bluuebunny/crossref_metadata_2025 huggingface dataset:
Replication of recently identified associated single-nucleotide polymorphisms from six autoimmune diseases in Genetic Analysis Workshop 16 rheumatoid arthritis data
Authors: Deshmukh Harshal , Kim-Howard Xana , Nath Swapan K
Published: December 2009

Many autoimmune diseases share similar underlying pathology and have a tendency to cluster within families, giving rise to the concept of shared susceptibility genes among them. In the Genetic Analysis Workshop 16 rheumatoid arthritis (RA) data we sought to replicate the genetic association between single-nucleotide polymorphisms (SNPs) identified in recent genome-wide association studies (GWAS) on RA and five other autoimmune diseases. We identified 164 significantly associated non-HLA SNPs (p < 10-5) from 16 GWAS and 13 candidate gene studies on six different autoimmune diseases, including RA, systemic lupus erythematosus, type 1 diabetes, Crohn disease, multiple sclerosis, and celiac disease. Using both direct and imputation-based association test, we replicated 16 shared susceptibility regions involving RA and at least one of the other autoimmune diseases. We also identified hidden population structure within cases and controls in Genetic Analysis Workshop 16 RA data and assessed the effect of population structure on the shared autoimmunity regions. Because multiple autoimmune diseases share common genetic origin, these could be areas of immense interest for further genetic and clinical association studies.
Genome-wide association studies using single-nucleotide polymorphisms versus haplotypes: an empirical comparison with data from the North American Rheumatoid Arthritis Consortium
Authors: Shim Heejung , Chun Hyonho , Engelman Corinne D , Payseur Bret A
Published: December 2009

The high genomic density of the single-nucleotide polymorphism (SNP) sets that are typically surveyed in genome-wide association studies (GWAS) now allows the application of haplotype-based methods. Although the choice of haplotype-based vs. individual-SNP approaches is expected to affect the results of association studies, few empirical comparisons of method performance have been reported on the genome-wide scale in the same set of individuals. To measure the relative ability of the two strategies to detect associations, we used a large dataset from the North American Rheumatoid Arthritis Consortium to: 1) partition the genome into haplotype blocks, 2) associate haplotypes with disease, and 3) compare the results with individual-SNP association mapping. Although some associations were shared across methods, each approach uniquely identified several strong candidate regions. Our results suggest that the application of both haplotype-based and individual-SNP testing to GWAS should be adopted as a routine procedure.
Using a latent growth curve model for an integrative assessment of the effects of genetic and environmental factors on multiple phenotypes
Authors: Hamid Jemila S , Roslin Nicole M , Paterson Andrew D , Beyene Joseph
Published: December 2009

We propose the use of latent growth curve model to assess the influence of genetic, environmental, demographic, and lifestyle factors on multiple phenotypes related to coronary heart disease. We model four quantitative traits (systolic blood pressure, high-density lipoprotein, low-density lipoprotein, and triglycerides) simultaneously in a multivariate framework that allows us to study their change over time, assess individual variation, and investigate cross-phenotype relationships. Environmental, demographic, and lifestyle covariates are included at different levels of the model as time-varying or time-invariant, as appropriate. To investigate the change over time attributed to genetic factors, we use candidate markers that have previously been shown to be associated with the quantitative traits. We illustrate our approach using independent observations from the offspring cohort of the Framingham Heart Study data.
Application of sex-specific single-nucleotide polymorphism filters in genome-wide association data
Authors: Ling Hua , Hetrick Kurt , Bailey-Wilson Joan E , Pugh Elizabeth W
Published: December 2009

We explored five sex-specific quality control filters in North American Rheumatoid Arthritis Consortium's Illumina 550 k datasets. Three X chromosome and three autosomal single-nucleotide polymorphisms flagged by sex quality control filters were missed by filters of call rate at 95% and Hardy-Weinberg equilibrium at 10-6. We applied a subset of these sex-specific quality control filters to eight chromosomes in the Framingham Heart Study samples genotyped by Affymetrix 500 k SNP arrays, and identified another two single-nucleotide polymorphisms that failed to be picked up by the above global filters.
A genome-wide association scan for rheumatoid arthritis data by Hotelling's T2tests
Authors: Chen Lianfu , Zhong Ming , Chen Wei Vivien , Amos Christopher I , Fan Ruzong
Published: December 2009

We performed a genome-wide association scan on the North American Rheumatoid Arthritis Consortium (NARAC) data using Hotelling's T
2 tests, i.e., T

H
based on allele coding and T

G
based on genotype coding. The objective was to identify associations between single-nucleotide polymorphisms (SNPs) or markers and rheumatoid arthritis. In specific candidate gene regions, we evaluated the performance of Hotelling's T
2 tests. Then Hotelling's T
2 tests were used as a tool to identify new regions that contain SNPs showing strong associations with disease. As expected, the strongest association evidence was found in the region of the HLA-DRB1 locus on chromosome 6. In the region of the TRAF1-C5 genes, we identified two SNPs, rs2900180 and rs3761847, with the largest and the second largest T

H
and T

G
scores among all SNPs on chromosome 9. We also identified one SNP, rs2476601, in the region of the PTPN22 gene that had the largest T

H
score and the second largest T

G
score among all SNPs on chromosome 1. In addition, SNPs with the largest T

H
score on each chromosome were identified. These SNPs may be located in the regions of genes that have modest effects on rheumatoid arthritis. These regions deserve further investigation.
Evaluation of random forests performance for genome-wide association studies in the presence of interaction effects
Authors: Kim Yoonhee , Wojciechowski Robert , Sung Heejong , Mathias Rasika A , Wang Li , Klein Alison P , Lenroot Rhoshel K , Malley James , Bailey-Wilson Joan E
Published: December 2009

Random forests (RF) is one of a broad class of machine learning methods that are able to deal with large-scale data without model specification, which makes it an attractive method for genome-wide association studies (GWAS). The performance of RF and other association methods in the presence of interactions was evaluated using the simulated data from Genetic Analysis Workshop 16 Problem 3, with knowledge of the major causative markers, risk factors, and their interactions in the simulated traits. There was good power to detect the environmental risk factors using RF, trend tests, or regression analyses but the power to detect the effects of the causal markers was poor for all methods. The causal marker that had an interactive effect with smoking did show moderate evidence of association in the RF and regression analyses, suggesting that RF may perform well at detecting such interactions in larger, more highly powered datasets.
Identification of gene-gene interaction using principal components
Authors: Li Jia , Tang Rui , Biernacka Joanna M , de Andrade Mariza
Published: December 2009

After more than 200 genome-wide association studies, there have been some successful identifications of a single novel locus. Thus, the identification of single-nucleotide polymorphisms (SNP) with interaction effects is of interest. Using the Genetic Analysis Workshop 16 data from the North American Rheumatoid Arthritis Consortium, we propose an approach to screen for SNP-SNP interaction using a two-stage method and an approach for detecting gene-gene interactions using principal components. We selected a set of 17 rheumatoid arthritis candidate genes to assess both approaches. Our approach using principal components holds promise in detecting gene-gene interactions. However, further study is needed to evaluate the power and the feasibility for a whole genome-wide association analysis using the principal components approach.
Application of Bayesian classification with singular value decomposition method in genome-wide association studies
Authors: Kwon Soonil , Cui Jinrui , Rhodes Shannon L , Tsiang Donald , Rotter Jerome I , Guo Xiuqing
Published: December 2009

To analyze multiple single-nucleotide polymorphisms simultaneously when the number of markers is much larger than the number of studied individuals, as is the situation we have in genome-wide association studies (GWAS), we developed the iterative Bayesian variable selection method and successfully applied it to the simulated rheumatoid arthritis data provided by the Genetic Analysis Workshop 15 (GAW15). One drawback for applying our iterative Bayesian variable selection method is the relatively long running time required for evaluation of GWAS data. To improve computing speed, we recently developed a Bayesian classification with singular value decomposition (BCSVD) method. We have applied the BCSVD method here to the rheumatoid arthritis data distributed by GAW16 Problem 1 and demonstrated that the BCSVD method works well for analyzing GWAS data.
Lewis y antigen promotes the proliferation of ovarian carcinoma-derived RMG-I cells through the PI3K/Akt signaling pathway
Authors: Liu Juanjuan , Lin Bei , Hao Yingying , Qi Yue , Zhu Liancheng , Li Feifei , Liu Dawo , Cong Jianping , Zhang Shulan , Iwamori Masao
Published: December 2009

Background

Lewis y antigen is difucosylated oligosaccharide and is carried by glycoconjugates at cell surface. Elevated expression of Lewis y has been found in 75% of ovarian tumor, and the high expression level is correlated to the tumor's pathological staging and prognosis. This study was to investigate the effect and the possible mechanism of Lewis y on the proliferation of human ovarian cancer cells.

Methods

We constructed a plasmid encoding α1,2-fucosyltransferase (α1,2-FT) gene and then transfected it into ovarian carcinoma-derived RMG-I cells with lowest Lewis y antigen expression level. Effect of Lewis y on cell proliferation was assessed after transfection. Changes in cell survival and signal transduction were evaluated after α-L-fucosidase, anti-Lewis y antibody and phosphatidylinositol 3-kinase (PI3K) inhibitor treatment.

Results

Our results showed that the levels of α1,2-FT gene and Lewis y increased significantly after transfection. The cell proliferation of ovarian carcinoma-derived RMG-I cells sped up as the Lewis y antigen was increased. Both of α-L-fucosidase and anti-Lewis y antibody inhibited the cell proliferation. The phosphorylation level of Akt was apparently elevated in Lewis y-overexpressing cells and the inhibitor of PI3K, LY294002, dramatically inhibited the growth of Lewis y-overexpressing cells. In addition, the phosphorylation intensity and difference in phosphorylation intensity between cells with different expression of α1,2-FT were attenuated significantly by the monoantibody to Lewis y and by the PI3K inhibitor LY294002.

Conclusions

Increased expression of Lewis y antigen plays an important role in promoting cell proliferation through activating PI3K/Akt signaling pathway in ovarian carcinoma-derived RMG-I cells. Inhibition of Lewis y expression may provide a new therapeutic approach for Lewis y positive ovarian cancer.
Recent developments in podiatric prescribing in the UK and Australia
Authors: Gilheany Mark F , Borthwick Alan M
Published: December 2009

Recent and substantial changes in access to restricted medicines by podiatrists in Australia are clearly consistent with healthcare policies aimed at reshaping the healthcare workforce. At the same time, prescribing and access to medicines by allied health professionals, including podiatrists, has been the focus of a recent scoping project by the UK Department of Health. In this commentary we explore the possible implications of these changes.
Local expression of tumor necrosis factor-receptor 1:immunoglobulin G can induce salivary gland dysfunction in a murine model of Sjögren's syndrome
Authors: Vosters Jelle L , Yin Hongen , Roescher Nienke , Kok Marc R , Tak Paul P , Chiorini John A
Published: December 2009

Introduction

Tumor necrosis factor is a pleiotropic cytokine with potent immune regulatory functions. Although tumor necrosis factor inhibitors have demonstrated great utility in treating other autoimmune diseases, such as rheumatoid arthritis, there are conflicting results in Sjögren's syndrome. The aim of this study was to assess the effect of a locally expressed tumor necrosis factor inhibitor on the salivary gland function and histopathology in an animal model of Sjögren's syndrome.

Methods

Using in vivo adeno associated viral gene transfer, we have stably expressed soluble tumor necrosis factor-receptor 1-Fc fusion protein locally in the salivary glands in the Non Obese Diabetic model of Sjögren's syndrome. Pilocarpine stimulated saliva flow was measured to address the salivary gland function and salivary glands were analyzed for focus score and cytokine profiles. Additionally, cytokines and autoantibody levels were measured in plasma.

Results

Local expression of tumor necrosis factor-receptor 1:immunoglobulin G fusion protein resulted in decreased saliva flow over time. While no change in lymphocytic infiltrates or autoantibody levels was detected, statistically significant increased levels of tumor growth factor-β1 and decreased levels of interleukin-5, interleukin-12p70 and interleukin -17 were detected in the salivary glands. In contrast, plasma levels showed significantly decreased levels of tumor growth factor-β1 and increased levels of interleukin-4, interferon-γ, interleukin-10 and interleukin-12p70.

Conclusions

Our findings suggest that expression of tumor necrosis factor inhibitors in the salivary gland can have a negative effect on salivary gland function and that other cytokines should be explored as points for therapeutic intervention in Sjögren's syndrome.
Combination effect of antithrombin and recombinant human soluble thrombomodulin in a lipopolysaccharide induced rat sepsis model
Authors: Iba Toshiaki , Nakarai Etsuro , Takayama Toshio , Nakajima Kenji , Sasaoka Tetsumasa , Ohno Yoichi
Published: December 2009

Introduction

Recombinant human soluble thrombomodulin (rhsTM) is newly developed for the treatment of DIC. The purpose of this study was to evaluate the efficacy of the concomitant administration of rhsTM and antithrombin (AT).

Methods

In the first series, rats were treated with either 62.5, 125, 250 or 500 IU/kg (n = 6, each) of AT or 0.125, 0.25, 0.5 or 1.0 mg/kg (n = 6, each) of rhsTM followed by lipopolysaccharide (LPS) injection. 8 h later, the fibrinogen level was examined. In the second series, TM group was pretreated with 0.25 mg/kg of rhsTM, AT group was pretreated with 125 IU/kg of AT, AT/TM group was pretreated with both AT and rhsTM, and control group was pretreated with saline (n = 7, each). The platelet count, fibrinogen, ALT, LDH and high-mobility group box 1 (HMGB1) levels were measured. In addition, histologic changes in liver were examined. In the third series, survival was calculated up to 24 h.

Results

Both AT and rhsTM produced a linear dose-response with regard to the fibrinogen level, with 125 IU/kg of AT and 0.25 mg/kg of rhsTM producing equivalent effects. The combined administration of AT and rhsTM significantly reduced the decrease in the platelet count and the fibrinogen level (P < 0.05, 0.01, respectively). The elevations in ALT and LDH were significantly suppressed in all treatment groups. The HMGB1 level and the histologic changes tended to indicate damage reduction. Survival was significantly better only in AT/TM group (P < 0.01).

Conclusions

The coadministration of AT and rhsTM might be effective for the treatment of severe sepsis.
Migration velocity analysis by double path-integral migration
Authors: Schleicher Jörg , Costa Jessé C.
Published: December 2009

The idea of path-integral imaging is to sum over the migrated images obtained for a set of migration velocity models. Velocities where common-image gathers align horizontally are stationary, thus favoring these images in the overall stack. The overall image forms with no knowledge of the true velocity model. However, the velocity information associated with the final image can be determined in the process. By executing the path-integral imaging twice and weighting one of the stacks with the velocity value, the stationary velocities that produce the final image can then be extracted by a division of the two images. The velocity extraction, interpola-tion, and smoothing can be done fully automatically, without the need for human interpretation or other intervention. A numerical example demonstrated that quantitative information about the migration velocity model can be determined by double path-integral migration. The so-obtained velocity model can then be used as a starting model for subsequent velocity analysis tools like migration velocity analysis or tomographic methods.
Diffraction imaging by multifocusing
Authors: Berkovitch Alex , Belfer Igor , Hassin Yehuda , Landa Evgeny
Published: December 2009

Correct identification of geologic discontinuities, such as faults, pinch-outs, and small-size scattering objects, is a primary challenge of the seismic method. Seismic response from these objects is encoded in diffractions. Our method images local heterogeneities of the subsurface using diffracted seismic events. The method is based on coherent summation of diffracted waves arising in media that include interface discontinuities and local velocity heterogeneities. This is done using a correlation procedure that coherently focuses diffraction energy on a seismic section by flattening diffraction events using a new local-time-correction formula to parameterize diffraction traveltime curves. This time correction, which is based on the multifocusing method, depends on two parameters: the emergent angle and the radius of curvature of the diffracted wavefront. These parameters are estimated directly from prestack seismic traces. The diffraction multifocusing stack (DMFS) can separate diffracted and reflected energy on a stacked section by focusing diffractions to the diffraction location and defocusing the reflection energy over a large area.
Optimized implicit finite-difference and Fourier finite-difference migration for VTI media
Authors: Shan Guojian
Published: December 2009

Propagation velocity of seismic waves in heterogeneous VTI media depends not only on spatial location but also on their propagation direction, which leads to a much more complex dispersion relation than in isotropic media. As a result, designing implicit finite-difference (FD) schemes for wavefield extrapolation in anisotropic media through analytic Taylor-series expansion is more difficult. Implicit FD and Fourier finite-difference (FFD) schemes are developed for vertical transversely isotropic (VTI) media based on function fitting. The dispersion relation of VTI media is approximated with a rational function and its coefficients are estimated by weighted least-squares optimization. Because these coefficients are functions of Thomsen anisotropy parameters ([Formula: see text] and [Formula: see text]) and vary laterally in heterogeneous VTI media, they are calculated before wavefield extrapolation and stored in a table. Implicit FD and FFD schemes for VTI media are almost the same as for isotropic media, except that coefficients are looked up in a precalculated table. Impulse responses and relative dispersion-relation error show that accuracy of the FD scheme for VTI media is similar to its counterpart in isotropic media. Application to a synthetic data set showed that implicit FD and FFD can handle laterally varying VTI media.
Target-oriented wave-equation least-squares migration/inversion with phase-encoded Hessian
Authors: Tang Yaxun
Published: December 2009

Prestack depth migration produces blurred images resulting from limited acquisition apertures, complexities in the velocity model, and band-limited characteristics of seismic waves. This distortion can be partially corrected using the model-space least-squares migration/inversion approach, where a target-oriented wave-equation Hessian operator is computed explicitly and then inverse filtering is applied iteratively to deblur or invert for the reflectivity. However, one difficulty is the cost of computing the explicit Hessian operator, which requires storing a large number of Green’s functions, making it challenging for large-scale applications. A new method to compute the Hessian operator for the wave-equation-based least-squares migration/inversion problem modifies the original explicit Hessian formula, enabling efficient computation of this operator. An advantage is that the method eliminates disk storage of Green’s functions. The modifications, however, also introduce undesired crosstalk artifacts. Two different phase-encoding schemes, plane-wave-phase encoding and random-phase encoding, suppress the crosstalk. When the randomly phase-encoded Hessian operator is applied to the Sigsbee2A synthetic data set, an improved subsalt image with more balanced amplitudes is obtained.
An overview of depth imaging in exploration geophysics
Authors: Etgen John , Gray Samuel H. , Zhang Yu
Published: December 2009

Prestack depth migration is the most glamorous step of seismic processing because it transforms mere data into an image, and that image is considered to be an accurate structural description of the earth. Thus, our expectations of its accuracy, robustness, and reliability are high. Amazingly, seismic migration usually delivers. The past few decades have seen migration move from its heuristic roots to mathematically sound techniques that, using relatively few assumptions, render accurate pictures of the interior of the earth. Interestingly, the earth and the subjects we want to image inside it are varied enough that, so far, no single migration technique has dominated practical application. All techniques continually improve and borrow from each other, so one technique may never dominate. Despite the progress in structural imaging, we have not reached the point where seismic images provide quantitatively accurate descriptions of rocks and fluids. Nor have we attained the goal of using migration as part of a purely computational process to determine subsurface velocity. In areas where images have the highest quality, we might be nearing those goals, collectively called inversion. Where data are more challenging, the goals seem elusive. We describe the progress made in depth migration to the present and the most significant barriers to attaining its inversion goals in the future. We also conjecture on progress likely to be made in the years ahead and on challenges that migration might not be able to meet.
Green’s theorem as a comprehensive framework for data reconstruction, regularization, wavefield separation, seismic interferometry, and wavelet estimation: A tutorial
Authors: Ramírez Adriana Citlali , Weglein Arthur B.
Published: December 2009

Almost every link in the chain of exploration seismology methods used to process recorded data has been affected by Green’s theorem. Among the seismic processes that can be related to, and/or have benefited from, Green’s theorem are wavelet estimation, multiple elimination, regularization, redatuming, imaging, deghosting, and interferometry. This tutorial on various seismic exploration methods derived from Green’s theorem emphasizes seismic data reconstruction (including regularization and redatuming) and its relationship to interferometry as well as to wavelet estimation and wavefield separation. The last decade has witnessed ever-increasing attention within the energy industry and its concomitant representation in the published literature to methods dealing with wavefield reconstruction through in-terferometry or virtual-source techniques. The attention has re- newed interest in Green’s theorem because all different ap-proaches to interferometry can be derived from it. This tutorial provides a derivation and explication of the limitations of interferometric techniques (when interferometry is used to process measured data from marine surface seismic experiments with controlled sources) as approximations to Green’s theorem. This tutorial provides a definite statement of the comprehensive framework given by Green’s theorem to wavefield reconstruction and shows how different techniques are directly understood as specific mathematical forms and/or approximations to the theorem. The use of approximations can have shortcomings and create artifacts. These artifacts and errors are also analyzed and explained. All methods discussed in this tutorial recognize their foundation on Green’s theorem and have a secure mathematical-physics cornerstone to recognize the assumptions behind distinct approximate solutions and to guide the search for more accurate, effective techniques.
Simultaneous time imaging, velocity estimation, and multiple suppression using local event slopes
Authors: Cooke Dennis , Bóna Andrej , Hansen Benn
Published: December 2009

Starting with the double-square-root equation we derive expressions for a velocity-independent prestack time migration and for the associated migration velocity. We then use that velocity to identify multiples and suppress them as part of the imaging step. To describe our algorithm, workflow, and products, we use the terms velocity-independent and oriented. While velocity-independent imaging does not require an input migration velocity, it does require input [Formula: see text]-values (also called local event slopes) measured in both the shot and receiver domains. There are many possible methods of calculating these required input [Formula: see text]-values, perhaps the simplest is to compute the ratio of instantaneous spatial frequency to instantaneous temporal frequency. Using a synthetic data set rich in multiples, we test the oriented algorithm and generate migrated prestack gathers, the oriented migration velocity field, and stacked migrations. We use oriented migration velocities for prestack multiple suppression. Without this multiple suppression step, the velocity-independent migration is inferior to a conventional Kirchhoff migration because the oriented migration will flatten primaries and multiples alike in the common image domain. With this multiple suppression step, the velocity-independent are very similar to a Kirchhoff migration generated using the known migration velocity of this test data set.
3D plane-wave migration in tilted coordinates: A field data example
Authors: Shan Guojian , Clapp Robert , Biondi Biondo
Published: December 2009

We have extended isotropic plane-wave migration in tilted coordinates to 3D anisotropic media and applied it on a Gulf of Mexico data set. Recorded surface data are transformed to plane-wave data by slant-stack processing in inline and crossline directions. The source plane wave and its corresponding slant-stacked data are extrapolated into the subsurface within a tilted coordinate system whose direction depends on the propagation direction of the plane wave. Images are generated by crosscorrelating these two wavefields. The shot sampling is sparse in the crossline direction, and the source generated by slant stacking is not really a plane-wave source but a phase-encoded source. We have discovered that phase-encoded source migration in tilted coordinates can image steep reflectors, using 2D synthetic data set examples. The field data example shows that 3D plane-wave migration in tilted coordinates can image steeply dipping salt flanks and faults, even though the one-way wave-equation operator is used for wavefield extrapolation.
Slowness-driven Gaussian-beam prestack depth migration for low-fold seismic data
Authors: Hu Chaoshun , Stoffa Paul L.
Published: December 2009

Subsurface images based on low-fold seismic reflection data or data with geometry acquisition limitations, such as obtained from ocean-bottom seismography (OBS), are often corrupted by migration swing artifacts. Incorporating prestack instantaneous slowness information into the imaging condition can significantly reduce these migration swing artifacts and improve image quality, especially for areas with poor illumination. We combine the horizontal surface slowness information of observed seismic data with Gaussian-beam depth migration to implement a new slowness-driven Gaussian-beam prestack depth migration whereby Fresnel weighting is combined naturally with beam summation. The prestack instantaneous slowness information is extracted from the original OBS or shot gathers using local slant stacks and is combined with a local semblance analysis. During migration, we propagate the seismic energy downward, knowing its instantaneous slowness information. At each image location, the beam summation is localized in a resolution-dependent Fresnel zone; the instantaneous slowness information controls the beam summation. Synthetic and real data examples confirm that slowness-driven Gaussian-beam migration can suppress most noise from inadequate stacking and give a clearer migration result.
Direct nonlinear inversion of multiparameter 1D elastic media using the inverse scattering series
Authors: Zhang Haiyan , Weglein Arthur B.
Published: December 2009

In the direct nonlinear inversion method and in algorithms for 1D elastic media, P-wave velocity, S-wave velocity, and density are depth dependent. “Direct nonlinear” means that the method uses explicit formulas that (1) input data and directly output changes in material properties without the need for indirect procedures such as model matching, searching, optimization, or other assumed aligned objectives or proxies and that (2) the algorithms recognize and directly invert the intrinsic nonlinear relationship between changes in material properties and the recorded reflection wavefields. To achieve full elastic inversion, all components of data (such as PP, SP, and SS data) are needed. The method assumes that only data and reference medium propertiesare input, and terms in the inverse series for moving mislocated reflectors resulting from the linear inverse term are separated from amplitude correction terms. Although in principle this direct inversion approach requires all components of elastic data, synthetic tests indicate that a consistent value-added result may be achieved given only PP data measurements, as long as the PP data are used to approximately synthesize the PS and SP components. Further value would be derived from measuring all components of the data as the method requires. If all components of data are available, one consistent method can solve for all of the second terms (the first terms beyond linear). The explicit nonlinear inversion formulas provide an unambiguous data requirement message as well as conceptual and practical added value beyond both linear approaches and all indirect methods.
Kinematics of shot-geophone migration
Authors: Stolk Christiaan C. , de Hoop Maarten V. , Symes William W.
Published: December 2009

Recent analysis and synthetic examples have shown that many prestack depth migration methods produce nonflat image gathers containing spurious events, even when provided with a kinematically correct migration velocity field, if this velocity field is highly refractive. This pathology occurs in all migration methods that produce partial images as independent migrations of data bins. Shot-geophone prestack depth migration is an exception to this pattern: each point in the prestack image volume depends explicitly on all traces within the migration aperture. Using a ray-theoretical analysis, we have found that shot-geophone migration produces focused (subsurface-offset domain) or flat (scattering-angle domain) image gathers, provided there is a curvilinear coordinate system defining pseudodepth with respect to which the rays carrying significant energy do not turn, and that the acquisition coverage is sufficient to determine all such rays. Although the analysis is theoretical and idealized, a synthetic example suggests that its implications remain valid for practical implementations, and that shot-geophone prestack depth migration could be a particularly appropriate tool for velocity analysis in a complex structure.
Clarifying the underlying and fundamental meaning of the approximate linear inversion of seismic data
Authors: Weglein Arthur B. , Zhang Haiyan , Ramírez Adriana C. , Liu Fang , Lira Jose Eduardo
Published: December 2009

Linear inversion is defined as the linear approximation of a direct-inverse solution. This definition leads to data requirements and specific direct-inverse algorithms, which differ with all current linear and nonlinear approaches, and is immediately relevant for target identification and inversion in an elastic earth. Common practice typically starts with a direct forward or modeling expression and seeks to solve a forward equation in an inverse sense. Attempting to solve a direct forward problem in an inverse sense is not the same as solving an inverse problem directly. Distinctions include differences in algorithms, in the need for a priori information, and in data requirements. The simplest and most accessible examples are the direct-inversion tasks, derived from the inverse scattering series (ISS), for the removal of free-surface and internal multiples. The ISS multiple-removal algorithms require no subsurface information, and they are independent of earth model type. A direct forward method solved in an inverse sense, for modeling and subtracting multiples, would require accurate knowledge of every detail of the subsurface the multiple has experienced. In addition, it requires a different modeling and subtraction algorithm for each different earth-model type. The ISS methods for direct removal of multiples are not a forward problem solved in an inverse sense. Similarly, the direct elastic inversion provided by the ISS is not a modeling formula for PP data solved in an inverse sense. Direct elastic inversion calls for [Formula: see text], [Formula: see text], [Formula: see text], … data, for direct linear and nonlinear estimates of changes in mechanical properties. In practice, a judicious combination of direct and indirect methods are called upon for effective field data application.
Statin Use and Prognosis in Patients With Diffuse Large B-Cell Lymphoma and Follicular Lymphoma in the Rituximab Era
Authors: Nowakowski Grzegorz S. , Maurer Matthew J. , Habermann Thomas M. , Ansell Stephen M. , Macon William R. , Ristow Kay M. , Allmer Cristine , Slager Susan L. , Witzig Thomas E. , Cerhan James R.
Published: December 2009

Purpose

Statins have antilymphoma properties but have also been shown to inhibit the binding of rituximab to the CD20 antigen, resulting in reduced antitumor activity of rituximab in vitro. The clinical impact of statin use on the outcome of lymphoma patients treated with a rituximab-containing regimen is unknown.

Patients and Methods

Consecutive patients with newly diagnosed, diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) were enrolled onto a registry and observed prospectively. The impact of statin use on patients' outcomes was analyzed.

Results

Two hundred twenty-eight patients with DLBCL and 293 patients with FL were enrolled from September 2002 through June 2007; 21% of patients with DLBCL and 19% of patients with FL were on statins at diagnosis, and 20% and 17% remained on statins during lymphoma treatment, respectively. All patients with DLBCL and 39% of patients with FL received initial therapy containing rituximab. The median follow-up time was 47 months (range, 13 to 80 months). Statin use had no impact on the overall response rate (P = .67), overall survival (P = .76), or event-free survival (EFS) in patients with DLBCL (hazard ratio [HR] = 0.85; 95% CI, 0.43 to 1.68). Statin use at diagnosis was associated with improved EFS in patients with FL (HR = 0.45; 95% CI, 0.26 to 0.77), including subgroups treated with rituximab or a rituximab-containing regimen (HR = 0.38; 95% CI, 0.14 to 1.07) and patients who were observed only (HR = 0.38; 95% CI, 0.17 to 0.84).

Conclusion

The concurrent use of statins during the treatment of patients with DLBCL and FL in the rituximab era did not adversely affect outcome. The apparent benefit of statin therapy on FL outcome requires further studies.
Safety and Efficacy of Romiplostim in Patients With Lower-Risk Myelodysplastic Syndrome and Thrombocytopenia
Authors: Kantarjian Hagop , Fenaux Pierre , Sekeres Mikkael A. , Becker Pamela S. , Boruchov Adam , Bowen David , Hellstrom-Lindberg Eva , Larson Richard A. , Lyons Roger M. , Muus Petra , Shammo Jamile , Siegel Robert , Hu Kuolung , Franklin Janet , Berger Dietmar P.
Published: December 2009

Purpose

To assess the safety and efficacy of romiplostim, a peptibody that increases platelet production, for treatment of thrombocytopenic patients with myelodysplastic syndromes (MDS).

Patients and Methods

Eligible patients had lower-risk MDS (International Prognostic Scoring System low or intermediate 1), a mean baseline platelet count ≤ 50 × 109/L, and were only receiving supportive care. Patients received three injections of 300, 700, 1,000, or 1,500 μg romiplostim at weekly intervals. After evaluation of platelet response at week 4, patients could continue to receive romiplostim in a treatment extension phase for up to 1 year.

Results

All 44 patients who enrolled completed the treatment phase; 41 patients continued into the extension phase. Median platelet counts increased throughout the study, from fewer than 30 × 109/L at baseline to 60, 73, 38, and 58 × 109/L at week 4 for the 300-, 700-, 1,000-, and 1,500 -μg dose cohorts, respectively. A durable platelet response (per International Working Group 2000 criteria for 8 consecutive weeks independent of platelet transfusions) was achieved by 19 patients (46%). The incidence of bleeding events and platelet transfusions was less common among patients who achieved a durable platelet response than those who did not (4.3 v 39.3 per 100 patient-weeks). Forty-three patients (98%) reported one or more adverse events. Treatment-related serious adverse events were reported in five patients (11%), all of whom were in the 1,500-μg dose cohort. Two patients progressed to acute myeloid leukemia during the study. No neutralizing antibodies to either romiplostim or endogenous thrombopoietin were seen.

Conclusion

Romiplostim appeared well-tolerated in this study and may be a useful treatment for patients with MDS and thrombocytopenia.
Phase III, Randomized, Open-Label Study of Daily Imatinib Mesylate 400 mg Versus 800 mg in Patients With Newly Diagnosed, Previously Untreated Chronic Myeloid Leukemia in Chronic Phase Using Molecular End Points: Tyrosine Kinase Inhibitor Optimization and Selectivity Study
Authors: Cortes Jorge E. , Baccarani Michele , Guilhot François , Druker Brian J. , Branford Susan , Kim Dong-Wook , Pane Fabrizio , Pasquini Ricardo , Goldberg Stuart L. , Kalaycio Matt , Moiraghi Beatriz , Rowe Jacob M. , Tothova Elena , De Souza Carmino , Rudoltz Marc , Yu Richard , Krahnke Tillmann , Kantarjian Hagop M. , Radich Jerald P. , Hughes Timothy P.
Published: December 2009

Purpose

To evaluate the safety and efficacy of initial treatment with imatinib mesylate 800 mg/d (400 mg twice daily) versus 400 mg/d in patients with newly diagnosed chronic myeloid leukemia in chronic phase.

Patients and Methods

A total of 476 patients were randomly assigned 2:1 to imatinib 800 mg (n = 319) or 400 mg (n = 157) daily. The primary end point was the major molecular response (MMR) rate at 12 months.

Results

At 12 months, differences in MMR and complete cytogenetic response (CCyR) rates were not statistically significant (MMR, 46% v 40%; P = .2035; CCyR, 70% v 66%; P = .3470). However, MMR occurred faster among patients randomly assigned to imatinib 800 mg/d, who had higher rates of MMR at 3 and 6 months compared with those in the imatinib 400-mg/d arm (P = .0035 by log-rank test). CCyR also occurred faster in the 800-mg/d arm (CCyR at 6 months, 57% v 45%; P = .0146). The most common adverse events were edema, gastrointestinal problems, and rash, and all were more common in patients in the 800-mg/d arm. Grades 3 to 4 hematologic toxicity also occurred more frequently in patients receiving imatinib 800 mg/d.

Conclusion

MMR rates at 1 year were similar with imatinib 800 mg/d and 400 mg/d, but MMR and CCyR occurred earlier in patients treated with 800 mg/d. Continued follow-up is needed to determine the clinical significance of earlier responses on high-dose imatinib.
Results of Dasatinib Therapy in Patients With Early Chronic-Phase Chronic Myeloid Leukemia
Authors: Cortes Jorge E. , Jones Dan , O'Brien Susan , Jabbour Elias , Ravandi Farhad , Koller Charles , Borthakur Gautam , Walker Brenda , Zhao Weiqiang , Shan Jianqin , Kantarjian Hagop
Published: December 2009

Purpose

Dasatinib is effective therapy for chronic myeloid leukemia (CML) after imatinib failure. In this study, we investigate the efficacy of dasatinib as initial therapy for patients with CML in early chronic phase.

Patients and Methods

Patients with newly diagnosed CML in early chronic phase were randomly assigned to receive dasatinib 100 mg once daily or 50 mg twice daily as initial therapy.

Results

Among 50 patients observed for at least 3 months, 49 patients (98%) achieved a complete cytogenetic response (CCyR), and 41 patients (82%) achieved a major molecular response (MMR). Responses occurred rapidly, with 94% of patients achieving CCyR by 6 months. There was no difference in response rate by treatment arm. The projected event-free survival rate at 24 months is 88%, and all patients are alive after a median follow-up time of 24 months. Grade ≥ 3 neutropenia and thrombocytopenia occurred in 21% and 10% of patients, respectively. Nonhematologic toxicity was usually grade 1 to 2. There was no significant difference in toxicity between the two arms, and the actual median dose at 12 months was 100 mg (range, 20 to 100 mg).

Conclusion

Dasatinib is an effective agent for the initial management of CML in early chronic phase, producing high rates of CCyR and MMR.
Recent loss of Gibraltar seagrasses
Authors: Bull James C. , Kenyon Emma J. , Edmunds Danny , Cook Kevan J.
Published: December 2009

Worldwide, seagrasses face threats including climate change, disease and anthropogenic disturbance, with populations at the extremes of species’ distributions likely presaging future problems elsewhere in their geographical ranges. At the geographic limits of two marine macrophytes (Zostera marina and Posidonia oceanica) and under intense urbanization, seagrasses around Gibraltar are particularly vulnerable. However, the last published survey of Gibraltar seagrass meadows, in 1993, showed both species were abundant. We resurveyed this area and were unable to locate any seagrass in Gibraltar waters. Extensive coastal development and land reclamation make much former seagrass habitat in Gibraltar waters unsuitable, presenting substantial hurdles to any future restoration efforts.
Prostate cancer screening: clinical impact of WHO calibration of Beckman Coulter Access® prostate-specific antigen assays
Authors: Fillée Catherine , Tombal Bertrand , Philippe Marianne
Published: December 2009

Background: The goal of this study was to evaluate the clinical impact of using the same total prostate-specific antigen (tPSA) and free PSA (fPSA) assays calibrated with World Health Organization (WHO) materials or with Hybritech Tandem-R calibrator.

Methods: From the initial correlation study that included 150 patients, the clinical impact of the WHO calibration was simulated using a large cohort (n=4548) of referred patients. Interim reports of the European Study of Screening for Prostate Cancer (ERSPC) were used to evaluate the clinical outcomes of patients and the risk of prostate cancer (PCa).

Results: WHO calibration of tPSA assays leads to a reduction of about 20% in measured results (tPSA WHO=0.81 tPSA Hybritech+0.04; fPSA WHO=0.78 fPSA Hybritech+0.00; %fPSA WHO=0.92 %fPSA Hybritech+0.00). The simulation showed that the WHO calibration is associated with a risk of missing 15% of PCa.

Conclusions: The discrepancies between the two calibrations lead to significant clinical misinterpretation with decreased detection of PCa if tPSA cut-off thresholds are not adjusted.

Clin Chem Lab Med 2010;48:285–8.
O-β-N-acetyl-D-glucosaminidase in erythrocytes of Italian air force acrobatic pilots
Authors: Corsi Massimiliano M. , Massaccesi Luca , Dogliotti Giada , Vianello Elena , Agrifoglio Marco , Palumbo Fabrizio , Goi Giancarlo
Published: December 2009

Background: Italian air force acrobatic pilots are occupationally susceptible to oxidative stress damage that can lead to overt signs and symptoms of hypoxia. We propose erythrocyte glycohydrolases as new, sensitive markers to assess oxidative stress.

Methods: We measured erythrocyte concentrations of β-D-glucuronidase (GCR), hexosaminidase, O-β-N-acetyl-D-glucosaminidase (O-GlcNAcase), plasma membrane fluidity and plasma hydroperoxides from 19 pilots and compared these to 40 matched healthy subjects.

Results: Plasma hydroperoxide concentrations and the erythrocyte ghosts' fluorescence anisotropy were significantly lower in the pilots. Concentrations of GCR, O-GlcNAcase and hexosaminidase in pilots were significantly different from controls, being lower, higher and higher, respectively.

Conclusions: Pilots, in spite of their oxidative stress, are better protected than controls, probably as a result of their physical training and proper diet. Our results confirm that erythrocytes, with their 120-day life span, are a useful model for investigating physiopathological conditions, and glycohydrolases are good markers for monitoring oxidative stress, even in healthy people.

Clin Chem Lab Med 2010;48:213–6.
Defining hyperandrogenism in polycystic ovary syndrome: measurement of testosterone and androstenedione by liquid chromatography–tandem mass spectrometry and analysis by receiver operator characteristic plots
Authors: Barth Julian H , Field Helen P , Yasmin Ephia , Balen Adam H
Published: December 2009

Objective

Hyperandrogenism is one of the diagnostic criteria for the polycystic ovary syndrome (PCOS) despite no agreed definition of hyperandrogenism. In part, this is due to the quality of testosterone immunoassays. We have developed liquid chromatography–tandem mass spectrometry methods for analysing testosterone and androstenedione (Ad) to study their reference ranges and diagnostic utility in PCOS.

Design, setting and subjects

A consecutive series of 122 women attending a reproductive medicine clinic.

Methods

Blood samples were taken during the early follicular phase for measurement of LH, FSH, oestradiol, Ad, testosterone and sex hormone-binding globulin (SHBG). Retrospective case note analysis was used to determine the clinical features and ultrasound findings.

Results

The incidence of PCOS was 13.9%. The reference interval for testosterone was <1.8 nmol/l and for Ad was 1.4–7.4 nmol/l. There were significant differences in total testosterone (P=0.001), Ad (P<0.05) and free androgen index (FAI; P<0.0001) between the women with and without PCOS. Diagnostic performance using receiver operator characteristic plots showed area under the curve (AUC) for FAI 0.81, testosterone 0.75 and Ad 0.66. The AUC for the LH:FSH ratio was 0.72.

Conclusions

Our analysis of a consecutive series of women attending a reproductive clinic has provided an appropriate series on which to construct reference ranges for key androgens in women. Secondly, it has allowed us to conclude that early follicular serum testosterone measured using tandem mass spectrometry, FAI and the LH:FSH ratio are valuable laboratory tests in the diagnosis of PCOS.