Evidence for impaired extinction learning in humans after distal stress exposure

Stressful or traumatic events can be risk factors for anxiety or trauma- and stressor-related disorders. In this regard, it has been shown that stress affects aversive learning and memory processes. In rodents, stress exposure 10 days prior to fear acquisition impairs fear extinction. However, in humans the effect of distal stress on fear conditioning is sparse. Therefore, we examined the influence of distal stress on fear memory in humans in two studies. In Study 1, participants underwent either socially evaluated cold-pressor test (SECPT) or sham procedure 10 days or 40 min before a fear conditioning paradigm (four groups, N = 78). In Study 2, context effects were examined by conducting SECPT and sham procedures 10 days prior conditioning either in the later fear conditioning context or in another context (three groups, N = 69). During acquisition phase, one geometrical shape (conditioned stimulus, CS+) was paired with painful electric shocks (unconditioned stimulus, US), but never a second shape (CS−). Extinction phase was identical to acquisition, but without US delivery. Importantly, for Study 1 these phases were conducted on one day, while for Study 2 on two separated days. Successful fear acquisition was indicated by aversive ratings and startle potentiation to CS+ versus CS− in both studies. Interestingly, participants stressed 10 days earlier showed impaired extinction on the implicit level (startle potentiation to CS+ vs. CS−) in Study 1 and only in the acquisition context on the explicit level (aversive ratings for CS+ vs. CS−) in Study 2. In sum, distal stress may strengthen later acquired fear memories and thereby impair fear extinction. This finding could have clinical implications, showing that prior stress exposure sensitizes later aversive processing and impairs therapy

Dark Energy and Projective Symmetry

Nurowski [arXiv:1003.1503] has recently suggested a link between the observation of Dark Energy in cosmology and the projective equivalence of certain Friedman-Lemaitre-Robertson-Walker (FLRW) metrics. Specifically, he points out that two FLRW metrics with the same unparameterized geodesics have their energy densities differing by a constant. From this he queries whether the existence of dark energy is meaningful. We point out that physical observables in cosmology are not projectively invariant and we relate the projective symmetry uncovered by Nurowski to some previous work on projective equivalence in cosmology

ECC2K-130 on NVIDIA GPUs

A major cryptanalytic computation is currently underway on multiple platforms, including standard CPUs, FPGAs, PlayStations and Graphics Processing Units (GPUs), to break the Certicom ECC2K-130 challenge. This challenge is to compute an elliptic-curve discrete logarithm on a Koblitz curve over $\rm F_{2^{131}}$ . Optimizations have reduced the cost of the computation to approximately 277 bit operations in 261 iterations. GPUs are not designed for fast binary-field arithmetic; they are designed for highly vectorizable floating-point computations that fit into very small amounts of static RAM. This paper explains how to optimize the ECC2K-130 computation for this unusual platform. The resulting GPU software performs more than 63 million iterations per second, including 320 million $\rm F_{2^{131}}$ multiplications per second, on a $500 NVIDIA GTX 295 graphics card. The same techniques for finite-field arithmetic and elliptic-curve arithmetic can be reused in implementations of larger systems that are secure against similar attacks, making GPUs an interesting option as coprocessors when a busy Internet server has many elliptic-curve operations to perform in parallel

Analgosedation in paediatric severe traumatic brain injury (TBI): practice, pitfalls and possibilities

Analgosedation is a fundamental part of traumatic brain injury (TBI) treatment guidelines, encompassing both first and second tier supportive strategies. Worldwide analgosedation practices continue to be heterogeneous due to the low level of evidence in treatment guidelines (level III) and the choice of analgosedative drugs is made by the treating clinician. Current practice is thus empirical and may result in unfavourable (often hemodynamic) side effects. This article presents an overview of current analgosedation practices in the paediatric intensive care unit (PICU) and addresses pitfalls both in the short and long term. We discuss innovative (pre-)clinical research that can provide the framework for initiatives to improve our pharmacological understanding of analgesic and sedative drugs used in paediatric severe TBI and ultimately facilitate steps towards evidence-based and precision pharmacotherapy in this vulnerable patient group

Geometric phases for generalized squeezed coherent states

A simple technique is used to obtain a general formula for the Berry phase (and the corresponding Hannay angle) for an arbitrary Hamiltonian with an equally-spaced spectrum and appropriate ladder operators connecting the eigenstates. The formalism is first applied to a general deformation of the oscillator involving both squeezing and displacement. Earlier results are shown to emerge as special cases. The analysis is then extended to multiphoton squeezed coherent states and the corresponding anholonomies deduced.Comment: 15 page

Expression in hematological malignancies of a glucocorticoid receptor splice variant that augments glucocorticoid receptor-mediated effects in transfected cells

Glucocorticoids play an important role in the treatment of a number of hematological malignancies, such as multiple myeloma. The effects of glucocorticoids are mediated through the glucocorticoid receptor alpha, the abundance of which can be modulated by alternative splicing of the glucocorticoid receptor mRNA. Two splice variants of the glucocorticoid receptor mRNA have been described: glucocorticoid receptor beta, which reportedly has a dominant negative effect on the actions of the glucocorticoid receptor alpha, and glucocorticoid receptor P, of which the effects are unknown. In this study, we have investigated the expression levels of these two splice variants at the mRNA level in multiple myeloma cells and in a number of other hematological tumors. Although the glucocorticoid receptor beta mRNA was, if at all, expressed at very low levels, considerable amounts (up to 50% of the total glucocorticoid receptor mRNA) glucocorticoid receptor P mRNA was present in most hematological malignancies. In transient transfection studies in several cell types and in multiple myeloma cell lines, the glucocorticoid receptor P increased the activity of the glucocorticoid receptor alpha. These results suggest that the relative levels of the glucocorticoid receptor alpha and the glucocorticoid receptor P may play a role in the occurrence of glucocorticoid resistance in tumor cells during the treatment of hematological malignancies with glucocorticoids

Matrix Models, Geometric Engineering and Elliptic Genera

We compute the prepotential of N=2 supersymmetric gauge theories in four dimensions obtained by toroidal compactifications of gauge theories from 6 dimensions, as a function of Kahler and complex moduli of T^2. We use three different methods to obtain this: matrix models, geometric engineering and instanton calculus. Matrix model approach involves summing up planar diagrams of an associated gauge theory on T^2. Geometric engineering involves considering F-theory on elliptic threefolds, and using topological vertex to sum up worldsheet instantons. Instanton calculus involves computation of elliptic genera of instanton moduli spaces on R^4. We study the compactifications of N=2* theory in detail and establish equivalence of all these three approaches in this case. As a byproduct we geometrically engineer theories with massive adjoint fields. As one application, we show that the moduli space of mass deformed M5-branes wrapped on T^2 combines the Kahler and complex moduli of T^2 and the mass parameter into the period matrix of a genus 2 curve.Comment: 90 pages, Late

Modeling oscillatory Microtubule--Polymerization

Polymerization of microtubules is ubiquitous in biological cells and under certain conditions it becomes oscillatory in time. Here simple reaction models are analyzed that capture such oscillations as well as the length distribution of microtubules. We assume reaction conditions that are stationary over many oscillation periods, and it is a Hopf bifurcation that leads to a persistent oscillatory microtubule polymerization in these models. Analytical expressions are derived for the threshold of the bifurcation and the oscillation frequency in terms of reaction rates as well as typical trends of their parameter dependence are presented. Both, a catastrophe rate that depends on the density of {\it guanosine triphosphate} (GTP) liganded tubulin dimers and a delay reaction, such as the depolymerization of shrinking microtubules or the decay of oligomers, support oscillations. For a tubulin dimer concentration below the threshold oscillatory microtubule polymerization occurs transiently on the route to a stationary state, as shown by numerical solutions of the model equations. Close to threshold a so--called amplitude equation is derived and it is shown that the bifurcation to microtubule oscillations is supercritical.Comment: 21 pages and 12 figure

Adaptive design: adaptation and adoption of patient safety practices in daily routines, a multi-site study

Background Most interventions to improve patient safety (Patient Safety Practices (PSPs)), are introduced without engaging front-line professionals. Administrative staff, managers and sometimes a few professionals, representing only one or two disciplines, decide what to change and how. Consequently, PSPs are not fully adapted to the professionals’ needs or to the local context and as a result, adoption is low. To support adoption, two theoretical concepts, Participatory Design and Experiential Learning were combined in a new model: Adaptive Design. The aim was to explore whether Adaptive Design supports adaptation and adoption of PSPs by engaging all professionals and creating time to (re) design, reflect and learn as a team. The Time Out Procedure (TOP) and Debriefing (plus) for improving patient safety in the operating theatre (OT) was used as PSP. Methods Qualitative exploratory multi-site study using participatory action research as a research design. The implementation process consisted of four phases: 1) start-up: providing information by presentations and team meetings, 2) pilot: testing the prototype with 100 surgical procedures, 3) small scale implementation: with one or two surgical disciplines, 4) implementation hospital-wide: including all surgical disciplines. In iterations, teams (re) designed, tested, evaluated, and if necessary adapted TOPplus. Gradually all professionals were included. Adaptations in content, process and layout of TOPplus were measured following each iteration. Adoption was monitored until final implementation in every hospital’s OT. Results 10 Dutch hospitals participated. Adaptations varied per hospital, but all hospitals adapted both procedures. Adaptations concerned the content, process and layout of TOPplus. Both procedures were adopted in all OTs, but user participation and time to include all users varied between hospitals. Ultimately all users were actively involved and TOPplus was implemented in all OTs. Conclusions Engaging all professionals in a structured bottom-up implementation approach with a focus on learning, improves adaptation and adoption of a PSP. As a result, all 10 participating hospitals implemented TOPplus with all surgical disciplines in all OTs. Adaptive Design gives professionals the opportunity to adapt the PSP to their own needs and their specific local context. All hospitals adapted TOPplus, but without compromising the essential features for its effectiveness

Malnutrition assessment methods in adult patients with tuberculosis:A systematic review

OBJECTIVES: Malnutrition is associated with a twofold higher risk of dying in patients with tuberculosis (TB) and considered an important potentially reversible risk factor for failure of TB treatment. The construct of malnutrition has three domains: intake or uptake of nutrition; body composition and physical and cognitive function. The objectives of this systematic review are to identify malnutrition assessment methods, and to quantify how malnutrition assessment methods capture the international consensus definition for malnutrition, in patients with TB. DESIGN: Different assessment methods were identified. We determined the extent of capturing of the three domains of malnutrition, that is, intake or uptake of nutrition, body composition and physical and cognitive function. RESULTS: Seventeen malnutrition assessment methods were identified in 69 included studies. In 53/69 (77%) of studies, body mass index was used as the only malnutrition assessment method. Three out of 69 studies (4%) used a method that captured all three domains of malnutrition. CONCLUSIONS: Our study focused on published articles. Implementation of new criteria takes time, which may take longer than the period covered by this review. Most patients with TB are assessed for only one aspect of the conceptual definition of malnutrition. The use of international consensus criteria is recommended to establish uniform diagnostics and treatment of malnutrition. PROSPERO REGISTRATION NUMBER: CRD42019122832