Wearable Haptic Devices for Gait Re-education by Rhythmic Haptic Cueing

This research explores the development and evaluation of wearable haptic devices for gait sensing and rhythmic haptic cueing in the context of gait re-education for people with neurological and neurodegenerative conditions. Many people with long-term neurological and neurodegenerative conditions such as Stroke, Brain Injury, Multiple Sclerosis or Parkinson’s disease suffer from impaired walking gait pattern. Gait improvement can lead to better fluidity in walking, improved health outcomes, greater independence, and enhanced quality of life. Existing lab-based studies with wearable devices have shown that rhythmic haptic cueing can cause immediate improvements to gait features such as temporal symmetry, stride length, and walking speed. However, current wearable systems are unsuitable for self-managed use for in-the-wild applications with people having such conditions. This work aims to investigate the research question of how wearable haptic devices can help in long-term gait re-education using rhythmic haptic cueing. A longitudinal pilot study has been conducted with a brain trauma survivor, providing rhythmic haptic cueing using a wearable haptic device as a therapeutic intervention for a two-week period. Preliminary results comparing pre and post-intervention gait measurements have shown improvements in walking speed, temporal asymmetry, and stride length. The pilot study has raised an array of issues that require further study. This work aims to develop and evaluate prototype systems through an iterative design process to make possible the self-managed use of such devices in-the-wild. These systems will directly provide therapeutic intervention for gait re-education, offer enhanced information for therapists, remotely monitor dosage adherence and inform treatment and prognoses over the long-term. This research will evaluate the use of technology from the perspective of multiple stakeholders, including clinicians, carers and patients. This work has the potential to impact clinical practice nationwide and worldwide in neuro-physiotherapy

Vector-field statistics for the analysis of time varying clinical gait data.

BACKGROUND: In clinical settings, the time varying analysis of gait data relies heavily on the experience of the individual(s) assessing these biological signals. Though three dimensional kinematics are recognised as time varying waveforms (1D), exploratory statistical analysis of these data are commonly carried out with multiple discrete or 0D dependent variables. In the absence of an a priori 0D hypothesis, clinicians are at risk of making type I and II errors in their analyis of time varying gait signatures in the event statistics are used in concert with prefered subjective clinical assesment methods. The aim of this communication was to determine if vector field waveform statistics were capable of providing quantitative corroboration to practically significant differences in time varying gait signatures as determined by two clinically trained gait experts. METHODS: The case study was a left hemiplegic Cerebral Palsy (GMFCS I) gait patient following a botulinum toxin (BoNT-A) injection to their left gastrocnemius muscle. FINDINGS: When comparing subjective clinical gait assessments between two testers, they were in agreement with each other for 61% of the joint degrees of freedom and phases of motion analysed. For tester 1 and tester 2, they were in agreement with the vector-field analysis for 78% and 53% of the kinematic variables analysed. When the subjective analyses of tester 1 and tester 2 were pooled together and then compared to the vector-field analysis, they were in agreement for 83% of the time varying kinematic variables analysed. INTERPRETATION: These outcomes demonstrate that in principle, vector-field statistics corroborates with what a team of clinical gait experts would classify as practically meaningful pre- versus post time varying kinematic differences. The potential for vector-field statistics to be used as a useful clinical tool for the objective analysis of time varying clinical gait data is established. Future research is recommended to assess the usefulness of vector-field analyses during the clinical decision making process

Genomic-Bioinformatic Analysis of Transcripts Enriched in the Third-Stage Larva of the Parasitic Nematode Ascaris suum

Differential transcription in Ascaris suum was investigated using a genomic-bioinformatic approach. A cDNA archive enriched for molecules in the infective third-stage larva (L3) of A. suum was constructed by suppressive-subtractive hybridization (SSH), and a subset of cDNAs from 3075 clones subjected to microarray analysis using cDNA probes derived from RNA from different developmental stages of A. suum. The cDNAs (n = 498) shown by microarray analysis to be enriched in the L3 were sequenced and subjected to bioinformatic analyses using a semi-automated pipeline (ESTExplorer). Using gene ontology (GO), 235 of these molecules were assigned to ‘biological process’ (n = 68), ‘cellular component’ (n = 50), or ‘molecular function’ (n = 117). Of the 91 clusters assembled, 56 molecules (61.5%) had homologues/orthologues in the free-living nematodes Caenorhabditis elegans and C. briggsae and/or other organisms, whereas 35 (38.5%) had no significant similarity to any sequences available in current gene databases. Transcripts encoding protein kinases, protein phosphatases (and their precursors), and enolases were abundantly represented in the L3 of A. suum, as were molecules involved in cellular processes, such as ubiquitination and proteasome function, gene transcription, protein–protein interactions, and function. In silico analyses inferred the C. elegans orthologues/homologues (n = 50) to be involved in apoptosis and insulin signaling (2%), ATP synthesis (2%), carbon metabolism (6%), fatty acid biosynthesis (2%), gap junction (2%), glucose metabolism (6%), or porphyrin metabolism (2%), although 34 (68%) of them could not be mapped to a specific metabolic pathway. Small numbers of these 50 molecules were predicted to be secreted (10%), anchored (2%), and/or transmembrane (12%) proteins. Functionally, 17 (34%) of them were predicted to be associated with (non-wild-type) RNAi phenotypes in C. elegans, the majority being embryonic lethality (Emb) (13 types; 58.8%), larval arrest (Lva) (23.5%) and larval lethality (Lvl) (47%). A genetic interaction network was predicted for these 17 C. elegans orthologues, revealing highly significant interactions for nine molecules associated with embryonic and larval development (66.9%), information storage and processing (5.1%), cellular processing and signaling (15.2%), metabolism (6.1%), and unknown function (6.7%). The potential roles of these molecules in development are discussed in relation to the known roles of their homologues/orthologues in C. elegans and some other nematodes. The results of the present study provide a basis for future functional genomic studies to elucidate molecular aspects governing larval developmental processes in A. suum and/or the transition to parasitism

Mirror gait retraining for the treatment of patellofemoral pain in female runners.

BACKGROUND: Abnormal hip mechanics are often implicated in female runners with patellofemoral pain. We sought to evaluate a simple gait retraining technique, using a full-length mirror, in female runners with patellofemoral pain and abnormal hip mechanics. Transfer of the new motor skill to the untrained tasks of single leg squat and step descent was also evaluated. METHODS: Ten female runners with patellofemoral pain completed 8 sessions of mirror and verbal feedback on their lower extremity alignment during treadmill running. During the last 4 sessions, mirror and verbal feedback were progressively removed. Hip mechanics were assessed during running gait, a single leg squat and a step descent, both pre- and post-retraining. Subjects returned to their normal running routines and analyses were repeated at 1-month and 3-month post-retraining. Data were analyzed via repeated measures analysis of variance. FINDINGS: Subjects reduced peaks of hip adduction, contralateral pelvic drop, and hip abduction moment during running (P<0.05, effect size=0.69-2.91). Skill transfer to single leg squatting and step descent was noted (P<0.05, effect size=0.91-1.35). At 1 and 3 months post retraining, most mechanics were maintained in the absence of continued feedback. Subjects reported improvements in pain and function (P<0.05, effect size=3.81-7.61) and maintained through 3 months post retraining. INTERPRETATION: Mirror gait retraining was effective in improving mechanics and measures of pain and function. Skill transfer to the untrained tasks of squatting and step descent indicated that a higher level of motor learning had occurred. Extended follow-up is needed to determine the long term efficacy of this treatment

Possible mechanisms of host resistance to Haemonchus contortus infection in sheep breeds native to the Canary Islands

Haemonchus contortus appears to be the most economically important helminth parasite for small ruminant production in many regions of the world. The two sheep breeds native to the Canary Islands display distinctly different resistant phenotypes under both natural and experimental infections. Canaria Hair Breed (CHB) tends to have significantly lower worm burden and delayed and reduced egg production than the susceptible Canaria Sheep (CS). To understand molecular mechanisms underlying host resistance, we compared the abomasal mucosal transcriptome of the two breeds in response to Haemonchus infection using RNAseq technology. The transcript abundance of 711 and 50 genes were significantly impacted by infection in CHB and CS, respectively (false discovery rate <0.05) while 27 of these genes were significantly affected in both breeds. Likewise, 477 and 16 Gene Ontology (GO) terms were significantly enriched in CHB and CS, respectively (P < 1.0 × 10(−4)). A broad range of mechanisms have evolved in resistant CHB to provide protection against the parasite. Our findings suggest that readily inducible acute inflammatory responses, complement activation, accelerated cell proliferation and subsequent tissue repair, and immunity directed against parasite fecundity all contributed to the development of host resistance to parasitic infection in the resistant breed

Multidimensional treatment foster care for preschoolers: early findings of an implementation in the Netherlands

Multidimensional Treatment Foster Care (MTFC) has been shown to be an evidence based alternative to residential rearing and an effective method to improve behavior and attachment of preschool foster children in the US. This preliminary study investigated an application of MTFC for preschoolers (MTFC-P) in the Netherlands focusing on behavioral outcomes in course of the intervention. To examine the following hypothesis: “the time in the MTFC-P intervention predicts a decline in problem behavior, as this is the desired outcome for children assigned to MTFC-P”, we assessed the daily occurrence of 38 problem behaviors via telephone interviews. Repeated measures revealed significant reduced problem behavior in course of the program. MTFC-P promises to be a treatment model suitable for high-risk foster children, that is transferable across centres and countries

Understanding Robustness and Generalization of Artificial Neural Networks Through Fourier Masks

Despite the enormous success of artificial neural networks (ANNs) in many disciplines, the characterization of their computations and the origin of key properties such as generalization and robustness remain open questions. Recent literature suggests that robust networks with good generalization properties tend to be biased toward processing low frequencies in images. To explore the frequency bias hypothesis further, we develop an algorithm that allows us to learn modulatory masks highlighting the essential input frequencies needed for preserving a trained network's performance. We achieve this by imposing invariance in the loss with respect to such modulations in the input frequencies. We first use our method to test the low-frequency preference hypothesis of adversarially trained or data-augmented networks. Our results suggest that adversarially robust networks indeed exhibit a low-frequency bias but we find this bias is also dependent on directions in frequency space. However, this is not necessarily true for other types of data augmentation. Our results also indicate that the essential frequencies in question are effectively the ones used to achieve generalization in the first place. Surprisingly, images seen through these modulatory masks are not recognizable and resemble texture-like patterns

Adaptive Evolution of Staphylococcus aureus during Chronic Endobronchial Infection of a Cystic Fibrosis Patient

The molecular adaptation of Staphylococcus aureus to its host during chronic infection is not well understood. Comparative genome sequencing of 3 S. aureus isolates obtained sequentially over 26 months from the airways of a cystic fibrosis patient, revealed variation in phage content, and genetic polymorphisms in genes which influence antibiotic resistance, and global regulation of virulence. The majority of polymorphisms were isolate-specific suggesting the existence of an heterogeneous infecting population that evolved from a single infecting strain of S. aureus. The genetic variation identified correlated with differences in growth rate, hemolytic activity, and antibiotic sensitivity, implying a profound effect on the ecology of S. aureus. In particular, a high frequency of mutations in loci associated with the alternate transcription factor SigB, were observed. The identification of genes under diversifying selection during long-term infection may inform the design of novel therapeutics for the control of refractory chronic infections

Identification of the amino-acetonitrile derivative monepantel (AAD 1566) as a new anthelmintic drug development candidate

Anthelmintic resistance has become a global phenomenon in gastro-intestinal nematodes of farm animals, including multi-drug resistance against the three major classes of anthelmintics. There is an urgent need for an anthelmintic with a new mode of action. The recently discovered amino-acetonitrile derivatives (AADs) offer a new class of synthetic chemicals with anthelmintic activity. The evaluation of AADs was pursued applying in vitro assays and efficacy and tolerability studies in rodents, sheep, and cattle. Amongst various suitable compounds, AAD 1566 eliminated many tested pathogenic nematode species, both at larval and adult stages, at a dose of 2.5 mg/kg bodyweight in sheep and 5.0 mg/kg bodyweight in cattle. The same doses were sufficient to cure animals infected with resistant or multi-drug-resistant nematode isolates. These findings, complemented by the good tolerability and low toxicity to mammals, suggest that AAD 1566, monepantel, would be a suitable anthelmintic drug development candidate