Individual differences in impulsive and risky choice: effects of environmental rearing conditions

The present experiment investigated early-rearing environment modulation of individual differences in impulsive and risky choice. Rats were reared in an isolated condition (IC; n = 12), in which they lived alone without novel stimuli, or an enriched condition (EC; n = 12), in which they lived among conspecifics with novel stimuli. The impulsive choice task involved choices between smaller-sooner (SS) versus larger-later (LL) rewards. The risky choice task involved choices between certain-smaller (C-S) versus uncertain-larger (U-L) rewards. Following choice testing, incentive motivation to work for food was measured using a progressive ratio task and correlated with choice behavior. HPLC analyses were conducted to determine how monoamine concentrations within the prefrontal cortex (PFC) and nucleus accumbens (NAC) related to behavior in different tasks. IC rats were more impulsive than EC rats, but they did not differ in risky choice behavior. However, choice behavior across tasks was significantly correlated (i.e., the more impulsive rats were also riskier). There were no group differences in monoamine levels, but noradrenergic and serotonergic concentrations were significantly correlated with impulsive and risky choice. Furthermore, serotonin and norepinephrine concentrations in the NAC significantly correlated with incentive motivation and the timing of the reward delays within the choice tasks. These results suggest a role for domain general processes in impulsive and risky choice and indicate the importance of the NAC and/or PFC in timing, reward processing, and choice behavior

Fatigue failure and success rate of lithium disilicate table-tops as a function of cement thickness

Purpose: Under thin, partial coverage restoration the proper cement thickness to be clinically employed still remains an issue. The aim of this study was to determine the failure and success rates of simplified lithium disilicate occlusal veneers as a function of cement thickness. The null hypothesis was that cement thickness has no effect on the fatigue resistance. Methods: Sound human molars were severed in a plane parallel to the occlusal surface to create a flat dentin surface surrounded by enamel edges. Forty-five occlusal veneers 1.0 mm thick (IPS e.max CAD LT) were luted to the teeth with Multilink Automix resin cement, creating 3 experimental groups (n=15) with cement thicknesses of 50, 100, and 200 µm. The restorations were fatigue-cycled using a ball mill machine containing zirconia and stainless steel spheres. Twelve 60 min cycles were performed. Survival statistics were applied to “failure” and “success” events, comparing the three groups using a log-rank Mantel– Cox test and a log-rank test for trends (alpha = 0.05). Results: The failure and success rates were not significantly influenced by cement thickness (P = 0.137 and P = 0.872, respectively); thus, the null hypothesis was accepted. However, when log-rank test for trends was applied to failure events, the tendency to have less failures with increasing thicknesses was found statistically significant (P = 0.047). Conclusions: The cement thickness within the range adopted here did not have a significant effect on the failure or success rate of lithium disilicate occlusal veneers when exposed to randomized impact stresses generating fatigue phenomena

The AMANDA Neutrino Telescope: Principle of Operation and First Results

AMANDA is a high-energy neutrino telescope presently under construction at the geographical South Pole. In the Antarctic summer 1995/96, an array of 80 optical modules (OMs) arranged on 4 strings (AMANDA-B4) was deployed at depths between 1.5 and 2 km. In this paper we describe the design and performance of the AMANDA-B4 prototype, based on data collected between February and November 1996. Monte Carlo simulations of the detector response to down-going atmospheric muon tracks show that the global behavior of the detector is understood. We describe the data analysis method and present first results on atmospheric muon reconstruction and separation of neutrino candidates. The AMANDA array was upgraded with 216 OMs on 6 new strings in 1996/97 (AMANDA-B10), and 122 additional OMs on 3 strings in 1997/98.Comment: 36 pages, 23 figures, submitted to Astroparticle Physic

Antipsychotics and Torsadogenic Risk: Signals Emerging from the US FDA Adverse Event Reporting System Database

Background: Drug-induced torsades de pointes (TdP) and related clinical entities represent a current regulatory and clinical burden. Objective: As part of the FP7 ARITMO (Arrhythmogenic Potential of Drugs) project, we explored the publicly available US FDA Adverse Event Reporting System (FAERS) database to detect signals of torsadogenicity for antipsychotics (APs). Methods: Four groups of events in decreasing order of drug-attributable risk were identified: (1) TdP, (2) QT-interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. The reporting odds ratio (ROR) with 95 % confidence interval (CI) was calculated through a cumulative analysis from group 1 to 4. For groups 1+2, ROR was adjusted for age, gender, and concomitant drugs (e.g., antiarrhythmics) and stratified for AZCERT drugs, lists I and II (http://www.azcert.org, as of June 2011). A potential signal of torsadogenicity was defined if a drug met all the following criteria: (a) four or more cases in group 1+2; (b) significant ROR in group 1+2 that persists through the cumulative approach; (c) significant adjusted ROR for group 1+2 in the stratum without AZCERT drugs; (d) not included in AZCERT lists (as of June 2011). Results: Over the 7-year period, 37 APs were reported in 4,794 cases of arrhythmia: 140 (group 1), 883 (group 2), 1,651 (group 3), and 2,120 (group 4). Based on our criteria, the following potential signals of torsadogenicity were found: amisulpride (25 cases; adjusted ROR in the stratum without AZCERT drugs = 43.94, 95 % CI 22.82-84.60), cyamemazine (11; 15.48, 6.87-34.91), and olanzapine (189; 7.74, 6.45-9.30). Conclusions: This pharmacovigilance analysis on the FAERS found 3 potential signals of torsadogenicity for drugs previously unknown for this risk

Limits to the muon flux from WIMP annihilation in the center of the Earth with the AMANDA detector

A search for nearly vertical up-going muon-neutrinos from neutralino annihilations in the center of the Earth has been performed with the AMANDA-B10 neutrino detector. The data sample collected in 130.1 days of live-time in 1997, ~10^9 events, has been analyzed for this search. No excess over the expected atmospheric neutrino background is oberved. An upper limit at 90% confidence level on the annihilation rate of neutralinos in the center of the Earth is obtained as a function of the neutralino mass in the range 100 GeV-5000 GeV, as well as the corresponding muon flux limit.Comment: 14 pages, 11 figures. Version accepted for publication in Physical Review

Results from the Antarctic Muon and Neutrino Detector Array (AMANDA)

We show new results from both the older and newer incarnations of AMANDA (AMANDA-B10 and AMANDA-II, respectively). These results demonstrate that AMANDA is a functioning, multipurpose detector with significant physics and astrophysics reach. They include a new higher-statistics measurement of the atmospheric muon neutrino flux and preliminary results from searches for a variety of sources of ultrahigh energy neutrinos: generic point sources, gamma-ray bursters and diffuse sources producing muons in the detector, and diffuse sources producing electromagnetic or hadronic showers in or near the detector.Comment: Invited talk at the XXth International Conference on Neutrino Physics and Astrophysics (Neutrino 2002), Munich, Germany, May 25-30, 200

The Effects of Cocaine on Different Redox Forms of Cysteine and Homocysteine, and on Labile, Reduced Sulfur in the Rat Plasma Following Active versus Passive Drug Injections

Received: 28 November 2012 / Revised: 19 April 2013 / Accepted: 6 May 2013 / Published online: 16 May 2013 The Author(s) 2013. This article is published with open access at Springerlink.comThe aim of the present studies was to evaluate cocaine-induced changes in the concentrations of different redox forms of cysteine (Cys) and homocysteine (Hcy), and products of anaerobic Cys metabolism, i.e., labile, reduced sulfur (LS) in the rat plasma. The above-mentioned parameters were determined after i.p. acute and subchronic cocaine treatment as well as following i.v. cocaine self-administration using the yoked procedure. Additionally, Cys, Hcy, and LS levels were measured during the 10-day extinction training in rats that underwent i.v. cocaine administration. Acute i.p. cocaine treatment increased the total and protein-bound Hcy contents, decreased LS, and did not change the concentrations of Cys fractions in the rat plasma. In turn, subchronic i.p. cocaine administration significantly increased free Hcy and lowered the total and protein-bound Cys concentrations while LS level was unchanged. Cocaine self-administration enhanced the total and protein-bound Hcy levels, decreased LS content, and did not affect the Cys fractions. On the other hand, yoked cocaine infusions did not alter the concentration of Hcy fractions while decreased the total and protein-bound Cys and LS content. This extinction training resulted in the lack of changes in the examined parameters in rats with a history of cocaine self-administration while in the yoked cocaine group an increase in the plasma free Cys fraction and LS was seen. Our results demonstrate for the first time that cocaine does evoke significant changes in homeostasis of thiol amino acids Cys and Hcy, and in some products of anaerobic Cys metabolism, which are dependent on the way of cocaine administration

Comparison of drug prescribing before and during the COVID-19 pandemic: A cross-national European study

Purpose: The COVID-19 pandemic had an impact on health care, with disruption to routine clinical care. Our aim was to describe changes in prescription drugs dispensing in the primary and outpatient sectors during the first year of the pandemic across Europe. Methods: We used routine administrative data on dispensed medicines in eight European countries (five whole countries, three represented by one region each) from January 2017 to March 2021 to compare the first year of the COVID-19 pandemic with the preceding 3 years. Results: In the 10 therapeutic subgroups with the highest dispensed volumes across all countries/regions the relative changes between the COVID-19 period and the year before were mostly of a magnitude similar to changes between previous periods. However, for drugs for obstructive airway diseases the changes in the COVID-19 period were stronger in several countries/regions. In all countries/regions a decrease in dispensed DDDs of antibiotics for systemic use (from −39.4% in Romagna to −14.2% in Scotland) and nasal preparations (from −34.4% in Lithuania to −5.7% in Sweden) was observed. We observed a stockpiling effect in the total market in March 2020 in six countries/regions. In Czechia the observed increase was not significant and in Slovenia volumes increased only after the end of the first lockdown. We found an increase in average therapeutic quantity per pack dispensed, which, however, exceeded 5% only in Slovenia, Germany, and Czechia. Conclusions: The findings from this first European cross-national comparison show a substantial decrease in dispensed volumes of antibiotics for systemic use in all countries/regions. The results also indicate that the provision of medicines for common chronic conditions was mostly resilient to challenges faced during the pandemic. However, there were notable differences between the countries/regions for some therapeutic areas