Precision, Reliability, and Responsiveness of a Novel Automated Quantification Tool for Cartilage Thickness: Data from the Osteoarthritis Initiative

Objective; Accurate automated segmentation of cartilage should provide rapid reliable outcomes for both epidemiological studies and clinical trials. We aimed to assess the precision and responsiveness of cartilage thickness measured with careful manual segmentation or a novel automated technique. Methods; Agreement of automated segmentation was assessed against two manual segmentation datasets: 379 MR images manually segmented in-house (Training set), and 582 from the OAI with data available at 0, 1, and 2 years (Biomarkers set). Agreement of mean thickness was assessed using Bland-Altman plots, change with pairwise Students t-test, in the central medial femur and tibia regions (cMF, cMT). Repeatability was assessed on a set of 19 knees imaged twice on the same day. Responsiveness was assessed using standardised response means (SRMs). Results; Agreement of manual vs automated methods was excellent with no meaningful systematic bias (Training set cMF bias 0.1mm 95%CI ±0.35, Biomarkers set bias 0.1mm ±0.4). The smallest detectable difference (SDD) for cMF was 0.13mm, coefficient of variation (CoV) 3.1%; cMT 0.16 mm, 2.65%. Reported change using manual segmentations in the cMF region at 1 year was -0.031mm, confidence limit (-0.022, -0.039), p<10-4, SRM -0.31 (-0.23,-0.38); at 2 years was -0.071 (-0.058,-0.085), p<10-4, SRM -0.43(-0.36,-0.49). Reported change using automated segmentations in the cMF at 1 year was - 0.059 (-0.047, -0.071), p<10-4, SRM -0.41(-0.34,-0.48) ; 2 years: -0.14 (-0.123,-0.157), p<10-4, SRM -0.67 (-0.6,-0.72). Conclusion; A novel cartilage segmentation method provides highly accurate and repeatable measures with comparable cartilage thickness measurements to careful manual segmentation, but with improved responsiveness

Levels of procoagulant microvesicles are elevated after traumatic injury and platelet microvesicles are negatively correlated with mortality

Background: Microvesicles (MV) have been implicated in the development of thrombotic disease, such as acute respiratory distress syndrome (ARDS) and multiple organ failure (MOF). Trauma patients are at increased risk of late thrombotic events, particularly those who receive a major transfusion. The aims of this study were: (a) to determine whether there were increased numbers of pro-coagulant MV following injury; (b) to determine their cellular origin; and (c) to explore the effects of MV with clinical outcomes; in particular red cell transfusion requirements and death. Methods: Trauma patients were recruited at a Level 1 trauma centre. The presence of MV procoagulant phospholipid (PPL) was assessed using 2 activity assays (PPL and thrombin generation). Enumeration and MV cellular origin was assessed using 2 colour flow cytometry. Results: Fifty consecutive patients were recruited; median age 38 (IQR: 24–55), median ISS 18 (IQR: 9–27). Circulating procoagulant MV, rich in phospholipid, were significantly elevated following traumatic injury relative to controls and remained elevated at 72 h post-injury. Red cell/AnnV+ and platelet/AnnV+ MV numbers were 6-fold and 2-fold higher than controls, respectively. Patients who died (n=9, 18%) had significantly fewer CD41/AnnV+ MV and lower endogenous thrombin potential relative to patients who survived. Conclusions: MV are elevated following traumatic injury and may be implicated in the increased risk of trauma patients to pro-thrombotic states such as MOF and ARDS. Lower levels of procoagulant MV are associated with mortality and further investigation of this association is warranted

Sectoral specialisation in the EU a macroeconomic perspective

This paper analyses trends in sectoral specialisation in the EU and concludes the following: 1) The European production structure appears more homogenous than that of the US. 2) While sectoral specialisation has shown a slight increase in some smaller euro area countries towards the end-1990s, it is too early to detect any potential impact of EMU. 3) Despite some changes in sectoral composition, the business cycles of euro area countries became more synchronised over the 1990s, which may be seen as reassuring from the point of view of the single monetary policy. 4) Sectoral re-allocation accounts for as much as 50% of the increase in labour productivity growth in business sector services in the euro area. 5) The slowdown of European labour productivity growth relative to the US since the mid-1990s is explained by a stronger performance in the US wholesale and retail trade, financial intermediation and high-tech manufacturing sectors.

Segond's fracture: a biomechanical cadaveric study using navigation

Background Segond’s fracture is a well-recognised radiological sign of an anterior cruciate ligament (ACL) tear. While previous studies evaluated the role of the anterolateral ligament (ALL) and complex injuries on rotational stability of the knee, there are no studies on the biomechanical effect of Segond’s fracture in an ACL deficient knee. The aim of this study was to evaluate the effect of a Segond’s fracture on knee rotation stability as evaluated by a navigation system in an ACL deficient knee. Materials and methods Three different conditions were tested on seven knee specimens: intact knee, ACL deficient knee and ACL deficient knee with Segond’s fracture. Static and dynamic measurements of anterior tibial translation (ATT) and axial tibial rotation (ATR) were recorded by the navigation system (2.2 OrthoPilot ACL navigation system B. Braun Aesculap, Tuttlingen, Germany). Results Static measurements at 30 showed that the mean ATT at 30 of knee flexion was 5.1 ± 2.7 mm in the ACL intact condition, 14.3 ± 3.1 mm after ACL cut (P = 0.005), and 15.2 ± 3.6 mm after Segond’s fracture (P = 0.08). The mean ATR at 30 of knee flexion was 20.7 ± 4.8 in the ACL intact condition, 26.9 ± 4.1 in the ACL deficient knee (P[0.05) and 30.9 ± 3.8 after Segond’s fracture (P = 0.005). Dynamic measurements during the pivot-shift showed that the mean ATT was 7.2 ± 2.7 mm in the intact knee, 9.1 ± 3.3 mm in the ACL deficient knee(P = 0.04) and 9.7 ± 4.3 mm in the ACL deficient knee with Segond’s fracture (P = 0.07). The mean ATR was 9.6 ± 1.8 in the intact knee, 12.3 ± 2.3 in the ACL deficient knee (P[0.05) and 19.1 ± 3.1 in the ACL deficient knee with Segond’s lesion (P = 0.016). Conclusion An isolated lesion of the ACL only affects ATT during static and dynamic measurements, while the addition of Segond’s fracture has a significant effect on ATR in both static and dynamic execution of the pivot-shift test, as evaluated with the aid of navigation

Recognizing Treelike k-Dissimilarities

A k-dissimilarity D on a finite set X, |X| >= k, is a map from the set of size k subsets of X to the real numbers. Such maps naturally arise from edge-weighted trees T with leaf-set X: Given a subset Y of X of size k, D(Y) is defined to be the total length of the smallest subtree of T with leaf-set Y . In case k = 2, it is well-known that 2-dissimilarities arising in this way can be characterized by the so-called "4-point condition". However, in case k > 2 Pachter and Speyer recently posed the following question: Given an arbitrary k-dissimilarity, how do we test whether this map comes from a tree? In this paper, we provide an answer to this question, showing that for k >= 3 a k-dissimilarity on a set X arises from a tree if and only if its restriction to every 2k-element subset of X arises from some tree, and that 2k is the least possible subset size to ensure that this is the case. As a corollary, we show that there exists a polynomial-time algorithm to determine when a k-dissimilarity arises from a tree. We also give a 6-point condition for determining when a 3-dissimilarity arises from a tree, that is similar to the aforementioned 4-point condition.Comment: 18 pages, 4 figure

Acceptability and Preliminary Efficacy of a Web- and Telephone-Based Personalised Exercise Intervention for Individuals with Metastatic Prostate Cancer: The ExerciseGuide Pilot Randomised Controlled Trial.

Preliminary research has shown the effectiveness of supervised exercise-based interventions in alleviating sequela resulting from metastatic prostate cancer. However, many individuals encounter barriers that limit the uptake of face-to-face exercise. Technology-enabled interventions offer a distance-based alternative. This pilot study aimed to explore the acceptability, safety and preliminary efficacy of a web-based exercise intervention (ExerciseGuide) in individuals with metastatic prostate cancer. Forty participants (70.2 ± 8.5 years) with metastatic prostate cancer were randomised into the 8-week intervention (N = 20) or a wait-list control (N = 20). The intervention arm had access to a computer-tailored website, personalised exercise prescription and remote supervision. ExerciseGuide was deemed acceptable with a score ≥20 on the client satisfaction questionnaire; however, the usability score was just below the pre-specified score of ≥68 on the software usability scale. There were no serious adverse events reported. Moderate-to-vigorous physical activity levels between baseline and follow-ups were significantly higher (10.0 min per day; 95% CI = (1.3-18.6); p = 0.01) in the intervention group compared to wait-list control. There were also greater improvements in step count (1332; 95% CI = (159-2505); p = 0.02) and identified motivation (0.4, 95% CI = (0.0, 0.7); p = 0.04). Our findings provide preliminary evidence that ExerciseGuide is acceptable, safe and efficacious among individuals with metastatic prostate cancer

Local Optical Probe of Motion and Stress in a multilayer graphene NEMS

Nanoelectromechanical systems (NEMSs) are emerging nanoscale elements at the crossroads between mechanics, optics and electronics, with significant potential for actuation and sensing applications. The reduction of dimensions compared to their micronic counterparts brings new effects including sensitivity to very low mass, resonant frequencies in the radiofrequency range, mechanical non-linearities and observation of quantum mechanical effects. An important issue of NEMS is the understanding of fundamental physical properties conditioning dissipation mechanisms, known to limit mechanical quality factors and to induce aging due to material degradation. There is a need for detection methods tailored for these systems which allow probing motion and stress at the nanometer scale. Here, we show a non-invasive local optical probe for the quantitative measurement of motion and stress within a multilayer graphene NEMS provided by a combination of Fizeau interferences, Raman spectroscopy and electrostatically actuated mirror. Interferometry provides a calibrated measurement of the motion, resulting from an actuation ranging from a quasi-static load up to the mechanical resonance while Raman spectroscopy allows a purely spectral detection of mechanical resonance at the nanoscale. Such spectroscopic detection reveals the coupling between a strained nano-resonator and the energy of an inelastically scattered photon, and thus offers a new approach for optomechanics

Collapse of superconductivity in a hybrid tin-graphene Josephson junction array

When a Josephson junction array is built with hybrid superconductor/metal/superconductor junctions, a quantum phase transition from a superconducting to a two-dimensional (2D) metallic ground state is predicted to happen upon increasing the junction normal state resistance. Owing to its surface-exposed 2D electron gas and its gate-tunable charge carrier density, graphene coupled to superconductors is the ideal platform to study the above-mentioned transition between ground states. Here we show that decorating graphene with a sparse and regular array of superconducting nanodisks enables to continuously gate-tune the quantum superconductor-to-metal transition of the Josephson junction array into a zero-temperature metallic state. The suppression of proximity-induced superconductivity is a direct consequence of the emergence of quantum fluctuations of the superconducting phase of the disks. Under perpendicular magnetic field, the competition between quantum fluctuations and disorder is responsible for the resilience at the lowest temperatures of a superconducting glassy state that persists above the upper critical field. Our results provide the entire phase diagram of the disorder and magnetic field-tuned transition and unveil the fundamental impact of quantum phase fluctuations in 2D superconducting systems.Comment: 25 pages, 6 figure

Ventricular function and biomarkers in relation to repair and pulmonary valve replacement for tetralogy of Fallot

Objective Cardiac surgery may cause temporarily impaired ventricular performance and myocardial injury. We aim to characterise the response to perioperative injury for patients undergoing repair or pulmonary valve replacement (PVR) for tetralogy of Fallot (ToF). Methods We enrolled children undergoing ToF repair or PVR from four tertiary centres in a prospective observational study. Assessment - including blood sampling and speckle tracking echocardiography - occurred before surgery (T1), at the first follow-up (T2) and 1 year after the procedures (T3). Ninety-two serum biomarkers were expressed as principal components to reduce multiple statistical testing. RNA Sequencing was performed on right ventricular (RV) outflow tract samples. Results We included 45 patients with ToF repair aged 4.3 (3.4 - 6.5) months and 16 patients with PVR aged 10.4 (7.8 - 12.7) years. Ventricular function following ToF repair showed a fall-and-rise pattern for left ventricular global longitudinal strain (GLS) (-18±4 to -13±4 to -20±2, p &lt; 0.001 for each comparison) and RV GLS (-19±5 to -14±4 to 20±4, p &lt; 0.002 for each comparison). This pattern was not seen for patients undergoing PVR. Serum biomarkers were expressed as three principal components. These phenotypes are related to: (1) surgery type, (2) uncorrected ToF and (3) early postoperative status. Principal component 3 scores were increased at T2. This increase was higher for ToF repair than PVR. The transcriptomes of RV outflow tract tissue are related to patients' sex, rather than ToF-related phenotypes in a subset of the study population. Conclusions The response to perioperative injury following ToF repair and PVR is characterised by specific functional and immunological responses. However, we did not identify factors relating to (dis)advantageous recovery from perioperative injury. Trial registration number Netherlands Trial Register: NL5129.</p

Collaborative denoising autoencoder for high glycated haemoglobin prediction.

A pioneering study is presented demonstrating that the presence of high glycated haemoglobin (HbA1c) levels in a patient’s blood can be reliably predicted from routinely collected clinical data. This paves the way for performing early detection of Type-2 Diabetes Mellitus (T2DM). This will save healthcare providers a major cost associated with the administration and assessment of clinical tests for HbA1c. A novel collaborative denoising autoencoder framework is used to address this challenge. The framework builds an independent denoising autoencoder model for the high and low HbA1c level, which extracts feature representations in the latent space. A baseline model using just three features: patient age together with triglycerides and glucose level achieves 76% F1-score with an SVM classifier. The collaborative denoising autoencoder uses 78 features and can predict HbA1c level with 81% F1-score