The Effect of Mutators on Adaptability in Time-Varying Fitness Landscapes

This Letter studies the quasispecies dynamics of a population capable of genetic repair evolving on a time-dependent fitness landscape. We develop a model that considers an asexual population of single-stranded, conservatively replicating genomes, whose only source of genetic variation is due to copying errors during replication. We consider a time-dependent, single-fitness-peak landscape where the master sequence changes by a single point mutation every time $\tau$. We are able to analytically solve for the evolutionary dynamics of the population in the point-mutation limit. In particular, our model provides an analytical expression for the fraction of mutators in the dynamic fitness landscape that agrees well with results from stochastic simulations.Comment: 4 pages, 3 figure

Effectiveness of continence promotion for older women via community organisations: A cluster randomised trial

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 3.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/3.0/Objectives: The primary objective of this cluster randomised controlled trial was to compare the effectiveness of the three experimental continence promotion interventions against a control intervention on urinary symptom improvement in older women with untreated incontinence recruited from community organisations. A second objective was to determine whether changes in incontinence-related knowledge and new uptake of risk-modifying behaviours explain these improvements. Setting: 71 community organisations across the UK. Participants: 259 women aged 60 years and older with untreated incontinence entered the trial; 88% completed the 3-month follow-up. Interventions: The three active interventions consisted of a single 60 min group workshop on (1) continence education (20 clusters, 64 women); (2) evidence-based self-management (17 clusters, 70 women); or (3) combined continence education and self-management (17 clusters, 61 women). The control intervention was a single 60 min educational group workshop on memory loss, polypharmacy and osteoporosis (17 clusters, 64 women). Primary and secondary outcome measures: The primary outcome was self-reported improvement in incontinence 3 months postintervention at the level of the individual. The secondary outcome was change in the International Consultation on Incontinence Questionnaire (ICIQ) from baseline to 3-month follow-up. Changes in incontinence-related knowledge and behaviours were also assessed. Results: The highest rate of urinary symptom improvement occurred in the combined intervention group (66% vs 11% of the control group, prevalence difference 55%, 95% CI 43% to 67%, intracluster correlation 0). 30% versus 6% of participants reported significant improvement respectively (prevalence difference 23%, 95% CI 10% to 36%, intracluster correlation 0). The number-needed-to-treat was 2 to achieve any improvement in incontinence symptoms, and 5 to attain significant improvement. Compared to controls, participants in the combined intervention reported an adjusted mean 2.05 point (95% CI 0.87 to 3.24) greater improvement on the ICIQ from baseline to 3-month follow-up. Changes in knowledge and self-reported risk-reduction behaviours paralleled rates of improvement in all intervention arms. Conclusions: Continence education combined with evidence-based self-management improves symptoms of incontinence among untreated older women. Community organisations represent an untapped vector for delivering effective continence promotion interventions.Canadian Institutes of Health Research – Institute on Aging and the Economic and Social Research Council (UK

Review of Engaging Education: Developing Emotional Literacy, Equity and Co-education. Brian Matthews. (Book Review)

The book is only about a fraction of its title Engaging Education. His section on ‘engaging the emotions’ sums this up: whereas the book is largely about engaging the emotions positively, the definition of ‘Engaging’ is more far reaching: “that pupils should be involved in their learning; be active and absorbed and not just passive recipients of a set curriculum. Additionally, they should feel engaged in the processes of education and have some input into creating their own agendas for learning” (p.2). Exploring the full impact of this statement across the curriculum really needs a different book

PHENIX Highlights

Recent highlights of measurements by the PHENIX experiment at RHIC are presented.Comment: 8 pages, 9 figures. Talk at Quark Matter 200

Recent results in relativistic heavy ion collisions: from ``a new state of matter'' to "the perfect fluid"

Experimental Physics with Relativistic Heavy Ions dates from 1992 when a beam of 197Au of energy greater than 10A GeV/c first became available at the Alternating Gradient Synchrotron (AGS) at Brookhaven National Laboratory (BNL) soon followed in 1994 by a 208Pb beam of 158A GeV/c at the Super Proton Synchrotron (SPS) at CERN (European Center for Nuclear Research). Previous pioneering measurements at the Berkeley Bevalac in the late 1970's and early 1980's were at much lower bombarding energies (~ 1 A GeV/c) where nuclear breakup rather than particle production is the dominant inelastic process in A+A collisions. More recently, starting in 2000, the Relativistic Heavy Ion Collider (RHIC) at BNL has produced head-on collisions of two 100A GeV beams of fully stripped Au ions, corresponding to nucleon-nucleon center-of-mass energy, sqrt(sNN)=200 GeV, total c.m. energy 200A GeV. The objective of this research program is to produce nuclear matter with extreme density and temperature, possibly resulting in a state of matter where the quarks and gluons normally confined inside individual nucleons (r < 1 fm) are free to act over distances an order of magnitude larger. Progress from the period 1992 to the present will be reviewed, with reference to previous results from light ion and proton-proton collisions where appropriate. Emphasis will be placed on the measurements which formed the basis for the announcements by the two major laboratories: "A new state of matter", by CERN on Feb 10, 2000 and "The perfect fluid", by BNL on April 19, 2005.Comment: 62 pages, 39 figures. Review article published in Reports on Progress in Physics on June 23, 2006. In this published version, mistakes, typographical errors, and citations have been corrected and a subsection has been adde

Asexual and sexual replication in sporulating organisms

This paper develops models describing asexual and sexual replication in sporulating organisms. Replication via sporulation is the replication strategy for all multicellular life, and may even be observed in unicellular life (such as with budding yeast). We consider diploid populations replicating via one of two possible sporulation mechanisms: (1) Asexual sporulation, whereby adult organisms produce single-celled diploid spores that grow into adults themselves. (2) Sexual sporulation, whereby adult organisms produce single-celled diploid spores that divide into haploid gametes. The haploid gametes enter a haploid "pool", where they may recombine with other haploids to form a diploid spore that then grows into an adult. We consider a haploid fusion rate given by second-order reaction kinetics. We work with a simplified model where the diploid genome consists of only two chromosomes, each of which may be rendered defective with a single point mutation of the wild-type. We find that the asexual strategy is favored when the rate of spore production is high compared to the characteristic growth rate from a spore to a reproducing adult. Conversely, the sexual strategy is favored when the rate of spore production is low compared to the characteristic growth rate from a spore to a reproducing adult. As the characteristic growth time increases, or as the population density increases, the critical ratio of spore production rate to organism growth rate at which the asexual strategy overtakes the sexual one is pushed to higher values. Therefore, the results of this model suggest that, for complex multicellular organisms, sexual replication is favored at high population densities, and low growth and sporulation rates.Comment: 8 pages, 5 figures, to be submitted to Journal of Theoretical Biology, figures not included in this submissio

Nearly optimal solutions for the Chow Parameters Problem and low-weight approximation of halfspaces

The \emph{Chow parameters} of a Boolean function $f: \{-1,1\}^n \to \{-1,1\}$ are its $n+1$ degree-0 and degree-1 Fourier coefficients. It has been known since 1961 (Chow, Tannenbaum) that the (exact values of the) Chow parameters of any linear threshold function $f$ uniquely specify $f$ within the space of all Boolean functions, but until recently (O'Donnell and Servedio) nothing was known about efficient algorithms for \emph{reconstructing} $f$ (exactly or approximately) from exact or approximate values of its Chow parameters. We refer to this reconstruction problem as the \emph{Chow Parameters Problem.} Our main result is a new algorithm for the Chow Parameters Problem which, given (sufficiently accurate approximations to) the Chow parameters of any linear threshold function $f$, runs in time \tilde{O}(n^2)\cdot (1/\eps)^{O(\log^2(1/\eps))} and with high probability outputs a representation of an LTF $f'$ that is \eps-close to $f$. The only previous algorithm (O'Donnell and Servedio) had running time \poly(n) \cdot 2^{2^{\tilde{O}(1/\eps^2)}}. As a byproduct of our approach, we show that for any linear threshold function $f$ over $\{-1,1\}^n$, there is a linear threshold function $f'$ which is \eps-close to $f$ and has all weights that are integers at most \sqrt{n} \cdot (1/\eps)^{O(\log^2(1/\eps))}. This significantly improves the best previous result of Diakonikolas and Servedio which gave a \poly(n) \cdot 2^{\tilde{O}(1/\eps^{2/3})} weight bound, and is close to the known lower bound of $\max\{\sqrt{n},$ (1/\eps)^{\Omega(\log \log (1/\eps))}\} (Goldberg, Servedio). Our techniques also yield improved algorithms for related problems in learning theory

Future directions for the management of pain in osteoarthritis.

Osteoarthritis (OA) is the predominant form of arthritis worldwide, resulting in a high degree of functional impairment and reduced quality of life owing to chronic pain. To date, there are no treatments that are known to modify disease progression of OA in the long term. Current treatments are largely based on the modulation of pain, including NSAIDs, opiates and, more recently, centrally acting pharmacotherapies to avert pain. This review will focus on the rationale for new avenues in pain modulation, including inhibition with anti-NGF antibodies and centrally acting analgesics. The authors also consider the potential for structure modification in cartilage/bone using growth factors and stem cell therapies. The possible mismatch between structural change and pain perception will also be discussed, introducing recent techniques that may assist in improved patient phenotyping of pain subsets in OA. Such developments could help further stratify subgroups and treatments for people with OA in future

Bulk Filling Branes and the Baryon Density in AdS/QCD with gravity back-reaction

We consider the gravity back reaction on the metric due to the baryon density in effective ads/qcd model by reconsidering the role of the charged AdS black hole. Previously it has been known that the U(1) charge is dual to the R-charge. Here we point out that if we consider the case where $AdS_5$ is completely filled with $N_f$ flavor branes, the gravity back reaction produces charged AdS black hole where the effect of charge on the metric is proportional to $N_f/N_c$. As a consequence, phase diagram changes qualitatively if we allow $N_f/N_c$ finite: it closes at the finite density unlike the probe brane embedding approach. Another issue we discuss here is the question whether there is any chemical potential dependence in the confining phase. We consider this problem in the hard wall model with baryon charge. We conclude that there is a non-trivial dependence on the chemical potential in this case also.Comment: 17 pages 3x2 figures, v2: references added;v3 published version, title change and reference adde