatric outcomes in ECMO survivors is important for 3 reasons. First, critically ill patients are at high risk of experiencing postintensive care syndrome (PICS), defined as new physical, cognitive, or psychological impairments that present in survivors of critical illness after hospital discharge.2 PICS is associated with more severe illness and longer intensive care unit length of stay.3 Because ECMO is reserved for patients with refractory shock or hypoxia, patients treated with ECMO represent a severely ill patient population with prolonged length of stay, putting them at particularly high risk of developing PICS. Second, ECMO is associated with direct neurologic injury, including both macrohemorrhages and microhemorrhages, infarcts, and diffuse hypoxic-ischemic brain injury that likely contribute to long-term outcomes.4 Finally, ECMO is very expensive. A recent study determined that the average cost per admission for patients with COVID-19 placed on ECMO was nearly $850,000 more than those who received only mechanical ventilation.5 Understanding patient-centered outcomes will be an integral part of future cost-effectiveness analyses.
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COVID-19 , Oxigenación por Membrana Extracorpórea , Paro Cardíaco , Humanos , HospitalizaciónRESUMEN
[This corrects the article DOI: 10.1371/journal.pone.0293477.].
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Extracorporeal membrane oxygenation (ECMO) is a form of temporary cardiopulmonary bypass for patients with acute respiratory or cardiac failure refractory to conventional therapy. Its usage has become increasingly widespread and while reported survival after ECMO has increased in the past 25 years, the incidence of neurological injury has not declined, leading to the pressing question of how to improve time-to-detection and diagnosis of neurological injury. The neurological status of patients on ECMO is clinically difficult to evaluate due to multiple factors including illness, sedation, and pharmacological paralysis. Thus, increasing attention has been focused on developing tools and techniques to measure and monitor the brain of ECMO patients to identify dynamic risk factors and monitor patients' neurophysiological state as a function in time. Such tools may guide neuroprotective interventions and thus prevent or mitigate brain injury. Current means to continuously monitor and prevent neurological injury in ECMO patients are rather limited; most techniques provide indirect or postinsult recognition of irreversible brain injury. This review will explore the indications, advantages, and disadvantages of standard-of-care, emerging, and investigational technologies for neurological monitoring on ECMO, focusing on bedside techniques that provide continuous assessment of neurological health.
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Lesiones Encefálicas , Oxigenación por Membrana Extracorpórea , Insuficiencia Cardíaca , Insuficiencia Respiratoria , Adulto , Humanos , Niño , Oxigenación por Membrana Extracorpórea/efectos adversos , Oxigenación por Membrana Extracorpórea/métodos , Insuficiencia Cardíaca/etiología , Encéfalo , Lesiones Encefálicas/prevención & control , Lesiones Encefálicas/etiología , Insuficiencia Respiratoria/terapia , Estudios RetrospectivosRESUMEN
In this article, we introduce a novel Bayesian Max-EWMA control chart under various loss functions to concurrently monitor the mean and variance of a normally distributed process. The Bayesian Max-EWMA control chart exhibit strong overall performance in detecting shifts in both mean and dispersion across various magnitudes. To evaluate the performance of the proposed control chart, we employ Monte Carlo simulation methods to compute their run length characteristics. We conduct an extensive comparative analysis, contrasting the run length performance of our proposed charts with that of existing ones. Our findings highlight the heightened sensitivity of Bayesian Max-EWMA control chart to shifts of diverse magnitudes. Finally, to illustrate the efficacy of our Bayesian Max-EWMA control chart using various loss functions, we present a practical case study involving the hard-bake process in semiconductor manufacturing. Our results underscore the superior performance of the Bayesian Max-EWMA control chart in detecting out-of-control signals.
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Quality control often employs memory-type control charts, including the exponentially weighted moving average (EWMA) and Shewhart control charts, to identify shifts in the location parameter of a process. This article pioneers a new Bayesian Adaptive EWMA (AEWMA) control chart, built on diverse loss functions (LFs) such as the square error loss function (SELF) and the Linex loss function (LLF). The proposed chart aims to enhance the process of identifying small to moderate as well as significant shifts in the mean, signifying a notable advancement in the field of quality control. These are implemented utilizing an informative prior for both posterior and posterior predictive distributions, employing various paired ranked set sampling (PRSS) schemes. The effectiveness of the suggested chart is appraised using average run length (ARL) and the standard deviation of run length (SDRL). Monte Carlo simulations are employed to contrast the recommended approach against other control charts. The outcomes demonstrate the dignitary performance of the recommended chart in identifying out-of-control signals, especially applying PRSS designs, in comparison to simple random sampling (SRS). Finally, a practical application was conducted in the semiconductor manufacturing context to appraise the efficacy of the offered chart using various paired ranked set sampling strategies. The results reveal that the suggested control chart performed well in capturing the out-of-control signals far better than the already in use control charts. Overall, this study interposes a new technique with diverse LFs and PRSS designs, improving the precision and effectiveness in detecting process mean shifts, thereby contributing to advancements in quality control and process monitoring.
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PURPOSE: The neurologic examination of patients undergoing extracorporeal membrane oxygenation (ECMO) is crucial for evaluating irreversible encephalopathy but is often obscured by sedation or neuromuscular blockade. Noninvasive neuromonitoring modalities including diffuse correlation spectroscopy and EEG measure cerebral perfusion and neuronal function, respectively. We hypothesized that encephalopathic ECMO patients with greater degree of irreversible cerebral injury demonstrate less correlation between electrographic activity and cerebral perfusion than those whose encephalopathy is attributable to medications. METHODS: We performed a prospective observational study of adults undergoing ECMO who underwent simultaneous continuous EEG and diffuse correlation spectroscopy monitoring. (Alpha + beta)/delta ratio and alpha/delta Rartio derived from quantitative EEG analysis were correlated with frontal cortical blood flow index. Patients who awakened and followed commands during sedation pauses were included in group 1, whereas patients who could not follow commands for most neuromonitoring were placed in group 2. (Alpha + beta)/delta ratio-blood flow index and ADR-BFI correlations were compared between the groups. RESULTS: Ten patients (five in each group) underwent 39 concomitant continuous EEG and diffuse correlation spectroscopy monitoring sessions. Four patients (80%) in each group received some form of analgosedation during neuromonitoring. (Alpha + beta)/delta ratio-blood flow index correlation was significantly lower in group 2 than group 1 (left: 0.05 vs. 0.52, P = 0.03; right: -0.12 vs. 0.39, P = 0.04). Group 2 ADR-BFI correlation was lower only over the right hemisphere (-0.06 vs. 0.47, P = 0.04). CONCLUSIONS: Correlation between (alpha + beta)/delta ratio and blood flow index were decreased in encephalopathic ECMO patients compared with awake ones, regardless of the analgosedation use. The combined use of EEG and diffuse correlation spectroscopy may have utility in monitoring cerebral function in ECMO patients.
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In recent times, there has been a growing focus among researchers on memory-based control charts. The Exponentially Weighted Moving Average (EWMA) and Cumulative Sum (CUSUM) charts and the adaptive control charting approaches got the attention. Control charts are commonly employed to oversee processes, assuming the monitored variable follows a normal distribution. However, it's worth noting that this assumption does not hold true in many real-world situations. The use of the algebraic expression for normalization, which can be used for all kinds of skewed distributions with a closed-form distribution function, using the proposed continuous function to adapt a smoothing constant, motivates this study. In the present manuscript, we design an EWMA statistic-based adaptive control chart to monitor the irregular variations in the mean of two parametric Weibull distribution and use Hasting approximation for normalization. The adaptive control charts are used to update the smoothing constant according to the estimated shift. Here we use the proposed continuous function to adapt the smoothing constant. The average run length and standard deviation of run length are calculated under different parameter settings. The effectiveness of the proposed chart is argued in terms of ARLs over the considered EWMA chart through Monte-Carlo (MC) simulation method. The proposed chart is examined, followed by a real data set to demonstrate the design and application procedures.
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The article introduces a novel Bayesian AEWMA Control Chart that integrates different loss functions (LFs) like the square error loss function and Linex loss function under an informative prior for posterior and posterior predictive distributions, implemented across diverse ranked set sampling (RSS) designs. The main objective is to detect small to moderate shifts in the process mean, with the average run length and standard deviation of run length serving as performance measures. The study employs a hard bake process in semiconductor production to demonstrate the effectiveness of the proposed chart, comparing it with existing control charts through Monte Carlo simulations. The results underscore the superiority of the proposed approach, particularly under RSS designs compared to simple random sampling (SRS), in identifying out-of-control signals. Overall, this study contributes a comprehensive method integrating various LFs and RSS schemes, offering a more precise and efficient approach for detecting shifts in the process mean. Real-world applications highlight the heightened sensitivity of the suggested chart in identifying out-of-control signals compared to existing Bayesian charts using SRS.