Widening Participation in Golf: Barriers to Participation and GolfMark

This research was commissioned by the EGU and R&A in 2010. The aims of the research project were threefold: 1) To review the academic literature on barriers to participation in sport, especially golf; 2) To survey clubs, members and nomadic golfers to describe their perceptions of GolfMark and the issues it intends to address; 3) To gather in-depth data from a range of golf clubs to help understand how different club cultures may lead to the exclusion of underrepresented demographic groups

Individual crypt genetic heterogeneity and the origin of metaplastic glandular epithelium in human Barrett’s oesophagus

OBJECTIVES: Current models of clonal expansion in human Barrett's oesophagus are based upon heterogenous, flow-purified biopsy analysis taken at multiple segment levels. Detection of identical mutation fingerprints from these biopsy samples led to the proposal that a mutated clone with a selective advantage can clonally expand to fill an entire Barrett's segment at the expense of competing clones (selective sweep to fixation model). We aimed to assess clonality at a much higher resolution by microdissecting and genetically analysing individual crypts. The histogenesis of Barrett's metaplasia and neo-squamous islands has never been demonstrated. We investigated the oesophageal gland squamous ducts as the source of both epithelial sub-types. METHODS: Individual crypts across Barrett's biopsy and oesophagectomy blocks were dissected. Determination of tumour suppressor gene loss of heterozygosity patterns, p16 and p53 point mutations were carried out on a crypt-by-crypt basis. Cases of contiguous neo-squamous islands and columnar metaplasia with oesophageal squamous ducts were identified. Tissues were isolated by laser capture microdissection and genetically analysed. RESULTS: Individual crypt dissection revealed mutation patterns that were masked in whole biopsy analysis. Dissection across oesophagectomy specimens demonstrated marked clonal heterogeneity, with multiple independent clones present. We identified a p16 point mutation arising in the squamous epithelium of the oesophageal gland duct, which was also present in a contiguous metaplastic crypt, whereas neo-squamous islands arising from squamous ducts were wild-type with respect to surrounding Barrett's dysplasia. CONCLUSIONS: By studying clonality at the crypt level we demonstrate that Barrett's heterogeneity arises from multiple independent clones, in contrast to the selective sweep to fixation model of clonal expansion previously described. We suggest that the squamous gland ducts situated throughout the oesophagus are the source of a progenitor cell that may be susceptible to gene mutation resulting in conversion to Barrett's metaplastic epithelium. Additionally, these data suggest that wild-type ducts may be the source of neo-squamous islands

The descriptive content of names as predicate modifiers

In this paper I argue that descriptive content associated with a proper name can serve as a truth-conditionally relevant adjunct and be an additional contribution of the name to the truth-conditions. Definite descriptions the so-and-so associated by speakers with a proper name can be used as qualifying prepositional phrases as so-and-so, so sentences containing a proper name NN is doing something could be understood as NN is doing something as NN (which means as so-and-so). Used as an adjunct, the descriptive content of a proper name expresses the additional circumstances of an action (a manner, reason, goal, time or purpose) and constitute a part of a predicate. I argue that qualifying prepositional phrases should be analyzed as predicate modifiers and propose a formal representation of modified predicates. The additional truth-conditional relevance of the descriptive content of a proper name helps to explain the phenomenon of the substitution failure of coreferential names in simple sentences

Canalization effect in the coagulation cascade and the interindividual variability of oral anticoagulant response. a simulation Study

<p>Abstract</p> <p>Background</p> <p>Increasing the predictability and reducing the rate of side effects of oral anticoagulant treatment (OAT) requires further clarification of the cause of about 50% of the interindividual variability of OAT response that is currently unaccounted for. We explore numerically the hypothesis that the effect of the interindividual expression variability of coagulation proteins, which does not usually result in a variability of the coagulation times in untreated subjects, is unmasked by OAT.</p> <p>Results</p> <p>We developed a stochastic variant of the Hockin-Mann model of the tissue factor coagulation pathway, using literature data for the variability of coagulation protein levels in the blood of normal subjects. We simulated <it>in vitro </it>coagulation and estimated the Prothrombin Time and the INR across a model population. In a model of untreated subjects a "canalization effect" can be observed in that a coefficient of variation of up to 33% of each protein level results in a simulated INR of 1 with a clinically irrelevant dispersion of 0.12. When the mean and the standard deviation of vitamin-K dependent protein levels were reduced by 80%, corresponding to the usual Warfarin treatment intensity, the simulated INR was 2.98 ± 0.48, a clinically relevant dispersion, corresponding to a reduction of the canalization effect.</p> <p>Then we combined the Hockin-Mann stochastic model with our previously published model of population response to Warfarin, that takes into account the genetical and the phenotypical variability of Warfarin pharmacokinetics and pharmacodynamics. We used the combined model to evaluate the coagulation protein variability effect on the variability of the Warfarin dose required to reach an INR target of 2.5. The dose variance when removing the coagulation protein variability was 30% lower. The dose was mostly related to the pretreatment levels of factors VII, X, and the tissue factor pathway inhibitor (TFPI).</p> <p>Conclusions</p> <p>It may be worth exploring in experimental studies whether the pretreatment levels of coagulation proteins, in particular VII, X and TFPI, are predictors of the individual warfarin dose, even though, maybe due to a canalization-type effect, their effect on the INR variance in untreated subjects appears low.</p

First bounds on the very high energy gamma-ray emission from Arp 220

Using the Major Atmospheric Gamma Imaging Cherenkov Telescope (MAGIC), we have observed the nearest ultra-luminous infrared galaxy Arp 220 for about 15 hours. No significant signal was detected within the dedicated amount of observation time. The first upper limits to the very high energy $\gamma$-ray flux of Arp 220 are herein reported and compared with theoretical expectations.Comment: Accepted for publication in Ap

Constraints on the steady and pulsed very high energy gamma-ray emission from observations of PSR B1951+32/CTB 80 with the MAGIC Telescope

We report on very high energy gamma-observations with the MAGIC Telescope of the pulsar PSR B1951+32 and its associated nebula, CTB 80. Our data constrain the cutoff energy of the pulsar to be less than 32 GeV, assuming the pulsed gamma-ray emission to be exponentially cut off. The upper limit on the flux of pulsed gamma-ray emission above 75 GeV is 4.3*10^-11 photons cm^-2 sec^-1, and the upper limit on the flux of steady emission above 140 GeV is 1.5*10^-11 photons cm^-2 sec^-1. We discuss our results in the framework of recent model predictions and other studies.Comment: 7 pages, 7 figures, replaced with published versio

MAGIC upper limits on the very high energy emission from GRBs

The fast repositioning system of the MAGIC Telescope has allowed during its first data cycle, between 2005 and the beginning of year 2006, observing nine different GRBs as possible sources of very high energy gammas. These observations were triggered by alerts from Swift, HETE-II, and Integral; they started as fast as possible after the alerts and lasted for several minutes, with an energy threshold varying between 80 and 200 GeV, depending upon the zenith angle of the burst. No evidence for gamma signals was found, and upper limits for the flux were derived for all events, using the standard analysis chain of MAGIC. For the bursts with measured redshift, the upper limits are compatible with a power law extrapolation, when the intrinsic fluxes are evaluated taking into account the attenuation due to the scattering in the Metagalactic Radiation Field (MRF).Comment: 25 pages, 9 figures, final version accepted by ApJ. Changet title to "MAGIC upped limits on the VERY high energy emission from GRBs", re-organized chapter with description of observation, removed non necessaries figures, added plot of effective area depending on zenith angle, added an appendix explaining the upper limit calculation, added some reference

Discovery of Very High Energy γ\gamma-Rays from Markarian~180 Triggered by an Optical Outburst

The high-frequency-peaked BL Lacertae object Markarian~180 (Mrk~180) was observed to have an optical outburst in 2006 March, triggering a Target of Opportunity observation with the MAGIC telescope. The source was observed for 12.4 hr and very high energy $\gamma$-ray emission was detected with a significance of 5.5 $\sigma$. An integral flux above 200 GeV of $(2.3\pm0.7)\times10^{-11} {cm}^{-2} {s}^{-1}$ was measured, corresponding to 11% of the Crab Nebula flux. A rather soft spectrum with a photon index of $-3.3\pm0.7$ has been determined. No significant flux variation was found.Comment: Accepted by ApJ Letters, minor revision