Evolution of cooperation driven by zealots

Recent experimental results with humans involved in social dilemma games suggest that cooperation may be a contagious phenomenon and that the selection pressure operating on evolutionary dynamics (i.e., mimicry) is relatively weak. I propose an evolutionary dynamics model that links these experimental findings and evolution of cooperation. By assuming a small fraction of (imperfect) zealous cooperators, I show that a large fraction of cooperation emerges in evolutionary dynamics of social dilemma games. Even if defection is more lucrative than cooperation for most individuals, they often mimic cooperation of fellows unless the selection pressure is very strong. Then, zealous cooperators can transform the population to be even fully cooperative under standard evolutionary dynamics.Comment: 5 figure

General practitioners’ perspectives on campaigns to promote rapid help-seeking behaviour at the onset of rheumatoid arthritis

Objective. To explore general practitioners’ (GPs’ ) perspectives on public health campaigns to encourage people with the early symptoms of rheumatoid arthritis (RA) to seek medical help rapidly. Design. Nineteen GPs participated in four semistructured focus groups. Focus groups were audio-recorded, transcribed verbatim, and analysed using thematic analysis. Results. GPs recognised the need for the early treatment of RA and identified that facilitating appropriate access to care was important. However, not all held the view that a delay in help seeking was a clinically significant issue. Furthermore, many were concerned that the early symptoms of RA were often non-specific, and that current knowledge about the nature of symptoms at disease onset was inadequate to inform the content of a help-seeking campaign. They argued that a campaign might not be able to specifically target those who need to present urgently. Poorly designed campaigns were suggested to have a negative impact on GPs’ workloads, and would “clog up” the referral pathway for genuine cases of RA. Conclusions. GPs were supportive of strategies to improve access to Rheumatological care and increase public awareness of RA symptoms. However, they have identified important issues that need to be considered in developing a public health campaign that forms part of an overall strategy to reduce time to treatment for patients with new onset RA. This study highlights the value of gaining GPs’ perspectives before launching health promotion campaigns

One-carbon metabolism in cancer

Cells require one-carbon units for nucleotide synthesis, methylation and reductive metabolism, and these pathways support the high proliferative rate of cancer cells. As such, anti-folates, drugs that target one-carbon metabolism, have long been used in the treatment of cancer. Amino acids, such as serine are a major one-carbon source, and cancer cells are particularly susceptible to deprivation of one-carbon units by serine restriction or inhibition of de novo serine synthesis. Recent work has also begun to decipher the specific pathways and sub-cellular compartments that are important for one-carbon metabolism in cancer cells. In this review we summarise the historical understanding of one-carbon metabolism in cancer, describe the recent findings regarding the generation and usage of one-carbon units and explore possible future therapeutics that could exploit the dependency of cancer cells on one-carbon metabolism

Does Medical Students' Preference of Test Format (Computer-based vs. Paper-based) have an Influence on Performance?

<p>Abstract</p> <p>Background</p> <p>Computer-based examinations (CBE) ensure higher efficiency with respect to producibility and assessment compared to paper-based examinations (PBE). However, students often have objections against CBE and are afraid of getting poorer results in a CBE.</p> <p>The aims of this study were (1) to assess the readiness and the objections of students to a CBE vs. PBE (2) to examine the acceptance and satisfaction with the CBE on a voluntary basis, and (3) to compare the results of the examinations, which were conducted in different formats.</p> <p>Methods</p> <p>Fifth year medical students were introduced to an examination-player and were free to choose their format for the test. The reason behind the choice of the format as well as the satisfaction with the choice was evaluated after the test with a questionnaire. Additionally, the expected and achieved examination results were measured.</p> <p>Results</p> <p>Out of 98 students, 36 voluntarily chose a CBE (37%), 62 students chose a PBE (63%). Both groups did not differ concerning sex, computer-experience, their achieved examination results of the test, and their satisfaction with the chosen format. Reasons for the students' objections against CBE include the possibility for outlines or written notices, a better overview, additional noise from the keyboard or missing habits normally present in a paper based exam. The students with the CBE tended to judge their examination to be more clear and understandable. Moreover, they saw their results to be independent of the format.</p> <p>Conclusions</p> <p>Voluntary computer-based examinations lead to equal test scores compared to a paper-based format.</p

Loss of Consciousness at Onset of Aneurysmal Subarachnoid Hemorrhage is Associated with Functional Outcomes in Good-Grade Patients

BACKGROUND Transient loss of consciousness (LOC) is one of the most common presentations of aneurysmal subarachnoid hemorrhage (SAH) and may be an indicator of early brain injury. The aim of the current study was to examine the association of LOC to functional outcomes in patients with good-grade SAH. METHODS We searched the Subarachnoid Hemorrhage International Trialists Repository for patients that presented with LOC at ictus of SAH. A propensity score analysis was performed on good-grade patients (defined as World Federation of Neurosurgical Societies grades 1-3) to balance selected covariates between those with and without LOC. Primary outcome was Glasgow Outcome Score (GOS) at 3 months (with poor outcome defined as GOS of 1-3). Secondary outcomes were delayed cerebral ischemia (DCI), rebleed, length of hospital stay, and time to death. RESULTS A propensity score-matching algorithm identified 337 patients (168 with LOC at ictus, and 168 without). The proportion of patients with poor functional outcome at 3-months was significantly higher in those who had LOC at ictus compared to the matched cohort without LOC (30% vs. 19%; P = 0.02). There was a non-significant trend toward higher mortality in patients with LOC (19% vs. 13%; P = 0.14). There were no differences in the secondary outcomes. CONCLUSIONS LOC of at ictus of SAH is associated with higher rate of unfavorable functional outcomes but not mortality, DCI or rebleed in good-grade SAH patients. Future studies should further investigate the putative mechanisms by which LOC mediates early brain injury in SAH

Therapeutic Effect of a Poly(ADP-Ribose) Polymerase-1 Inhibitor on Experimental Arthritis by Downregulating Inflammation and Th1 Response

Poly(ADP-ribose) polymerase-1 (PARP-1) synthesizes and transfers ADP ribose polymers to target proteins, and regulates DNA repair and genomic integrity maintenance. PARP-1 also plays a crucial role in the progression of the inflammatory response, and its inhibition confers protection in several models of inflammatory disorders. Here, we investigate the impact of a selective PARP-1 inhibitor in experimental arthritis. PARP-1 inhibition with 5-aminoisoquinolinone (AIQ) significantly reduces incidence and severity of established collagen-induced arthritis, completely abrogating joint swelling and destruction of cartilage and bone. The therapeutic effect of AIQ is associated with a striking reduction of the two deleterious components of the disease, i.e. the Th1-driven autoimmune and inflammatory responses. AIQ downregulates the production of various inflammatory cytokines and chemokines, decreases the antigen-specific Th1-cell expansion, and induces the production of the anti-inflammatory cytokine IL-10. Our results provide evidence of the contribution of PARP-1 to the progression of arthritis and identify this protein as a potential therapeutic target for the treatment of rheumatoid arthritis