983 research outputs found
Temporal trends in mode, site and stage of presentation with the introduction of colorectal cancer screening: a decade of experience from the West of Scotland
background:Â Â Population colorectal cancer screening programmes have been introduced to reduce cancer-specific mortality through the detection of early-stage disease. The present study aimed to examine the impact of screening introduction in the West of Scotland.
methods:Â Â Data on all patients with a diagnosis of colorectal cancer between January 2003 and December 2012 were extracted from a prospectively maintained regional audit database. Changes in mode, site and stage of presentation before, during and after screening introduction were examined.
results:  In a population of 2.4 million, over a 10-year period, 14 487 incident cases of colorectal cancer were noted. Of these, 7827 (54%) were males and 7727 (53%) were socioeconomically deprived. In the postscreening era, 18% were diagnosed via the screening programme. There was a reduction in both emergency presentation (20% prescreening vs 13% postscreening, P0.001) and the proportion of rectal cancers (34% prescreening vs 31% pos-screening, P0.001) over the timeframe. Within non-metastatic disease, an increase in the proportion of stage I tumours at diagnosis was noted (17% prescreening vs 28% postscreening, P0.001).
conclusions:Â Â Within non-metastatic disease, a shift towards earlier stage at diagnosis has accompanied the introduction of a national screening programme. Such a change should lead to improved outcomes in patients with colorectal cancer
Sharp transition towards shared vocabularies in multi-agent systems
What processes can explain how very large populations are able to converge on
the use of a particular word or grammatical construction without global
coordination? Answering this question helps to understand why new language
constructs usually propagate along an S-shaped curve with a rather sudden
transition towards global agreement. It also helps to analyze and design new
technologies that support or orchestrate self-organizing communication systems,
such as recent social tagging systems for the web. The article introduces and
studies a microscopic model of communicating autonomous agents performing
language games without any central control. We show that the system undergoes a
disorder/order transition, going trough a sharp symmetry breaking process to
reach a shared set of conventions. Before the transition, the system builds up
non-trivial scale-invariant correlations, for instance in the distribution of
competing synonyms, which display a Zipf-like law. These correlations make the
system ready for the transition towards shared conventions, which, observed on
the time-scale of collective behaviors, becomes sharper and sharper with system
size. This surprising result not only explains why human language can scale up
to very large populations but also suggests ways to optimize artificial
semiotic dynamics.Comment: 12 pages, 4 figure
Hofstadter butterflies of carbon nanotubes: Pseudofractality of the magnetoelectronic spectrum
The electronic spectrum of a two-dimensional square lattice in a
perpendicular magnetic field has become known as the Hofstadter butterfly
[Hofstadter, Phys. Rev. B 14, 2239 (1976).]. We have calculated
quasi-one-dimensional analogs of the Hofstadter butterfly for carbon nanotubes
(CNTs). For the case of single-wall CNTs, it is straightforward to implement
magnetic fields parallel to the tube axis by means of zone folding in the
graphene reciprocal lattice. We have also studied perpendicular magnetic fields
which, in contrast to the parallel case, lead to a much richer, pseudofractal
spectrum. Moreover, we have investigated magnetic fields piercing double-wall
CNTs and found strong signatures of interwall interaction in the resulting
Hofstadter butterfly spectrum, which can be understood with the help of a
minimal model. Ubiquitous to all perpendicular magnetic field spectra is the
presence of cusp catastrophes at specific values of energy and magnetic field.
Resolving the density of states along the tube circumference allows recognition
of the snake states already predicted for nonuniform magnetic fields in the
two-dimensional electron gas. An analytic model of the magnetic spectrum of
electrons on a cylindrical surface is used to explain some of the results.Comment: 14 pages, 12 figures update to published versio
A Crystal Structure of the Bifunctional Antibiotic Simocyclinone D8, Bound to DNA Gyrase
Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme. We report the crystal structure of the complex formed between the N-terminal domain of the Escherichia coli gyrase A subunit and simocyclinone D8, revealing two binding pockets that separately accommodate the aminocoumarin and polyketide moieties of the antibiotic. These are close to, but distinct from, the quinolone-binding site, consistent with our observations that several mutations in this region confer resistance to both agents. Biochemical studies show that the individual moieties of simocyclinone D8 are comparatively weak inhibitors of gyrase relative to the parent compound, but their combination generates a more potent inhibitor. Our results should facilitate the design of drug molecules that target these unexploited binding pockets
Calibration of optimal execution of financial transactions in the presence of transient market impact
Trading large volumes of a financial asset in order driven markets requires
the use of algorithmic execution dividing the volume in many transactions in
order to minimize costs due to market impact. A proper design of an optimal
execution strategy strongly depends on a careful modeling of market impact,
i.e. how the price reacts to trades. In this paper we consider a recently
introduced market impact model (Bouchaud et al., 2004), which has the property
of describing both the volume and the temporal dependence of price change due
to trading. We show how this model can be used to describe price impact also in
aggregated trade time or in real time. We then solve analytically and calibrate
with real data the optimal execution problem both for risk neutral and for risk
averse investors and we derive an efficient frontier of optimal execution. When
we include spread costs the problem must be solved numerically and we show that
the introduction of such costs regularizes the solution.Comment: 31 pages, 8 figure
THSim v3.2: The Talking Heads simulation tool
The field of language evolution and computation may benefit from using efficient and robust simulation tools that are based on widely exploited principles within the field. The tool presented in this paper is one that could fulfil such needs. The paper presents an overview of the tool -- THSim v3.2 -- and discusses some research questions that can be investigated with it
Bistability in Apoptosis by Receptor Clustering
Apoptosis is a highly regulated cell death mechanism involved in many
physiological processes. A key component of extrinsically activated apoptosis
is the death receptor Fas, which, on binding to its cognate ligand FasL,
oligomerize to form the death-inducing signaling complex. Motivated by recent
experimental data, we propose a mathematical model of death ligand-receptor
dynamics where FasL acts as a clustering agent for Fas, which form locally
stable signaling platforms through proximity-induced receptor interactions.
Significantly, the model exhibits hysteresis, providing an upstream mechanism
for bistability and robustness. At low receptor concentrations, the bistability
is contingent on the trimerism of FasL. Moreover, irreversible bistability,
representing a committed cell death decision, emerges at high concentrations,
which may be achieved through receptor pre-association or localization onto
membrane lipid rafts. Thus, our model provides a novel theory for these
observed biological phenomena within the unified context of bistability.
Importantly, as Fas interactions initiate the extrinsic apoptotic pathway, our
model also suggests a mechanism by which cells may function as bistable
life/death switches independently of any such dynamics in their downstream
components. Our results highlight the role of death receptors in deciding cell
fate and add to the signal processing capabilities attributed to receptor
clustering.Comment: Accepted by PLoS Comput Bio
Classical kinetic energy, quantum fluctuation terms and kinetic-energy functionals
We employ a recently formulated dequantization procedure to obtain an exact
expression for the kinetic energy which is applicable to all kinetic-energy
functionals. We express the kinetic energy of an N-electron system as the sum
of an N-electron classical kinetic energy and an N-electron purely quantum
kinetic energy arising from the quantum fluctuations that turn the classical
momentum into the quantum momentum. This leads to an interesting analogy with
Nelson's stochastic approach to quantum mechanics, which we use to conceptually
clarify the physical nature of part of the kinetic-energy functional in terms
of statistical fluctuations and in direct correspondence with Fisher
Information Theory. We show that the N-electron purely quantum kinetic energy
can be written as the sum of the (one-electron) Weizsacker term and an
(N-1)-electron kinetic correlation term. We further show that the Weizsacker
term results from local fluctuations while the kinetic correlation term results
from the nonlocal fluctuations. For one-electron orbitals (where kinetic
correlation is neglected) we obtain an exact (albeit impractical) expression
for the noninteracting kinetic energy as the sum of the classical kinetic
energy and the Weizsacker term. The classical kinetic energy is seen to be
explicitly dependent on the electron phase and this has implications for the
development of accurate orbital-free kinetic-energy functionals. Also, there is
a direct connection between the classical kinetic energy and the angular
momentum and, across a row of the periodic table, the classical kinetic energy
component of the noninteracting kinetic energy generally increases as Z
increases.Comment: 10 pages, 1 figure. To appear in Theor Chem Ac
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