bluuebunny/crossref_metadata_2025 huggingface dataset:
Troubleshooting a missing intra-cardiac tumor at the time of bypass
Authors: Forcillo Jessica , Lalonde Alexandre , Stevens Louis-Mathieu , Noiseux Nicolas
Published: October 2010

Background: Primary cardiac tumors are rare and the only curative treatment consists of complete excision under cardiopulmonary bypass (CPB). This case report presents an unusual case of an intra-cardiac tumor which was missing at the time of surgical excision. Method and Results: The patient was scheduled to undergo surgical tumor removal and double coronary artery bypass grafting (CABG). Intraoperatively, transesophageal echocardiography (TEE) demonstrated a mobile and pediculated tumor in the left ventricular outflow tract (LVOT). Unfortunately, at the time of tumor excision under CPB, this was missing. Before confirming tumor embolization, the CPB system was inspected. The tumor was found on the lateral part of the defoaming filter. Conclusion: Careful mobilization of the heart is recommended during surgery. In this case, it was unexpected that the tumor made its way through the vent line and unidirectional valve up to the venous reservoir where it was fortunately found.
Spasticity and contractures at the wrist after stroke: time course of development and their association with functional recovery of the upper limb
Authors: Malhotra S. , Pandyan AD , Rosewilliam S. , Roffe C. , Hermens H.
Published: October 2010

Objective: To investigate the time course of development of spasticity and contractures at the wrist after stroke and to explore if these are associated with upper limb functional recovery.

Design: Longitudinal observational study using secondary data from the control group of a randomized controlled trial.

Setting: The Acute Stroke Unit at the University Hospital of North Staffordshire.

Subjects: Patients without useful arm function (Action Research Arm Test — ARAT) score of 0 within 6 weeks of a first stroke.

Main measures: Spasticity was measured by quantifying muscle activity during passively imposed stretches at two velocities. Contractures were measured by quantifying passive range of movement and stiffness. Upper limb functional movement was assessed using the ARAT. All assessments were conducted at baseline, and at 6, 12, 24 and 36 weeks after recruitment.

Results: Thirty patients (43% male, median age 70 (range 52—90) years, median time since stroke onset 3 (range 1—5) weeks) were included. Twenty-eight (92%) demonstrated signs of spasticity throughout the study period. Participants who recovered arm function (n = 5) showed signs of spasticity at all assessment points but did not develop contractures. Patients who did not recover useful arm function (n = 25) had signs of spasticity and changes associated with contracture formation at all time points tested.

Conclusion: In this group of patients who had no arm function within the first 6 weeks of stroke, spasticity was seen early, but did not necessarily hinder functional recovery. Contractures were more likely to develop in patients who did not recover arm function.
The Dependence of China’s Economic Growth on Exports and Investment
Authors: Zhu Andong , Kotz David M.
Published: October 2010

This paper analyzes the growing role played by exports and investment in China’s rapid economic growth since 1978. It examines the reasons for the shift over time in China’s growth model, which occurred in stages, and it questions the sustainability of the recent dependence on exports and investment. It proposes structural changes in China’s growth model and considers the obstacles to such changes.

JEL classification:O53, F43, O11
Treatment Outcomes for Older Adults Who Abuse Substances
Authors: Outlaw Freida H. , Marquart Jules M. , Roy Ajanta , Luellen Jason K. , Moran Mary , Willis Amy , Doub Thomas
Published: October 2010

A Center for Substance Abuse Treatment Knowledge Application Program based on cognitive-behavioral and self-management treatment approaches and targeted to older adults with substance abuse was provided through a community behavioral health center. A sample of 199 adults aged 50 and above participated in the 18-session program. Observations were made at intake and 6 months after intake. Program completers versus noncompleters differed significantly over time, favoring completers with regard to decreased use of nonmedical prescription drugs, improved cognitive functioning, improved mental health, increased vitality, and lack of bodily pain. Significant time effects were noted in participants’ decreased use of alcohol and binge drinking, reduced stress, fewer emotional problems, a decrease in having to reduce important activities, and increased prescription of medication for psychological problems. Participants also reported significant improvement in their social functioning, and their physical health and emotional problems had less impact on what they were able to do.
Sex Differences in Math-Intensive Fields
Authors: Ceci Stephen J. , Williams Wendy M.
Published: October 2010

Despite impressive employment gains in many fields of science, women remain underrepresented in fields requiring intensive use of mathematics. Here we discuss three potential explanations for women’s underrepresentation: (a) male–female mathematical and spatial ability gaps, (b) sex discrimination, and (c) sex differences in career preferences and lifestyle choices. Synthesizing findings from psychology, endocrinology, sociology, economics, and education leads to the conclusion that, among a combination of interrelated factors, preferences and choices—both freely made and constrained—are the most significant cause of women’s underrepresentation.
Multi-agency and specialist working to meet the mental health needs of children in care and adopted
Authors: Golding Kim S.
Published: October 2010

Many of the children and young people who are looked after in foster and residential care or are adopted have complex mental health needs that are not well met by traditional mental health services. These vulnerabilities stem from an interaction between pre- and post-care experience, and often include trauma, attachment and developmental difficulties. It is now widely recognized that these children are best served by dedicated services provided by professionals with expertise in meeting the needs of looked after and adopted children. This involves effective joint working between health, education and social care services and requires supportive policies and structures at all levels of the organizations. This paper will explore the strengths, challenges and barriers of multi-agency and specialist working to meet the needs of these vulnerable children and young people.This will be illustrated with case examples drawn from a multi-agency service in Worcestershire, UK.
Is There a Relationship Between Forefoot Alignment and Ingrown Toenail? A Case-Control Study
Authors: Kose Ozkan , Celiktas Mustafa , Kisin Bulent , Ozyurek Selahattin , Yigit Seyhmus
Published: October 2010

Biomechanical imbalance between the hallux and the second toe and external compression of the lateral nail fold are proposed as the main reasons for ingrown toenail. Therefore, any anatomical predisposition facilitating this compression may play a role in the occurrence of ingrown toenail. The purpose of this study is to investigate the relationship between forefoot alignment and ingrown toenail. The authors retrospectively reviewed radiographs of 81 patients with ingrown toenails and compared them with 100 healthy subjects regarding forefoot alignment. Hallux valgus angle (HVA), intermetatarsal angle (IMA), and interphalangeal angle (IPA) were measured, and feet were classified according to digital formula as Egyptian, Greek, and square. The mean HVA was 14.5° ± 5.0° in the case group and 13.2° ± 5.9° in the control group. The mean IMA was 9.1° ± 2.5° in the case group and 8.6° ± 3.1° in the control group. The mean IPA was 11.9° ± 4.1° in the case group and 12.0° ± 5.1° in the control group. There was no statistically significant difference between the groups regarding HVA, IMA, or IPA (P = .123, P = .198, and P = .925, respectively). The distribution of foot types between groups was also similar (P = .967). This study has failed to demonstrate any abnormality in forefoot alignment in patients with symptomatic ingrowing toenails, and it is suggested that treatment should not be based on the correction of the anatomy if no abnormality exists.

Levels of Evidence: Prognostic, Level IV
Moral Hypocrisy
Authors: Tong Eddie M. W. , Yang Ziyi
Published: October 2010

Moral hypocrisy occurs when a person explicitly endorses a moral standard and yet behaves in violation of it. This study examined the effects of two positive emotions, pride and gratitude, on moral hypocrisy in an Asian context. Under a neutral mood condition, the level of moral hypocrisy found in the current Asian sample was about as high as that found in previous American studies. More importantly, compared to this neutral mood condition, participants induced to feel pride showed a similarly high level of moral hypocrisy, but those induced to feel gratitude exhibited little evidence of it.
Endogenous oncogenic Nras mutation promotes aberrant GM-CSF signaling in granulocytic/monocytic precursors in a murine model of chronic myelomonocytic leukemia
Authors: Wang Jinyong , Liu Yangang , Li Zeyang , Du Juan , Ryu Myung-Jeom , Taylor Philip R. , Fleming Mark D. , Young Ken H. , Pitot Henry , Zhang Jing
Published: October 2010

Oncogenic NRAS mutations are frequently identified in myeloid diseases involving monocyte lineage. However, its role in the genesis of these diseases remains elusive. We report a mouse bone marrow transplantation model harboring an oncogenic G12D mutation in the Nras locus. Approximately 95% of recipient mice develop a myeloproliferative disease resembling the myeloproliferative variant of chronic myelomonocytic leukemia (CMML), with a prolonged latency and acquisition of multiple genetic alterations, including uniparental disomy of oncogenic Nras allele. Based on single-cell profiling of phospho-proteins, a novel population of CMML cells is identified to display aberrant granulocyte-macrophage colony stimulating factor (GM-CSF) signaling in both the extracellular signal-regulated kinase (ERK) 1/2 and signal transducer and activator of transcription 5 (Stat5) pathways. This abnormal signaling is acquired during CMML development. Further study suggests that aberrant Ras/ERK signaling leads to expansion of granulocytic/monocytic precursors, which are highly responsive to GM-CSF. Hyperactivation of Stat5 in CMML cells is mainly through expansion of these precursors rather than up-regulation of surface expression of GM-CSF receptors. Our results provide insights into the aberrant cytokine signaling in oncogenic NRAS-associated myeloid diseases.
Combination of HOXB4 and Delta-1 ligand improves expansion of cord blood cells
Authors: Watts Korashon L. , Delaney Colleen , Humphries R. Keith , Bernstein Irwin D. , Kiem Hans-Peter
Published: October 2010

Umbilical cord blood (UCB) is an attractive cell source for hematopoietic cell transplantation (HCT). Here we examine whether the combination of homeobox B4 (HOXB4) and Delta-1 ligand (DL) synergize when used together. Monkey and human UCB CD34+ cells were transduced with a HOXB4-expressing gammaretroviral vector and cultured with DL. Individual and combined effects of HOXB4 and DL were assessed by colony-forming unit assays, flow cytometry, and nonobese diabetic/severe combined immune deficienct mouse transplantation. The presence of DL yielded higher percentage of CD34+ and CD7+ cells and lower percentages of CD14+ cells than non-DL cultures. Furthermore, HOXB4 yielded higher percentages of CD34+ and CD14+ cells than non-HOXB4 cultures. Interestingly, coculture with DL-expressing OP9 cells resulted in better maintenance of HOXB4 than culture in DL-conditioned medium. Culture of HOXB4-transduced human cells in the presence of DL yielded enhanced generation of repopulating cells with higher levels of engraftment of human CD45+, CD34+, CD3+, CD20+, and CD41+ cells compared with either factor individually. Our results demonstrate enhanced generation of hematopoietic progenitors by combining HOXB4 and DL; addition of DL further enhances expansion of multipotent cells capable of repopulating lymphoid and megakaryocyte lineages, which is not observed with HOXB4 alone.
The evolutionary trajectory of mitochondrial carrier family during metazoan evolution
Authors: Gong Ming , Li Jie , Wang Meng , Wang Jin , Zen Ke , Zhang Chen-Yu
Published: October 2010

Background

Exploring metabolic evolution is a way to understand metabolic complexity. The substrate transport of mitochondrial carrier family (MCF) influences direct metabolic activities, making it possible to understand indirectly metabolic evolution from the evolution of substrate transport of MCF. However, the evolutionary study of substrate transport of MCF does not mean that all the concrete structures of mitochondrial carriers (MCs) must first be gained.

Results

Here we studied the alternation of MCF structure and potential correlated functions of MCF during metazoan evolution. The data analysis indicates that the types of substrates transported by MCF as a whole were maintained during metazoan evolution. However, the size of the substrates transported by members of MCs continuously diminished during the evolutionary process. We have found that the ratio of hydrophobic amino acids at specific helix-helix interfaces increases significantly during vertebrate evolution. Amino acid's spatial positioning and the calculating of packing values both indicate the increase in the number of hydrophobic amino acids would lead to a more "tight" structure of the TR domain, which is in agreement with the trend of diminishing size of substrates transported by MCs. In addition, there was a significant increase in the number of carriers of MCF during vertebrate evolution.

Conclusions

We propose that the more "tight" TR structure generated by the increase of the hydrophobic amino acids at specific helix-helix interfaces during vertebrate evolution enhances the substrate selectivity of MCF, reflecting the evolutionary trajectory of MCF during metazoan evolution.
Gene discovery for the bark beetle-vectored fungal tree pathogen Grosmannia clavigera
Authors: Hesse-Orce Uljana , DiGuistini Scott , Keeling Christopher I , Wang Ye , Li Maria , Henderson Hannah , Docking T Roderick , Liao Nancy Y , Robertson Gordon , Holt Robert A , Jones Steven JM , Bohlmann Jörg , Breuil Colette
Published: October 2010

Background

Grosmannia clavigerais a bark beetle-vectored fungal pathogen of pines that causes wood discoloration and may kill trees by disrupting nutrient and water transport. Trees respond to attacks from beetles and associated fungi by releasing terpenoid and phenolic defense compounds. It is unclear which genes are important forG. clavigera's ability to overcome antifungal pine terpenoids and phenolics.

Results

We constructed seven cDNA libraries from eightG. clavigeraisolates grown under various culture conditions, and Sanger sequenced the 5' and 3' ends of 25,000 cDNA clones, resulting in 44,288 high quality ESTs. The assembled dataset of unique transcripts (unigenes) consists of 6,265 contigs and 2,459 singletons that mapped to 6,467 locations on theG. clavigerareference genome, representing ~70% of the predictedG. clavigeragenes. Although only 54% of the unigenes matched characterized proteins at the NCBI database, this dataset extensively covers major metabolic pathways, cellular processes, and genes necessary for response to environmental stimuli and genetic information processing. Furthermore, we identified genes expressed in spores prior to germination, and genes involved in response to treatment with lodgepole pine phloem extract (LPPE).

Conclusions

We provide a comprehensively annotated EST dataset forG. clavigerathat represents a rich resource for gene characterization in this and other ophiostomatoid fungi. Genes expressed in response to LPPE treatment are indicative of fungal oxidative stress response. We identified two clusters of potentially functionally related genes responsive to LPPE treatment. Furthermore, we report a simple method for identifying contig misassemblies inde novoassembled EST collections caused by gene overlap on the genome.
High-resolution melting curve analysis for rapid detection of mutations in a Medaka TILLING library
Authors: Ishikawa Tomoko , Kamei Yasuhiro , Otozai Shinji , Kim Jinhyong , Sato Ayuko , Kuwahara Yoshikazu , Tanaka Minoru , Deguchi Tomonori , Inohara Hidenori , Tsujimura Tohru , Todo Takeshi
Published: October 2010

Background

During the last two decades, DNA sequencing has led to the identification of numerous genes in key species; however, in most cases, their functions are still unknown. In this situation, reverse genetics is the most suitable method to assign function to a gene. TILLING (Targeting Induced Local Lesions IN Genomes) is a reverse-genetic strategy that combines random chemical mutagenesis with high-throughput discovery of the induced mutations in target genes. The method has been applied to a variety of plant and animal species. Screening of the induced mutations is the most important step in TILLING. Currently, direct sequencing or nuclease-mediated screening of heteroduplexes is widely used for detection of mutations in TILLING. Both methods are useful, but the costs are substantial and turnaround times are relatively long. Thus, there is a need for an alternative method that is of higher throughput and more cost effective.

Results

In this study, we developed a high resolution melting (HRM) assay and evaluated its effectiveness for screening ENU-induced mutations in a medaka TILLING library. We had previously screened mutations in thep53gene by direct sequencing. Therefore, we first tested the efficiency of the HRM assay by screening mutations inp53, which indicated that the HRM assay is as useful as direct sequencing. Next, we screened mutations in theatrandatmgenes with the HRM assay. Nonsense mutations were identified in each gene, and the phenotypes of these nonsense mutants confirmed their loss-of-function nature.

Conclusions

These results demonstrate that the HRM assay is useful for screening mutations in TILLING. Furthermore, the phenotype of the obtained mutants indicates that medaka is an excellent animal model for investigating genome stability and gene function, especially when combined with TILLING.
Young patients with colorectal cancer have poor survival in the first twenty months after operation and predictable survival in the medium and long-term: Analysis of survival and prognostic markers
Authors: Chan KK , Dassanayake B , Deen R , Wickramarachchi RE , Kumarage SK , Samita S , Deen KI
Published: October 2010

Objectives

This study compares clinico-pathological features in young (<40 years) and older patients (>50 years) with colorectal cancer, survival in the young and the influence of pre-operative clinical and histological factors on survival.

Materials and methods

A twelve year prospective database of colorectal cancer was analysed. Fifty-three young patients were compared with forty seven consecutive older patients over fifty years old. An analysis of survival was undertaken in young patients using Kaplan Meier graphs, non parametric methods, Cox's Proportional Hazard Ratios and Weibull Hazard models.

Results

Young patients comprised 13.4 percent of 397 with colorectal cancer. Duration of symptoms and presentation in the young was similar to older patients (median, range; young patients; 6 months, 2 weeks to 2 years, older patients; 4 months, 4 weeks to 3 years, p > 0.05). In both groups, the majority presented without bowel obstruction (young - 81%, older - 94%). Cancer proximal to the splenic flexure was present more in young than in older patients. Synchronous cancers were found exclusively in the young. Mucinous tumours were seen in 16% of young and 4% of older patients (p < 0.05). Ninety four percent of young cancer deaths were within 20 months of operation. At median follow up of 50 months in the young, overall survival was 70% and disease free survival 66%. American Joint Committee on Cancer (AJCC) stage 4 and use of pre-operative chemoradiation in rectal cancer was associated with poor survival in the young.

Conclusion

If patients, who are less than 40 years old with colorectal cancer, survive twenty months after operation, the prognosis improves and their survival becomes predictable.
Viral replication is enhanced by an HIV-1 intersubtype recombination-derived Vpu protein
Authors: De Candia Cristian , Espada Constanza , Duette Gabriel , Ghiglione Yanina , Turk Gabriela , Salomón Horacio , Carobene Mauricio
Published: October 2010

Background

Multiple HIV-1 intersubtype recombinants have been identified in human populations. Previous studies from our lab group have shown that the epidemic in Argentina is characterized by the high prevalence of a circulating recombinant form, CRF12_BF, and many related BF recombinant forms. In these genomic structures a recombination breakpoint frequently involved the vpu coding region. Due to the scarce knowledge of Vpu participation in the virion release process and its impact on pathogenesis and of the functional capacities of intersubtype recombinant Vpu proteins, the aim of this work was to perform a comparative analysis on virion release capacity and relative replication capacity among viral variants harboring either a BF recombinant Vpu or a subtype B Vpu.

Results

Our results showed that BF recombinant Vpu was associated to an increased viral particles production when compared to WT B variant in tetherin-expressing cell lines. This observation was tested in the context of a competition assay between the above mentioned variants. The results showed that the replication of the BF Vpu-harboring variant was more efficient in cell cultures than subtype B, reaching a higher frequency in the viral population in a short period of time.

Conclusion

This study showed that as a result of intersubtype recombination, a structurally re-organized HIV-1 Vpu has an improved in vitro capacity of enhancing viral replication, and provides evidence of the changes occurring in this protein function that could play an important role in the successful spread of intersubtype recombinant variants.
Caspase-1 is Involved in the Genesis of Inflammatory Hypernociception by Contributing to Peripheral IL-1β Maturation
Authors: Cunha Thiago M , Talbot Jhimmy , Pinto Larissa G , Vieira Silvio M , Souza Guilherme R , Guerrero Ana T , Sonego Fabiane , Verri Waldiceu A , Zamboni Dario S , Ferreira Sergio H , Cunha Fernando Q
Published: October 2010

Background:

Caspase-1 is a cysteine protease responsible for the processing and secretion of IL-1β and IL-18, which are closely related to the induction of inflammation. However, limited evidence addresses the participation of caspase-1 in inflammatory pain. Here, we investigated the role of caspase-1 in inflammatory hypernociception (a decrease in the nociceptive threshold) using caspase-1 deficient mice (casp1−/−).

Results:

Mechanical inflammatory hypernociception was evaluated using an electronic version of the von Frey test. The production of cytokines, PGE2 and neutrophil migration were evaluated by ELISA, radioimmunoassay and myeloperoxidase activity, respectively. The interleukin (IL)-1β and cyclooxygenase (COX)-2 protein expression were evaluated by western blotting. The mechanical hypernociception induced by intraplantar injection of carrageenin, tumour necrosis factor (TNF)α and CXCL1/KC was reduced in casp1−/− mice compared with WT mice. However, the hypernociception induced by IL-1β and PGE2 did not differ in WT and casp1−/− mice. Carrageenin-induced TNF-α and CXCL1/KC production and neutrophil recruitment in the paws of WT mice were not different from casp1−/−mice, while the maturation of IL-1β was reduced in casp1−/− mice. Furthermore, carrageenin induced an increase in the expression of COX-2 and PGE2 production in the paw of WT mice, but was reduced in casp1−/− mice.

Conclusion:

These results suggest that caspase-1 plays a critical role in the cascade of events involved in the genesis of inflammatory hypernociception by promoting IL-1β maturation. Because caspase-1 is involved in the induction of COX-2 expression and PGE2 production, our data support the assertion that caspase-1 is a key target to control inflammatory pain.
Audiomagnetotelluric studies to trace the hydrological system of thermal fluid flow of Bakreswar Hot Spring, Eastern India: A case history
Authors: Sinharay Rajib K. , Srivastava Shalivahan , Bhattacharya Bimalendu B.
Published: October 2010

An audiomagnetotelluric (AMT) study has been carried out in the Bakreswar Hot Spring (BHS) area of eastern India to locate the geothermal source in the vicinity of BHS. Phase-tensor analysis of the AMT data shows that the region is broadly 2D. Rapid relaxation inversion (RRI) for both transverse-electric (TE) and transverse-magnetic (TM) modes has been carried out to obtain resistivity images of the subsurface. AMT results show that the north-south fault close to Bakreswar is a shallow feature, not deeper than [Formula: see text], and thus cannot act as a heat source. The subsurface formation below the fault zone is highly resistive up to a great depth, indicating the absence of a heat source and geothermal reservoir in the vicinity of the BHS. AMT results indicate that the location of the geothermal reservoir is deep and lies beyond the profiles of measurement in the northwestern side of the Bakreswar Hot Spring.
Pore-scale modeling of electrical and fluid transport in Berea sandstone
Authors: Zhan Xin , Schwartz Lawrence M. , Toksöz M. Nafi , Smith Wave C. , Morgan F. Dale
Published: October 2010

The purpose of this paper is to test how well numerical calculations can predict transport properties of porous permeable rock, given its 3D digital microtomography [Formula: see text] image. For this study, a Berea 500 sandstone sample is used, whose [Formula: see text] images have been obtained with resolution of [Formula: see text]. Porosity, electrical conductivity, permeability, and surface area are calculated from the [Formula: see text] image and compared with laboratory-measured values. For transport properties (electrical conductivity, permeability), a finite-difference scheme is adopted. The calculated and measured properties compare quite well. Electrical transport in Berea 500 sandstone is complicated by the presence of surface conduction in the electric double layer at the grain-electrolyte boundary. A three-phase conductivity model is proposed to compute surface conduction on the rock [Formula: see text] image. Effects of image resolution and computation sample size on the accuracy of numerical predictions are also investigated. Reducing resolution (i.e., increasing the voxel dimensions) decreases the calculated values of electrical conductivity and hydraulic permeability. Increasing computation sample volume gives a better match between laboratory measurements and numerical results. Large sample provides a better representation of the rock.
A solution to the airwave-removal problem in shallow-water marine EM
Authors: Løseth Lars O. , Amundsen Lasse , Jenssen Arne J.
Published: October 2010

A new method is presented for removing the airwave in shallow-water electromagnetic (EM) data. By using pairs of receivers or pairs of source points along a towline and forming weighted differences of an EM field component, the airwave is significantly attenuated. The weights are related to the geometric spreading of the airwave. Specifically, the horizontal electric and magnetic field components are weighted with the horizontal offset to the power of three before their differences are calculated. One can also first calculate difference data without weights in the common-source domain to remove correlated noise and then use the resulting data to perform a second-order difference with weights. In this case, the weights should equal the horizontal offset to the power of four. Moreover, the weighted difference data can be integrated to obtain an estimate of the physical field void of the airwave. Additionally, the airwave contribution to the physical field can be estimated. The theory behind the method is presented and demonstrated on a real controlled-source EM (CSEM) data set.
True-amplitude one-way wave equation migration in the mixed domain
Authors: Vivas Flor A. , Pestana Reynam C.
Published: October 2010

One-way wave equation migration is a powerful imaging tool for locating accurately reflectors in complex geologic structures; however, the classical formulation of one-way wave equations does not provide accurate amplitudes for the reflectors. When dynamic information is required after migration, such as studies for amplitude variation with angle or when the correct amplitudes of the reflectors in the zero-offset images are needed, some modifications to the one-way wave equations are required. The new equations, which are called “true-amplitude one-way wave equations,” provide amplitudes that are equivalent to those provided by the leading order of the ray-theoretical approximation through the modification of the transverse Laplacian operator with dependence of lateral velocity variations, the introduction of a new term associated with the amplitudes, and the modification of the source representation. In a smoothly varying vertical medium,the extrapolation of the wavefields with the true-amplitude one-way wave equations simplifies to the product of two separable and commutative factors: one associated with the phase and equal to the phase-shift migration conventional and the other associated with the amplitude. To take advantage of this true-amplitude phase-shift migration, we developed the extension of conventional migration algorithms in a mixed domain, such as phase shift plus interpolation, split step, and Fourier finite difference. Two-dimensional numerical experiments that used a single-shot data set showed that the proposed mixed-domain true-amplitude algorithms combined with a deconvolution-type imaging condition recover the amplitudes of the reflectors better than conventional mixed-domain algorithms. Numerical experiments with multiple-shot Marmousi data showed improvement in the amplitudes of the deepest structures and preservation of higher frequency content in the migrated images.
Including lateral velocity variations into true-amplitude common-shot wave-equation migration
Authors: Amazonas Daniela , Aleixo Rafael , Melo Gabriela , Schleicher Jörg , Novais Amélia , Costa Jessé C.
Published: October 2010

In heterogeneous media, standard one-way wave equations describe only the kinematic part of one-way wave propagation correctly. For a correct description of amplitudes, the one-way wave equations must be modified. In media with vertical velocity variations only, the resulting true-amplitude one-way wave equations can be solved analytically. In media with lateral velocity variations, these equations are much harder to solve and require sophisticated numerical techniques. We present an approach to circumvent these problems by implementing approximate solutions based on the one-dimensional analytic amplitude modifications. We use these approximations to show how to modify conventional migration methods such as split-step and Fourier finite-difference migrations in such a way that they more accurately handle migration amplitudes. Simple synthetic data examples in media with a constant vertical gradient demonstrate that the correction achieves the recovery of true migration amplitudes. Applications to the SEG/EAGE salt model and the Marmousi data show that the technique improves amplitude recovery in the migrated images in more realistic situations.
Relating shear sonic anisotropy directions to stress in deviated wells
Authors: Sun Haitao , Prioul Romain
Published: October 2010

We develop a model that relates the polarization direction of a dipole sonic fast shear wave propagating along the borehole (hereafter called FSA) to the relative deviatoric stress tensor for arbitrary well orientations. We first define stress quantities, or “subsidiary principal stress,” relevant for sonic dipole shear characterized sufficiently far away into the formation to be unaffected by borehole stress concentration. Next, we show analytically for wells oriented within principal stress planes and numerically for wells outside principal stress planes that the stress-induced FSA coincides with the maximum normal stress direction orthogonal to the borehole (“maximum subsidiary principal stress”) using a nonlinear elastic model for isotropic unstressed background media and plane wave solutions. This model is independent of stress sensitivity parameters. This result is a consequence of, first, the direct relationship between the stressellipsoid factor and the shear stiffness difference ratio, [Formula: see text], and, second, the almost elliptical nature of stress-induced orthorhombic media. Using published laboratory data relating stiffnesses to applied differential stress for isotropic unstressed limestone and sandstone rocks, the model is confirmed for most well orientations except in the vicinity of the stress nodal point within the maximum and minimum principal stress plane, due to small anellipticity as stress increases. The orientations near the nodal point are also the zones of weakest stress-induced anisotropy zones and are therefore the least likely to be measured in practice as long as a quality indicator depending on both the degree of anellipticity and the strength of the shear anisotropy is below 0.5. Finally, we present a synthetic example of the application of this model to estimate the relative deviatoric stress tensor using two wells with different orientations.
Pilot Study Using Molecular Profiling of Patients' Tumors to Find Potential Targets and Select Treatments for Their Refractory Cancers
Authors: Von Hoff Daniel D. , Stephenson Joseph J. , Rosen Peter , Loesch David M. , Borad Mitesh J. , Anthony Stephen , Jameson Gayle , Brown Susan , Cantafio Nina , Richards Donald A. , Fitch Tom R. , Wasserman Ernesto , Fernandez Cristian , Green Sylvan , Sutherland William , Bittner Michael , Alarcon Arlet , Mallery David , Penny Robert
Published: October 2010

Purpose

To compare the progression-free survival (PFS) using a treatment regimen selected by molecular profiling (MP) of a patient's tumor with the PFS for the most recent regimen on which the patient had experienced progression (ie, patient as his own control).

Patients and Methods

Patients with refractory metastatic cancer had tissue samples submitted for MP in two formats including formalin-fixed tissue for immunohistochemistry and fluorescent in situ hybridization assays and immediately frozen tissue for oligonucleotide microarray (MA) gene expression assays (all performed in a Clinical Laboratory Improvement Amendments [ CLIA ] –certified laboratory). The MP approach was deemed of clinical benefit for the individual patient who had a PFS ratio (PFS on MP-selected therapy/PFS on prior therapy) of ≥ 1.3.

Results

In 86 patients who had MP attempted, there was a molecular target detected in 84 (98%). Sixty-six of the 84 patients were treated according to MP results. Eighteen (27%) of 66 patients had a PFS ratio of ≥ 1.3 (95% CI, 17% to 38%; one-sided, one-sample P = .007). Therefore, the null hypothesis (that ≤ 15% of this patient population would have a PFS ratio of ≥ 1.3) was rejected.

Conclusion

It is possible to identify molecular targets in patients' tumors from nine different centers across the United States. In 27% of patients, the MP approach resulted in a longer PFS on an MP-suggested regimen than on the regimen on which the patient had just experienced progression. Issues to be considered in interpretation of this study include limited prior experience with patients as their own controls as a study end point and overall patient attrition.
Personalized Medicine in Non–Small-Cell Lung Cancer: Is KRAS a Useful Marker in Selecting Patients for Epidermal Growth Factor Receptor–Targeted Therapy?
Authors: Roberts Patrick J. , Stinchcombe Thomas E. , Der Channing J. , Socinski Mark A.
Published: October 2010

In patients with metastatic colorectal cancer, the predictive value of KRAS mutational status in the selection of patients for treatment with anti–epidermal growth factor (EGFR) monoclonal antibodies is established. In patients with non–small-cell lung cancer (NSCLC), the utility of determining KRAS mutational status to predict clinical benefit to anti-EGFR therapies remains unclear. This review will provide a brief description of Ras biology, provide an overview of aberrant Ras signaling in NSCLC, and summarize the clinical data for using KRAS mutational status as a negative predictive biomarker to anti-EGFR therapies. Retrospective investigations of KRAS mutational status as a negative predictor of clinical benefit from anti-EGFR therapies in NSCLC have been performed; however, small samples sizes as a result of low prevalence of KRAS mutations and the low rate of tumor sample collection have limited the strength of these analyses. Although an association between the presence of KRAS mutation and lack of response to EGFR tyrosine kinase inhibitors (TKIs) has been observed, it remains unclear whether there is an association between KRAS mutation and EGFR TKI progression-free and overall survival. Unlike colorectal cancer, KRAS mutations do not seem to identify patients who do not benefit from anti-EGFR monoclonal antibodies in NSCLC. The future value of testing for KRAS mutational status may be to exclude the possibility of an EGFR mutation or anaplastic lymphoma kinase translocation or to identify a molecular subset of patients with NSCLC in whom to pursue a drug development strategy that targets the KRAS pathway.
Randomized, Phase III Trial of Panitumumab With Infusional Fluorouracil, Leucovorin, and Oxaliplatin (FOLFOX4) Versus FOLFOX4 Alone As First-Line Treatment in Patients With Previously Untreated Metastatic Colorectal Cancer: The PRIME Study
Authors: Douillard Jean-Yves , Siena Salvatore , Cassidy James , Tabernero Josep , Burkes Ronald , Barugel Mario , Humblet Yves , Bodoky György , Cunningham David , Jassem Jacek , Rivera Fernando , Kocákova Ilona , Ruff Paul , Błasińska-Morawiec Maria , Šmakal Martin , Canon Jean-Luc , Rother Mark , Oliner Kelly S. , Wolf Michael , Gansert Jennifer
Published: October 2010

Purpose

Panitumumab, a fully human anti–epidermal growth factor receptor (EGFR) monoclonal antibody that improves progression-free survival (PFS), is approved as monotherapy for patients with chemotherapy-refractory metastatic colorectal cancer (mCRC). The Panitumumab Randomized Trial in Combination With Chemotherapy for Metastatic Colorectal Cancer to Determine Efficacy (PRIME) was designed to evaluate the efficacy and safety of panitumumab plus infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as initial treatment for mCRC.

Patients and Methods

In this multicenter, phase III trial, patients with no prior chemotherapy for mCRC, Eastern Cooperative Oncology Group performance status of 0 to 2, and available tissue for biomarker testing were randomly assigned 1:1 to receive panitumumab-FOLFOX4 versus FOLFOX4. The primary end point was PFS; overall survival (OS) was a secondary end point. Results were prospectively analyzed on an intent-to-treat basis by tumor KRAS status.

Results

KRAS results were available for 93% of the 1,183 patients randomly assigned. In the wild-type (WT) KRAS stratum, panitumumab-FOLFOX4 significantly improved PFS compared with FOLFOX4 (median PFS, 9.6 v 8.0 months, respectively; hazard ratio [HR], 0.80; 95% CI, 0.66 to 0.97; P = .02). A nonsignificant increase in OS was also observed for panitumumab-FOLFOX4 versus FOLFOX4 (median OS, 23.9 v 19.7 months, respectively; HR, 0.83; 95% CI, 0.67 to 1.02; P = .072). In the mutant KRAS stratum, PFS was significantly reduced in the panitumumab-FOLFOX4 arm versus the FOLFOX4 arm (HR, 1.29; 95% CI, 1.04 to 1.62; P = .02), and median OS was 15.5 months versus 19.3 months, respectively (HR, 1.24; 95% CI, 0.98 to 1.57; P = .068). Adverse event rates were generally comparable across arms with the exception of toxicities known to be associated with anti-EGFR therapy.

Conclusion

This study demonstrated that panitumumab-FOLFOX4 was well tolerated and significantly improved PFS in patients with WT KRAS tumors and underscores the importance of KRAS testing for patients with mCRC.
Definition of Disease-Risk Stratification Groups in Childhood Medulloblastoma Using Combined Clinical, Pathologic, and Molecular Variables
Authors: Ellison David W. , Kocak Mehmet , Dalton James , Megahed Hisham , Lusher Meryl E. , Ryan Sarra L. , Zhao Wei , Nicholson Sarah Leigh , Taylor Roger E. , Bailey Simon , Clifford Steven C.
Published: October 2010

Purpose

Medulloblastomas are heterogeneous and include relatively good-prognosis tumors characterized by Wnt pathway activation, as well as those that cannot be successfully treated with conventional therapy. Developing a practical therapeutic stratification that allows accurate identification of disease risk offers the potential to individualize adjuvant therapy and to minimize long-term adverse effects in a subgroup of survivors.

Methods

Using formalin-fixed paraffin-embedded (FFPE) tissue for immunohistochemistry, fluorescent in situ hybridization, and direct sequencing to identify tumors with a Wnt pathway signature and those harboring copy number abnormalities (CNAs) of potential prognostic significance (MYC/MYCN amplification, CNAs of chromosome 6 and 17), we evaluated clinical, pathologic, and molecular outcome indicators and stratification models in a cohort (n = 207) of patients with medulloblastoma 3 to 16 years of age from the International Society of Pediatric Oncology CNS9102 (PNET3) trial.

Results

Metastatic disease and large-cell/anaplastic (LC/A) phenotype were the clinicopathologic variables associated with poor progression-free survival (PFS). Nuclear immunoreactivity for β-catenin, CTNNB1 mutation, and monosomy 6 all identified a group of good-prognosis patients. MYC amplification was associated with poor outcome, but other CNAs were not. Low-risk medulloblastomas were defined as β-catenin nucleopositive tumors without metastasis at presentation, LC/A phenotype, or MYC amplification. High-risk medulloblastomas were defined as tumors with metastatic disease, LC/A phenotype, or MYC amplification. Low-risk, standard-risk, and high-risk categories of medulloblastoma had significantly (P < .0001) different outcomes.

Conclusion

Integrating assays of molecular biomarkers undertaken on routinely collected diagnostic FFPE tissue into stratification schemes for medulloblastoma alongside clinical and pathologic outcome indicators can refine current definition of disease risk and guide adjuvant therapy.
Phase I Study of Vandetanib During and After Radiotherapy in Children With Diffuse Intrinsic Pontine Glioma
Authors: Broniscer Alberto , Baker Justin N. , Tagen Michael , Onar-Thomas Arzu , Gilbertson Richard J. , Davidoff Andrew M. , Panandiker Atmaram Pai , Leung Wing , Chin Thomas K. , Stewart Clinton F. , Kocak Mehmet , Rowland Christopher , Merchant Thomas E. , Kaste Sue C. , Gajjar Amar
Published: October 2010

Purpose

To evaluate the safety, maximum-tolerated dose, pharmacokinetics, and pharmacodynamics of vandetanib, an oral vascular endothelial growth factor receptor 2 (VEGFR2) and epidermal growth factor receptor inhibitor, administered once daily during and after radiotherapy in children with newly diagnosed diffuse intrinsic pontine glioma.

Patients and Methods

Radiotherapy was administered as 1.8-Gy fractions (total cumulative dose of 54 Gy). Vandetanib was administered concurrently with radiotherapy for a maximum of 2 years. Dose-limiting toxicities (DLTs) were evaluated during the first 6 weeks of therapy. Pharmacokinetic studies were obtained for all patients. Plasma angiogenic factors and VEGFR2 phosphorylation in mononuclear cells were analyzed before and during therapy.

Results

Twenty-one patients were administered 50 (n = 3), 65 (n = 3), 85 (n = 3), 110 (n = 6), and 145 mg/m2 (n = 6) of vandetanib. Only one patient developed DLT (grade 3 diarrhea) at dosage level 5. An expanded cohort of patients were treated at dosage levels 4 (n = 10) and 5 (n = 4); two patients developed grade 4 hypertension and posterior reversible encephalopathy syndrome while also receiving high-dose dexamethasone. Despite significant interpatient variability, exposure to vandetanib increased with higher dosage levels. The bivariable analysis of vascular endothelial growth factor (VEGF) before and during therapy showed that patients with higher levels of VEGF before therapy had a longer progression-free survival (PFS; P = .022), whereas patients with increases in VEGF during treatment had a shorter PFS (P = .0015). VEGFR2 phosphorylation was inhibited on day 8 or 29 of therapy compared with baseline (P = .039).

Conclusion

The recommended phase II dose of vandetanib in children is 145 mg/m2 per day. Close monitoring and management of hypertension is required, particularly for patients receiving corticosteroids.
“A Weapon as Powerful as the Vote”: Urban Protest and Electoral Politics in Venezuela, 1978–1983
Authors: Velasco Alejandro
Published: October 2010

Scholarship on Venezuela has long cast the first decades after the founding of democracy in 1958 as a period of popular passivity, when citizen demands were effectively channeled through elections and state institutions before these broke down in the late 1980s. This article complicates such a reading and considers the role that street protest played in expanding the meaning of democracy among urban popular sectors to include a more dynamic interplay of institutional and extrainstitutional, legal and illegal protest. It focuses on a weeks-long hijacking of public service vehicles in the early 1980s by residents of Venezuela’s largest urban housing project, the 23 de Enero in downtown Caracas. Coupling archival data and oral history interviews, the article reconstructs the protest and its context to show how residents balanced a formerly contradictory experience of electoral support for the democratic regime on one hand and violent antiestablishment opposition on the other to mobilize the state around their demands. In particular it considers how residents seized on new discourses of accountability and participation emanating from political elites to lend their protest legitimacy, showing that the process to recalibrate Venezuelan democracy involved greater interaction between popular and elite-level actors than hitherto recognized.
Photoinduced Charge Separation after Excited Energy Transfer in Snowflake-Shaped Zn–Porphyrin Dendrimer with Anthraquinone Terminals: Enhancement of the Electron-Transfer Rates by “Dendrimer Effect”
Authors: Kozaki Masatoshi , Akita Kogen , Okada Keiji , Islam D-M Shafiqul , Ito Osamu
Published: October 2010

Photoinduced electron transfer (ET) and energy transfer (EnT) of a snowflake-shaped Zn–porphyrin dendrimer with anthraquinone terminals (dendrimer-1), which has four rigid ethynylene–phenylene conjugated chains covered by soft benzyl ether (BE) branches, is investigated by means of steady-state and time-resolved fluorescence measurements. Dendrimer-2 without anthraquinone terminals undergoes a nearly quantitative EnT from the excited singlet states of BE branches to the Zn–porphyrin core, where the conjugated chain plays an important role as a mediator of EnT within this antenna type dendrimer (the dendrimer effect on EnT). A comparison of the rates of charge separation via the singlet excited state of Zn–porphyrin to the anthraquinone terminals through oligo(ethynylenephenylene)s in a series of model compounds reveals considerable acceleration of the rate constants by the dendrimer architecture (the dendrimer effect on ET). This acceleration is attributed to hydrophobic interactions between the flexible BE chains within dendrimer-1, resulting in a significant conformational change into coplanar forms between the Zn–porphyrin plane and the ethynylene–phenylene–anthraquinone plane.