Mixture modeling for joint analysis of survival, discrete, and continuous data

Mixture modeling is commonly used to model categorical latent variables that represent subpopulations in which population membership is unknown but can be inferred from the data. In relatively recent years, the potential of finite mixture models has been applied in time-to-event data. However, the commonly used survival mixture model assumes that the effects of the covariates involved in failure times differ across latent classes, but the covariate distribution is homogeneous. The aim of this dissertation is to develop a method to examine time-to-event data in the presence of unobserved heterogeneity under a framework of mixture modeling. A joint model is developed to incorporate the latent survival trajectory along with the observed information for the joint analysis of a time-to-event variable, its discrete and continuous covariates, and a latent class variable. It is assumed that the effects of covariates on survival times and the distribution of covariates vary across different latent classes. The unobservable survival trajectories are identified through estimating the probability that a subject belongs to a particular class based on observed information. We applied this method to a Hodgkin lymphoma study with long-term follow-up and observed four distinct latent classes in terms of long-term survival and distributions of prognostic factors. Our results from simulation studies and from the Hodgkin lymphoma study demonstrated the superiority of our joint model compared with the conventional survival model. This flexible inference method provides more accurate estimation and accommodates unobservable heterogeneity among individuals while taking involved interactions between covariates into consideration.^

Evaluation of PRESAGE® dosimeters for brachytherapy sources and the 3D dosimetry and characterization of the new AgX100 125I seed model

With continuous new improvements in brachytherapy source designs and techniques, method of 3D dosimetry for treatment dose verifications would better ensure accurate patient radiotherapy treatment. This study was aimed to first evaluate the 3D dose distributions of the low-dose rate (LDR) Amersham 6711 OncoseedTM using PRESAGE® dosimeters to establish PRESAGE® as a suitable brachytherapy dosimeter. The new AgX100 125I seed model (Theragenics Corporation) was then characterized using PRESAGE® following the TG-43 protocol. PRESAGE® dosimeters are solid, polyurethane-based, 3D dosimeters doped with radiochromic leuco dyes that produce a linear optical density response to radiation dose. For this project, the radiochromic response in PRESAGE® was captured using optical-CT scanning (632 nm) and the final 3D dose matrix was reconstructed using the MATLAB software. An Amersham 6711 seed with an air-kerma strength of approximately 9 U was used to irradiate two dosimeters to 2 Gy and 11 Gy at 1 cm to evaluate dose rates in the r=1 cm to r=5 cm region. The dosimetry parameters were compared to the values published in the updated AAPM Report No. 51 (TG-43U1). An AgX100 seed with an air-kerma strength of about 6 U was used to irradiate two dosimeters to 3.6 Gy and 12.5 Gy at 1 cm. The dosimetry parameters for the AgX100 were compared to the values measured from previous Monte-Carlo and experimental studies. In general, the measured dose rate constant, anisotropy function, and radial dose function for the Amersham 6711 showed agreements better than 5% compared to consensus values in the r=1 to r=3 cm region. The dose rates and radial dose functions measured for the AgX100 agreed with the MCNPX and TLD-measured values within 3% in the r=1 to r=3 cm region. The measured anisotropy function in PRESAGE® showed relative differences of up to 9% with the MCNPX calculated values. It was determined that post-irradiation optical density change over several days was non-linear in different dose regions, and therefore the dose values in the r=4 to r=5 cm regions had higher uncertainty due to this effect. This study demonstrated that within the radial distance of 3 cm, brachytherapy dosimetry in PRESAGE® can be accurate within 5% as long as irradiation times are within 48 hours.

Longitudinal categorical data analysis: A continuous -time Markov chain approach

In this dissertation, we propose a continuous-time Markov chain model to examine the longitudinal data that have three categories in the outcome variable. The advantage of this model is that it permits a different number of measurements for each subject and the duration between two consecutive time points of measurements can be irregular. Using the maximum likelihood principle, we can estimate the transition probability between two time points. By using the information provided by the independent variables, this model can also estimate the transition probability for each subject. The Monte Carlo simulation method will be used to investigate the goodness of model fitting compared with that obtained from other models. A public health example will be used to demonstrate the application of this method. ^

Planktonic and benthic stables Isotopes, age model and carbon analysis of HUD91/039 from the northernmost Baffin Bay

A multiproxy study of palaeoceanographic and climatic changes in northernmost Baffin Bay shows that major environmental changes have occurred since the deglaciation of the area at about 12 500 cal. yr BP. The interpretation is based on sedimentology, benthic and planktonic foraminifera and their isotopic composition, as well as diatom assemblages in the sedimentary records at two core sites, one located in the deeper central part of northernmost Baffin Bay and one in a separate trough closer to the Greenland coast. A revised chronology for the two records is established on the basis of 15 previously published AMS 14C age determinations. A basal diamicton is overlain by laminated, fossil-free sediments. Our data from the early part of the fossiliferous record (12 300 - 11 300 cal. yr BP), which is also initially laminated, indicate extensive seasonal sea-ice cover and brine release. There is indication of a cooling event between 11 300 and 10 900 cal. yr BP, and maximum Atlantic Water influence occurred between 10 900 and 8200 cal. yr BP (no sediment recovery between 8200 and 7300 cal. yr BP). A gradual, but fluctuating, increase in sea-ice cover is seen after 7300 cal. yr BP. Sea-ice diatoms were particularly abundant in the central part of northernmost Baffin Bay, presumably due to the inflow of Polar waters from the Arctic Ocean, and less sea ice occurred at the near-coastal site, which was under continuous influence of the West Greenland Current. Our data from the deep, central part show a fluctuating degree of upwelling after c. 7300 cal. yr BP, culminating between 4000 and 3050 cal. yr BP. There was a gradual increase in the influence of cold bottom waters from the Arctic Ocean after about 3050 cal. yr BP, when agglutinated foraminifera became abundant. A superimposed short-term change in the sea-surface proxies is correlated with the Little Ice Age cooling.

Model results of ocean physical field of the reference state and the targets in NetCDF format

In a feasibility study, the potential of proxy data for the temperature and salinity during the Last Glacial Maximum (LGM, about 19 000 to 23 000 years before present) in constraining the strength of the Atlantic meridional overturning circulation (AMOC) with a general ocean circulation model was explored. The proxy data were simulated by drawing data from four different model simulations at the ocean sediment core locations of the Multiproxy Approach for the Reconstruction of the Glacial Ocean surface (MARGO) project, and perturbing these data with realistic noise estimates. The results suggest that our method has the potential to provide estimates of the past strength of the AMOC even from sparse data, but in general, paleo-sea-surface temperature data without additional prior knowledge about the ocean state during the LGM is not adequate to constrain the model. On the one hand, additional data in the deep-ocean and salinity data are shown to be highly important in estimating the LGM circulation. On the other hand, increasing the amount of surface data alone does not appear to be enough for better estimates. Finally, better initial guesses to start the state estimation procedure would greatly improve the performance of the method. Indeed, with a sufficiently good first guess, just the sea-surface temperature data from the MARGO project promise to be sufficient for reliable estimates of the strength of the AMOC.

EOT11a - Global Empirical Ocean Tide model from multi-mission satellite altimetry, with links to model results

EOT11a is a global (E)mpirical (O)cean (T)ide model derived in 2011 by residual analysis of multi-mission satellite (a)ltimeter data. EOT11a includes amplitudes and phases of the main astronomical tides M2, S2, N2, K2, 2N2, O1, K1, P2, and Q1, the non-linear constituent M4, the long period tides Mm and Mf, and the radiational tide S1. Ocean tides as well as loading tides are provided. EOT11a was computed by means of residual tidal analysis of multi-mission altimeter data from TOPEX/Poseidon, ERS-2, ENVISAT, and Jason-1/2, as far as acquired between September 1992 and April 2010. The resolution of 7.5'x7.5' is identical with FES2004 which was used as reference model for the residual tide analysis. The development of EOT11a was funded by the Deutsche Forschungsgemeinschaft (DFG) under grant BO1228/6-2.

Holocene carbon cycle dynamics, links to model files

We are investigating the late Holocene rise in CO2 by performing four experiments with the climate-carbon-cycle model CLIMBER2-LPJ. Apart from the deep sea sediments, important carbon cycle processes considered are carbon uptake or release by the vegetation, carbon uptake by peatlands, and CO 2 release due to shallow water sedimentation of CaCO3. Ice core data of atmospheric CO2 between 8 ka BP and preindustrial climate can only be reproduced if CO2 outgassing due to shallow water sedimentation of CaCO3 is considered. In this case the model displays an increase of nearly 20 ppmv CO2 between 8 ka BP and present day. Model configurations that do not contain this forcing show a slight decrease in atmospheric CO2. We can therefore explain the late Holocene rise in CO2 by invoking natural forcing factors only, and anthropogenic forcing is not required to understand preindustrial CO2 dynamics.

Marine Isotope Stage (MIS) 11 results of model data with Community Climate System Model version 3 including the Dynamic Global Vegetation Model (CCSM3-DGVM) in NetCDF format at global and regional scale

The climate of Marine Isotope Stage (MIS) 11, the interglacial roughly 400,000 years ago, is investigated for four time slices, 416, 410, 400, and 394 ka. The overall picture is that MIS 11 was a relatively warm interglacial in comparison to preindustrial, with Northern Hemisphere (NH) summer temperatures early in MIS 11 (416-410 ka) warmer than preindustrial, though winters were cooler. Later in MIS 11, especially around 400 ka, conditions were cooler in the NH summer, mainly in the high latitudes. Climate changes simulated by the models were mainly driven by insolation changes, with the exception of two local feedbacks that amplify climate changes. Here, the NH high latitudes, where reductions in sea ice cover lead to a winter warming early in MIS 11, as well as the tropics, where monsoon changes lead to stronger climate variations than one would expect on the basis of latitudinal mean insolation change alone, are especially prominent. The results support a northward expansion of trees at the expense of grasses in the high northern latitudes early during MIS 11, especially in northern Asia and North America.