3,395 research outputs found
Pooling overdispersed binomial data to estimate event rate
<p>Abstract</p> <p>Background</p> <p>The beta-binomial model is one of the methods that can be used to validly combine event rates from overdispersed binomial data. Our objective is to provide a full description of this method and to update and broaden its applications in clinical and public health research.</p> <p>Methods</p> <p>We describe the statistical theories behind the beta-binomial model and the associated estimation methods. We supply information about statistical software that can provide beta-binomial estimations. Using a published example, we illustrate the application of the beta-binomial model when pooling overdispersed binomial data.</p> <p>Results</p> <p>In an example regarding the safety of oral antifungal treatments, we had 41 treatment arms with event rates varying from 0% to 13.89%. Using the beta-binomial model, we obtained a summary event rate of 3.44% with a standard error of 0.59%. The parameters of the beta-binomial model took the values of 1.24 for alpha and 34.73 for beta.</p> <p>Conclusion</p> <p>The beta-binomial model can provide a robust estimate for the summary event rate by pooling overdispersed binomial data from different studies. The explanation of the method and the demonstration of its applications should help researchers incorporate the beta-binomial method as they aggregate probabilities of events from heterogeneous studies.</p
Non-perturbative dynamics of hot non-Abelian gauge fields: beyond leading log approximation
Many aspects of high-temperature gauge theories, such as the electroweak
baryon number violation rate, color conductivity, and the hard gluon damping
rate, have previously been understood only at leading logarithmic order (that
is, neglecting effects suppressed only by an inverse logarithm of the gauge
coupling). We discuss how to systematically go beyond leading logarithmic order
in the analysis of physical quantities. Specifically, we extend to
next-to-leading-log order (NLLO) the simple leading-log effective theory due to
Bodeker that describes non-perturbative color physics in hot non-Abelian
plasmas. A suitable scaling analysis is used to show that no new operators
enter the effective theory at next-to-leading-log order. However, a NLLO
calculation of the color conductivity is required, and we report the resulting
value. Our NLLO result for the color conductivity can be trivially combined
with previous numerical work by G. Moore to yield a NLLO result for the hot
electroweak baryon number violation rate.Comment: 20 pages, 1 figur
Electrokinetic behavior of two touching inhomogeneous biological cells and colloidal particles: Effects of multipolar interactions
We present a theory to investigate electro-kinetic behavior, namely,
electrorotation and dielectrophoresis under alternating current (AC) applied
fields for a pair of touching inhomogeneous colloidal particles and biological
cells. These inhomogeneous particles are treated as graded ones with physically
motivated model dielectric and conductivity profiles. The mutual polarization
interaction between the particles yields a change in their respective dipole
moments, and hence in the AC electrokinetic spectra. The multipolar
interactions between polarized particles are accurately captured by the
multiple images method. In the point-dipole limit, our theory reproduces the
known results. We find that the multipolar interactions as well as the spatial
fluctuations inside the particles can affect the AC electrokinetic spectra
significantly.Comment: Revised version with minor changes: References added and discussion
extende
Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model
This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model.
Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded.
Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure).
Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan
Archaerhodopsin variants with enhanced voltage-sensitive fluorescence in mammalian and Caenorhabditis elegans neurons
Probing the neural circuit dynamics underlying behaviour would benefit greatly from improved genetically encoded voltage indicators. The proton pump Archaerhodopsin-3 (Arch), an optogenetic tool commonly used for neuronal inhibition, has been shown to emit voltage-sensitive fluorescence. Here we report two Arch variants with enhanced radiance (Archers) that in response to 655 nm light have 3–5 times increased fluorescence and 55–99 times reduced photocurrents compared with Arch WT. The most fluorescent variant, Archer1, has 25–40% fluorescence change in response to action potentials while using 9 times lower light intensity compared with other Arch-based voltage sensors. Archer1 is capable of wavelength-specific functionality as a voltage sensor under red light and as an inhibitory actuator under green light. As a proof-of-concept for the application of Arch-based sensors in vivo, we show fluorescence voltage sensing in behaving Caenorhabditis elegans. Archer1’s characteristics contribute to the goal of all-optical detection and modulation of activity in neuronal networks in vivo
Evolution in random fitness landscapes: the infinite sites model
We consider the evolution of an asexually reproducing population in an
uncorrelated random fitness landscape in the limit of infinite genome size,
which implies that each mutation generates a new fitness value drawn from a
probability distribution . This is the finite population version of
Kingman's house of cards model [J.F.C. Kingman, \textit{J. Appl. Probab.}
\textbf{15}, 1 (1978)]. In contrast to Kingman's work, the focus here is on
unbounded distributions which lead to an indefinite growth of the
population fitness. The model is solved analytically in the limit of infinite
population size and simulated numerically for finite . When
the genome-wide mutation probability is small, the long time behavior of
the model reduces to a point process of fixation events, which is referred to
as a \textit{diluted record process} (DRP). The DRP is similar to the standard
record process except that a new record candidate (a number that exceeds all
previous entries in the sequence) is accepted only with a certain probability
that depends on the values of the current record and the candidate. We develop
a systematic analytic approximation scheme for the DRP. At finite the
fitness frequency distribution of the population decomposes into a stationary
part due to mutations and a traveling wave component due to selection, which is
shown to imply a reduction of the mean fitness by a factor of compared to
the limit.Comment: Dedicated to Thomas Nattermann on the occasion of his 60th birthday.
Submitted to JSTAT. Error in Section 3.2 was correcte
Corrections to the Electroweak Effective Action at Finite Temperature
We calculate contributions to the finite temperature effective action for the
electroweak phase transition (EWPT) at \O(g^4), {\it i.e.} at second order in
(g^2 T/\M) and all orders in (g^2 T^2/\M^2). This requires plasma-mass
corrections in the calculation of the effective potential, inclusion of the
``lollipop'' diagram, and an estimate of derivative corrections. We find the
EWPT remains too weakly first-order to drive baryogenesis. We calculate some
one loop kinetic energy corrections using both functional and diagrammatic
methods; these may be important for saddlepoint configurations such as the
bounce or sphaleron.Comment: LaTeX, 6 figures available by email, CALT-68-1795, HUTP-92-A027,
EFI-92-2
Detecting the direction of a signal on high-dimensional spheres: Non-null and Le Cam optimality results
We consider one of the most important problems in directional statistics,
namely the problem of testing the null hypothesis that the spike direction
of a Fisher-von Mises-Langevin distribution on the -dimensional
unit hypersphere is equal to a given direction . After a reduction
through invariance arguments, we derive local asymptotic normality (LAN)
results in a general high-dimensional framework where the dimension goes
to infinity at an arbitrary rate with the sample size , and where the
concentration behaves in a completely free way with , which
offers a spectrum of problems ranging from arbitrarily easy to arbitrarily
challenging ones. We identify various asymptotic regimes, depending on the
convergence/divergence properties of , that yield different
contiguity rates and different limiting experiments. In each regime, we derive
Le Cam optimal tests under specified and we compute, from the Le Cam
third lemma, asymptotic powers of the classical Watson test under contiguous
alternatives. We further establish LAN results with respect to both spike
direction and concentration, which allows us to discuss optimality also under
unspecified . To investigate the non-null behavior of the Watson test
outside the parametric framework above, we derive its local asymptotic powers
through martingale CLTs in the broader, semiparametric, model of rotationally
symmetric distributions. A Monte Carlo study shows that the finite-sample
behaviors of the various tests remarkably agree with our asymptotic results.Comment: 47 pages, 4 figure
Chaos in an Exact Relativistic 3-body Self-Gravitating System
We consider the problem of three body motion for a relativistic
one-dimensional self-gravitating system. After describing the canonical
decomposition of the action, we find an exact expression for the 3-body
Hamiltonian, implicitly determined in terms of the four coordinate and momentum
degrees of freedom in the system. Non-relativistically these degrees of freedom
can be rewritten in terms of a single particle moving in a two-dimensional
hexagonal well. We find the exact relativistic generalization of this
potential, along with its post-Newtonian approximation. We then specialize to
the equal mass case and numerically solve the equations of motion that follow
from the Hamiltonian. Working in hexagonal-well coordinates, we obtaining
orbits in both the hexagonal and 3-body representations of the system, and plot
the Poincare sections as a function of the relativistic energy parameter . We find two broad categories of periodic and quasi-periodic motions that we
refer to as the annulus and pretzel patterns, as well as a set of chaotic
motions that appear in the region of phase-space between these two types.
Despite the high degree of non-linearity in the relativistic system, we find
that the the global structure of its phase space remains qualitatively the same
as its non-relativisitic counterpart for all values of that we could
study. However the relativistic system has a weaker symmetry and so its
Poincare section develops an asymmetric distortion that increases with
increasing . For the post-Newtonian system we find that it experiences a
KAM breakdown for : above which the near integrable regions
degenerate into chaos.Comment: latex, 65 pages, 36 figures, high-resolution figures available upon
reques
Drug Adverse Event Detection in Health Plan Data Using the Gamma Poisson Shrinker and Comparison to the Tree-based Scan Statistic
Background: Drug adverse event (AE) signal detection using the Gamma Poisson Shrinker (GPS) is commonly applied in spontaneous reporting. AE signal detection using large observational health plan databases can expand medication safety surveillance. Methods: Using data from nine health plans, we conducted a pilot study to evaluate the implementation and findings of the GPS approach for two antifungal drugs, terbinafine and itraconazole, and two diabetes drugs, pioglitazone and rosiglitazone. We evaluated 1676 diagnosis codes grouped into 183 different clinical concepts and four levels of granularity. Several signaling thresholds were assessed. GPS results were compared to findings from a companion study using the identical analytic dataset but an alternative statistical method—the tree-based scan statistic (TreeScan). Results: We identified 71 statistical signals across two signaling thresholds and two methods, including closely-related signals of overlapping diagnosis definitions. Initial review found that most signals represented known adverse drug reactions or confounding. About 31% of signals met the highest signaling threshold. Conclusions: The GPS method was successfully applied to observational health plan data in a distributed data environment as a drug safety data mining method. There was substantial concordance between the GPS and TreeScan approaches. Key method implementation decisions relate to defining exposures and outcomes and informed choice of signaling thresholds
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