Quantification of head motion in children with cerebral palsy when testing segmental trunk control

The development of objective assessment tools to complement subjective evaluations could have a major impact in the evaluation of the consequences of neuromotor disabilities, specifically in the assessment of trunk control in children with cerebral palsy (CP). Current assessments are subjective and typically assess the general control status of a child under unbalancing situations. Only the Segmental Assessment of Trunk Control (SATCo) evaluates static, active and reactive control at six discrete trunk segmental levels and free sitting to identify the topmost trunk segment where the child does not demonstrate control. The characteristics of the SATCo make it an ideal start point to generate an objective measurement tool of control. Motion of the head is one of the main characteristics observed during a SATCo to determine the child's segmental level of control. This pilot study measured head motion during a SATCo to determine if the measurement reflected the clinical observations. Three children with different degrees of neuromotor disability were tested using the SATCo while a video camera recorded sagittal plane movements. A Head segment was defined by markers on the ear tragus and temporal fossa in vertical line with the ear when the head was aligned. Head segmental angles were calculated in relation to a real vertical, and the cumulative displacement was normalised by time (deg·s-1). One segment where external support was provided high on the trunk (Upper-Thoracic, UT) and one where external support was at the pelvis i.e. low on the trunk (Lower-Lumbar, LL) were selected for the analysis. Overall, head motion values were larger for the lower trunk tests (LL) than for the tests at the higher segment (UT) with greater external support provided. The poorer lumbar control of Child 2 and Child 3 was demonstrated in both active (39.9°·s-1, 23.3°·s-1) and reactive tests (37.3°·s-1, 13.8°·s-1). The results also showed how increasing task complexity (static to reactive) and reducing the level of support (UT to LL), increased head motion in the presence of a neuromotor disability. The results presented here corroborated the clinical evaluation of the SATCo. Head motion will have small values when children with CP are tested at a trunk segmental level where control has already been learnt or where external support is provided; children with poorer lumbar control will have an increased head motion when testing is below their trunk segmental level of assured control. This video-based approach represents a step towards the development of an objective tool for the assessment of head/trunk control in children with CP

Fully automated image-based estimation of postural point-features in children with cerebral palsy using deep learning

The aim of this study was to provide automated identification of postural point-features required to estimate the location and orientation of the head, multi-segmented trunk and arms from videos of the clinical test ‘Segmental Assessment of Trunk Control’ (SATCo). Three expert operators manually annotated 13 point-features in every fourth image of 177 short (5–10 s) videos (25 Hz) of 12 children with cerebral palsy (aged: 4.52 ± 2.4 years), participating in SATCo testing. Linear interpolation for the remaining images resulted in 30 825 annotated images. Convolutional neural networks were trained with cross-validation, giving held-out test results for all children. The point-features were estimated with error 4.4 ± 3.8 pixels at approximately 100 images per second. Truncal segment angles (head, neck and six thoraco-lumbar–pelvic segments) were estimated with error 6.4 ± 2.8°, allowing accurate classification (F1 > 80%) of deviation from a reference posture at thresholds up to 3°, 3° and 2°, respectively. Contact between arm point-features (elbow and wrist) and supporting surface was classified at F1 = 80.5%. This study demonstrates, for the first time, technical feasibility to automate the identification of (i) a sitting segmental posture including individual trunk segments, (ii) changes away from that posture, and (iii) support from the upper limb, required for the clinical SATCo

Democratization and gender-neutrality in English(es)

"Democratization" and "gender-neutrality" are two concepts commonly used in recent studies on language variation. While both concepts link linguistic phenomena to sociocultural changes, the extent to which they overlap and/or interact has not been studied in detail. In particular, not much is known about how linguistic changes related to democratization and gender-neutrality spread across registers or varieties of English, as well as whether speakers are aware of the changes that are taking place. In this paper we review the main theoretical issues regarding these concepts and relate them to the main findings in the articles in this issue, all of which study lexical and grammatical variation from a corpus-based perspective. Taken together, they help unveil some of the conscious and unconscious mechanisms that operate at the interface between democratization and gender-neutrality.Peer reviewe

The Semiotic Fractures of Vulnerable Bodies: Resistance to the Gendering of Legal Subjects

While the turn to vulnerability in law responds to a recurrent critique by feminist scholars on the disembodiment of legal personhood, this article suggests that the mobilization of vulnerability in the criminal courts does not necessarily offer female drug mules a direct path to justice. Through an analysis of sentencing appeals of female drug mules in England and Wales, this article presents a feminist critique of the dispositif of the person and its relation to vulnerability. Discourses on drug mules’ vulnerability mobilize the trope of the colonial victim in need of protection, which is often translated into legal mercy. But mercy is rather an expression of biopower which inscribes not only fragility onto the bodies of drug mules by figuring them as exemplar paradigms of colonial subjectivity, but also reinvigorates the dispositif of gender implicit in the legal person. In this set-up, it would appear as if law and politics totalize the registers of life, in this case the contours of vulnerable body. The article suggests we must revisit the image of the wounded body in order to carve out a space for resistance. Drawing on Elaine Scarry and Judith Butler, it suggests vulnerable bodies are marked by a semiotic openness, which renders them subject to appropriation but also able to signify the precarity produced by the law through their resistance to representation

The Base Excision Repair System of Salmonella enterica serovar Typhimurium Counteracts DNA Damage by Host Nitric Oxide

Intracellular pathogens must withstand nitric oxide (NO·) generated by host phagocytes. Salmonella enterica serovar Typhimurium interferes with intracellular trafficking of inducible nitric oxide synthase (iNOS) and possesses multiple systems to detoxify NO·. Consequently, the level of NO· stress encountered by S. Typhimurium during infection in vivo has been unknown. The Base Excision Repair (BER) system recognizes and repairs damaged DNA bases including cytosine and guanine residues modified by reactive nitrogen species. Apurinic/apyrimidinic (AP) sites generated by BER glycosylases require subsequent processing by AP endonucleases. S. Typhimurium xth nfo mutants lacking AP endonuclease activity exhibit increased NO· sensitivity resulting from chromosomal fragmentation at unprocessed AP sites. BER mutant strains were thus used to probe the nature and extent of nitrosative damage sustained by intracellular bacteria during infection. Here we show that an xth nfo S. Typhimurium mutant is attenuated for virulence in C3H/HeN mice, and virulence can be completely restored by the iNOS inhibitor L-NIL. Inactivation of the ung or fpg glycosylase genes partially restores virulence to xth nfo mutant S. Typhimurium, demonstrating that NO· fluxes in vivo are sufficient to modify cytosine and guanine bases, respectively. Mutants lacking ung or fpg exhibit NO·–dependent hypermutability during infection, underscoring the importance of BER in protecting Salmonella from the genotoxic effects of host NO·. These observations demonstrate that host-derived NO· damages Salmonella DNA in vivo, and the BER system is required to maintain bacterial genomic integrity

The life history of 21 breast cancers.

Cancer evolves dynamically as clonal expansions supersede one another driven by shifting selective pressures, mutational processes, and disrupted cancer genes. These processes mark the genome, such that a cancer's life history is encrypted in the somatic mutations present. We developed algorithms to decipher this narrative and applied them to 21 breast cancers. Mutational processes evolve across a cancer's lifespan, with many emerging late but contributing extensive genetic variation. Subclonal diversification is prominent, and most mutations are found in just a fraction of tumor cells. Every tumor has a dominant subclonal lineage, representing more than 50% of tumor cells. Minimal expansion of these subclones occurs until many hundreds to thousands of mutations have accumulated, implying the existence of long-lived, quiescent cell lineages capable of substantial proliferation upon acquisition of enabling genomic changes. Expansion of the dominant subclone to an appreciable mass may therefore represent the final rate-limiting step in a breast cancer's development, triggering diagnosis

Mutational processes molding the genomes of 21 breast cancers.

All cancers carry somatic mutations. The patterns of mutation in cancer genomes reflect the DNA damage and repair processes to which cancer cells and their precursors have been exposed. To explore these mechanisms further, we generated catalogs of somatic mutation from 21 breast cancers and applied mathematical methods to extract mutational signatures of the underlying processes. Multiple distinct single- and double-nucleotide substitution signatures were discernible. Cancers with BRCA1 or BRCA2 mutations exhibited a characteristic combination of substitution mutation signatures and a distinctive profile of deletions. Complex relationships between somatic mutation prevalence and transcription were detected. A remarkable phenomenon of localized hypermutation, termed "kataegis," was observed. Regions of kataegis differed between cancers but usually colocalized with somatic rearrangements. Base substitutions in these regions were almost exclusively of cytosine at TpC dinucleotides. The mechanisms underlying most of these mutational signatures are unknown. However, a role for the APOBEC family of cytidine deaminases is proposed

The development of a video retrieval system using a clinician-led approach

Patient video taken at home can provide valuable insights into the recovery progress during a programme of physical therapy, but is very time consuming for clinician review. Our work focussed on (i) enabling any patient to share information about progress at home, simply by sharing video and (ii) building intelligent systems to support Physical Therapists (PTs) in reviewing this video data and extracting the necessary detail. This paper reports the development of the system, appropriate for future clinical use without reliance on a technical team, and the clinician involvement in that development. We contribute an interactive content-based video retrieval system that significantly reduces the time taken for clinicians to review videos, using human head movement as an example. The system supports query-by-movement (clinicians move their own body to define search queries) and retrieves the essential fine-grained movements needed for clinical interpretation. This is done by comparing sequences of image-based pose estimates (here head rotations) through a distance metric (here Fréchet distance) and presenting a ranked list of similar movements to clinicians for review. In contrast to existing intelligent systems for retrospective review of human movement, the system supports a flexible analysis where clinicians can look for any movement that interests them. Evaluation by a group of PTs with expertise in training movement control showed that 96% of all relevant movements were identified with time savings of as much as 99.1% compared to reviewing target videos in full. The novelty of this contribution includes retrospective progress monitoring that preserves context through video, and content-based video retrieval that supports both fine-grained human actions and query-by-movement. Future research, including large clinician-led studies, will refine the technical aspects and explore the benefits in terms of patient outcomes, PT time, and financial savings over the course of a programme of therapy. It is anticipated that this clinician-led approach will mitigate the reported slow clinical uptake of technology with resulting patient benefit

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe