Publications by authors named "S P Knowler"

23 Publications

Facial changes related to brachycephaly in Cavalier King Charles Spaniels with Chiari-like malformation associated pain and secondary syringomyelia.

J Vet Intern Med 2020 Jan 5;34(1):237-246. Epub 2019 Nov 5.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, Daphne Jackson Road, Guildford, Surrey, GU7 Q22, United Kingdom.

Background: Recent studies including an innovative machine learning technique indicated Chiari-like malformation (CM) is influenced by brachycephalic features.

Objectives: Morphometric analysis of facial anatomy and dysmorphia in CM-associated pain (CM-P) and syringomyelia (SM) in the Cavalier King Charles Spaniel (CKCS).

Animals: Sixty-six client-owned CKCS.

Methods: Retrospective study of anonymized T2W sagittal magnetic resonance imaging of 3 clinical groups: (1) 11 without central canal dilation (ccd) or SM (CM-N), (2) 15 with CM-P with no SM or <2 mm ccd (CM-P), and (3) 40 with syrinx width ≥4 mm (SM-S). Morphometric analysis assessed rostral skull flattening and position of the hard and soft palate relative to the cranial base in each clinical group and compared CKCS with and without SM-S.

Results: Sixteen of 28 measured variables were associated to SM-S compared to CM-N and CM-P. Of these 6 were common to both groups. Predictive variables determined by discriminant analysis were (1) the ratio of cranial height with cranial length (P < .001 between SM-S and CM-N) and (2) the distance between the cerebrum and the frontal bone (P < .001 between SM-S and CM-P). CM-P had the lowest mean height of the maxillary area.

Conclusions And Clinical Importance: CKCS with CM-P and SM-S have cranial brachycephaly with osseous insufficiency in the skull with rostral flattening and increased proximity of the hard and soft palate to the cranial base. Changes are greatest with CM-P. These findings have relevance for understanding disease pathogenesis and for selection of head conformation for breeding purposes.
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January 2020

Using machine learning to understand neuromorphological change and image-based biomarker identification in Cavalier King Charles Spaniels with Chiari-like malformation-associated pain and syringomyelia.

J Vet Intern Med 2019 Nov 24;33(6):2665-2674. Epub 2019 Sep 24.

CVSSP, Centre for Vision, Speech and Signal Processing, University of Surrey, Guildford, United Kingdom.

Background: Chiari-like malformation (CM) is a complex malformation of the skull and cranial cervical vertebrae that potentially results in pain and secondary syringomyelia (SM). Chiari-like malformation-associated pain (CM-P) can be challenging to diagnose. We propose a machine learning approach to characterize morphological changes in dogs that may or may not be apparent to human observers. This data-driven approach can remove potential bias (or blindness) that may be produced by a hypothesis-driven expert observer approach.

Hypothesis/objectives: To understand neuromorphological change and to identify image-based biomarkers in dogs with CM-P and symptomatic SM (SM-S) using a novel machine learning approach, with the aim of increasing the understanding of these disorders.

Animals: Thirty-two client-owned Cavalier King Charles Spaniels (CKCSs; 11 controls, 10 CM-P, 11 SM-S).

Methods: Retrospective study using T2-weighted midsagittal Digital Imaging and Communications in Medicine (DICOM) anonymized images, which then were mapped to images of an average clinically normal CKCS reference using Demons image registration. Key deformation features were automatically selected from the resulting deformation maps. A kernelized support vector machine was used for classifying characteristic localized changes in morphology.

Results: Candidate biomarkers were identified with receiver operating characteristic curves with area under the curve (AUC) of 0.78 (sensitivity 82%; specificity 69%) for the CM-P biomarkers collectively and an AUC of 0.82 (sensitivity, 93%; specificity, 67%) for the SM-S biomarkers, collectively.

Conclusions And Clinical Importance: Machine learning techniques can assist CM/SM diagnosis and facilitate understanding of abnormal morphology location with the potential to be applied to a variety of breeds and conformational diseases.
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November 2019

Bacteriophages in Natural and Artificial Environments.

Pathogens 2019 Jul 12;8(3). Epub 2019 Jul 12.

Department of Physiology, Anatomy & Microbiology, La Trobe University, Bundoora, VIC 3086, Australia.

Bacteriophages (phages) are biological entities that have attracted a great deal of attention in recent years. They have been reported as the most abundant biological entities on the planet and their ability to impact the composition of bacterial communities is of great interest. In this review, we aim to explore where phages exist in natural and artificial environments and how they impact communities. The natural environment in this review will focus on the human body, soils, and the marine environment. In these naturally occurring environments there is an abundance of phages suggesting a role in the maintenance of bacterial community homeostasis. The artificial environment focuses on wastewater treatment plants, industrial processes, followed by pharmaceutical formulations. As in natural environments, the existence of bacteria in manmade wastewater treatment plants and industrial processes inevitably attracts phages. The presence of phages in these environments can inhibit the bacteria required for efficient water treatment or food production. Alternatively, they can have a positive impact by eliminating recalcitrant organisms. Finally, we conclude by describing how phages can be manipulated or formulated into pharmaceutical products in the laboratory for use in natural or artificial environments.
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July 2019

Pilot study of head conformation changes over time in the Cavalier King Charles spaniel breed.

Vet Rec 2019 01 11;184(4):122. Epub 2019 Jan 11.

Faculty of Health and Medical Sciences, School of Veterinary Medicine, University of Surrey, Guildford, UK.

Modern interpretation of head conformation in the Cavalier King Charles spaniel (CKCS) has favoured a smaller, more exaggerated, brachycephalic type than originally described in the 1929 breed standard. Recent research studies identified brachycephaly and reduced hind cranium as two conformational (dysmorphic) features that increase risk for symptomatic Chiari-like malformation and secondary syringomyelia (SM). A prospective pilot study investigated the hypothesis that dysmorphic head features could be assessed visually and correlated with risk of SM. Thirteen CKCS, selected from anonymised photographic evidence, were physically appraised by authorised Kennel Club judges using a head shape checklist. These subjective evaluations were then matched with objective measurements of the cranium (cephalic index and rostrocaudal doming) and their subsequent MRI. A positive correlation (P=0.039) between the judges' checklist score and rostrocaudal doming (hindskull ratio) and a positive correlation between the cephalic index and hindskull ratio (P=0.042) were identified. Five CKCS had no SM and their status tallied with 62 per cent of the judges' evaluation. Although the ability of adjudicators to identify differences in head conformation varied, there was sufficient association between the dysmorphic parameters and the risk of SM to cause concern and propose a larger study in CKCS breed.
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January 2019

Clinical Application of Diagnostic Imaging of Chiari-Like Malformation and Syringomyelia.

Front Vet Sci 2018 28;5:280. Epub 2018 Nov 28.

School of Veterinary Medicine, Faculty of Health & Medical Sciences, University of Surrey, Guildford, United Kingdom.

Chiari-like malformation (CM) and syringomyelia (SM) is a frequent diagnosis in predisposed brachycephalic toy breeds since increased availability of MRI. However, the relevance of that MRI diagnosis has been questioned as CM, defined as identification of a cerebellar herniation, is ubiquitous in some breeds and SM can be asymptomatic. This article reviews the current knowledge of neuroanatomical changes in symptomatic CM and SM and diagnostic imaging modalities used for the clinical diagnosis of CM-pain or myelopathy related to SM. Although often compared to Chiari type I malformation in humans, canine CM-pain and SM is more comparable to complex craniosynostosis syndromes (i.e., premature fusion of multiple skull sutures) characterized by a short skull (cranial) base, rostrotentorial crowding with rostral forebrain flattening, small, and ventrally orientated olfactory bulbs, displacement of the neural tissue to give increased height of the cranium and further reduction of the functional caudotentorial space with hindbrain herniation. MRI may further reveal changes suggesting raised intracranial pressure such as loss of sulci definition in conjunction with ventriculomegaly. In addition to these brachycephalic changes, dogs with SM are more likely to have craniocervical junction abnormalities including rostral displacement of the axis and atlas with increased odontoid angulation causing craniospinal junction deformation and medulla oblongata elevation. Symptomatic SM is diagnosed on the basis of signs of myelopathy and presence of a large syrinx that is consistent with the neuro-localization. The imaging protocol should establish the longitudinal and transverse extent of the spinal cord involvement by the syrinx. Phantom scratching and cervicotorticollis are associated with large mid-cervical syringes that extend to the superficial dorsal horn. If the cause of CSF channel disruption and syringomyelia is not revealed by anatomical MRI then other imaging modalities may be appropriate with radiography or CT for any associated vertebral abnormalities.
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November 2018