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Industrial control systems (ICS) are vital parts of the physical infrastructure for many industrial assets, such as oil and gas fields, water stations, and power generation plants. Inadequate protection of such critical assets may lead to disruption of vital services and substantial monetary losses. Therefore, the safety of these assets is prioritized as national security. Operational technology networks have a unique nature and different requirements than conventional enterprise networks as they seek tailored security solutions to detect and prevent cyberattacks on such attractive targets. Motivated by a necessary need from industry and academia, this paper aims to present a broad survey of the research works related to developing Intrusion Detection Systems in ICS networks focusing on using recent machine learning techniques. A proposed review methodology is presented and applied to the relevant selected literature. The paper offers a comparative analysis to provide better insights into this domain, where it identifies several unresolved challenges that present intriguing research prospects for the industry and academic community. [ABSTRACT FROM AUTHOR]

This paper introduces the Integrated Security Embedded Resilience Architecture (ISERA) as an advanced resilience mechanism for Industrial Control Systems (ICS) and Operational Technology (OT) environments. The ISERA framework integrates security by design principles, micro-segmentation, and Island Mode Operation (IMO) to enhance cyber resilience and ensure continuous, secure operations. The methodology deploys a Forward-Thinking Architecture Strategy (FTAS) algorithm, which utilises an industrial Intrusion Detection System (IDS) implemented with Python's Network Intrusion Detection System (NIDS) library. The FTAS algorithm successfully identified and responded to cyber-attacks, ensuring minimal system disruption. ISERA has been validated through comprehensive testing scenarios simulating Denial of Service (DoS) attacks and malware intrusions, at both the IT and OT layers where it successfully mitigates the impact of malicious activity. Results demonstrate ISERA's efficacy in real-time threat detection, containment, and incident response, thus ensuring the integrity and reliability of critical infrastructure systems. ISERA's decentralised approach contributes to global net zero goals by optimising resource use and minimising environmental impact. By adopting a decentralised control architecture and leveraging virtualisation, ISERA significantly enhances the cyber resilience and sustainability of critical infrastructure systems. This approach not only strengthens defences against evolving cyber threats but also optimises resource allocation, reducing the system's carbon footprint. As a result, ISERA ensures the uninterrupted operation of essential services while contributing to broader net zero goals. [ABSTRACT FROM AUTHOR]

The purpose of this paper is to emphasize the importance of application of the appropriate model for security management in contemporary security emergencies. Given the complex nature of security situations and the involvement of multiple security actors i.e. institutions in their management, it is essential to deliver an effective outcome and minimize consequences and further escalation. In the direction of descriptive elaboration, the models of the incident command system and the incident command system of the next generation, which is the officially adopted crisis management mechanism in the Republic of North Macedonia, are briefly defined and presented. With their organizational hierarchy characteristics for human and material resources designation, they counterpoise a common platform for real-time data sharing and situational awareness. North Macedonia has adapted the NICS system which is used to coordinate the national all-hazards response within the context of civil-military cooperation in various security circumstances. The NICS is developed on the Incident Command System developed by the Federal Emergency Management Agency as a standardized approach to multifaceted incidents for a coordinated response among different jurisdictions and entities. The initial hypothesis in this paper refers to the premise that in a contemporary environment, the implementation of the optimal security management model should include the dimension of communication in the form of information and data sharing, coordination of the execution of the decisions made, and a standardized approach to action. The independent variable in addition to the hypothesis is that the application of an appropriate management model aims to create a flexible response with unified action from multiple relevant institutions from different domains of social activities and should standardize and coordinate the efforts undertaken. The methodology applied for this research includes qualitative and quantitative data analysis from relevant primary and secondary sources extracted from field simulation and empirical examples, deductive argumentation, comparison method, retrospective review and forecasting conclusions.

Abstract Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators.

Security is a complex issue in critical infrastructure like industrial control systems (ICS) since its leakages cause critical damage. Protecting the ICS environment from external threats, cyber-attacks, and natural disasters is important. Various works have been done on anomaly detection in ICS, and it has been identified that these proposed approaches are the sole models associated with them. Although there is a research gap in anomaly detection methodologies because of their computational complexity. To overcome the research gap of high false positive rate (precision), accuracy, and computational complexity in the literature, the study presents an Improved autoencoder (ImpAE) anomaly detection methodology for anomaly detection in ICS. The proposed methodology is a deep learning-based model to build anomaly detectors that alarm the attacks affecting ICS security. This methodology follows a flexible and modular design that permits a group of numerous detectors to get suitable detection. To express the suitability of the proposed model, we implemented it on the Secure water testbed (SWat) dataset, which is collected from a working water treatment plant. Experimental work shows that by using ImpAE, gaining a precision of 0.993 and an accuracy of 96%, in comparision to the existing results in the literature. With precision and accuracy, we gained a recall of 0.673 and an F1-Score of 0.771, which is better than the average of the other works. The used dataset was attained from ITrust Center, Singapore University of Digital Science, reliable for anomaly detection in an ICS environment. [ABSTRACT FROM AUTHOR]

Inhaler therapy and physical activity (PA) are important methods of chronic obstructive pulmonary disease (COPD) management. This study aimed to investigate the additional benefit of moderate-to-vigorous PA (MVPA) in patients with COPD using a long-acting beta-agonists (LABA)/long-acting muscarinic antagonist (LAMA) combination. We emulated a target trial to estimate the benefit of MVPA in patients with COPD using a dual ultra-long-acting bronchodilators. We enrolled patients aged ≥ 40 who were diagnosed with COPD between 2014 and 2018, initiated a LABA/LAMA combination, and had not undergone regular MVPA. The main exposure was the initiation of MVPA, defined as vigorous aerobic exercise > 20 min per day on ≥ 3 days/week or moderate aerobic exercise > 30 min per day on ≥ 5 days/week. The main outcomes were the future usage of inhaled corticosteroids (ICS) and severe exacerbation. We identified 1,526 patients who initiated MVPA and 4,516 who did not. The median follow-up period was 3.0 years. The hazard ratio (HR) for future ICS usage in the MVPA initiation group was 0.83 (95% confidence intervals (CI): 0.72, 0.97) compared to the control group. The HR for severe exacerbation in the MVPA initiation group was 0.81 (95% CI: 0.68, 0.96) compared to the control group. Subgroup analyses by age, sex, body mass index, residence area, smoking and drinking status showed consistent benefits in these outcomes. Initiation of MVPA may offer an additional benefit for even COPD patients who use a dual ultra-long-acting bronchodilators. [ABSTRACT FROM AUTHOR]

Main conclusion: The key genetic variation underlying the evo-devo of ICS in Solanaceae may be further pinpointed using an integrated strategy of forward and reverse genetics studies under the framework of phylogeny. The calyx of Physalis remains persistent throughout fruit development. Post-flowering, the fruiting calyx is inflated rapidly to encapsulate the berry, giving rise to a “Chinese lantern” structure called inflated calyx syndrome (ICS). It is unclear how this novelty arises. Over the past 2 decades, the role of MADS-box genes in the evolutionary development (evo-devo) of ICS has mainly been investigated within Solanaceae. In this review, we analyze the main achievements, challenges, and new progress. ICS acts as a source for fruit development, provides a microenvironment to protect fruit development, and assists in long-distance fruit dispersal. ICS is a typical post-floral trait, and the onset of its development is triggered by specific developmental signals that coincide with fertilization. These signals can be replaced by exogenous gibberellin and cytokinin application. MPF2-like heterotopic expression and MBP21-like loss have been proposed to be two essential evolutionary events for ICS origin, and manipulating the related MADS-box genes has been shown to affect the ICS size, sepal organ identity, and/or male fertility, but not completely disrupt ICS. Therefore, the core genes or key links in the ICS biosynthesis pathways may have undergone secondary mutations during evolution, or they have not yet been pinpointed. Recently, we have made some encouraging progress in acquiring lantern mutants in Physalis floridana. In addition to technological innovation, we propose an integrated strategy to further analyze the evo-devo mechanisms of ICS in Solanaceae using forward and reverse genetics studies under the framework of phylogeny. [ABSTRACT FROM AUTHOR]

The use of digital twins (DTs) in the electric power industry and other industries is a hot topic of research, especially concerning the potential of DTs to improve processes and management. This paper aims to present approaches to the creation of DTs and models in general. It also examines the key parameters of these models and presents the challenges that need to be addressed in the future development of this field. Our analysis of the DTs and models discussed in this paper is carried out on the basis of identified key characteristics, which serve as criteria for an evaluation and comparison that sets the basis for further investigation. A discussion of the findings shows the potential of DTs and models in different sectors. The proposed recommendations are based on this analysis, and aim to support the further development and use of DTs. Research into DTs represents a promising sector with high potential. However, several key issues and challenges need to be addressed in order to fully realize their benefits in practice.

Key management is critical to secure operation. Distributed control systems, such as Supervisory Control and Data Acquisition (SCADA) systems, have unique operational requirements that make conventional key management solutions less effectiveand burdensome. This paper pres-ents a novel Kerberos-based framework for automated, disruption-tolerant key management for control system environments. Experimental tests and their results are presented to quantify the expected performance overhead of this approach. Additionally, Zeek sensor analytics are presented to aid in monitoring the health and security of the key management framework operation.

Due to an increase in the number of attacks on Industrial Control Systems (ICS), the security of these systems is now of paramount concern. Many solutions have been proposed to defend such systems, particularly those adopting Machine Learning (ML). The goal of this study is to increase the likelihood of the solution being deployed into a real environment. As part of that, multiple interviews were held with industry experts who have been embedded within ICS cyber-security for decades. The findings revealed that the current security solutions for ICS lack the sophistication required to be adopted due to flawed assumptions made about the end-user. Therefore, this work provides personas of each end-user group within ICS that need to be taken into consideration when designing a security solution. In addition, wireframes are provided showing what a desired solution could look like. By sharing these findings, it is hoped to inform those working within this space and increase the likelihood of their solutions being adopted within a real environment. Furthermore, the expert panel requested a number of features that do not currently exist within the ICS cyber-security space, therefore, by sharing these with the wider community, it is hoped that the field will move closer towards providing solutions containing these features. [ABSTRACT FROM AUTHOR]

Introduction: Nyctereutes procyonoides koreensis (Korean raccoon dog), a member of the Canidae family, is anatomically similar to dogs. Previous studies have used vertebral heart scale measurements to measure the cardiac size of Korean raccoon dogs on thoracic radiographs; however, the use of additional cardiac size indices, such as vertebral left arial score, intercostal space, cardiothoracic ratio, and echocardiographic indices, has not been reported. Therefore, this study aimed to establish normal reference ranges for various thoracic radiographic and echocardiographic indices in normal Korean raccoon dogs. Methods: Twenty-six Korean raccoon dogs (11 males and 15 females) were included in this study. The thoracic radiographic indices, vertebral heart scale score, and vertebral left atrial score were measured in the right lateral view. The intercostal space and cardiothoracic ratio were measured in the ventrodorsal view. The echocardiograms were evaluated in the right parasternal long and short axis view and left parasternal apical view. Results: The mean values for the thoracic radiographic and echocardiographic indices were as follows: vertebral heart scale, 9.12 ± 0.74; vertebral left atrial score, 1.5 ± 0.31; intercostal spaces, 3.17 ± 0.34; cardiothoracic ratio, 0.69 ± 0.07; left atrial to aortic root ratio, 1.22 ± 0.14; main pulmonary artery to aorta ratio, 1.22 ± 0.14; left ventricular end-diastolic internal diameter normalized for body weight, 1.36 ± 0.19; end-diastolic volume index, 51.07 ± 19.6; end-systolic volume index, 16.54 ± 7.45; the peak velocity of early diastolic transmitral flow, 73.13 ± 15.46 cm/s; and the ratio between the transmitral flow velocities and the peak early diastolic velocity, 1.77 ± 0.47. Only percent increase in the left ventricular end-systolic internal diameter was negatively correlated with body weight. The remaining indices showed no correlations with body weight. Conclusion: To the best of our knowledge, this is the first case report covering both thoracic radiographic and endocardiographic indices for Korean raccoon dogs. Thus, the thoracic radiographic and echocardiographic indices established in this study may be used to evaluate the cardiac condition of Korean raccoon dogs. [ABSTRACT FROM AUTHOR]

Background: Asthma is routinely treated with inhaled corticosteroids (ICS). Asthma patients on ICS are at increased risk of adrenal suppression, a potentially serious effect of long‐term glucocorticoid exposure; however, this relationship is poorly understood. Therefore, this study aims to identify metabolite biomarkers related to adrenal suppression in asthma patients taking ICS. Methods: A total of 571 urine metabolites from 200 children with asthma on ICS in the Pharmacogenetics of Adrenal Suppression with Inhaled Steroids (PASS) cohort were profiled. Samples were grouped by peak plasma cortisol measurement as adrenal sufficient (>350 nmol/L) or insufficient (≤350 nmol/L) (outcome). Regression and discriminant‐based statistical models combined with network analyses were utilized to assess relationships between metabolites and the outcome. Finally, prioritized metabolites were validated using data from an ancillary study of the Childhood Asthma Management (CAMP) cohort with similar characteristics to PASS. Results: Ninety metabolites were significantly associated with adrenal suppression, of which 57 also could discriminate adrenal status. While 26 metabolites (primarily steroids) were present at lower levels in the adrenal insufficient patients, 14 were significantly elevated in this group; the top metabolite, mannitol/sorbitol, was previously associated with asthma exacerbations. Network analyses identified unique clusters of metabolites related to steroids, fatty acid oxidation, and nucleoside metabolism, respectively. Four metabolites including urocanic acid, acetylcarnitine, uracil, and sorbitol were validated in CAMP cohort for adrenal suppression. Conclusions: Urinary metabolites differ among asthma patients on ICS, by adrenal status. While steroid metabolites were reduced in patients with poor adrenal function, our findings also implicate previously unreported metabolites involved in amino acid, lipid, and nucleoside metabolism. [ABSTRACT FROM AUTHOR]

The increased short-channel effects in the ultra-nanoscale regime limit the operation of complementary metal oxide semiconductor (CMOS) technology. To combat the issues in the ultra-nanoscale regime, fin-shaped field effect transistor (FinFET) technology is the best choice because of its numerous advantages over CMOS technology. FinFET enhances the further scaling of the devices and control over the channel. Therefore, this research paper presents the implementation of a low leakage 4:2 compressor in FinFET technology. A compressor is a general block, especially used in multiplier units and hence in digital signal processing (DSP) systems. The design of the low power compressor improves the overall efficiency of the DSP systems. An extensive study of the proposed low power 4:2 compressor at 7 nm technology node is done in the paper. Mentor Graphics tools are used for the circuit simulations and analyzes. The key parameters, such as leakage power, delay, power delay product (PDP), and the process voltage temperature (PVT) variations, are estimated for the performance evaluation. The proposed 4:2 compressor saves 87.33% of leakage power and is 75.90% more energy efficient compared to its conventional counterpart. [ABSTRACT FROM AUTHOR]

Rigorous testing methods are essential for ensuring the security and reliability of industrial controller software. Fuzzing, a technique that automatically discovers software bugs, has also proven effective in finding software vulnerabilities. Unsurprisingly, fuzzing has been applied to a wide range of platforms, including programmable logic controllers (PLCs). However, current approaches, such as coverage-guided evolutionary fuzzing implemented in the popular fuzzer American Fuzzy Lop Plus Plus (AFL++), are often inadequate for finding logical errors and bugs in PLC control logic applications. They primarily target generic programming languages like C/C++, Java, and Python, and do not consider the unique characteristics and behaviors of PLCs, which are often programmed using specialized programming languages like Structured Text (ST). Furthermore, these fuzzers are ill suited to deal with complex input structures encapsulated in ST, as they are not specifically designed to generate appropriate input sequences. This renders the application of traditional fuzzing techniques less efficient on these platforms. To address this issue, this paper presents a fuzzing framework designed explicitly for PLC software to discover logic bugs in applications written in ST specified by the IEC 61131-3 standard. The proposed framework incorporates a custom-tailored PLC runtime and a fuzzer designed for the purpose. We demonstrate its effectiveness by fuzzing a collection of ST programs that were crafted for evaluation purposes. We compare the performance against a popular fuzzer, namely, AFL++. The proposed fuzzing framework demonstrated its capabilities in our experiments, successfully detecting logic bugs in the tested PLC control logic applications written in ST. On average, it was at least 83 times faster than AFL++, and in certain cases, for example, it was more than 23,000 times faster. [ABSTRACT FROM AUTHOR]

Security is a complex issue in critical infrastructure like industrial control systems (ICS) since its leakages cause critical damage. Protecting the ICS environment from external threats, cyber-attacks, and natural disasters is important. Various works have been done on anomaly detection in ICS, and it has been identified that these proposed approaches are the sole models associated with them. Although there is a research gap in anomaly detection methodologies because of their computational complexity. To overcome the research gap of high false positive rate (precision), accuracy, and computational complexity in the literature, the study presents an Improved autoencoder (ImpAE) anomaly detection methodology for anomaly detection in ICS. The proposed methodology is a deep learning-based model to build anomaly detectors that alarm the attacks affecting ICS security. This methodology follows a flexible and modular design that permits a group of numerous detectors to get suitable detection. To express the suitability of the proposed model, we implemented it on the Secure water testbed (SWat) dataset, which is collected from a working water treatment plant. Experimental work shows that by using ImpAE, gaining a precision of 0.993 and an accuracy of 96%, in comparision to the existing results in the literature. With precision and accuracy, we gained a recall of 0.673 and an F1-Score of 0.771, which is better than the average of the other works. The used dataset was attained from ITrust Center, Singapore University of Digital Science, reliable for anomaly detection in an ICS environment.

The security of industrial control protocol is the cornerstone to ensure ICS’s stable operation, a large number of industrial control protocols in the design phase ignore the consideration of security, resulting in most of the mainstream industrial control protocols generally having vulnerabilities. Considering the ICS architecture and the developmental characteristics of industrial control protocols, the various vulnerabilities and attack threats commonly faced by industrial control protocols were systematically summarized. At the same time, for the unknown potential vulnerabilities of industrial control protocols, the vulnerability mining techniques of industrial control protocols were analyzed in-depth, including the static symbolic execution-based, code audit-based, and fuzzing-based. The protocol design security protection technology was comprehensively dissected from the three directions of industrial control protocol specification design, communication mechanism, and third-party middleware. In addition, the future development trend of industrial control protocol security was further prospected from the aspects of sandbox development, security protection, and vulnerability mining.

Ying Lan,1 Die Hu,1 Shijing Huang,1 Qing Ma,1 Li Chen,2,3 Min Xu,1 Qin He1 1Department of Pharmacy, Affiliated Hospital of Southwest Jiaotong University, The Third People’s Hospital of Chengdu, Chengdu, Sichuan, 610031, People’s Republic of China; 2Department of Pharmacology, Faculty of Medicine, University of the Basque Country, UPV/EHU, Leioa, Spain; 3Department of Pharmacy and Evidence-Based Pharmacy Center, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Ying Lan; Li Chen, Email lanying0212@126.com; chenl_hxey@scu.edu.cnPurpose: This study conducted a pharmacovigilance analysis based on the FDA Adverse Event Reporting System (FAERS) database to compare the infection risk of inhaled or nasal Beclomethasone, Fluticasone, Budesonide, Ciclesonide, Mometasone, and Triamcinolone Acetonide.Methods: We used proportional imbalance analysis to evaluate the correlation between ICS /INCs and infection events. The data was extracted from the FAERS database from April 2015 to September 2023. Further analysis was conducted on the clinical characteristics, site of infection, and pathogenic bacteria of ICS and INCs infection adverse events (AEs). We used bubble charts to display their top 5 infection adverse events.Results: We analyzed 21,837 reports of infection AEs related to ICS and INCs, with an average age of 62.12 years. Among them, 61.14% of infection reports were related to females. One-third of infections reported to occur in the lower respiratory tract with Fluticasone, Budesonide, Ciclesonidec, and Mometasone; over 40% of infections reported by Triamcinolone Acetonide were eye infections; the rate of oral infections caused by Beclomethasone were 7.39%. The reported rates of fungal and viral infections caused by beclomethasone were 21.15% and 19.2%, respectively. The mycobacterial infections caused by Budesonide and Ciclesonidec account for 3.29% and 2.03%, respectively. Bubble plots showed that the ICS group had more fungal infections, oral infections, pneumonia, tracheitis, etc. The INCs group had more eye symptoms, rhinitis, sinusitis, nasopharyngitis, etc.Conclusion: Women who use ICS and INCs are more prone to infection events. Compared to Budesonide, Fluticasone seemed to have a higher risk of pneumonia and oral candidiasis. Mometasone might lead to more upper respiratory tract infections. The risk of oral infection was higher with Beclomethasone. Beclomethasone causes more fungal and viral infections, while Ciclesonide and Budesonide are more susceptible to mycobacterial infections.Keywords: data mining, FAERS, ICS, INCs, pharmacovigilance, infections

Introduction: Despite the proven benefits of inhaled corticosteroid (ICS)-containing triple therapy for chronic obstructive pulmonary disease (COPD), clinicians limit patient exposure to ICS due to the risk of pneumonia. However, there are multiple factors associated with the risk of pneumonia in patients with COPD. This post hoc analysis of IMPACT trial data aims to set the risks associated with ICS into a context of specific patient-related factors that contribute to the risk of pneumonia. Methods: The 52-week, double-blind IMPACT trial randomized patients with symptomatic COPD and ≥1 exacerbation in the prior year 2:2:1 to once-daily fluticasone furoate (FF)/umeclidinium (UMEC)/vilanterol (VI), FF/VI or UMEC/VI. Annual rate of on-treatment pneumonias in the intent-to-treat population associated with age, body mass index (BMI), percent predicted forced expiratory volume in 1 s (FEV1) and blood eosinophil count (BEC) was evaluated. Results: This analysis revealed that the annual rate of pneumonia showed the lowest risk at the age of 50 years. The 95% confidence intervals (CI) between ICS-containing and non-ICS containing treatments diverged in ages > 63 years, suggesting a significantly increased ICS-related risk in older patients. In contrast, the annual rate of pneumonia rose in both groups below BMI of 22.5 kg/m2, but above that, there was no relationship to pneumonia rate and no differential effect between the two groups. The relationship between BEC and pneumonia was flat up to > 300/µL cells with ICS-containing treatment and then rose. In contrast, the rate of pneumonia with non-ICS containing treatment appeared to increase at a lower level of BEC (~ 200/µL). Conclusions: There was little evidence of a differential effect of older age, lower BMI, lower FEV1 and BEC on the pneumonia rate between ICS-containing and non-ICS containing treatments. This analysis points to the need for a balanced approach to risk versus benefit in the use of ICS-containing treatments in COPD. Clinical trial registration: IMPACT ClinicalTrials.gov number, NCT02164513. [ABSTRACT FROM AUTHOR]

PRRS is a viral disease that profoundly impacts the global swine industry, causing significant economic losses. The development of a novel and effective vaccine is crucial to halt the rapid transmission of this virus. There have been several vaccination attempts against PRRSV using both traditional and alternative vaccine design development approaches. Unfortunately, there is no currently available vaccine that can completely control this disease. Thus, our study aimed to develop an mRNA vaccine using the antigens expressed by single or fused PRRSV structural proteins. In this study, the nucleotide sequence of the immunogenic mRNA was determined by considering the antigenicity of structural proteins and the stability of spatial structure. Purified GP5 protein served as the detection antigen in the immunological evaluation. Furthermore, cellular mRNA expression was detected by immunofluorescence and western blotting. In a mice experiment, the Ab titer in serum and the activation of spleen lymphocytes triggered by the antigen were detected by ELISA and ICS, respectively. Our findings demonstrated that both mRNA vaccines can significantly stimulate cellular and humoral immune responses. More specifically, the GP5-mRNA exhibited an immunological response that was similar to that of the commercially available vaccine when administered in high doses. To conclude, our vaccine may show promising results against the wild-type virus in a natural host. [ABSTRACT FROM AUTHOR]

Driven by the Industry 4.0 paradigm and the resulting demand for connectivity in industrial networking, there is a convergence of formerly isolated operational technology and information technology networks. This convergence leads to attack surfaces on industrial networks. Therefore, a holistic approach of countermeasures is needed to protect against cyber attacks. One element of these countermeasures is the use of certificate-based authentication for industrial components communicating on the field level. This in turn requires the management of certificates, private keys, and trust anchors in the communication endpoints. The work at hand surveys the topic of certificate management in industrial networking environments throughout their life cycle, from manufacturing until their disposal. To the best of the authors' knowledge, there is no work yet that surveys the topic of certificate management in industrial networking environments. The work at hand considers contributions from research papers, industrial communication standards, and contributions that originate from the IT domain. In total, 2042 results from IEEE Xplore, Science Direct, Scopus, and Springer Link were taken into account. After applying inclusion and exclusion criteria and title, abstract, and full-text analysis, 20 contributions from research papers were selected. In addition to the presentation of their key contributions, the work at hand provides a synopsis that compares the overarching aspects. This comprises different proposed entity architectures, certificate management functions, involvement of different stakeholders, and consideration of life cycle stages. Finally, research gaps that are to be filled by further work are identified. While the topic of certificate management has already been addressed by the IT domain, its incorporation into industrial communication standards began significantly later and is still the subject of research work. [ABSTRACT FROM AUTHOR]

Due to an increase in the number of attacks on Industrial Control Systems (ICS), the security of these systems is now of paramount concern. Many solutions have been proposed to defend such systems, particularly those adopting Machine Learning (ML). The goal of this study is to increase the likelihood of the solution being deployed into a real environment. As part of that, multiple interviews were held with industry experts who have been embedded within ICS cyber-security for decades. The findings revealed that the current security solutions for ICS lack the sophistication required to be adopted due to flawed assumptions made about the end-user. Therefore, this work provides personas of each end-user group within ICS that need to be taken into consideration when designing a security solution. In addition, wireframes are provided showing what a desired solution could look like. By sharing these findings, it is hoped to inform those working within this space and increase the likelihood of their solutions being adopted within a real environment. Furthermore, the expert panel requested a number of features that do not currently exist within the ICS cyber-security space, therefore, by sharing these with the wider community, it is hoped that the field will move closer towards providing solutions containing these features.

Abstract Background This study assessed hospitalisation frequency and related clinical outcomes among adult Aboriginal Australians with bronchiectasis over a ten-year study period. Method This retrospective study included patients aged ≥ 18 years diagnosed with bronchiectasis between 2011 and 2020 in the Top End, Northern Territory of Australia. Hospital admissions restricted to respiratory conditions (International Classification of Diseases (ICD) code J) and relevant clinical parameters were assessed and compared between those with and without hospital admissions. Results Of the 459 patients diagnosed to have bronchiectasis, 398 (87%) recorded at least one respiratory related (ICD-J code) hospitalisation during the 10-year window. In comparison to patients with a recorded hospitalisation against those without—hospitalised patients were older (median 57 vs 53 years), predominantly females (54 vs 46%), had lower body mass index (23 vs 26 kg/m2) and had greater concurrent presence of chronic obstructive pulmonary disease (COPD) (88 vs 47%), including demonstrating lower spirometry values (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) (median FVC 49 vs 63% & FEV1 36 vs 55% respectively)). The total hospitalisations accounted for 3,123 admissions (median 4 per patient (IQR 2, 10)), at a median rate of 1 /year (IQR 0.5, 2.2) with a median length of 3 days (IQR 1, 6). Bronchiectasis along with COPD with lower respiratory tract infection (ICD code-J44) was the most common primary diagnosis code, accounting for 56% of presentations and 46% of days in hospital, which was also higher for patients using inhaled corticosteroids (81 vs 52%, p = 0.007). A total of 114 (29%) patients were recorded to have had an ICU admission, with a higher rate, including longer hospital stay among those patients with bronchiectasis and respiratory failure related presentations (32/35, 91%). In multivariate regression model, concurrent presence of COPD or asthma alongside bronchiectasis was associated with shorter times between subsequent hospitalisations (-423 days, p = 0.007 & -119 days, p = 0.02 respectively). Conclusion Hospitalisation rates among adult Aboriginal Australians with bronchiectasis are high. Future interventions are required to explore avenues to reduce the overall morbidity associated with bronchiectasis among Aboriginal Australians.

Background and Objective: One of the most important challenges that is considered in process industries to improve performance and increase productivity is the optimization of the incident command system (ICS). It is a standard approach to control and coordinate the management of incidents on the scene. The present study aims to evaluate and prioritize the factors affecting the effectiveness of the ICS using analytic hierarchy process (AHP) and decision-making trial and evaluation laboratory (DEMATEL) methods in process industries in Iran. Materials and Methods: In this research, firstly, a questionnaire was compiled and designed using the AHP method in order to weigh the criteria and prioritize them, and a questionnaire was designed using the DEMATEL method in order to determine the effectiveness and mutual effect of the criteria and sub-criteria. Thereafter, the questionnaires were completed by 15 incident commanders, process industry safety officials, and crisis management activists working in the oil and petrochemical industry. Results: Based on the results, AHP analysis ranked 'command' highest with a standard weight of 0.256. DEMATEL results demonstrated 'command' as the most influential (standard weight of 10.59), effective (11.9), and interactive (21.96) indicator. 'Standardization' (1.35) and 'professionalism' (1.19) emerged as causal factors, while 'command' (-0.50), 'planning/organizational structure' (-1), 'facilities and resources' (-0.18), and 'disability index' were responsive indicators. Conclusion: According to the results of both AHP and DEMATEL methods, the command index assumes critical importance and effectiveness in the success of the incident command system in process industries in Iran.

Background: This study assessed hospitalisation frequency and related clinical outcomes among adult Aboriginal Australians with bronchiectasis over a ten-year study period. Method: This retrospective study included patients aged ≥ 18 years diagnosed with bronchiectasis between 2011 and 2020 in the Top End, Northern Territory of Australia. Hospital admissions restricted to respiratory conditions (International Classification of Diseases (ICD) code J) and relevant clinical parameters were assessed and compared between those with and without hospital admissions. Results: Of the 459 patients diagnosed to have bronchiectasis, 398 (87%) recorded at least one respiratory related (ICD-J code) hospitalisation during the 10-year window. In comparison to patients with a recorded hospitalisation against those without—hospitalised patients were older (median 57 vs 53 years), predominantly females (54 vs 46%), had lower body mass index (23 vs 26 kg/m2) and had greater concurrent presence of chronic obstructive pulmonary disease (COPD) (88 vs 47%), including demonstrating lower spirometry values (forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV1) (median FVC 49 vs 63% & FEV1 36 vs 55% respectively)). The total hospitalisations accounted for 3,123 admissions (median 4 per patient (IQR 2, 10)), at a median rate of 1 /year (IQR 0.5, 2.2) with a median length of 3 days (IQR 1, 6). Bronchiectasis along with COPD with lower respiratory tract infection (ICD code-J44) was the most common primary diagnosis code, accounting for 56% of presentations and 46% of days in hospital, which was also higher for patients using inhaled corticosteroids (81 vs 52%, p = 0.007). A total of 114 (29%) patients were recorded to have had an ICU admission, with a higher rate, including longer hospital stay among those patients with bronchiectasis and respiratory failure related presentations (32/35, 91%). In multivariate regression model, concurrent presence of COPD or asthma alongside bronchiectasis was associated with shorter times between subsequent hospitalisations (-423 days, p = 0.007 & -119 days, p = 0.02 respectively). Conclusion: Hospitalisation rates among adult Aboriginal Australians with bronchiectasis are high. Future interventions are required to explore avenues to reduce the overall morbidity associated with bronchiectasis among Aboriginal Australians. [ABSTRACT FROM AUTHOR]

Background: The population in India has been growing rapidly; world population is also a major problem with more than 6.3 billion living on this earth and 26 children born every second. The intrauterine device (IUD), being a reversible and effective contraception method, is the most widely used worldwide. Aims and objectives: A comparative study of IUCD insertion in postpartum and intracearean Materials and Method: The study was a prospective Interventional analytical study looking for comparative study of Post- Partum IUCD insertion in women having normal vaginal delivery and the women undergoing caesarean section in terms of menorrhagia, infection, expulsion, anemia, string visibility and removal. Results: The maximum number of women in each group were between 21 to 25 year with mean ± SD being 22.94±3.13, t (A, B) 0.06 (p > 0.05) in IPP group. Mean age 22.98±3.03 was in EPP group and in Intracaesarean it was 22.73±2.85. Haemoglobin level at different time interval and correlated with each other groups were having p value > 0.05. It shows that the value is statistically not significant. At 6 months, most common complication was irregular bleeding per vaginum. It was about 18% in ICS group, 14% in EPP group and 12% in IPP group. Missing string rate at 6 months in different group was 20% in ICS group. It was 9 in EPP group and only 6 cases in IPP group, out of 50 cases in each group of normally delivered women. USG results indicate that the most of missing IUCD in cases of ICS were found to be in utero was 20%. While in IPP and EPP group it was absent, as most probably it was expelled out. IUD present was significantly higher in ICS type (p < 0.001). Conclusion: To conclude, Post-Partum IUCD is a convenient, safe and effective method of post- partum family planning and more and more women should be counselled for accepting this method. [ABSTRACT FROM AUTHOR]

Since T cells are key mediators in the adaptive immune system, evaluating antigen-specific T cell immune responses is pivotal to understanding immune function. Commonly used methods for measuring T cell responses include Activation-Induced Marker (AIM) assays and Intracellular Cytokine Staining (ICS). However, combining these approaches has rarely been reported. This study describes a combined AIM + ICS assay and the effect of collecting the supernatant. Peripheral blood mononuclear cells (PBMCs) from seven healthy donors were stimulated with DMSO (negative control), Epstein-Barr virus (EBV) peptide pools, and PHA (positive control). The AIM markers OX40 + CD137+ were used for CD4+ T cells and CD69 + CD137+ and CD107a + CD137+ for CD8+ T cells. Cytokine-secreting cells were identified as CD40L+ cytokine+ for CD4+ and CD69+ or CD107 + cytokine+ for CD8+ T cells. Half of the supernatant was collected before adding the BFA/Monensin/CD137 antibody solution to assess the impact on T cell responses. The CD107a + CD137+ AIM markers combination had a lower background than CD69 + CD137+, making CD107a+ a more sensitive marker for CD8+ AIM markers. Collecting half of the supernatant did not significantly affect the immune responses. Our AIM + ICS combined protocol enables the simultaneous assessment of activation and cytokine release reducing the sample volume for testing T cell responses. We also show that collecting half of the supernatant does not significantly interfere with immune responses detection. [ABSTRACT FROM AUTHOR]

Xiubin Zhang, Jennifer K Quint National Heart and Lung Institute, Imperial College London, London, W12 0BZ, United KingdomCorrespondence: Jennifer K Quint, National Heart and Lung Institute, Imperial College London, Level 9, Sir Michael Uren Hub, White City Campus, 86 Wood Lane, London, W12 0BZ, United Kingdom, Email j.quint@imperial.ac.ukBackground: High short-acting β2-agonist (SABA) use and/or inhaled corticosteroid (ICS) underuse are common and are associated with poor asthma outcomes. This study explored patients’ and healthcare practitioners’ (HCPs’) perspectives to contextualize asthma treatment patterns observed in real-world studies.Methods: Data were collected using online surveys from HCPs and people with asthma (≥ 18 years old with a confirmed asthma diagnosis of any severity) who had consented to research participation through the Clinical Practice Research Datalink. Data were analysed using descriptive statistics.Results: In total, 76 HCPs and 63 patients were invited to take part. Of 48 valid HCP responders, 54.2% (n=26) reported scheduling an annual asthma treatment review with their patients and 83.3% of general practitioners (n=40) had prescribed repeated inhalers at the patient’s request. Of 47 valid patient responders, 57.4% (n=27) reported using their reliever (SABA) inhaler daily and 55.3% of patients (n=26) reported being prescribed a preventer inhaler. Of the total patient responders, 31.9% (n=15) reported that they never used their preventer inhaler. Consistent annual adherence with preventer inhalers was reported by 44.7% of all valid responders (n=21), while other patients admitted to using preventers intermittently.Conclusion: SABA and ICS prescription patterns are driven by a combination of HCP and patient factors. Opportunities exist to improve asthma control and behaviours around inhaler use.Keywords: asthma, adherence, healthcare professional, ICS, prescription, SABA

Key management is critical to secure operation. Distributed control systems, such as Supervisory Control and Data Acquisition (SCADA) systems, have unique operational requirements that make conventional key management solutions less effectiveand burdensome. This paper pres-ents a novel Kerberos-based framework for automated, disruption-tolerant key management for control system environments. Experimental tests and their results are presented to quantify the expected performance overhead of this approach. Additionally, Zeek sensor analytics are presented to aid in monitoring the health and security of the key management framework operation.

Manganese is essential trace elements, to participate in the body a variety of biochemical reactions, has important physiological functions, such as stimulate the immune cell proliferation, strengthen the cellular immunity, etc. However, excessive manganese exposure can cause damage to multiple systems of the body.The immune system is extremely vulnerable to external toxicants, however manganese research on the immune system are inadequate and biomarkers are lacking. Therefore, here we applied a manganese-exposed rat model to make preliminary observations on the immunotoxic effects of manganese. We found that manganese exposure inhibited humoral immune function in rats by decreasing peripheral blood IgG (ImmunoglobulinG, IgG), IgM (ImmunoglobulinM, IgM) and complement C3 levels; It also regulates rat cellular immune activity by influencing peripheral blood, spleen, and thymus T cell numbers and immune organ ICs (Immune Checkpoints, ICs) and cytokine expression. Furthermore, it was revealed that the impact of manganese exposure on the immune function of rats exhibited a correlation with both the dosage and duration of exposure. Notably, prolonged exposure to high doses of manganese had the most pronounced influence on rat immune function, primarily manifesting as immunosuppression.The above findings suggest that manganese exposure leads to impaired immune function and related changes in immune indicators, or may provide clues for the discovery of its biomarkers.

Background and Objective: One of the most important challenges that is considered in process industries to improve performance and increase productivity is the optimization of the incident command system (ICS). It is a standard approach to control and coordinate the management of incidents on the scene. The present study aims to evaluate and prioritize the factors affecting the effectiveness of the ICS using analytic hierarchy process (AHP) and decision-making trial and evaluation laboratory (DEMATEL) methods in process industries in Iran. Materials and Methods: In this research, firstly, a questionnaire was compiled and designed using the AHP method in order to weigh the criteria and prioritize them, and a questionnaire was designed using the DEMATEL method in order to determine the effectiveness and mutual effect of the criteria and sub-criteria. Thereafter, the questionnaires were completed by 15 incident commanders, process industry safety officials, and crisis management activists working in the oil and petrochemical industry. Results: Based on the results, AHP analysis ranked 'command' highest with a standard weight of 0.256. DEMATEL results demonstrated 'command' as the most influential (standard weight of 10.59), effective (11.9), and interactive (21.96) indicator. 'Standardization' (1.35) and 'professionalism' (1.19) emerged as causal factors, while 'command' (-0.50), 'planning/organizational structure' (-1), 'facilities and resources' (-0.18), and 'disability index' were responsive indicators. Conclusion: According to the results of both AHP and DEMATEL methods, the command index assumes critical importance and effectiveness in the success of the incident command system in process industries in Iran. [ABSTRACT FROM AUTHOR]

Digital transformation of engineering practice, paradigms, processes, and workforce engender agreement uncertainty among professionals, particularly in the critical industry control system field. Control systems are susceptible to cyber‐mediated changes that can uniquely affect the control of the physical world from data‐centric information systems. Change to the system can be introduced by any proposed or forced alteration that affects the acceptability, suitability, feasibility, or resiliency to perform its intended mission, either positively or negatively. The potential impact of the cybersecurity threat on control systems is difficult to quantify. Agreement among professionals about decision authority and Command and Control (C2) over this threat is even more challenging to quantify. Understanding what cybersecurity entails still needs to be widely understood by the critical infrastructure control system workforce, and the control system assets are not widely understood by the Information Technology (IT) workforce. This research introduces a model and methodology for measuring multi‐concern assurance through the statistical uncertainty analysis of Likert semantic differential scales. The model addresses agreement in priority, the lack of which means there might be competing aims, competing spending, and competing focus on different aspects of the cybersecurity governance or policy as examples. The outcome identifies where different types of professionals do not agree about cybersecurity readiness and best practices for critical infrastructure control systems. [ABSTRACT FROM AUTHOR]

Summary: Cyber‐attacks are considered the most significant threat to organizations from different sectors, including critical infrastructure. Access to critical assets, including industrial control systems, and control over their usage is one of the security approaches implemented to protect those systems from unauthorized access. However, existing implementations do not support the enforcement of fine‐grained authorization policies and do not provide continuous control over data access. Furthermore, existing implementations of the access control paradigm require policy‐makers to perform a manual update of policies that do not consider information about potential or ongoing cyber attacks. In this work, we propose a framework that enables continuous control on the execution of access rights in the industrial domain. Furthermore, the framework relies on cyber incident information shared by trusted entities. This information is used for updating security policies in order to prevent possible incidents within the smart factory infrastructure. We also provide experimental results that show the operability and the efficiency of the proposed framework. [ABSTRACT FROM AUTHOR]