Deletion of annexin 2 light chain p11 in nociceptors causes deficits in somatosensory coding and pain behavior

The S100 family protein p11 (S100A10, annexin 2 light chain) is involved in the trafficking of the voltage-gated sodium channel Na(V)1.8, TWIK-related acid-sensitive K+ channel (TASK-1), the ligand-gated ion channels acid-sensing ion channel 1a (ASIC1a) and transient receptor potential vanilloid 5/6 (TRPV5/V6), as well as 5-hydroxytryptamine receptor 1B (5-HT1B), a G-protein-coupled receptor. To evaluate the role of p11 in peripheral pain pathways, we generated a loxP-flanked (floxed) p11 mouse and used the Cre-loxP recombinase system to delete p11 exclusively from nociceptive primary sensory neurons in mice. p11-null neurons showed deficits in the expression of NaV1.8, but not of annexin 2. Damage-sensing primary neurons from these animals show a reduced tetrodotoxin-resistant sodium current density, consistent with a loss of membrane-associated NaV1.8. Noxious coding in wide-dynamic-range neurons in the dorsal horn was markedly compromised. Acute pain behavior was attenuated in certain models, but no deficits in inflammatory pain were observed. A significant deficit in neuropathic pain behavior was also apparent in the conditional-null mice. These results confirm an important role for p11 in nociceptor function

Complexity and Expressivity of Branching- and Alternating-Time Temporal Logics with Finitely Many Variables

We show that Branching-time temporal logics CTL and CTL*, as well as Alternating-time temporal logics ATL and ATL*, are as semantically expressive in the language with a single propositional variable as they are in the full language, i.e., with an unlimited supply of propositional variables. It follows that satisfiability for CTL, as well as for ATL, with a single variable is EXPTIME-complete, while satisfiability for CTL*, as well as for ATL*, with a single variable is 2EXPTIME-complete,--i.e., for these logics, the satisfiability for formulas with only one variable is as hard as satisfiability for arbitrary formulas.Comment: Prefinal version of the published pape

Holographic two-point functions for 4d log-gravity

We compute holographic one- and two-point functions of critical higher-curvature gravity in four dimensions. The two most important operators are the stress tensor and its logarithmic partner, sourced by ordinary massless and by logarithmic non-normalisable gravitons, respectively. In addition, the logarithmic gravitons source two ordinary operators, one with spin-one and one with spin-zero. The one-point function of the stress tensor vanishes for all Einstein solutions, but has a non-zero contribution from logarithmic gravitons. The two-point functions of all operators match the expectations from a three-dimensional logarithmic conformal field theory.Comment: 35 pages; v2: typos corrected, added reference; v3: shorter introduction, minor changes in the text in section 3, added reference; published versio

History of early life adversity is associated with increased food addiction and sex-specific alterations in reward network connectivity in obesity.

Background:Neuroimaging studies have identified obesity-related differences in the brain's resting state activity. An imbalance between homeostatic and reward aspects of ingestive behaviour may contribute to obesity and food addiction. The interactions between early life adversity (ELA), the reward network and food addiction were investigated to identify obesity and sex-related differences, which may drive obesity and food addiction. Methods:Functional resting state magnetic resonance imaging was acquired in 186 participants (high body mass index [BMI]: ≥25: 53 women and 54 men; normal BMI: 18.50-24.99: 49 women and 30 men). Participants completed questionnaires to assess ELA (Early Traumatic Inventory) and food addiction (Yale Food Addiction Scale). A tripartite network analysis based on graph theory was used to investigate the interaction between ELA, brain connectivity and food addiction. Interactions were determined by computing Spearman rank correlations, thresholded at q < 0.05 corrected for multiple comparisons. Results:Participants with high BMI demonstrate an association between ELA and food addiction, with reward regions playing a role in this interaction. Among women with high BMI, increased ELA was associated with increased centrality of reward and emotion regulation regions. Men with high BMI showed associations between ELA and food addiction with somatosensory regions playing a role in this interaction. Conclusions:The findings suggest that ELA may alter brain networks, leading to increased vulnerability for food addiction and obesity later in life. These alterations are sex specific and involve brain regions influenced by dopaminergic or serotonergic signalling

Nonlinear Dynamics of Parity-Even Tricritical Gravity in Three and Four Dimensions

Recently proposed "multicritical" higher-derivative gravities in Anti de Sitter space carry logarithmic representations of the Anti de Sitter isometry group. While generically non-unitary already at the quadratic, free-theory level, in special cases these theories admit a unitary subspace. The simplest example of such behavior is "tricritical" gravity. In this paper, we extend the study of parity-even tricritical gravity in d = 3, 4 to the first nonlinear order. We show that the would-be unitary subspace suffers from a linearization instability and is absent in the full non-linear theory.Comment: 22 pages; v2: references added, published versio

Phaeochrornocytorna: A Case Report

A 52-year-old man presented with a 4-year history of paroxysmal attacks of anxiety, giddiness, palpitation, sweating, and severe headache. These symptoms were associated with sudden increases in his blood pressure; and a provisional diagnosis of phaeochromocytoma was made. Collections of urine were submitted for catecholamine assay. One collection showed a slight increase in catecholamines but the rest were normal, including a collection made after a provocation test, using histamine 0,025 mg intravenously. The histamine test did, however, cause systolic and diastolic blood pressure to rise by 20 mmHg. As he was mildly hypertensive between paroxysms, a phentolamine test was carried out, utilising 5 mg well diluted, intravenously, over 5 minutes under basal conditions. This, too, was negative. An aortogram failed to demonstrate convincingly tumour vascularisation, but there was a mild hypertensive crisis during this examination. At laparotomy, a single phaeochromocytoma was found in the right adrenal gland, and was successfully removed. Recovery was uneventful and the patient was discharged, normotensive and not requiring hypotensive therapy, though mild hypertension has developed since. No residual catecholamine activity has been detected. The preparation of the patient for surgery and the control of operative complications are described, and the salient diagnostic features of phaeochromocytoma are briefly discussed.S. Afr. Med. J. 48, 401 (1974

Cost-effectiveness of noninvasive liver fibrosis tests for treatment decisions in patients with chronic hepatitis C

The cost-effectiveness of noninvasive tests (NITs) as alternatives to liver biopsy is unknown. We compared the cost-effectiveness of using NITs to inform treatment decisions in adult patients with chronic hepatitis C (CHC). We conducted a systematic review and meta-analysis to calculate the diagnostic accuracy of various NITs using a bivariate random-effects model. We constructed a probabilistic decision analytical model to estimate health care costs and outcomes (quality-adjusted life-years; QALYs) using data from the meta-analysis, literature, and national UK data. We compared the cost-effectiveness of four treatment strategies: testing with NITs and treating patients with fibrosis stage ≥F2; testing with liver biopsy and treating patients with ≥F2; treat none; and treat all irrespective of fibrosis. We compared all NITs and tested the cost-effectiveness using current triple therapy with boceprevir or telaprevir, but also modeled new, more-potent antivirals. Treating all patients without any previous NIT was the most effective strategy and had an incremental cost-effectiveness ratio (ICER) of £9,204 per additional QALY gained. The exploratory analysis of currently licensed sofosbuvir treatment regimens found that treat all was cost-effective, compared to using an NIT to decide on treatment, with an ICER of £16,028 per QALY gained. The exploratory analysis to assess the possible effect on results of new treatments, found that if SVR rates increased to >90% for genotypes 1-4, the incremental treatment cost threshold for the "treat all" strategy to remain the most cost-effective strategy would be £37,500. Above this threshold, the most cost-effective option would be noninvasive testing with magnetic resonance elastography (ICER=£9,189). Conclusions: Treating all adult patients with CHC, irrespective of fibrosis stage, is the most cost-effective strategy with currently available drugs in developed countries. © 2014 The Authors

Risk of miscarriage among users of corticosteroid hormones: A population-based nested case-control study

Background: The purpose of this nested case-control study in Denmark was to study the association between use of corticosteroids and risk of miscarriage. Methods: We identified prescriptions for corticosteroids before the miscarriage/index date. We estimated odds ratios (ORs) for miscarriage and for early (<13 weeks) and late (13-21 weeks) miscarriage adjusting for age, history of diabetes and epilepsy, and nonsteroidal anti-inflammatory drug use. Results: We identified 10,974 women with miscarriage and 109,740 controls. Prevalence of inhaled corticosteroid use within 60 days before the index date was 1.3% among the cases and 1.0% among the controls (OR = 1.20; 95% confidence interval [CI] 1.01-1.44). Prevalence of oral corticosteroid use within 60 days before the index date was 0.3% for both cases and controls (OR = 0.78; 95% CI 0.53-1.15). For inhaled and oral corticosteroids, the ORs of early miscarriage were 1.22 (95% CI 1.01-1.49) and 0.81 (95% CI 0.55-1.20), respectively. Conclusion: Use of inhaled corticosteroids was associated with a slightly increased risk of early miscarriage, but explanations alternative to causal ones were possible. © 2013 Bjørn et al, publisher and licensee Dove Medical Press Ltd

The Minimum Shared Edges Problem on Grid-like Graphs

We study the NP-hard Minimum Shared Edges (MSE) problem on graphs: decide whether it is possible to route $p$ paths from a start vertex to a target vertex in a given graph while using at most $k$ edges more than once. We show that MSE can be decided on bounded (i.e. finite) grids in linear time when both dimensions are either small or large compared to the number $p$ of paths. On the contrary, we show that MSE remains NP-hard on subgraphs of bounded grids. Finally, we study MSE from a parametrised complexity point of view. It is known that MSE is fixed-parameter tractable with respect to the number $p$ of paths. We show that, under standard complexity-theoretical assumptions, the problem parametrised by the combined parameter $k$, $p$, maximum degree, diameter, and treewidth does not admit a polynomial-size problem kernel, even when restricted to planar graphs