Individual heat map assessments demonstrate vestronidase alfa treatment response in a highly heterogeneous mucopolysaccharidosis VII study population.

Mucopolysaccharidosis (MPS) VII is an ultra-rare, progressively debilitating, life-threatening lysosomal disease caused by deficiency of the enzyme, β-glucuronidase. Vestronidase alfa is an approved enzyme replacement therapy for MPS VII. UX003-CL301 was a phase 3, randomized, placebo-controlled, blind-start study examining the efficacy and safety of vestronidase alfa 4 mg/kg intravenously administered every 2 weeks to 12 patients with MPS VII. Due to the rarity of disease, broad eligibility criteria resulted in a highly heterogeneous population with variable symptoms. For an integrated view of the diverse data, the changes from baseline (or randomization for the placebo period) in clinical endpoints were grouped into three functional domains (mobility, fatigue, and fine motor + self-care) and analyzed post-hoc as subject-level heat maps. Mobility assessments included the 6-minute walk test, 3-minute stair climb test, Bruininks-Oseretsky test (BOT-2) gross motor function subtests, and patient-reported outcome assessments (PROs) related to movement, pain, and ambulation. Fatigue assessments included the Pediatric Quality of Life Multidimensional Fatigue Scale and other fatigue-related PROs. Fine motor + self-care assessments included BOT-2 fine motor function subtests and PROs for eating, dressing, hygiene, and caregiver assistance. Most subjects showed improvement in at least one domain. Two subjects improved in two or more domains and two subjects did not show clear improvement in any domain. Both severely and mildly affected subjects improved with vestronidase alfa in clinical assessments, PRO results, or both. Heat map analysis demonstrates how subjects responded to treatment across multiple domains, providing a useful visual tool for studying rare diseases with variable symptoms

Locomotor adjustments during stair ascent in children with Down Syndrome: Comparison between walking and crawling strategies

Stair negotiation provides an important yet different paradigm to study environment navigation. As one has constantly move himself up while adjusting step length and foot placement due to the stair constraints, this paradigm is ideal to study motor strategy and adaptation in children with and without disabilities. Down syndrome (DS) is the most common genetic condition and causes significant delays in motor and cognitive development. Children with DS show poor postural control and less efficient gait patterns. When negotiating obstacles, they often select a more conservative strategy (i.e. crawling instead of walking). This study aimed to examine motor strategy and spatiotemporal gait patterns in children with DS while ascending stairs of different heights

Simulation and experimental study of rheological properties of CeO2 – water nanofluid

Open Access. This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.Metal oxide nanoparticles offer great merits over controlling rheological, thermal, chemical and physical properties of solutions. The effectiveness of a nanoparticle to modify the properties of a fluid depends on its diffusive properties with respect to the fluid. In this study, rheological properties of aqueous fluids (i.e. water) were enhanced with the addition of CeO2 nanoparticles. This study was characterized by the outcomes of simulation and experimental results of nanofluids. The movement of nanoparticles in the fluidic media was simulated by a large-scale molecular thermal dynamic program (i.e. LAMMPS). The COMPASS force field was employed with smoothed particle hydrodynamic potential (SPH) and discrete particle dynamics potential (DPD). However, this study develops the understanding of how the rheological properties are affected due to the addition of nanoparticles in a fluid and the way DPD and SPH can be used for accurately estimating the rheological properties with Brownian effect. The rheological results of the simulation were confirmed by the convergence of the stress autocorrelation function, whereas experimental properties were measured using a rheometer. These rheological values of simulation were obtained and agreed within 5 % of the experimental values; they were identified and treated with a number of iterations and experimental tests. The results of the experiment and simulation show that 10 % CeO2 nanoparticles dispersion in water has a viscosity of 2.0–3.3 mPasPeer reviewedFinal Published versio

Content Placement in Cache-Enabled Sub-6 GHz and Millimeter-Wave Multi-antenna Dense Small Cell Networks

This paper studies the performance of cache-enabled dense small cell networks consisting of multi-antenna sub-6 GHz and millimeter-wave base stations. Different from the existing works which only consider a single antenna at each base station, the optimal content placement is unknown when the base stations have multiple antennas. We first derive the successful content delivery probability by accounting for the key channel features at sub-6 GHz and mmWave frequencies. The maximization of the successful content delivery probability is a challenging problem. To tackle it, we first propose a constrained cross-entropy algorithm which achieves the near-optimal solution with moderate complexity. We then develop another simple yet effective heuristic probabilistic content placement scheme, termed two-stair algorithm, which strikes a balance between caching the most popular contents and achieving content diversity. Numerical results demonstrate the superior performance of the constrained cross-entropy method and that the two-stair algorithm yields significantly better performance than only caching the most popular contents. The comparisons between the sub-6 GHz and mmWave systems reveal an interesting tradeoff between caching capacity and density for the mmWave system to achieve similar performance as the sub-6 GHz system.Comment: 14 pages; Accepted to appear in IEEE Transactions on Wireless Communication

Investigating the physiological underpinnings of proactive and reactive behavioural types in grey seals (Halichoerus grypus): Trial deployment of a minimally invasive data logger for recording heart rate and heart rate variability in a wild free-ranging breeding pinniped species

Individuals differ non-randomly in their responses to stressors, exhibiting consistent individual differences (CIDs) in behavioural and physiological coping mechanisms commonly referred to as coping styles. Grey seals (Halichoerus grypus) are one of the few mammal species in which CIDs in stress responses have been documented in wild populations, though evidence thus far has been purely behavioural. Physiologically, coping styles can be distinguished by differences in the autonomic regulation of cardiac activity, which can be measured using heart rate variability (HRV). The objectives of this study were two-fold. First, to assess the suitability of Polar® RS800CX monitors and H2/H3 sensors for conducting HRV analyses in grey seals. Second, to quantify inter-individual variation, repeatability, and reproductive performance correlates of baseline HRV. Polar® devices were deployed successfully during the 2013 breeding season on female grey seals (N = 15) on the Isle of May, Scotland, and were capable of recording HR patterns that characterise phocid seals at rest on land. However, artefacts were widespread and biased HRV metrics. Filtration and correction protocols were able to counteract the effects of artefacts, but severely limited the amount of data available for analysis. There were significant inter-individual differences in baseline HRV, which could not be explained by factors associated with the breeding season (e.g. percentage mass loss, day of lactation), diurnal rhythms (e.g. time of day), or stressors (e.g. days since capture). These differences in baseline HRV showed consistency across early and late lactation. Individuals appeared to separate into two groups: those with consistently lower or higher baseline HRV, characteristic of proactive and reactive coping styles, respectively. Furthermore, females with lower baseline HRV showed greater maternal transfer efficiency – though there were no associations between baseline HRV and maternal expenditure (i.e. maternal mass loss, kgday–1) or fitness outcomes (i.e. pup mass gain, kgday–1). These findings build upon previous studies on behavioural CIDs in female grey seals by providing the first preliminary evidence for physiological CIDs that are associated with maternal investment. However, due to small sample sizes, further studies are required to determine whether these findings are truly indicative of coping styles. In their current form, the use of Polar® devices requires several caveats and further studies are needed to fully realise their potential. Future research should focus on validation against simultaneously recorded ECGs to improve artefact detection and correction, and modification to minimise the occurrence of artefacts. Despite their limitations, Polar® devices have immense potential as a minimally invasive research tool for conducting HRV analyses in the field

Overcoming barriers and increasing independence: service robots for elderly and disabled people

This paper discusses the potential for service robots to overcome barriers and increase independence of elderly and disabled people. It includes a brief overview of the existing uses of service robots by disabled and elderly people and advances in technology which will make new uses possible and provides suggestions for some of these new applications. The paper also considers the design and other conditions to be met for user acceptance. It also discusses the complementarity of assistive service robots and personal assistance and considers the types of applications and users for which service robots are and are not suitable

A Genetic Algorithm with Design of Experiments Approach to Predict the Optimal Process Parameters for FDM

This paper describes a Genetic Algorithm (GA) with Design of Experiments (DoE) approach to predict the optimized surface roughness and porosity characteristics of the parts produced using ABS material on stratasys FDM 2000 machine. The Mathematical Model (MM) was developed by using Response Surface Methodology (RSM). It is to predict and investigate the influence of selected process parameters namely slice thickness, road width, liquefier temperature and air gap and their interactions on the surface roughness and porosity. The developed MM is the fitness function in GA in order to find out the optimal sets of process parameters and to predict the corresponding surface quality characteristics. These results have been validated and the experimental results after GA are found to be in conformance with the predicted process parameters.Mechanical Engineerin