Non-invasive computer-assisted measurement of knee alignment

The quantification of knee alignment is a routine part of orthopaedic practice and is important for monitoring disease progression, planning interventional strategies, and follow-up of patients. Currently available technologies such as radiographic measurements have a number of drawbacks. The aim of this study was to validate a potentially improved technique for measuring knee alignment under different conditions. An image-free navigation system was adapted for non-invasive use through the development of external infrared tracker mountings. Stability was assessed by comparing the variance (F-test) of repeated mechanical femoro-tibial (MFT) angle measurements for a volunteer and a leg model. MFT angles were then measured supine, standing and with varus-valgus stress in asymptomatic volunteers who each underwent two separate registrations and repeated measurements for each condition. The mean difference and 95% limits of agreement were used to assess intra-registration and inter-registration repeatability. For multiple registrations the range of measurements for the external mountings was 1° larger than for the rigid model with statistically similar variance (p=0.34). Thirty volunteers were assessed (19 males, 11 females) with a mean age of 41 years (range: 20-65) and a mean BMI of 26 (range: 19-34). For intra-registration repeatability, consecutive coronal alignment readings agreed to almost ±1°, with up to ±0.5° loss of repeatability for coronal alignment measured before and after stress maneuvers, and a ±0.2° loss following stance trials. Sagittal alignment measurements were less repeatable overall by an approximate factor of two. Inter-registration agreement limits for coronal and sagittal supine MFT angles were ±1.6° and ±2.3°, respectively. Varus and valgus stress measurements agreed to within ±1.3° and ±1.1°, respectively. Agreement limits for standing MFT angles were ±2.9° (coronal) and ±5.0° (sagittal), which may have reflected a variation in stance between measurements. The system provided repeatable, real-time measurements of coronal and sagittal knee alignment under a number of dynamic, real-time conditions, offering a potential alternative to radiographs

Should We Learn Probabilistic Models for Model Checking? A New Approach and An Empirical Study

Many automated system analysis techniques (e.g., model checking, model-based testing) rely on first obtaining a model of the system under analysis. System modeling is often done manually, which is often considered as a hindrance to adopt model-based system analysis and development techniques. To overcome this problem, researchers have proposed to automatically "learn" models based on sample system executions and shown that the learned models can be useful sometimes. There are however many questions to be answered. For instance, how much shall we generalize from the observed samples and how fast would learning converge? Or, would the analysis result based on the learned model be more accurate than the estimation we could have obtained by sampling many system executions within the same amount of time? In this work, we investigate existing algorithms for learning probabilistic models for model checking, propose an evolution-based approach for better controlling the degree of generalization and conduct an empirical study in order to answer the questions. One of our findings is that the effectiveness of learning may sometimes be limited.Comment: 15 pages, plus 2 reference pages, accepted by FASE 2017 in ETAP

How many independent bets are there?

The benefits of portfolio diversification is a central tenet implicit to modern financial theory and practice. Linked to diversification is the notion of breadth. Breadth is correctly thought of as the number of in- dependent bets available to an investor. Conventionally applications us- ing breadth frequently assume only the number of separate bets. There may be a large discrepancy between these two interpretations. We uti- lize a simple singular-value decomposition (SVD) and the Keiser-Gutman stopping criterion to select the integer-valued effective dimensionality of the correlation matrix of returns. In an emerging market such as South African we document an estimated breadth that is considerably lower than anticipated. This lack of diversification may be because of market concentration, exposure to the global commodity cycle and local currency volatility. We discuss some practical extensions to a more statistically correct interpretation of market breadth, and its theoretical implications for both global and domestic investors.Comment: Less technical rewrite. 12 Pages, 6 Figures (.eps

Nanoscale phase-engineering of thermal transport with a Josephson heat modulator

Macroscopic quantum phase coherence has one of its pivotal expressions in the Josephson effect [1], which manifests itself both in charge [2] and energy transport [3-5]. The ability to master the amount of heat transferred through two tunnel-coupled superconductors by tuning their phase difference is the core of coherent caloritronics [4-6], and is expected to be a key tool in a number of nanoscience fields, including solid state cooling [7], thermal isolation [8, 9], radiation detection [7], quantum information [10, 11] and thermal logic [12]. Here we show the realization of the first balanced Josephson heat modulator [13] designed to offer full control at the nanoscale over the phase-coherent component of thermal currents. Our device provides magnetic-flux-dependent temperature modulations up to 40 mK in amplitude with a maximum of the flux-to-temperature transfer coefficient reaching 200 mK per flux quantum at a bath temperature of 25 mK. Foremost, it demonstrates the exact correspondence in the phase-engineering of charge and heat currents, breaking ground for advanced caloritronic nanodevices such as thermal splitters [14], heat pumps [15] and time-dependent electronic engines [16-19].Comment: 6+ pages, 4 color figure

Prevalence of childhood disability and the characteristics and circumstances of disabled children in the UK : secondary analysis of the Family Resources Survey

Background: Robust data on the prevalence of childhood disability and the circumstances and characteristics of disabled children is crucial to understanding the relationship between impairment and social disadvantage. It is also crucial for public policy development aimed at reducing the prevalence of childhood disability and providing appropriate and timely service provision. This paper reports prevalence rates for childhood disability in the United Kingdom (UK) and describes the social and household circumstances of disabled children, comparing these where appropriate to those of non-disabled children. Methods: Data were generated from secondary analysis of the Family Resources Survey, a national UK cross-sectional survey, (2004/5) which had data on 16,012 children aged 0-18 years. Children were defined as disabled if they met the Disability Discrimination Act (DDA) definition (1995 and 2005). Frequency distributions and cross-tabulations were run to establish prevalence estimates, and describe the circumstances of disabled children. To establish the association between individual social and material factors and childhood disability when other factors were controlled for, logistic regression models were fitted on the dependent variable 'DDA defined disability'. Results: 7.3% (CI 6.9, 7.7) of UK children were reported by as disabled according to the DDA definition. Patterns of disability differed between sexes with boys having a higher rate overall and more likely than girls to experience difficulties with physical coordination; memory, concentration and learning; communication. Disabled children lived in different personal situations from their non-disabled counterparts, and were more likely to live with low-income, deprivation, debt and poor housing. This was particularly the case for disabled children from black/minority ethnic/ mixed parentage groups and lone-parent households. Childhood disability was associated with lone parenthood and parental disability and these associations persisted when social disadvantage was controlled for. Conclusion: These analyses suggest that UK disabled children experience higher levels of poverty and personal and social disadvantage than other children. Further research is required to establish accurate prevalence estimates of childhood disability among different black and minority ethnic groups and to understand the associations between childhood disability and lone parenthood and the higher rates of sibling and parental disability in households with disabled children

The Human Fungal Pathogen Cryptococcus neoformans Escapes Macrophages by a Phagosome Emptying Mechanism That Is Inhibited by Arp2/3 Complex-Mediated Actin Polymerisation

The lysis of infected cells by disease-causing microorganisms is an efficient but risky strategy for disseminated infection, as it exposes the pathogen to the full repertoire of the host's immune system. Cryptococcus neoformans is a widespread fungal pathogen that causes a fatal meningitis in HIV and other immunocompromised patients. Following intracellular growth, cryptococci are able to escape their host cells by a non-lytic expulsive mechanism that may contribute to the invasion of the central nervous system. Non-lytic escape is also exhibited by some bacterial pathogens and is likely to facilitate long-term avoidance of the host immune system during latency. Here we show that phagosomes containing intracellular cryptococci undergo repeated cycles of actin polymerisation. These actin ‘flashes’ occur in both murine and human macrophages and are dependent on classical WASP-Arp2/3 complex mediated actin filament nucleation. Three dimensional confocal imaging time lapse revealed that such flashes are highly dynamic actin cages that form around the phagosome. Using fluorescent dextran as a phagosome membrane integrity probe, we find that the non-lytic expulsion of Cryptococcus occurs through fusion of the phagosome and plasma membranes and that, prior to expulsion, 95% of phagosomes become permeabilised, an event that is immediately followed by an actin flash. By using pharmacological agents to modulate both actin dynamics and upstream signalling events, we show that flash occurrence is inversely related to cryptococcal expulsion, suggesting that flashes may act to temporarily inhibit expulsion from infected phagocytes. In conclusion, our data reveal the existence of a novel actin-dependent process on phagosomes containing cryptococci that acts as a potential block to expulsion of Cryptococcus and may have significant implications for the dissemination of, and CNS invasion by, this organism.\ud \u

Dissociable effects of 5-HT2C receptor antagonism and genetic inactivation on perseverance and learned non-reward in an egocentric spatial reversal task

Cognitive flexibility can be assessed in reversal learning tests, which are sensitive to modulation of 5-HT2C receptor (5-HT2CR) function. Successful performance in these tests depends on at least two dissociable cognitive mechanisms which may separately dissipate associations of previous positive and negative valence. The first is opposed by perseverance and the second by learned non-reward. The current experiments explored the effect of reducing function of the 5-HT2CR on the cognitive mechanisms underlying egocentric reversal learning in the mouse. Experiment 1 used the 5-HT2CR antagonist SB242084 (0.5 mg/kg) in a between-groups serial design and Experiment 2 used 5-HT2CR KO mice in a repeated measures design. Animals initially learned to discriminate between two egocentric turning directions, only one of which was food rewarded (denoted CS+, CS−), in a T- or Y-maze configuration. This was followed by three conditions; (1) Full reversal, where contingencies reversed; (2) Perseverance, where the previous CS+ became CS− and the previous CS− was replaced by a novel CS+; (3) Learned non-reward, where the previous CS− became CS+ and the previous CS+ was replaced by a novel CS-. SB242084 reduced perseverance, observed as a decrease in trials and incorrect responses to criterion, but increased learned non-reward, observed as an increase in trials to criterion. In contrast, 5-HT2CR KO mice showed increased perseverance. 5-HT2CR KO mice also showed retarded egocentric discrimination learning. Neither manipulation of 5-HT2CR function affected performance in the full reversal test. These results are unlikely to be accounted for by increased novelty attraction, as SB242084 failed to affect performance in an unrewarded novelty task. In conclusion, acute 5-HT2CR antagonism and constitutive loss of the 5-HT2CR have opposing effects on perseverance in egocentric reversal learning in mice. It is likely that this difference reflects the broader impact of 5HT2CR loss on the development and maintenance of cognitive function