Tensor electrical impedance myography identifies bulbardisease progression in amyotrophic lateral sclerosis

Objective Electrical impedance myography (EIM) is a promising biomarker for amyotrophic lateral sclerosis (ALS). A key issue is how best to utilise the complex high dimensional, multi-frequency data output by EIM to fully characterise the progression of disease. Methods Muscle volume conduction properties were obtained from EIM recordings of the tongue across three electrode configurations and 14 input frequencies (76 Hz–625 kHz). Analyses of individual frequencies, averaged EIM spectra and non-negative tensor factorisation were undertaken. Longitudinal data were collected from 28 patients and 17 healthy volunteers at 3-monthly intervals for a maximum of 9 months. EIM was evaluated against the Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) bulbar sub-score, tongue strength and an overall bulbar disease burden score. Results Longitudinal changes to individual patient EIM spectra demonstrated complex shifts in the spectral shape. At a group level, a clear pattern emerged over time, characterised by an increase in centre frequency and general shift to the right of the spectral shape. Tensor factorisation reduced the spectral data from a total of 168 data points per participant per recording to a single value which captured the complexity of the longitudinal data and which we call tensor EIM (T-EIM). The absolute change in tensor EIM significantly increased within 3 months and continued to do so over the 9-month study duration. In a hypothetical clinical trial scenario tensor EIM required fewer participants (n = 64 at 50% treatment effect), than single frequency measures (n range 87–802) or ALSFRS-R bulbar subscore (n = 298). Conclusions Changes to tongue EIM spectra over time in ALS are complex. Tensor EIM captured and quantified disease progression and was more sensitive to changes than single frequency EIM measures and other biomarkers of bulbar disease. Significance Objective biomarkers for the assessment of bulbar disease in ALS are lacking. Tensor EIM enhances the biomarker potential of EIM data and can improve bulbar symptom monitoring in clinical trials

Tensor electrical impedance myography identifies clinically relevant features in amyotrophic lateral sclerosis

Objective. Electrical impedance myography (EIM) shows promise as an effective biomarker in amyotrophic lateral sclerosis (ALS). EIM applies multiple input frequencies to characterise muscle properties, often via multiple electrode configurations. Herein, we assess if non-negative tensor factorisation (NTF) can provide a framework for identifying clinically relevant features within a high dimensional EIM dataset. Approach. EIM data were recorded from the tongue of healthy and ALS diseased individuals. Resistivity and reactivity measurements were made for 14 frequencies, in three electrode configurations. This gives 84 (2 × 14 × 3) distinct data points per participant. NTF was applied to the dataset for dimensionality reduction, termed tensor EIM. Significance tests, symptom correlation and classification approaches were explored to compare NTF to using all raw data and feature selection. Main Results. Tensor EIM provides highly significant differentiation between healthy and ALS patients (p < 0.001, AUROC = 0.78). Similarly tensor EIM differentiates between mild and severe disease states (p < 0.001, AUROC = 0.75) and significantly correlates with symptoms (ρ = 0.7, p < 0.001). A trend of centre frequency shifting to the right was identified in diseased spectra, which is in line with the electrical changes expected following muscle atrophy. Significance. Tensor EIM provides clinically relevant metrics for identifying ALS-related muscle disease. This procedure has the advantage of using the whole spectral dataset, with reduced risk of overfitting. The process identifies spectral shapes specific to disease allowing for a deeper clinical interpretation

Modelling and analysis of electrical impedance myography of the lateral tongue

Objective: Electrical impedance myography (EIM) performed on the centre of the tongue shows promise in detecting amyotrophic lateral sclerosis (ALS). Lateral recordings may improve diagnostic performance and provide pathophysiological insights through the assessment of asymmetry. However, it is not known if electrode proximity to the muscle edge, or electrode rotation, distort spectra. We evaluated this using finite element-based modelling. Approach: Nine thousand EIM from patients and healthy volunteers were used to develop a finite element model for phase and magnitude. Simulations varied electrode proximity to the muscle edge and electrode rotation. LT-Spice simulations assessed disease effects. Patient data were assessed for reliability, agreement and classification performance. Main results: No effect on phase spectra was seen if all electrodes remained in contact with the tissue. Small effects on magnitude were observed. Cole-Cole circuit simulations indicated capacitance reduced with disease severity. Lateral tongue muscle recordings in both patients and healthy volunteers were reproducible and symmetrical. Combined lateral/central tongue EIM improved disease classification compared to either placement alone. Significance: Lateral EIM tongue measurements using phase angle are feasible. Such measurements are reliable, find no evidence of tongue muscle asymmetry in ALS and improve disease classification. Lateral measurements enhance tongue EIM in ALS

Multi-dimensional electrical impedance myography of the tongue as a potential biomarker for amyotrophic lateral sclerosis

Objective In amyotrophic lateral sclerosis (ALS) bulbar disease biomarkers are lacking. We evaluated a novel tongue electrical impedance myography (EIM) system, utilising both 2D and 3D electrode configurations for detection of tongue pathology. Methods Longitudinal multi-frequency phase angle spectra were recorded from 41 patients with ALS (baseline, 3 and 6 months) and 30 healthy volunteers (baseline and 6 months). ALS functional rating scale-revised (ALSFRS-R) data and quantitative tongue strength measurements were collected. EIM data were analysed for reliability (intra-class correlation coefficient; ICC) and differences between patients and volunteers ascertained using both univariate (Mann-Whitney U test) and multivariate techniques (feature selection and L2 norm). Results The device produced highly reliable data (pooled ICC: 0.836). Significant EIM differences were apparent between ALS patients and healthy volunteers (P<0.001). EIM data demonstrated a significant relationship to tongue strength and bulbar ALSFRS-R scores (P<0.015). The EIM recordings revealed a group level longitudinal change over 6 months and consistently identified patients in whom symptoms or tongue strength changed. Conclusions The novel EIM tongue system produces reliable data and can differentiate between healthy muscle and ALS-related disease. Significance Tongue EIM utilising multiple frequencies and electrode configurations has potential as a bulbar disease biomarker in ALS

NEOTROPICAL XENARTHRANS: a data set of occurrence of xenarthran species in the Neotropics

Xenarthrans – anteaters, sloths, and armadillos – have essential functions for ecosystem maintenance, such as insect control and nutrient cycling, playing key roles as ecosystem engineers. Because of habitat loss and fragmentation, hunting pressure, and conflicts with 24 domestic dogs, these species have been threatened locally, regionally, or even across their full distribution ranges. The Neotropics harbor 21 species of armadillos, ten anteaters, and six sloths. Our dataset includes the families Chlamyphoridae (13), Dasypodidae (7), Myrmecophagidae (3), Bradypodidae (4), and Megalonychidae (2). We have no occurrence data on Dasypus pilosus (Dasypodidae). Regarding Cyclopedidae, until recently, only one species was recognized, but new genetic studies have revealed that the group is represented by seven species. In this data-paper, we compiled a total of 42,528 records of 31 species, represented by occurrence and quantitative data, totaling 24,847 unique georeferenced records. The geographic range is from the south of the USA, Mexico, and Caribbean countries at the northern portion of the Neotropics, to its austral distribution in Argentina, Paraguay, Chile, and Uruguay. Regarding anteaters, Myrmecophaga tridactyla has the most records (n=5,941), and Cyclopes sp. has the fewest (n=240). The armadillo species with the most data is Dasypus novemcinctus (n=11,588), and the least recorded for Calyptophractus retusus (n=33). With regards to sloth species, Bradypus variegatus has the most records (n=962), and Bradypus pygmaeus has the fewest (n=12). Our main objective with Neotropical Xenarthrans is to make occurrence and quantitative data available to facilitate more ecological research, particularly if we integrate the xenarthran data with other datasets of Neotropical Series which will become available very soon (i.e. Neotropical Carnivores, Neotropical Invasive Mammals, and Neotropical Hunters and Dogs). Therefore, studies on trophic cascades, hunting pressure, habitat loss, fragmentation effects, species invasion, and climate change effects will be possible with the Neotropical Xenarthrans dataset

New insights into the genetic etiology of Alzheimer's disease and related dementias

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele

The best of both:a study of the feasibility of integrating scale of design and production for sustainable products

Contemporary design assumes and employs a highly diverse range of materials, skills and technologies to create new products for production. A close consideration of the relationships and characteristics of this multifaceted design and production system can help designers better understand the social and environmental implications of current practices, and help move us in constructive and positive directions for change. Academic researchers are able to take the long view on such change, they can analyse the existing situation and suggest beneficial possibilities for the future. This discussion takes such a view by bringing together design research, systems thinking and product design explorations. From this, we have developed a fresh approach that we have termed ‘integrated scales of design and production for sustainability’ (ISDPS). This integrated approach was first proposed by Walker in 2000. Since then the concept has been developed and elaborated upon (Dogan and Walker, Restoring Local Scale: Rethinking the Company Structures for Sustainable Product Design. Sustainable Innovation Conference 3, October 26–27, Stockholm, Sweden). This present discussion focuses on the feasibility and implications of sustainability of the ISDPS concept