Predictors of HIV testing among injection drug users

The current analysis examined the association of several demographic and behavioral variables with prior HIV testing within a population of injection drug users (IDUs) living in Harris County, Texas in 2005 (n=563). After completing the initial univariate analyses of all potential predictors, a multivariable model was created. This model was designed to guide future intervention efforts. Data used in this analysis were collected by the University of Texas School of Public Health in association with the Houston Department of Health and Human Services for the first IDU cycle of the National HIV Behavioral Surveillance System. About 76% of the IDUs reported previously being tested for HIV. Demographic variables that displayed a significant association with prior testing during the univariate analyses include age, race/ethnicity, birth outside the United States, education level, recent arrest, and current health insurance coverage. Several drug-related and sexual behaviors also demonstrated significant associations with prior testing, including age of first injection drug use, heroin use, methamphetamine use, source of needles or syringes, consistent use of new needles, recent visits to a shooting gallery or similar location, previous alcohol or drug treatment, condom use during their most recent sexual encounter, and having sexual partners who also used injection drugs. Additionally, the univariate analyses revealed that recent use of health or HIV prevention services was associated with previously testing for HIV. The final multivariable model included age, race/ethnicity, recent arrest, previous alcohol or drug treatment, and heroin use. ^

Functional data analysis approaches for genotype-phenotype association studies from next-generation sequencing

Next-generation DNA sequencing platforms can effectively detect the entire spectrum of genomic variation and is emerging to be a major tool for systematic exploration of the universe of variants and interactions in the entire genome. However, the data produced by next-generation sequencing technologies will suffer from three basic problems: sequence errors, assembly errors, and missing data. Current statistical methods for genetic analysis are well suited for detecting the association of common variants, but are less suitable to rare variants. This raises great challenge for sequence-based genetic studies of complex diseases.^ This research dissertation utilized genome continuum model as a general principle, and stochastic calculus and functional data analysis as tools for developing novel and powerful statistical methods for next generation of association studies of both qualitative and quantitative traits in the context of sequencing data, which finally lead to shifting the paradigm of association analysis from the current locus-by-locus analysis to collectively analyzing genome regions.^ In this project, the functional principal component (FPC) methods coupled with high-dimensional data reduction techniques will be used to develop novel and powerful methods for testing the associations of the entire spectrum of genetic variation within a segment of genome or a gene regardless of whether the variants are common or rare.^ The classical quantitative genetics suffer from high type I error rates and low power for rare variants. To overcome these limitations for resequencing data, this project used functional linear models with scalar response to develop statistics for identifying quantitative trait loci (QTLs) for both common and rare variants. To illustrate their applications, the functional linear models were applied to five quantitative traits in Framingham heart studies. ^ This project proposed a novel concept of gene-gene co-association in which a gene or a genomic region is taken as a unit of association analysis and used stochastic calculus to develop a unified framework for testing the association of multiple genes or genomic regions for both common and rare alleles. The proposed methods were applied to gene-gene co-association analysis of psoriasis in two independent GWAS datasets which led to discovery of networks significantly associated with psoriasis.^

Sedimentation rate calculations and isotopic analysis on sediment cores along the IODP Expedition 311 transect

The oceanographic and tectonic conditions of accretionary margins are well-suited for several potential processes governing methane generation, storage and release. To identify the relevant methane evolution pathways in the northern Cascadia accretionary margin, a four-site transect was drilled during Integrated Ocean Drilling Program Expedition 311. The d13C values of methane range from a minimum value of -82.2 per mil on an uplifted ridge of accreted sediment near the deformation front (Site U1326, 1829 mbsl, meters below sea level) to a maximum value of -39.5 per mil at the most landward location within an area of steep canyons near the shelf edge (Site U1329, 946 mbsl). An interpretation based solely on methane isotope values might conclude the 13C-enrichment of methane indicates a transition from microbially- to thermogenically-sourced methane. However, the co-existing CO2 exhibits a similar trend of 13C-enrichment along the transect with values ranging from -22.5 per mil to +25.7 per mil. The magnitude of the carbon isotope separation between methane and CO2 (Ec = 63.8 ± 5.8) is consistent with isotope fractionation during microbially mediated carbonate reduction. These results, in conjunction with a transect-wide gaseous hydrocarbon content composed of > 99.8% (by volume) methane and uniform dDCH4 values (-172 per mil ± 8) that are distinct from thermogenic methane at a seep located 60 km from the Expedition 311 transect, suggest microbial CO2 reduction is the predominant methane source at all investigated sites. The magnitude of the intra-site downhole 13C-enrichment of CO2 within the accreted ridge (Site U1326) and a slope basin nearest the deformation front (Site U1325, 2195 mbsl) is ~ 5 per mil. At the mid-slope site (Site U1327, 1304 mbsl) the downhole 13C-enrichment of the CO2 is ~ 25 per mil and increases to ~ 40 per mil at the near-shelf edge Site U1329. This isotope fractionation pattern is indicative of more extensive diagenetic alteration at sites with greater 13C-enrichment. The magnitude of the 13C-enrichment of CO2 correlates with decreasing sedimentation rates and a diminishing occurrence of stratigraphic gas hydrate. We suggest the decreasing sedimentation rates increase the exposure time of sedimentary organic matter to aerobic and anaerobic degradation, during burial, thereby reducing the availability of metabolizable organic matter available for methane production. This process is reflected in the occurrence and distribution of gas hydrate within the northern Cascadia margin accretionary prism. Our observations are relevant for evaluating methane production and the occurrence of stratigraphic gas hydrate within other convergent margins.

Element abundances and Nd isotopic composition in boninite and tholeiite from DSDP Hole 60-458

Boninites are unusual high MgO-high SiO2 volcanic rocks found in several western Pacific island arcs. Their high Mg/(Mg + total Fe) (0.55-0.83) and compatible element contents (Ni = 70-450 ppm, Cr = 200-1800 ppm) indicate equilibration with mantle peridotite, but their low TiO2 contents (0.1-0.5%) indicate severe depletion of this source. K, Rb, Sr and Ba abundances in boninites are typical of primitive arc basalts, but ratios such as Ti/Zr and La/Yb are variable (Ti/Zr = 23-67, (La/Yb)e.f. = 0.6-4.7). Evidence for both enrichment and depletion of incompatible elements suggests that boninites are derived from refractory peridotite which has been metasomatically enriched in LREE, Zr, Sr, Ba and alkalis. Wide variations in 143Nd/144Nd (0.51262-0.51296) are correlated with La/Sm, Sm/Nd and Ti/Zr, which enables identification of components in the boninite source. Possible LREE depleted components have relative REE and Ti abundances like those in depleted peridotites and high 143Nd/144Nd ratios which reach MORB-like values. Possible LREE enriched components have relative REE abundances similar to those in metasomatized mantle peridotite nodules, and low 143Nd/144Nd ratios which indicate either sedimentary sources or mantle sources with recent to ancient LREE enrichment. Relative abundances of Ba and Sr in boninites decrease with increasing LREE enrichment and suggest a non-sedimentary source for the LREE enriched material. Enrichment in Ba, Sr and alkalis may result from a third component derived from subducted oceanic crust. Two models can account for the successive generation of boninites and arc tholeiites within a single area: 1) boninites can be derived from the peridotite residue of earlier arc tholeiite generation which is metasomatically enriched in LREE before boninite volcanism, or 2) arc tholeiites and boninites can be derived from a variably depleted peridotite source which has been pervasively enriched in LREE. Areas of fertile peridotite would yield tholeiites while refractory areas would yield boninites.

Diversity of zooplankton assemblages at Station L4, Western English Channel, measured using next generation DNA sequencing

Background: Zooplankton play an important role in our oceans, in biogeochemical cycling and providing a food source for commercially important fish larvae. However, difficulties in correctly identifying zooplankton hinder our understanding of their roles in marine ecosystem functioning, and can prevent detection of long term changes in their community structure. The advent of massively parallel Next Generation Sequencing technology allows DNA sequence data to be recovered directly from whole community samples. Here we assess the ability of such sequencing to quantify the richness and diversity of a mixed zooplankton assemblage from a productive monitoring site in the Western English Channel. Methodology/Principle Findings: Plankton WP2 replicate net hauls (200 µm) were taken at the Western Channel Observatory long-term monitoring station L4 in September 2010 and January 2011. These samples were analysed by microscopy and metagenetic analysis of the 18S nuclear small subunit ribosomal RNA gene using the 454 pyrosequencing platform. Following quality control a total of 419,042 sequences were obtained for all samples. The sequences clustered in to 205 operational taxonomic units using a 97% similarity cut-off. Allocation of taxonomy by comparison with the National Centre for Biotechnology Information database identified 138 OTUs to species level, 11 to genus level and 1 to order, <2.5% of sequences were classified as unknowns. By comparison a skilled microscopic analyst was able to routinely enumerate only 75 taxonomic groups. Conclusions: The percentage of OTUs assigned to major eukaryotic taxonomic groups broadly aligns between the metagenetic and morphological analysis and are dominated by Copepoda. However, the metagenetics reveals a previously hidden taxonomic richness, especially for Copepoda and meroplankton such as Bivalvia, Gastropoda and Polychaeta. It also reveals rare species and parasites. We conclude that Next Generation Sequencing of 18S amplicons is a powerful tool for estimating diversity and species richness of zooplankton communities.

Organic geochemistry, visual composition, atomic ratios, and reflectance at DSDP Site 87-582, 87-583 and 87-584

Geochemical analyses of organic matter were carried out on Quaternary sediments from Sites 582 and 583 (Nankai Trough) and on Pliocene to Miocene sediments from Site 584 (Japan Trench), DSDP Leg 87, to evaluate petroleum-generating potential and to characterize the organic matter. The vitrinite-huminite reflectances of indigenous materials for these sites are less than 0.3% indicating the immature nature of the sediments. The sediments, however, contain remarkable amounts of recycled organic materials. The Quaternary sediments from Sites 582 and 583 contain small amounts of amorphous organic matter (less than 0.75 wt.% organic carbon and 66-90% amorphous debris), which is composed of predominantly recycled, oxidized, and over-matured (or matured) Type III material. The amount of hydrocarbon yield indicates that those sediments have lean-source potential for commercial hydrocarbon generation. The Pliocene to Miocene sediments from Site 584 contain organic matter (0.3-1.09 wt.% organic carbon) of predominantly amorphous debris (68-96%) that originated in two sources, an indigenous Type II material and a recycled, over-matured material. Pyrolysis shows an upward increase in the section of hydrocarbon yield and the same trend is also observed in organic-carbon content. The amount of the yield indicates that the Miocene sediments have lean-to-fair source potential and the Pliocene sediments have fair-to-good source potential.

Petrology and geochemistry of oceanic intraplate sheet-flow basalts at DSDP Hole 89-462A

Reentry of Hole 462A during Leg 89 resulted in the penetration of a further 140 m of basalt sheet-flows similar to those found during Leg 61 at the same site. Twelve volcanic units (45 to 56) were recognized, comprising a series of rapidly extruded, interlayered aphyric and poorly clinopyroxene-plagioclase-olivine phyric, nonvesicular basalts. All exhibit variable, mild hydration and oxidation, relative to fresh oceanic basalts, produced under reducing, low-CO2-activity conditions within the zeolite facies. Secondary assemblages are dominated by smectites, zeolites, and pyrite, produced by low-temperature reaction with poorly oxygenated seawater. No systematic mineralogical or chemical changes are observed with depth, although thin quenched units and more massive hypocrystalline units exhibit slightly different alteration parageneses. Chemically, the basalts are olivine- and quartz-normative tholeiites, characterized by low incompatible-element abundances, similar to mildly enriched MORB (approaching T-type), with moderate, chrondite-normalized, large-ionlithophile- element depletion patterns and generally lower or near-chrondritic ratios for many low-distribution-coefficient (KD) element pairs. In general, relative to cyclic MORB chemical variation, they are uniform throughout, although 3 chemical megagroups and 22 subgroups are recognized. It is considered that the megagroups represent separate low-pressure-fractionated systems (olivine + Plagioclase ± clinopyroxene), whereas minor variations within them (subgroups) indicate magma mixing and generation of near-steady-state conditions. Overall, relatively minor fractionation coupled with magma mixing produced a series of compositionally uniform lavas. Parental melts were produced by similar degrees of partial melting, although the source may have varied slightly in LIL-element content.

Isotopic geochemistry of granitoids in the Jinshajiang suture zone, SW China

The Jinshajiang suture zone, located in the eastern part of the Tethyan tectonic domain, is noticeable for a large-scale distribution of Late Jurassic to Triassic granitoids. These granitoids were genetically related to the evolution of the Paleo-Tethys Ocean. The Beiwu, Linong and Lunong granitoids occur in the middle zone of the Jinshajiang Suture Zone, and possess similar geochemical features, indicating they share a common magma source. SIMS zircon U-Pb dating reveals the Beiwu, Linong and Lunong granitic intrusions were emplaced at 233.9±1.4 Ma (2 sigma), 233.1 ±1.4 Ma (2 sigma) and 231.0±1.6 Ma (2 sigma), respectively. All of these granitoids are enriched in abundances of Si (SiO2 =65.2-73.5 wt.%), and large-ion-lithophile-elements (LILEs), but depleted in high-field-strength-elements contents (HFSEs, e.g., Nb, Ta, Ti). In addition, they have low P2O5 contents (0.06-0.11 wt.%), A/CNK values ([molecular Al2O3/(CaO+Na2O+K2O)], mostly<1.1) and 10000Ga/Al ratios (1.7-2.2), consistent with the characteristics of I-type granites. In terms of isotopic compositions, these granitoids have high initial 87Sr/86Sr ratios (0.7078-0.7148), Pb isotopic compositions [(206Pb/204Pb)t=18.213-18.598, (207Pb/204Pb)t=15.637-15.730 and (208Pb/204Pb)t=38.323-38.791], zircon d18O values (7. per mil-9.3 per mil) and negative eNd(t) values (-5.1 to -6.7), suggesting they were predominantly derived from the continental crust. Their Nb/Ta ratios (average value=8.6) are consistent with those of the lower continental crust (LCC). However, variable ?Hf(t) values (-8.6 to +2.8) and the occurrences of mafic microgranular enclaves (MMEs) suggest that mantle-derived melts and lower crustal magmas were involved in the generation of these granitoids. Moreover, the high Pb isotopic ratios and elevated zircon d18O values of these rocks indicate a significant contribution of the upper crustal composition. We propose a model in which the Beiwu, Linong and Lunong granitoids were generated under a late collisional or post-collisional setting. It is possible that this collision was completed before Late Triassic. Decompression induced mantle-derived magmas underplated and provided the heat for the anatexis of the crust. Hybrid melts including mantle-derived and the lower crustal magmas were then generated. The hybrid melts thereafter ascended to a shallow depth and resulted in some degree of sedimentary rocks assimilation. Such three-component mixing magmas source and subsequent fractional crystallization could be responsible for the formation of the Beiwu, Linong and Lunong granitoids.

Low-molecular-weight hydrocarbon concentrations, organic carbon contents, and Rock-Eval pyrolysis hydrogen indices at DSDP Holes 75-530A and 75-532

A series of C2-C8 hydrocarbons (including saturated, aromatic, and olefinic compounds) from deep-frozen core samples taken during DSDP Leg 75 (Holes 530A and 532) were analyzed by a combined hydrogen-stripping/thermovaporization method. Concentrations representing both hydrocarbons dissolved in the pore water and adsorbed on the mineral surfaces vary in Hole 530A from about 10 to 15,000 ng/g of dry sediment weight depending on the lithology (organic-carbon-lean calcareous oozes versus "black shales"). Likewise, the organic-carbon-normalized C2-C8 hydrocarbon concentrations vary from 3,500 to 93,100 ng/g Corg, reflecting drastic differences in the hydrogen contents and hence the hydrocarbon potential of the kerogens. The highest concentrations measured of nearly 10**5 ng/g Corg are about two orders of magnitude below those usually encountered in Type-II kerogen-bearing source beds in the main phase of petroleum generation. Therefore, it was concluded that Hole 530A sediments, even at 1100 m depth, are in an early stage of evolution. The corresponding data from Hole 532 indicated lower amounts (3,000-9,000 ng/g Corg), which is in accordance with the shallow burial depth and immaturity of these Pliocene/late Miocene sediments. Significant changes in the light hydrocarbon composition with depth were attributed either to changes in kerogen type or to maturity related effects. Redistribution pheonomena, possibly the result of diffusion, were recognized only sporadically in Hole 530A, where several organic-carbon lean samples were enriched by migrated gaseous hydrocarbons. The core samples from Hole 530A were found to be severely contaminated by large quantities of acetone, which is routinely used as a solvent during sampling procedures on board Glomar Challenger.