Estimating Bayes factors via thermodynamic integration and population MCMC

A Bayesian approach to model comparison based on the integrated or marginal likelihood is considered, and applications to linear regression models and nonlinear ordinary differential equation (ODE) models are used as the setting in which to elucidate and further develop existing statistical methodology. The focus is on two methods of marginal likelihood estimation. First, a statistical failure of the widely employed Posterior Harmonic Mean estimator is highlighted. It is demonstrated that there is a systematic bias capable of significantly skewing Bayes factor estimates, which has not previously been highlighted in the literature. Second, a detailed study of the recently proposed Thermodynamic Integral estimator is presented, which characterises the error associated with its discrete form. An experimental study using analytically tractable linear regression models highlights substantial differences with recently published results regarding optimal discretisation. Finally, with the insights gained, it is demonstrated how Population MCMC and thermodynamic integration methods may be elegantly combined to estimate Bayes factors accurately enough to discriminate between nonlinear models based on systems of ODEs, which has important application in describing the behaviour of complex processes arising in a wide variety of research areas, such as Systems Biology, Computational Ecology and Chemical Engineering. (C) 2009 Elsevier B.V. All rights reserve

Witnessing multipartite entanglement by detecting asymmetry

The characterization of quantum coherence in the context of quantum information theory and its interplay with quantum correlations is currently subject of intense study. Coherence in a Hamiltonian eigenbasis yields asymmetry, the ability of a quantum system to break a dynamical symmetry generated by the Hamiltonian. We here propose an experimental strategy to witness multipartite entanglement in many-body systems by evaluating the asymmetry with respect to an additive Hamiltonian. We test our scheme by simulating asymmetry and entanglement detection in a three-qubit Greenberger-Horne-Zeilinger (GHZ) diagonal state

Interplay between computable measures of entanglement and other quantum correlations

Composite quantum systems can be in generic states characterized not only by entanglement, but also by more general quantum correlations. The interplay between these two signatures of nonclassicality is still not completely understood. In this work we investigate this issue focusing on computable and observable measures of such correlations: entanglement is quantified by the negativity N, while general quantum correlations are measured by the (normalized) geometric quantum discord D_G. For two-qubit systems, we find that the geometric discord reduces to the squared negativity on pure states, while the relationship $D_G \geq N^2$ holds for arbitrary mixed states. The latter result is rigorously extended to pure, Werner and isotropic states of two-qudit systems for arbitrary d, and numerical evidence of its validity for arbitrary states of a qubit and a qutrit is provided as well. Our results establish an interesting hierarchy, that we conjecture to be universal, between two relevant and experimentally friendly nonclassicality indicators. This ties in with the intuition that general quantum correlations should at least contain and in general exceed entanglement on mixed states of composite quantum systems.Comment: 10 pages, 4 figure

Main clinical manifestations of a bleeding diathesis: an often disregarded aspect of medical and surgical history taking

Summary.  A suitable clinical evaluation of a bleeding diathesis is often forgone. The young doctor is often unprepared to describe in an accurate way the different types of bleeding. An adequate classification and adequate clinical information about a bleeding diathesis are instead of paramount importance. Bleeding may be cutaneous, mucous, articular, muscular, parenchymal, intracavitary, orificial. Each of these sites and forms may have diagnostic implications. An accurate description of the several forms of cutaneous bleeding (petechiae, purpuric spots, ecchymosis, haematomas, etc.) is needed for referrals and for controls. The correct evaluation of cutaneous bleeding manifestations of children (battered child syndrome) is absolutely important for clinical and medico‐legal purposes. The same is true for the battering syndrome seen in women abused by their spouses. The grading of haemarthrosis in haemophilia patients is important for the follow‐up. A proper description of haematuria is essential in suggesting the probable site of bleeding (kidney or bladder or urethra). A proper evaluation of bleeding may give also useful information on the general health status of the patients (presence of anaemia, poor nutrition, renal insufficiency, etc.). The combination of bleeding and thrombosis in the same patient is also a clinical challenge. The relationship between haemorrhage and thrombosis may be sequential or concomitant. Sequential thrombosis may occur in a patient confined in bed for a brain haemorrhage. Concomitant thrombosis and bleeding occur in DIC and in patients with thrombosis being treated with anticoagulants. Finally, it should be kept in mind that a proper evaluation of the bleeding diathesis of a given patient may help the caring doctor in ordering appropriate laboratory tests (e.g. a platelet count for petechiae, a PTT for a patient with haemarthrosis, etc.)

Coherence and quantum correlations measure sensitivity to dephasing channels

We introduce measures of quantum coherence as the speed of evolution of a system under decoherence. That is, coherence is the ability to estimate a dephasing channel, quantified by the quantum Fisher information. We extend the analysis to interferometric noise estimation, proving that quantum discord is the minimum sensitivity to local dephasing. A physically motivated set of free operations for discord is proposed. The amount of discord created by strictly incoherent operations is upper bounded by the initial coherence

Store-Operated Ca 2+ Entry in Skeletal Muscle Contributes to the Increase in Body Temperature during Exertional Stress

Exertional heat stroke (HS) is a hyperthermic crisis triggered by an excessive accumulation of Ca2+ in skeletal muscle fibers. We demonstrated that exercise leads to the formation of calcium entry units (CEUs), which are intracellular junctions that reduce muscle fatigue by promoting the recovery of extracellular Ca2+ via store-operated Ca2+ entry (SOCE). Here, we tested the hypothesis that exercise-induced assembly of CEUs may increase the risk of HS when physical activity is performed in adverse environmental conditions (high temperature and humidity). Adult mice were: (a) first, divided into three experimental groups: control, trained-1 month (voluntary running in wheel cages), and acutely exercised-1 h (incremental treadmill run); and (b) then subjected to an exertional stress (ES) protocol, a treadmill run in an environmental chamber at 34◦C and 40% humidity. The internal temperature of the mice at the end of the ES was higher in both pre-exercised groups. During an ES ex-vivo protocol, extensor digitorum longus(EDL) muscles from the trained-1 month and exercised-1 h mice generated greater basal tension than in the control and were those that contained a greater number of CEUs, assessed by electron microscopy. The data collected suggest that the entry of Ca2+ from extracellular space via CEUs could contribute to exertional HS when exercise is performed in adverse environmental conditions

Ablation of Calsequestrin-1, Ca2+ unbalance, and susceptibility to heat stroke

Introduction: Ca2+ levels in adult skeletal muscle fibers are mainly controlled by excitation-contraction (EC) coupling, a mechanism that translates action potentials in release of Ca2+ from the sarcoplasmic reticulum (SR) release channels, i.e. the ryanodine receptors type-1 (RyR1). Calsequestrin (Casq) is a protein that binds large amounts of Ca2+ in the lumen of the SR terminal cisternae, near sites of Ca2+ release. There is general agreement that Casq is not only important for the SR ability to store Ca2+, but also for modulating the opening probability of the RyR Ca2+ release channels. The initial studies: About 20 years ago we generated a mouse model lacking Casq1 (Casq1-null mice), the isoform predominantly expressed in adult fast twitch skeletal muscle. While the knockout was not lethal as expected, lack of Casq1 caused a striking remodeling of membranes of SR and of transverse tubules (TTs), and mitochondrial damage. Functionally, CASQ1-knockout resulted in reduced SR Ca2+ content, smaller Ca2+ transients, and severe SR depletion during repetitive stimulation. The myopathic phenotype of Casq1-null mice: After the initial studies, we discovered that Casq1-null mice were prone to sudden death when exposed to halogenated anaesthetics, heat and even strenuous exercise. These syndromes are similar to human malignant hyperthermia susceptibility (MHS) and environmental-exertional heat stroke (HS). We learned that mechanisms underlying these syndromes involved excessive SR Ca2+ leak and excessive production of oxidative species: indeed, mortality and mitochondrial damage were significantly prevented by administration of antioxidants and reduction of oxidative stress. Though, how Casq1-null mice could survive without the most important SR Ca2+ binding protein was a puzzling issue that was not solved. Unravelling the mystery: The mystery was finally solved in 2020, when we discovered that in Casq1-null mice the SR undergoes adaptations that result in constitutively active store-operated Ca2+ entry (SOCE). SOCE is a mechanism that allows skeletal fibers to use external Ca2+ when SR stores are depleted. The post-natal compensatory mechanism that allows Casq1-null mice to survive involves the assembly of new SR-TT junctions (named Ca2+ entry units) containing Stim1 and Orai1, the two proteins that mediate SOCE

Converting Coherence to Quantum Correlations

Recent results in quantum information theory characterize quantum coherence in the context of resource theories. Here, we study the relation between quantum coherence and quantum discord, a kind of quantum correlation which appears even in nonentangled states. We prove that the creation of quantum discord with multipartite incoherent operations is bounded by the amount of quantum coherence consumed in its subsystems during the process. We show how the interplay between quantum coherence consumption and creation of quantum discord works in the preparation of multipartite quantum correlated states and in the model of deterministic quantum computation with one qubit

Statistical Inference for Generative Models with Maximum Mean Discrepancy

While likelihood-based inference and its variants provide a statistically efficient and widely applicable approach to parametric inference, their application to models involving intractable likelihoods poses challenges. In this work, we study a class of minimum distance estimators for intractable generative models, that is, statistical models for which the likelihood is intractable, but simulation is cheap. The distance considered, maximum mean discrepancy (MMD), is defined through the embedding of probability measures into a reproducing kernel Hilbert space. We study the theoretical properties of these estimators, showing that they are consistent, asymptotically normal and robust to model misspecification. A main advantage of these estimators is the flexibility offered by the choice of kernel, which can be used to trade-off statistical efficiency and robustness. On the algorithmic side, we study the geometry induced by MMD on the parameter space and use this to introduce a novel natural gradient descent-like algorithm for efficient implementation of these estimators. We illustrate the relevance of our theoretical results on several classes of models including a discrete-time latent Markov process and two multivariate stochastic differential equation models

Enactive explorations of children's sensory-motor play and therapeutic handling in physical therapy

Introduction: In pediatric physical therapy, there is an ongoing debate about the use of therapeutic handling and its potential effects on motor learning. In this study, we build on enactive theoretical perspectives to explore the role of therapeutic handling in connection to children's sensory-motor play, engagement, and performance during a single physical therapy session. Material and methods: This is a qualitative study based on video observations of therapy sessions and interviews with 15 physical therapists (PTs) each treating two different children aged 0–3. The authors utilized a framework of co-reviewing, discussing, and reflecting on the sessions. Themes were identified and used to describe the ways by which PTs’ therapeutic handling unfolds, with connections to theories on sensory-motor play and learning, along with enactive perspectives on embodiment, experience, mutual incorporation, and sense-of-agency. Results: The characteristics and purposes of therapeutic handling are presented in two main themes: (1) position and support, and (2) directing movement. We found that position and support promoted sensory-motor improvement when the PTs’ handling aligned with the child's play interests and engagements. As part of play, the children used new and additional support surfaces to self-initiate better posture and movement solutions and reach play goals. The PTs’ ways of directing movements varied. To awaken curiosity and induce a child's self-driven motor exploration the PT needs to be subtle, flexible, and precise in the directing of movement. This entails responsiveness to the child's signals and bodily know-how in the placing of hands and direction of pressure to enable the child to actively participate in and eventually self-drive movement. Discussion: Therapeutic handling that is mutually incorporated between PT and child can enrich the child's playing-to-learn-to-move process by providing novelty and facilitating the child's sense-of-agency in the self-initiated exploration and refinement of movement possibilities. In the PTs’ effort to merge therapeutic handling with children's play, the momentum of interaction can open new therapeutic windows of movement experience and learning opportunities