ASSESSMENT OF ERROR LEVELS ACROSS THE DOMAIN OF A THREE DIMENSIONAL UNDERWATER MOTION CAPTURE METHODOLOGY

Assessing human movement underwater presents many challenges, and it is therefore important to understand error across the whole capture domain to ensure accuracy in resulting kinematics. This study assessed the accuracy across the capture domain of a submerged motion capture methodology. Six Qualisys cameras created an underwater capture volume of 8x2x2m. Average error levels across the domain were acceptable in two uncertainty trials (1.23mm ± 8.23mm and 1.34mm ± 9.65mm), but error increased at the ends and top of the domain. By selecting an area of interest for assessment that excluded areas with lower accuracy, error was reduced to 0.53mm (± 1.45mm). This study highlights the need to investigate error levels across a motion capture domain, particularly when this is a large volume, to ensure results obtained from investigations are reliable

IMPACT OF KINEMATIC MODIFICATION IN THE UNDERWATER UNDULATORY SWIMMING PERFORMANCE OF A SWIMMER

This work is a case study observing the impact of various kinematics modifications in the simulated pressure forces and hydrodynamic work done by an athlete performing maximum effort Underwater Undulatory Swimming (UUS). The studied athlete was recorded using a Motion Capture methodology. Seven key joints were identified to represent the athlete’s motion and their position were fitted with a fourth order Fourier series. This kinematic data was then modified to reduce or amplify the upper-body and lower-body motion but also to have a linear wave propagation. The kinematics (10 in total) were inputted in an unsteady 2D Computational Fluid Dynamics (CFD) solver, Lily Pad. Results suggest directions for improvement in the execution of the athlete’s swimming style, whether it is for reducing the hydrodynamic work done or minimising resistive forces

TWO AND THREE-DIMENSIONAL ASSESSMENTS OF LOWER-LIMB KINEMATICS IN UNDERWATER FLY KICK

The purpose of this study was to compare sagittal plane lower limb kinematics of underwater fly kick measured using two and three-dimensional methods. Eight male participants (average FINA points score 801±138) completed underwater fly kick trials, recorded using a six camera Qualisys underwater system. Each trial was analysed using both two and three-dimensional methods. Lower-limb angles were significantly underestimated using two-dimensional methods, particularly at the hip where flexion and range of motion reduced by 13.73 degrees and 15.91 degrees respectively. The ankle and hip produce a large amount motion in the transverse and frontal planes. The results of two-dimensional analyses of underwater fly kick should be interpreted with caution due reductions in measured angles, and exclusion of out-of-plane kinematic information

Antibodies Targeted to the Brain with Image-Guided Focused Ultrasound Reduces Amyloid-β Plaque Load in the TgCRND8 Mouse Model of Alzheimer's Disease

Immunotherapy for Alzheimer's disease (AD) relies on antibodies directed against toxic amyloid-beta peptide (Aβ), which circulate in the bloodstream and remove Aβ from the brain [1], [2]. In mouse models of AD, the administration of anti-Aβ antibodies directly into the brain, in comparison to the bloodstream, was shown to be more efficient at reducing Aβ plaque pathology [3], [4]. Therefore, delivering anti-Aβ antibodies to the brain of AD patients may also improve treatment efficiency. Transcranial focused ultrasound (FUS) is known to transiently-enhance the permeability of the blood-brain barrier (BBB) [5], allowing intravenously administered therapeutics to enter the brain [6]–[8]. Our goal was to establish that anti-Aβ antibodies delivered to the brain using magnetic resonance imaging-guided FUS (MRIgFUS) [9] can reduce plaque pathology. To test this, TgCRND8 mice [10] received intravenous injections of MRI and FUS contrast agents, as well as anti-Aβ antibody, BAM-10. MRIgFUS was then applied transcranially. Within minutes, the MRI contrast agent entered the brain, and BAM-10 was later found bound to Aβ plaques in targeted cortical areas. Four days post-treatment, Aβ pathology was significantly reduced in TgCRND8 mice. In conclusion, this is the first report to demonstrate that MRIgFUS delivery of anti-Aβ antibodies provides the combined advantages of using a low dose of antibody and rapidly reducing plaque pathology

Lack of Protection following Passive Transfer of Polyclonal Highly Functional Low-Dose Non-Neutralizing Antibodies

Recent immune correlates analysis from the RV144 vaccine trial has renewed interest in the role of non-neutralizing antibodies in mediating protection from infection. While neutralizing antibodies have proven difficult to induce through vaccination, extra-neutralizing antibodies, such as those that mediate antibody-dependent cellular cytotoxicity (ADCC), are associated with long-term control of infection. However, while several non-neutralizing monoclonal antibodies have been tested for their protective efficacy in vivo, no studies to date have tested the protective activity of naturally produced polyclonal antibodies from individuals harboring potent ADCC activity. Because ADCC-inducing antibodies are highly enriched in elite controllers (EC), we passively transferred highly functional non-neutralizing polyclonal antibodies, purified from an EC, to assess the potential impact of polyclonal non-neutralizing antibodies on a stringent SHIV-SF162P3 challenge in rhesus monkeys. Passive transfer of a low-dose of ADCC inducing antibodies did not protect from infection following SHIV-SF162P3 challenge. Passively administered antibody titers and gp120-specific, but not gp41-specific, ADCC and antibody induced phagocytosis (ADCP) were detected in the majority of the monkeys, but did not correlate with post infection viral control. Thus these data raise the possibility that gp120-specific ADCC activity alone may not be sufficient to control viremia post infection but that other specificities or Fc-effector profiles, alone or in combination, may have an impact on viral control and should be tested in future passive transfer experiments

Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer.

Inactivation of the von Hippel-Lindau tumor suppressor gene, VHL, is an archetypical tumor-initiating event in clear cell renal carcinoma (ccRCC) that leads to the activation of hypoxia-inducible transcription factors (HIFs). However, VHL mutation status in ccRCC is not correlated with clinical outcome. Here we show that during ccRCC progression, cancer cells exploit diverse epigenetic alterations to empower a branch of the VHL-HIF pathway for metastasis, and the strength of this activation is associated with poor clinical outcome. By analyzing metastatic subpopulations of VHL-deficient ccRCC cells, we discovered an epigenetically altered VHL-HIF response that is specific to metastatic ccRCC. Focusing on the two most prominent pro-metastatic VHL-HIF target genes, we show that loss of Polycomb repressive complex 2 (PRC2)-dependent histone H3 Lys27 trimethylation (H3K27me3) activates HIF-driven chemokine (C-X-C motif) receptor 4 (CXCR4) expression in support of chemotactic cell invasion, whereas loss of DNA methylation enables HIF-driven cytohesin 1 interacting protein (CYTIP) expression to protect cancer cells from death cytokine signals. Thus, metastasis in ccRCC is based on an epigenetically expanded output of the tumor-initiating pathway