Iridium nanoparticles for multichannel luminescence lifetime imaging, mapping localization in live cancer cells

The development of long-lived luminescent nanoparticles for multiphoton lifetime imaging is of high interest in cancer research especially for in vivo experiments which allows for quantification of angiogenesis and cancer metastasis. Multiphoton imaging can reach up to several millimetres in depth detection, thus providing invaluable information on tumour vasculature and the microenvironment of the tumour. Detection of luminescence lifetimes is extremely sensitive to local environmental changes and is independent of probe concentration. Luminescent cyclometalated iridium(III) complexes were conjugated onto gold nanoparticles to produce novel multiphoton lifetime imaging nanoprobes. These nanoprobes show characteristic long luminescent lifetimes from the iridium(III) complex in the range of hundreds of nanoseconds and a short-lived signal on the scale of picoseconds from the gold, allowing for multichannel detection of these nanoprobes through lifetime imaging. This is the first report of multichannel phosphorescence and fluorescence lifetime imaging being applied to functionalised gold nanoparticle within cancer cells. The sensitivity of the iridium signal on the local environment of the cell was used to successfully map localisation within HeLa cells. The combination of the sensitivity of the iridium signal to the cellular environment together with the targeting nanoscaffold to guide delivery, offer opportunities for iridium nanoparticles to be used for targeting and tracking in in vivo models. The ability for these nanoprobes to selectively target cancer cells was investigated by conjugating monoclonal antibodies and SiRNA. Multiphoton lifetime imaging revealed uptake of these nanoprobes into cancer cells, and detection of luminescence lifetimes were sensitive to local changes in the environment. These functionalised nanoprobes were investigated in applications for selectively targeting angiogenesis in cancer

Objective classification and scoring of movement deficiencies in patients with anterior cruciate ligament reconstruction

Motion analysis systems are widely employed to identify movement deficiencies-e.g. patterns that potentially increase the risk of injury or inhibit performance. However, findings across studies are often conflicting in respect to what a movement deficiency is or the magnitude of association to a specific injury. This study tests the information content within movement data using a data driven framework that was taught to classify movement data into the classes: NORM, ACLOP and ACLNO OP, without the input of expert knowledge. The NORM class was presented by 62 subjects (124 NORM limbs), while 156 subjects with ACL reconstruction represented the ACLOP and ACLNO OP class (156 limbs each class). Movement data from jumping, hopping and change of direction exercises were examined, using a variety of machine learning techniques. A stratified shuffle split cross-validation was used to obtain a measure of expected accuracy for each step within the analysis. Classification accuracies (from best performing classifiers) ranged from 52 to 81%, using up to 5 features. The exercise with the highest classification accuracy was the double leg drop jump (DLDJ; 81%), the highest classification accuracy when considering only the NORM class was observed in the single leg hop (81%), while the DLDJ demonstrated the highest classification accuracy when considering only for the ACLOP and ACLNO OP class (84%). These classification accuracies demonstrate that biomechanical data contains valuable information and that it is possible to differentiate normal from rehabilitating movement patterns. Further, findings highlight that a few features contain most of the information, that it is important to seek to understand what a classification model has learned, that symmetry measures are important, that exercises capture different qualities and that not all subjects within a normative cohort utilise 'true' normative movement patterns (only 27 to 71%)

COMPARISON OF THE PERFORMANCE AND LOWER LIMB BIOMECHANICS OF DROP JUMP AND 10-5 REPETITVE REBOUND TESTS IN ACLR ATHLETES.

Double and single leg drop jump (DLDJ & SLDJ) assessments tend to be performed during the later stages of rehabilitation from an anterior cruciate ligament (ACL) injury due to the mechanical demands these assessments place on the lower limbs. Double and single leg 10-5 repetitive rebound tests (DLRJT and SLRJT) may be effective alternatives to examine lower limb mechanics at an earlier stage of rehabilitation. The purpose of this study was 1) to compare inter-limb performance and biomechanical differences within each jump test and 2) to compare biomechanical differences between the double and single leg versions of each test. Significant (

Can a single-legged squat provide insight into movement control and loading during dynamic sporting actions in athletic groin pain patients?

Context: Chronic athletic groin pain (AGP) is common in field sports and has been associated with abnormal movement control and loading of the hip and pelvis during play. A single-legged squat (SLS) is commonly used by clinicians to assess movement control but whether it can provide insight into control during more dynamic sporting movements in AGP patients is unclear. Objective: To determine the relationships between biomechanical measures in a SLS and these same measures in a single-legged drop landing, single-legged hurdle hop and a cutting manoeuvre in AGP patients. Design: Cross-sectional study. Setting: Biomechanics laboratory. Patients: Forty recreational field sports players diagnosed with AGP. Intervention: A biomechanical analysis of each individual’s SLS, drop-landing, hurdle hop and cut was undertaken. Main Outcome Measures: Hip, knee and pelvis angular displacement, and hip and knee peak moments. Pearson product moment correlations were used to examine relationships between SLS measures and equivalent measures in the other movements. Results: There were no significant correlations between any hip or pelvis measure in the SLS with these same measures in the drop landing, hurdle hop or cut (r range = 0.03 - 0.43, P > 0.05). Knee frontal and transverse plane angular displacement were related in the SLS and drop landing only, while knee moments were related in the SLS, drop-landing and hurdle hop (r range = 0.50 - 0.67, P < 0.05). Conclusion: For AGP patients, a SLS did not provide a meaningful insight into hip and pelvis control or loading during sporting movements that are associated with injury development. The usefulness of a SLS test in the assessment of movement control and loading in AGP patients is thus limited. The SLS provided a moderate insight into knee control while landing and therefore may be of use in the examination of knee injury risk

Athletic groin pain: a biomechanical diagnosis

Introduction: Chronic athletic groin pain is commonly experienced in a range of football codes including soccer (Holmich et al. 2014) and gaelic football (Murphy et al. 2012). Much debate surrounds the specific aetiology of AGP but several authors have implicated, at least in part, abnormal movement control and loading in and around the hip and pelvis during play (Rabe et al. 2010, Pizarri et al. 2008). Movement control during change of direction cutting is of particular interest as it is this dynamic movement that is frequently associated with groin pain development (Falvey et al. 2009). No previous studies have attempted to describe the key characteristics of cutting mechanics that may be prevalent in AGP populations, that is, what are the potential biomechanical diagnoses that exist in this cohort. Purpose: To describe the key characteristics of three dimensional cutting mechanics that exist within a large cohort of AGP patients. Methods: Four hundred (n = 400) recreational field sports players diagnosed with chronic athletic groin pain were recruited (mean ± SD: age, 27 ± 8 years; height, 1.80 ± 0.06m; mass, 81.9 ± 9.4 kg; time with groin pain, 66.2 ± 96.7 weeks). The study attained ethical approval and participants completed and signed an informed consent form before taking part. Participants underwent biomechanical testing before commencing rehabilitation. Testing involved three trials (both left and right side) of a change-of-direction cut. For the cut, participants ran as fast as possible for five meters toward a marker placed on the floor and performed an approximate 75° cut before running maximally to the finish. An eight camera 3D motion analysis system (Vicon - Bonita B10, UK), synchronized with two 40x60cm force platforms (AMTI – BP400600, USA), collected biomechanical data. Data analysis utilized the mean of each participant’s three trials on the symptomatic side, or for those with bi-lateral groin pain (n = 80), the side that was most symptomatic. A cluster analysis was undertaken using kinematic data as input (ankle, knee, hip, pelvis and trunk angles). Repeated measure ANOVAs with bonferroni post-hoc corrections were then used to determine between sub-group differences in biomechanical variables of interest. A significance level of (α = 0.05) was adopted. Results: Three distinct subgroups were created: C1 (containing 40% of participants), C2 (containing 15% of participants) and C3 (containing 45% of participants). C1 had significantly greater hip flexion and hip-pelvo-trunk rotation than C2 and C3. C3 and C2 had significantly greater hip-pelvo-trunk lateral side flexion than C1. C2 had significantly greater trunk flexion than both C1 and C3. Conclusion: Different sub-groups existed within the large cohort that exhibited distinctive cutting mechanics. Our findings may go some way toward identifying the potential cutting characteristics/diagnoses that exist in AGP patients. Rehabilitation specilaists may look to utilise such information when attempting to affect their patients cutting mechanics. Future studies are required to confirm the clinical relevance of the cutting characteristics/diagnoses identified herein. An examination of the effects of individualising groin rehabilitation programs based on a cutting mechanics assessment appears warrented. Given the inter-individual differences in cutting mechanics observed, caution is advised in the use of traditional group based analyses in future AGP biomechanical studies. This is due to the potential masking of significant findings when using heterogenous data (Bates 2005). Clustering techniques, such as employed here, may be useful in identifying homogenous sub-groups before undertaking more traditional statistical analyses

Development of a framework for reporting health service models for managing rheumatoid arthritis

The purpose of this study was to develop a framework for reporting health service models for managing rheumatoid arthritis (RA). We conducted a search of the health sciences literature for primary studies that described interventions which aimed to improve the implementation of health services in adults with RA. Thereafter, a nominal group consensus process was used to synthesize the evidence for the development of the reporting framework. Of the 2,033 citations screened, 68 primary studies were included which described 93 health service models for RA. The origin and meaning of the labels given to these health service delivery models varied widely and, in general, the reporting of their components lacked detail or was absent. The six dimensions underlying the framework for reporting RA health service delivery models are: (1) Why was it founded? (2) Who was involved? (3) What were the roles of those participating? (4) When were the services provided? (5) Where were the services provided/received? (6) How were the services/interventions accessed and implemented, how long was the intervention, how did individuals involved communicate, and how was the model supported/sustained? The proposed framework has the potential to facilitate knowledge exchange among clinicians, researchers, and decision makers in the area of health service delivery. Future work includes the validation of the framework with national and international stakeholders such as clinicians, health care administrators, and health services researchers

Clinical and biomechanical outcomes of rehabilitation targeting intersegmental control in athletic groin pain:prospective cohort of 205 patients

Background: Clinical assessments and rehabilitation in athletic groin pain (AGP) have focused on specific anatomical structures and uniplanar impairments rather than whole body movement. Objective: To examine the effectiveness of rehabilitation that targeted intersegmental control in patients with AGP and to investigate post rehabilitation changes in cutting biomechanics. Methods: Two hundred and five patients with AGP were rehabilitated focusing on clinical assessment of intersegmental control, linear running and change of direction mechanics in this prospective case series. Hip and Groin Outcome Score (HAGOS) was the primary outcome measure. Secondary measures included pain-free return to play rates and times, pain provocation on squeeze tests and three-dimensional (3D) biomechanical analysis during a 110° cutting manoeuvre. Results: Following rehabilitation, patients demonstrated clinically relevant improvements in HAGOS scores (effect size (ES): 0.6–1.7). 73% of patients returned to play pain-free at a mean of 9.9 weeks (±3.5). Squeeze test values also improved (ES: 0.49–0.68). Repeat 3D analysis of the cutting movement demonstrated reductions in ipsilateral trunk side flexion (ES: 0.79) and increased pelvic rotation in the direction of travel (ES: 0.76). Changes to variables associated with improved cutting performance: greater centre of mass translation in the direction of travel relative to centre of pressure (ES: 0.4), reduced knee flexion angle (ES: 0.3) and increased ankle plantar flexor moment (ES: 0.48) were also noted. Conclusions: Rehabilitation focused on intersegmental control was associated with improved HAGOS scores, high rates of pain-free return to sporting participation and biomechanical changes associated with improved cutting performance across a range of anatomical diagnoses seen in AGP

Factors Influencing Return to Play and Second Anterior Cruciate Ligament Injury Rates in Level 1 Athletes After Primary Anterior Cruciate Ligament Reconstruction:2-Year Follow-up on 1432 Reconstructions at a Single Center

BACKGROUND: Despite the importance of return-to-play (RTP) rates, second anterior cruciate ligament (ACL) injury rates, and patient-reported outcomes of athletes returning to sports after ACL reconstruction (ACLR), these outcomes have not been evaluated together across a single cohort nor the pre- and intraoperative factors influencing outcomes explored. PURPOSE: To prospectively report outcomes after ACLR relating to RTP, second ACL injury, and International Knee Document Committee (IKDC) scores in a large cohort of athletes at a single center to examine the influence of pre- and intraoperative variables on these outcomes. DESIGN: Cohort study; Level of evidence, 3. METHODS: A consecutive cohort of 1432 athletes undergoing primary ACLR by 2 orthopaedic surgeons was followed up prospectively more than 2 years after surgery. Pre- and intraoperative findings were reported with outcomes at follow-up relating to RTP, second ACL injury, and IKDC. Between-group differences for each outcome were reported and the predictive ability of pre- and intraoperative variables relating to each outcome assessed with logistic regression. RESULTS: There was >95% follow-up 2 years after surgery. The RTP rate was 81%, and of those who returned, 1.3% of those with patellar tendon grafts and 8.3% of those with hamstring grafts experienced ipsilateral rerupture (hazard ratio, 0.17). The contralateral ACL injury rate was 6.6%, and the IKDC score at follow-up was 86.8, with a greater proportion of patients with patellar tendon grafts scoring <80 on the IKDC (odds ratio, 1.56; 95% CI, 1.15–3.12). There was no relationship between time to RTP and second ACL injury, and there was a moderate correlation between ACL–Return to Sport After Injury score and RTP at follow-up (P < .001, rho = 0.46). There were a number of differences in pre- and intraoperative variables between groups for each outcome, but they demonstrated a poor ability to predict outcomes in level 1 athletes at 2-year follow-up. CONCLUSION: Findings demonstrated high overall RTP rates, lower reinjury rates with patellar tendon graft after 2-year follow-up in level 1 athletes, and no influence of time to RTP on second ACL injury. Despite differences between groups, there was poor predictive ability of pre- and intraoperative variables. Results suggest pre- and intraoperative variables for consideration to optimize outcomes in level 1 athletes after ACLR, but future research exploring other factors, such as physical and psychological recovery, may be needed to improve outcome prediction after ACLR