Metal Artifact Reduction in Pelvic Computed Tomography With Hip Prostheses: Comparison of Virtual Monoenergetic Extrapolations From Dual-Energy Computed Tomography and an Iterative Metal Artifact Reduction Algorithm in a Phantom Study.

OBJECTIVE The aim of this study was to directly compare metal artifact reduction (MAR) of virtual monoenergetic extrapolations (VMEs) from dual-energy computed tomography (CT) with iterative MAR (iMAR) from single energy in pelvic CT with hip prostheses. MATERIALS AND METHODS A human pelvis phantom with unilateral or bilateral metal inserts of different material (steel and titanium) was scanned with third-generation dual-source CT using single (120 kVp) and dual-energy (100/150 kVp) at similar radiation dose (CT dose index, 7.15 mGy). Three image series for each phantom configuration were reconstructed: uncorrected, VME, and iMAR. Two independent, blinded radiologists assessed image quality quantitatively (noise and attenuation) and subjectively (5-point Likert scale). Intraclass correlation coefficients (ICCs) and Cohen κ were calculated to evaluate interreader agreements. Repeated measures analysis of variance and Friedman test were used to compare quantitative and qualitative image quality. Post hoc testing was performed using a corrected (Bonferroni) P < 0.017. RESULTS Agreements between readers were high for noise (all, ICC ≥ 0.975) and attenuation (all, ICC ≥ 0.986); agreements for qualitative assessment were good to perfect (all, κ ≥ 0.678). Compared with uncorrected images, VME showed significant noise reduction in the phantom with titanium only (P < 0.017), and iMAR showed significantly lower noise in all regions and phantom configurations (all, P < 0.017). In all phantom configurations, deviations of attenuation were smallest in images reconstructed with iMAR. For VME, there was a tendency toward higher subjective image quality in phantoms with titanium compared with uncorrected images, however, without reaching statistical significance (P > 0.017). Subjective image quality was rated significantly higher for images reconstructed with iMAR than for uncorrected images in all phantom configurations (all, P < 0.017). CONCLUSIONS Iterative MAR showed better MAR capabilities than VME in settings with bilateral hip prosthesis or unilateral steel prosthesis. In settings with unilateral hip prosthesis made of titanium, VME and iMAR performed similarly well.

An improved single-plaquette gauge action

We describe and test a nonperturbatively improved single-plaquette lattice action for 4-d SU(2) and SU(3) pure gauge theory, which suppresses large fluctuations of the plaquette, without requiring the naive continuum limit for smooth fields. We tune the action parameters based on torelon masses in moderate cubic physical volumes, and investigate the size of cut-off effects in other physical quantities, including torelon masses in asymmetric spatial volumes, the static quark potential, and gradient flow observables. In 2-d O(N) models similarly constructed nearest-neighbor actions have led to a drastic reduction of cut-off effects, down to the permille level, in a wide variety of physical quantities. In the gauge theories, we find significant reduction of lattice artifacts, and for some observables, the coarsest lattice result is very close to the continuum value. We estimate an improvement factor of 40 compared to using the Wilson gauge action to achieve the same statistical accuracy and suppression of cut-off effects.

A Single-blinded, Randomized Clinical Trial of How to Implement an Evidence-based Treatment for Generalized Anxiety Disorder [IMPLEMENT] — Effects of Three Different Strategies of Implementation

BACKGROUND: Despite long-standing calls to disseminate evidence-based treatments for generalized anxiety (GAD), modest progress has been made in the study of how such treatments should be implemented. The primary objective of this study was to test three competing strategies on how to implement a cognitive behavioral treatment (CBT) for out-patients with GAD (i.e., comparison of one compensation vs. two capitalization models). METHODS: For our three-arm, single-blinded, randomized controlled trial (implementation of CBT for GAD [IMPLEMENT]), we recruited adults with GAD using advertisements in high-circulation newspapers to participate in a 14-session cognitive behavioral treatment (Mastery of your Anxiety and Worry, MAW-packet). We randomly assigned eligible patients using a full randomization procedure (1:1:1) to three different conditions of implementation: adherence priming (compensation model), which had a systematized focus on patients' individual GAD symptoms and how to compensate for these symptoms within the MAW-packet, and resource priming and supportive resource priming (capitalization model), which had systematized focuses on patients' strengths and abilities and how these strengths can be capitalized within the same packet. In the intention-to-treat population an outcome composite of primary and secondary symptoms-related self-report questionnaires was analyzed based on a hierarchical linear growth model from intake to 6-month follow-up assessment. This trial is registered at ClinicalTrials.gov (identifier: NCT02039193) and is closed to new participants. FINDINGS: From June 2012 to Nov. 2014, from 411 participants that were screened, 57 eligible participants were recruited and randomly assigned to three conditions. Forty-nine patients (86%) provided outcome data at post-assessment (14% dropout rate). All three conditions showed a highly significant reduction of symptoms over time. However, compared with the adherence priming condition, both resource priming conditions indicated faster symptom reduction. The observer ratings of a sub-sample of recorded videos (n = 100) showed that the therapists in the resource priming conditions conducted more strength-oriented interventions in comparison with the adherence priming condition. No patients died or attempted suicide. INTERPRETATION: To our knowledge, this is the first trial that focuses on capitalization and compensation models during the implementation of one prescriptive treatment packet for GAD. We have shown that GAD related symptoms were significantly faster reduced by the resource priming conditions, although the limitations of our study included a well-educated population. If replicated, our results suggest that therapists who implement a mental health treatment for GAD might profit from a systematized focus on capitalization models. FUNDING: Swiss Science National Foundation (SNSF-Nr. PZ00P1_136937/1) awarded to CF. KEYWORDS: Cognitive behavioral therapy; Evidence-based treatment; Implementation strategies; Randomized controlled trial

The temporal evolution of nonverbal synchrony in outpatient psychotherapy: An aggregation of single-case studies

Objective: The authors quantified nonverbal synchrony—the coordination of patient's and therapist's movement—in a random sample of same-sex psychotherapy dyads. The authors contrasted nonverbal synchrony in these dyads with a control condition and assessed its association with session-level and overall psychotherapy outcome. Method: Using an automated objective video analysis algorithm (Motion Energy Analysis; MEA), the authors calculated nonverbal synchrony in (n = 104) videotaped psychotherapy sessions from 70 Caucasian patients (37 women, 33 men, mean age = 36.5 years, SD = 10.2) treated at an outpatient psychotherapy clinic. The sample was randomly drawn from an archive (N = 301) of routinely videotaped psychotherapies. Patients and their therapists assessed session impact with self-report postsession questionnaires. A battery of pre- and postsymptomatology questionnaires measured therapy effectiveness. Results: The authors found that nonverbal synchrony is higher in genuine interactions contrasted with pseudointeractions (a control condition generated by a specifically designed shuffling procedure). Furthermore, nonverbal synchrony is associated with session-level process as well as therapy outcome: It is increased in sessions rated by patients as manifesting high relationship quality and in patients experiencing high self-efficacy. Higher nonverbal synchrony characterized psychotherapies with higher symptom reduction. Conclusions: The results suggest that nonverbal synchrony embodies the patients' self-reported quality of the relationship and further variables of therapy process. This hitherto overlooked facet of therapeutic relationships might prove useful as an indicator of therapy progress and outcome. (PsycINFO Database Record (c) 2015 APA, all rights reserved)

Revealing Assembly of a Pore-Forming Complex Using Single-Cell Kinetic Analysis and Modeling

Many biological processes depend on the sequential assembly of protein complexes. However, studying the kinetics of such processes by direct methods is often not feasible. As an important class of such protein complexes, pore-forming toxins start their journey as soluble monomeric proteins, and oligomerize into transmembrane complexes to eventually form pores in the target cell membrane. Here, we monitored pore formation kinetics for the well-characterized bacterial pore-forming toxin aerolysin in single cells in real time to determine the lag times leading to the formation of the first functional pores per cell. Probabilistic modeling of these lag times revealed that one slow and seven equally fast rate-limiting reactions best explain the overall pore formation kinetics. The model predicted that monomer activation is the rate-limiting step for the entire pore formation process. We hypothesized that this could be through release of a propeptide and indeed found that peptide removal abolished these steps. This study illustrates how stochasticity in the kinetics of a complex process can be exploited to identify rate-limiting mechanisms underlying multistep biomolecular assembly pathways.

Chromium uptake and adsorption in marine phytoplankton - Implications for the marine chromium cycle

Using the radioisotope 51Cr, we investigated the controls of cellular Cr accumulation in an array of marine phytoplankton grown in environmentally relevant Cr concentrations (1–10 nM). Given the affinity of Cr(III) for amorphous Fe-hydroxide mineral surfaces, and the formation of these mineral phases on the outside of phytoplankton cells, extracellular Cr was monitored in a model diatom species (Thalassiosira weissflogii) as extracellular Fe concentrations varied. Extracellular Cr in T. weissflogii increased with increasing extracellular Fe, demonstrating that Cr may be removed from seawater via extracellular adsorption to phytoplankton. Short-term Cr(VI) and Cr(III) uptake experiments performed with T. weissflogii demonstrated that Cr(III) was the primary oxidation state adsorbing to cells and being internalized by them. Cellular Cr:C ratios (<0.5 μmol Cr mol C−1) of the eight phytoplankton species surveyed were significantly lower than previously reported Cr:C ratios in marine particles with a high biogenic component (10–300 μmol Cr mol C−1). This indicates that Cr(III) likely accumulates in marine particles due to uptake and/or adsorption. Mass balance calculations demonstrate that surface water Cr deficits can be explained via loss of Cr(III) to exported particles, thereby providing a mechanism to account for the nutrient depth profile for Cr in modern seawater. Given the large fractionation of stable Cr isotopes during Cr(VI) reduction, Cr(III) associated with exported organic carbon is likely enriched in lighter isotopes. Most sedimentary Cr isotope studies have thus far neglected internal fractionating processes in the marine Cr cycle, but our data indicate that loss of Cr to exported particles may be traced in the sedimentary d53Cr record.

Single nucleotide polymorphism (SNP) selection for genotype-phenotype association studies

With hundreds of single nucleotide polymorphisms (SNPs) in a candidate gene and millions of SNPs across the genome, selecting an informative subset of SNPs to maximize the ability to detect genotype-phenotype association is of great interest and importance. In addition, with a large number of SNPs, analytic methods are needed that allow investigators to control the false positive rate resulting from large numbers of SNP genotype-phenotype analyses. This dissertation uses simulated data to explore methods for selecting SNPs for genotype-phenotype association studies. I examined the pattern of linkage disequilibrium (LD) across a candidate gene region and used this pattern to aid in localizing a disease-influencing mutation. The results indicate that the r2 measure of linkage disequilibrium is preferred over the common D′ measure for use in genotype-phenotype association studies. Using step-wise linear regression, the best predictor of the quantitative trait was not usually the single functional mutation. Rather it was a SNP that was in high linkage disequilibrium with the functional mutation. Next, I compared three strategies for selecting SNPs for application to phenotype association studies: based on measures of linkage disequilibrium, based on a measure of haplotype diversity, and random selection. The results demonstrate that SNPs selected based on maximum haplotype diversity are more informative and yield higher power than randomly selected SNPs or SNPs selected based on low pair-wise LD. The data also indicate that for genes with small contribution to the phenotype, it is more prudent for investigators to increase their sample size than to continuously increase the number of SNPs in order to improve statistical power. When typing large numbers of SNPs, researchers are faced with the challenge of utilizing an appropriate statistical method that controls the type I error rate while maintaining adequate power. We show that an empirical genotype based multi-locus global test that uses permutation testing to investigate the null distribution of the maximum test statistic maintains a desired overall type I error rate while not overly sacrificing statistical power. The results also show that when the penetrance model is simple the multi-locus global test does as well or better than the haplotype analysis. However, for more complex models, haplotype analyses offer advantages. The results of this dissertation will be of utility to human geneticists designing large-scale multi-locus genotype-phenotype association studies. ^

The imaging and dosimetric capabilities of a CT/MR-suitable, anatomically adaptive, shielded intracavitary brachytherapy applicator for the treatment of cervical cancer

Introduction. Investigations into the shortcomings of current intracavitary brachytherapy (ICBT) technology has lead us to design an Anatomically Adaptive Applicator (A3). The goal of this work was to design and characterize the imaging and dosimetric capabilities of this device. The A3 design incorporates a single shield that can both rotate and translate within the colpostat. We hypothesized that this feature, coupled with specific A3 component construction materials and imaging techniques, would facilitate artifact-free CT and MR image acquisition. In addition, by shaping the delivered dose distribution via the A3 movable shield, dose delivered to the rectum will be less compared to equivalent treatments utilizing current state-of-the-art ICBT applicators. ^ Method and materials. A method was developed to facilitate an artifact-free CT imaging protocol that used a "step-and-shoot" technique: pausing the scanner midway through the scan and moving the A 3 shield out of the path of the beam. The A3 CT imaging capabilities were demonstrated acquiring images of a phantom that positioned the A3 and FW applicators in a clinically-applicable geometry. Artifact-free MRI imaging was achieved by utilizing MRI-compatible ovoid components and pulse-sequences that minimize susceptibility artifacts. Artifacts were qualitatively compared, in a clinical setup. For the dosimetric study, Monte-Carlo (MC) models of the A3 and FW (shielded and unshielded) applicators were validated. These models were incorporated into a MC model of one cervical cancer patient ICBT insertion, using 192Ir (mHDR v2 source). The A3 shield's rotation and translation was adjusted for each dwell position to minimize dose to the rectum. Superposition of dose to rectum for all A3 dwell sources (4 per ovoid) was applied to obtain a comparison of equivalent FW treatments. Rectal dose-volume histograms (absolute and HDR/PDR biologically effective dose (BED)) and BED to 2 cc (BED2cc ) were determined for all applicators and compared. ^ Results. Using a "step-and-shoot" CT scanning method and MR compliant materials and optimized pulse-sequences, images of the A 3 were nearly artifact-free for both modalities. The A3 reduced BED2cc by 18.5% and 7.2% for a PDR treatment and 22.4% and 8.7% for a HDR treatment compared to treatments delivered using an uFW and sFW applicator, respectively. ^ Conclusions. The novel design of the A3 facilitated nearly artifact-free image quality for both CT and MR clinical imaging protocols. The design also facilitated a reduction in BED to the rectum compared to equivalent ICBT treatments delivered using current, state-of-the-art applicators. ^

Birth prevalence of isolated congenital limb reduction defects in Texas 1999--2001

Objective. Congenital limb defects are common birth defects occurring in approximately 2-7/10,000 live births. Because congenital limb defects are pervasive throughout all populations, and the conditions profoundly affect quality of life, they represent a significant public health concern. Currently there is a paucity of etiologic information in the literature regarding congenital limb reduction defects which represents a major limitation in developing treatment strategies as well as identifying high risk pregnancies. ^ Additionally, despite the fact that the majority of congenital limb reduction defects are isolated, most previous studies have not separated them from those occurring as part of a known syndrome or with multiple additional congenital anomalies of unknown etiology. It stands to reason that factors responsible for multiple congenital anomalies that happen to include congenital limb reduction defects may be quite different from those factors leading to an isolated congenital limb reduction defect. ^ As a first step toward gaining etiologic understanding, this cross-sectional study was undertaken to determine the birth prevalence and obtain demographic information about non-syndromic (isolated) congenital limb reduction defects that occurred in Texas from 1999-2001. ^ Methods. The study population included all infants/fetuses with isolated congenital limb reduction defects born in Texas during 1999-2001; the comparison population was all infants who were born to mothers who were residents of Texas during the same period of time. The overall birth prevalence of limb reduction defects was determined and adjusted for ethnicity, gender, site of defect (upper limb versus lower limb), county of residence, maternal age and maternal education. ^ Results. In Texas, the overall birth prevalence of isolated CLRDs was 2.1/10,000 live births (1.5 and 0.6/10,000 live births for upper limb and lower limb, respectively). ^ The risk of isolated lower limb CLRDs in Texas was significantly lower in females when gender was examined individually (crude prevalence odds ratio of 0.57, 95% CI of 0.36-0.91) as well as in relation to all other variables used in the analysis (adjusted prevalence odds ratio of 0.58, 95% CI of 0.36-0.93). ^ Harris County (which includes the Houston metropolitan area) had significantly lower risks of all (upper limb and lower limb combined) isolated CLRDs when examined in relation to other counties in Texas, with a crude prevalence odds ratio of 0.4 (95% CI: 0.29-0.72) and an adjusted prevalence odds ratio of 0.50 (95% CI: 0.31-0.80). The risk of isolated upper limb CLRDs was significantly lower in Harris County (crude prevalence odds ratio of 0.45, CI of 0.26-0.76 and adjusted prevalence odds ratio of 0.49, CI of 0.28-0.84). This trend toward decreased risk in Harris County was not observed for isolated lower limb reduction defects (adjusted prevalence odds ratio of 0.50, 95% confidence interval: 0.22-1.12). ^ Conclusions. The birth prevalence of isolated congenital limb reduction defects in Texas is in the lower limits of the range of rates that have been reported by other authors for other states (Alabama, Arkansas, California, Georgia, Hawaii, Iowa, Maryland, Massachusetts, North Carolina, Oklahoma, Utah, Washington) and other countries (Argentina, Australia, Austria, Bolivia, Brazil, Canada, Chile, China, Colombia, Costa Rica, Croatia, Denmark, Ecuador, England, Finland, France, Germany, Hungary, Ireland, Israel, Italy, Lithuania, Mexico, Norway, Paraguay, Peru, Spain, Scotland, Sweden, Switzerland, Uruguay, and Venezuela). In Texas, the birth prevalence of isolated congenital lower limb reduction defects was greater for males than females, while the birth prevalence of isolated congenital upper limb reduction defects was not significantly different between males and females. The reduced rates of limb reduction defects in Harris County warrant further investigation. This study has provided an important first step toward gaining etiologic understanding in the study of isolated congenital limb reduction defects. ^

A critical review: Why isn't "cold pasteurization" being used widespread as a method to prevent food-related illnesses as a result of the consumption of ready-to-eat, fresh fruits, and vegetables

The Centers for Disease Control estimates that foodborne diseases cause approximately 76 million illnesses, 325,000 hospitalizations, and 5,000 deaths in the United States each year. The American public is becoming more health conscious and there has been an increase in the dietary intake of fresh fruits and vegetables. Affluence and demand for convenience has allowed consumers to opt for pre-processed packaged fresh fruits and vegetables. These pre-processed foods are considered Ready-to-Eat. They have many of the advantages of fresh produce without the inconvenience of processing at home. After seeing a decline in food-related illnesses between 1996 and 2004, due to an improvement in meat and poultry safety, tainted produce has tilted the numbers back. This has resulted in none of the Healthy People 2010 targets for food-related illness reduction being reached. Irradiation has been shown to be effective in eliminating many of the foodborne pathogens. The application of irradiation as a food safety treatment has been widely endorsed by many of the major associations involved with food safety and public health. Despite these endorsements there has been very little use of this technology to date for reducing the disease burden associated with the consumption of these products. A review of the available literature since the passage of the 1996 Food Quality Protection Act was conducted on the barriers to implementing irradiation as a food safety process for fresh fruits and vegetables. The impediments to adopting widespread utilization of irradiation food processing as a food safety measure involve a complex array of legislative, regulatory, industry, and consumer issues. The FDA’s approval process limits the expansion of the list of foods approved for the application of irradiation as a food safety process. There is also a lack of capacity within the industry to meet the needs of a geographically dispersed industry.^

TIME SERIES ANALYSIS AS INPUT FOR PREDICTIVE MODELING: PREDICTING CARDIAC ARREST IN A PEDIATRIC INTENSIVE CARE UNIT

The first manuscript, entitled "Time-Series Analysis as Input for Clinical Predictive Modeling: Modeling Cardiac Arrest in a Pediatric ICU" lays out the theoretical background for the project. There are several core concepts presented in this paper. First, traditional multivariate models (where each variable is represented by only one value) provide single point-in-time snapshots of patient status: they are incapable of characterizing deterioration. Since deterioration is consistently identified as a precursor to cardiac arrests, we maintain that the traditional multivariate paradigm is insufficient for predicting arrests. We identify time series analysis as a method capable of characterizing deterioration in an objective, mathematical fashion, and describe how to build a general foundation for predictive modeling using time series analysis results as latent variables. Building a solid foundation for any given modeling task involves addressing a number of issues during the design phase. These include selecting the proper candidate features on which to base the model, and selecting the most appropriate tool to measure them. We also identified several unique design issues that are introduced when time series data elements are added to the set of candidate features. One such issue is in defining the duration and resolution of time series elements required to sufficiently characterize the time series phenomena being considered as candidate features for the predictive model. Once the duration and resolution are established, there must also be explicit mathematical or statistical operations that produce the time series analysis result to be used as a latent candidate feature. In synthesizing the comprehensive framework for building a predictive model based on time series data elements, we identified at least four classes of data that can be used in the model design. The first two classes are shared with traditional multivariate models: multivariate data and clinical latent features. Multivariate data is represented by the standard one value per variable paradigm and is widely employed in a host of clinical models and tools. These are often represented by a number present in a given cell of a table. Clinical latent features derived, rather than directly measured, data elements that more accurately represent a particular clinical phenomenon than any of the directly measured data elements in isolation. The second two classes are unique to the time series data elements. The first of these is the raw data elements. These are represented by multiple values per variable, and constitute the measured observations that are typically available to end users when they review time series data. These are often represented as dots on a graph. The final class of data results from performing time series analysis. This class of data represents the fundamental concept on which our hypothesis is based. The specific statistical or mathematical operations are up to the modeler to determine, but we generally recommend that a variety of analyses be performed in order to maximize the likelihood that a representation of the time series data elements is produced that is able to distinguish between two or more classes of outcomes. The second manuscript, entitled "Building Clinical Prediction Models Using Time Series Data: Modeling Cardiac Arrest in a Pediatric ICU" provides a detailed description, start to finish, of the methods required to prepare the data, build, and validate a predictive model that uses the time series data elements determined in the first paper. One of the fundamental tenets of the second paper is that manual implementations of time series based models are unfeasible due to the relatively large number of data elements and the complexity of preprocessing that must occur before data can be presented to the model. Each of the seventeen steps is analyzed from the perspective of how it may be automated, when necessary. We identify the general objectives and available strategies of each of the steps, and we present our rationale for choosing a specific strategy for each step in the case of predicting cardiac arrest in a pediatric intensive care unit. Another issue brought to light by the second paper is that the individual steps required to use time series data for predictive modeling are more numerous and more complex than those used for modeling with traditional multivariate data. Even after complexities attributable to the design phase (addressed in our first paper) have been accounted for, the management and manipulation of the time series elements (the preprocessing steps in particular) are issues that are not present in a traditional multivariate modeling paradigm. In our methods, we present the issues that arise from the time series data elements: defining a reference time; imputing and reducing time series data in order to conform to a predefined structure that was specified during the design phase; and normalizing variable families rather than individual variable instances. The final manuscript, entitled: "Using Time-Series Analysis to Predict Cardiac Arrest in a Pediatric Intensive Care Unit" presents the results that were obtained by applying the theoretical construct and its associated methods (detailed in the first two papers) to the case of cardiac arrest prediction in a pediatric intensive care unit. Our results showed that utilizing the trend analysis from the time series data elements reduced the number of classification errors by 73%. The area under the Receiver Operating Characteristic curve increased from a baseline of 87% to 98% by including the trend analysis. In addition to the performance measures, we were also able to demonstrate that adding raw time series data elements without their associated trend analyses improved classification accuracy as compared to the baseline multivariate model, but diminished classification accuracy as compared to when just the trend analysis features were added (ie, without adding the raw time series data elements). We believe this phenomenon was largely attributable to overfitting, which is known to increase as the ratio of candidate features to class examples rises. Furthermore, although we employed several feature reduction strategies to counteract the overfitting problem, they failed to improve the performance beyond that which was achieved by exclusion of the raw time series elements. Finally, our data demonstrated that pulse oximetry and systolic blood pressure readings tend to start diminishing about 10-20 minutes before an arrest, whereas heart rates tend to diminish rapidly less than 5 minutes before an arrest.

Nonlinear dimension reduction in pathway-based genome-wide association analysis

Pathway based genome wide association study evolves from pathway analysis for microarray gene expression and is under rapid development as a complementary for single-SNP based genome wide association study. However, it faces new challenges, such as the summarization of SNP statistics to pathway statistics. The current study applies the ridge regularized Kernel Sliced Inverse Regression (KSIR) to achieve dimension reduction and compared this method to the other two widely used methods, the minimal-p-value (minP) approach of assigning the best test statistics of all SNPs in each pathway as the statistics of the pathway and the principal component analysis (PCA) method of utilizing PCA to calculate the principal components of each pathway. Comparison of the three methods using simulated datasets consisting of 500 cases, 500 controls and100 SNPs demonstrated that KSIR method outperformed the other two methods in terms of causal pathway ranking and the statistical power. PCA method showed similar performance as the minP method. KSIR method also showed a better performance over the other two methods in analyzing a real dataset, the WTCCC Ulcerative Colitis dataset consisting of 1762 cases, 3773 controls as the discovery cohort and 591 cases, 1639 controls as the replication cohort. Several immune and non-immune pathways relevant to ulcerative colitis were identified by these methods. Results from the current study provided a reference for further methodology development and identified novel pathways that may be of importance to the development of ulcerative colitis.^

Isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) at different cold seep provinces

Anaerobic methane-oxidizing microbial communities in sediments at cold methane seeps are important factors in controlling methane emission to the ocean and atmosphere. Here, we investigated the distribution and carbon isotopic signature of specific biomarkers derived from anaerobic methanotrophic archaea (ANME groups) and sulphate-reducing bacteria (SRB) responsible for the anaerobic oxidation of methane (AOM) at different cold seep provinces of Hydrate Ridge, Cascadia margin. The special focus was on their relation to in situ cell abundances and methane turnover. In general, maxima in biomarker abundances and minima in carbon isotope signatures correlated with maxima in AOM and sulphate reduction as well as with consortium biomass. We found ANME-2a/DSS aggregates associated with high abundances of sn-2,3-di-O-isoprenoidal glycerol ethers (archaeol, sn-2-hydroxyarchaeol) and specific bacterial fatty acids (C16:1omega5c, cyC17:0omega5,6) as well as with high methane fluxes (Beggiatoa site). The low to medium flux site (Calyptogena field) was dominated by ANME-2c/DSS aggregates and contained less of both compound classes but more of AOM-related glycerol dialkyl glycerol tetraethers (GDGTs). ANME-1 archaea dominated deeper sediment horizons at the Calyptogena field where sn-1,2-di-O-alkyl glycerol ethers (DAGEs), archaeol, methyl-branched fatty acids (ai-C15:0, i-C16:0, ai-C17:0), and diagnostic GDGTs were prevailing. AOM-specific bacterial and archaeal biomarkers in these sediment strata generally revealed very similar d13C-values of around -100 per mill. In ANME-2-dominated sediment sections, archaeal biomarkers were even more 13C-depleted (down to -120 per mill), whereas bacterial biomarkers were found to be likewise 13C-depleted as in ANME-1-dominated sediment layers (d13C: -100 per mill). The zero flux site (Acharax field), containing only a few numbers of ANME-2/DSS aggregates, however, provided no specific biomarker pattern. Deeper sediment sections (below 20 cm sediment depth) from Beggiatoa covered areas which included solid layers of methane gas hydrates contained ANME-2/DSS typical biomarkers showing subsurface peaks combined with negative shifts in carbon isotopic compositions. The maxima were detected just above the hydrate layers, indicating that methane stored in the hydrates may be available for the microbial community. The observed variations in biomarker abundances and 13C-depletions are indicative of multiple environmental and physiological factors selecting for different AOM consortia (ANME-2a/DSS, ANME-2c/DSS, ANME-1) along horizontal and vertical gradients of cold seep settings.

Mineralogy and structural specification of ODP Leg 125 peridotite samples

Abundant serpentinite seamounts are found along the outer high of the Mariana forearc at the top of the inner slope of the trench. One of them, Conical Seamount, was drilled at Sites 778, 779, and 780 during Leg 125. The rocks recovered at Holes 779A and 780C, respectively, on the flanks and at the summit of the seamount, include moderately serpentinized depleted harzburgites and some dunites. These rocks exhibit evidence of resorption of the orthopyroxene, when present, and the local presence of very calcic-rich diopside in veins oblique to the main high-temperature foliation of the rock. The peridotites, initially well-foliated with locally poikiloblastic textures, show overprints of a two-stage deformation history: (1) a high-temperature (>1000°C), low-stress (0.02 GPa), homogeneous deformation that has led to the present Porphyroclastic textures displayed by the rocks and (2) heterogeneous ductile shearing at a much higher stress (0.05 GPa). This heterogeneous shearing probably describes a single tectonic event because it began at high temperatures, producing dynamic recrystallization of olivine in the shear zone, and ended at low temperatures in the stability field of chlorite and serpentine. In a few samples, olivine shows evidence of quasi-hydrostatic recrystallization at a very high temperature. Here, we propose that this recrystallization was related to fluid/magma percolation, a process that can also account for the resorption of the orthopyroxene and for the late crystallization of diopside veins in the rock. The impregnation by fluid or magma, development of the main high-temperature, low-stress deformation, and subsequent migration recrystallization of olivine probably occurred in a mantle fragment involved in the arc formation. In addition, this mantle has preserved structures that may have formed earlier in the oceanic lithosphere upon which the arc formed. Heterogeneous ductile shear zones in the peridotites may have developed during uplift. The "cold" deformation may have taken place during diapiric rise of hot mantle that underwent subsequent serpentinization or gliding along normal faults associated with the extension of the eastern margin of the forearc.

Chemical and Sr isotopic compositions of 3 step leachates and residues of bulk samples, zeolites, and smectites from Lower Miocene sediments at ODP Site 166-1007

Massive clinoptilolite authigenesis was observed at about 1105 meters below sea floor (mbsf) in lower Miocene wellcompacted carbonate periplatform sediments from the Great Bahama Bank [Ocean Drilling Program, ODP Leg 166, Site 1007]. The diagenetic assemblage comprises abundant zeolite crystallized within foraminifer tests and sedimentary matrix, as well as Mg smectites. In carbonate-rich deposits, the formation of the zeolite requires a supply of silica. Thus, the objective of the study is to determine the origin of the silica supply, its diagenetic evolution, and consequently the related implications on interpretation of the sedimentary record, in terms of local or global paleoceanographic change. For lack of evidence for any volcaniclastic input or traces of Si-enriched deep fluids circulation, an in situ biogenic source of silica is validated by isotopic data and chemical modeling for the formation of such secondary minerals in shallow-water carbonate sequences. Geochemical and strontium isotopic data clearly establish the marine signature of the diagenetic zeolite, as well as its contemporaneous formation with the carbonate deposition (Sr model ages of 19.6-23.2 Ma). The test of saturation for the pore fluids specifies the equilibrium state of the present mineralogical assemblage. Seawater-rock modeling specifies that clinoptilolite precipitates from the dissolution of biogenic silica, which reacts with clay minerals. The amount of silica (opal-A) involved in the reaction has to be significant enough, at least 10 wt.%, to account for the observed content of clinoptilolite occurring at the most zeolite-rich level. Modeling also shows that the observed amount of clinoptilolite (~19%) reflects an in situ and short-term reaction due to the high reactivity of primary biogenic silica (opal-A) until its complete depletion. The episodic occurrence of these well-lithified zeolite-rich levels is consistent with the occurrence of seismic reflectors, particularly the P2 seismic sequence boundary located at 1115 mbsf depth and dated as 23.2 Ma. The age range of most zeolitic sedimentary levels (biostratigraphic ages of 21.5-22 Ma) correlates well with that of the early Miocene glaciation Mi-1 and Mi-1a global events. Thus, the clinoptilolite occurrence in the shallow carbonate platform environment far from volcanogenic supply, or in other sensitive marine areas, is potentially a significant new proxy for paleoproductivity and oceanic global events, such as the Miocene events, which are usually recognized in deep-sea pelagic sediments and high latitude deposits.