How democracy resolves conflict in difficult games

Democracy resolves conflicts in difficult games like Prisoners’ Dilemma and Chicken by stabilizing their cooperative outcomes. It does so by transforming these games into games in which voters are presented with a choice between a cooperative outcome and a Pareto-inferior noncooperative outcome. In the transformed game, it is always rational for voters to vote for the cooperative outcome, because cooperation is a weakly dominant strategy independent of the decision rule and the number of voters who choose it. Such games are illustrated by 2-person and n-person public-goods games, in which it is optimal to be a free rider, and a biblical story from the book of Exodus

Editorial: Observational studies in ADHD: the effects of switching to modified-release methylphenidate preparations on clinical outcomes and adherence

Patients with ADHD may have better adherence to treatment with modified-release methylphenidate (MPH-MR) formulations, which are taken once daily, compared with immediate-release (IR) formulations, which need to be taken several times a day. Data on long-term outcomes such as adherence may be lacking from randomised controlled trials as these are usually only short-term. Observational studies, if performed and reported appropriately, can provide valuable long-term data on such outcomes, as well as additional information on effectiveness and efficiency, from a real-life setting. By reviewing previous observational studies that have investigated switching treatment from MPH-IR to MPH-MR, results from a new, naturalistic observational study, the OBSEER study, are put into context. We conclude that, based on observational trial data, switching from MPH-IR to MPH-MR is a valid clinical approach, with the potential for improved clinical outcome and treatment adherence

Global quantitative indices reflecting provider process-of-care: data-base derivation

Background: Controversy has attended the relationship between risk-adjusted mortality and process-of-care. There would be advantage in the establishment, at the data-base level, of global quantitative indices subsuming the diversity of process-of-care. Methods: A retrospective, cohort study of patients identified in the Australian and New Zealand Intensive Care Society Adult Patient Database, 1993-2003, at the level of geographic and ICU-level descriptors (n = 35), for both hospital survivors and non-survivors. Process-of-care indices were established by analysis of: (i) the smoothed time-hazard curve of individual patient discharge and determined by pharmaco-kinetic methods as area under the hazard-curve (AUC), reflecting the integrated experience of the discharge process, and time-to-peak-hazard (TMAX, in days), reflecting the time to maximum rate of hospital discharge; and (ii) individual patient ability to optimize output (as length-of-stay) for recorded data-base physiological inputs; estimated as a technical production-efficiency (TE, scaled [0,(maximum)1]), via the econometric technique of stochastic frontier analysis. For each descriptor, multivariate correlation-relationships between indices and summed mortality probability were determined. Results: The data-set consisted of 223129 patients from 99 ICUs with mean (SD) age and APACHE III score of 59.2(18.9) years and 52.7(30.6) respectively; 41.7% were female and 45.7% were mechanically ventilated within the first 24 hours post-admission. For survivors, AUC was maximal in rural and for-profit ICUs, whereas TMAX (≥ 7.8 days) and TE (≥ 0.74) were maximal in tertiary-ICUs. For non-survivors, AUC was maximal in tertiary-ICUs, but TMAX (≥ 4.2 days) and TE (≥ 0.69) were maximal in for-profit ICUs. Across descriptors, significant differences in indices were demonstrated (analysisof- variance, P ≤ 0.0001). Total explained variance, for survivors (0.89) and non-survivors (0.89), was maximized by combinations of indices demonstrating a low correlation with mortality probability. Conclusions: Global indices reflecting process of care may be formally established at the level of national patient databases. These indices appear orthogonal to mortality outcome.John L Moran, Patricia J Solomon and the Adult Database Management Committee (ADMC) of the Australian and New Zealand Intensive Care Society (ANZICS

Dimeric SecA Couples the Preprotein Translocation in an Asymmetric Manner

The Sec translocase mediates the post-translational translocation of a number of preproteins through the inner membrane in bacteria. In the initiatory translocation step, SecB targets the preprotein to the translocase by specific interaction with its receptor SecA. The latter is the ATPase of Sec translocase which mediates the post-translational translocation of preprotein through the protein-conducting channel SecYEG in the bacterial inner membrane. We examined the structures of Escherichia coli Sec intermediates in solution as visualized by negatively stained electron microscopy in order to probe the oligomeric states of SecA during this process. The symmetric interaction pattern between the SecA dimer and SecB becomes asymmetric in the presence of proOmpA, and one of the SecA protomers predominantly binds to SecB/proOmpA. Our results suggest that during preprotein translocation, the two SecA protomers are different in structure and may play different roles

Fats and Factors: Lipid Profiles Associate with Personality Factors and Suicidal History in Bipolar Subjects

Polyunsaturated fatty acids (PUFA) have shown efficacy in the treatment of bipolar disorder, however their specific role in treating the illness is unclear. Serum PUFA and dietary intakes of PUFA associate with suicidal behavior in epidemiological studies. The objective of this study was to assess serum n-3 and n-6 PUFA levels in bipolar subjects and determine possible associations with suicidal risk, including suicidal history and relevant personality factors that have been associated with suicidality. We studied 27 bipolar subjects using the NEO-PI to assess the big five personality factors, structured interviews to verify diagnosis and assess suicidal history, and lipomics to quantify n-3 and n-6 PUFA in serum. We found positive associations between personality factors and ratios of n-3 PUFA, suggesting that conversion of short chain to long chain n-3s and the activity of enzymes in this pathway may associate with measures of personality. Thus, ratios of docosahexaenoic acid (DHA) to alpha linolenic acid (ALA) and the activity of fatty acid desaturase 2 (FADS2) involved in the conversion of ALA to DHA were positively associated with openness factor scores. Ratios of eicosapentaenoic acid (EPA) to ALA and ratios of EPA to DHA were positively associated with agreeableness factor scores. Finally, serum concentrations of the n-6, arachidonic acid (AA), were significantly lower in subjects with a history of suicide attempt compared to non-attempters. The data suggest that specific lipid profiles, which are controlled by an interaction between diet and genetics, correlate with suicidal history and personality factors related to suicidal risk. This study provides preliminary data for future studies to determine whether manipulation of PUFA profiles (through diet or supplementation) can affect personality measures and disease outcome in bipolar subjects and supports the need for further investigations into individualized specific modulations of lipid profiles to add adjunctive value to treatment paradigms

Metabolic Factors Limiting Performance in Marathon Runners

Each year in the past three decades has seen hundreds of thousands of runners register to run a major marathon. Of those who attempt to race over the marathon distance of 26 miles and 385 yards (42.195 kilometers), more than two-fifths experience severe and performance-limiting depletion of physiologic carbohydrate reserves (a phenomenon known as ‘hitting the wall’), and thousands drop out before reaching the finish lines (approximately 1–2% of those who start). Analyses of endurance physiology have often either used coarse approximations to suggest that human glycogen reserves are insufficient to fuel a marathon (making ‘hitting the wall’ seem inevitable), or implied that maximal glycogen loading is required in order to complete a marathon without ‘hitting the wall.’ The present computational study demonstrates that the energetic constraints on endurance runners are more subtle, and depend on several physiologic variables including the muscle mass distribution, liver and muscle glycogen densities, and running speed (exercise intensity as a fraction of aerobic capacity) of individual runners, in personalized but nevertheless quantifiable and predictable ways. The analytic approach presented here is used to estimate the distance at which runners will exhaust their glycogen stores as a function of running intensity. In so doing it also provides a basis for guidelines ensuring the safety and optimizing the performance of endurance runners, both by setting personally appropriate paces and by prescribing midrace fueling requirements for avoiding ‘the wall.’ The present analysis also sheds physiologically principled light on important standards in marathon running that until now have remained empirically defined: The qualifying times for the Boston Marathon

A Close Eye on the Eagle-Eyed Visual Acuity Hypothesis of Autism

Autism spectrum disorders (ASD) have been associated with sensory hypersensitivity. A recent study reported visual acuity (VA) in ASD in the region reported for birds of prey. The validity of the results was subsequently doubted. This study examined VA in 34 individuals with ASD, 16 with schizophrenia (SCH), and 26 typically developing (TYP). Participants with ASD did not show higher VA than those with SCH and TYP. There were no substantial correlations of VA with clinical severity in ASD or SCH. This study could not confirm the eagle-eyed acuity hypothesis of ASD, or find evidence for a connection of VA and clinical phenotypes. Research needs to further address the origins and circumstances associated with altered sensory or perceptual processing in ASD

Relationship between body image disturbance and incidence of depression: the SUN prospective cohort

<p>Abstract</p> <p>Background</p> <p>Body image disturbance is an increasing problem in Western societies and is associated with a number of mental health outcomes including anorexia, bulimia, body dysmorphia, and depression. The aim of this study was to assess the association between body image disturbance and the incidence of depression.</p> <p>Methods</p> <p>This study included 10,286 participants from a dynamic prospective cohort of Spanish university graduates, who were followed-up for a median period of 4.2 years (Seguimiento Universidad de Navarra – the SUN study). The key characteristic of the study is the permanently open recruitment that started in 1999. The baseline questionnaire included information about body mass index (BMI) and the nine figure schemes that were used to assess body size perception. These variables were grouped according to recommended classifications and the difference between BMI and body size perception was considered as a proxy of body image disturbance. A subject was classified as an incident case of depression if he/she was initially free of depression and reported a physician-made diagnosis of depression and/or the use of antidepressant medication in at least one of the follow-up questionnaires. The association between body image disturbance and the incidence of depression was estimated by calculating the multivariable adjusted Odds Ratio (OR) and its 95% Confidence Interval (95% CI), using logistic regression models.</p> <p>Results</p> <p>The cumulative incidence of depression during follow-up in the cohort was 4.8%. Men who underestimated their body size had a high percentage of overweight and obesity (50.1% and 12.6%, respectively), whereas women who overestimated their body size had a high percentage of underweight (87.6%). The underestimation exhibited a negative association with the incidence of depression among women (OR: 0.72, 95% CI: 0.54 – 0.95), but this effect disappeared after adjusting for possible confounding variables. The proportion of participants who correctly perceived their body size was high (53.3%) and gross misperception was seldom found, with most cases selecting only one silhouette below (42.7%) or above (2.6%) their actual BMI.</p> <p>Conclusion</p> <p>We found no association between body image disturbance and subsequent depression in a cohort of university graduates in Spain.</p

A comparative study on the efficacy of 10% hypertonic saline and equal volume of 20% mannitol in the treatment of experimentally induced cerebral edema in adult rats

<p>Abstract</p> <p>Background</p> <p>Hypertonic saline and mannitol are commonly used in the treatment of cerebral edema and elevated intracranial pressure (ICP) at present. In this connection, 10% hypertonic saline (HS) alleviates cerebral edema more effectively than the equal volume of 20% mannitol. However, the exact underlying mechanism for this remains obscure. This study aimed to explore the possible mechanism whereby 10% hypertonic saline can ameliorate cerebral edema more effectively than mannitol.</p> <p>Results</p> <p>Adult male Sprague-Dawley (SD) rats were subjected to permanent right-sided middle cerebral artery occlusion (MCAO) and treated with a continuous intravenous infusion of 10% HS, 20% mannitol or D-[1-³H(N)]-mannitol. Brain water content (BWC) as analyzed by wet-to-dry ratios in the ischemic hemisphere of SD rats decreased more significantly after 10% HS treatment compared with 20% mannitol. Concentration of serum Na⁺and plasma crystal osmotic pressure of the 10% HS group at 2, 6, 12 and 18 h following permanent MCAO increased significantly when compared with 20% mannitol treated group. Moreover, there was negative correlation between the BWC of the ipsilateral ischemic hemisphere and concentration of serum Na⁺, plasma crystal osmotic pressure and difference value of concentration of serum Na⁺and concentration of brain Na⁺in ipsilateral ischemic hemisphere in the 10% HS group at the various time points after MCAO. A remarkable finding was the progressive accumulation of mannitol in the ischemic brain tissue.</p> <p>Conclusions</p> <p>We conclude that 10% HS is more effective in alleviating cerebral edema than the equal volume of 20% mannitol. This is because 10% HS contributes to establish a higher osmotic gradient across BBB and, furthermore, the progressive accumulation of mannitol in the ischemic brain tissue counteracts its therapeutic efficacy on cerebral edema.</p

Tau Reduction Does Not Prevent Motor Deficits in Two Mouse Models of Parkinson's Disease

Many neurodegenerative diseases are increasing in prevalence and cannot be prevented or cured. If they shared common pathogenic mechanisms, treatments targeting such mechanisms might be of benefit in multiple conditions. The tau protein has been implicated in the pathogenesis of diverse neurodegenerative disorders, including Alzheimer's disease (AD) and Parkinson's disease (PD). Tau reduction prevents cognitive deficits, behavioral abnormalities and other pathological changes in multiple AD mouse models. Here we examined whether tau reduction also prevents motor deficits and pathological alterations in two mouse models of PD, generated by unilateral striatal injection of 6-hydroxydopamine (6-OHDA) or transgene-mediated neuronal expression of human wildtype α-synuclein. Both models were evaluated on Tau+/+, Tau+/– and Tau–/– backgrounds in a variety of motor tests. Tau reduction did not prevent motor deficits caused by 6-OHDA and slightly worsened one of them. Tau reduction also did not prevent 6-OHDA-induced loss of dopaminergic terminals in the striatum. Similarly, tau reduction did not prevent motor deficits in α-synuclein transgenic mice. Our results suggest that tau has distinct roles in the pathogeneses of AD and PD and that tau reduction may not be of benefit in the latter condition