Estimation of colorectal adenoma recurrence with dependent censoring

<p>Abstract</p> <p>Background</p> <p>Due to early colonoscopy for some participants, interval-censored observations can be introduced into the data of a colorectal polyp prevention trial. The censoring could be dependent of risk of recurrence if the reasons of having early colonoscopy are associated with recurrence. This can complicate estimation of the recurrence rate.</p> <p>Methods</p> <p>We propose to use midpoint imputation to convert interval-censored data problems to right censored data problems. To adjust for potential dependent censoring, we use information from auxiliary variables to define risk groups to perform the weighted Kaplan-Meier estimation to the midpoint imputed data. The risk groups are defined using two risk scores derived from two working proportional hazards models with the auxiliary variables as the covariates. One is for the recurrence time and the other is for the censoring time. The method described here is explored by simulation and illustrated with an example from a colorectal polyp prevention trial.</p> <p>Results</p> <p>We first show that midpoint imputation under an assumption of independent censoring will produce an unbiased estimate of recurrence rate at the end of the trial, which is often the main interest of a colorectal polyp prevention trial, and then show in simulations that the weighted Kaplan-Meier method using the information from auxiliary variables based on the midpoint imputed data can improve efficiency in a situation with independent censoring and reduce bias in a situation with dependent censoring compared to the conventional methods, while estimating the recurrence rate at the end of the trial.</p> <p>Conclusion</p> <p>The research in this paper uses midpoint imputation to handle interval-censored observations and then uses the information from auxiliary variables to adjust for dependent censoring by incorporating them into the weighted Kaplan-Meier estimation. This approach can handle a situation with multiple auxiliary variables by deriving two risk scores from two working PH models. Although the idea of this approach might appear simple, the results do show that the weighted Kaplan-Meier approach can gain efficiency and reduce bias due to dependent censoring.</p

Flood impact assessment under climate change scenarios in central Taipei area, Taiwan

Providing effective information regarding flood control for responding climate change is essential to future flood risk management for cities. This study simulated and assessed the impacts of flooding for future climate change scenarios in Taipei city, Taiwan. We modelled rainfall events, generated by general circulation models, with different return periods. The flood extents and damage in the Central Taipei Area for the A1B climate change scenarios were compared to the ones, caused by the rainfall events with same return periods, without climate change (baseline scenario). The proposed approach provides potential flooding maps and flood damage assessment for climate change scenarios as useful information for flood risk management in urban areas.The work is supported by the National Science Council, Taiwan (NSC 99-2915-I-002-120) and the CORFU project, funded by the European Commission through Framework Programme 7, Grant Number 244047

Staggered local density-of-states around the vortex in underdoped cuprates

We have studied a single vortex with the staggered flux (SF) core based on the SU(2) slave-boson theory of high $T_c$ superconductors. We find that whereas the center in the vortex core is a SF state, as one moves away from the core center, a correlated staggered modulation of the hopping amplitude $\chi$ and pairing amplitude $\Delta$ becomes predominant. We predict that in this region, the local density-of-states (LDOS) exhibits staggered modulation when measured on the bonds, which may be directly detected by STM experiments.Comment: 4 pages, 3 figure

Observation of Magnetic Moments in the Superconducting State of YBa2_2Cu3_3O6.6_{6.6}

Neutron Scattering measurements for YBa$_2$Cu$_3$O$_{6.6}$ have identified small magnetic moments that increase in strength as the temperature is reduced below $T^\ast$ and further increase below $T_c$. An analysis of the data shows the moments are antiferromagnetic between the Cu-O planes with a correlation length of longer than 195 \AA in the $a$-$b$ plane and about 35 \AA along the c-axis. The origin of the moments is unknown, and their properties are discusssed both in terms of Cu spin magnetism and orbital bond currents.Comment: 9 pages, and 4 figure

Survivin a radiogenetic promoter for glioblastoma viral gene therapy independently from CArG motifs

BACKGROUND: Radiogenetic therapy is a novel approach in the treatment of cancer, which employs genetic modification to alter the sensitivity of tumor cells to the effect of applied radiation. AIM: To select a potent radiation inducible promoter in the context of brain tumors and to investigate if CArG radio responsive motifs or other elements in the promoter nucleotide sequences can correlate to its response to radiation. METHODS: To select initial candidates for promoter inducible elements, the levels of mRNA expression of six different promoters were assessed using Quantitative RTPCR in D54 MG cells before and after radiation exposure. Recombinant Ad/reporter genes driven by five different promoters; CMV, VEGF, FLT-1, DR5 and survivin were constructed. Glioma cell lines were infected with different multiplicity of infection of the (promoter) Ad or CMV Ad. Cells were then exposed to a range of radiation (0–12 Gy) at single fraction. Fluorescent microscopy, Luc assay and X-gal staining was used to detect the level of expression of related genes. Different glioma cell lines and normal astrocytes were infected with Ad survivin and exposed to radiation. The promoters were analyzed for presence of CArG radio-responsive motifs and CCAAT box consensus using NCBI blast bioinformatics software. RESULTS: Radiotherapy increases the expression of gene expression by 1.25–2.5 fold in different promoters other than survivin after 2 h of radiation. RNA analysis was done and has shown an increase in copy number of tenfold for survivin. Most importantly cells treated with RT and Ad Luc driven by survivin promoter showed a fivefold increase in expression after 2 Gy of radiation in comparison to non-irradiated cells. Presence or absence of CArG motifs did not correlate with promoter response to radiation. Survivin with the best response to radiation had the lowest number of CCAAT box. CONCLUSION: Survivin is a selective potent radiation inducible promoter for glioblastoma viral gene therapy and this response to radiation could be independent of CArG motifs

Validating pore size estimates in a complex microfiber environment on a human MRI system

PURPOSE: Recent advances in diffusion-weighted MRI provide "restricted diffusion signal fraction" and restricting pore size estimates. Materials based on co-electrospun oriented hollow cylinders have been introduced to provide validation for such methods. This study extends this work, exploring accuracy and repeatability using an extended acquisition on a 300 mT/m gradient human MRI scanner, in substrates closely mimicking tissue, that is, non-circular cross-sections, intra-voxel fiber crossing, intra-voxel distributions of pore-sizes, and smaller pore-sizes overall. METHODS: In a single-blind experiment, diffusion-weighted data were collected from a biomimetic phantom on a 3T Connectom system using multiple gradient directions/diffusion times. Repeated scans established short-term and long-term repeatability. The total scan time (54 min) matched similar protocols used in human studies. The number of distinct fiber populations was estimated using spherical deconvolution, and median pore size estimated through the combination of CHARMED and AxCaliber3D framework. Diffusion-based estimates were compared with measurements derived from scanning electron microscopy. RESULTS: The phantom contained substrates with different orientations, fiber configurations, and pore size distributions. Irrespective of one or two populations within the voxel, the pore-size estimates (~5 μm) and orientation-estimates showed excellent agreement with the median values of pore-size derived from scanning electron microscope and phantom configuration. Measurement repeatability depended on substrate complexity, with lower values seen in samples containing crossing-fibers. Sample-level repeatability was found to be good. CONCLUSION: While no phantom mimics tissue completely, this study takes a step closer to validating diffusion microstructure measurements for use in vivo by demonstrating the ability to quantify microgeometry in relatively complex configurations

Multiregional Satellite Precipitation Products Evaluation over Complex Terrain

An extensive evaluation of nine global-scale high-resolution satellite-based rainfall (SBR) products is performed using a minimum of 6 years (within the period of 2000-13) of reference rainfall data derived from rain gauge networks in nine mountainous regions across the globe. The SBR products are compared to a recently released global reanalysis dataset from the European Centre for Medium-Range Weather Forecasts (ECMWF). The study areas include the eastern Italian Alps, the Swiss Alps, the western Black Sea of Turkey, the French Cévennes, the Peruvian Andes, the Colombian Andes, the Himalayas over Nepal, the Blue Nile in East Africa, Taiwan, and the U.S. Rocky Mountains. Evaluation is performed at annual, monthly, and daily time scales and 0.25° spatial resolution. The SBR datasets are based on the following retrieval algorithms: Tropical Rainfall Measuring Mission Multisatellite Precipitation Analysis (TMPA), the NOAA/Climate Prediction Center morphing technique (CMORPH), Precipitation Estimation from Remotely Sensed Information Using Artificial Neural Networks (PERSIANN), and Global Satellite Mapping of Precipitation (GSMaP). SBR products are categorized into those that include gauge adjustment versus unadjusted. Results show that performance of SBR is highly dependent on the rainfall variability. Many SBR products usually underestimate wet season and overestimate dry season precipitation. The performance of gauge adjustment to the SBR products varies by region and depends greatly on the representativeness of the rain gauge network

Comparative Toxicity of Fumigants and a Phosphine Synergist Using a Novel Containment Chamber for the Safe Generation of Concentrated Phosphine Gas

BACKGROUND: With the phasing out of ozone-depleting substances in accordance with the United Nations Montreal Protocol, phosphine remains as the only economically viable fumigant for widespread use. However the development of high-level resistance in several pest insects threatens the future usage of phosphine; yet research into phosphine resistance mechanisms has been limited due to the potential for human poisoning in enclosed laboratory environments. PRINCIPAL FINDINGS: Here we describe a custom-designed chamber for safely containing phosphine gas generated from aluminium phosphide tablets. In an improvement on previous generation systems, this chamber can be completely sealed to control the escape of phosphine. The device has been utilised in a screening program with C. elegans that has identified a phosphine synergist, and quantified the efficacy of a new fumigant against that of phosphine. The phosphine-induced mortality at 20°C has been determined with an LC(50) of 732 ppm. This result was contrasted with the efficacy of a potential new botanical pesticide dimethyl disulphide, which for a 24 hour exposure at 20°C is 600 times more potent than phosphine (LC(50) 1.24 ppm). We also found that co-administration of the glutathione depletor diethyl maleate (DEM) with a sublethal dose of phosphine (70 ppm, <LC(5)), results in a doubling of mortality in C. elegans relative to DEM alone. CONCLUSIONS: The prohibitive danger associated with the generation, containment, and use of phosphine in a laboratory environment has now been substantially reduced by the implementation of our novel gas generation chamber. We have also identified a novel phosphine synergist, the glutathione depletor DEM, suggesting an effective pathway to be targeted in future synergist research; as well as quantifying the efficacy of a potential alternative to phosphine, dimethyl disulphide

Efficient simulation of the spatial transmission dynamics of influenza

Early data from the 2009 H1N1 pandemic (H1N1pdm) suggest that previous studies over-estimated the within-country rate of spatial spread of pandemic influenza. As large spatially resolved data sets are constructed, the need for efficient simulation code with which to investigate the spatial patterns of the pandemic becomes clear. Here, we present a significant improvement to the efficiency of an individual based stochastic disease simulation framework commonly used in multiple previous studies. We quantify the efficiency of the revised algorithm and present an alternative parameterization of the model in terms of the basic reproductive number. We apply the model to the population of Taiwan and demonstrate how the location of the initial seed can influence spatial incidence profiles and the overall spread of the epidemic. Differences in incidence are driven by the relative connectivity of alternate seed locations. The ability to perform efficient simulation allows us to run a batch of simulations and take account of their average in real time. The averaged data are stable and can be used to differentiate spreading patterns that are not readily seen by only conducting a few runs. © 2010 Tsai et al.published_or_final_versio