The role of learning-related dopamine signals in addiction vulnerability

Dopaminergic signals play a mathematically precise role in reward-related learning, and variations in dopaminergic signaling have been implicated in vulnerability to addiction. Here, we provide a detailed overview of the relationship between theoretical, mathematical, and experimental accounts of phasic dopamine signaling, with implications for the role of learning-related dopamine signaling in addiction and related disorders. We describe the theoretical and behavioral characteristics of model-free learning based on errors in the prediction of reward, including step-by-step explanations of the underlying equations. We then use recent insights from an animal model that highlights individual variation in learning during a Pavlovian conditioning paradigm to describe overlapping aspects of incentive salience attribution and model-free learning. We argue that this provides a computationally coherent account of some features of addiction.

An account of the conversion of Theodore John, a late teacher among the Jews, together with his confession of the Christian faith ...

transl. out of High Dutch into English

The history of the Jews, from the taking of Jerusalem by Titus, to the present time, comprising a narrative of their wanderings, persecutions, commercial enterprises, literature, manners, customs, and forms of worship : with an account of the various efforts made for their conversion

[James A. Huie]

Modern judaism : or, a brief account of the opinions, traditions, rites and ceremonies of the Jews in modern times

by John Allen

The present state of the Jews : wherein is contained an exact account of their customs, secular and religious ; to which is annexed a summary discourse of the Misna, Talmud, and Gemara

by L. Addison

Assessment of patient setup errors in IGRT in combination with a six degrees of freedom couch

PURPOSE The range of patient setup errors in six dimensions detected in clinical routine for cranial as well as for extracranial treatments, were analyzed while performing linear accelerator based stereotactic treatments with frameless patient setup systems. Additionally, the need for re-verification of the patient setup for situations where couch rotations are involved was analyzed for patients treated in the cranial region. METHODS AND MATERIALS A total of 2185 initial (i.e. after pre-positioning the patient with the infrared system but before image guidance) patient setup errors (1705 in the cranial and 480 in the extracranial region) obtained by using ExacTrac (BrainLAB AG, Feldkirchen, Germany) were analyzed. Additionally, the patient setup errors as a function of the couch rotation angle were obtained by analyzing 242 setup errors in the cranial region. Before the couch was rotated, the patient setup error was corrected at couch rotation angle 0° with the aid of image guidance and the six degrees of freedom (6DoF) couch. For both situations attainment rates for two different tolerances (tolerance A: ± 0.5mm, ± 0.5°; tolerance B: ± 1.0 mm, ± 1.0°) were calculated. RESULTS The mean (± one standard deviation) initial patient setup errors for the cranial cases were -0.24 ± 1.21°, -0.23 ± 0.91° and -0.03 ± 1.07° for the pitch, roll and couch rotation axes and 0.10 ± 1.17 mm, 0.10 ± 1.62 mm and 0.11 ± 1.29 mm for the lateral, longitudinal and vertical axes, respectively. Attainment rate (all six axes simultaneously) for tolerance A was 0.6% and 13.1% for tolerance B, respectively. For the extracranial cases the corresponding values were -0.21 ± 0.95°, -0.05 ± 1.08° and -0.14 ± 1.02° for the pitch, roll and couch rotation axes and 0.15 ± 1.77 mm, 0.62 ± 1.94 mm and -0.40 ± 2.15 mm for the lateral, longitudinal and vertical axes. Attainment rate (all six axes simultaneously) for tolerance A was 0.0% and 3.1% for tolerance B, respectively. After initial setup correction and rotation of the couch to treatment position a re-correction has to be performed in 77.4% of all cases to fulfill tolerance A and in 15.6% of all cases to fulfill tolerance B. CONCLUSION The analysis of the data shows that all six axes of a 6DoF couch are used extensively for patient setup in clinical routine. In order to fulfill high patient setup accuracies (e.g. for stereotactic treatments), a 6DoF couch is recommended. Moreover, re-verification of the patient setup after rotating the couch is required in clinical routine.

An account of the recent persecution of the Jews at Damascus : with reflections thereon ; an app., cont. various documents connected with the subject

by David Salomons

Risk factors for patient-reported medical errors in eleven countries

OBJECTIVES The aim of this study was to identify common risk factors for patient-reported medical errors across countries. In country-level analyses, differences in risks associated with error between health care systems were investigated. The joint effects of risks on error-reporting probability were modelled for hypothetical patients with different health care utilization patterns. DESIGN Data from the Commonwealth Fund's 2010 lnternational Survey of the General Public's Views of their Health Care System's Performance in 11 Countries. SETTING Representative population samples of 11 countries were surveyed (total sample = 19,738 adults). Utilization of health care, coordination of care problems and reported errors were assessed. Regression analyses were conducted to identify risk factors for patients' reports of medical, medication and laboratory errors across countries and in country-specific models. RESULTS Error was reported by 11.2% of patients but with marked differences between countries (range: 5.4-17.0%). Poor coordination of care was reported by 27.3%. The risk of patient-reported error was determined mainly by health care utilization: Emergency care (OR = 1.7, P < 0.001), hospitalization (OR = 1.6, P < 0.001) and the number of providers involved (OR three doctors = 2.0, P < 0.001) are important predictors. Poor care coordination is the single most important risk factor for reporting error (OR = 3.9, P < 0.001). Country-specific models yielded common and country-specific predictors for self-reported error. For high utilizers of care, the probability that errors are reported rises up to P = 0.68. CONCLUSIONS Safety remains a global challenge affecting many patients throughout the world. Large variability exists in the frequency of patient-reported error across countries. To learn from others' errors is not only essential within countries but may also prove a promising strategy internationally.

Systematic diagonal and vertical errors in antisaccades and memory-guided saccades

Studies of memory-guided saccades in monkeys show an upward bias, while studies of antisaccades in humans show a diagonal effect, a deviation of endpoints toward the 45° diagonal. To determine if these two different spatial biases are specific to different types of saccades, we studied prosaccades, antisaccades and memory-guided saccades in humans. The diagonal effect occurred not with prosaccades but with antisaccades and memory-guided saccades with long intervals, consistent with hypotheses that it originates in computations of goal location under conditions of uncertainty. There was a small upward bias for memory-guided saccades but not prosaccades or antisaccades. Thus this bias is not a general effect of target uncertainty but a property specific to memory-guided saccades.

The impact of medical errors on Swiss anaesthesiologists: a cross-sectional survey.

BACKGROUND Clinicians involved in medical errors can experience significant distress. This study aims to examine (1) how medical errors impact anaesthesiologists in key work and life domains; (2) anaesthesiologists' attitudes regarding support after errors; (3) and which anaesthesiologists are most affected by errors. METHODS This study is a mailed cross-sectional survey completed by 281 of the 542 clinically active anaesthesiologists (52% response rate) working at Switzerland's five university hospitals between July 2012 and April 2013. RESULTS Respondents reported that errors had negatively affected anxiety about future errors (51%), confidence in their ability as a doctor (45%), ability to sleep (36%), job satisfaction (32%), and professional reputation (9%). Respondents' lives were more likely to be affected as error severity increased. Ninety per cent of respondents disagreed that hospitals adequately support them in coping with the stress associated with medical errors. Nearly all of the respondents (92%) reported being interested in psychological counselling after a serious error, but many identified barriers to seeking counselling. However, there were significant differences between departments regarding error-related stress levels and attitudes about error-related support. Respondents were more likely to experience certain distress if they were female, older, had previously been involved in a serious error, and were dissatisfied with their last error disclosure. CONCLUSION Medical errors, even minor errors and near misses, can have a serious effect on clinicians. Health-care organisations need to do more to support clinicians in coping with the stress associated with medical errors.

Disclosing and reporting medical errors: Cross-sectional survey of Swiss anaesthesiologists.

BACKGROUND There is limited research on anaesthesiologists' attitudes and experiences regarding medical error communication, particularly concerning disclosing errors to patients. OBJECTIVE To characterise anaesthesiologists' attitudes and experiences regarding disclosing errors to patients and reporting errors within the hospital, and to examine factors influencing their willingness to disclose or report errors. DESIGN Cross-sectional survey. SETTING Switzerland's five university hospitals' departments of anaesthesia in 2012/2013. PARTICIPANTS Two hundred and eighty-one clinically active anaesthesiologists. MAIN OUTCOME MEASURES Anaesthesiologists' attitudes and experiences regarding medical error communication. RESULTS The overall response rate of the survey was 52% (281/542). Respondents broadly endorsed disclosing harmful errors to patients (100% serious, 77% minor errors, 19% near misses), but also reported factors that might make them less likely to actually disclose such errors. Only 12% of respondents had previously received training on how to disclose errors to patients, although 93% were interested in receiving training. Overall, 97% of respondents agreed that serious errors should be reported, but willingness to report minor errors (74%) and near misses (59%) was lower. Respondents were more likely to strongly agree that serious errors should be reported if they also thought that their hospital would implement systematic changes after errors were reported [(odds ratio, 2.097 (95% confidence interval, 1.16 to 3.81)]. Significant differences in attitudes between departments regarding error disclosure and reporting were noted. CONCLUSION Willingness to disclose or report errors varied widely between hospitals. Thus, heads of department and hospital chiefs need to be aware of the importance of local culture when it comes to error communication. Error disclosure training and improving feedback on how error reports are being used to improve patient safety may also be important steps in increasing anaesthesiologists' communication of errors.

Sensitivity of the WRF model to PBL parametrisations and nesting techniques: evaluation of wind storms over complex terrain

Simulating surface wind over complex terrain is a challenge in regional climate modelling. Therefore, this study aims at identifying a set-up of the Weather Research and Forecasting Model (WRF) model that minimises system- atic errors of surface winds in hindcast simulations. Major factors of the model configuration are tested to find a suitable set-up: the horizontal resolution, the planetary boundary layer (PBL) parameterisation scheme and the way the WRF is nested to the driving data set. Hence, a number of sensitivity simulations at a spatial resolution of 2 km are carried out and compared to observations. Given the importance of wind storms, the analysis is based on case studies of 24 historical wind storms that caused great economic damage in Switzerland. Each of these events is downscaled using eight different model set-ups, but sharing the same driving data set. The results show that the lack of representation of the unresolved topography leads to a general overestimation of wind speed in WRF. However, this bias can be substantially reduced by using a PBL scheme that explicitly considers the effects of non-resolved topography, which also improves the spatial structure of wind speed over Switzerland. The wind direction, although generally well reproduced, is not very sensitive to the PBL scheme. Further sensitivity tests include four types of nesting methods: nesting only at the boundaries of the outermost domain, analysis nudging, spectral nudging, and the so-called re-forecast method, where the simulation is frequently restarted. These simulations show that restricting the freedom of the model to develop large-scale disturbances slightly increases the temporal agreement with the observations, at the same time that it further reduces the overestimation of wind speed, especially for maximum wind peaks. The model performance is also evaluated in the outermost domains, where the resolution is coarser. The results demonstrate the important role of horizontal resolution, where the step from 6 to 2 km significantly improves model performance. In summary, the combination of a grid size of 2 km, the non-local PBL scheme modified to explicitly account for non-resolved orography, as well as analysis or spectral nudging, is a superior combination when dynamical downscaling is aimed at reproducing real wind fields.