PROCESS VALIDATION IN CALCULATING MEDIAN PROXIMITY IN TIBIOFEMORAL CARTILAGE DEFORMATION UNDER FULL BODY LOADING

INTRODUCTION Knee osteoarthritis (OA) is characterized by progressive and irreversible degradation of tibiofemoral (TF) cartilages. Anterior cruciate ligament (ACL) rupture is a known risk factor for post-traumatic OA (PTOA) [1]. However, there are currently no in-vivo tests to diagnose pre-radiographic PTOA. Following injury, the cartilage macromolecular matrix weakens, cartilage swells and consequently cartilage softness increases [2]. This research investigates the in-vivo effects of ACL injury on cartilage deformation magnitude and rate under full body loading. The objective of this project was to determine the consequences of cartilage model mesh types and incremental mesh simplifications on the accuracy of resultant TF cartilage proximities. METHODS The affected knee of a 37 year old male PTOA subject (ACL deficient for 6 years) was imaged using Magnetic Resonance Imaging (FIESTA sequence; 3T GE Discovery 750). 3D TF bone and cartilage models were generated in Amira (VSG, Germany). The subject performed a 10 minute standing task in the Dual Fluoroscopic (DF) laboratory. DF images (32LP/mm) were collected at 6Hz. Bone alignments were reconstructed from DF images using AutoScoper (Brown University, USA) and cartilage models were co-registered. TF cartilage surface proximity was determined as the surface normal distance from each triangular mesh face onto the opposing cartilage. (Matlab, v2014b, The MathWorks, USA). The effects on surface proximities of three types of triangular cartilage surface meshes, generated in Amira, were analysed: 1) Basic Simplification - reducing face numbers with variable mesh size; 2) Remeshed Surface – isotropic mesh; 3) Iteratively Smoothed Remeshed Surface. Face numbers were reduced at 10% increments from the original surface for each surface type. RESULTS Median proximity errors for the Remeshed Surface were consistently smaller than the other mesh types across all four cartilage surface compartments. The medial tibial plateau displayed a rapid increase in error (Figure 1) indicating a high sensitivity to model simplification. This may have been due to its more complex surface geometry. The maximum acceptable error was chosen to match the minimum detectable displacement of 0.05mm for this DF system [3]. DISCUSSION AND CONCLUSIONS The findings of this investigation identified differences in the error of cartilage surface proximities under loading due to the use of different mesh types and simplifications. The smoothing technique used by Amira did not consistently converge to a surface and the variable triangle size in Basic Simplification affected the computation of proximity, resulting in unpredictable error spikes in cartilage surface proximity calculations. The results suggest that surface modeling parameters are surface geometry specific. The limiting case of the medial tibial plateau showed the optimal simplification was 0.594mm triangle mesh side length (40% of the original faces). These results inform ongoing work toward an in-vivo pre-radiographic diagnostic of PTOA

DYNAMIC VALIDATION OF TIBIOFEMORAL KINEMATICS MEASURED USING A DUAL FLUOROSCOPY SYSTEM: A MARKER-BASED APPROACH

INTRODUCTION Knee joint cartilage degeneration in post-traumatic osteoarthritis is initiated at the point of injury and progresses through abnormal movement mechanics [1]. Anterior cruciate ligament rupture influences the development and progression of osteoarthritis [1], however the specific in vivo effects of abnormal bone and joint kinematics and kinetics on human cartilage health remain largely unknown.  Quantifying in vivo knee kinematics with submillimeter accuracies may elucidate injurious movement alterations.  Dual Fluoroscopy (DF) allows for accurate, high-speed, and non-invasive skeletal kinematics assessment, but requires validation.  The aim of this project was to quantify the in vitro accuracy and precision of a high-speed dual fluoroscopy system for measuring 6 degree of freedom (DOF) knee kinematics obtained from a marker-less 2D-3D registration approach as compared to the gold standard marker-based method. For this preliminary work, we hypothesized that the precision of inter-bead 3D Euclidean distance measurement is less than or equal to 0.10 mm [2]. METHODS Upon approval by the local ethics committee, one female cadaveric human leg was obtained through the local body donation program. Four 3mm metal beads were surgically implanted in the distal femur and proximal tibia.  Thereafter, the limb was scanned using computed tomography (CT). Following imaging, the soft tissues of the proximal shaft of the femur were dissected to expose the bone and the femoral head was removed. The proximal shaft of the femur was then fixed in a custom-made metal cylinder using fixation screws and potted using polymethyl methacrylate (PMMA). The free end of the metal cylinder was in turn fixed to an articulated 6 DOF tripod mount (Manfrotto, Italy).  In the DF laboratory the limb was suspended in the DF field of view using a custom steel frame. A rope pulley system, fixed around the ankle joint, was used to manipulate the limb. DF images were acquired at 60 Hz during manipulation of the limb into knee flexion. All images were distortion corrected and calibrated using established procedures. Marker-based tracking was conducted on 75 DF frames using in-house software to determine the 2D coordinates of the bead centroids in each image pair.  Subsequently, a modified direct linear transform was applied to obtain the 3D bead centroid coordinates. Matlab (MathWorks, v2014b, USA) code was written in order to determine the Euclidean distance between beads. RESULTSTable 1: The mean distance between beads in the femur and tibia ± SD (mm) calculated over 75 DF frames.  Right: Camera 1 DF image demonstrating the numbering of beads.DISCUSSION AND CONCLUSIONS The data indicated inter-bead distance variabilities consistent with previously observed system errors (for static imaging), when investigating a moving limb (Table 1). The observed variations could be due to multiple contributors. A lack of bead sphericity and bead deformation, as a result of surgical bead implantation, may have caused erroneous bead centroid estimates. Further, DF image distortions may have persisted even after distortion correction, contributing to observed error. Future steps include improved image calibration using a sophisticated bundle adjustment algorithm to further reduce system errors [3]

Human-Centered Tools for Coping with Imperfect Algorithms during Medical Decision-Making

Machine learning (ML) is increasingly being used in image retrieval systems for medical decision making. One application of ML is to retrieve visually similar medical images from past patients (e.g. tissue from biopsies) to reference when making a medical decision with a new patient. However, no algorithm can perfectly capture an expert's ideal notion of similarity for every case: an image that is algorithmically determined to be similar may not be medically relevant to a doctor's specific diagnostic needs. In this paper, we identified the needs of pathologists when searching for similar images retrieved using a deep learning algorithm, and developed tools that empower users to cope with the search algorithm on-the-fly, communicating what types of similarity are most important at different moments in time. In two evaluations with pathologists, we found that these refinement tools increased the diagnostic utility of images found and increased user trust in the algorithm. The tools were preferred over a traditional interface, without a loss in diagnostic accuracy. We also observed that users adopted new strategies when using refinement tools, re-purposing them to test and understand the underlying algorithm and to disambiguate ML errors from their own errors. Taken together, these findings inform future human-ML collaborative systems for expert decision-making

Theory of Rare-earth Infinite Layer Nickelates

The recent discovery of superconductivity in oxygen-reduced monovalent nickelates has raised a new platform for the study of unconventional superconductivity, with similarities and differences with the cuprate high temperature superconductors. In this paper we discuss general trends of the infinite-layer nickelate RNiO$_2$ with rare-earth R spanning across the lanthanide series. We determine that the role of oxygen charge transfer diminishes when traversing from La to Lu, with a prominent role played by rare-earth 5d electrons near the Fermi level. A decrease in lattice volume indicates that the magnetic exchange additionally grows, which may be favorable for superconductivity. However compensation effects from the itinerant 5d electrons present a closer analogy to Kondo lattices, indicating a more complex interplay between charge transfer, bandwidth renormalization, compensation, and magnetic exchange

Impact of cumulative complications on 1-year treatment-related healthcare costs in patients with colorectal peritoneal metastases undergoing cytoreductive surgery with hyperthermic intraperitoneal chemotherapy

BACKGROUND: The aim of this study was to evaluate the impact of all minor and major complications on treatment-related healthcare costs in patients who undergo cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of colorectal peritoneal metastases (PMs). METHOD: Patients with histologically proven colorectal PMs who underwent CRS + HIPEC from March 2006 to October 2019 in a tertiary referral centre were retrospectively identified from a prospectively maintained database. Patients were divided into six subgroups according to the severity of the complications, which were scored using the comprehensive complication index (CCI) (CCI 0-9.9, CCI 10-19.9, CCI 20-29.9, CCI 30-39.9, CCI 40-49.9, and CCI 50 or higher). Treatment-related healthcare costs up to 1 year after CRS + HIPEC were obtained from the financial department. Differences in costs and survival outcomes were compared using the chi-squared test and Kruskal-Wallis H test. RESULTS: A total of 142 patients were included (CCI 0-9.9, 53 patients; CCI 10-19.9, 0 patients; CCI 20-29.9, 45 patients; CCI 30-39.9, 14 patients; CCI 40-49, 9 patients; and CCI 50 or higher, 21 patients). Median (interquartile range) treatment-related healthcare costs increased significantly and exponentially for the CCI 30-39, CCI 40-49, and CCI 50 or higher groups (€48 993 (€44 262-€84 805); €57 167 (€43 047-€67 591); and €82 219 (€55 487-€145 314) respectively) compared with those for the CCI 0-9.9 and CCI 20-29.9 groups (€33 856 (€24 433-€40 779) and €40 621 (€31 501-€58 761) respectively, P < 0.010). CONCLUSION: Treatment-related healthcare costs increase exponentially as more complications develop among patients who undergo CRS + HIPEC for the treatment of colorectal PMs. Anastomotic leakages after CRS + HIPEC lead to an increase of 295 per cent of treatment-related healthcare costs

Consortium for the Study of Pregnancy Treatments (Co-OPT): An international birth cohort to study the effects of antenatal corticosteroids

BACKGROUND: Antenatal corticosteroids (ACS) are widely prescribed to improve outcomes following preterm birth. Significant knowledge gaps surround their safety, long-term effects, optimal timing and dosage. Almost half of women given ACS give birth outside the "therapeutic window" and have not delivered over 7 days later. Overtreatment with ACS is a concern, as evidence accumulates of risks of unnecessary ACS exposure. METHODS: The Consortium for the Study of Pregnancy Treatments (Co-OPT) was established to address research questions surrounding safety of medications in pregnancy. We created an international birth cohort containing information on ACS exposure and pregnancy and neonatal outcomes by combining data from four national/provincial birth registers and one hospital database, and follow-up through linked population-level data from death registers and electronic health records. RESULTS AND DISCUSSION: The Co-OPT ACS cohort contains 2.28 million pregnancies and babies, born in Finland, Iceland, Israel, Canada and Scotland, between 1990 and 2019. Births from 22 to 45 weeks' gestation were included; 92.9% were at term (≥ 37 completed weeks). 3.6% of babies were exposed to ACS (67.0% and 77.9% of singleton and multiple births before 34 weeks, respectively). Rates of ACS exposure increased across the study period. Of all ACS-exposed babies, 26.8% were born at term. Longitudinal childhood data were available for 1.64 million live births. Follow-up includes diagnoses of a range of physical and mental disorders from the Finnish Hospital Register, diagnoses of mental, behavioural, and neurodevelopmental disorders from the Icelandic Patient Registers, and preschool reviews from the Scottish Child Health Surveillance Programme. The Co-OPT ACS cohort is the largest international birth cohort to date with data on ACS exposure and maternal, perinatal and childhood outcomes. Its large scale will enable assessment of important rare outcomes such as perinatal mortality, and comprehensive evaluation of the short- and long-term safety and efficacy of ACS

Effect of remote ischaemic conditioning on clinical outcomes in patients with acute myocardial infarction (CONDI-2/ERIC-PPCI): a single-blind randomised controlled trial.

BACKGROUND: Remote ischaemic conditioning with transient ischaemia and reperfusion applied to the arm has been shown to reduce myocardial infarct size in patients with ST-elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). We investigated whether remote ischaemic conditioning could reduce the incidence of cardiac death and hospitalisation for heart failure at 12 months. METHODS: We did an international investigator-initiated, prospective, single-blind, randomised controlled trial (CONDI-2/ERIC-PPCI) at 33 centres across the UK, Denmark, Spain, and Serbia. Patients (age >18 years) with suspected STEMI and who were eligible for PPCI were randomly allocated (1:1, stratified by centre with a permuted block method) to receive standard treatment (including a sham simulated remote ischaemic conditioning intervention at UK sites only) or remote ischaemic conditioning treatment (intermittent ischaemia and reperfusion applied to the arm through four cycles of 5-min inflation and 5-min deflation of an automated cuff device) before PPCI. Investigators responsible for data collection and outcome assessment were masked to treatment allocation. The primary combined endpoint was cardiac death or hospitalisation for heart failure at 12 months in the intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02342522) and is completed. FINDINGS: Between Nov 6, 2013, and March 31, 2018, 5401 patients were randomly allocated to either the control group (n=2701) or the remote ischaemic conditioning group (n=2700). After exclusion of patients upon hospital arrival or loss to follow-up, 2569 patients in the control group and 2546 in the intervention group were included in the intention-to-treat analysis. At 12 months post-PPCI, the Kaplan-Meier-estimated frequencies of cardiac death or hospitalisation for heart failure (the primary endpoint) were 220 (8·6%) patients in the control group and 239 (9·4%) in the remote ischaemic conditioning group (hazard ratio 1·10 [95% CI 0·91-1·32], p=0·32 for intervention versus control). No important unexpected adverse events or side effects of remote ischaemic conditioning were observed. INTERPRETATION: Remote ischaemic conditioning does not improve clinical outcomes (cardiac death or hospitalisation for heart failure) at 12 months in patients with STEMI undergoing PPCI. FUNDING: British Heart Foundation, University College London Hospitals/University College London Biomedical Research Centre, Danish Innovation Foundation, Novo Nordisk Foundation, TrygFonden

Emil Been - Ricci Scholar-Research conducted during study abroad in JFRC Fall 2019 and LVC-LUC in Spring 2020

During my time in Italy and Vietnam, I spoke to queer-identifying artists and attended queer arts festivals in order to learn more about how society, culture, and identity affect art