Functional Safety Research Articles

Stored platelet hemostatic phenotype and function is not altered when donors are on testosterone replacement therapy.

Critical shortages in the national blood supply have led to a re-evaluation of previously overlooked donor sources for blood products. As a part of that effort, red blood cells collected from therapeutic phlebotomy of donors on testosterone replacement therapy (TRT) have been conditionally approved for transfusion. However, platelets from TRT donors are not currently approved for use due to limited data on effects of supraphysiologic testosterone on recipient safety and platelet function. The objective of this study was to provide a comprehensive profile of phenotype and function in platelets from TRT and control donors. Platelets in plasma were collected from TRT and control donors (N = 10 per group; age- and sex-matched) and stored at room temperature for 7 days. On storage Day 1 (D1) and Day 7 (D7), platelet products were analyzed for platelet count, metabolic parameters (i.e., glucose, lactate, mitochondrial function), surface receptor expression, aggregation, thrombin generation, and thrombus formation under physiological flow conditions. TRT donor platelets were not significantly different than control donor platelets in terms of count, surface phenotype, metabolic function, ability to aggregate, thrombin generation, or ability to form occlusive thrombus under arterial flow regimes. Both groups were similar to each other by D7, but had significantly lost hemostatic function compared to D1. Platelets derived from donors undergoing TRT have similar phenotypic and functional profiles compared to those derived from control donors. This suggests that therapeutic phlebotomy of TRT donors may provide a useful source for platelet products.

Methodology for risk assessment of multi-event scenarios on radioactive waste repository

Deep geological disposal, which is a permanent method that isolates a storage facility in rocks 200 to 1000 m deep underground, plays a role in safely disposing spent nuclear fuel to prevent excessive radioactive species from leaking out and its safety should be primarily proved. Risk for various radionuclide leakage scenarios should be calculated to be used as a safety indicator. One of the scenarios that significantly affects the safety of repository is the occurrence of external events such as an earthquake scenario. Several occurrences of such external disasters are expected over a long period of time which the safety functions of the deep disposal site must be maintained. Rather than performing a conservative single event evaluation, we expected that performing a more realistic evaluation, such as considering the number of events, is preferrable for design and operation optimization, particularly in an early project phase. This paper suggests a need for assessing multi-event scenarios and the methodology for simulation of several external disasters using earthquakes as an example. The methodology and algorithm of simulating multiple earthquakes and assessing risk distribution under those events at repository site is introduced in GoldSim software, and its results are expected to be used at simulating other event scenarios.

Peer-to-Peer Ultra-Wideband Localization for Hands-Free Control of a Human-Guided Smart Stroller.

We propose a hands-free control system for a human-guided smart stroller. The proposed method uses real-time peer-to-peer localization technology of the human and stroller to realize an intuitive hands-free control system based on the relative position between the human and the stroller. The control method is also based on functional and mechanical safety to ensure the safety of the stroller's occupant (child) and the pilot (parent) during locomotion. In this paper, first, we present a preliminary investigation of the humans' preference for the relative position in the context of hands-free guided strollers. Then, we present the control method and a prototype implemented with an electric wheelchair and UWB sensors for localization. We present an experimental evaluation of the proposed method with 14 persons walking with the developed prototype to investigate the usability and soundness of the proposed method compared to a remote joystick and manual operation. The evaluation experiments were conducted in an indoor environment and revealed that the proposed method matches the performance of joystick control but does not perform as well as manual operation. Notably, for female participants, the proposed method significantly surpasses joystick performance and achieves parity with manual operation, which shows its efficacy and potential for a smart stroller. Also, the results revealed that the proposed method significantly decreased the user's physical load compared to the manual operation. We present discussions on the controllability, usability, task load, and safety features of the proposed method, and conclude this work with a summary assessment.

Efficacy and Safety of Exogenous Ketones in People with Mild Neurocognitive Disorder and Alzheimer's Disease: A Systematic Literature Review.

Mild neurocognitive disorder (NCD), formally known as mild cognitive impairment, is usually the clinical stage preceding the development of Alzheimer's disease (AD), the most prevalent major NCD, and other causes of dementia. Glucose is a major source of energy for human brain metabolism and the uptake of glucose is reduced in patients with mild NCD, AD, and other NCDs. Unlike glucose, the uptake of ketones remains normal in people with mild NCD and AD, suggesting that the use of ketone bodies may compensate for glucose energy deficiency in patients with mild NCD and AD. The aim of this systematic review was to summarize the efficacy and safety of exogenic ketones, including medium chain triglycerides (MCTs), on cognitive function in patients with mild NCD and AD. The Embase, MEDLINE, MEDLINE In-Process, PubMed Ahead-of-Print, Cochrane Central Register of Controlled Trials, Europe PMC databases were searched from inception to April 2022. Studies reporting cognitive function efficacy and safety outcomes from randomized controlled trials of exogenic ketones in patients with mild NCD and AD were included. Data were extracted by 1 reviewer and checked by a second reviewer. Risk of bias was assessed using the Cochrane risk of bias tool, version 2. This review identified 13 individual trials investigating the efficacy and safety of MCT or coconut oil for patients with mild NCD or with AD. Because of the heterogeneity of the studies, a narrative synthesis was used. Overall, improvements associated with exogenic ketones were observed in multiple aspects of cognitive abilities, although the large heterogeneity between the included studies makes it difficult to draw firm conclusions from the current literature. Although some studies investigated the impact of the apolipoprotein E ε4 allele status on treatment efficacy, the current data are insufficient to conclude whether such an effect is present. PROSPERO registration No. CRD42022336664.

Operational Amplifiers Defect Detection and Localization Using Digital Injectors and Observer Circuits

Operational amplifiers (op amps) are fundamental blocks that find wide application both as stand-alone devices and as crucial blocks embedded in various Systems on Chips (SoCs). Achieving high defect coverage, as well as performing defect localization in these circuits, has proven to be a difficult/expensive task, even with sophisticated testing circuitry. The ISO 26262 standard for functional safety (FuSa) includes the stringent requirement that an automotive IC must have a very high defect coverage. This reinforces the need to ensure the functionality of analog and mixed (AMS) circuits, especially in mission critical applications. This paper presents an all-digital op amp defect detection, diagnosis, and localization method that can be used both for production and in-field tests and discusses various implementation of the proposed method. We validated our results using extensive transistor-level simulations of multiple op amp architectures using TSMC 180 nm technology. Across op amp architectures and multiple implementation approaches, we achieved a worst-case and best-case defect coverage of 94.5% and 99%, respectively. Furthermore, in this work, we also propose a defect diagnosis and localization strategy using recorded bit streams from states of digital injectors and detectors.

Targeted Ablation Using Ultrasound-Guided Irreversible Electroporation of Index Tumors (TARGET Study): Prospective Development Study Evaluating Safety, Patient-Reported Outcomes, and Oncologic Efficacy.

We studied patient-reported functional outcomes, safety, and oncologic efficacy of focal irreversible electroporation as a primary treatment for intermediate-risk prostate cancer. Between February 2015 and April 2017, 20 consecutive patients elected irreversible electroporation and underwent 22 treatments. All underwent MRI-targeted and systematic transrectal biopsies. Eligibility criteria were grade group 2/3 prostate cancer in a maximum of 2 adjacent sextant prostate sectors in 1 hemigland without extraprostatic extension on MRI. Ablation was performed with a 5-mm cancer margin. Any grade group 1 cancer outside mapped index lesion was untreated. Outcome measures were based on the Prostate Quality of Life Survey, Male Sexual Health Questionnaire, and MRI-targeted and systematic biopsies at 3 and 12 months. Nineteen patients completed irreversible electroporation. One had electrocardiographic changes, and irreversible electroporation was aborted. No deterioration was detected in urinary or sexual domains (-0.2, 95% CI -1.4, 0.9, P = .7, and -1.9, 95% CI -10.1, 6.4, P = .6, respectively) or health-related quality of life (-0.2, 95% CI -1.4, 1.0, P = .7) at 6 months post ablation. Ejaculation volume decreased at 12 months (-1.5 points, 95% CI -2.4, -0.5, P = .003). At 12 months of follow-up, 14/19 patients (74%, 95% CI 49%, 91%) had no clinically significant cancer anywhere in the prostate. Radical treatment-free survival was 79% at 2 years (95% CI 53%, 92%) and 73% at 4 years (95% CI 47%, 88%). Our data show promising oncologic and functional outcomes following focal irreversible electroporation treatment for carefully selected patients with intermediate-risk prostate cancer. Further research should compare irreversible electroporation with active surveillance.

Endovascular Thrombectomy With and Without Preceding Thrombolysis in Posterior Circulation Stroke—Insights From STAR

Background Multiple randomized trials could not establish the noninferiority of endovascular thrombectomy (EVT) alone without preceding intravenous thrombolysis (IVT) or superiority of IVT followed by EVT in anterior circulation large‐vessel occlusion stroke. The role of prior IVT in posterior circulation large‐vessel occlusion remains controversial. Methods In this multicenter, retrospective study, patients with stroke with large‐vessel occlusion in the posterior circulation who received EVT alone or with IVT were selected from the stroke thrombectomy and aneurysm registry between 2013 and 2022. Effects of IVT followed by thrombectomy on favorable functional outcome (defined as modified Rankin scale≤3 at 90 days) and safety were investigated using multivariable logistic and linear regression models. Results Of the 588 included patients, 67% (n = 394) were treated with EVT alone and 29% (n = 170) with EVT after IVT, and 4% (n = 24) have missing values on this variable. Controlling for multiple confounding factors, IVT was not associated with a higher likelihood of favorable functional outcome at 90 days (odds ratio, 1.04 [95% CI, 0.52–2.09; P = 0.901). Thrombectomy alone did not show any safety advantages compared with those receiving IVT. Conclusion Similar functional outcomes and complication rates were seen in patients with posterior circulation large‐vessel occlusion treated with EVT alone versus EVT after IVT. Further prospective studies are required to determine the utility of IVT in posterior circulation stroke, especially in patients being directly admitted to thrombectomy centers.

Comparative evaluation of reproductive organ-preserving versus standard radical cystectomy in female: a meta-analysis and systematic review of perioperative, oncological, and functional outcomes.

To evaluate the perioperative, oncological, and functional outcomes of reproductive organ-preserving radical cystectomy (ROPRC) compared to standard radical cystectomy (SRC) in the treatment of female bladder cancer. A systematic search was conducted in November 2023 across several scientific databases. We executed a systematic review and cumulative meta-analysis of the primary outcomes of interest, adhering to the PRISMA and AMSTAR guidelines. The study was registered in PROSPERO (CRD42024501522). The meta-analysis included 10 studies with a total of 2015 participants. ROPRC showed a significant reduction in operative time and postoperative fasting period compared to SRC (MD -45.69, 95% CI -78.91 ~ -12.47, p = 0.007, and MD -0.69, 95% CI -1.25 ~ -0.13, p = 0.02, respectively). Functional outcomes, both daytime continence rate (OR 4.94, 95% CI 1.53 ~ 15.91, p = 0.008) and nighttime continence rate (OR 5.91, 95% CI 1.94 ~ 18.01, p = 0.002), and sexual function measured by the Female Sexual Function Index (MD 5.72, 95% CI 0.19 ~ 11.26, p = 0.04), were significantly improved in the ROPRC group. There were no significant differences between ROPRC and SRC in terms of estimated blood loss, length of hospital stay, overall postoperative complications, minor complications or major complications. Oncologically, both procedures showed comparable outcomes with no significant differences in positive surgical margins, tumor recurrence rates, overall survival, cancer-specific survival, recurrence-free survival, or progression-free survival. ROPRC is a viable and effective alternative to SRC in female bladder cancer patients, offering enhanced functional outcomes and similar oncological safety. These findings suggest that ROPRC can improve the quality of life in female bladder cancer patients without compromising the efficacy of cancer treatment.

Virtual Reality Application for the Safety Improvement of Intralogistics Systems

Immersive technologies from the spectrum of Industry 4.0, such as Virtual Reality (VR), are increasingly used in research and safety analysis in industrial and intralogistics systems, including distribution warehouses and production plants. Safety in intralogistics systems is influenced by design and management processes, human behavior, and device performance. In all these areas, VR can serve as a supportive technology for visualization, testing, and employee training. However, this requires the development of principles for integrating VR into standard procedures for the design, modernization, and analysis of intralogistics and production systems. This article discusses the use of VR to analyze the occupational and functional safety of intralogistics systems. It reviews the literature and VR implementations aimed at examining and improving safety in industrial systems. The article explores the integration of VR into the design and analysis procedures for intralogistics and production systems. The authors present a five-dimensional decision space for assessing the use of VR, including identifying subjects of safety analysis, threats and hazards specific to intralogistics, countermeasures for these threats, factors affecting safety, and mechanisms by which VR can improve safety in intralogistics systems. As a subsequent step, the authors discuss using universal simulation environments that support VR technology to study and enhance safety in intralogistics systems, providing a framework example based on the FlexSim (2023 update 2) environment. Finally, this article addresses the threats and limitations of VR technology, along with the challenges and future prospects of VR in the context of Industry 4.0. The article concludes that VR can be an essential tool for increasing safety in the future, albeit with some reservations about certain features of this technology.

Concept design, application and optimization of operational parameters for new forced safety injection tank system

Background The engineered safety systems are designed to execute fundamental safety functions encompassing reactivity confinement, reactivity control and decay heat removal. Failure of any one of these functions can result in severe accident conditions. Passive systems have been implemented as a better option for plant safety. This research proposes a modification of existing safety injection tanks to the new forced safety injection tanks (FSITs) that utilize the backpressure from the pressurizer or steam generator to drive coolant into the reactor core under high pressure conditions. Methods FSITs aim to extend the coping-time during accidents like Station Blackout, providing an extended timing window for deployment of FLEX systems. The mathematical design is proposed and implemented into the thermal-hydraulic input of a nuclear power plant to demonstrate the system’s applicability that was demonstrated by leveraging the conventional PRA approach and risk quantification. Results The suggested system useful when used in the accident scenario of Station black out in-coincident with turbine-driven pumps fail to run. As the proposed design is a conceptual design, the optimization of associated operational parameters and set points is necessary. This optimization is performed using the risk analysis and virtual control environment-based Dynamic Probabilistic Risk Assessment framework. The method and findings of this study affirm that the coping-time for Station Blackout can be significantly extended, ensuring a substantial margin for the effective deployment of the FLEX. Conclusions A concept design of a passive forced safety injection system was suggested and demonstrated by integrating the mathematical model into a thermal-hydraulic model of a nuclear power plant. The parameters were optimized and the results demonstrated that the new system was effective in recovering the nuclear power plant from the accidents such as SBO with turbine-driven pumps fail to operate.

Final outcome analysis from the phase II TUXEDO-1 trial of trastuzumab-deruxtecan in HER2-positive breast cancer patients with active brain metastases

Brain metastases (BM) are a devastating complication of HER2-positive metastatic breast cancer (BC) and treatment strategies providing optimized local and systemic disease control are urgently required. The antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) improved progression-free survival (PFS) and overall survival (OS) over trastuzumab emtansine but data regarding intracranial activity is limited. In the primary outcome analysis of TUXEDO-1, a high intracranial response rate (RR) was reported with T-DXd. Here, we report final PFS and OS results. TUXEDO-1 accrued adult patients with HER2-positive BC and active BM (newly diagnosed or progressing) without indication for immediate local therapy. The primary endpoint was intracranial RR; secondary endpoints included PFS, OS, safety, quality-of-life (QoL), and neurocognitive function. PFS and OS were estimated with the Kaplan-Meier method and analysed in the per-protocol population. At 26.5 months median follow-up, median PFS was 21 months (95% CI 13.3-n.r.) and median OS was not reached (95% CI 22.2-n.r.). With longer follow-up, no new safety signals were observed. The most common grade 3 adverse event was fatigue (20%). Grade 2 interstitial lung disease and a grade 3 symptomatic drop of left-ventricular ejection fraction were observed in one patient each. QoL was maintained over the treatment period. T-DXd yielded prolonged intra- and extracranial disease control in patients with active HER2-positive BC BM in line with results from the pivotal trials. These results support the concept of ADCs as systemic therapy for active BM.

In-situ measurements of contact evolution for fractal rough surfaces under normal compression

The contact interface plays a key role in the overall functionality and stability of structures. Understanding the evolution of the contact interface over time and its dependency on materials and load is crucial for functional integrity and operational safety assessment. In this study, we employ in-situ three-dimensional X-ray computed tomography (3DXRCT) to examine the creep behavior of 3D-printed surfaces exhibiting various roughness under constant normal compression. We observe that the overall contact area enlargement during the contact creep decreases with roughness amplitude and fractal dimension. The variation of interfacial separation distance is found to increase with roughness amplitude and decrease with fractal dimension. Correlation analysis reveals that the microcontact size played a more important role than the asperity shape in determining the microcontact enlargement. By examining the calculated interfacial strains extracted from XRCT measurements, significant deformations are found to occur at the non-contacting zones, indicating strong asperity interactions. This study offers high-resolution experimental measurements and unravels the asperity micromechanics for contact creep on rough surfaces, providing insights into understanding and optimizing the performance of rough interfaces.

Safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy for living donor kidney transplantation: A comparison with left retroperitoneal laparoscopic donor nephrectomy.

The left kidney is often preferred for living donor kidney transplantation because of its anatomical advantages. However, the right kidney may be procured due to donor conditions. Few studies have assessed the safety and graft outcome of right retroperitoneal laparoscopic donor nephrectomy (RDN). This study aimed to compare the outcomes between right and left RDN with respect to donor outcome and the graft function of recipients. This retrospective study included 230 consecutive living donor kidney transplants performed at our institution between May 2019 and March 2023. We reviewed the outcomes of kidney transplant in the right and left kidneys after RDN. A total of 230 living donor kidney transplants were performed, with 32 donors receiving right RDN (right RDN group) and 198 donors receiving left RDN (left RDN group). The renal veins and ureters were significantly shorter in the right RDN group than in the left RDN group (both p < .001). Donor operation and warm ischemia time were significantly longer in the right RDN group than in the left RDN group (p = .012 and p < .001, respectively). None of the groups exhibited any cases of delayed graft function owing to donor-related reasons. Perioperative changes in the estimated glomerular filtration rate of recipients and death-censored graft survival were not significantly different between the two groups. In RDN, the outcomes of right donor nephrectomy were comparable to those of left donor nephrectomy in terms of donor safety and recipient renal function.

EXTENDING SYSTEMS ENGINEERING FOR SAFETY‐CRITICAL DEFENCE APPLICATIONS

AbstractDefence sector applications are often characterised by a high level of complexity: in the technical systems involved, in their management and supply chain arrangements, and in the dynamic nature of the risks involved. ISO/IEC/IEEE 15288 is well established as a standard that provides a common set of life cycle processes and terminology for engineering complex systems. However, it takes a generic approach that does not directly address the needs of systems with a safety impact. In contrast, safety‐specific standards like IEC 61508 provide a well‐known framework for the functional safety of electrical, electronic, and programmable electronic safety‐related systems, but do not address the complexity commonly found in systems in the defence sector.In IEC 63187‐1, the International Electrotechnical Commission is drafting a new standard to provide a safety framework for defence applications. It uses modern systems engineering principles that build on ISO/IEC/IEEE 15288, extending it with requirements to make it appropriate for critical systems in the defence sector. This paper discusses how IEC 63187‐1 uses ISO/IEC/IEEE 15288 to achieve the goals of system safety, why this approach was adopted, the expected benefits and some of the impacts of designing the new safety framework this way.

Enhancing equipment qualification testing facility for nuclear power plants: Achieving rapid temperature and pressure increase during design basis events

The present study focuses on the development of an equipment qualification (EQ) testing facility for Class 1E equipment in nuclear power plants (NPPs), emphasizing the need to ensure safety functions under design basis events (DBEs). The Republic of Korea (ROK) has implemented international safety standards to support large NPP projects, necessitating the development of domestic EQ testing facilities to reduce the dependence on foreign facilities. To address this need, herein, a specialized facility capable of simulating harsh DBE conditions that may occur in NPPs in ROK was constructed. Through exhaustive research, target temperature and pressure profiles were developed for pressurized water reactors, and a superheated steam injection technique was devised for rapid temperature and pressure changes. The present study contributes to the advancement of domestic EQ testing capabilities, achieving up to 230 °C and 700 kPa within 30 s.

Deep learning-driven optimization design for the configuration of lazy-wave umbilical cables

Umbilical cables are essential components of subsea production systems for deep sea oil and gas exploration. Umbilical cables are often set to specific configurations that compensate for the motion of the floating body resulting from harsh environmental loads during operation to ensure structural safety and proper functioning. However, the optimization design of the umbilical cable configuration is a challenging problem owing to highly nonlinear relationship between loads and structural responses as well as the huge computational cost of evaluating numerous sea state combinations. This study proposes a deep learning-driven optimization design framework based on the residual artificial neural network to address the configuration design of lazy-wave umbilical cables. A parallel accelerated computation method based on Adam optimizer was established for the generation of the database. The transfer learning technique was also introduced into the deep learning model to build a configuration design prediction model based on small samples, which significantly reduced the cost of model building and training. Based on the above optimization design framework, a combination of tensile and bending optimization for a lazy-wave umbilical cable configuration was achieved, verifying the effectiveness and practicality of the proposed approach. This study provides an important reference for the rapid engineering design of umbilical cables.

Concept of Multifactor Method and Non-Functional Requirements Solution to Increase Resilience through Functional Safety with Cybersecurity Analysis

In the process of designing safety systems, an integrated approach in safety and cybersecurity analysis is necessary. The paper describes a new technique of increasing resilience through integrated analysis of functional safety and cybersecurity. It is a modeling methodology based on the combination of the multifactor method utilizing modified risk graphs, used previously for Safety Integrity Level (SIL) assessment, and the Non-Functional Requirements (NFR) approach. The NFR approach, based on the analysis of graphical representation of conceptual and physical components of the system, contributes a technique to include cybersecurity through the Softgoal Interdependency Graph. The assessment methodology is outlined in detail and applied to a case study involving an industrial control system. The analysis turns out to be effective in both aspects: confirming the findings of the multifactor approach based on modified risk graphs and complementing the traditional analysis to increase resilience in discovering and mitigating security vulnerabilities for SIL assessment by the use of NFR.

Diagnosis-based design of electric power steering system considering multiple degradations: role of designable generative adversarial network anomaly detection

Abstract Recently, interest in functional safety has surged because vehicle technology increasingly relies on electronics and automation. Failure of certain system components can endanger driver safety and is costly to address. The detection of abnormal data is crucial for enhancing the reliability, safety, and efficiency. This study introduces a novel anomaly-detection method of designable generative adversarial network anomaly detection (DGANomaly). DGANomaly combines the data augmentation method of a designable generative adversarial network (DGAN) with a generative adversarial network anomaly-detection data classification technique. DGANomaly not only generates virtual data that are challenging to obtain or simulate but also produces a range of statistical design variables for normal and abnormal data. This approach enables the specific identification of normal and abnormal design variables. To demonstrate its effectiveness, the DGANomaly method was applied to an electric power steering (EPS) model when multiple degradations of gear stiffness, gear friction, and rack displacement were considered. An EPS model was constructed and validated using simulation programs such as Prescan, Amesim, and Simulink. Consequently, DGANomaly exhibited a higher classification accuracy than the other methods, allowing for more accurate detection of abnormal data. Additionally, a clearer range of statistical designs can be obtained for normal data. These results indicate that the statistical design variables that are less likely to fail can be obtained using minimal data.

Assessment of continuous low-dose and high-dose burst of inhaled nitric oxide in spontaneously breathing COVID-19 patients: A randomized controlled trial

BackgroundInhaled nitric oxide (iNO) showed to improve oxygenation at low doses by reducing intrapulmonary shunt and to display antiviral properties at high doses. To assess the safety and potential benefits, we designed an exploratory clinical trial comparing low-dose with intermittent high-dose iNO to only intermittent high-dose iNO in hypoxemic COVID-19 patients. MethodsIn this single-center interventional non-inferiority randomized trial (ClinicalTrials.gov, NCT04476992), twenty oxygen-dependent COVID-19 patients were randomly assigned to the high-dose (200 ppm for 30 min) + continuous low-dose (20 ppm) iNO group (iNO200/20) or the high-dose iNO group (iNO200). Methemoglobinemia (MetHb) assessed 48 h after iNO initiation was the primary endpoint. Reverse-transcription polymerase chain reaction for SARS-CoV-2, inflammatory markers during hospitalization, and heart ultrasounds during the iNO200 treatments were evaluated. ResultsMetHb difference between iNO groups remained within the non-inferiority limit of 3 %, indicating comparable treatments despite being statistically different (p-value<0.01). Both groups presented similar SpO2/FiO2 ratio at 48 h (iNO200 vs. iNO200/20 341[334–356] vs. 359 [331–380], respectively, p-value = 0.436). Both groups showed the same time to SARS-CoV-2 negativization, hospital length of stay, and recovery time. iNO-treated patients showed quicker SARS-CoV-2 negativization compared to a similar group of non-iNO patients (HR 2.57, 95%CI 1.04–6.33). During the 228 treatments, iNO200 and iNO200/20 groups were comparable for safety, hemodynamic stability, and respiratory function improvement. ConclusionsiNO200/20 and iNO200 are equally safe in non-intubated patients with COVID-19-induced respiratory failure with regards to MetHb and NO2. Larger studies should investigate whether iNO200/20 leads to better outcomes compared to non-iNO treated patients.

Embedding More Autonomous Safety in MCUs-Based Embedded Systems using Project-Based Learning (case study)

In this research, we present a new technique for learning embedded systems design (ES) that integrates Project-Based Learning (PBL) with conventional face-to-face learning. The PBL course uses a project-based learning approach which offers insights for effective safety feature implementation, concentrates on ES or IoT applications and highlights security in the developed system. This is achieved by using Safety co-processors and Microcontrollers which are secure and cost-effective. Furthermore, the study highlights the key safety modules suitable for integration into MCUs. Additionally, we propose implementing a functional safety layer including a safety co-processor equipped with trusted input/output controllers that contribute to identifying potential failures and increase the system fault tolerance.