Redefining Knee Balance in a Medially Stabilized Prosthesis: An In-Vitro Study

Background To date, there is still no consensus on what soft tissues must be preserved and what structures can be safely released during total knee arthroplasty (TKA) with a medially stabilized implant. Objective The aim of this study was to analyze the effect of a progressive selective release of the medial and lateral soft tissues in a knee implanted with a medially stabilized prosthesis. Method Six cadaveric fresh-frozen full leg specimens were tested. In each case, kinematic pattern and mediolateral laxity were measured in three stages: firstly, prior to implantation; secondly, after the implantation of the trial components, but before any soft tissue release; and thirdly, progressively as soft tissue was released with the trial implant in place. The incremental impact of each selective release on knee balance was then analyzed. Results In all cases sagittal stability was not affected by the progressive release of the lateral soft tissue envelope. It was possible to perform progressive lateral release provided the anterior one-third of the iliotibial band (ITB) remained intact. Progressive medial release could be performed on the medial side provided the anterior fibers of the superficial medial collateral ligament (sMCL) remained intact. Conclusion The medially conforming implant remains stable provided the anterior fibers of sMCL and the anterior fibers of the ITB remain intact. The implant's sagittal stability is mainly dependent on its medial ball-in-socket design

ISB clinical biomechanics award winner 2021: Tibio-femoral kinematics of natural versus replaced knees - A comparison using dynamic videofluoroscopy

BACKGROUND A comparison of natural versus replaced tibio-femoral kinematics in vivo during challenging activities of daily living can help provide a detailed understanding of the mechanisms leading to unsatisfactory results and lay the foundations for personalised implant selection and surgical implantation, but also enhance further development of implant designs towards restoring physiological knee function. The aim of this study was to directly compare in vivo tibio-femoral kinematics in natural versus replaced knees throughout complete cycles of different gait activities using dynamic videofluoroscopy. METHODS Twenty-seven healthy and 30 total knee replacement subjects (GMK Sphere, GMK PS, GMK UC) were assessed during multiple complete gait cycles of level walking, downhill walking, and stair descent using dynamic videofluoroscopy. Following 2D/3D registration, tibio-femoral rotations, condylar antero-posterior translations, and the location of the centre of rotation were compared. FINDINGS The total knee replacement groups predominantly experienced reduced tibial internal/external rotation and altered medial and lateral condylar antero-posterior translations compared to natural knees. An average medial centre of rotation was found for the natural and GMK sphere groups in all three activities, whereas the GMK PS and UC groups experienced a more central to lateral centre of rotation. INTERPRETATION Each total knee replacement design exhibited characteristic motion patterns, with the GMK Sphere most closely replicating the medial centre of rotation found for natural knees. Despite substantial similarities between the subject groups, none of the implant geometries was able to replicate all aspects of natural tibio-femoral kinematics, indicating that different implant geometries might best address individual functional needs

Detection and Exclusion of False-Positive Molecular Formula Assignments via Mass Error Distributions in UHR Mass Spectra of Natural Organic Matter

Ultrahigh resolution mass spectrometry (UHRMS) routinely detects and identifies thousands of mass peaks in complex mixtures, such as natural organic matter (NOM) and petroleum. The assignment of several chemically plausible molecular formulas (MFs) for a single accurate mass still poses a major problem for the reliable interpretation of NOM composition in a biogeochemical context. Applying sensible chemical rules for MF validation is often insufficient to eliminate multiple assignments (MultiAs)─especially for mass peaks with low abundance or if ample heteroatoms or isotopes are included - and requires manual inspection or expert judgment. Here, we present a new approach based on mass error distributions for the identification of true and false assignments among MultiAs. To this end, we used the mass error in millidalton (mDa), which was superior to the commonly used relative mass error in ppm. We developed an automatic workflow to group MultiAs based on their shared formula units and Kendrick mass defect values and to evaluate the mass error distribution. In this way, the number of valid assignments of chlorinated disinfection byproducts was increased by 8-fold as compared to only applying 37Cl/35Cl isotope ratio filters. Likewise, phosphorus-containing MFs can be differentiated against chlorine-containing MFs with high confidence. Further, false assignments of highly aromatic sulfur-containing MFs (“black sulfur”) to sodium adducts in negative ionization mode can be excluded by applying our approach. Overall, MFs for mass peaks that are close to the detection limit or where naturally occurring isotopes are rare (e.g., 15N) or absent (e.g., P and F) can now be validated, substantially increasing the reliability of MF assignments and broadening the applicability of UHRMS analysis to even more complex samples and processes

A Large Catalog of Homogeneous Ultra-Violet/Optical GRB Afterglows: Temporal and Spectral Evolution

We present the second Swift Ultra-Violet/Optical Telescope (UVOT) gamma-ray burst (GRB) afterglow catalog, greatly expanding on the first Swift UVOT GRB afterglow catalog. The second catalog is constructed from a database containing over 120,000 independent UVOT observations of 538 GRBs first detected by Swift, the High Energy Transient Explorer 2 (HETE2), the INTErnational Gamma-Ray Astrophysics Laboratory (INTEGRAL), the Interplanetary Network (IPN), Fermi, and Astro-rivelatore Gamma a Immagini Leggero (AGILE). The catalog covers GRBs discovered from 2005 Jan 17 to 2010 Dec 25. Using photometric information in three UV bands, three optical bands, and a `white' or open filter, the data are optimally co-added to maximize the number of detections and normalized to one band to provide a detailed light curve. The catalog provides positional, temporal, and photometric information for each burst, as well as Swift Burst Alert Telescope (BAT) and X-Ray Telescope (XRT) GRB parameters. Temporal slopes are provided for each UVOT filter. The temporal slope per filter of almost half the GRBs are fit with a single power-law, but one to three breaks are required in the remaining bursts. Morphological comparisons with the X-ray reveal that approximately 75% of the UVOT light curves are similar to one of the four morphologies identified by Evans et al. (2009). The remaining approximately 25% have a newly identified morphology. For many bursts, redshift and extinction corrected UV/optical spectral slopes are also provided at 2000, 20,000, and 200,000 seconds.Comment: 44 pages, 14 figures, to be published in Astrophysical Journal Supplementa

AMiBA Wideband Analog Correlator

A wideband analog correlator has been constructed for the Yuan-Tseh Lee Array for Microwave Background Anisotropy. Lag correlators using analog multipliers provide large bandwidth and moderate frequency resolution. Broadband IF distribution, backend signal processing and control are described. Operating conditions for optimum sensitivity and linearity are discussed. From observations, a large effective bandwidth of around 10 GHz has been shown to provide sufficient sensitivity for detecting cosmic microwave background variations.Comment: 28 pages, 23 figures, ApJ in press

Segmentation of Retinal Low-Cost Optical Coherence Tomography Images using Deep Learning

The treatment of age-related macular degeneration (AMD) requires continuous eye exams using optical coherence tomography (OCT). The need for treatment is determined by the presence or change of disease-specific OCT-based biomarkers. Therefore, the monitoring frequency has a significant influence on the success of AMD therapy. However, the monitoring frequency of current treatment schemes is not individually adapted to the patient and therefore often insufficient. While a higher monitoring frequency would have a positive effect on the success of treatment, in practice it can only be achieved with a home monitoring solution. One of the key requirements of a home monitoring OCT system is a computer-aided diagnosis to automatically detect and quantify pathological changes using specific OCT-based biomarkers. In this paper, for the first time, retinal scans of a novel self-examination low-cost full-field OCT (SELF-OCT) are segmented using a deep learning-based approach. A convolutional neural network (CNN) is utilized to segment the total retina as well as pigment epithelial detachments (PED). It is shown that the CNN-based approach can segment the retina with high accuracy, whereas the segmentation of the PED proves to be challenging. In addition, a convolutional denoising autoencoder (CDAE) refines the CNN prediction, which has previously learned retinal shape information. It is shown that the CDAE refinement can correct segmentation errors caused by artifacts in the OCT image.Comment: Accepted for SPIE Medical Imaging 2020: Computer-Aided Diagnosi

Lepton pairs from thermal mesons

We study the net dielectron production rates from an ensemble of thermal mesons, using an effective Lagrangian to model their interaction. The coupling between the electromagnetic and the hadronic sectors is done through the vector meson dominance approach. For the first time, a complete set of light mesons is considered. We include contributions from decays of the type V~(PS)~$\rightarrow$~PS~(V)~+~$e^+~e^-$, where V is a vector meson and PS is a pseudoscalar, as well as those from binary reactions PS~+~PS, V~+~V, and V~+~PS~$\rightarrow~e^+e^-$. Direct decays of the type V~$\rightarrow~e^+ e^-$ are included and shown to be important. We find that the dielectron invariant mass spectrum naturally divides in distinct regions: in the low mass domain the decays from vector and pseudoscalar mesons form the dominant contribution. The pion--pion annihilation and direct decays then pick up and form the leading signal in an invariant mass region that includes the $\rho - \omega$ complex and extends up to the $\phi$. Above invariant mass $M\ \approx$~1~GeV other two-body reactions take over as the prominent mechanisms for lepton pair generation. These facts will have quantitative bearing on the eventual identification of the quark--gluon plasma.Comment: In ReVTeX 3.0, 9 figs. available from above email address. McGill 93/8, TPI-MINN-93/19-

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Three-Dimensional Iron Oxide Nanoparticle-Based Contrast-Enhanced Magnetic Resonance Imaging for Characterization of Cerebral Arteriogenesis in the Mouse Neocortex

Purpose: Subsurface blood vessels in the cerebral cortex have been identified as a bottleneck in cerebral perfusion with the potential for collateral remodeling. However, valid techniques for non-invasive, longitudinal characterization of neocortical microvessels are still lacking. In this study, we validated contrast-enhanced magnetic resonance imaging (CE-MRI) for in vivo characterization of vascular changes in a model of spontaneous collateral outgrowth following chronic cerebral hypoperfusion. Methods: C57BL/6J mice were randomly assigned to unilateral internal carotid artery occlusion or sham surgery and after 21 days, CE-MRI based on T2*-weighted imaging was performed using ultra-small superparamagnetic iron oxide nanoparticles to obtain subtraction angiographies and steady-state cerebral blood volume (ss-CBV) maps. First pass dynamic susceptibility contrast MRI (DSC-MRI) was performed for internal validation of ss-CBV. Further validation at the histological level was provided by ex vivo serial two-photon tomography (STP). Results: Qualitatively, an increase in vessel density was observed on CE-MRI subtraction angiographies following occlusion; however, a quantitative vessel tracing analysis was prone to errors in our model. Measurements of ss-CBV reliably identified an increase in cortical vasculature, validated by DSC-MRI and STP. Conclusion: Iron oxide nanoparticle-based ss-CBV serves as a robust, non-invasive imaging surrogate marker for neocortical vessels, with the potential to reduce and refine preclinical models targeting the development and outgrowth of cerebral collateralization