2,569 research outputs found
Effect of Variable Selection Strategy on the Performance of Prognostic Models When Using Multiple Imputation
BACKGROUND: Variable selection is an important issue when developing
prognostic models. Missing data occur frequently in clinical research.
Multiple imputation is increasingly used to address the presence of
missing data in clinical research. The effect of different variable selection
strategies with multiply imputed data on the external performance of
derived prognostic models has not been well examined.
METHODS AND RESULTS: We used backward variable selection with
9 different ways to handle multiply imputed data in a derivation sample
to develop logistic regression models for predicting death within 1 year
of hospitalization with an acute myocardial infarction. We assessed
the prognostic accuracy of each derived model in a temporally distinct
validation sample. The derivation and validation samples consisted of
11524 patients hospitalized between 1999 and 2001 and 7889 patients
hospitalized between 2004 and 2005, respectively. We considered 41
candidate predictor variables. Missing data occurred frequently, with
only 13% of patients in the derivation sample and 31% of patients in the
validation sample having complete data. Regardless of the significance
level for variable selection, the prognostic model developed using only
the complete cases in the derivation sample had substantially worse
performance in the validation sample than did the models for which
variables were selected using the multiply imputed versions of the
derivation sample. The other 8 approaches to handling multiply imputed
data resulted in prognostic models with performance similar to one
another.
CONCLUSIONS: Ignoring missing data and using only subjects with
complete data can result in the derivation of prognostic models with poor
performance. Multiple imputation should be used to account for missing
data when developing prognostic models
Simple, Fast and Accurate Implementation of the Diffusion Approximation Algorithm for Stochastic Ion Channels with Multiple States
The phenomena that emerge from the interaction of the stochastic opening and
closing of ion channels (channel noise) with the non-linear neural dynamics are
essential to our understanding of the operation of the nervous system. The
effects that channel noise can have on neural dynamics are generally studied
using numerical simulations of stochastic models. Algorithms based on discrete
Markov Chains (MC) seem to be the most reliable and trustworthy, but even
optimized algorithms come with a non-negligible computational cost. Diffusion
Approximation (DA) methods use Stochastic Differential Equations (SDE) to
approximate the behavior of a number of MCs, considerably speeding up
simulation times. However, model comparisons have suggested that DA methods did
not lead to the same results as in MC modeling in terms of channel noise
statistics and effects on excitability. Recently, it was shown that the
difference arose because MCs were modeled with coupled activation subunits,
while the DA was modeled using uncoupled activation subunits. Implementations
of DA with coupled subunits, in the context of a specific kinetic scheme,
yielded similar results to MC. However, it remained unclear how to generalize
these implementations to different kinetic schemes, or whether they were faster
than MC algorithms. Additionally, a steady state approximation was used for the
stochastic terms, which, as we show here, can introduce significant
inaccuracies. We derived the SDE explicitly for any given ion channel kinetic
scheme. The resulting generic equations were surprisingly simple and
interpretable - allowing an easy and efficient DA implementation. The algorithm
was tested in a voltage clamp simulation and in two different current clamp
simulations, yielding the same results as MC modeling. Also, the simulation
efficiency of this DA method demonstrated considerable superiority over MC
methods.Comment: 32 text pages, 10 figures, 1 supplementary text + figur
Heralded Noiseless Amplification of a Photon Polarization Qubit
Non-deterministic noiseless amplification of a single mode can circumvent the
unique challenges to amplifying a quantum signal, such as the no-cloning
theorem, and the minimum noise cost for deterministic quantum state
amplification. However, existing devices are not suitable for amplifying the
fundamental optical quantum information carrier, a qubit coherently encoded
across two optical modes. Here, we construct a coherent two-mode amplifier, to
demonstrate the first heralded noiseless linear amplification of a qubit
encoded in the polarization state of a single photon. In doing so, we increase
the transmission fidelity of a realistic qubit channel by up to a factor of
five. Qubit amplifiers promise to extend the range of secure quantum
communication and other quantum information science and technology protocols.Comment: 6 pages, 3 figure
Measuring measurement
Measurement connects the world of quantum phenomena to the world of classical
events. It plays both a passive role, observing quantum systems, and an active
one, preparing quantum states and controlling them. Surprisingly - in the light
of the central status of measurement in quantum mechanics - there is no general
recipe for designing a detector that measures a given observable. Compounding
this, the characterization of existing detectors is typically based on partial
calibrations or elaborate models. Thus, experimental specification (i.e.
tomography) of a detector is of fundamental and practical importance. Here, we
present the realization of quantum detector tomography: we identify the optimal
positive-operator-valued measure describing the detector, with no ancillary
assumptions. This result completes the triad, state, process, and detector
tomography, required to fully specify an experiment. We characterize an
avalanche photodiode and a photon number resolving detector capable of
detecting up to eight photons. This creates a new set of tools for accurately
detecting and preparing non-classical light.Comment: 6 pages, 4 figures,see video abstract at
http://www.quantiki.org/video_abstracts/0807244
Predictor Model of Root Caries in Older Adults: Reporting of Evidence to the Translational Evidence Mechanism
Compared to younger adults, older adults are at greater risk for root caries. A model of root caries may assist dentists in predicting disease outcomes. OBJECTIVES: Using the Iowa 65+ Oral Health Survey, analysis was done to model the patterns of the root caries development in older adults
An association between K65R and HIV-1 subtype C viruses in patients treated with multiple NRTIs
Objectives: HIV-1 subtype C might have a greater propensity to develop K65R mutations in patients with virological failure compared with other subtypes. However, the strong association between viral subtype and confounding factors such as exposure groups and ethnicity affects the calculation of this propensity. We exploited the diversity of viral subtypes within the UK to undertake a direct comparative analysis. Patients and methods: We analysed only sequences with major IAS-defined mutations from patients with virological failure. Prevalence of K65R was related to subtype and exposure to the NRTIs that primarily select for this mutation (tenofovir, abacavir, didanosine and stavudine). A multivariate logistic regression model quantified the effect of subtype on the prevalence of K65R, adjusting for previous and current exposure to all four specified drugs. Results: Subtype B patients ( n = 3410) were mostly MSM (78%) and those with subtype C ( n = 810) were mostly heterosexual (82%). K65R was detected in 7.8% of subtype B patients compared with 14.2% of subtype C patients. The subtype difference in K65R prevalence was observed irrespective of NRTI exposure and K65R was frequently selected by abacavir, didanosine and stavudine in patients with no previous exposure to tenofovir. Multivariate logistic regression confirmed that K65R was significantly more common in subtype C viruses (adjusted OR = 2.02, 95% CI = 1.55-2.62, P < 0.001). Conclusions: Patients with subtype C HIV-1 have approximately double the frequency of K65R in our database compared with other subtypes. The exact clinical implications of this finding need to be further elucidated
The what and where of adding channel noise to the Hodgkin-Huxley equations
One of the most celebrated successes in computational biology is the
Hodgkin-Huxley framework for modeling electrically active cells. This
framework, expressed through a set of differential equations, synthesizes the
impact of ionic currents on a cell's voltage -- and the highly nonlinear impact
of that voltage back on the currents themselves -- into the rapid push and pull
of the action potential. Latter studies confirmed that these cellular dynamics
are orchestrated by individual ion channels, whose conformational changes
regulate the conductance of each ionic current. Thus, kinetic equations
familiar from physical chemistry are the natural setting for describing
conductances; for small-to-moderate numbers of channels, these will predict
fluctuations in conductances and stochasticity in the resulting action
potentials. At first glance, the kinetic equations provide a far more complex
(and higher-dimensional) description than the original Hodgkin-Huxley
equations. This has prompted more than a decade of efforts to capture channel
fluctuations with noise terms added to the Hodgkin-Huxley equations. Many of
these approaches, while intuitively appealing, produce quantitative errors when
compared to kinetic equations; others, as only very recently demonstrated, are
both accurate and relatively simple. We review what works, what doesn't, and
why, seeking to build a bridge to well-established results for the
deterministic Hodgkin-Huxley equations. As such, we hope that this review will
speed emerging studies of how channel noise modulates electrophysiological
dynamics and function. We supply user-friendly Matlab simulation code of these
stochastic versions of the Hodgkin-Huxley equations on the ModelDB website
(accession number 138950) and
http://www.amath.washington.edu/~etsb/tutorials.html.Comment: 14 pages, 3 figures, review articl
Consequences of converting graded to action potentials upon neural information coding and energy efficiency
Information is encoded in neural circuits using both graded and action potentials, converting between them within single neurons and successive processing layers. This conversion is accompanied by information loss and a drop in energy efficiency. We investigate the biophysical causes of this loss of information and efficiency by comparing spiking neuron models, containing stochastic voltage-gated Na+ and K+ channels, with generator potential and graded potential models lacking voltage-gated Na+ channels. We identify three causes of information loss in the generator potential that are the by-product of action potential generation: (1) the voltage-gated Na+ channels necessary for action potential generation increase intrinsic noise and (2) introduce non-linearities, and (3) the finite duration of the action potential creates a ‘footprint’ in the generator potential that obscures incoming signals. These three processes reduce information rates by ~50% in generator potentials, to ~3 times that of spike trains. Both generator potentials and graded potentials consume almost an order of magnitude less energy per second than spike trains. Because of the lower information rates of generator potentials they are substantially less energy efficient than graded potentials. However, both are an order of magnitude more efficient than spike trains due to the higher energy costs and low information content of spikes, emphasizing that there is a two-fold cost of converting analogue to digital; information loss and cost inflation
Re-Assembly of the Genome of Francisella tularensis Subsp. holarctica OSU18
Francisella tularensis is a highly infectious human intracellular pathogen that is the causative agent of tularemia. It occurs in several major subtypes, including the live vaccine strain holarctica (type B). F. tularensis is classified as category A biodefense agent in part because a relatively small number of organisms can cause severe illness. Three complete genomes of subspecies holarctica have been sequenced and deposited in public archives, of which OSU18 was the first and the only strain for which a scientific publication has appeared [1]. We re-assembled the OSU18 strain using both de novo and comparative assembly techniques, and found that the published sequence has two large inversion mis-assemblies. We generated a corrected assembly of the entire genome along with detailed information on the placement of individual reads within the assembly. This assembly will provide a more accurate basis for future comparative studies of this pathogen
Where does the transport current flow in Bi2Sr2CaCu2O8 crystals?
A new measurement technique for investigation of vortex dynamics is
introduced. The distribution of the transport current across a crystal is
derived by a sensitive measurement of the self-induced magnetic field of the
transport current. We are able to clearly mark where the flow of the transport
current is characterized by bulk pinning, surface barrier, or a uniform current
distribution. One of the novel results is that in BSCCO crystals most of the
vortex liquid phase is affected by surface barriers resulting in a thermally
activated apparent resistivity. As a result the standard transport measurements
in BSCCO do not probe the dynamics of vortices in the bulk, but rather measure
surface barrier properties.Comment: 11 pages, 4 figures, accepted for publication in Natur
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