On the Generalizability of Experimental Results

The age-old question of the generalizability of the results of experiments that are conducted in artificial laboratory settings to more realistic inferential and decision making situations is considered in this paper. Conservatism in probability revision provides an example of a result that 1) has received wide attention, including attention in terms of implications for real-world decision making, on the basis of experiments conducted in artificial settings and 2) is now apparently thought by many to be highly situational and not at all a ubiquitous phenomenon, in which case its implications for real-world decision making are not as extensive as originally claimed. In this paper we consider the questions of generalizations from the laboratory to the real world in some detail, both within the context of the experiments regarding conservatism and within a more general context. In addition, we discuss some of the difficulties inherent in experimentation in realistic settings, suggest possible procedures for avoiding or at least alleviating such difficulties, and make a plea for more realistic experiments

Endogenous cholinergic inputs and local circuit mechanisms govern the phasic mesolimbic dopamine response to nicotine

Nicotine exerts its reinforcing action by stimulating nicotinic acetylcholine receptors (nAChRs) and boosting dopamine (DA) output from the ventral tegmental area (VTA). Recent data have led to a debate about the principal pathway of nicotine action: direct stimulation of the DAergic cells through nAChR activation, or disinhibition mediated through desensitization of nAChRs on GABAergic interneurons. We use a computational model of the VTA circuitry and nAChR function to shed light on this issue. Our model illustrates that the α4β2-containing nAChRs either on DA or GABA cells can mediate the acute effects of nicotine. We account for in vitro as well as in vivo data, and predict the conditions necessary for either direct stimulation or disinhibition to be at the origin of DA activity increases. We propose key experiments to disentangle the contribution of both mechanisms. We show that the rate of endogenous acetylcholine input crucially determines the evoked DA response for both mechanisms. Together our results delineate the mechanisms by which the VTA mediates the acute rewarding properties of nicotine and suggest an acetylcholine dependence hypothesis for nicotine reinforcement.Peer reviewe

A Career in Surgical Oncology: Finding Meaning, Balance, and Personal Satisfaction

The practice of surgical oncology provides opportunities for both personal distress as well as personal satisfaction. While many surgical oncologists experience career burnout, others derive great meaning and satisfaction from their work. In this article, we review the literature on surgeon burnout, discuss potential personal and professional consequences, and consider steps individual surgeons can take to promote personal and professional satisfaction

Stability and change in health behaviours as predictors for disability pension: a prospective cohort study of Swedish twins

<p>Abstract</p> <p>Background</p> <p>Stability or changes of health behaviours have not been studied in association with incidence of disability pension (DP). The aims were to (1) investigate if stability or changes in health behaviours predict DP due to musculoskeletal diagnosis (MSD), (2) to evaluate if an association exists for DP in general, and (3) after taking familial confounding into account.</p> <p>Methods</p> <p>The study sample was 16,713 like-sexed twin individuals born in Sweden between 1935-1958 (6195 complete twin pairs) who had participated in two surveys 25 years apart, were alive, and not pensioned at the time of the latest survey. Cox proportional hazards analysis was used to assess the associations (hazard ratios (HR) with 95% confidence intervals (CI)) between stability and change in health behaviours (physical activity, tobacco and alcohol use, body mass index (BMI)), and number of pain locations collected at two time points 25 years apart and the incidence of DP until 2008.</p> <p>Results</p> <p>During the follow-up, 1843 (11%) individuals were granted DP with 747 of these due to MSD. A higher proportion of women were granted DP than men. Increase in BMI and stable use of tobacco products were predictors for DP due to MSD (HR 1.21-1.48) and DP in general (HR 1.10-1.41). The stability in the frequency of physical activity and increased frequency of physical activity were protective factors for DP due to MSD only when accounting for familial confounding. However, the number of pain locations (stability, increase, or decrease) was the strongest predictor for future DP due to MSD (HR 3.69, CI 2.99-4.56) and DP in general (HR 2.15, CI 1.92-2.42). In discordant pair analysis, the HRs for pain were lower, indicating potential familial confounding.</p> <p>Conclusions</p> <p>Health behaviours in adulthood, including an increase in pain locations were associated with the incidence of DP. The association between physical activity and DP was especially related to adulthood choices or habits, i.e., the individual decision about frequency of exercising. Thus, it is important to e.g. increase public awareness of the potential beneficial effects of exercise throughout life to avoid permanent exclusion from the labour market for medical reasons.</p

Professional quality of life and organizational changes: a five-year observational study in Primary Care

<p>Abstract</p> <p>Background</p> <p>The satisfaction and the quality of life perceived by professionals have implications for the performance of health organizations. We have assessed the variations in professional quality of life (PQL) and their explanatory factors during a services management decentralization process.</p> <p>Methods</p> <p>It was designed as a longitudinal analytical observational study in a Health Area in Madrid, Spain. Three surveys were sent out during an ongoing management decentralization process between 2001 and 2005. The professionals surveyed were divided into three groups: Group I (97.3% physicians), group II (92.5% nurses) and group III (auxiliary personnel). Analysis of the tendency and elaboration of an explanatory multivariate model was made. The PQL -35 questionnaire, based on Karasek's demand-control theory, was used to measure PQL. This questionnaire recognizes three PQL dimensions: management support (MS), workload (WL) and intrinsic motivation (IM).</p> <p>Results</p> <p>1444 responses were analyzed. PQL increased 0.16 (CI 95% 0.04 – 0.28) points in each survey. Group II presents over time a higher PQL score than group I of 0.38 (IC 95% 0.18 – 0.59) points. There is no difference between groups I and III.</p> <p>For each point that MS increases, PQL increases between 0.44 and 0.59 points. PQL decreases an average of between 0.35 and 0.49 point, for each point that WL increases.</p> <p>Age appears to have a marginal association with PQL (CI 95% 0.00 – 0.02), as it occurs with being single or not having a stable relationship (CI 95% 0.01 – 0.41). Performing management tasks currently or in the past is related to poorer PQL perception (CI 95% -0.45 – -0.06), and the same occurs with working other than morning shifts (CI 95% -0.03 – -0.40 points).</p> <p>PQL is not related to sex, location of the centre (rural/urban), time spent working in the organization or contractual situation.</p> <p>Conclusion</p> <p>With the improvement in work control and avoiding increases in workloads, PQL perception can be maintained despite deep organizational changes at the macro-management level. Different professional groups experience different perceptions depending on how the changes impact their position in the organization.</p

The effect of immunomodulators on the immunogenicity of TNF-blocking therapeutic monoclonal antibodies: a review

Therapeutic monoclonal antibodies have revolutionized the treatment of various inflammatory diseases. Immunogenicity against these antibodies has been shown to be clinically important: it is associated with shorter response duration because of diminishing concentrations in the blood and with infusion reactions. Concomitant immunomodulators in the form of methotrexate or azathioprine reduced the immunogenicity of therapeutic antibodies in rheumatoid arthritis, Crohn disease, and juvenile idiopathic arthritis. The occurrence of adverse events does not increase when immunomodulators are added to therapeutic antibodies. The mechanism whereby methotrexate and azathioprine influence immunogenicity remains unclear. Evidence-based consensus on prescribing concomitant immunomodulators is needed

Association of Transcription Factor Gene LMX1B with Autism

Multiple lines of evidence suggest a serotoninergic dysfunction in autism. The role of LMX1B in the development and maintenance of serotoninergic neurons is well known. In order to examine the role, if any, of LMX1B with autism pathophysiology, a trio-based SNP association study using 252 family samples from the AGRE was performed. Using pair-wise tagging method, 24 SNPs were selected from the HapMap data, based on their location and minor allele frequency. Two SNPs (rs10732392 and rs12336217) showed moderate association with autism with p values 0.018 and 0.022 respectively in transmission disequilibrium test. The haplotype AGCGTG also showed significant association (p = 0.008). Further, LMX1B mRNA expressions were studied in the postmortem brain tissues of autism subjects and healthy controls samples. LMX1B transcripts was found to be significantly lower in the anterior cingulate gyrus region of autism patients compared with controls (p = 0.049). Our study suggests a possible role of LMX1B in the pathophysiology of autism. Based on previous reports, it is likely to be mediated through a seretoninergic mechanism. This is the first report on the association of LMX1B with autism, though it should be viewed with some caution considering the modest associations we report

Pediatric interventional radiography equipment: safety considerations

This paper discusses pediatric image quality and radiation dose considerations in state-of-the-art fluoroscopic imaging equipment. Although most fluoroscopes are capable of automatically providing good image quality on infants, toddlers, and small children, excessive radiation dose levels can result from design deficiencies of the imaging device or inappropriate configuration of the equipment’s capabilities when imaging small body parts. Important design features and setup choices at installation and during the clinical use of the imaging device can improve image quality and reduce radiation exposure levels in pediatric patients. Pediatric radiologists and cardiologists, with the help of medical physicists, need to understand the issues involved in creating good image quality at reasonable pediatric patient doses. The control of radiographic technique factors by the generator of the imaging device must provide a large dynamic range of mAs values per exposure pulse during both fluoroscopy and image recording as a function of patient girth, which is the thickness of the patient in the posterior–anterior projection at the umbilicus (less than 10 cm to greater than 30 cm). The range of pulse widths must be limited to less than 10 ms in children to properly freeze patient motion. Variable rate pulsed fluoroscopy can be leveraged to reduce radiation dose to the patient and improve image quality. Three focal spots with nominal sizes of 0.3 mm to 1 mm are necessary on the pediatric unit. A second, lateral imaging plane might be necessary because of the child’s limited tolerance of contrast medium. Spectral and spatial beam shaping can improve image quality while reducing the radiation dose. Finally, the level of entrance exposure to the image receptor of the fluoroscope as a function of operator choices, of added filter thickness, of selected pulse rate, of the selected field-of-view and of the patient girth all must be addressed at installation