5,320 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
Emergent Quantum Near-Criticality from Baryonic Black Branes
We find new black 3-brane solutions describing the "conifold gauge theory" at
nonzero temperature and baryonic chemical potential. Of particular interest is
the low-temperature limit where we find a new kind of weakly curved
near-horizon geometry; it is a warped product AdS_2 x R^3 x T^{1,1} with warp
factors that are powers of the logarithm of the AdS radius. Thus, our solution
encodes a new type of emergent quantum near-criticality. We carry out some
stability checks for our solutions. We also set up a consistent ansatz for
baryonic black 2-branes of M-theory that are asymptotic to AdS_4 x Q^{1,1,1}.Comment: 29 pages, 4 figures; v2 discussion of entropy revised, minor changes;
v3 note added, minor improvements, version published in JHE
Momentum modes of M5-branes in a 2d space
We study M5 branes by considering the selfdual strings parallel to a plane.
With the internal oscillation frozen, each selfdual string gives a 5d SYM
field. All selfdual strings together give a 6d field with 5 scalars, 3 gauge
degrees of freedom and 8 fermionic degrees of freedom in adjoint representation
of U(N). Selfdual strings with the same orientation have the SYM-type
interaction. For selfdual strings with the different orientations, which could
also be taken as the unparallel momentum modes of the 6d field on that plane or
the (p,q) (r,s) strings on D3 with (p,q)\neq (r,s), the [i,j]+[j,k]\rightarrow
[i,k] relation is not valid, so the coupling cannot be written in terms of the
standard N \times N matrix multiplication. 3-string junction, which is the
bound state of the unparallel [i,j] [j,k] selfdual strings, may play a role
here.Comment: 37 pages, 5 figures, to appear in JHEP; v2: reference adde
Assessing methods for dealing with treatment switching in randomised controlled trials: a simulation study
<p>Abstract</p> <p>Background</p> <p>We investigate methods used to analyse the results of clinical trials with survival outcomes in which some patients switch from their allocated treatment to another trial treatment. These included simple methods which are commonly used in medical literature and may be subject to selection bias if patients switching are not typical of the population as a whole. Methods which attempt to adjust the estimated treatment effect, either through adjustment to the hazard ratio or via accelerated failure time models, were also considered. A simulation study was conducted to assess the performance of each method in a number of different scenarios.</p> <p>Results</p> <p>16 different scenarios were identified which differed by the proportion of patients switching, underlying prognosis of switchers and the size of true treatment effect. 1000 datasets were simulated for each of these and all methods applied. Selection bias was observed in simple methods when the difference in survival between switchers and non-switchers were large. A number of methods, particularly the AFT method of Branson and Whitehead were found to give less biased estimates of the true treatment effect in these situations.</p> <p>Conclusions</p> <p>Simple methods are often not appropriate to deal with treatment switching. Alternative approaches such as the Branson & Whitehead method to adjust for switching should be considered.</p
Holographic Superconductor/Insulator Transition at Zero Temperature
We analyze the five-dimensional AdS gravity coupled to a gauge field and a
charged scalar field. Under a Scherk-Schwarz compactification, we show that the
system undergoes a superconductor/insulator transition at zero temperature in
2+1 dimensions as we change the chemical potential. By taking into account a
confinement/deconfinement transition, the phase diagram turns out to have a
rich structure. We will observe that it has a similarity with the RVB
(resonating valence bond) approach to high-Tc superconductors via an emergent
gauge symmetry.Comment: 25 pages, 23 figures; A new subsection on a concrete string theory
embedding added, references added (v2); Typos corrected, references added
(v3
Exact results for static and radiative fields of a quark in N=4 super Yang-Mills
In this work (which supersedes our previous preprint arXiv:1112.2345) we
determine the expectation value of the N=4$ SU(N) SYM Lagrangian density
operator in the presence of an infinitely heavy static particle in the
symmetric representation of SU(N), by means of a D3-brane probe computation.
The result that we obtain coincides with two previous computations of different
observables, up to kinematical factors. We argue that these agreements go
beyond the D-brane probe approximation, which leads us to propose an exact
formula for the expectation value of various operators. In particular, we
provide an expression for the total energy loss by radiation of a heavy
particle in the fundamental representation.Comment: 14 pages. This submission supersedes our previous preprint
arXiv:1112.2345. v2: numerical factors fixed, minor clarifications, added
reference
Comprehensive methylome map of lineage commitment from haematopoietic progenitors.
Epigenetic modifications must underlie lineage-specific differentiation as terminally differentiated cells express tissue-specific genes, but their DNA sequence is unchanged. Haematopoiesis provides a well-defined model to study epigenetic modifications during cell-fate decisions, as multipotent progenitors (MPPs) differentiate into progressively restricted myeloid or lymphoid progenitors. Although DNA methylation is critical for myeloid versus lymphoid differentiation, as demonstrated by the myeloerythroid bias in Dnmt1 hypomorphs, a comprehensive DNA methylation map of haematopoietic progenitors, or of any multipotent/oligopotent lineage, does not exist. Here we examined 4.6 million CpG sites throughout the genome for MPPs, common lymphoid progenitors (CLPs), common myeloid progenitors (CMPs), granulocyte/macrophage progenitors (GMPs), and thymocyte progenitors (DN1, DN2, DN3). Marked epigenetic plasticity accompanied both lymphoid and myeloid restriction. Myeloid commitment involved less global DNA methylation than lymphoid commitment, supported functionally by myeloid skewing of progenitors following treatment with a DNA methyltransferase inhibitor. Differential DNA methylation correlated with gene expression more strongly at CpG island shores than CpG islands. Many examples of genes and pathways not previously known to be involved in choice between lymphoid/myeloid differentiation have been identified, such as Arl4c and Jdp2. Several transcription factors, including Meis1, were methylated and silenced during differentiation, indicating a role in maintaining an undifferentiated state. Additionally, epigenetic modification of modifiers of the epigenome seems to be important in haematopoietic differentiation. Our results directly demonstrate that modulation of DNA methylation occurs during lineage-specific differentiation and defines a comprehensive map of the methylation and transcriptional changes that accompany myeloid versus lymphoid fate decisions
Symmetries of Abelian Orbifolds
Using the Polya Enumeration Theorem, we count with particular attention to
C^3/Gamma up to C^6/Gamma, abelian orbifolds in various dimensions which are
invariant under cycles of the permutation group S_D. This produces a collection
of multiplicative sequences, one for each cycle in the Cycle Index of the
permutation group. A multiplicative sequence is controlled by its values on
prime numbers and their pure powers. Therefore, we pay particular attention to
orbifolds of the form C^D/Gamma where the order of Gamma is p^alpha. We propose
a generalization of these sequences for any D and any p.Comment: 75 pages, 13 figures, 30 table
A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited.BACKGROUND: The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. METHODS: We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. RESULTS: We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. CONCLUSIONS: Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.CC is a recipient of a Vanier Canada Graduate Scholarship from the Canadian Institutes of Health Research (funding reference numberâCGV 121171) and is a trainee on the Canadian Institutes of Health Research Drug Safety and Effectiveness Network team grant (funding reference numberâ116573). BH is funded by a New Investigator award from the Canadian Institutes of Health Research and the Drug Safety and Effectiveness Network. This research was partly supported by funding from CADTH as part of a project to develop Excel-based tools to support the conduct of health technology assessments. This research was also supported by Cornerstone Research Group
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