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

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

Pregnancy in women with pulmonary hypertension

Women with pulmonary hypertension have a high risk of morbidity and mortality during pregnancy. The inability to increase cardiac output leads to heart failure while further risks are introduced with hypercoagulability and decrease in systemic vascular resistance. There is no proof that new advanced therapies for pulmonary hypertension decrease the risk, though some promising results have been reported. However, pregnancy should still be regarded as contraindicated in women with pulmonary hypertension. When pregnancy occurs and termination is declined, pregnancy and delivery should be managed by multidisciplinary services with experience in the management of both pulmonary hypertension and high-risk pregnancies

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

Electrodynamics of a Clean Vortex Lattice

We report on a microscopic evaluation of electrodynamic response for the vortex lattice state of a model s-wave superconductor. Our calculation accounts self-consistently for both quasiparticle and order parameter response and establishes the collective nature of linear response in the clean limit. We discuss the effects of homogeneous and inhomogeneous pinning on the optical conductivity and the penetration depth, and comment on the relationship between macroscopic and local penetration depths. We find unexpected relationships between pinning arrangements and conductivity due to the strongly non-local response.Comment: 4 pages, 2 figure

Dirac, Anderson, and Goldstone on the Kagome

We show that there exists a long-range RVB state for the kagome lattice spin-1/2 Heisenberg antiferromagnet for which the spinons have a massless Dirac spectrum. By considering various perturbations of the RVB state which give mass to the fermions by breaking a symmetry, we are able to describe a wide-ranging class of known states on the kagome lattice, including spin-Peierls solid and chiral spin liquid states. Using an RG treatment of fluctuations about the RVB state, we propose yet a different symmetry breaking pattern and show how collective excitations about this state account for the gapless singlet modes seen experimentally and numerically. We make further comparison with numerics for Chern numbers, dimer-dimer correlation functions, the triplet gap, and other quantities. To accomplish these calculations, we propose a variant of the SU(N) theory which enables us to include many of the effects of Gutzwiller projection at the mean-field level.Comment: 18 pages, 6 figures; added references, minor correction

UMP/CMPK Is Not the Critical Enzyme in the Metabolism of Pyrimidine Ribonucleotide and Activation of Deoxycytidine Analogs in Human RKO Cells

Human UMP/CMP kinase was identified based on its enzymatic activity in vitro. The role of this protein is considered critical for the maintenance of pyrimidine nucleotide pool profile and for the metabolism of pyrimidine analogs in cells, based on the in vitro study of partially purified enzyme and recombinant protein. However, no detailed study has yet addressed the role of this protein in nucleotide metabolism in cells.Two stable cell lines in which UMP/CMP kinase (mRNA: AF087865, EC 2.7.4.14) can be either up-regulated or down-regulated were developed using Tet-On Gene Expression Systems. The amount and enzymatic activity of UMP/CMP kinase extracted from these two cell lines can be induced up by 500% or down by 95-98%. The ribonucleotides of endogenous pyrimidine as well as the metabolism of exogenous natural pyrimidine nucleosides and their analogs were not susceptible to the altered amount of UMP/CMP kinase in these two stable RKO cell lines. The level of incorporation of pyrimidine nucleoside analogs, such as gemcitabine (dFdC) and troxacitabine (L-OddC), into cellular DNA and their potency in inhibiting cell growth were not significantly altered by up-regulation or down-regulation of UMP/CMP kinase expression in cells.The UMP/CMP kinase (EC 2.7.4.14) expressed in RKO cells is not critical for the phosphorylation of (d)CMP and the maintenance of natural nucleotide pools. It also does not play an important role in the activation of dFdC and L-OddC. The increase by 500% or decrease by 95-98% in the levels of UMP/CMP kinase do not affect steady state levels of dFdC and L-OddC in RKO cells. Overall, the activity and possible mechanisms of recombinant UMP/CMP kinase expressed in the in vitro system can not be extended to that of UMP/CMP kinase expressed in a cell system or an in vivo system

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

Signature of the staggered flux state around a superconducting vortex in underdoped cuprates

Based on the SU(2) lattice gauge theory formulation of the t-J model, we discuss possible signature of the unit cell doubling associated with the staggered flux (SF) state in the lightly doped spin liquid. Although the SF state appears only dynamically in a uniform d-wave superconducting (SC) state, a topological defect [SU(2) vortex] freezes the SF state inside the vortex core. Consequently, the unit cell doubling shows up in the hopping ($\chi_{ij}$) and pairing ($\Delta_{ij}$) order parameters of physical electrons. 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 $\chi_{ij}$ and $\Delta_{ij}$ becomes predominant. We predict that over the region outside the core and inside the internal gauge field penetration depth around a vortex center, the local density-of-states (LDOS) exhibits staggered peak-dip (SPD) structure inside the V-shaped profile when measured on the bonds. The SPD structure has its direct origin in the unit cell doubling associated with the SF core and the robust topological texture, which has little to do with the symmetry of the d-wave order parameter. Therefore the structure may survive the tunneling matrix element effects and easily be detected by STM experiment.Comment: 27 pages, 14 figures in GIF format, typo correcte