Search Results (8)

Differences in gait patterns of children with Duchenne muscular dystrophy (DMD) and typically developing (TD) peers are visible to the eye, but quantifications of those differences outside of the gait laboratory have been elusive. In this work, we measured vertical, mediolateral, and anteroposterior acceleration using a waist-worn iPhone accelerometer during ambulation across a typical range of velocities. Fifteen TD and fifteen DMD children from 3 to 16 years of age underwent eight walking/running activities, including five 25 m walk/run speed-calibration tests at a slow walk to running speeds (SC-L1 to SC-L5), a 6-min walk test (6MWT), a 100 m fast walk/jog/run (100MRW), and a free walk (FW). For clinical anchoring purposes, participants completed a Northstar Ambulatory Assessment (NSAA). We extracted temporospatial gait clinical features (CFs) and applied multiple machine learning (ML) approaches to differentiate between DMD and TD children using extracted temporospatial gait CFs and raw data. Extracted temporospatial gait CFs showed reduced step length and a greater mediolateral component of total power (TP) consistent with shorter strides and Trendelenberg-like gait commonly observed in DMD. ML approaches using temporospatial gait CFs and raw data varied in effectiveness at differentiating between DMD and TD controls at different speeds, with an accuracy of up to 100%. We demonstrate that by using ML with accelerometer data from a consumer-grade smartphone, we can capture DMD-associated gait characteristics in toddlers to teens. Full article

Brain function and its effect on motor performance in Duchenne muscular dystrophy (DMD) is an emerging concept. The present study explored how cumulative dystrophin isoform loss, age, and a corticosteroid treatment affect DMD motor outcomes. A total of 133 genetically confirmed DMD patients from Sri Lanka were divided into two groups based on whether their shorter dystrophin isoforms (Dp140, Dp116, and Dp71) were affected: Group 1, containing patients with Dp140, Dp116, and Dp71 affected (n = 98), and Group 2, containing unaffected patients (n = 35). A subset of 52 patients (Group 1, n = 38; Group 2, n = 14) was followed for up to three follow-ups performed in an average of 28-month intervals. The effect of the cumulative loss of shorter dystrophin isoforms on the natural history of DMD was analyzed. A total of 74/133 (56%) patients encountered developmental delays, with 66/74 (89%) being in Group 1 and 8/74 (11%) being in Group 2 (p < 0.001). Motor developmental delays were predominant. The hip and knee muscular strength, according to the Medical Research Council (MRC) scale and the North Star Ambulatory Assessment (NSAA) activities, “standing on one leg R”, “standing on one leg L”, and “walk”, declined rapidly in Group 1 (p < 0.001 In the follow-up analysis, Group 1 patients became wheelchair-bound at a younger age than those of Group 2 (p = 0.004). DMD motor dysfunction is linked to DMD mutations that affect shorter dystrophin isoforms. When stratifying individuals for clinical trials, considering the DMD mutation site and its impact on a shorter dystrophin isoform is crucial. Full article

(1) Background: Duchenne (DMD) is a rare neuromuscular disease that progressively weakens muscles, which severely impairs gait capacity. The Six Minute-Walk Test (6MWT), which is commonly used to evaluate and monitor the disease’s evolution, presents significant variability due to extrinsic factors such as patient motivation, fatigue, and learning effects. Therefore, there is a clear need for the establishment of precise clinical endpoints to measure patient mobility. (2) Methods: A novel score (6M+ and 2M+) is proposed, which is derived from the use of a new portable monitoring system capable of carrying out a complete gait analysis. The system includes several biomechanical sensors: a heart rate band, inertial measurement units, electromyography shorts, and plantar pressure insoles. The scores were obtained by processing the sensor signals and via gaussian-mixture clustering. (3) Results: The 6M+ and 2M+ scores were evaluated against the North Star Ambulatory Assessment (NSAA), the gold-standard for measuring DMD, and six- and two-minute distances. The 6M+ and 2M+ tests led to superior distances when tested against the NSAA. The 6M+ test and the 2M+ test in particular were the most correlated with age, suggesting that these scores better characterize the gait regressions in DMD. Additionally, the 2M+ test demonstrated an accuracy and stability similar to the 6M+ test. (4) Conclusions: The novel monitoring system described herein exhibited good usability with respect to functional testing in a clinical environment and demonstrated an improvement in the objectivity and reliability of monitoring the evolution of neuromuscular diseases. Full article

Network slicing is a vital component of the 5G system to support diverse network scenarios, creating virtual networks (slices) by mapping virtual network requests to real networks. The mapping is an arduous computing process, mathematically studied and known as the Virtual Network Embedding (VNE) problem, and its complexity is NP-Hard. The mapping process is oriented to respect the QoS demands from the virtual network requests and the available resources in the physical-substrate infrastructure. Meta-heuristic approaches are a suitable way to solve the VNE problems because of their capacity to escape from the local optimum and adapt the solution search to complex networks; these abilities are essential in 5G networks scenarios. This article presents a systematic review of meta-heuristics organized by application, development and problem-solving approaches to VNE. It also provides the standard parameters to model the infrastructure and virtual network requests to simulate network slicing as a service. Finally, our work proposes some future research based on the discovered gaps. Full article

Objective: The North Star Ambulatory Assessment (NSAA) is a validated 17-item functional rating scale and widely used to assess motor function in boys with Duchenne muscular dystrophy (DMD). The SARS-CoV-2 pandemic and subsequent Government ‘lockdown’ resulted in no face-to-face clinic visits hence the motor abilities were not monitored. The aim was to investigate whether the NSAA was feasible and reliable by video assessment. Method: Ten ambulant DMD boys were selected from the electronic hospital records. Two physiotherapists scored the boys’ NSAA independently and the intraclass correlation coefficient was used to assess agreement. The video scores were compared to two previous NSAA in-clinic scores. Results: Mean scores (SD) for clinic visit one were 22.6 (4.19) and clinic visit two 21.8 (5.3). The two physiotherapists video mean scores were 20.6 (5.66) for physiotherapist 1 and 20.6 (6.53) for physiotherapist 2. The intraclass correlation coefficient was 0.98 (95% CI 0.93–1.00) for the total NSAA and 1.00 (95% CI 1.00 to 1.00) for the rise time. The mean decline in score from clinic visit one (−12 months) to video assessment was 2.0 (2.8SD). Conclusion: The results from the study suggest that video NSAA is partially feasible and reliable. Full article

The genetic code defines how information in the genome is translated into protein. Aside from a handful of isolated exceptions, this code is universal. Researchers have developed techniques to artificially expand the genetic code, repurposing codons and translational machinery to incorporate nonstandard amino acids (nsAAs) into proteins. A key challenge for robust genetic code expansion is orthogonality; the engineered machinery used to introduce nsAAs into proteins must co-exist with native translation and gene expression without cross-reactivity or pleiotropy. The issue of orthogonality manifests at several levels, including those of codons, ribosomes, aminoacyl-tRNA synthetases, tRNAs, and elongation factors. In this concept paper, we describe advances in genome recoding, translational engineering and associated challenges rooted in establishing orthogonality needed to expand the genetic code. Full article

Background: Combined androgen blockade (CAB) is a promising treatment modality for prostate cancer (PCA). In the present meta-analysis, we compared the efficacy and safety of first-line CAB using an antiandrogen (AA) with castration monotherapy in patients with advanced PCA. Methods: PubMed, embase, Cochrane, and Google Scholar were searched for randomized controlled trials (RCTS) published through 12 December 2016. Hazard ratios (HRS) with 95% confidence intervals (CIS) were determined for primary outcomes: overall survival (OS) and progression-free survival (PFS). Subgroup analyses were performed for Western compared with Eastern patients and use of a nonsteroidal AA (NSAA) compared with a steroidal AA (SAA). Results: Compared with castration monotherapy, CAB using an AA was associated with significantly improved OS (n = 14; HR: 0.90; 95% CI: 0.84 to 0.97; p = 0.003) and PFS (n = 13; HR: 0.89; 95% CI: 0.80 to 1.00; p = 0.04). No significant difference in OS (p = 0.71) and PFS (p = 0.49) was observed between the Western and Eastern patients. Compared with castration monotherapy, CAB using a NSAA was associated with significantly improved OS (HR: 0.88; 95% CI: 0.82 to 0.95; p = 0.0009) and PFS (HR: 0.85; 95% CI: 0.73 to 0.98; p = 0.007)—a result that was not achieved with CAB using a SAA. The safety profiles of CAB and monotherapy were similar in terms of adverse events, including hot flushes, impotence, and grade 3 or 4 events, with the exception of risk of diarrhea and liver dysfunction or elevation in liver enzymes, which were statistically greater with CAB using an AA. Conclusions: Compared with castration monotherapy, first-line CAB therapy with an AA, especially a NSAA, resulted in significantly improved OS and PFS, and had an acceptable safety profile in patients with advanced PCA. Full article

Introduction: Maximal androgen blockade (mab) versus castration alone in patients with metastatic prostate cancer has been extensively evaluated in randomized trials. The inconsistent results have led to the publication of multiple meta-analyses. The present review examines the evidence from meta-analytic reports to determine whether mab using agents such as flutamide, nilutamide, and cyproterone acetate (cpa) is associated with a survival advantage. Methods: We conducted a systematic review of the literature (medline, embase, and the Cochrane Library through July 2004; cancerlit through October 2002) for meta-analyses that compared mab with castration alone in previously untreated men with metastatic prostate cancer (D1 or D2, N+/M0 or M1). Two reviewers selected papers for eligibility; disagreement was resolved by all the authors through consensus. Results: The literature search identified six meta-analyses that met the eligibility criteria of the review. Two of those reports were based on individual patient data (ipd), and four were based on data from the published literature. All six meta-analyses pooled data on overall survival. The best evidence came from the largest meta-analysis, conducted by the Prostate Cancer Trialists Collaborative Group and based on ipd (8725 patients) from 27 trials. That analysis detected no difference in overall survival between mab and castration alone at 2 or 5 years. However, a subgroup analysis showed that mab with nonsteroidal anti-androgens (nsaas) was associated with a statistically significant improvement in 5-year survival over castration alone (27.6% vs. 24.7%; p = 0.005). The combination of mab with cpa, a steroidal anti-androgen, was associated with a statistically significant increased risk of death (15.4% vs. 18.1%; p = 0.04). Compared with castration alone, mab was associated with more side effects (that is, gastrointestinal, endocrine function) and reduced quality of life in domains related to treatment symptoms and emotional functioning. Conclusions: The small survival benefit conferred by mab with nsaa is of questionable clinical significance given the added toxicity and concomitant decline in quality of life observed in patients treated with mab. Therefore, combined treatment with flutamide or nilutamide should not be routinely offered to patients with meta-static prostate cancer beyond the purpose of blocking testosterone flare. Monotherapy, consisting of orchiectomy or the administration of a luteinizing hormone–releasing hormone agonist is recommended as standard treatment. Full article