Session 3: Natural Selection as a Causal Theory

Proceedings of the Pittsburgh Workshop in History and Philosophy of Biology, Center for Philosophy of Science, University of Pittsburgh, March 23-24 2001 Session 3: Natural Selection as a Causal Theor

Prevalence and Risk Factors for Presumptive Ascending/Descending Myelomalacia in Dogs after Thoracolumbar Intervertebral Disk Herniation

Background: Ascending/descending myelomalacia (ADMM) is a severe complication of thoracolumbar intervertebral disk herniation (TL-IVDH) in dogs. Hypothesis/Objectives: To investigate the prevalence and risk factors for ADMM in nonambulatory dogs with surgically treated TL-IVDH. Animals: Six-hundred and fifty-two client-owned dogs evaluated for TL-IVDH that underwent decompressive spinal surgery. Methods: Retrospective medical record review from February 2007 through December 2015. Results: Thirteen dogs developed ADMM, with an overall prevalence of 2.0%. The prevalence of ADMM was 0% in dogs with neurological signs graded 1 or 2 at admission or before magnetic resonance imaging (MRI) or surgical procedures, 0.6% in dogs with neurological signs graded 3, 2.7% in dogs with neurological signs graded 4, and 14.5% in dogs with neu- rological signs graded 5. Age (4.57 were significant risk factors in the univariate analysis for development of ADMM. Conclusions and Clinical Importance: The factors identified in this study may be useful for the prediction of ADMM. Multicenter studies with a higher number of dogs with ADMM are required to confirm these data

Comparison of regional gene expression differences in the brains of the domestic dog and human

Comparison of the expression profiles of 2,721 genes in the cerebellum, cortex and pituitary gland of three American Staffordshire terriers, one beagle and one fox hound revealed regional expression differences in the brain but failed to reveal marked differences among breeds, or even individual dogs. Approximately 85 per cent (42 of 49 orthologue comparisons) of the regional differences in the dog are similar to those that differentiate the analogous human brain regions. A smaller percentage of human differences were replicated in the dog, particularly in the cortex, which may generally be evolving more rapidly than other brain regions in mammals. This study lays the foundation for detailed analysis of the population structure of transcriptional variation as it relates to cognitive and neurological phenotypes in the domestic dog

Evaluation of magnetic resonance imaging guidelines for differentiation between thoracolumbar intervertebral disk extrusions and intervertebral disk protrusions in dogs

Four MRI variables have recently been suggested to be independently associated with a diagnosis of thoracolumbar intervertebral disk extrusion or protrusion. Midline intervertebral disk herniation, and partial intervertebral disk degeneration were associated with intervertebral disk protrusion, while presence of a single intervertebral disk herniation and disk material dispersed beyond the boundaries of the intervertebral disk space were associated with intervertebral disk extrusion. The aim of this retrospective, cross‐sectional study was to determine whether using these MRI variables improves differentiation between thoracolumbar intervertebral disk extrusions and protrusions. Eighty large breed dogs with surgically confirmed thoracolumbar intervertebral disk extrusions or protrusions were included. Randomized MRI studies were presented on two occasions to six blinded observers, which were divided into three experience categories. During the first assessment, observers made a presumptive diagnosis of thoracolumbar intervertebral disk extrusion or protrusion without guidelines. During the second assessment they were asked to make a presumptive diagnosis with the aid of guidelines. Agreement was evaluated by Kappa‐statistics. Diagnostic accuracy significantly improved from 70.8 to 79.6% and interobserver agreement for making a diagnosis of intervertebral disk extrusion or intervertebral disk protrusion improved from fair (κ = 0.27) to moderate (κ = 0.41) after using the proposed guidelines. Diagnostic accuracy was significantly influenced by degree of observer experience. Intraobserver agreement for the assessed variables ranged from fair to excellent and interobserver agreement ranged from fair to moderate. The results of this study suggest that the proposed imaging guidelines can aid in differentiating thoracolumbar intervertebral disk extrusions from protrusions

Centronuclear myopathy in labrador retrievers: a recent founder mutation in the PTPLA gene has rapidly disseminated worldwide

Centronuclear myopathies (CNM) are inherited congenital disorders characterized by an excessive number of internalized nuclei. In humans, CNM results from ~70 mutations in three major genes from the myotubularin, dynamin and amphiphysin families. Analysis of animal models with altered expression of these genes revealed common defects in all forms of CNM, paving the way for unified pathogenic and therapeutic mechanisms. Despite these efforts, some CNM cases remain genetically unresolved. We previously identified an autosomal recessive form of CNM in French Labrador retrievers from an experimental pedigree, and showed that a loss-of-function mutation in the protein tyrosine phosphatase-like A (PTPLA) gene segregated with CNM. Around the world, client-owned Labrador retrievers with a similar clinical presentation and histopathological changes in muscle biopsies have been described. We hypothesized that these Labradors share the same PTPLA<sup>cnm</sup> mutation. Genotyping of an international panel of 7,426 Labradors led to the identification of PTPLA<sup>cnm</sup> carriers in 13 countries. Haplotype analysis demonstrated that the PTPLA<sup>cnm</sup> allele resulted from a single and recent mutational event that may have rapidly disseminated through the extensive use of popular sires. PTPLA-deficient Labradors will help define the integrated role of PTPLA in the existing CNM gene network. They will be valuable complementary large animal models to test innovative therapies in CNM

Comparison of medical and surgical treatment for acute cervical compressive hydrated nucleus pulposus extrusion in dogs

Although successful outcomes have been reported after medical and surgical treatment for dogs with cervical hydrated nucleus pulposus extrusion (HNPE), it is unknown which treatment option is preferred. Thirty-four dogs treated medically (n=18) or surgically (n=16) for cervical HNPE were retrospectively identified. Signalment, clinical presentation and imaging findings were compared between medically and surgically treated dogs. Medical management consisted of restricted exercise in combination with physiotherapy. Surgical treatment consisted of a ventral slot procedure. Short-term follow-up information was retrieved from re-examination visits. Long-term outcome was obtained via telephone interviews. More dogs in the surgical group demonstrated cervical hyperaesthesia on initial clinical presentation (P=0.045), otherwise there was no significant difference in signalment, clinical presentation or imaging findings between both groups. Two dogs in the medically managed group underwent surgical decompression due to an unsatisfactory response to medical management. All cases for which long-term information was available (n=30) were neurologically normal at the time of data collection. There were no significant differences for any of the short-term or long-term outcome variables between both treatment groups. This study demonstrated successful outcomes after medical or surgical treatment and suggests that both treatment modalities can be considered for dogs with cervical HNPE

Nonintegrability, Chaos, and Complexity

Two-dimensional driven dissipative flows are generally integrable via a conservation law that is singular at equilibria. Nonintegrable dynamical systems are confined to n*3 dimensions. Even driven-dissipative deterministic dynamical systems that are critical, chaotic or complex have n-1 local time-independent conservation laws that can be used to simplify the geometric picture of the flow over as many consecutive time intervals as one likes. Those conserevation laws generally have either branch cuts, phase singularities, or both. The consequence of the existence of singular conservation laws for experimental data analysis, and also for the search for scale-invariant critical states via uncontrolled approximations in deterministic dynamical systems, is discussed. Finally, the expectation of ubiquity of scaling laws and universality classes in dynamics is contrasted with the possibility that the most interesting dynamics in nature may be nonscaling, nonuniversal, and to some degree computationally complex

Low-field magnetic resonance imaging and multislice computed tomography for the detection of cervical syringomyelia in dogs

Background: Syringomyelia (SM) is defined as the presence of fluid- containing cavities within the parenchyma of the spinal cord. Sagittal magnetic resonance (MR) images have been described as the preferred technique for visualizing SMin dogs and humans. Objective: To investigate whether computed tomography (CT) can be used to diagnose SM. Animals: Thirty- two client- owned dogs referred for investigation of the cervical spine on magnetic resonance imaging (MRI) and CT. Methods: Two reviewers retrospectively analyzed sagittal and transverse T1- weighted spin echo (T1WSE) MR images and CT images from each dog for the presence of SM and, if SM was present, the width (mm, syrinx width [ SW]) was measured. The results were analyzed statistically. Results: For the presence of SM there was a moderate interobserver agreement for MR (81%, j = 0.54) and almost perfect agreement for CT (94%, j = 0.87). There was a moderate intramodality agreement for both observers (observer 1 81%, j = 0.59; observer 2 81%, j = 0.57). For measurement of SW the repeatability was the best on the midsagittal T1WSE images (95% repeatability coefficient < 0.52 mm) and the reproducibility was the best on midsagittal images in both modalities (95% limits of agreement 0.55- 0.45; P = 0.002). Conclusion and Clinical Importance: Both techniques can be used to detect SM. Midsagittal MR and CT images are best used for measuring SW. Computed tomography can be used as a diagnostic tool for SM when MRI is not available, but CT cannot replace MRI as the standard screening technique for the detection of SM in Cavalier King Charles Spaniel for breeding purposes