Development of an In-Vitro Passive and Active Motion Simulator for the Investigation of Shoulder Function and Kinematics

Injuries and degenerative diseases of the shoulder are common and may relate to the joint’s complex biomechanics, which rely primarily on soft tissues to achieve stability. Despite the prevalence of these disorders, there is little information about their effects on the biomechanics of the shoulder, and a lack of evidence with which to guide clinical practice. Insight into these disorders and their treatments can be gained through in-vitro biomechanical experiments where the achieved physiologic accuracy and repeatability directly influence their efficacy and impact. This work’s rationale was that developing a simulator with greater physiologic accuracy and testing capabilities would improve the quantification of biomechanical parameters. This dissertation describes the development and validation of a simulator capable of performing passive assessments, which use experimenter manipulation, and active assessments – produced through muscle loading. Respectively, these allow the assessment of functional parameters such as stability, and kinematic/kinetic parameters including joint loading. The passive functionality enables specimen motion to be precisely controlled through independent manipulation of each rotational degree of freedom (DOF). Compared to unassisted manipulation, the system improved accuracy and repeatability of positioning the specimen (by 205% & 163%, respectively), decreased variation in DOF that are to remain constant (by 6.8°), and improved achievement of predefined endpoints (by 21%). Additionally, implementing a scapular rotation mechanism improved the physiologic accuracy of simulation. This enabled the clarification of the effect of secondary musculature on shoulder function, and the comparison of two competing clinical reconstructive procedures for shoulder instability. This was the first shoulder system to use real time kinematic feedback and PID control to produce active motion, which achieved unmatched accuracy ( These developments can be a powerful tool for increasing our understanding of the shoulder and also to provide information which can assist surgeons and improve patient outcomes

Effects of Material Mapping Agnostic Partial Volume Correction for Subject Specific Finite Elements Simulations

Partial Volume effects are present at the boundary between any two types of material in a CT image due to the scanner's Point Spread Function, finite voxel resolution, and importantly, the discrepancy in radiodensity between the two materials. In this study a new algorithm is developed and validated that builds on previously published work to enable the correction of partial volume effects at cortical bone boundaries. Unlike past methods, this algorithm does not require pre-processing or user input to achieve the correction, and the correction is applied directly onto a set of CT images, which enables it to be used in existing computational modelling workflows. The algorithm was validated by performing experimental three point bending tests on porcine fibulae specimen and comparing the experimental results to finite element results for models created using either the original, uncorrected CT images or the partial volume corrected images. Results demonstrated that the models created using the partial volume corrected images did improved the accuracy of the surface strain predictions. Given this initial validation, this algorithm is a viable method for overcoming the challenge of partial volume effects in CT images. Thus, future work should be undertaken to further validate the algorithm with human tissues and through coupling it with a range of different finite element creation workflows to verify that it is robust and agnostic to the chosen material mapping strategy

A rigid body model for the assessment of glenohumeral joint mechanics: Influence of osseous defects on range of motion and dislocation

© 2016. The purpose of this study was to employ subject-specific computer models to evaluate the interaction of glenohumeral range-of-motion and Hill-Sachs humeral head bone defect size on engagement and shoulder dislocation. We hypothesized that the rate of engagement would increase as defect size increased, and that greater shoulder ROM would engage smaller defects. Three dimensional computer models of 12 shoulders were created. For each shoulder, additional models were created with simulated Hill-Sachs defects of varying severities (XS=15%, S=22.5%, M=30%, L=37.5%, XL=45% and XXL=52.5% of the humeral head diameter, respectively). Rotational motion simulations without translation were conducted. The simulations ended if the defect engaged the anterior glenoid rim with resultant dislocation. The results showed that the rate of engagement was significantly different between defect sizes (0.00

An In Vitro Study Comparing Limited to Full Cementation of Polyethylene Glenoid Components

BACKGROUND: Glenoid component survival is critical to good long-term outcomes in total shoulder arthroplasty. Optimizing the fixation environment is paramount. The purpose of this study was to compare two glenoid cementing techniques for fixation in total shoulder arthroplasty. METHODS: Sixteen cadaveric specimens were randomized to receive peg-only cementation (CPEG) or full back-side cementation (CBACK). Physiological cyclic loading was performed and implant displacement was recorded using an optical tracking system. The cement mantle was examined with micro-computed tomography before and after cyclic loading. RESULTS: Significantly greater implant displacement away from the inferior portion of the glenoid was observed in the peg cementation group when compared to the fully cemented group during the physiological loading. The displacement was greatest at the beginning of the loading protocol and persisted at a diminished rate during the remainder of the loading protocol. Micro-CT scanning demonstrated that the cement mantle remained intact in both groups and that three specimens in the CBACK group demonstrated microfracturing in one area only. DISCUSSION: Displacement of the CPEG implants away from the inferior subchondral bone may represent a suboptimal condition for long-term implant survival. Cement around the back of the implant is suggested to improve initial stability of all polyethylene glenoid implants. CLINICAL RELEVANCE: Full cementation provides greater implant stability when compared to limited cementation techniques for insertion of glenoid implants. Loading characteristics are more favorable when cement is placed along the entire back of the implant contacting the subchondral bone

Complex patterns of human antisera reactivity to novel 2009 H1N1 and historical H1N1 influenza strains

Background: During the 2009 influenza pandemic, individuals over the age of 60 had the lowest incidence of infection with approximately 25% of these people having pre-existing, cross-reactive antibodies to novel 2009 H1N1 influenza isolates. It was proposed that older people had pre-existing antibodies induced by previous 1918-like virus infection(s) that cross-reacted to novel H1N1 strains. Methodology/Principal Findings: Using antisera collected from a cohort of individuals collected before the second wave of novel H1N1 infections, only a minority of individuals with 1918 influenza specific antibodies also demonstrated hemagglutination-inhibition activity against the novel H1N1 influenza. In this study, we examined human antisera collected from individuals that ranged between the ages of 1 month and 90 years to determine the profile of seropositive influenza immunity to viruses representing H1N1 antigenic eras over the past 100 years. Even though HAI titers to novel 2009 H1N1 and the 1918 H1N1 influenza viruses were positively associated, the association was far from perfect, particularly for the older and younger age groups. Conclusions/Significance: Therefore, there may be a complex set of immune responses that are retained in people infected with seasonal H1N1 that can contribute to the reduced rates of H1N1 influenza infection in older populations. © 2012 Carter et al

The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

A Cryogenic Silicon Interferometer for Gravitational-wave Detection

The detection of gravitational waves from compact binary mergers by LIGO has opened the era of gravitational wave astronomy, revealing a previously hidden side of the cosmos. To maximize the reach of the existing LIGO observatory facilities, we have designed a new instrument able to detect gravitational waves at distances 5 times further away than possible with Advanced LIGO, or at greater than 100 times the event rate. Observations with this new instrument will make possible dramatic steps toward understanding the physics of the nearby Universe, as well as observing the Universe out to cosmological distances by the detection of binary black hole coalescences. This article presents the instrument design and a quantitative analysis of the anticipated noise floor

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest