Understanding Babinski's anosognosia : 100 years later

Non peer reviewedFinal Accepted Versio

The relationship between apamin binding and channel block in KCa2 potassium channels.

Small conductance calcium-activated potassium channels (KCa2.1,2.2,2.3) are widely distributed throughout the body and are involved in diverse physiological processes including the regulation of neuronal firing and smooth muscle contraction. They are also potential targets in the treatment of cardiac arrhythmia. The KCa2.2 and 2.3 members of the family are blocked by the peptide toxin apamin at low concentrations, however, the mechanism of block by apamin is unclear. In electrophysiological experiments apamin has been reported to block Kca2.2 and 2.3 with IC50 ~100 pM and ~1nM respectively. In contrast, in ligand binding experiments using [125I]-mono-iodoapamin it has been found that apamin does not discriminate between Kca2.2 and 2.3 and that it binds with significantly higher affinity ( ~5pM). This discrepancy has led to the suggestion that, rather than acting as a classical pore blocker, apamin exerts its action by an allosteric mechanism. It is notable that the ligand binding studies reported so far have been conducted with isolated cell membranes in non-physiological solution with low ionic strength. We have investigated this discrepancy between results from ligand binding and electrophysiological studies by comparing binding of [125I]-mono-iodoapamin and inhibition of KCa2 current in intact HEK 293 cells using identical physiological solutions. In these conditions we found that apamin bound to KCa2.1 and KCa 2.3 with KL 60 and 606 pM, close to values of IC50 from electrophysiological experiments. We also compared the ability of some known SK channel blockers, UCL 1848, UCL 1684, gallamine and dequalinium, to displace labelled apamin and inhibit KCa2 current. With these compounds we found a good correlation between K¬i and IC50. These findings suggest that the discrepancy between binding and block might arise from differences in the experimental protocols used. To examine this we examined apamin block of KCa2 current in low ionic strength solutions in which NaCl was iso-osmotically replaced by sucrose. In these conditions 100 pM apamin caused 92 ± 0.1 % block as against 51 ± 5 % block in physiological ionic strength. We conclude that binding data obtained from membrane preparations must be interpreted with care when making comparisons with data from functional experiments and that this has implications for current views on the mechanism of action of apamin as an SK channel blocke

Rigorous effective bounds on the Hausdorff dimension of continued fraction Cantor sets: A hundred decimal digits for the dimension of &ITE&IT2

We prove that the algorithm of [13] for approximating the Hausdorff dimension of dynamically defined Cantor sets, using periodic points of the underlying dynamical system, can be used to establish completely rigorous high accuracy bounds on the dimension. The effectiveness of these rigorous estimates is illustrated for Cantor sets consisting of continued fraction expansions with restricted digits. For example the Hausdorff dimension of the set $E_2$ (of those reals whose continued fraction expansion only contains digits 1 and 2) can be rigorously approximated, with an accuracy of over 100 decimal places, using points of period up to 25. The method for establishing rigorous dimension bounds involves the holomorphic extension of mappings associated to the allowed continued fraction digits, an appropriate disc which is contracted by these mappings, and an associated transfer operator acting on the Hilbert Hardy space of analytic functions on this disc. We introduce methods for rigorously bounding the approximation numbers for the transfer operators, showing that this leads to effective estimates on the Taylor coefficients of the associated determinant, and hence to explicit bounds on the Hausdorff dimension.Comment: Advances in Mathematics, to appea

Eltrombopag for the treatment of chronic idiopathic (immune) thrombocytopenic purpura : A Single Technology Appraisal

Evidence Review Group (ERG) final report for the National Institute for Health and Clinical ExcellencePublisher PD

Consumer preferences for scanning modality to diagnose focal liver lesions

Objectives: Differences in the process of using liver imaging technologies might be important to patients. This study aimed to investigate preferences for scanning modalities used in diagnosing focal liver lesions. Methods: A discrete choice experiment was administered to 504 adults aged 25 years. Respondents made repeated choices between two hypothetical scans, described according to waiting time for scan and results, procedure type, the chance of minor side-effects, and whether further scanning procedures were likely to be required. Choice data were analyzed using mixed-logit models with respondent characteristics used to explain preference heterogeneity. Results: Respondents preferred shorter waiting times, the procedure to be undertaken with a handheld scanner on a couch instead of within a body scanner, no side-effects, and no follow–up scans (p .01). The average respondent was willing to wait an additional 2 weeks for the scan if it resulted in avoiding side-effects, 1.5 weeks to avoid further procedures or to be told the results immediately, and 1 week to have the scan performed on a couch with a handheld scanner. However, substantial heterogeneity was observed in the strength of preference for desirable imaging characteristics. Conclusions: An average individual belonging to a general population sub–group most likely to require imaging to characterize focal liver lesions in the United Kingdom would prefer contrast–enhanced ultrasound over magnetic resonance imaging or computed tomography. Insights into the patient perspective around differential characteristics of imaging modalities have the potential to be used to guide recommendations around the use of these technologies

Systematic review of the efficacy and safety of using mesh in surgery for uterine or vaginal vault prolapse

The original publication is available at www.springerlink.comPeer reviewedPostprin

Rigorous Computation of Diffusion Coefficients for Expanding Maps

For real analytic expanding interval maps, a novel method is given for rigorously approximating the diffusion coefficient of real analytic observables. As a theoretical algorithm, our approximation scheme is shown to give quadratic exponential convergence to the diffusion coefficient. The method for converting this rapid convergence into explicit high precision rigorous bounds is illustrated in the setting of Lanford’s map x↦2x+12x(1−x)(mod1)

Embodied Precision : Intranasal Oxytocin Modulates Multisensory Integration

© 2018 Massachusetts Institute of Technology.Multisensory integration processes are fundamental to our sense of self as embodied beings. Bodily illusions, such as the rubber hand illusion (RHI) and the size-weight illusion (SWI), allow us to investigate how the brain resolves conflicting multisensory evidence during perceptual inference in relation to different facets of body representation. In the RHI, synchronous tactile stimulation of a participant's hidden hand and a visible rubber hand creates illusory body ownership; in the SWI, the perceived size of the body can modulate the estimated weight of external objects. According to Bayesian models, such illusions arise as an attempt to explain the causes of multisensory perception and may reflect the attenuation of somatosensory precision, which is required to resolve perceptual hypotheses about conflicting multisensory input. Recent hypotheses propose that the precision of sensorimotor representations is determined by modulators of synaptic gain, like dopamine, acetylcholine, and oxytocin. However, these neuromodulatory hypotheses have not been tested in the context of embodied multisensory integration. The present, double-blind, placebo-controlled, crossover study ( N = 41 healthy volunteers) aimed to investigate the effect of intranasal oxytocin (IN-OT) on multisensory integration processes, tested by means of the RHI and the SWI. Results showed that IN-OT enhanced the subjective feeling of ownership in the RHI, only when synchronous tactile stimulation was involved. Furthermore, IN-OT increased an embodied version of the SWI (quantified as estimation error during a weight estimation task). These findings suggest that oxytocin might modulate processes of visuotactile multisensory integration by increasing the precision of top-down signals against bottom-up sensory input.Peer reviewedFinal Accepted Versio

Damage to the right insula disrupts the perception of affective touch

© 2020 Kirsch et al. This article is distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use and redistribution provided that the original author and source are credited.Specific, peripheral C-tactile afferents contribute to the perception of tactile pleasure, but the brain areas involved in their processing remain debated. We report the first human lesion study on the perception of C-tactile touch in right hemisphere stroke patients (N = 59), revealing that right posterior and anterior insula lesions reduce tactile, contralateral and ipsilateral pleasantness sensitivity, respectively. These findings corroborate previous imaging studies regarding the role of the posterior insula in the perception of affective touch. However, our findings about the crucial role of the anterior insula for ipsilateral affective touch perception open new avenues of enquiry regarding the cortical organization of this tactile system.Peer reviewe

On the zero-temperature limit of Gibbs states

We exhibit Lipschitz (and hence H\"older) potentials on the full shift $\{0,1\}^{\mathbb{N}}$ such that the associated Gibbs measures fail to converge as the temperature goes to zero. Thus there are "exponentially decaying" interactions on the configuration space $\{0,1\}^{\mathbb Z}$ for which the zero-temperature limit of the associated Gibbs measures does not exist. In higher dimension, namely on the configuration space $\{0,1\}^{\mathbb{Z}^{d}}$, $d\geq3$, we show that this non-convergence behavior can occur for finite-range interactions, that is, for locally constant potentials.Comment: The statement of Theorem 1.2 is more accurate and some new comment follow i