Biomechanical comparison of standing posture and during trot between German shepherd and Labrador retriever dogs.

Funder: The Kennel Club Charitable Trust; Grant(s): Project ID: 4093 Project Code: 9653It is widely accepted that canine breeds stand and move differently. The prevalence of various musculoskeletal disorders such as hip and elbow dysplasia is also different between breeds. German shepherd dog (GSD) and Labrador retriever dog (LRD) are two large breeds with different conformations that have high prevalence of these disorders. This study quantifies the movement and standing posture of twelve healthy GSDs and twelve healthy LRDs to identify biomechanical similarities and differences that may be linked to sub-optimal hip and elbow mechanics. A pressure walkway and a motion capture system obtained measures of kinetics, kinematics and conformation during standing and trot. During standing, LRDs carry a greater percentage of the weight on the forelimbs (69%±5% vs. GSDs: 62%±2%, p<0.001) and their body Centre of Pressure (CoP) is located more cranially (p<0.001). GSDs had a greater pelvic tilt (79°±8 vs. 66°±9°, p = 0.004), more flexed stifles (44°±9° vs. LRDs: 34°±10°, p<0.05) and hocks (58°±11° vs. 26°±9°, p<0.01) and more extended hips (-10°±11° vs. 30°±12°, p<0.001). During trot, the GSDs' CoP had a longer anterior-posterior trajectory (151%±22% vs. LRDs: 93%±25% of the withers height, p<0.001). Stride parameters and loading of limbs were similar when normalised to the size and weight of the dog, respectively. The LRDs had a more extended thoracolumbar angle (p<0.001) and a less flexed lumbosacral angle (p<0.05). The LRDs' hip remained flexed during trot whereas the GSDs' hip joint was less flexed during swing (p<0.001) and more extended in late stance and early swing (p<0.001). In conclusion, the LRDs and GSDs differ in the way they stand and move and this would result in different loading pattern of the joints. Further investigation is required to determine the extent to which biomechanical differences are linked to musculoskeletal problems presented clinically

Sucrose-Formulated Recombinant Factor VIII Dosing Flexibility in Prophylaxis Regimens: Experience from Postmarketing Surveillance Studies

Objectives. Prophylaxis regimens for severe hemophilia A allowing more flexible dosing while maintaining efficacy may improve adherence and decrease the cost of prophylaxis. Here, we compared the clinical effectiveness of once- or twice-weekly versus ≥3-times-weekly prophylaxis with sucrose-formulated recombinant factor VIII (rFVIII-FS) in a “real-world” practice setting. Methods. Data from 3 postmarketing studies were pooled. Patients with severe hemophilia A receiving ≥1 prophylaxis infusion/wk of rFVIII-FS for ≥80% of a prophylaxis observation period (≥5 months) were included. Patients were categorized based on physician-assigned treatment regimens of 1-2 prophylaxis injections/wk (n=63) or ≥3 prophylaxis injections/wk (n=76). Descriptive statistics were determined for annualized bleeding rates (ABRs). Results. Median (quartile 1; quartile 3) ABR for all bleeds was 2.0 (0; 4.0) in the 1-2 prophylaxis injections/wk group and 3.9 (1.5; 9.3) in the ≥3 prophylaxis injections/wk group. Median ABRs for joint, spontaneous, and trauma-related bleeds were numerically lower with 1-2 prophylaxis injections/wk. As an estimate of prophylaxis success, 63% (≥3 prophylaxis injections/wk) to 84% of patients (1-2 prophylaxis injections/wk) had ≤4 annualized joint bleeds. Conclusions. Dosing flexibility and successful prophylaxis with rFVIII-FS were demonstrated. Very good bleeding control was achieved with both once-twice-weekly and ≥3-times-weekly prophylaxis dosing regimens

Dopamine-modulated dynamic cell assemblies generated by the GABAergic striatal microcircuit

The striatum, the principal input structure of the basal ganglia, is crucial to both motor control and learning. It receives convergent input from all over the neocortex, hippocampal formation, amygdala and thalamus, and is the primary recipient of dopamine in the brain. Within the striatum is a GABAergic microcircuit that acts upon these inputs, formed by the dominant medium-spiny projection neurons (MSNs) and fast-spiking interneurons (FSIs). There has been little progress in understanding the computations it performs, hampered by the non-laminar structure that prevents identification of a repeating canonical microcircuit. We here begin the identification of potential dynamically-defined computational elements within the striatum. We construct a new three-dimensional model of the striatal microcircuit's connectivity, and instantiate this with our dopamine-modulated neuron models of the MSNs and FSIs. A new model of gap junctions between the FSIs is introduced and tuned to experimental data. We introduce a novel multiple spike-train analysis method, and apply this to the outputs of the model to find groups of synchronised neurons at multiple time-scales. We find that, with realistic in vivo background input, small assemblies of synchronised MSNs spontaneously appear, consistent with experimental observations, and that the number of assemblies and the time-scale of synchronisation is strongly dependent on the simulated concentration of dopamine. We also show that feed-forward inhibition from the FSIs counter-intuitively increases the firing rate of the MSNs. Such small cell assemblies forming spontaneously only in the absence of dopamine may contribute to motor control problems seen in humans and animals following a loss of dopamine cells. (C) 2009 Elsevier Ltd. All rights reserved

The Profiling Potential of Computer Vision and the Challenge of Computational Empiricism

Computer vision and other biometrics data science applications have commenced a new project of profiling people. Rather than using 'transaction generated information', these systems measure the 'real world' and produce an assessment of the 'world state' - in this case an assessment of some individual trait. Instead of using proxies or scores to evaluate people, they increasingly deploy a logic of revealing the truth about reality and the people within it. While these profiling knowledge claims are sometimes tentative, they increasingly suggest that only through computation can these excesses of reality be captured and understood. This article explores the bases of those claims in the systems of measurement, representation, and classification deployed in computer vision. It asks if there is something new in this type of knowledge claim, sketches an account of a new form of computational empiricism being operationalised, and questions what kind of human subject is being constructed by these technological systems and practices. Finally, the article explores legal mechanisms for contesting the emergence of computational empiricism as the dominant knowledge platform for understanding the world and the people within it

Reconstructing the three-dimensional GABAergic microcircuit of the striatum

A system's wiring constrains its dynamics, yet modelling of neural structures often overlooks the specific networks formed by their neurons. We developed an approach for constructing anatomically realistic networks and reconstructed the GABAergic microcircuit formed by the medium spiny neurons (MSNs) and fast-spiking interneurons (FSIs) of the adult rat striatum. We grew dendrite and axon models for these neurons and extracted probabilities for the presence of these neurites as a function of distance from the soma. From these, we found the probabilities of intersection between the neurites of two neurons given their inter-somatic distance, and used these to construct three-dimensional striatal networks. The MSN dendrite models predicted that half of all dendritic spines are within 100 mu m of the soma. The constructed networks predict distributions of gap junctions between FSI dendrites, synaptic contacts between MSNs, and synaptic inputs from FSIs to MSNs that are consistent with current estimates. The models predict that to achieve this, FSIs should be at most 1% of the striatal population. They also show that the striatum is sparsely connected: FSI-MSN and MSN-MSN contacts respectively form 7% and 1.7% of all possible connections. The models predict two striking network properties: the dominant GABAergic input to a MSN arises from neurons with somas at the edge of its dendritic field; and FSIs are interconnected on two different spatial scales: locally by gap junctions and distally by synapses. We show that both properties influence striatal dynamics: the most potent inhibition of a MSN arises from a region of striatum at the edge of its dendritic field; and the combination of local gap junction and distal synaptic networks between FSIs sets a robust input-output regime for the MSN population. Our models thus intimately link striatal micro-anatomy to its dynamics, providing a biologically grounded platform for further study

The Strayed Reveller, No. 3

The third issue of The Strayed Revellerhttps://scholarworks.sfasu.edu/reveller/1002/thumbnail.jp