Formal Definitions of Unbounded Evolution and Innovation Reveal Universal Mechanisms for Open-Ended Evolution in Dynamical Systems

Open-ended evolution (OEE) is relevant to a variety of biological, artificial and technological systems, but has been challenging to reproduce in silico. Most theoretical efforts focus on key aspects of open-ended evolution as it appears in biology. We recast the problem as a more general one in dynamical systems theory, providing simple criteria for open-ended evolution based on two hallmark features: unbounded evolution and innovation. We define unbounded evolution as patterns that are non-repeating within the expected Poincare recurrence time of an equivalent isolated system, and innovation as trajectories not observed in isolated systems. As a case study, we implement novel variants of cellular automata (CA) in which the update rules are allowed to vary with time in three alternative ways. Each is capable of generating conditions for open-ended evolution, but vary in their ability to do so. We find that state-dependent dynamics, widely regarded as a hallmark of life, statistically out-performs other candidate mechanisms, and is the only mechanism to produce open-ended evolution in a scalable manner, essential to the notion of ongoing evolution. This analysis suggests a new framework for unifying mechanisms for generating OEE with features distinctive to life and its artifacts, with broad applicability to biological and artificial systems.Comment: Main document: 17 pages, Supplement: 21 pages Presented at OEE2: The Second Workshop on Open-Ended Evolution, 15th International Conference on the Synthesis and Simulation of Living Systems (ALIFE XV), Canc\'un, Mexico, 4-8 July 2016 (http://www.tim-taylor.com/oee2/

The urban-rural divide in complementary and alternative medicine use: A longitudinal study of 10,638 women

Background: Research has identified women in rural and remote areas as higher users of complementary and alternative medicine (CAM) practitioners than their urban counterparts. However, we currently know little about what influences women's CAM consumption across the urban/rural divide. This paper analyses 10,638 women's CAM use across urban and rural Australia.Methods: Data for this research comes from Survey 5 of the Australian Longitudinal Study on Women's Health conducted in 2007. The participants were aged 56-61years. The health status and health service use of CAM users and non-users were compared using chi-square tests for categorical variables and t-tests for continuous variables.Results: Women who consulted a CAM practitioner varied significantly by place of residence: 28%, 32% and 30% for urban, rural and remote areas respectively (P < .005). CAM users tended to be more dissatisfied with conventional care than CAM non-users, but this was consistent across the 3 areas of residence. CAM users have higher percentages of most symptoms but the only rural/urban differences were for severe tiredness, night sweats, depression and anxiety. For diagnosed diseases, CAM users have higher percentages of most diagnoses but only hypertension and skin cancer were statistically significantly higher for rural and remote but not urban women (P < .005).Conclusions: In contrast to some recent claims, our analysis suggests the lack of access to and/or patient dissatisfaction with conventional health practitioners may not play a central role in explaining higher use of CAM by women in rural and remote areas when compared to women in urban areas. © 2011 Adams et al; licensee BioMed Central Ltd

Fibrinogen is not elevated in the cerebrospinal fluid of patients with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Elevated plasma fibrinogen levels are a well known finding in acute infectious diseases, acute stroke and myocardial infarction. However its role in the cerebrospinal fluid (CSF) of acute and chronic central (CNS) and peripheral nervous system (PNS) diseases is unclear.</p> <p>Findings</p> <p>We analyzed CSF and plasma fibrinogen levels together with routine parameters in patients with multiple sclerosis (MS), acute inflammatory diseases of the CNS (bacterial and viral meningoencephalitis, BM and VM) and PNS (Guillain-Barré syndrome; GBS), as well as in non-inflammatory neurological controls (OND) in a total of 103 patients. Additionally, MS patients underwent cerebral MRI scans at time of lumbar puncture.</p> <p>CSF and plasma fibrinogen levels were significantly lower in patients with MS and OND patients as compared to patients with BM, VM and GBS. There was a close correlation between fibrinogen levels and albumin quotient (rho = 0.769, <it>p </it>< 0.001) which strongly suggests passive transfer of fibrinogen through the blood-CSF-barrier during acute inflammation. Hence, in MS, the prototype of chronic neuroinflammation, CSF fibrinogen levels were not elevated and could not be correlated to clinical and neuroradiological outcome parameters.</p> <p>Conclusions</p> <p>Although previous work has shown clear evidence of the involvement of fibrinogen in MS pathogenesis, this is not accompanied by increased fibrinogen in the CSF compartment.</p

Prolonged Fasting Reduces IGF-1/PKA to Promote Hematopoietic-Stem-Cell-Based Regeneration and Reverse Immunosuppression

Immune system defects are at the center of aging and a range of diseases. Here, we show that prolonged fasting reduces circulating IGF-1 levels and PKA activity in various cell populations, leading to signal transduction changes in long-term hematopoietic stem cells (LT-HSCs) and niche cells that promote stress resistance, self-renewal, and lineage-balanced regeneration. Multiple cycles of fasting abated the immunosuppression and mortality caused by chemotherapy and reversed age-dependent myeloid-bias in mice, in agreement with preliminary data on the protection of lymphocytes from chemotoxicity in fasting patients. The proregenerative effects of fasting on stem cells were recapitulated by deficiencies in either IGF-1 or PKA and blunted by exogenous IGF-1. These findings link the reduced levels of IGF-1 caused by fasting to PKA signaling and establish their crucial role in regulating hematopoietic stem cell protection, self-renewal, and regeneration

Using a formative simulated patient exercise for curriculum evaluation

BACKGROUND: It is not clear that teaching specific history taking, physical examination and patient teaching techniques to medical students results in durable behavioural changes. We used a quasi-experimental design that approximated a randomized double blinded trial to examine whether a Participatory Decision-Making (PDM) educational module taught in a clerkship improves performance on a Simulated Patient Exercise (SPE) in another clerkship, and how this is influenced by the time between training and assessment. METHODS: Third year medical students in an internal medicine clerkship were assessed on their use of PDM skills in an SPE conducted in the second week of the clerkship. The rotational structure of the third year clerkships formed a pseudo-randomized design where students had 1) completed the family practice clerkship containing a training module on PDM skills approximately four weeks prior to the SPE, 2) completed the family medicine clerkship and the training module approximately 12 weeks prior to the SPE or 3) had not completed the family medicine clerkship and the PDM training module at the time they were assessed via the SPE. RESULTS: Based on limited pilot data there were statistically significant differences between students who received PDM training approximately four weeks prior to the SPE and students who received training approximately 12 weeks prior to the SPE. Students who received training 12 weeks prior to the SPE performed better than those who received training four weeks prior to the SPE. In a second comparison students who received training four weeks prior to the SPE performed better than those who did not receive training but the differences narrowly missed statistical significance (P < 0.05). CONCLUSION: This pilot study demonstrated the feasibility of a methodology for conducting rigorous curricular evaluations using natural experiments based on the structure of clinical rotations. In addition, it provided preliminary data suggesting targeted educational interventions can result in marked improvements in the clinical skills spontaneously exhibited by physician trainees in a setting different from which the skills were taught

Global aspects of the space of 6D N = 1 supergravities

We perform a global analysis of the space of consistent 6D quantum gravity theories with N = 1 supersymmetry, including models with multiple tensor multiplets. We prove that for theories with fewer than T = 9 tensor multiplets, a finite number of distinct gauge groups and matter content are possible. We find infinite families of field combinations satisfying anomaly cancellation and admitting physical gauge kinetic terms for T > 8. We find an integral lattice associated with each apparently-consistent supergravity theory; this lattice is determined by the form of the anomaly polynomial. For models which can be realized in F-theory, this anomaly lattice is related to the intersection form on the base of the F-theory elliptic fibration. The condition that a supergravity model have an F-theory realization imposes constraints which can be expressed in terms of this lattice. The analysis of models which satisfy known low-energy consistency conditions and yet violate F-theory constraints suggests possible novel constraints on low-energy supergravity theories.Comment: 41 pages, 1 figur

Pericardial effusion as the only manifestation of infection with Francisella tularensis: a case report

<p>Abstract</p> <p>Introduction</p> <p><it>Francisella tularensis</it>, a facultative intracellular Gram-negative bacterium, has rarely been reported as an agent of pericarditis, generally described as a complication of tularemia sepsis. <it>F. tularensis </it>is a fastidious organism that grows poorly on standard culture media and diagnosis is usually based on serological tests. However, cross-reactions may occur. Western blotting allows the correct diagnosis.</p> <p>Case presentation</p> <p>A non-smoking 53-year-old woman was admitted to hospital with a large posterior pericardial effusion. Serological tests showed a seroconversion in antibody titers to <it>F. tularensis </it>(IgG titer = 400) and <it>Legionella pneumophila </it>(IgG titer = 512). <it>F. tularensis </it>was identified by Western immunoblotting following cross-adsorption. The patient reported close contact with rabbits 2 weeks prior to the beginning of symptoms of pericarditis.</p> <p>Conclusion</p> <p>We report a rare case of pericardial effusion as the only manifestation of infection by <it>F. tularensis</it>. The etiological diagnosis is based on serology. Western blotting and cross-adsorption allow differential diagnosis.</p

Lifshitz spacetimes from AdS null and cosmological solutions

We describe solutions of 10-dimensional supergravity comprising null deformations of $AdS_5\times S^5$ with a scalar field, which have $z=2$ Lifshitz symmetries. The bulk Lifshitz geometry in 3+1-dimensions arises by dimensional reduction of these solutions. The dual field theory in this case is a deformation of the N=4 super Yang-Mills theory. We discuss the holographic 2-point function of operators dual to bulk scalars. We further describe time-dependent (cosmological) solutions which have anisotropic Lifshitz scaling symmetries. We also discuss deformations of $AdS\times X$ in 11-dimensional supergravity, which are somewhat similar to the solutions above. In some cases here, we expect the field theory duals to be deformations of the Chern-Simons theories on M2-branes stacked at singularities.Comment: Latex, 29pgs, v3. references, minor clarifications (subsection on Lifshitz geometry seen by scalar probes) added, to appear in JHE

HAGE (DDX43) is a biomarker for poor prognosis and a predictor of chemotherapy response in breast cancer

Background: HAGE protein is a known immunogenic cancer-specific antigen. Methods: The biological, prognostic and predictive values of HAGE expression was studied using immunohistochemistry in three cohorts of patients with BC (n=2147): early primary (EP-BC; n=1676); primary oestrogen receptor-negative (PER-BC; n=275) treated with adjuvant anthracycline-combination therapies (Adjuvant-ACT); and primary locally advanced disease (PLA-BC) who received neo-adjuvant anthracycline-combination therapies (Neo-adjuvant-ACT; n=196). The relationship between HAGE expression and the tumour-infiltrating lymphocytes (TILs) in matched prechemotherapy and postchemotherapy samples were investigated. Results: Eight percent of patients with EP-BC exhibited high HAGE expression (HAGEþ) and was associated with aggressive clinico-pathological features (Ps<0.01). Furthermore, HAGEþexpression was associated with poor prognosis in both univariate and multivariate analysis (Ps<0.001). Patients with HAGE+ did not benefit from hormonal therapy in high-risk ER-positive disease. HAGE+ and TILs were found to be independent predictors for pathological complete response to neoadjuvant-ACT; P<0.001. A statistically significant loss of HAGE expression following neoadjuvant-ACT was found (P=0.000001), and progression-free survival was worse in those patients who had HAGE+ residual disease (P=0.0003). Conclusions: This is the first report to show HAGE to be a potential prognostic marker and a predictor of response to ACT in patients with BC