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

Novel approaches for the serodiagnosis of louse-borne relapsing fever

Louse-borne relapsing fever (LBRF) caused by B. recurrentis is a poverty-related and neglected infectious disease with an endemic focus in the Horn of Africa. Re-emergence of the disease occurred in Europe during the refugee crisis in 2015 and sporadic outbreaks were frequently reported in Eastern Africa where poor settings lack affordable diagnostics. Currently, there are no validated in vitro assays available for the serodiagnosis of LBRF. The aim of this study was to develop novel and reliable immunoassays by investigating clinically suspected and culture-confirmed serum samples from LBRF patients and a broad panel of serum samples from patients with other spirochetal, bacterial, and parasitic diseases. We identified two immunoreactive antigens (complement-inhibiting protein CihC and the glycerophosphodiester phosphodiesterase GlpQ of B. recurrentis) as the most promising target candidates leading to the evaluation of two immunoassays (line immunoblot and ELISA) for IgM and IgG. To optimize the IgM immunoassay, we conducted a bioinformatic approach to localize the relevant immunogenic regions within CihC. By utilizing a N-terminal CihC fragment, the sensitivity and specificity of both immunoassays (CihC and GlpQ) were high (IgM: sensitivity 100%, specificity of 89.9%, IgG: sensitivity 100%, specificity 99.2%). In conclusion, our findings indicate the diagnostic potential of CihC and GlpQ as valuable markers for the serodiagnosis of LBRF even at early time points of infection. Here, we provide strong evidence for the utilization of these immunoassays as reliable tools in clinical practice

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

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

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

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

Reproducibility in modeling and simulation of the knee:Academic, industry, and regulatory perspectives

Stakeholders in the modeling and simulation (M&amp;S) community organized a workshop at the 2019 Annual Meeting of the Orthopaedic Research Society (ORS) entitled “Reproducibility in Modeling and Simulation of the Knee: Academic, Industry, and Regulatory Perspectives.” The goal was to discuss efforts among these stakeholders to address irreproducibility in M&amp;S focusing on the knee joint. An academic representative from a leading orthopedic hospital in the United States described a multi-institutional, open effort funded by the National Institutes of Health to assess model reproducibility in computational knee biomechanics. A regulatory representative from the United States Food and Drug Administration indicated the necessity of standards for reproducibility to increase utility of M&amp;S in the regulatory setting. An industry representative from a major orthopedic implant company emphasized improving reproducibility by addressing indeterminacy in personalized modeling through sensitivity analyses, thereby enhancing preclinical evaluation of joint replacement technology. Thought leaders in the M&amp;S community stressed the importance of data sharing to minimize duplication of efforts. A survey comprised 103 attendees revealed strong support for the workshop and for increasing emphasis on computational modeling at future ORS meetings. Nearly all survey respondents (97%) considered reproducibility to be an important issue. Almost half of respondents (45%) tried and failed to reproduce the work of others. Two-thirds of respondents (67%) declared that individual laboratories are most responsible for ensuring reproducible research whereas 44% thought that journals are most responsible. Thought leaders and survey respondents emphasized that computational models must be reproducible and credible to advance knee M&amp;S.</p

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

Sheep Updates 2005 - Part 7

This session covers eight papers from different authors: POSTERS 1. Sulpher in wool and its implications for fleece weight and sheep health, SM Liu, AC Schlink, JR Williams, CSIRO Livestock Industries Wembley WA, ME Dowling,JCGreef, Department of Agriculture Western Australia. 2. Stubbles for sheep: a reality check, Roy Butler, Keith Croker, Department of Agriculture Western Australia. 3. Genetic benchmarking using artificial insemination, LC Butler, JC Greeff, Department of Agriculture Western Australia. 4. The potential lambing performances of ewes in mixed age flocks, Kieth Croker, Department of Agriculture Western Australia, Rob Davidson, WAMMCO International, formally University of Western Australia, Ken Hart, Department of Agriculture Western Australia,Doug Harrington Cowcher Farms Narrogin, Mario D\u27Antuono, Department of Agriculture Western Australia. 5. National Livestock Identification System (Sheep) in Western Australia, Julian Gardner, Department of Agriculture Western Australia. DISPLAYS - TOOLS 6. To Feed or Not to Feed - I Only Hamlet had the Calculator!, Geoff Duddy, Livestock Officer(Sheep & Wool) Yanco. 7. WormBoss - a national Australian computer-based sheep worm control tool, RG Woodgate, Department of Agriculture Western Australia, A LeFeuvre, Queensland Department of Primary Industries and Fisheries, and Genie Pty Ltd, Warwick Qld, A Bailey, Department of Primary Industries, Water and Environment, Kings Meadow Tas, RB Besier, Department of Agriculture Western Australia, N. Campbell, Department of Primary Industries Victoria, Attwood Vic, I Carmichael, South Australian Research and Development Institute, Glenside SA, S. Love, NSW Department of Primary Industries, Armidale NSW. 8. \u27Eye in the sky\u27 takes guesswork out of farmers pasture decisions, Richard Stovold, Department of Land Informatio