Time Period Research Articles

The value of quantitative flow ratio in the hemodynamic evaluation of myocardial bridge

Objective: To explore the application value of quantitative flow ratio (QFR) in the hemodynamic evaluation of myocardial bridge and to preliminarily evaluate the correlation and related influencing factors between deformation quantitative flow ratio (D-QFR) and QFR. Methods: This is a cross-sectional study. Patients with CAG-confirmed simple myocardial bridge of the middle anterior descending coronary artery from June 2012 to June 2022 at the Air Force Medical Center were retrospectively included in this study. Systolic stenosis of mural coronary arteries (MCA) and myocardial bridge length were measured using quantitative coronary angiography. The patients were divided into mild stenosis group (<50% systolic stenosis) and moderate-to-severe stenosis group (≥50% systolic stenosis) according to the Nobel grading criteria. At different time periods (systolic and diastolic), the QFR values were measured at 3 locations (1 to 2 cm before the MCA entrance, the middle segment of the MCA, and 1 to 2 cm after the MCA exit), denoted as QFRa, QFRb, and QFRc, respectively, and the D-QFR values, incorporating vessel deformation information, were recorded. The MCA distal QFR≤0.8 in either stage was defined as an abnormal QFR value. QFR values were compared between the two groups at different locations and within each group. Factors associated with abnormal QFR values were analysed using multifactorial logistic regression. Spearman rank correlation analysis was used to examine the correlation between D-QFR values and systolic and diastolic QFR values.Multiple linear regression was used to analyse the factors associated with D-QFR. Results: A total of 83 patients were enrolled, including 58 males, aged (57.1±13.1) years. There were 48 cases in the mild stenosis group and 35 cases in the moderate-to-severe stenosis group, and the differences in systolic and diastolic QFRb and QFRc values between the two groups were statistically significant (all P<0.05). Within-group comparisons showed the values of QFRb and QFRc in the systolic phase were lower than those in the diastolic phase; QFRb and QFRc were both lower than QFRa during the same period (all P<0.05). Multifactorial logistic regression analysis showed that MCA systolic stenosis (OR=1.225, 95%CI 1.093-1.372, P<0.001) was an influential factor for abnormal QFR. D-QFR values were positively correlated with both systolic and diastolic QFR values (correlation coefficients were 0.849 and 0.675, respectively, both P<0.01). Multiple linear regression analysis showed that D-QFR values were negatively correlated with age (β=-0.208, P=0.029), systolic stenosis (β=-0.500, P<0.001), and myocardial bridge length (β=-0.211, P=0.036). Conclusions: The QFR values in middle and distal of myocardial bridge decrease. The systolic stenosis rate of myocardial bridge is an important factor affecting QFR value. D-QFR is positively correlated with both systolic and diastolic QFR values. Age, myocardial bridge systolic stenosis rate and length are factors influencing the D-QFR values.

Serum microRNA profile of rhesus macaques following ionizing radiation exposure and treatment with a medical countermeasure, Ex-Rad

Exposure to ionizing radiation (IR) presents a formidable clinical challenge. Total-body or significant partial-body exposure at a high dose and dose rate leads to acute radiation syndrome (ARS), the complex pathologic effects that arise following IR exposure over a short period of time. Early and accurate diagnosis of ARS is critical for assessing the exposure dose and determining the proper treatment. Serum microRNAs (miRNAs) may effectively predict the impact of irradiation and assess cell viability/senescence changes and inflammation. We used a nonhuman primate (NHP) model—rhesus macaques (Macaca mulatta)—to identify the serum miRNA landscape 96 h prior to and following 7.2 Gy total-body irradiation (TBI) at four timepoints: 24, 36, 48, and 96 h. To assess whether the miRNA profile reflects the therapeutic effect of a small molecule ON01210, commonly known as Ex-Rad, that has demonstrated radioprotective efficacy in a rodent model, we administered Ex-Rad at two different schedules of NHPs; either 36 and 48 h post-irradiation or 48 and 60 h post-irradiation. Results of this study corroborated our previous findings obtained using a qPCR array for several miRNAs and their modulation in response to irradiation: some miRNAs demonstrated a temporary increased serum concentration within the first 24–36 h (miR-375, miR-185-5p), whereas others displayed either a prolonged decline (miR-423-5p) or a long-term increase (miR-30a-5p, miR-27b-3p). In agreement with these time-dependent changes, hierarchical clustering of differentially expressed miRNAs showed that the profiles of the top six miRNA that most strongly correlated with radiation exposure were inconsistent between the 24 and 96 h timepoints following exposure, suggesting that different biodosimetry miRNA markers might be required depending on the time that has elapsed. Finally, Ex-Rad treatment restored the level of several miRNAs whose expression was significantly changed after radiation exposure, including miR-16-2, an miRNA previously associated with radiation survival. Taken together, our findings support the use of miRNA expression as an indicator of radiation exposure and the use of Ex-Rad as a potential radioprotectant.

THREAT TO PERSONAL SECURITY – CONSEQUENCES OF POST-TRAUMATIC STRESS AMONG POLISH SOLDIERS PARTICIPATING IN MISSIONS ABROAD

Soldiers participating in various types of missions abroad experience stress almost every day.This indispensable element of military service is caused primarily by numerous military threats.Functioning under chronic stress for a long period of time leads to consequences on many levels.Most scientists dealing with this topic unanimously emphasize that living under chronic stresscauses the body to react both mentally and physically. Moreover, the paper covers the emotional,cognitive, biological and behavioural spheres. The purpose of the research was to determine theextent to which soldiers deployed on missions experience negative and positive consequences oftraumatic experiences, what relationships exist between negative and positive consequences oftraumatic experience, and whether they are related to demographic variables.Results. The results of the authors’ research indicated that the surveyed soldiers deployed onoverseas missions, exposed to a traumatic event connected with the performance of their serviceduties, are affected by both negative and positive consequences of the events experienced.Conclusions. Therefore, the results obtained confirmed the possibility of the co-occurrence ofnegative and positive effects of the experienced trauma.

Brachial neuralgic amyotrophy, a rare disease with serious diagnostic problems - case report

Neuralgic amyotrophy(NA), is a rare and highly variable neurological disorder of unknown aetiology that causes serious diagnostic problems. We described a case of NA with atrophy of the brachialis muscle in order to enrich clinicians’ knowledge about this disorder and to help them in the proper diagnosis of NA. A 21-year-old man presented with sudden, severe pain in the right biceps muscle. The man had consultations with several doctors and physiotherapists. Three magnetic resonance imaging (MRI) examinations, a nerve conduction study (NCS) and needle electromyography (EMG) were performed. Only after 6 months, based on medical history, physical examination and ultrasound imaging (USI), the physiotherapist suggested NA, which was later on confirmed by a neurologist. This case description of NA showed a variety of symptoms that made it difficult to establish an accurate diagnosis for a longer period of time. The diagnostic procedure, as well as the prolonged time between the onset of symptoms and diagnosis, indicates the need for further education of clinicians to better understand the symptoms of NA.

Microwave-assisted hydrothermal synthesis of ZnO@ZrO2 nanohybrid for biomedical and photocatalytic applications

The present study was conducted to synthesize zinc oxide decorated on zirconium oxide (ZnO@ZrO2) nanohybrid synthesized through microwave-hydrothermal (MW-HT) method. Various analytical techniques were used to analyze the morphology, surface properties, constitution of hybrid, and elemental composition. Additionally, the anti-microbial activity of ZnO@ZrO2 nanohybrid was assessed against Gram-positive and Gram-negative pathogenic bacteria, hemolytic, anti-oxidant as well as anti-inflammatory assay. The hexagonal wurtzite phase of the ZnO was revealed by the XRD analysis. The experimental results reveal that the synergetic effect between the Zn and Zr active sites results an excellent biomedical activity. The ZnO@ZrO2 nanohybrid was successfully applied to the photocatalytic degradation of basic fuchsin (BF) dye within short period of time under visible light (VL) radiation. Moreover, the ZnO@ZrO2 nanohybrid exhibited an extraordinary performance for photocatalytic degradation of BF with a pseudo-first order rate constant (k) of ca. 0.1702 min−1, which was 2.5 and 1.8 fold compared to ZnO and ZrO2 photocatalysts. These results indicated that the ZnO@ZrO2 nanohybrid can be used as a potential biomaterial for bioengineering and photocatalytic applications.

Interplay of Transcriptional Factors In Beta Cells Development and Maturation

Diabetes is a group of metabolic disorders resulting from defects in insulin secretion, insulin action, or both. It is characterized by high blood sugar levels over a prolonged period of time with disturbances of carbohydrate, protein, and fat metabolism. It is a global disorder affecting about half a billion or 536.6 million people worldwide, which is said to rise to 783.2 million by 2045. To maintain normoglycemia, pancreatic β-cells release insulin in proportion to the amounts of nutrients in the blood. Through a process of postnatal development, β-cells learn to connect insulin release to food cues. The insulin secretory response in mature β-cells adjusts to alterations in nutritional status. The interaction between transcriptional programs specific to each cell type and external stimuli is necessary for both β-cell maturation and functional adaptation. In this review, we examine the growing data that suggests lineage-determining and signal-dependent transcription factors (LDTFs and SDTFs, respectively) work together to regulate β-cell activity during development and homeostasis. In-depth knowledge of β-cell SDTFs and their corresponding signals would clarify the processes involved in β-cell maturation and functional adaptation, directly affecting diabetes treatments and the production of mature β-cells from stem cells.

Scoping an Integrated Ecosystem Assessment for the southern Benguela: fisheries still biggest risk

Abstract The southern Benguela ecosystem faces complex pressures from anthropogenic activities and climate change, leading to structural and functional changes. To counter ecosystem service losses, intergovernmental marine science organizations propose integrated management. However, predictions to evaluate alternative strategies are challenging due to multifaceted sector interactions affecting ecological components. Scoping phases of Integrated Ecosystem Assessments (IEA), such as the Options for Delivering Ecosystem-Based Marine Management (ODEMM), identify priority sectors and pressures for management using linkage chains and impact risk scores. This study expands a South African-wide ODEMM assessment to investigate dependent sectors in the southern Benguela. Fishing emerged as the primary sector, exhibiting high connectance and impact risk on ecological components. Disaggregation of the fishing sector into sub-sectors and over three 21-year time periods revealed the demersal trawl and mixed species inshore trawl sectors to still have the greatest impact despite recent mitigation efforts, driven by species extraction, bycatch, and ‘incidental loss’. Research gaps, such as the effects of recreational fisheries and underwater noise, were identified and need to be addressed to improve future ecosystem assessments. Additionally, the effects of climate on long-term, ecosystem-scale variability and change need more attention in IEAs and should be incorporated into frameworks such as ODEMM.

The Effectiveness of Hand Exercise on Limb Function in Patient Coronary Artery Disease Posttransradial Artery Catheterization: Systematic Review

Coronary Artery Disease (CAD) is leading cause of mortality worldwide. Catheterization using the transradial arterial (TRA) technique has been able to reduce morbidity and mortality rates from CAD, but this procedure also contributes to the occurrence of complications. The aim of this study was to search literature and analyse articles discussing the use of hand exercise on improving limb function in patients posttransradial cardiac catheterization. Methods: The design used was a systematic review with PRISMA adaptation. Articles were searched using databases: ScienceDirect, ProQuest, PubMed, Scopus and Hand Searching in Google Scholar. The keywords of article search were using “Coronary artery disease” AND “transradial artery catheterization” OR “Trans cardiac Catheterization” AND “hand exercise” AND “limb function. In the initial stage of information search on 5 October 2023, the total number of articles obtained before selection was carried out based on inclusion and exclusion criteria was 7273 articles. From the five databases used, selection was then carried out according to the inclusion and exclusion criteria. The inclusion criteria were research articles published in the last 10 years (2013-2023); use English; a journal article and open access; Involves adult respondents and full text articles. Exclusion criteria were encyclopedia articles, book chapters, conferences, correspondence, editorials, news, practice guidelines, protocols, systematic reviews, literature reviews and meta analysis. The results are discussing 7 articles published from 2013-2023. Conclusions Hand exercises are useful for restoring limb function within two hours after the procedure and over a long period of time.

Identification of residential building typologies by applying clustering techniques to cadastral data

Building typologies are usually classified according to their shape, distribution and construction features depending on the time period they were built. As a result, a subjective classification arises which highly depends on the criteria used to differentiate buildings. When this analysis is carried out at the urban scale, data sets become bigger, making patterns difficult to uncover. Mistakes in deciding the variables to classify buildings lead to incorrect typologies and, consequently, wrong results. The aim of this study is to test a new methodology based on clustering techniques to identify typologies related to energy retrofitting, which would allow obtaining a more objective classification and better pattern recognition by reducing human intervention. To that end, a data set from the Spanish cadastre is used, with additional information to reflect the influence of existing standards on constructive solutions. By applying three clustering techniques (Ward's method, Partitioning Around Medoids, and a combination of both), new proposals of building typologies are obtained and discussed in comparison to traditional classifications. The results show that the Ward's method produces building typologies with significantly high quality metrics and meaningfulness. The agglomeration coefficient is 99.8%, which indicates that hardly another hierarchical method could generate a better clusters structure. Six clusters comprise 86% of the dwellings as most occupants do not declare retrofitting works, thus not being reflected in the cadastre database. This research provides a new classification method that can notably influence the estimation of costs, environmental impact and cost effectiveness of energy retrofitting actions at urban scale.

Covid-19: The impact of lockdown on the dispensing of hospital drugs to outpatients

In response to the COVID-19 pandemic, France was under lockdown for the first time from March 17 to May 10, 2020. The aim of this work is to study the impact of lockdown on outpatients’ visits to the hospital pharmacy to collect chronic medication, in order to highlight the pharmaceutical classes concerned and to assess whether a decrease in medication adherence could be observed. Retrospectively, using hospital dispensing traceability software, the dispensing of drugs during the eight weeks of lockdown was compared with that during the two eight-week periods before and after lockdown. Evolutions in the number of medicine lines dispensed and outpatient visits were analyzed over the three time periods, according to pharmaceutical classes. A specific analysis was performed between drugs only available at the hospital pharmacy and drugs available at both the community and hospital pharmacy. During lockdown, 67% of patients still came regularly, but a significant decrease in the average number of lines dispensed was observed. 15% of regular patients limited their visits during this period. Patients taking drugs available at both the community and hospital pharmacy were significantly more impacted than those taking drugs that could only be dispensed at the hospital pharmacy. On the other hand, age is not a factor associated with the restriction of visits. Lockdown affected the visits to the hospital pharmacy of at least one in ten regular outpatients. Sending hospital drugs to community pharmacies and the help of home health care providers limited therapeutic disruptions.

Urban green land use efficiency of resource-based cities in China: Multidimensional measurements, spatial-temporal changes, and driving factors

The green use of urban land has become a key for the sustainable transformation of resource-based cities. This paper selects 116 Chinese resource-based cities to construct an evaluation system for urban green land use and measure its efficiency. Secondly, it identifies driving factors affecting urban green land use efficiency (UGLUE) and comprehensively analyze the heterogeneity of these factors. The important findings of this paper include: (1) The UGLUE of resource-based cities in China has experienced a trend of first fluctuating and then improving. However, there are obvious regional differences. The UGLUE in the eastern and western regions are higher than those in the central and northeastern regions. (2) Industrial upgrading, financial development and technological innovation are key factors affecting UGLUE in resource-based cities. (3) There is significant heterogeneity in the impact of different factors in different city types, different regions and different time periods. The land use in resource-based cities should transform from blind expansion in pursuit of short-term economic benefits to a green development that pursues the coordination of economic, social, and ecological benefits based on the local conditions.

Predictors of unplanned emergency hospital admissions among patients aged 65+ with multimorbidity and depression in Northwest London during and after the Covid-19 lockdown in England.

Individuals with multimorbidity have an increased likelihood of using unplanned secondary care including emergency department visits and emergency hospitalisations. Those with mental health comorbidities are affected to a greater extent. The Covid-19 pandemic has negatively impacted on psychosocial wellbeing and multimorbidity care, especially among vulnerable older individuals. To examine the risk of unplanned hospital admissions among patients aged 65+ with multimorbidity and depression in Northwest London, England, during- and post-Covid-19 lockdown. Retrospective cross-sectional data analysis with the Discover-NOW database for Northwest London was conducted. The overall sample consisted of 20,165 registered patients aged 65+ with depression. Two time periods were compared to observe the impact of the Covid-19 lockdown on emergency hospital admissions between 23rd March 2020 to 21st June 2021 (period 1) and equivalent-length post-lockdown period from 22nd June 2021 to 19th September 2022 (period 2). Multivariate logistic regression was conducted on having at least one emergency hospital admission in each period against sociodemographic and multimorbidity-related characteristics. The odds of having an emergency hospitalisation were greater in men than women (OR = 1.19 (lockdown); OR = 1.29 (post-lockdown)), and significantly increased with age, higher deprivation, and greater number of comorbidities in both periods across the majority of categories. There was an inconclusive pattern with ethnicity; with a statistically significant protective effect among Asian (OR = 0.66) and Black ethnicities (OR = 0.67) compared to White patients during post-lockdown period only. The likelihood of unplanned hospitalisation was higher in men than women, and significantly increased with age, higher deprivation, and comorbidities. Despite modest increases in magnitude of risk between lockdown and post-lockdown periods, there is evidence to support proactive case-review by multi-disciplinary teams to avoid unplanned admissions, particularly men with multimorbidity and comorbid depression, patients with higher number of comorbidities and greater deprivation. Further work is needed to determine admission reasons, multimorbidity patterns, and other clinical and lifestyle predictors.

Route Planning Algorithms for Unmanned Surface Vehicles (USVs): A Comprehensive Analysis

This review paper provides a structured analysis of obstacle avoidance and route planning algorithms for unmanned surface vehicles (USVs) spanning both numerical simulations and real-world applications. Our investigation encompasses the development of USV route planning from the year 2000 to date, classifying it into two main categories: global and local route planning. We emphasize the necessity for future research to embrace a dual approach incorporating both simulation-based assessments and real-world field tests to comprehensively evaluate algorithmic performance across diverse scenarios. Such evaluation systems offer valuable insights into the reliability, endurance, and adaptability of these methodologies, ultimately guiding the development of algorithms tailored to specific applications and evolving demands. Furthermore, we identify the challenges to determining optimal collision avoidance methods and recognize the effectiveness of hybrid techniques in various contexts. Remarkably, artificial potential field, reinforcement learning, and fuzzy logic algorithms emerge as standout contenders for real-world applications as consistently evaluated in simulated environments. The innovation of this paper lies in its comprehensive analysis and critical evaluation of USV route planning algorithms validated in real-world scenarios. By examining algorithms across different time periods, the paper provides valuable insights into the evolution, trends, strengths, and weaknesses of USV route planning technologies. Readers will benefit from a deep understanding of the advancements made in USV route planning. This analysis serves as a road map for researchers and practitioners by furnishing insights to advance USV route planning and collision avoidance techniques.

What do consumers understand about predispute arbitration agreements? an empirical investigation.

The results of a survey of 1,071 adults in the United States reveal that most consumers do not pay attention to, let alone understand, arbitration clauses in their everyday lives. The vast majority of survey respondents (over 97%) report having opened an account with a company that requires disputes to be submitted to binding arbitration (e.g., Netflix, Hulu, Cash App, a phone or cable company), yet most are unaware that they have, in fact, agreed to mandatory arbitration (also known as "forced arbitration"). Indeed, over 99% of respondents who think they have never entered into an arbitration agreement likely have done so. Over 92% of respondents report that they have never based a decision to use a product or service on whether the terms and conditions contain an arbitration agreement. When prompted, they largely endorse the following reasons: they were unaware of the arbitration clause, they did not read the terms and conditions, and they thought they had no choice but to agree to mandatory arbitration. Moreover, many respondents presume that if a dispute arises, they will still be able to access the public courts, notwithstanding that they agreed to the terms and conditions. Consumers are largely unaware of opportunities to opt out of mandatory arbitration. They generally do not pay attention to or retain information about the steps required to opt out successfully (e.g., contacting the company within a specified time period). Generally, consumers are unaware that companies like Cash App and Venmo (mobile payment systems utilized by nearly 60% of respondents) allow customers to opt out of mandatory arbitration if they act within a limited time period. Among the minority of respondents (21%) who stated that they had been given an opportunity to opt out, vanishingly few could name any of the steps required to opt out successfully. When presented with a run-of-the-mill contract, of the type consumers routinely encounter, most respondents did not take notice of the arbitration clause. Less than 5% of respondents could recall that the contract they were shown had said anything at all about arbitration. Furthermore, most consumers misperceive the consequences of signing a predispute arbitration agreement. Most mistakenly believe that, after agreeing to terms and conditions mandating binding arbitration, they can still choose to settle their dispute in court, have a jury decide their case, join a class action, and appeal a decision made based on a legal error. For instance, less than 5% of respondents correctly reported that they could neither appeal an erroneous decision to another arbitrator (or set of arbitrators) nor start all over again in court. Less than 1% of respondents correctly understood the full significance of the arbitration agreement, as indicated by their responses to questions about whether they retained the rights to sue, have a jury decide their case, access the public courts, and appeal a decision based on a legal error. In summary, consumers are generally unaware of arbitration clauses, and they tend to hold mistaken beliefs about how arbitration agreements affect consumers' procedural rights.

Mid-long term boundary dynamic optimization of open-pit coal mine considering coal price fluctuation.

The delineation of the open-pit mining boundary, particularly in the context of medium to long-term planning, forms the foundation of mining design. However, due to the non-linear and dynamic nature of the economic and technical parameters influencing boundary delineation, determining the optimal mining boundary can be exceedingly challenging. Currently, most boundary optimization methods assume that block parameters remain fixed, which results in enterprises assuming a certain level of risk when facing changes in internal and external conditions. In this regard, this paper introduces the concept of "achievement degree" to reflect the risk associated with the results of boundary design. Using coal prices as an example, this article applies the predicted coal price curve to boundary optimization adjustments by specifying the "achievement degree" requirements for various time periods, thereby facilitating risk-controlled and economically optimal boundary decisions. Taking the illustrative case of an idealized small-scale inclined coal seam open-pit mine, adjustments to the boundary closely track variations in coal prices, further enhancing returns. The results demonstrate that the method proposed in this paper can increase overall revenue by approximately 51.15% within the forecast period, while effectively managing risks.

Potential bottom‐up control of Metamasius callizona in Florida, USA

AbstractMetamasius callizona (Chevrolat) (Coleoptera: Curculionidae) is an invasive weevil destroying Tillandsia utriculata L. (Bromeliaceae) populations in Florida, USA. A T. utriculata population in Belize coexists with M. callizona without adverse effects. Tillandsia utriculata and M. callizona from Belize and Florida were studied in the laboratory to determine how Belize T. utriculata can coexist with Belize M. callizona, using Florida and Belize T. utriculata, as well as pineapple, Ananas comosus (L.) Merr. (Bromeliaceae), as host plants. Florida M. callizona on pineapple leaves produced more eggs per female per day and had a shorter developmental time and pupation period, as well as a smaller adult width, than Belize M. callizona. Florida and Belize weevils did not differ significantly in rates of egg hatch, pupation, and adult emergence. Florida M. callizona laid similar numbers of eggs per day on Florida and Belize T. utriculata. Egg hatch rates were similar on pineapple and Florida and Belize T. utriculata. Pupation rates were similar on pineapple and Florida T. utriculata leaves; no larvae on Belize T. utriculata attained fourth instar. Field and laboratory observations revealed that Belize and Florida M. callizona mined Belize T. utriculata without destroying the meristem, allowing plants to survive, but Belize M. callizona destroyed the core of pineapple tops. Soluble solids were greatest in pineapple and least in Belize T. utriculata. Leaf toughness was greatest in pineapple and least in Florida T. utriculata. Metamasius callizona biology and behavior and T. utriculata plant characteristics may drive the severity of weevil damage on populations of T. utriculata. The discovery of a T. utriculata population in Belize coexisting with M. callizona offers a possible way to control M. callizona in Florida.

The limits of autocratisation in Indonesia: power dispersal and elite competition in a compromised democracy

How does democracy survive in a polity that has witnessed consistent autocratisation trends for an extended period of time? In Indonesia, new patterns of autocratisation and broader democratic decline emerged in the late 2000s, but unlike some of its Southeast Asian neighbours, the country has not crossed over into the territory of full-fledged autocracy. This article argues that two interrelated factors explain this outcome: first, power was so widely dispersed in the early democratic transition that its renewed monopolisation would be hard to achieve; and, second, this power dispersal has underpinned an intense inter-elite rivalry that rebels against any attempt at restoring personalist autocracy. At the same time, elites have cooperated in the weakening of democracy as long as a residual framework for competitive rotation of power remains in place.

Quality by Design and Characterization of Nimodipine Novel Carriers for the Treatment of Hypertension: Assessment of the Pharmacokinetic Profile

Background: Nimodipine is a highly lipophilic anti-hypertensive drug having 13% oral bioavailability (log P 3.41). Nimodipine is a prominent calcium channel blocker that must be given intravenously for an extended period of time (1-2 weeks) in order to treat cerebral vasospasm. It might be possible to substitute a sustained-release biodegradable formulation for the ongoing intravenous infusion used in this traditional therapy. Objectives: The primary goal of this study was to formulate and evaluate the potentiality of ethosomes to deliver nimodipine, a potent water-insoluble anti-hypertensive drug, through the deeper layers of the skin. The greatest challenge for drug formulation is its poor oral bioavailability and solubility. Methods: Nimodipine-loaded ethosomal gel was developed for transdermal drug delivery to increase solubility and skin penetration and to promote oral bioavailability. Central composite design employing a thin-film hydration method was used to prepare and optimize ethosomes. A better dispersion medium for nimodipine's preparation in ethosomes was selected based on the effect. The design consisted of independent variables as lipid (X1), ethanol (X2), and sonication time (X3). Concentrations were manipulated to examine the effects on three responses, namely the %entrapment efficiency (Y1), vesicle size (Y2), and %cumulative drug release (Y3). Surface morphology and other in vitro tests were used to identify ethosomes containing nimodipine. The preparation of ethosomal gel formulations began with incorporating a single ethosomal formulation (F4) into various concentrations of gelling agents. These studies performed physicochemical characterization, compatibility testing, and in vitro drug release tests on ethosomal gels. In vivo studies involving hypertensive rats were conducted after skin permeation, and ex vivo studies were performed. In order to assess the drug's permeability and deposition, we employed the abdomen skin of rats. Results: The optimal process parameters resulted in ethosomes with 89.9 ± 0.19 percent entrapment efficiency, a vesicle size of 102.37 ± 5.84 nm, and a cumulative drug release of 98.3 ± 0.13%. pH and drug content measurements were consistent with the homogeneous ethosomal gels. Viscosity was found to increase with the spreadability. The ethosomal gel formulation (G2) met the regulatory standards regarding appearance, spreadability, viscosity, and in vitro release studies. Compared to pure nimodipine, ethosomal suspension (F4) and ethosomal gel (G2) formulations had higher ex vivo permeation, steady-state flux, and drug retention. Rats' mean arterial pressure (146.11 ± 0.84 mmHg) was significantly lower (p &lt; 0.01) after after two hours of the experiment than it had been (p &lt; 0.001) (98.88 ± 0.63 mmHg) after six hours. Conclusion: To summarize, ethosomal gels have been found to be lipid carriers that enhance skin permeation and extend the anti-hypertensive effect of nimodipine. Compared to plain gel, ex vivo drug permeation through rat abdominal skin in ethosomal gel was enhanced. Gel-based ethosomal transdermal drug delivery formulations of nimodipine can be used to achieve a faster rate and extend the duration of drug delivery by more than 24 hours.

Automated One-Sided Learning Fault Detection System for Reaction Wheel Bearing Friction Anomalies

Monitoring a satellite’s health during a mission has become critical in space engineering. In-flight anomaly detection is difficult for ground operators, placing space missions at risk of failure. Machine learning algorithms are data-driven methods that could autonomously detect faults in situ. In this paper, a new application of machine learning algorithms in space engineering is introduced for detecting reaction wheel bearing anomalies that only relies on nominal data (no failure data) for training and with no prior knowledge of the system dynamics. Using a one-sided regression method, an automated fault detection system was designed to monitor the attitude dynamics control system for a small satellite. The proposed detection algorithm was first trained using a simulated attitude dynamics control system for the small satellite. Next, the detection system was trained with only nominal behavioral data of the control system for a designated period of time. Then, different types of bearing friction failures were added to the simulated system to test the trained fault detection system. The empirical rule (68-95-99.7 rule) was used as a failure detection criterion to differentiate failure data from nominal. Similar physical tests were conducted using a combination of a brushless motor and drone propellers. Both simulation and experimental results demonstrated the robustness of detection accuracy, were model-free, and verified the feasibility of an easy-to-use, accurate, and autonomous anomaly detection system for reaction wheels that could be extended to other space systems.

Toward a Real-Time TCP SYN Flood DDoS Mitigation Using Adaptive Neuro-Fuzzy Classifier and SDN Assistance in Fog Computing

The growth of the Internet of Things (IoT) has recently impacted our daily lives in many ways. As a result, a massive volume of data are generated and need to be processed in a short period of time. Therefore, a combination of computing models such as cloud computing is necessary. The main disadvantage of the cloud platform is its high latency due to the centralized mainframe. Fortunately, a distributed paradigm known as fog computing has emerged to overcome this problem, offering cloud services with low latency and high-access bandwidth to support many IoT application scenarios. However, attacks against fog servers can take many forms, such as distributed denial of service (DDoS) attacks that severely affect the reliability and availability of fog services. To address these challenges, we propose mitigation of fog computing-based SYN Flood DDoS attacks using an adaptive neuro-fuzzy inference system (ANFIS) and software defined networking (SDN) assistance (FASA). The simulation results show that the FASA system outperforms other algorithms in terms of accuracy, precision, recall, and F1-score. This shows how crucial our system is for detecting and mitigating TCP-SYN floods and DDoS attacks.