1,815 research outputs found
Multimodal nested sampling: an efficient and robust alternative to MCMC methods for astronomical data analysis
In performing a Bayesian analysis of astronomical data, two difficult
problems often emerge. First, in estimating the parameters of some model for
the data, the resulting posterior distribution may be multimodal or exhibit
pronounced (curving) degeneracies, which can cause problems for traditional
MCMC sampling methods. Second, in selecting between a set of competing models,
calculation of the Bayesian evidence for each model is computationally
expensive. The nested sampling method introduced by Skilling (2004), has
greatly reduced the computational expense of calculating evidences and also
produces posterior inferences as a by-product. This method has been applied
successfully in cosmological applications by Mukherjee et al. (2006), but their
implementation was efficient only for unimodal distributions without pronounced
degeneracies. Shaw et al. (2007), recently introduced a clustered nested
sampling method which is significantly more efficient in sampling from
multimodal posteriors and also determines the expectation and variance of the
final evidence from a single run of the algorithm, hence providing a further
increase in efficiency. In this paper, we build on the work of Shaw et al. and
present three new methods for sampling and evidence evaluation from
distributions that may contain multiple modes and significant degeneracies; we
also present an even more efficient technique for estimating the uncertainty on
the evaluated evidence. These methods lead to a further substantial improvement
in sampling efficiency and robustness, and are applied to toy problems to
demonstrate the accuracy and economy of the evidence calculation and parameter
estimation. Finally, we discuss the use of these methods in performing Bayesian
object detection in astronomical datasets.Comment: 14 pages, 11 figures, submitted to MNRAS, some major additions to the
previous version in response to the referee's comment
Inhibition of the \u3cem\u3edapE\u3c/em\u3e-Encoded \u3cem\u3eN\u3c/em\u3e-Succinyl- ʟ, ʟ-diaminopimelic Acid Desuccinylase from \u3cem\u3eNeisseria meningitidis\u3c/em\u3e by ʟ-Captopril
Binding of the competitive inhibitor ʟ-captopril to the dapE-encoded N-succinyl-ʟ, ʟ-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. ʟ-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Escherichia coli. ʟ-Captopril is also a competitive inhibitor of NmDapE with a Ki of 2.8 μM. To examine the nature of the interaction of ʟ-captopril with the dinuclear active site of DapE, we have obtained electron paramagnetic resonance (EPR) and magnetic circular dichroism (MCD) data for the enzymatically hyperactive Co(II)-substituted forms of both HiDapE and NmDapE. EPR and MCD data indicate that the two Co(II) ions in DapE are antiferromagnetically coupled, yielding an S = 0 ground state, and suggest a thiolate bridge between the two metal ions. Verification of a thiolate-bridged dinuclear complex was obtained by determining the three-dimensional X-ray crystal structure of NmDapE in complex with ʟ-captopril at 1.8 Å resolution. Combination of these data provides new insights into binding of ʟ-captopril to the active site of DapE enzymes as well as important inhibitor–active site residue interaction’s. Such information is critical for the design of new, potent inhibitors of DapE enzymes
Exploring differences in adverse symptom event grading thresholds between clinicians and patients in the clinical trial setting
Symptomatic adverse event (AE) monitoring is essential in cancer clinical trials to assess patient safety, as well as inform decisions related to treatment and continued trial participation. As prior research has demonstrated that conventional concordance metrics (e.g., intraclass correlation) may not capture nuanced aspects of the association between clinician and patient-graded AEs, we aimed to characterize differences in AE grading thresholds between doctors (MDs), registered nurses (RNs), and patients using the Bayesian Graded Item Response Model (GRM)
Efficient Bayesian inference for multimodal problems in cosmology
Bayesian model selection provides the cosmologist with an exacting tool to
distinguish between competing models based purely on the data, via the Bayesian
evidence. Previous methods to calculate this quantity either lacked general
applicability or were computationally demanding. However, nested sampling
(Skilling 2004), which was recently applied successfully to cosmology by
Muhkerjee et al. 2006, overcomes both of these impediments. Their
implementation restricts the parameter space sampled, and thus improves the
efficiency, using a decreasing ellipsoidal bound in the n-dimensional parameter
space centred on the maximum likelihood point. However, if the likelihood
function contains any multi-modality, then the ellipse is prevented from
constraining the sampling region efficiently. In this paper we introduce a
method of clustered ellipsoidal nested sampling which can form multiple
ellipses around each individual peak in the likelihood.
In addition we have implemented a method for determining the expectation and
variance of the final evidence value without the need to use sampling error
from repetitions of the algorithm ; this further reduces the computational load
by at least an order of magnitude. We have applied our algorithm to a pair of
toy models and one cosmological example where we demonstrate that the number of
likelihood evaluations required is ~ 4% of that necessary for using previous
algorithms.
We have produced a fortran library containing our routines which can be
called from any sampling code, in addition for convenience we have incorporated
it into the popular CosmoMC code as CosmoClust. Both are available for download
at http://www.mrao.cam.ac.uk/software/cosmoclust .Comment: 7 pages, 8 figures, changed to match version accepted by MNRA
Experiences of Interventions Aiming to Improve the Mental Health and Wellbeing of Children and Young People with a Long-Term Physical Condition: A Systematic Review and Meta-ethnography
This is the author accepted manuscript. The final version is available from Wiley via the DOI in this recordBackground
Children and young people with long term physical health conditions are at increased risk of experiencing mental health and wellbeing difficulties. However, there is a lack of research that explores the experiences of, and attitudes towards interventions aiming to improve their mental health and wellbeing. This systematic review seeks to address this gap in the literature by exploring what children and young people with long term conditions, their caregivers and health practitioners perceive to be important aspects of interventions aiming to improve their mental health and wellbeing.
Methods
An information specialist searched five academic databases using pre‐defined criteria for qualitative evaluations of interventions aiming to improve the mental health or wellbeing of children with long term physical conditions. Reviewers also performed supplementary citation and grey literature searches. Two reviewers independently screened titles, abstracts and full texts which met the inclusion criteria and conducted data extraction and quality assessment. Meta‐ethnography was used to synthesise the findings.
Results
Screening identified 60 relevant articles. We identified five overarching constructs through the synthesis: i) Getting In and Staying In, ii) Therapeutic Foundation, iii) Social Support, iv) A Hopeful Alternative and v) Empowerment. The line of argument which links these constructs together indicates that when interventions can provide an environment that allows young people to share their experiences and build empathetic relationships; it can enable participants to access social support and increase feelings of hope and empowerment.
Conclusion
These findings may provide a framework to inform the development of mental health interventions for this population, and evaluate existing interventions which already include some of the components or processes identified by this research. Further research is needed to establish which of the constructs identified by the line of argument are most effective in improving the mental wellbeing of young people living with long term conditions.National Institute for Health Research (NIHR
Utility of Hemoglobin A1c for Diagnosing Prediabetes and Diabetes in Obese Children and Adolescents
OBJECTIVE-Hemoglobin A(1c) (A1C) has emerged as a recommended diagnostic tool for identifying diabetes and subjects at risk for the disease. This recommendation is based on data in adults showing the relationship between A1C with future development of diabetes and microvascular complications. However, studies in the pediatric population are lacking. RESEARCH DESIGN AND METHODS-We studied a multiethnic cohort of 1,156 obese children and adolescents without a diagnosis of diabetes (male, 40%/female, 60%). All subjects underwent an oral glucose tolerance test (OGTT) and A1C measurement. These tests were repeated after a follow-up time of similar to 2 years in 218 subjects. RESULTS-At baseline, subjects were stratified according to A1C categories: 77% with normal glucose tolerance (A1C 6.5%). In the at risk for diabetes category, 47% were classified with prediabetes or diabetes, and in the diabetes category, 62% were classified with type 2 diabetes by the OGTT. The area under the curve receiver operating characteristic for A1C was 0.81 (95% Cl 0.70-0.92). The threshold for identifying type 2 diabetes was 5.8%, with 78% specificity and 68% sensitivity. In the subgroup with repeated measures, a multivariate analysis showed that the strongest predictors of 2-h glucose at follow-up were baseline A1C and 2-h glucose, independently of age, ethnicity, sex, fasting glucose, and follow-up time. CONCLUSIONS-The American Diabetes Association suggested that an A1C of 6.5% underestimates the prevalence of prediabetes and diabetes in obese children and adolescents. Given the low sensitivity and specificity, the use of A1C by itself represents a poor diagnostic tool for prediabetes and type 2 diabetes in obese children and adolescents
Adapting preference-based utility measures to capture the impact of cancer treatment-related symptoms
It is important that patient-reported outcome (PRO) measures used to assess cancer therapies adequately capture the benefits and risks experienced by patients, particularly when adverse event profiles differ across therapies. This study explores the case for augmenting preference-based utility measures to capture the impact of cancer treatment-related symptoms. Additional cancer treatment-related items could be specific (e.g., rash) or global. While specific items are easier to describe and understand, their use may miss rarer symptoms and those that are currently unknown but will arise from future medical advancements. The appropriate number of additional items, the independence of those items, and their impact on the psychometric properties of the core instrument require consideration. Alternatively, a global item could encompass all potential treatment-related symptoms, of any treatments for any disease. However, such an item may not be well understood by general public respondents in valuation exercises. Further challenges include the decision about whether to generate de novo value sets for the modified instrument or to map to existing tariffs. The fluctuating and transient nature of treatment-related symptoms may be inconsistent with the methods used in conventional valuation exercises. Fluctuating symptoms could be missed by sub-optimal measure administration timing. The addition of items also poses double-counting risks. In summary, the addition of treatment-related symptom items could increase the sensitivity of existing utility measures to capture known and unknown treatment effects in oncology, while retaining the core domains. However, more research is needed to investigate the challenges, particularly regarding valuation
The ISW-tSZ cross correlation: ISW extraction out of pure CMB data
If Dark Energy introduces an acceleration in the universal expansion then
large scale gravitational potential wells should be shrinking, causing a
blueshift in the CMB photons that cross such structures (Integrated Sachs-Wolfe
effect, [ISW]). Galaxy clusters are known to probe those potential wells. In
these objects, CMB photons also experience inverse Compton scattering off the
hot electrons of the intra-cluster medium, and this results in a distortion
with a characteristic spectral signature of the CMB spectrum (the so-called
thermal Sunyaev-Zel'dovich effect, [tSZ]). Since both the ISW and the tSZ
effects take place in the same potential wells, they must be spatially
correlated. We present how this cross ISW-tSZ signal can be detected in a
CMB-data contained way by using the frequency dependence of the tSZ effect in
multi frequency CMB experiments like {\it Planck}, {\em without} requiring the
use of external large scale structure tracers data. We find that by masking low
redshift clusters, the shot noise level decreases significantly, boosting the
signal to noise ratio of the ISW--tSZ cross correlation. We also find that
galactic and extragalactic dust residuals must be kept at or below the level of
~0.04 muK^2 at l=10, a limit that is a factor of a few below {\it Planck}'s
expectations for foreground subtraction. If this is achieved, CMB observations
of the ISW-tSZ cross correlation should also provide an independent probe for
the existence of Dark Energy and the amplitude of density perturbations.Comment: submitted to MNRA
The Atacama Cosmology Telescope: Cosmological Parameters from the 2008 Power Spectra
We present cosmological parameters derived from the angular power spectrum of
the cosmic microwave background (CMB) radiation observed at 148 GHz and 218 GHz
over 296 deg^2 with the Atacama Cosmology Telescope (ACT) during its 2008
season. ACT measures fluctuations at scales 500<l<10000. We fit a model for the
lensed CMB, Sunyaev-Zel'dovich (SZ), and foreground contribution to the 148 GHz
and 218 GHz power spectra, including thermal and kinetic SZ, Poisson power from
radio and infrared point sources, and clustered power from infrared point
sources. The power from thermal and kinetic SZ at 148 GHz is estimated to be
B_3000 = 6.8+-2.9 uK^2, where B_l=l(l+1)C_l/2pi. We estimate primary
cosmological parameters from the 148 GHz spectrum, marginalizing over SZ and
source power. The LCDM cosmological model is a good fit to the data, and LCDM
parameters estimated from ACT+WMAP are consistent with the 7-year WMAP limits,
with scale invariant n_s = 1 excluded at 99.7% CL (3sigma). A model with no CMB
lensing is disfavored at 2.8sigma. By measuring the third to seventh acoustic
peaks, and probing the Silk damping regime, the ACT data improve limits on
cosmological parameters that affect the small-scale CMB power. The ACT data
combined with WMAP give a 6sigma detection of primordial helium, with Y_P =
0.313+-0.044, and a 4sigma detection of relativistic species, assumed to be
neutrinos, with Neff = 5.3+-1.3 (4.6+-0.8 with BAO+H0 data). From the CMB alone
the running of the spectral index is constrained to be dn/dlnk = -0.034 +-
0.018, the limit on the tensor-to-scalar ratio is r<0.25 (95% CL), and the
possible contribution of Nambu cosmic strings to the power spectrum is
constrained to string tension Gmu<1.6 \times 10^-7 (95% CL).Comment: 20 pages, 13 figures. Submitted to ApJ. This paper is a companion to
Hajian et al. (2010) and Das et al. (2010
Quantum Convolutional Coding with Shared Entanglement: General Structure
We present a general theory of entanglement-assisted quantum convolutional
coding. The codes have a convolutional or memory structure, they assume that
the sender and receiver share noiseless entanglement prior to quantum
communication, and they are not restricted to possess the
Calderbank-Shor-Steane structure as in previous work. We provide two
significant advances for quantum convolutional coding theory. We first show how
to "expand" a given set of quantum convolutional generators. This expansion
step acts as a preprocessor for a polynomial symplectic Gram-Schmidt
orthogonalization procedure that simplifies the commutation relations of the
expanded generators to be the same as those of entangled Bell states (ebits)
and ancilla qubits. The above two steps produce a set of generators with
equivalent error-correcting properties to those of the original generators. We
then demonstrate how to perform online encoding and decoding for a stream of
information qubits, halves of ebits, and ancilla qubits. The upshot of our
theory is that the quantum code designer can engineer quantum convolutional
codes with desirable error-correcting properties without having to worry about
the commutation relations of these generators.Comment: 23 pages, replaced with final published versio
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