Distribution of quality adjusted life expectancy: A systems approach

Statistical methods are developed which assess survival data for two attributes; (1) prolongation of life, (2) quality of life. Health state transition probabilities correspond to prolongation of life and are modeled as a discrete-time semi-Markov process. Imbedded within the sojourn time of a particular health state are the quality of life transitions. They reflect events which differentiate perceptions of pain and suffering over a fixed time period. Quality of life transition probabilities are derived from the assumptions of a simple Markov process. These probabilities depend on the health state currently occupied and the next health state to which a transition is made. Utilizing the two forms of attributes the model has the capability to estimate the distribution of expected quality adjusted life years (in addition to the distribution of expected survival times). The expected quality of life can also be estimated within the health state sojourn time making more flexible the assessment of utility preferences. The methods are demonstrated on a subset of follow-up data from the Beta Blocker Heart Attack Trial (BHAT). This model contains the structure necessary to make inferences when assessing a general survival problem with a two dimensional outcome. ^

Spatial distribution of orofacial cleft birth defects and uranium-radium concentrations in tap water in Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala Counties, Texas

Background Past and recent evidence shows that radionuclides in drinking water may be a public health concern. Developmental thresholds for birth defects with respect to chronic low level domestic radiation exposures, such as through drinking water, have not been definitely recognized, and there is a strong need to address this deficiency in information. In this study we examined the geographic distribution of orofacial cleft birth defects in and around uranium mining district Counties in South Texas (Atascosa, Bee, Brooks, Calhoun, Duval, Goliad, Hidalgo, Jim Hogg, Jim Wells, Karnes, Kleberg, Live Oak, McMullen, Nueces, San Patricio, Refugio, Starr, Victoria, Webb, and Zavala), from 1999 to 2007. The probable association of cleft birth defect rates by ZIP codes classified according to uranium and radium concentrations in drinking water supplies was evaluated. Similar associations between orofacial cleft birth defects and radium/radon in drinking water were reported earlier by Cech and co-investigators in another of the Gulf Coast region (Harris County, Texas).50, 55 Since substantial uranium mining activity existed and still exists in South Texas, contamination of drinking water sources with radiation and its relation to birth defects is a ground for concern. ^ Methods Residential addresses of orofacial cleft birth defect cases, as well as live births within the twenty Counties during 1999-2007 were geocoded and mapped. Prevalence rates were calculated by ZIP codes and were mapped accordingly. Locations of drinking water supplies were also geocoded and mapped. ZIP codes were stratified as having high combined uranium (≥30μg/L) vs. low combined uranium (<30μg/L). Likewise, ZIP codes having the uranium isotope, Ra-226 in drinking water, were also stratified as having elevated radium (≥3 pCi/L) vs. low radium (<3 pCi/L). A linear regression was performed using STATA® generalized linear model (GLM) program to evaluate the probable association between cleft birth defect rates by ZIP codes and concentration of uranium and radium via domestic water supply. These rates were further adjusted for potentially confounding variables such as maternal age, education, occupation, and ethnicity. ^ Results This study showed higher rates of cleft births in ZIP codes classified as having high combined uranium versus ZIP codes having low combined uranium. The model was further improved by adding radium stratified as explained above. Adjustment for maternal age and ethnicity did not substantially affect the statistical significance of uranium or radium concentrations in household water supplies. ^ Conclusion Although this study lacks individual exposure levels, the findings suggest a significant association between elevated uranium and radium concentrations in tap water and high orofacial birth defect rates by ZIP codes. Future case-control studies that can measure individual exposure levels and adjust for contending risk factors could result in a better understanding of the exposure-disease association.^

Comparison of Tumor Shrinkage and Cumulative Dose Distribution for Lung Cancers

Background: The physical characteristic of protons is that they deliver most of their radiation dose to the target volume and deliver no dose to the normal tissue distal to the tumor. Previously, numerous studies have shown unique advantages of proton therapy over intensity-modulated radiation therapy (IMRT) in conforming dose to the tumor and sparing dose to the surrounding normal tissues and the critical structures in many clinical sites. However, proton therapy is known to be more sensitive to treatment uncertainties such as inter- and intra-fractional variations in patient anatomy. To date, no study has clearly demonstrated the effectiveness of proton therapy compared with the conventional IMRT under the consideration of both respiratory motion and tumor shrinkage in non-small cell lung cancer (NSCLC) patients. Purpose: This thesis investigated two questions for establishing a clinically relevant comparison of the two different modalities (IMRT and proton therapy). The first question was whether or not there are any differences in tumor shrinkage between patients randomized to IMRT versus passively scattered proton therapy (PSPT). Tumor shrinkage is considered a standard measure of radiation therapy response that has been widely used to gauge a short-term progression of radiation therapy. The second question was whether or not there are any differences between the planned dose and 5D dose under the influence of inter- and intra-fractional variations in the patient anatomy for both modalities. Methods: A total of 45 patients (25 IMRT patients and 20 PSPT patients) were used to quantify the tumor shrinkage in terms of the change of the primary gross tumor volume (GTVp). All patients were randomized to receive either IMRT or PSPT for NSCLC. Treatment planning goals were identical for both groups. All patients received 5 to 8 weekly repeated 4-dimensional computed tomography (4DCT) scans during the course of radiation treatments. The original GTVp contours were propagated to T50 of weekly 4DCT images using deformable image registration and their absolute volumes were measured. Statistical analysis was performed to compare the distribution of tumor shrinkage between the two population groups. In order to investigate the difference between the planned dose and the 5D dose with consideration of both breathing motion and anatomical change, we re-calculated new dose distributions at every phase of the breathing cycle for all available weekly 4DCT data sets which resulted 50 to 80 individual dose calculations for each of the 7 patients presented in this thesis. The newly calculated dose distributions were then deformed and accumulated to T50 of the planning 4DCT for comparison with the planned dose distribution. Results: At the end of the treatment, both IMRT and PSPT groups showed mean tumor volume reductions of 23.6% ( 19.2%) and 20.9% ( 17.0 %) respectively. Moreover, the mean difference in tumor shrinkage between two groups is 3% along with the corresponding 95% confidence interval, [-8%, 14%]. The rate of tumor shrinkage was highly correlated with the initial tumor volume size. For the planning dose and 5D dose comparison study, all 7 patients showed a mean difference of 1 % in terms of target coverage for both IMRT and PSPT treatment plans. Conclusions: The results of the tumor shrinkage investigation showed no statistically significant difference in tumor shrinkage between the IMRT and PSPT patients, and the tumor shrinkage between the two modalities is similar based on the 95% confidence interval. From the pilot study of comparing the planned dose with the 5D dose, we found the difference to be only 1%. Overall impression of the two modalities in terms of treatment response as measured by the tumor shrinkage and 5D dose under the influence of anatomical change that were designed under the same protocol (i.e. randomized trial) showed similar result.

Making genetic biodiversity measurable : a review of statistical multivariate methods to study variability at gene level

Measures of agro-ecosystems genetic variability are essential to sustain scientific-based actions and policies tending to protect the ecosystem services they provide. To build the genetic variability datum it is necessary to deal with a large number and different types of variables. Molecular marker data is highly dimensional by nature, and frequently additional types of information are obtained, as morphological and physiological traits. This way, genetic variability studies are usually associated with the measurement of several traits on each entity. Multivariate methods are aimed at finding proximities between entities characterized by multiple traits by summarizing information in few synthetic variables. In this work we discuss and illustrate several multivariate methods used for different purposes to build the datum of genetic variability. We include methods applied in studies for exploring the spatial structure of genetic variability and the association of genetic data to other sources of information. Multivariate techniques allow the pursuit of the genetic variability datum, as a unifying notion that merges concepts of type, abundance and distribution of variability at gene level.

Organic-walled dinoflagellate cysts analysis and statistical analysis of 116 surface sediment samples from the eastern Indian Ocean

Assemblages of organic-walled dinoflagellate cysts (dinocysts) from 116 marine surface samples have been analysed to assess the relationship between the spatial distribution of dinocysts and modern local environmental conditions [e.g. sea surface temperature (SST), sea surface salinity (SSS), productivity] in the eastern Indian Ocean. Results from the percentage analysis and statistical methods such as multivariate ordination analysis and end-member modelling, indicate the existence of three distinct environmental and oceanographic regions in the study area. Region 1 is located in western and eastern Indonesia and controlled by high SSTs and a low nutrient content of the surface waters. The Indonesian Throughflow (ITF) region (Region 2) is dominated by heterotrophic dinocyst species reflecting the region's high productivity. Region 3 is encompassing the area offshore north-west and west Australia which is characterised by the water masses of the Leeuwin Current, a saline and nutrient depleted southward current featuring energetic eddies.

Diatom distribution in sediments of the Peruvian coastal upwelling

Two shelf and upper-slope sites (681 and 686) near present cores of active coastal upwelling on the Peruvian margin were sampled continuously at 7.5 cm intervals down to approximately 25 meters below the seafloor (mbsf). Sedimentary structures were subdivided into homogeneous/bioturbated, laminated, and laminated-varved intervals. Diatom analysis and statistical treatment of data revealed almost persistent upwelling over the last 400,000 yr, with slightly increased upwelling during oxygen-isotope Stages 3, 5, 7, and 8 that resulted in anoxic bottom-water conditions and deposition of laminated/undisturbed primary sedimentary structures.

Export-Led Growth and Geographic Distribution of the Poultry Meat Industry in Brazil

This paper includes an examination of the sustainability of recent high growth in the poultry meat industry in Brazil. In addition, an assessment is made of the impact of increased production of poultry meat products on the development of local industries. Comparative studies of leading companies in the United States, Mexico, and Brazil reveal competitive advantages in the low costs of feedstuff and labor as well as disadvantages in the scale of business and management efficiency in the Brazilian poultry sector. Increases in domestic and foreign demand for Brazilian poultry meat have promoted development of the Brazilian poultry sector in local areas. The formation of industrial clusters is observed using regional data related to the location of slaughterhouses and the number of chickens farmed. Statistical analyses support observations made in this paper.

Origin and patterns of distribution of trace elements in street dust. Unleaded petrol and urban lead

The elemental composition, patterns of distribution and possible sources of street dust are not common to all urban environments, but vary according to the peculiarities of each city. The common features and dissimilarities in the origin and nature of street dust were investigated through a series of studies in two widely different cities, Madrid (Spain) and Oslo (Norway), between 1990 and 1994. The most comprehensive sampling campaign was carried out in the Norwegian capital during the summer of 1994. An area of 14 km2, covering most of downtown Oslo and some residential districts to the north of the city, was divided into 1 km2 mapping units, and 16 sampling increments of approximately 150 g were collected from streets and roads in each of them. The fraction below 100 μm was acid-digested and analysed by ICP-MS. Statistical analyses of the results suggest that chemical elements in street dust can be classified into three groups: “urban” elements (Ba, Cd, Co, Cu, Mg, Pb, Sb, Ti, Zn), “natural” elements (Al, Ga, La, Mn, Na, Sr, Th, Y) and elements of a mixed origin or which have undergone geochemical changes from their original sources (Ca, Cs, Fe, Mo, Ni, Rb, Sr, U). Soil resuspension and/or mobilisation appears to be the most important source of “natural” elements, while “urban” elements originate primarily from traffic and from the weathering and corrosion of building materials. The data for Pb seem to prove that the gradual shift from leaded to unleaded petrol as fuel for automobiles has resulted in an almost proportional reduction in the concentration of Pb in dust particles under 100 μm. This fact and the spatial distribution of Pb in the city strongly suggest that lead sources other than traffic (i.e. lead accumulated in urban soil over the years) may contribute as much lead, if not more, to urban street dust.

Thermodynamic aproach to particle size distribution in granular media

The study of particulate systems is of great interest in many fields of science and technology. Soil, sediments, powders, granular materials, colloidal and particulate suspensions are examples of systems involving many size particles. For those systems, the statistical description of the particle size distribution (PSD), that is, the mathematical distribution that defines the relative amounts of particles present, sorted according to size, is a crutial issue. The PSD can be important in understanding soil hydraulic properties, the geological origin or sediments or the physical and chemical properties of granular materials and ceramics, among others.

Three-dimensional spatial distribution of synapses in the neocortex: A dual-beam electron microscopy study

In the cerebral cortex, most synapses are found in the neuropil, but relatively little is known about their 3-dimensional organization. Using an automated dual-beam electron microscope that combines focused ion beam milling and scanning electron microscopy, we have been able to obtain 10 three-dimensional samples with an average volume of 180 µm(3) from the neuropil of layer III of the young rat somatosensory cortex (hindlimb representation). We have used specific software tools to fully reconstruct 1695 synaptic junctions present in these samples and to accurately quantify the number of synapses per unit volume. These tools also allowed us to determine synapse position and to analyze their spatial distribution using spatial statistical methods. Our results indicate that the distribution of synaptic junctions in the neuropil is nearly random, only constrained by the fact that synapses cannot overlap in space. A theoretical model based on random sequential absorption, which closely reproduces the actual distribution of synapses, is also presented.

Spatio-temporal distribution of pyrethroids in soil in Mediterranean paddy fields

Purpose The demand of rice by the increase in population in many countries has intensified the application of pesticides and the use of poor quality water to irrigate fields. The terrestrial environment is one compartment affected by these situations, where soil is working as a reservoir, retaining organic pollutants. Therefore, it is necessary to develop methods to determine insecticides in soil and monitor susceptible areas to be contaminated, applying adequate techniques to remediate them. Materials and methods This study investigates the occurrence of ten pyrethroid insecticides (PYs) and its spatio-temporal variance in soil at two different depths collected in two periods (before plow and during rice production), in a paddy field area located in the Mediterranean coast. Pyrethroids were quantified using gas chromatography?mass spectrometry (GC?MS) after ultrasound-assisted extraction with ethyl acetate. The results obtained were assessed statistically using non-parametric methods, and significant statistical differences (p < 0.05) in pyrethroids content with soil depth and proximity to wastewater treatment plants were evaluated. Moreover, a geographic information system (GIS) was used to monitor the occurrence of PYs in paddy fields and detect risk areas. Results and discussion Pyrethroids were detected at concentrations ?57.0 ng g?1 before plow and ?62.3 ng g?1 during rice production, being resmethrin and cyfluthrin the compounds found at higher concentrations in soil. Pyrethroids were detected mainly at the top soil, and a GIS program was used to depict the obtained results, showing that effluents from wastewater treatment plants (WWTPs) were the main sources of soil contamination. No toxic effects were expected to soil organisms, but it is of concern that PYs may affect aquatic organisms, which represents the worst case scenario. Conclusions A methodology to determine pyrethroids in soil was developed to monitor a paddy field area. The use of water fromWWTPs to irrigate rice fields is one of the main pollution sources of pyrethroids. It is a matter of concern that PYs may present toxic effects on aquatic organisms, as they can be desorbed from soil. Phytoremediation may play an important role in this area, reducing the possible risk associated to PYs levels in soil.

Statistical modelling of variability in sediment-water nutrient and oxygen fluxes

Peer reviewed

Estimating the probability for a protein to have a new fold: A statistical computational model

Structural genomics aims to solve a large number of protein structures that represent the protein space. Currently an exhaustive solution for all structures seems prohibitively expensive, so the challenge is to define a relatively small set of proteins with new, currently unknown folds. This paper presents a method that assigns each protein with a probability of having an unsolved fold. The method makes extensive use of protomap, a sequence-based classification, and scop, a structure-based classification. According to protomap, the protein space encodes the relationship among proteins as a graph whose vertices correspond to 13,354 clusters of proteins. A representative fold for a cluster with at least one solved protein is determined after superposition of all scop (release 1.37) folds onto protomap clusters. Distances within the protomap graph are computed from each representative fold to the neighboring folds. The distribution of these distances is used to create a statistical model for distances among those folds that are already known and those that have yet to be discovered. The distribution of distances for solved/unsolved proteins is significantly different. This difference makes it possible to use Bayes' rule to derive a statistical estimate that any protein has a yet undetermined fold. Proteins that score the highest probability to represent a new fold constitute the target list for structural determination. Our predicted probabilities for unsolved proteins correlate very well with the proportion of new folds among recently solved structures (new scop 1.39 records) that are disjoint from our original training set.