412 research outputs found
Does sampling using random digit dialling really cost more than sampling from telephone directories: Debunking the myths
BACKGROUND: Computer assisted telephone interviewing (CATI) is widely used for health surveys. The advantages of CATI over face-to-face interviewing are timeliness and cost reduction to achieve the same sample size and geographical coverage. Two major CATI sampling procedures are used: sampling directly from the electronic white pages (EWP) telephone directory and list assisted random digit dialling (LA-RDD) sampling. EWP sampling covers telephone numbers of households listed in the printed white pages. LA-RDD sampling has a better coverage of households than EWP sampling but is considered to be more expensive due to interviewers dialling more out-of-scope numbers. METHODS: This study compared an EWP sample and a LA-RDD sample from the New South Wales Population Health Survey in 2003 on demographic profiles, health estimates, coefficients of variation in weights, design effects on estimates, and cost effectiveness, on the basis of achieving the same level of precision of estimates. RESULTS: The LA-RDD sample better represented the population than the EWP sample, with a coefficient of variation of weights of 1.03 for LA-RDD compared with 1.21 for EWP, and average design effects of 2.00 for LA-RDD compared with 2.38 for EWP. Also, a LA-RDD sample can save up to 14.2% in cost compared to an EWP sample to achieve the same precision for health estimates. CONCLUSION: A LA-RDD sample better represents the population, which potentially leads to reduced bias in health estimates, and rather than costing more than EWP actually costs less
Offline parameter estimation using EnKF and maximum likelihood error covariance estimates: Application to a subgrid-scale orography parameterization
International audienceRecent works show that the parameters controlling the parameterizations of the physical processes in climate models can be estimated from observations using filtering techniques. In this paper, we propose an offline parameter estimation approach, without estimating the state of the climate model. It is based on the Ensemble Kalman Filter (EnKF) and an iterative estimation of the error covariance matrices and of the background state using a maximum likelihood algorithm. The technique is implemented in a subgrid-scale orography (SSO) parameterization scheme that works in a single vertical column. First, the parameter estimation technique is evaluated using twin experiments. Then, the technique is used with synthetic observations to estimate how the parameters of the SSO scheme should change when the resolution of the input orography dataset of a general circulation model is increased. Our analysis reveals that when the resolution of the orography dataset increases, the scheme should take into account the dynamical sheltering that can occur at low levels between mountain peaks located within the same gridbox area
State and parameter estimation using Monte Carlo evaluation of path integrals
Transferring information from observations of a dynamical system to estimate
the fixed parameters and unobserved states of a system model can be formulated
as the evaluation of a discrete time path integral in model state space. The
observations serve as a guiding potential working with the dynamical rules of
the model to direct system orbits in state space. The path integral
representation permits direct numerical evaluation of the conditional mean path
through the state space as well as conditional moments about this mean. Using a
Monte Carlo method for selecting paths through state space we show how these
moments can be evaluated and demonstrate in an interesting model system the
explicit influence of the role of transfer of information from the
observations. We address the question of how many observations are required to
estimate the unobserved state variables, and we examine the assumptions of
Gaussianity of the underlying conditional probability.Comment: Submitted to the Quarterly Journal of the Royal Meteorological
Society, 19 pages, 5 figure
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X-ray crystallographic study of DNA duplex cross-linking: simultaneous binding to two d(CGTACG)(2) molecules by a bis(9-aminoacridine-4-carboxamide) derivative
Acridine-4-carboxamides form a class of known DNA mono-intercalating agents that exhibit cytotoxic activity against tumour cell lines due to their ability to inhibit topoisomerases. Previous studies of bis-acridine derivatives have yielded equivocal results regarding the minimum length of linker necessary between the two acridine chromophores to allow bis-intercalation of duplex DNA. We report here the 1.7 angstrom resolution X-ray crystal structure of a six-carbon-linked bis(acridine-4-carboxamide) ligand bound to d(CGTACG)(2) molecules by non-covalent duplex cross-linking. The asymmetric unit consists of one DNA duplex containing an intercalated acridine-4-carboxamide chromophore at each of the two CG steps. The other half of each ligand is bound to another DNA molecule in a symmetry-related manner, with the alkyl linker threading through the minor grooves. The two crystallographically independent ligand molecules adopt distinct side chain interactions, forming hydrogen bonds to either O6 or N7 on the major groove face of guanine, in contrast to the semi-disordered state of mono-intercalators bound to the same DNA molecule. The complex described here provides the first structural evidence for the non-covalent cross-linking of DNA by a small molecule ligand and suggests a possible explanation for the inconsistent behaviour of six-carbon linked bis-acridines in previous assays of DNA bis-intercalation
Predicting flow reversals in chaotic natural convection using data assimilation
A simplified model of natural convection, similar to the Lorenz (1963)
system, is compared to computational fluid dynamics simulations in order to
test data assimilation methods and better understand the dynamics of
convection. The thermosyphon is represented by a long time flow simulation,
which serves as a reference "truth". Forecasts are then made using the
Lorenz-like model and synchronized to noisy and limited observations of the
truth using data assimilation. The resulting analysis is observed to infer
dynamics absent from the model when using short assimilation windows.
Furthermore, chaotic flow reversal occurrence and residency times in each
rotational state are forecast using analysis data. Flow reversals have been
successfully forecast in the related Lorenz system, as part of a perfect model
experiment, but never in the presence of significant model error or unobserved
variables. Finally, we provide new details concerning the fluid dynamical
processes present in the thermosyphon during these flow reversals
Oracle-based optimization applied to climate model calibration
In this paper, we show how oracle-based optimization can be effectively used for the calibration of an intermediate complexity climate model. In a fully developed example, we estimate the 12 principal parameters of the C-GOLDSTEIN climate model by using an oracle- based optimization tool, Proximal-ACCPM. The oracle is a procedure that finds, for each query point, a value for the goodness-of-fit function and an evaluation of its gradient. The difficulty in the model calibration problem stems from the need to undertake costly calculations for each simulation and also from the fact that the error function used to assess the goodness-of-fit is not convex. The method converges to a Fbest fit_ estimate over 10 times faster than a comparable test using the ensemble Kalman filter. The approach is simple to implement and potentially useful in calibrating computationally demanding models based on temporal integration (simulation), for which functional derivative information is not readily available
A high-throughput and sensitive method to measure Global DNA Methylation: Application in Lung Cancer
<p>Abstract</p> <p>Background</p> <p>Genome-wide changes in DNA methylation are an epigenetic phenomenon that can lead to the development of disease. The study of global DNA methylation utilizes technology that requires both expensive equipment and highly specialized skill sets.</p> <p>Methods</p> <p>We have designed and developed an assay, <it>CpG</it>lobal, which is easy-to-use, does not utilize PCR, radioactivity and expensive equipment. <it>CpG</it>lobal utilizes methyl-sensitive restriction enzymes, HRP Neutravidin to detect the biotinylated nucleotides incorporated in an end-fill reaction and a luminometer to measure the chemiluminescence. The assay shows high accuracy and reproducibility in measuring global DNA methylation. Furthermore, <it>CpG</it>lobal correlates significantly with High Performance Capillary Electrophoresis (HPCE), a gold standard technology. We have applied the technology to understand the role of global DNA methylation in the natural history of lung cancer. World-wide, it is the leading cause of death attributed to any cancer. The survival rate is 15% over 5 years due to the lack of any clinical symptoms until the disease has progressed to a stage where cure is limited.</p> <p>Results</p> <p>Through the use of cell lines and paired normal/tumor samples from patients with non-small cell lung cancer (NSCLC) we show that global DNA hypomethylation is highly associated with the progression of the tumor. In addition, the results provide the first indication that the normal part of the lung from a cancer patient has already experienced a loss of methylation compared to a normal individual.</p> <p>Conclusion</p> <p>By detecting these changes in global DNA methylation, <it>CpG</it>lobal may have a role as a barometer for the onset and development of lung cancer.</p
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Large-scale features and evaluation of the PMIP4-CMIP6 midHolocene simulations
The mid-Holocene (6,000 years ago) is a standard experiment for the evaluation of the simulated response of global climate models using paleoclimate reconstructions. The latest mid-Holocene simulations are a contribution by the Palaeoclimate Model Intercomparison Project (PMIP4) to the current phase of the Coupled Model Intercomparison Project (CMIP6). Here we provide an initial analysis and evaluation of the results of the experiment for the mid-Holocene. We show that state-of-the-art models produce climate changes that are broadly consistent with theory and observations, including increased summer warming of the northern hemisphere and associated shifts in tropical rainfall. Many features of the PMIP4-CMIP6 simulations were present in the previous generation (PMIP3-CMIP5) of simulations. The PMIP4-CMIP6 ensemble for the mid-Holocene has a global mean temperature change of -0.3 K, which is -0.2 K cooler that the PMIP3-CMIP5 simulations predominantly as a result of the prescription of realistic greenhouse gas concentrations in PMIP4-CMIP6. Neither this difference nor the improvement in model complexity and resolution seems to improve the realism of the simulations. Biases in the magnitude and the sign of regional responses identified in PMIP3-CMIP5, such as the amplification of the northern African monsoon, precipitation changes over Europe and simulated aridity in mid-Eurasia, are still present in the PMIP4-CMIP6 simulations. Despite these issues, PMIP4-CMIP6 and the mid-Holocene provide an opportunity both for quantitative evaluation and derivation of
emergent constraints on climate sensitivity and feedback strength
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