Voltage sensitivity of NMDA-receptor mediated postsynaptic currents.

Patch-clamp techniques were used to record pharmacologically-isolated N-methyl-D-aspartate-mediated excitatory postsynaptic currents (NMDA-EPSCs) from dentate granule cells in thin rat hippocampal slices. Membrane voltage modulated these EPSCs in two ways. Firstly, depolarization from resting potential enhanced EPSC amplitudes, as expected for a voltage-dependent block by Mg2+ of synaptically activated NMDA receptor channels. Secondly, depolarization markedly prolonged the time course of decay of NMDA-EPSCs in normal and low extracellular Mg2+. Both mechanisms were complementary in establishing a strong dependence between membrane potential and the amount of charge, namely Ca2+, transferred through synaptically activated NMDA receptor channels, that presumably underlies induction of long-term potentiation in the hippocampus

The in-medium isovector pi N amplitude from low energy pion scattering

Differential cross sections for elastic scattering of 21.5 MeV positive and negative pions by Si, Ca, Ni and Zr have been measured as part of a study of the pion-nucleus potential across threshold. The `anomalous' repulsion in the s-wave term was observed, as is the case with pionic atoms. The extra repulsion can be accounted for by a chiral-motivated model where the pion decay constant is modified in the medium. Unlike in pionic atoms, the anomaly cannot be removed by merely introducing an empirical on-shell energy dependence.Comment: 9 pages, 2 figures. Minor changes, to appear in PR

Elastic scattering of low energy pions by nuclei and the in-medium isovector pi N amplitude

Measurements of elastic scattering of 21.5 MeV pi+ and pi- by Si, Ca, Ni and Zr were made using a single arm magnetic spectrometer. Absolute calibration was made by parallel measurements of Coulomb scattering of muons. Parameters of a pion-nucleus optical potential were obtained from fits to all eight angular distributions put together. The `anomalous' s-wave repulsion known from pionic atoms is clearly observed and could be removed by introducing a chiral-motivated density dependence of the isovector scattering amplitude, which also greatly improved the fits to the data. The empirical energy dependence of the isoscalar amplitude also improves the fits to the data but, contrary to what is found with pionic atoms, on its own is incapable of removing the anomaly.Comment: 20 pages, 5 figures, 5 tables. V2 added details on uncertainties,extended discussion. To appear in PR

Runaway Events Dominate the Heavy Tail of Citation Distributions

Statistical distributions with heavy tails are ubiquitous in natural and social phenomena. Since the entries in heavy tail have disproportional significance, the knowledge of its exact shape is very important. Citations of scientific papers form one of the best-known heavy tail distributions. Even in this case there is a considerable debate whether citation distribution follows the log-normal or power-law fit. The goal of our study is to solve this debate by measuring citation distribution for a very large and homogeneous data. We measured citation distribution for 418,438 Physics papers published in 1980-1989 and cited by 2008. While the log-normal fit deviates too strong from the data, the discrete power-law function with the exponent $\gamma=3.15$ does better and fits 99.955% of the data. However, the extreme tail of the distribution deviates upward even from the power-law fit and exhibits a dramatic "runaway" behavior. The onset of the runaway regime is revealed macroscopically as the paper garners 1000-1500 citations, however the microscopic measurements of autocorrelation in citation rates are able to predict this behavior in advance.Comment: 6 pages, 5 Figure

Under stochastic dominance Choquet-expected utility and anticipated utility are identical

The aim of this paper is to convince the reader that Choquet-expected utility, as initiated by Schmeidler (1982, 1989) for decision making under uncertainty, when formulated for decision making under risk naturally leads to anticipated utility, as initiated by Quiggin/Yaari. Thus the two generalizations of expected utility in fact are one

Socioeconomic conditions and number of pain sites in women

<p>Abstract</p> <p>Background</p> <p>Women in deprived socioeconomic situations run a high pain risk. Although number of pain sites (NPS) is considered highly relevant in pain assessment, little is known regarding the relationship between socioeconomic conditions and NPS.</p> <p>Methods</p> <p>The study population comprised 653 women; 160 recurrence-free long-term gynecological cancer survivors, and 493 women selected at random from the general population. Demographic characteristics and co-morbidity over the past 12 months were assessed. Socioeconomic conditions were measured by Socioeconomic Condition Index (SCI), comprising education, employment status, income, ability to pay bills, self-perceived health, and satisfaction with number of close friends. Main outcome measure NPS was recorded using a body outline diagram indicating where the respondents had experienced pain during the past week. Chi-square test and forward stepwise logistic regression were applied.</p> <p>Results and Conclusion</p> <p>There were only minor differences in SCI scores between women with 0, 1-2 or 3 NPS. Four or more NPS was associated with younger age, higher BMI and low SCI. After adjustment for age, BMI and co-morbidity, we found a strong association between low SCI scores and four or more NPS, indicating that there is a threshold in the NPS count for when socioeconomic determinants are associated to NPS in women.</p

Evaluation of dose-dependent treatment effects after mid-trial dose escalation in biomarker, clinical, and cognitive outcomes for gantenerumab or solanezumab in dominantly inherited Alzheimer's disease

Introduction: While the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) was ongoing, external data suggested higher doses were needed to achieve targeted effects; therefore, doses of gantenerumab were increased 5-fold, and solanezumab was increased 4-fold. We evaluated to what extent mid-trial dose increases produced a dose-dependent treatment effect. Methods: Using generalized linear mixed effects (LME) models, we estimated the annual low- and high-dose treatment effects in clinical, cognitive, and biomarker outcomes. Results: Both gantenerumab and solanezumab demonstrated dose-dependent treatment effects (significant for gantenerumab, non-significant for solanezumab) in their respective target amyloid biomarkers (Pittsburgh compound B positron emission tomography standardized uptake value ratio and cerebrospinal fluid amyloid beta 42), with gantenerumab demonstrating additional treatment effects in some downstream biomarkers. No dose-dependent treatment effects were observed in clinical or cognitive outcomes. Conclusions: Mid-trial dose escalation can be implemented as a remedy for an insufficient initial dose and can be more cost effective and less burdensome to participants than starting a new trial with higher doses, especially in rare diseases. Highlights: We evaluated the dose-dependent treatment effect of two different amyloid-specific immunotherapies. Dose-dependent treatment effects were observed in some biomarkers. No dose-dependent treatment effects were observed in clinical/cognitive outcomes, potentially due to the fact that the modified study may not have been powered to detect such treatment effects in symptomatic subjects at a mild stage of disease exposed to high (or maximal) doses of medication for prolonged durations