Tilting homeostatic and dyshomeostatic microglial balance in health and disease:transforming growth factor-beta1 as a critical protagonist

Adult microglia,by continuously sensing changes in their environment and communicating with nearly all brain cell types,are considered to be the immune sentinels of the brain.In the healthy central nervous system(CNS),microglia display a unique molecular homeostatic signature(i.e.,Tmem119,P2ry12,Sall1,Siglech,Gpr34,and Hexb)(Figure 1A).

Unlocking hypoglycemia–associated brain microvascular dysfunction:critical insights from proteomic analysis

Hypoglycemia-a critical complication linked to worsened brain function in diabetic subjects:Hypoglycemia is characterized by a decline in circulatory glucose levels below sta nda rd physiological thresholds.Mild hypoglycemia,classified as level 1 hypoglycemia,is defined by blood glucose levels below 70 mg/dL and can be effectively addressed through carbohydrate intake.Severe hypoglycemia,denoted by blood glucose levels less than 54 mg/dL,poses a life-threatening risk if left untreated.Individuals with type 1 and type 2 diabetes undergoing insulin treatment are particularly susceptible to hypoglycemia due to impaired counterregulatory mechanisms.

Deep eutectic solvents for separation and purification applications in critical metal metallurgy:Recent advances and perspectives

Solvent extraction,a separation and purification technology,is crucial in critical metal metallurgy.Organic solvents commonly used in solvent extraction exhibit disadvantages,such as high volatility,high toxicity,and flammability,causing a spectrum of hazards to human health and environmental safety.Neoteric solvents have been recognized as potential alternatives to these harmful organic solvents.In the past two decades,several neoteric solvents have been proposed,including ionic liquids(ILs)and deep eutectic solvents(DESs).DESs have gradually become the focus of green solvents owing to several advantages,namely,low toxicity,degradability,and low cost.In this critical review,their classification,formation mechanisms,preparation methods,characterization technologies,and special physicochemical properties based on the most recent advancements in research have been systematically described.Subsequently,the major separation and purification applications of DESs in critical metal metallurgy were comprehensively summarized.Finally,future opportunities and challenges of DESs were explored in the current research area.In conclusion,this review provides valuable insights for improving our overall understanding of DESs,and it holds important potential for expanding separation and purification applications in critical metal metallurgy.

Integrated risk management: a Petrobras application in offshore well construction safety to minimize critical emergency disconnections

In order to avoid mistakes and to save a great deal of time in analysis, an innovative methodology was developed that can analyze the well operations and rig characteristics involved to define the best emergency disconnect sequence （EDS） available. A solution was developed based on the characteristics of the rigs and blowout preventers （BOPs）, and six variables were considered that directly affect the choice of EDS. All possible combinations of 64 scenarios were analyzed, and the priority of choice of the EDS was defined empirically. This paper presents an approach to EDS risk management and examples of exposure time （time without riser safety margin and shear capability） for the same well, which can be lowered from 13% to 0.1%. The impact of this reduction is related to the ability of the BOP to cut some of the heavy casings, in addition to improved availability of EDS modes. This implementation opened up many possibilities for the performance of risk exposure analysis, enabling comparison of several BOP configurations of contracted rigs and selection of the best options. This innovative approach allowed a better management of the rig schedules, prioritizing safety aspects and making it possible to allocate the fleet in a systematic way.

Endoscopic ultrasound guided radiofrequency ablation for pancreatic tumors: A critical review focusing on safety, efficacy and controversies

The role of endoscopic ultrasound(EUS)in the last two decades has shifted from a diagnostic tool to an important therapeutic tool treating mainly pancreatobiliary disorders.In recent years,its applications for treating pancreatic diseases have broadened,including the implementation of radiofrequency ablation(RFA),which has been traditionally used for treating solid tumors.In this critical indepth review,we summarized all the papers throughout the literature regarding EUS-RFA for pancreatic neuroendocrine neoplasms,adenocarcinoma,and pancreatic cystic lesions.Overall,for pancreatic neuroendocrine neoplasms we identified 16 papers that reported 96 patients who underwent EUS-RFA,with acceptable adverse events that were rated mild to moderate and a high complete radiological resolution rate of 90%.For pancreatic adenocarcinoma,we identified 8 papers with 121 patients.Adverse events occurred in 13%of patients,mostly rated mild.However,no clear survival benefit was demonstrated.For pancreatic cystic lesions,we identified 4 papers with 38 patients.The adverse events were mostly mild and occurred in 9.1%of patients,and complete or partial radiological resolution of the cysts was reported in 36.8%.Notably,the procedure was technically feasible for most of the patients.Nevertheless,a long road remains before this technique finds its definite place in guidelines due to several controversies.EUS-RFA for pancreatic tumors seems to be safe and effective,especially for pancreatic neuroendocrine neoplasms,but multicenter prospective trials are needed to consider this treatment as a gold standard.

The Efficacy and Safety of Continuous Popliteal Sciatic Nerve Block for the Relief of Pain Associated with Critical Limb Ischemia: A Retrospective Study

Background: Patients with critical limb ischemia (CLI) often suffer from severe pain. A continuous peripheral nerve block has been shown to provide effective analgesia for patients having lower limb surgery. We have been administering continuous sciatic nerve block (CSNB) for patients with CLI whose pain could not be relieved by other analgesic tools. The aim of this retrospective study was to investigate the efficacy and safety of CSNB for patients with CLI. Method: We retrospectively investigated 99 patients who received CSNB for the relief of severe pain in the lower limb associated with CLI. Patient demographics, neurological history, complications, and subjective evaluation of the effectiveness of CSNB were investigated from their clinical records. The distal tips of 108 catheters were cultured. Result: One hundred and seventy-two catheters were placed in 99 patients. More than 90% of the patients enjoyed considerable relief of severe pain. The analgesic effect of CSNB was greater in patients with older age and hemodialysis. Thirty-one catheters had positive bacterial colonization. However, no severe infectious complication was found. There was no relationship between the co-existence of diabetes and positive bacterial colonization. We encountered a patient with ASO and diabetes who suffered from persistent motor weakness and hypesthesia even after 3 months of CSNB placement. Conclusions: CSNB provided good pain control for patients with severe pain caused by CLI. Although catheters were frequently found to be colonized, infection at the catheter site was self-limiting even in patients with diabetes.

Anti-lipid-oxidation effects and edible safety evaluation of the oil extracted by a supercritical CO_(2) process from coix seed fermented by Monascus purpureus

The physicochemical properties and composition of coix seed oil produced by Monascus purpureus fermentation and supercritical CO_(2)extraction were determined.Anti-lipid-oxidation and edible safety were evaluated using a cholesterol-fish oil model,acute oral toxicity assay,and genetic toxicity assay in vitro and in vivo,respectively.The results show that the extraction oil from fermented coix seed(FCS-O)had good physicochemical quality and abundant active components with physiological function.In particular,γ-tocotrienol,γ-oryzanol,coixenolide and oleic acid concentrations reached 72.83μg/g,745.96μg/g,9.65 mg/g and 316.58 mg/100 g DW,respectively.The FCS-O exhibited higher antioxidant capability in inhibiting lipid oxidation and peroxidation.Compared to the blank control,the concentrations of 7-ketocholestreol and peroxide only were 8.42μg/mL and 16.16 mmol/kg at 168 h of oxidation(P<0.01).In addition,the FCS-O has been confirmed to be a very safe edible oil,with no acute toxicity(LD50>10 g/kg bw,considered actually non-toxic)and no induced mutagenicity,cytotoxicity or genotoxicity.These results serve as a good safety reference for future application of the oil from fermented coix seed.The development and utilization of this kind of oil will be beneficial as a food,food ingredient,nutritional supplement,or natural food antioxidant to promote good health function.

Nursing Diagnoses of the Domain Safety/Protection and Socioeconomic and Clinical Aspects of Critical Patients

Objective: The objective is to correlate the nursing diagnoses of the domain Safety/Protection of NANDA-I in critically ill patients with sociodemographic and clinical data. Method: A cross-sectional study with 86 individuals was conducted, from October 2013 to May 2014 in the Intensive Care Unit of a university hospital in northeastern Brazil, through a formal interview and physical examination. Results: It was possible to identify a total of 20 significant statistical associations, and 15 were clinically justified by the literature, namely: risk for aspiration and reason for admission;impaired dentition and age;risk for peripheral neurovascular dysfunction and sex and comorbidity;skin integrity and comorbidity;risk for impaired skin integrity and gender and reason for admission;impaired tissue integrity and gender and reason for admission;risk for perioperative positioning injury and reason for admission;risk for thermal injury and age and comorbidity;delayed surgical recovery and reason for admission;risk for poisoning and years of schooling;and risk for imbalanced body temperature and age. Conclusions: By understanding the relationship between customers’ answers and the sociodemographic and clinical profile, positive health outcomes can be achieved in particular in the prevention of risks facing vulnerability characteristics, providing greater safety and protection for the critical customer.

Cross-Layer Safety-Critical Broadcast Service Architecture Integrating VANETs with 3G Networks in loT Environments

As Vehicle Ad Hoc Networks (VANETs) is part of the applications of the Internet of Things (IoT), and Vehicles in VANETs periodically broadcast the beacon message for status advertisement to provide public safety, the impacts of the network parameters on the reliability of broadcast messages are investigated and discussed; meanwhile, a cross-layer safety-critical broadcast service architecture is proposed to obtain an optimized set of packet loss rate and delay based on the Neural Networks (NN) and Back Propagation (BP) algorithm to dynamically adjust the transmission rate-power pairs. Simulation results illustrate that the proposed mechanism can effectively improve the reliability performance while maintaining the fairness among vehicles.

Safety-Critical System Reliability Modeling and Their Analyses in Terms of Effects of Component Failure Modes

New models of safety-critical systems are built here. In these systems, when components fail, different defect states have different effects, hence need different ways to measure. In the models, there are two kinds of failure modes of the components： one could be called failed-safe, and the other may be named failed- dangerous In practice, the so-called failed-dangerous components may lead a system to peril. However, failed-safe components will not. Reliability and safety issues are analyzed using Ion-Channel modeling theory to get count of repairs and time duration before the system becomes dangerous. In the closing section a numerical example is presented to illustrate the results obtained in the paper.

面向Critical MTC的无连接传输

关键机器类通信(Critical MTC)对时延和可靠性都有极高的要求。支持海量Critical MTC的终端是一个巨大挑战。提出了一种面向海量Critical MTC终端的无连接传输方案。为了降低时延,提出了基于竞争的无连接单次传输方案;为了实现高可靠性,设计了具有极低导频碰撞概率的稀疏正交多导频。进一步利用大规模多输入多输出(MIMO)的增益来提高可靠性以及在空域复用大量用户。仿真结果表明,提出的方案可以支持海量Critical MTC终端,同时满足低时延和高可靠的严格要求。

An Augmented Framework for Formal Analysis of Safety Critical Systems

This paper presents an augmented framework for analyzing Safety Critical Systems (SCSs) formally. Due to high risk of failure, development process of SCSs is required more attention. Model driven approaches are the one of ways to develop SCSs for accomplishing critical and complex function what SCSs are supposed to do. Two model driven approaches: Unified Modeling Language (UML) and Formal Methods are combined in proposed framework which enables the analysis, designing and testing safety properties of SCSs more rigorously in order to reduce the ambiguities and enhance the correctness and completeness of SCSs. A real time case study has been discussed in order to validate the proposed framework.

基于openSAFETY的功能安全通信协议研究

针对数据传输可靠性低导致功能安全事故频发的问题,进行了基于POWERLINK的openSAFETY功能安全通信协议研究;在实时工业以太网协议POWERLINK的基础上设计了以PCP-AP为架构的openSAFETY安全节点,设计了基于FPGA软核处理器的POWERLINK内核层的软件硬件结构,设计了基于单片机MCU的openSAFETY安全应用接口程序以及近底层通信接口程序,搭建了以贝加莱PLC为安全控制节点的功能安全通信实验平台,依据故障分析设计了电磁干扰实验,模拟了工业现场中出现不同程度电磁干扰情况下功能安全通信平台的通信情况,并与非功能安全通信平台进行对比,验证了安全节点的可靠性和必要性。

Relationship between critical seismic acceleration coefficient and static factor of safety of 3D slopes

Many analytical methods have been adopted to estimate the slope stability by providing various stability numbers,e.g.static safety of factor(static FoS)or the critical seismic acceleration coefficient,while little attention has been given to the relationship between the slope stability numbers and the critical seismic acceleration coefficient.This study aims to investigate the relationship between the static FoS and the critical seismic acceleration coefficient of soil slopes in the framework of the upper-bound limit analysis.Based on the 3D rotational failure mechanism,the critical seismic acceleration coefficient using the pseudo-static method and the static FoS using the strength reduction technique are first determined.Then,the relationship between the static FoS and the critical seismic acceleration coefficient is presented under considering the slope angleβ,the frictional angleφ,and the dimensionless coefficients B/H and c/γH.Finally,a fitting formula between the static FoS and the critical seismic acceleration coefficient is proposed and validated by analytical and numerical results.

Safety and effectiveness of butorphanol in epidural labor analgesia:A protocol for a systematic review and meta-analysis

BACKGROUND Epidural analgesia is the most effective analgesic method during labor.Butorphanol administered epidurally has been shown to be a successful analgesic method during labor.However,no comprehensive study has examined the safety and efficacy of using butorphanol as an epidural analgesic during labor.AIM To assess butorphanol's safety and efficacy for epidural labor analgesia.METHODS The PubMed,Cochrane Library,EMBASE,Web of Science,China National Knowledge Infrastructure,and Google Scholar databases will be searched from inception.Other types of literature,such as conference abstracts and references to pertinent reviews,will also be reviewed.We will include randomized controlled trials comparing butorphanol with other opioids combined with local anesthetics for epidural analgesia during labor.There will be no language restrictions.The primary outcomes will include the visual analog scale score for the first stage of labor,fetal effects,and Apgar score.Two independent reviewers will evaluate the full texts,extract data,and assess the risk of bias.Publication bias will be evaluated using Egger's or Begg's tests as well as visual analysis of a funnel plot,and heterogeneity will be evaluated using the Cochran Q test,P values,and I2 values.Meta-analysis,subgroup analysis,and sensitivity analysis will be performed using RevMan software version 5.4.This protocol was developed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses(PRISMA)Protocols statement,and the PRISMA statement will be used for the systematic review.RESULTS This study provides reliable information regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.CONCLUSION To support clinical practice and development,this study provides evidence-based findings regarding the safety and efficacy of using butorphanol as an epidural analgesic during labor.

Why Formal Methods Are Considered for Safety Critical Systems?

Formal methods are the mathematically techniques and tools which are used at early stages of software development lifecycle processes. The utter need of using formal methods in safety critical system leads to accuracy, consistency and correctness in proposed system. In safety critical real time application, requirements should be unambiguous and very accurate which can be achieved by using mathematical theorems. There is utter need to focus on the requirement phase which is the most critical phase of SDLC. This paper focuses on the use of Z notation for incorporating the accuracy, consistency, and eliminates ambiguity in safety critical system: Road Traffic Management System as a case study. The syntax, semantics, type checking and domain checking are further verified by using Z/EVES: a Z notation type checker tool.

Mental health status among COVID-19 patients survivors of critical illness in Saudi Arabia:A 6-month follow-up questionnaire study

BACKGROUND Psychological assessment after intensive care unit(ICU)discharge is increasingly used to assess patients'cognitive and psychological well-being.However,few studies have examined those who recovered from coronavirus disease 2019(COVID-19).There is a paucity of data from the Middle East assessing the post-ICU discharge mental health status of patients who had COVID-19.AIM To evaluate anxiety and depression among patients who had severe COVID-19.METHODS This is a prospective single-center follow-up questionnaire-based study of adults who were admitted to the ICU or under ICU consultation for>24 h for COVID-19.Eligible patients were contacted via telephone.The patient’s anxiety and depression six months after ICU discharge were assessed using the Hospital Anxiety and Depression Scale(HADS).The primary outcome was the mean HADS score.The secondary outcomes were risk factors of anxiety and/or depression.RESULTS Patients who were admitted to the ICU because of COVID-19 were screened(n=518).Of these,48 completed the questionnaires.The mean age was 56.3±17.2 years.Thirty patients(62.5%)were male.The main comorbidities were endocrine(n=24,50%)and cardiovascular(n=21,43.8%)diseases.The mean overall HADS score for anxiety and depression at 6 months post-ICU discharge was 11.4(SD±8.5).A HADS score of>7 for anxiety and depression was detected in 15 patients(30%)and 18 patients(36%),respectively.Results from the multivariable ordered logistic regression demonstrated that vasopressor use was associated with the development of anxiety and depression[odds ratio(OR)39.06,95% confidence interval:1.309-1165.8;P<0.05].CONCLUSION Six months after ICU discharge,30% of patients who had COVID-19 demonstrated a HADS score that confirmed anxiety and depression.To compare the psychological status of patients following an ICU admission(with vs without COVID-19),further studies are warranted.

Testing Result Statistics-Based Rapid Testing Method for Safety-Critical System

Safety-critical system （SCS） has highly demand for dependability, which requires plenty of resource to ensure that the system under test （SUT） satisfies the dependability requirement. In this paper, a new SCS rapid testing method is proposed to improve SCS adaptive dependability testing. The result of each test execution is saved in calculation memory unit and evaluated as an algorithm model. Then the least quantity of scenario test case for next test execution will be calculated according to the promised SUT＇s confidence level. The feedback data are generated to weight controller as the guideline for the further testing. Finally, a compre- hensive experiment study demonstrates that this adaptive testing method can really work in practice. This rapid testing method, testing result statistics-based adaptive control, makes the SCS dependability testing much more effective.

Thermal safety boundary of lithium-ion battery at different state of charge

Thermal runaway(TR)is a critical issue hindering the large-scale application of lithium-ion batteries(LIBs).Understanding the thermal safety behavior of LIBs at the cell and module level under different state of charges(SOCs)has significant implications for reinforcing the thermal safety design of the lithium-ion battery module.This study first investigates the thermal safety boundary(TSB)correspondence at the cells and modules level under the guidance of a newly proposed concept,safe electric quantity boundary(SEQB).A reasonable thermal runaway propagation(TRP)judgment indicator,peak heat transfer power(PHTP),is proposed to predict whether TRP occurs.Moreover,a validated 3D model is used to quantitatively clarify the TSB at different SOCs from the perspective of PHTP,TR trigger temperature,SOC,and the full cycle life.Besides,three different TRP transfer modes are discovered.The interconversion relationship of three different TRP modes is investigated from the perspective of PHTP.This paper explores the TSB of LIBs under different SOCs at both cell and module levels for the first time,which has great significance in guiding the thermal safety design of battery systems.

Efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer

BACKGROUND Ovarian cancer is one of the most common malignant tumors in female reproductive system in the world,and the choice of its treatment is very important for the survival rate and prognosis of patients.Traditional open surgery is the main treatment for ovarian cancer,but it has the disadvantages of big trauma and slow recovery.With the continuous development of minimally invasive technology,minimally invasive laparoscopic surgery under general anesthesia has been gradually applied to the treatment of ovarian cancer because of its advantages of less trauma and quick recovery.However,the efficacy and safety of minimally invasive laparoscopic surgery under general anesthesia in the treatment of ovarian cancer are still controversial.AIM To explore the efficacy and safety of general anesthesia minimally invasive surgery in the treatment of ovarian cancer.METHODS The clinical data of 90 patients with early ovarian cancer in our hospital were analyzed retrospectively.According to the different surgical treatment methods,patients were divided into study group and control group(45 cases in each group).The study group received minimally invasive laparoscopic surgery under general anesthesia for ovarian cancer,while the control group received traditional open surgery for ovarian cancer.The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire(EORTC QLQ-C30),clinical efficacy and safety of the two groups were compared.RESULTS The intraoperative blood loss,length of hospital stay,postoperative gas evacuation time,and postoperative EORTC QLQ-C30 score of the study group were significantly better than those of the control group(P<0.05).The incidence of postoperative complications in the study group was significantly lower than in the control group(P<0.05).The two groups had no significant differences in the preoperative adrenocorticotropic hormone(ACTH),androstenedione(AD),cortisol(Cor),cluster of differentiation 3 positive(CD3+),and cluster of differentiation 4 positive(CD4+)indexes(P>0.05).In contrast,postoperatively,the study group's ACTH,AD,and Cor indexes were lower,and the CD3+and CD4+indexes were higher than those in the control group(P<0.05).CONCLUSION Minimally invasive laparoscopic surgery under general anesthesia in patients with early ovarian cancer can significantly improve the efficacy and safety,improve the short-term prognosis and quality of life of patients,and is worth popularizing.