Dependable Sensor Fault Reconstruction in Air-Path System of Heavy-Duty Diesel Engines.

This paper addresses the problem of robust sensor faults detection and isolation in the air-path system of heavy-duty diesel engines, which has not been completely considered in the literature. Calibration or the total failure of a sensor can cause sensor faults. In the worst-case scenario, the engines can be totally damaged by the sensor faults. For this purpose, a second-order sliding mode observer is proposed to reconstruct the sensor faults in the presence of unknown external disturbances. To this aim, the concept of the equivalent output error injection method and the linear matrix inequality (LMI) tool are utilized to minimize the effects of uncertainties and disturbances on the reconstructed fault signals. The simulation results verify the performance and robustness of the proposed method. By reconstructing the sensor faults, the whole system can be prevented from failing before the corrupted sensor measurements are used by the controller.

The TREAT-NMD DMD Global Database: analysis of more than 7,000 Duchenne muscular dystrophy mutations.

Analyzing the type and frequency of patient-specific mutations that give rise to Duchenne muscular dystrophy (DMD) is an invaluable tool for diagnostics, basic scientific research, trial planning, and improved clinical care. Locus-specific databases allow for the collection, organization, storage, and analysis of genetic variants of disease. Here, we describe the development and analysis of the TREAT-NMD DMD Global database (http://umd.be/TREAT_DMD/). We analyzed genetic data for 7,149 DMD mutations held within the database. A total of 5,682 large mutations were observed (80% of total mutations), of which 4,894 (86%) were deletions (1 exon or larger) and 784 (14%) were duplications (1 exon or larger). There were 1,445 small mutations (smaller than 1 exon, 20% of all mutations), of which 358 (25%) were small deletions and 132 (9%) small insertions and 199 (14%) affected the splice sites. Point mutations totalled 756 (52% of small mutations) with 726 (50%) nonsense mutations and 30 (2%) missense mutations. Finally, 22 (0.3%) mid-intronic mutations were observed. In addition, mutations were identified within the database that would potentially benefit from novel genetic therapies for DMD including stop codon read-through therapies (10% of total mutations) and exon skipping therapy (80% of deletions and 55% of total mutations).

The TREAT-NMD Duchenne muscular dystrophy registries: conception, design, and utilization by industry and academia.

Duchenne muscular dystrophy (DMD) is an X-linked genetic disease, caused by the absence of the dystrophin protein. Although many novel therapies are under development for DMD, there is currently no cure and affected individuals are often confined to a wheelchair by their teens and die in their twenties/thirties. DMD is a rare disease (prevalence <5/10,000). Even the largest countries do not have enough affected patients to rigorously assess novel therapies, unravel genetic complexities, and determine patient outcomes. TREAT-NMD is a worldwide network for neuromuscular diseases that provides an infrastructure to support the delivery of promising new therapies for patients. The harmonized implementation of national and ultimately global patient registries has been central to the success of TREAT-NMD. For the DMD registries within TREAT-NMD, individual countries have chosen to collect patient information in the form of standardized patient registries to increase the overall patient population on which clinical outcomes and new technologies can be assessed. The registries comprise more than 13,500 patients from 31 different countries. Here, we describe how the TREAT-NMD national patient registries for DMD were established. We look at their continued growth and assess how successful they have been at fostering collaboration between academia, patient organizations, and industry.

Barrier function-based adaptive nonsingular terminal sliding mode control technique for a class of disturbed nonlinear systems.

In this article, an adaptive non-singular terminal sliding mode controller (NTSMC) is designed based on a barrier function for the robust stability of a category of non-linear dynamic systems in the existence of the external disturbances. The planned approach implements a non-singular terminal sliding mode controller (NTSMC) to ensure robust performance with finite time convergence and singularity-free dynamics. It also uses Barrier Functions (BFs) as an adaptation approach for the NTSMC to attain the tracking errors' convergence to a pre-defined neighbourhood of origin, with a controller gain that is not over-estimated and without requiring any knowledge about the upper bounds of disturbances. The Lyapunov-based stability analysis is carried out to confirm the asymptotic convergence of tracking errors to a pre-defined neighbourhood of zero. The effectiveness and performance of the planned approach is illustrated through simulations and experiments.

Iranian Registry of Duchenne and Becker Muscular Dystrophies: Characterization and Preliminary Data.

Duchenne (DMD) and Becker muscular dystrophies (BMD) are rare neuromuscular disorders caused by mutations in the dystrophin gene and failure in its protein production. The absence or the reduced expression of dystrophin render muscles prone to damage, including the cardiac and respiratory muscles with reduced life expectancy. Careful planning for clinical trials will require a sufficient number of confirmed cases to meet the inclusion criteria. National registries for rare disorders serve as an essential tool for personalized medicines or mutation-specific trials to facilitate patient recruitment. The Iranian Registry of DMD and BMD (IRDAB) collects detailed molecular data of Iranian DMD/BMD patients and carriers according to the TREAT-NMD Global Neuromuscular Network guidelines. As of March 2020, five hundred and twenty-two cases are registered. The registry incorporates multi-level web and database technologies, where registrants can access their data and compare it to the cumulative data. The registry's objectives are to recruit eligible patients for clinical trials and provide sufficient data for the national program of disease surveillance and social planning. Furthermore, the registry provides accurate epidemiological data, phenotype/genotype correlation, and evaluate the standards of care in Iran.

The Effects of Transdermal Estrogen Delivery on Bone Mineral Density in Postmenopausal Women: A Meta-analysis.

Due to its minimal systematic adverse effects, transdermal estrogen is widely used for the prevention of osteoporosis in postmenopausal women. The present meta-analysis aimed to clarify the effects of transdermal estrogen on bone mineral density (BMD) of postmenopausal women. Studies were identified by searching electronic databases including Cochrane Library, MEDLINE, Embase , and CINAHL databases, and also the Sciences Citation Index. Systematic review of articles was published between January 1989 to February 2016.Reference lists of the included articles were also evaluated and consultations were made with relevant experts. While 132 studies included the desired keywords, only nine clinical trials met the inclusion criteria and were finally reviewed. The pooled percent change in BMD was statistically significant in favor of transdermal estrogen. According to resulting pooled estimate, lumbar spine BMD one and two years after transdermal estrogen therapy was respectively 3.4% (95% CI: 1.7-5.1) and 3.7% (95% CI: 1.7-5.7) higher than the baseline values. The test for heterogeneity was not statistically significant based on the I2 heterogeneity index. One-two years of transdermal estrogen delivery can effectively increase BMD and protect the bone structure in postmenopausal women.

Clinical Outcomes in Duchenne Muscular Dystrophy: A Study of 5345 Patients from the TREAT-NMD DMD Global Database.

BACKGROUND: Recent short-term clinical trials in patients with Duchenne Muscular Dystrophy (DMD) have indicated greater disease variability in terms of progression than expected. In addition, as average life-expectancy increases, reliable data is required on clinical progression in the older DMD population. OBJECTIVE: To determine the effects of corticosteroids on major clinical outcomes of DMD in a large multinational cohort of genetically confirmed DMD patients. METHODS: In this cross-sectional study we analysed clinical data from 5345 genetically confirmed DMD patients from 31 countries held within the TREAT-NMD global DMD database. For analysis patients were categorised by corticosteroid background and further stratified by age. RESULTS: Loss of ambulation in non-steroid treated patients was 10 years and in corticosteroid treated patients 13 years old (p = 0.0001). Corticosteroid treated patients were less likely to need scoliosis surgery (p < 0.001) or ventilatory support (p < 0.001) and there was a mild cardioprotective effect of corticosteroids in the patient population aged 20 years and older (p = 0.0035). Patients with a single deletion of exon 45 showed an increased survival in contrast to other single exon deletions. CONCLUSIONS: This study provides data on clinical outcomes of DMD across many healthcare settings and including a sizeable cohort of older patients. Our data confirm the benefits of corticosteroid treatment on ambulation, need for scoliosis surgery, ventilation and, to a lesser extent, cardiomyopathy. This study underlines the importance of data collection via patient registries and the critical role of multi-centre collaboration in the rare disease field.

Finite-time tracking control of nth-order chained-form non-holonomic systems in the presence of disturbances.

This paper addresses the problem of finite-time tracking controller design for nth-order chained-form non-holonomic systems in the presence of unknown disturbances. To this aim, a generalized disturbance observer based controller is proposed and combined with a recursive terminal sliding mode approach which guarantees finite-time convergence of the disturbance observer dynamic. By introducing a time-varying transformation and introducing a new control law, the existence of the sliding around the recursive terminal sliding mode surfaces is guaranteed. Finally, the proposed approach is applied for a wheeled mobile robot with a fourth-order chained-form non-holonomic model. The simulation results demonstrate the desirable and robust tracking performance of the proposed approach in the presence of unknown disturbance.

Two-stage observer based offset-free MPC.

This paper addresses design of model predictive control (MPC) for dynamic systems in the presence of disturbances. For the systems with disturbances, it is common to use observers to estimate states and disturbances, allowing control algorithm to reject disturbances. In this paper, we demonstrate how one can extend model predictive control for systems with disturbances by applying full state and disturbance observer. To this aim, a two-stage approach is proposed where the observer design procedure is completely decoupled from the MPC problem, known as the separation principle. We focus on the decoupling principal and it is shown that the observer can be designed independently via a norm minimization problem to reduce effects of disturbances and model mismatch. On the other hand, the MPC law is obtained using the multi-parametric quadratic programming approach where the parameters are the components of the state vector.