Rank and Wormhole Attack Detection Model for RPL-Based Internet of Things Using Machine Learning.

The proliferation of the internet of things (IoT) technology has led to numerous challenges in various life domains, such as healthcare, smart systems, and mission-critical applications. The most critical issue is the security of IoT nodes, networks, and infrastructures. IoT uses the routing protocol for low-power and lossy networks (RPL) for data communication among the devices. RPL comprises a lightweight core and thus does not support high computation and resource-consuming methods for security implementation. Therefore, both IoT and RPL are vulnerable to security attacks, which are broadly categorized into RPL-specific and sensor-network-inherited attacks. Among the most concerning protocol-specific attacks are rank attacks and wormhole attacks in sensor-network-inherited attack types. They target the RPL resources and components including control messages, repair mechanisms, routing topologies, and sensor network resources by consuming. This leads to the collapse of IoT infrastructure. In this paper, a lightweight multiclass classification-based RPL-specific and sensor-network-inherited attack detection model called MC-MLGBM is proposed. A novel dataset was generated through the construction of various network models to address the unavailability of the required dataset, optimal feature selection to improve model performance, and a light gradient boosting machine-based algorithm optimized for a multiclass classification-based attack detection. The results of extensive experiments are demonstrated through several metrics including confusion matrix, accuracy, precision, and recall. For further performance evaluation and to remove any bias, the multiclass-specific metrics were also used to evaluate the model, including cross-entropy, Cohn's kappa, and Matthews correlation coefficient, and then compared with benchmark research.

Long-Term Safety and Efficacy Data of Golodirsen in Ambulatory Patients with Duchenne Muscular Dystrophy Amenable to Exon 53 Skipping: A First-in-human, Multicenter, Two-Part, Open-Label, Phase 1/2 Trial.

The aim of this Phase 1/2, 2-part, multicenter trial was to report clinical safety and efficacy of long-term golodirsen treatment among ambulatory patients with exon 53 skip-amenable Duchenne muscular dystrophy (DMD). Part 1 was a 12-week, randomized, double-blind, placebo-controlled, dose-titration study followed by 9-week safety review. Part 2 was a 168-week, open-label evaluation of golodirsen 30 mg/kg. Part 1 primary endpoint was safety. Part 2 primary endpoints were dystrophin protein expression and 6-minute walk test (6MWT); secondary endpoints were percent predicted forced vital capacity (FVC%p) and safety. Post hoc ambulation analyses used mutation-matched external natural history controls. All patients from Part 1 (golodirsen, n = 8; placebo, n = 4) plus 13 additional patients entered Part 2; 23 completed the study. Adverse events were generally mild, nonserious, and unrelated to golodirsen, with no safety-related discontinuations or deaths. Golodirsen increased dystrophin protein (16.0-fold; P < 0.001) and exon skipping (28.9-fold; P < 0.001). At 3 years, 6MWT change from baseline was -99.0 m for golodirsen-treated patients versus -181.4 m for external controls (P = 0.067), and loss of ambulation occurred in 9% versus 26% (P = 0.21). FVC%p declined 8.4% over 3 years in golodirsen-treated patients, comparing favorably with literature-reported rates. This study provides evidence for golodirsen biologic activity and long-term safety in a declining DMD population and suggests functional benefit versus external controls. Clinical Trial Registration number: NCT02310906.

Prevalence and impact of the use of electronic gadgets on the health of children in secondary schools in Bangladesh: A cross-sectional study.

BACKGROUND AND AIMS: Use of technological gadgets has rapidly been increasing among adolescents, which may result in health issues and technology addiction. This study focuses on the prevalence of usage of technological gadgets and health-related complications among secondary school-going children of Bangladesh. METHODS: A total of 1803 secondary school students from 21 different districts of Bangladesh participated in the study. The children were asked questions relating to their access to electronic gadgets, time spent on outdoor activities, and whether they experienced any health-complications as an after-effect of the usage. A binary logistic regression model was adapted considering time spent on gadgets as an independent variable and health problems (physical and mental) as the dependent variable. RESULTS: Among all the gadgets, 67.11% of the participants were reported to use mobile phones on a daily basis. Due to the ongoing COVID-19 pandemic, 24.48% of respondents used electronic gadgets for attending online classes. The participants were reported to use gadgets significantly more (P < .05) in 2020 as compared to 2019. Children showed less tendency to spend time in outdoor activities. More than 50% of the participants spend time doing outdoor activities for less than 1 hour daily. An association between gadget use and health problems like headache, backache, visual disturbance, and sleeping disturbance has been observed in our study. CONCLUSION: This study demonstrates that different socio-demographic factors have influence on the use of gadgets by children, and this use has greatly been affecting both the physical and mental health of the secondary school-going students of Bangladesh.

5G and IoT Based Reporting and Accident Detection (RAD) System to Deliver First Aid Box Using Unmanned Aerial Vehicle.

Internet of Things (IoT) and 5G are enabling intelligent transportation systems (ITSs). ITSs promise to improve road safety in smart cities. Therefore, ITSs are gaining earnest devotion in the industry as well as in academics. Due to the rapid increase in population, vehicle numbers are increasing, resulting in a large number of road accidents. The majority of the time, casualties are not appropriately discovered and reported to hospitals and relatives. This lack of rapid care and first aid might result in life loss in a matter of minutes. To address all of these challenges, an intelligent system is necessary. Although several information communication technologies (ICT)-based solutions for accident detection and rescue operations have been proposed, these solutions are not compatible with all vehicles and are also costly. Therefore, we proposed a reporting and accident detection system (RAD) for a smart city that is compatible with any vehicle and less expensive. Our strategy aims to improve the transportation system at a low cost. In this context, we developed an android application that collects data related to sound, gravitational force, pressure, speed, and location of the accident from the smartphone. The value of speed helps to improve the accident detection accuracy. The collected information is further processed for accident identification. Additionally, a navigation system is designed to inform the relatives, police station, and the nearest hospital. The hospital dispatches UAV (i.e., drone with first aid box) and ambulance to the accident spot. The actual dataset from the Road Safety Open Repository is used for results generation through simulation. The proposed scheme shows promising results in terms of accuracy and response time as compared to existing techniques.

Open-Label Evaluation of Eteplirsen in Patients with Duchenne Muscular Dystrophy Amenable to Exon 51 Skipping: PROMOVI Trial.

BackgroundEteplirsen received accelerated FDA approval for treatment of Duchenne muscular dystrophy (DMD) with mutations amenable to exon 51 skipping, based on demonstrated dystrophin production.ObjectiveTo report results from PROMOVI, a phase 3, multicenter, open-label study evaluating efficacy and safety of eteplirsen in a larger cohort.MethodsAmbulatory patients aged 7-16 years, with confirmed mutations amenable to exon 51 skipping, received eteplirsen 30 mg/kg/week intravenously for 96 weeks. An untreated cohort with DMD not amenable to exon 51 skipping was also enrolled.Results78/79 eteplirsen-treated patients completed 96 weeks of treatment. 15/30 untreated patients completed the study; this cohort was considered an inappropriate control group because of genotype-driven differences in clinical trajectory. At Week 96, eteplirsen-treated patients showed increased exon skipping (18.7-fold) and dystrophin protein (7-fold) versus baseline. Post-hoc comparisons with patients from eteplirsen phase 2 studies (4658-201/202) and mutation-matched external natural history controls confirmed previous results, suggesting clinically notable attenuation of decline on the 6-minute walk test over 96 weeks (PROMOVI: -68.9 m; phase 2 studies: -67.3 m; external controls: -133.8 m) and significant attenuation of percent predicted forced vital capacity annual decline (PROMOVI: -3.3%, phase 2 studies: -2.2%, external controls: -6.0%; p < 0.001). Adverse events were generally mild to moderate and unrelated to eteplirsen. Most frequent treatment-related adverse events were headache and vomiting; none led to treatment discontinuation.ConclusionsThis large, multicenter study contributes to the growing body of evidence for eteplirsen, confirming a positive treatment effect, favorable safety profile, and slowing of disease progression versus natural history.

Comparison of Long-term Ambulatory Function in Patients with Duchenne Muscular Dystrophy Treated with Eteplirsen and Matched Natural History Controls.

BACKGROUND: Duchenne muscular dystrophy (DMD) is a rare, X-linked, fatal, degenerative neuromuscular disease caused by DMD gene mutations. A relationship between exon skipping and dystrophin production in exon 51-amenable patients treated with eteplirsen (EXONDYS 51®) is established. Once-weekly eteplirsen significantly increased dystrophin, with slower decline in ambulatory function compared to baseline. Long-term treatment with eteplirsen leads to accumulation of dystrophin over time and observed functional benefits in patients with DMD. OBJECTIVE: Compare long-term ambulatory function in eteplirsen-treated patients versus controls. METHODS: Study 201/202 included 12 eteplirsen-treated patients assessed twice/year for ambulatory function over 4 years. Ambulatory evaluations (6-minute walk test [6MWT], loss of ambulation, and North Star Ambulatory Assessment [NSAA]) were compared with matched controls from Italian Telethon and Leuven registries. RESULTS: At Years 3 and 4, eteplirsen-treated patients demonstrated markedly greater mean 6MWT than controls (difference in change from baseline of 132 m [95%CI (29, 235), p = 0.015] at Year 3 and 159 m [95%CI (66, 253), p = 0.002] at Year 4). At Year 4, a significantly greater proportion of eteplirsen-treated patients were still ambulant versus controls (10/12 vs 3/11; p = 0.020). At Year 3, eteplirsen-treated patients demonstrated milder NSAA decline versus controls (difference in change from baseline of 2.6, 95%CI [-6, 11]), however, the difference was not statistically significant; Year 4 control NSAA data were not available. CONCLUSION: In this retrospective matched control study, eteplirsen treatment resulted in attenuation of ambulatory decline over a 4-year observation period, supporting long-term benefit in patients with DMD.

Clinical development on the frontier: gene therapy for duchenne muscular dystrophy.

Introduction: The development of adeno-associated virus (AAV) vectors as safe vehicles for in vivo delivery of therapeutic genes has been a major milestone in the advancement of gene therapy, enabling a promising strategy for ameliorating a wide range of diseases, including Duchenne muscular dystrophy (DMD).Areas covered: Based on experience with the development of a gene transfer therapy agent for DMD, we discuss ways in which gene therapy for rare disease challenges traditional clinical development paradigms, and recommend a step-wise approach for design and evaluation to support broader applicability of gene therapy.Expert opinion: The gene therapy development approach should intentionally design the therapeutic construct and the clinical study to systematically evaluate agent delivery, safety, and efficacy. Rigorous preclinical work is essential for establishing an effective gene delivery platform and determining the efficacious dose. Clinical studies should thoroughly evaluate transduction, on-target transgene expression at the tissue and cellular level, and functional efficacy.

Eteplirsen Treatment Attenuates Respiratory Decline in Ambulatory and Non-Ambulatory Patients with Duchenne Muscular Dystrophy.

BACKGROUND: Duchenne muscular dystrophy (DMD) patients experience skeletal muscle degeneration, including respiratory muscles. Respiratory decline in glucocorticoid-treated DMD patients, measured by percent predicted forced vital capacity (FVC% p), is typically 5% annually in patients aged 10 to 18 years. OBJECTIVE: Evaluate the effects of eteplirsen on FVC% p annual change in 3 trials versus matched Cooperative International Neuromuscular Research Group Duchenne Natural History Study (CINRG DNHS) controls. METHODS: Eteplirsen studies 201/202 evaluated eligible ambulatory DMD patients for at least 4 years, study 204 evaluated primarily non-ambulatory DMD patients for 2 years, and ongoing study 301 is evaluating ambulatory DMD patients for 2 years (interim analysis is included). Eteplirsen-treated patients (n = 74) were amenable to exon 51 skipping and were receiving glucocorticoids. Three CINRG DNHS cohorts included: glucocorticoid-treated patients amenable to exon 51 skipping (Exon 51 CINRG DNHS; n = 20), all glucocorticoid-treated CINRG patients (All CINRG DNHS; n = 172), and all glucocorticoid-treated genotyped CINRG DNHS patients (Genotyped CINRG DNHS; n = 148). FVC% p assessments between ages 10 and <18 years were included for all patients; mixed-model analyses characterized FVC% p annual change. RESULTS: FVC% p annual change was greater for CINRG DNHS Exon 51 controls (- 6.00) versus patients in studies 201/202, study 204, and study 301 (- 2.19, P < 0.001; - 3.66, P 0.004; and - 3.79, P 0.017, respectively). FVC% p annual change in all eteplirsen studies suggested treatment benefit compared with the Genotyped CINRG DNHS (- 5.67) and All CINRG DNHS (- 5.56) cohorts (P < 0.05, all comparisons). CONCLUSIONS: Significant, clinically meaningful attenuation of FVC%p decline was observed in eteplirsen-treated patients versus CINRG DNHS controls.

A novel primary amine-based anion exchange membrane adsorber.

A novel anion exchange membrane adsorber is presented which shows excellent impurity removal under different buffer conductivities ranging from 2 to 2 7mS/cm. The membrane utilizes a primary amine ligand (polyallylamine) and was designed specifically to bind impurities at high salt concentrations. Studies with DNA, endotoxin, and virus spiked into buffer at varying salt conditions were done, resulting in clearance of >3, 4, and 4 LRV, respectively, with negligible change on increasing salt up to 27 mS/cm conductivities. Verification of virus removal in mAb feedstocks is also shown. The data are compared with other membrane adsorbers and a conventional resin which utilize traditional chemistries to demonstrate improved purification performance with the primary amine ligand. Additional data on scale-up of the membrane adsorber device is discussed. A stacked flat-sheet design was implemented to ensure linear scale-up of performance using bovine serum albumin (BSA) as a model. The linearly scalable device, coupled with the highly effective membrane for virus, DNA, and endotoxin removal, represents a step forward in polishing technology for the purification of monoclonal antibodies and recombinant proteins.

Filter preconditioning enables representative scaled-down modelling of filter capacity and viral clearance by mitigating the impact of virus spike impurities.

Endogenous and adventitious virus removal by size-exclusion membrane filtration is a critical dedicated step in an overall viral clearance strategy employed by biologics manufacturers as required by industry regulators. However, the addition of impurities from virus spike preparations used in validation studies can significantly reduce filter capacity, resulting in an oversized and suboptimal virus filtration step. The hydraulic filter performance and virus retention observed in conventional scaled-downed validation models may not necessarily represent performance observed during process development, nor be predictive of manufacturing performance. Using filter flow decay as a relevant processing endpoint, an alternative and more comprehensive approach to virus filter validation has been developed to overcome the limitations imposed by virus spike impurities. With a model feedstream, we have demonstrated comparable virus removal using the conventional virus spiking approach and a complementary preconditioned virus challenge. Similar to a currently accepted method used in the validation of sterilizing-grade filters, this method entails processing non-spiked feed to a volumetric throughput target, followed by processing virus-spiked feed to a final flow decay endpoint to determine viral clearance. This comprehensive approach yields predictive virus retention data under protein-dominant fouling conditions that better model the hydraulic performance of the manufacturing-scale virus filtration operation.