Projecting the self to past and future in mental time

Introduction: Human experience takes place in the line of mental-time (MT) created through imagination of oneself in different time-points in past or future (self-projection in time). Here we manipulated self-projection in MT not only with respect to one's life-events but also with respect to one's faces from different past and future time-points. Methods: We here compared MTT with respect to one's facial images from different time points in past and future (study 1: MT-faces) as well as with respect to different past and future life events (study 2: MT-events). Participants were asked to make judgments about past and future face images and past and future events from three different time-points: the present (Now), eight years earlier (Past) or eight years later (Future). In addition, as a control task participants were asked to make recognition judgments with respect to faces and memory-related judgments with respect to events without changing their habitual self-location in time. Behavioral measures and functional magnetic resonance imaging (fMRI) activity after subtraction of recognition and memory related activities show both absolute MT and relative MT effects for faces and events, signifying a fundamental brain mechanism of MT, disentangled from episodic memory functions. Results: Behavioural and event-related fMRI activity showed three independent effects characterized by (1) similarity between past recollection and future imagination, (2) facilitation of judgments related to the future as compared to the past, and (3) facilitation of judgments related to time-points distant from the present. These effects were found with respect to faces and events suggesting that the brain mechanisms of MT are independent of whether actual life episodes have to be re-/pre-experienced and recruited a common cerebral network including the medial-temporal, precuneus, inferior-frontal, temporo-parietal, and insular cortices. Conclusions: These behavioural and neural data suggest that self-projection in time is a crucial aspect of MT, relying on neural structures encoding memory, mental imagery, and self. Furthermore our results emphasize the idea that mental temporal processing is more strongly directed to future prediction than to past recollection.

Equivalence of paper and pencil vs internet forms of the ZKPQ-50-CC in Spanish and French samples

This study was designed to check for the equivalence of the ZKPQ-50-CC (Spanish and French versions) through Internet on-line (OL) and paper and pencil (PP) answer format. Differences in means and devia- tions were significant in some scales, but effect sizes are minimal except for Sociability in the Spanish sample. Alpha reliabilities are also very similar in both versions with no significant differences between formats. A robust factorial structure was found for the two formats and the average congruency coefficients were 0.98. The goodness-of-fit indexes obtained by confirmatory factorial analysis are very similar to those obtained in the ZKPQ-50-CC validation study and they do not differ between the two formats. The multi-group analysis confirms the equivalence among the OL-PP formats in both countries. These results in general support the validity and reliability of the Internet as a method in investigations using the ZKPQ-50-CC.

Nicotine vaccines for smoking cessation.

BACKGROUND: By reducing the amount of nicotine that reaches the brain when a person smokes a cigarette, nicotine vaccines may help people to stop smoking or to prevent recent quitters from relapsing. OBJECTIVES: The aims of this review are to assess the efficacy of nicotine vaccines for smoking cessation and for relapse prevention, and to assess the frequency and type of adverse events associated with the use of nicotine vaccines. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Review Group specialised register for trials, using the term 'vaccine' in the title or abstract, or in a keyword (date of most recent search April 2012). To identify any other material including reviews and papers potentially relevant to the background or discussion sections, we also searched MEDLINE, EMBASE, and PsycINFO, combining terms for nicotine vaccines with terms for smoking and tobacco use, without design limits or limits for human subjects. We searched the Annual Meeting abstracts of the Society for Research on Nicotine and Tobacco up to 2012, using the search string 'vaccin'. We searched Google Scholar for 'nicotine vaccine'. We also searched company websites and Google for information related to specific vaccines. We searched clinicaltrials.gov in March 2012 for 'nicotine vaccine' and for the trade names of known vaccine candidates. SELECTION CRITERIA: We included randomized controlled trials of nicotine vaccines, at Phase II and Phase III trial stage and beyond, in adult smokers or recent ex-smokers. We included studies of nicotine vaccines used as part of smoking cessation or relapse prevention interventions. DATA COLLECTION AND ANALYSIS: We extracted data on the type of participants, the dose and duration of treatment, the outcome measures, the randomization procedure, concealment of allocation, blinding of participants and personnel, reporting of outcomes, and completeness of follow-up.Our primary outcome measure was a minimum of six months abstinence from smoking. We used the most rigorous definition of abstinence, and preferred cessation rates at 12 months and biochemically validated rates where available. We have used the risk ratio (RR) to summarize individual trial outcomes. We have not pooled the current group of included studies as they cover different vaccines and variable regimens. MAIN RESULTS: There are no nicotine vaccines currently licensed for public use, but there are a number in development. We found four trials which met our inclusion criteria, three comparing NicVAX to placebo and one comparing NIC002 (formerly NicQbeta) to placebo. All were smoking cessation trials conducted by pharmaceutical companies as part of the drug development process, and all trials were judged to be at high or unclear risk of bias in at least one domain. Overall, 2642 smokers participated in the included studies in this review. None of the four included studies detected a statistically significant difference in long-term cessation between participants receiving vaccine and those receiving placebo. The RR for 12 month cessation in active and placebo groups was 1.35 (95% Confidence Interval (CI) 0.82 to 2.22) in the trial of NIC002 and 1.74 (95% CI 0.73 to 4.18) in one NicVAX trial. Two Phase III NicVAX trials, for which full results were not available, reported similar quit rates of approximately 11% in both groups. In the two studies with full results available, post hoc analyses detected higher cessation rates in participants with higher levels of nicotine antibodies, but these findings are not readily generalisable. The two studies with full results showed nicotine vaccines to be well tolerated, with the majority of adverse events classified as mild or moderate. In the study of NIC002, participants receiving the vaccine were more likely to report mild to moderate adverse events, most commonly flu-like symptoms, whereas in the study of NicVAX there was no significant difference between the two arms. Information on adverse events was not available for the large Phase III trials of NicVAX.Vaccine candidates are likely to undergo significant changes before becoming available to the general public, and those included in this review may not be the first to reach market; this limits the external validity of the results reported in this review in terms of both effectiveness and tolerability. AUTHORS' CONCLUSIONS: There is currently no evidence that nicotine vaccines enhance long-term smoking cessation. Rates of serious adverse events recorded in the two trials with full data available were low, and the majority of adverse events reported were at mild to moderate levels. The evidence available suggests nicotine vaccines do not induce compensatory smoking or affect withdrawal symptoms. No nicotine vaccines are currently licensed for use in any country but a number are under development.Further trials of nicotine vaccines are needed, comparing vaccines with placebo for smoking cessation. Further trials are also needed to explore the potential of nicotine vaccines to prevent relapse. Results from past, current and future research should be reported in full. Adverse events and serious adverse events should continue to be carefully monitored and thoroughly reported.

Science, practice and patient needs: the work of the Plinius Maior Society.

The Plinius Maior Society is a European multinational, multidisciplinary group of clinicians and researchers in the alcoholism field, which strives for a comprehensive care concept in the management of alcoholism and alcohol-related problems. The Society, using evidence-based medicine, has developed a set of protocols, in the forms of guidelines, flow-charts, leaflets and booklets, for use as tools in research on and treatment of alcohol dependence, with a view to standardize clinical research procedures and to bridge the gap between the alcoholism researcher, practitioner and patient. These protocols or tools have been subjected to a review process during their preparation, and further comments on their validity will be integrated in their updates. Seven protocols have so far been developed, two of which, 'Guidelines on Evaluation of Treatment of Alcohol Dependence' and 'Detection and Management of Patients with Psychiatric and Alcohol Use Disorders', are aimed at the clinical researcher and specialists, whereas three others [in the form of decision trees (flow-charts)] are aimed at the general practitioner and other primary health care providers. These are entitled 'Alcohol Risk Assessment and Intervention in Primary Care', 'Withdrawal from Alcohol at Home' and 'Brief Intervention in Patients with Alcohol-Related Problems'. The remaining two tools are booklets aimed at the patient, one to support initiatives for detection of drinking problems and primary intervention, namely 'Do you have this Problem? Discuss it with your Doctor!', and the other to assist the patient in relapse prevention after the early stages of treatment, namely 'On the Way to Recovery'. The protocols for the general practitioners and patients have so far been produced in seven European languages, and, as with the Guidelines, feedback from target users will be collected and incorporated in future updates. The Society continually seeks to consider areas of clinical importance for its work and, as it enters the new millennium, it hopes to address and make a significant contribution to the most pressing problem in the management of alcohol dependence, namely relapse.

Group 4: Career development for diverse and underserved populations

Globalization and diverse populations due to migration imply that counselors are expected to deliver career services to populations from a large array of cultural settings. Moreover, individuals belonging to minority or non-dominant groups may be underserved or misserved, thus decreasing their chances of finding employment opportunities through career counseling. To develop specific interventions minority or non-dominant groups, it seems important to understand their strength and weaknesses. These strengths and weaknesses will be presented in terms of risk and resilience factors, such as low future orientation and social support respectively. In the last two decades, several authors have made contributions to adapt and improve career services in order to best meet these minority groups' needs. A review of this literature identified thirteen keys to effective practice. For example, one key is to take responsibility for one's own biases and prejudices. Nonetheless, some underserved groups remain difficult to identify. Comparing some basic national demographic data with data from our counseling centers may be helpful in this context in identifying specific groups and assessing needs. One solution, in order to promote social justice across (all) cultural groups, is to encourage multiculturalism in both career counseling and society as a whole. A more inclusive society would allow each person in a minority or non-dominant group to contribute more effectively to the development and growth of this society.

The 5th anniversary of "Patient Safety in Surgery" - from the Journal's origin to its future vision.

A prospective study was undertaken to determine prognostic markers for patients with obstructive jaundice. Along with routine liver function tests, antipyrine clearance was determined in 20 patients. Four patients died after basal investigations. Five patients underwent definitive surgery. The remaining 11 patients were subjected to percutaneous transhepatic biliary decompression. Four patients died during the drainage period, while surgery was carried out for seven patients within 1-3 weeks of drainage. Of 20 patients, only six patients survived. Basal liver function tests were comparable in survivors and nonsurvivors. Discriminant analysis of the basal data revealed that plasma bilirubin, proteins and antipyrine half-life taken together had a strong association with mortality. A mathematical equation was derived using these variables and a score was computed for each patient. It was observed that a score value greater than or equal to 0.84 indicated survival. Omission of antipyrine half-life from the data, however, resulted in prediction of false security in 55% of patients. This study highlights the importance of addition of antipyrine elimination test to the routine liver function tests for precise identification of high risk patients.

Regulation of nonphosphorylated and phosphorylated forms of neurofilament proteins in the prefrontal cortex of human opioid addicts.

The neurofilament (NF) proteins (NF-H, NF-M, and NF-L for high, medium, and low molecular weights) play a crucial role in the organization of neuronal shape and function. In a preliminary study, the abundance of total NF-L was shown to be decreased in brains of opioid addicts. Because of the potential relevance of NF abnormalities in opioid addiction, we quantitated nonphosphorylated and phosphorylated NF in postmortem brains from 12 well-defined opioid abusers who had died of an opiate overdose (heroin or methadone). Levels of NF were assessed by immunoblotting techniques using phospho-independent and phospho-dependent antibodies, and the relative (% changes in immunoreactivity) and absolute (changes in ng NF/microg total protein) amounts of NF were calculated. Decreased levels of nonphosphorylated NF-H (42-32%), NF-M (14-9%) and NF-L (30-29%) were found in the prefrontal cortex of opioid addicts compared with sex, age, and postmortem delay-matched controls. In contrast, increased levels of phosphorylated NF-H (58-41%) and NF-M (56-28%) were found in the same brains of opioid addicts. The ratio of phosphorylated to nonphosphorylated NF-H in opioid addicts (3.4) was greater than that in control subjects (1.6). In the same brains of opioid addicts, the levels of protein phosphatase of the type 2A were found unchanged, which indicated that the hyperphosphorylation of NF-H is not the result of a reduced dephosphorylation process. The immunodensities of GFAP (the specific glial cytoskeletol protein), alpha-internexin (a neuronal filament related to NF-L) and synaptophysin (a synapse-specific protein) were found unchanged, suggesting a lack of gross changes in glial reaction, other intermediate filaments of the neuronal cytoskeletol, and synaptic density in the prefrontal cortex of opioid addicts. These marked reductions in total NF proteins and the aberrant hyperphosphorylation of NF-H in brains of opioid addicts may play a significant role in the cellular mechanisms of opioid addiction.

Prevalence of patients' difficulties in swallowing solid oral dosage forms

Introduction Swallowing difficulties, or dysphagia, can occur in anyage group, although it is most common among elderly people. It canaffect patients' ability to take solid oral dosage forms, thus compromisingmedication adherence. Although literature is poor, availabledata show that prevalence in the general population ranges from 25 to60%. Prevalence in community pharmacies needs to be explored.Materials & Methods Community pharmacies were recruited from arandom selection in three Swiss states: Basel-Stadt (BS), Basel-Landschaft (BL) and Lausanne (LA). Patients' ability to swallowsolid oral medications was enquired with a semi-structured interview;the interviewer spent 4 h in each included pharmacy. Each consecutivepatient (18 years and older) entering the pharmacy with aprescription for at least 3 different solid oral forms was enrolled.Study was approved by the Lausanne ethics committee.Results Sixty pharmacies took part in the study (20 in BS, 10 in BL,30 in LA) between March and May 2010. Patient inclusion rate was77.8% (410/527). Prevalence of swallowing disorders was 22.4% (92/410). Patients with swallowing disorders were older (mean age: 67.5± 16 years vs. 63.0 ± 14 years, range 19-96; p = 0.03) and moreoften women (69.6% vs. 59.1%; Chi2 = 3.3, p = 0.04) than patientswithout swallowing disorders. They had on average 4.6 ± 2.7 drugswith a mean number of 5.5 ± 3.3 tablets or capsules to take daily,which didn't differ from the number of drugs taken by patientswithout swallowing difficulties (4.9 ± 2.5 drugs and 5.9 ± 3.5 tablets;n.s.). The difficulty was mainly related to the big size (63%) orthe quality of pill coating (rough, sticky, 14%). Twenty-one patients(37.5%) stated that their swallowing disorders resulted in nonadherence, rated as rarely (12 patients), sometimes (6 patients), veryoften (1 patient) or always (2 patients). According to patients, nopharmacist and only 2 physicians enquired about patients' swallowingissue.Discussion & Conclusion Swallowing difficulties are frequent amongpatients in community pharmacies in Switzerland with an estimatedprevalence of 22%. The problem resulted in non adherence or partialadherence in at least 35% of these patients. However, pharmacists andphysicians did not routinely inquire about the disorder. Guidelinesshould be developed for promoting systematic approaches of patientsin community pharmacies.

The past, present and future of renin-angiotensin aldosterone system inhibition.

The renin-angiotensin aldosterone system (RAAS) is central to the pathogenesis of cardiovascular disease. RAAS inhibition can reduce blood pressure, prevent target organ damage in hypertension and diabetes, and improve outcomes in patients with heart failure and/or myocardial infarction. This review presents the history of RAAS inhibition including a summary of key heart failure, myocardial infarction, hypertension and atrial fibrillation trials. Recent developments in RAAS inhibition are discussed including implementation and optimization of current drug therapies. Finally, ongoing clinical trials, opportunities for future trials and issues related to the barriers and approvability of novel RAAS inhibitors are highlighted.