The Reliability of Foot and Ankle Bone and Joint Kinematics Measured With Biplanar Videoradiography and Manual Scientific Rotoscoping

The intricate motion of the small bones of the feet are critical for its diverse function. Accurately measuring the 3-dimensional (3D) motion of these bones has attracted much attention over the years and until recently, was limited to invasive techniques or quantification of functional segments using multi-segment foot models. Biplanar videoradiography and model-based scientific rotoscoping offers an exciting alternative that allows us to focus on the intricate motion of individual bones in the foot. However, scientific rotoscoping, the process of rotating and translating a 3D bone model so that it aligns with the captured x-ray images, is either semi- or completely manual and it is unknown how much human error affects tracking results. Thus, the aim of this study was to quantify the inter- and intra-operator reliability of manually rotoscoping in vivo bone motion of the tibia, talus, and calcaneus during running. Three-dimensional CT bone volumes and high-speed biplanar videoradiography images of the foot were acquired on six participants. The six-degree-of-freedom motions of the tibia, talus, and calcaneus were determined using a manual markerless registration algorithm. Two operators performed the tracking, and additionally, the first operator re-tracked all bones, to test for intra-operator effects. Mean RMS errors were 1.86 mm and 1.90° for intra-operator comparisons and 2.30 mm and 2.60° for inter-operator comparisons across all bones and planes. The moderate to strong similarity values indicate that tracking bones and joint kinematics between sessions and operators is reliable for running. These errors are likely acceptable for defining gross joint angles. However, this magnitude of error may limit the capacity to perform advanced analyses of joint interactions, particularly those that require precise (sub-millimeter) estimates of bone position and orientation. Optimizing the view and image quality of the biplanar videoradiography system as well as the automated tracking algorithms for rotoscoping bones in the foot are required to reduce these errors and the time burden associated with the manual processing

A Direct Comparison of Biplanar Videoradiography and Optical Motion Capture for Foot and Ankle Kinematics

Measuring motion of the human foot presents a unique challenge due to the large number of closely packed bones with congruent articulating surfaces. Optical motion capture (OMC) and multi-segment models can be used to infer foot motion, but might be affected by soft tissue artifact (STA). Biplanar videoradiography (BVR) is a relatively new tool that allows direct, non-invasive measurement of bone motion using high-speed, dynamic x-ray images to track individual bones. It is unknown whether OMC and BVR can be used interchangeably to analyse multi-segment foot motion. Therefore, the aim of this study was to determine the agreement in kinematic measures of dynamic activities. Nine healthy participants performed three walking and three running trials while BVR was recorded with synchronous OMC. Bone position and orientation was determined through manual scientific-rotoscoping. The OMC and BVR kinematics were co-registered to the same coordinate system, and BVR tracking was used to create virtual markers for comparison to OMC during dynamic trials. Root mean square (RMS) differences in marker positions and joint angles as well as a linear fit method (LFM) was used to compare the outputs of both methods. When comparing BVR and OMC, sagittal plane angles were in good agreement (ankle: R2 = 0.947, 0.939; Medial Longitudinal Arch (MLA) Angle: R2 = 0.713, 0.703, walking and running, respectively). When examining the ankle, there was a moderate agreement between the systems in the frontal plane (R2 = 0.322, 0.452, walking and running, respectively), with a weak to moderate correlation for the transverse plane (R2 = 0.178, 0.326, walking and running, respectively). However, root mean squared error (RMSE) showed angular errors ranging from 1.06 to 8.31° across the planes (frontal: 3.57°, 3.67°, transverse: 4.28°, 4.70°, sagittal: 2.45°, 2.67°, walking and running, respectively). Root mean square (RMS) differences between OMC and BVR marker trajectories were task dependent with the largest differences in the shank (6.0 ± 2.01 mm) for running, and metatarsals (3.97 ± 0.81 mm) for walking. Based on the results, we suggest BVR and OMC provide comparable solutions to foot motion in the sagittal plane, however, interpretations of out-of-plane movement should be made carefully

Infusion of Reconstituted High-Density Lipoprotein, CSL112, in Patients With Atherosclerosis: Safety and Pharmacokinetic Results From a Phase 2a Randomized Clinical Trial

Background CSL112 is a new formulation of human apolipoprotein A‐I (apoA‐I) being developed to reduce cardiovascular events following acute coronary syndrome. This phase 2a, randomized, double‐blind, multicenter, dose‐ranging trial represents the first clinical investigation to assess the safety and pharmacokinetics/pharmacodynamics of a CSL112 infusion among patients with stable atherosclerotic disease. Methods and Results Patients were randomized to single ascending doses of CSL112 (1.7, 3.4, or 6.8 g) or placebo, administered over a 2‐hour period. Primary safety assessments consisted of alanine aminotransferase or aspartate aminotransferase elevations \u3e3× upper limits of normal and study drug–related adverse events. Pharmacokinetic/pharmacodynamic assessments included apoA‐I plasma concentration and measures of the ability of serum to promote cholesterol efflux from cells ex vivo. Of 45 patients randomized, 7, 12, and 14 received 1.7‐, 3.4‐, and 6.8‐g CSL112, respectively, and 11 received placebo. There were no clinically significant elevations (\u3e3× upper limit of normal) in alanine aminotransferase or aspartate aminotransferase. Adverse events were nonserious and mild and occurred in 5 (71%), 5 (41%), and 6 (43%) patients in the CSL112 1.7‐, 3.4‐, and 6.8‐g groups, respectively, compared with 3 (27%) placebo patients. The imbalance in adverse events was attributable to vessel puncture/infusion‐site bruising. CSL112 resulted in rapid (Tmax≈2 hours) and dose‐dependent increases in apoA‐I (145% increase in the 6.8‐g group) and total cholesterol efflux (up to 3.1‐fold higher than placebo) (P\u3c0.001). Conclusions CSL112 infusion was well tolerated in patients with stable atherosclerotic disease. CSL112 immediately raised apoA‐I levels and caused a rapid and marked increase in the capacity of serum to efflux cholesterol. This potential novel approach for the treatment of atherosclerosis warrants further investigation. Clinical Trial Registration URL: http://www.ClinicalTrials.gov. Unique identifier: NCT01499420

Creation of an Open-Access, Mutation-Defined Fibroblast Resource for Neurological Disease Research

Our understanding of the molecular mechanisms of many neurological disorders has been greatly enhanced by the discovery of mutations in genes linked to familial forms of these diseases. These have facilitated the generation of cell and animal models that can be used to understand the underlying molecular pathology. Recently, there has been a surge of interest in the use of patient-derived cells, due to the development of induced pluripotent stem cells and their subsequent differentiation into neurons and glia. Access to patient cell lines carrying the relevant mutations is a limiting factor for many centres wishing to pursue this research. We have therefore generated an open-access collection of fibroblast lines from patients carrying mutations linked to neurological disease. These cell lines have been deposited in the National Institute for Neurological Disorders and Stroke (NINDS) Repository at the Coriell Institute for Medical Research and can be requested by any research group for use in in vitro disease modelling. There are currently 71 mutation-defined cell lines available for request from a wide range of neurological disorders and this collection will be continually expanded. This represents a significant resource that will advance the use of patient cells as disease models by the scientific community

A somato-cognitive action network alternates with effector regions in motor cortex

Motor cortex (M1) has been thought to form a continuous somatotopic homunculus extending down the precentral gyrus from foot to face representation

An Expanded Evaluation of Protein Function Prediction Methods Shows an Improvement In Accuracy

Background: A major bottleneck in our understanding of the molecular underpinnings of life is the assignment of function to proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, assessing methods for protein function prediction and tracking progress in the field remain challenging. Results: We conducted the second critical assessment of functional annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. We evaluated 126 methods from 56 research groups for their ability to predict biological functions using Gene Ontology and gene-disease associations using Human Phenotype Ontology on a set of 3681 proteins from 18 species. CAFA2 featured expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis compared the best methods from CAFA1 to those of CAFA2. Conclusions: The top-performing methods in CAFA2 outperformed those from CAFA1. This increased accuracy can be attributed to a combination of the growing number of experimental annotations and improved methods for function prediction. The assessment also revealed that the definition of top-performing algorithms is ontology specific, that different performance metrics can be used to probe the nature of accurate predictions, and the relative diversity of predictions in the biological process and human phenotype ontologies. While there was methodological improvement between CAFA1 and CAFA2, the interpretation of results and usefulness of individual methods remain context-dependent

Towards design of a stumble detection system for artificial legs

Recent advances in design of powered artificial legs have led to increased potential to allow lower limb amputees to actively recover from stumbles. To achieve this goal, promptly and accurately identifying stumbles is essential. This study aimed to 1) select potential stumble detection data sources that react reliably and quickly to stumbles and can be measured from a prosthesis, and 2) investigate two different approaches based on selected data sources to detect stumbles and classify stumble types in patients with transfemoral (TF) amputations during ambulation. In the experiments, the normal gait of TF amputees was perturbed by a controllable treadmill or when they walked on an obstacle course. The results showed that the acceleration of prosthetic foot can accurately detect the tested stumbling events 140-240 ms before the critical timing of falling and precisely classify the stumble type. However, the detector based on foot acceleration produced high false alarm rates, which challenged its real application. Combining electromyographic (EMG) signals recorded from the residual limb with the foot acceleration significantly reduced the false alarm rate but sacrificed the detection response time. The results of this study may lead to design of a stumble detection system for instrumented, powered artificial legs; however, continued engineering efforts are required to improve the detection performance and resolve the challenges that remain for implementing the stumble detector on prosthetic legs. © 2011 IEEE

Using Group Work Strategies to Continue the National Discussion on Race, Justice, and Peace

There is increasing empirical evidence demonstrating the negative impact of racism and other social injustices on individuals\u27 mental and emotional health. Those findings challenge counselor educators and practitioners to address social injustices in professional training programs and communities across the country. This article illustrates a national advocacy project, whereby a group approach is applied to address social injustices. Application of the model is presented, along with a description of the specific group constructs and skills that were used in the intervention