bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigation of three‐dimensional wind flow behaviour over coastal dune morphology under offshore winds using computational fluid dynamics (CFD) and ultrasonic anemometry
Authors: Jackson D. W. T. , Beyers J. H. M. , Lynch K. , Cooper J. A. G. , Baas A. C. W. , Delgado‐Fernandez I.
Published: June 2011

The behaviour of offshore‐directed winds over coastal dune and beach morphology was examined using a combination of modelling (3‐D computational fluid dynamics (CFD)) and field measurement. Both model simulations and field measurements showed reversal of offshore flows at the back beach and creation of an onshore sediment transport potential. The influence of flow reversals on the beach‐dune transport system and foredune growth patterns has previously received little attention. Detailed wind flow measurements were made using an extensive array of mast‐mounted, 3‐D ultrasonic anemometers (50 Hz), arranged parallel to the dominant incident wind direction. Large eddy simulation (LES) of the offshore wind flow over the dune was conducted using the open‐source CFD tool openFOAM. The computational domain included a terrain model obtained by airborne LiDAR and detailed ground DGPS measurements. The computational grid (~22 million cells) included localized mesh refinement near the complex foredune terrain to capture finer details of the dune morphology that might affect wind flows on the adjacent beach.

Measured and simulated wind flow are presented and discussed. The CFD simulations offer new insights into the flow mechanics associated with offshore winds and how the terrain steering of wind flow impacts on the geomorphological behaviour of the dune system. Simulation of 3‐D wind flows over complex terrain such as dune systems, presents a valuable new tool for geomorphological research, as it enables new insights into the relationship between the wind field and the underlying topography. The results show that offshore and obliquely offshore winds result in flow reversal and onshore directed winds at distances of up to 20 m from the embryo dune toe. The potential geomorphological significance of the findings are discussed and simple calculations show that incoming offshore and obliquely offshore winds with mean velocities over 13 m s−1 and 7 m s−1, respectively, have the potential to create onshore‐directed winds at the back beach with mean velocities above 3.3 m s−1. These are above the threshold of movement for dry sand and support previous conclusions about the significance of offshore winds in dune and beach budget calculations. Copyright © 2011 John Wiley & Sons, Ltd.
A comparative study of range‐based stock return volatility estimators for the German market
Authors: Todorova Neda , Husmann Sven
Published: June 2011

This study investigates the relative performance of various volatility estimators based on daily and intraday price ranges of 25 German equities, with the two‐scales realized volatility used as a benchmark. The empirical results show that all estimators based on daily ranges are by far superior to the classical estimator but are severely negatively biased due to discrete trading. The realized range obtained from intraday ranges performs better in terms of both bias and efficiency, although its performance still suffers from discrete trading. In these settings, the bias correcting procedure developed by Christensen and Podolskij (2007) appears to consistently outperform all other alternatives, including the scaled version of Martens and van Dijk (2007), and provides evidence of the relative advantages of the realized range. © 2011 Wiley Periodicals, Inc. Jrl Fut Mark 32:560–586, 2012
Auditory motion direction encoding in auditory cortex and high‐level visual cortex
Authors: Alink Arjen , Euler Felix , Kriegeskorte Nikolaus , Singer Wolf , Kohler Axel
Published: June 2011

The aim of this functional magnetic resonance imaging (fMRI) study was to identify human brain areas that are sensitive to the direction of auditory motion. Such directional sensitivity was assessed in a hypothesis‐free manner by analyzing fMRI response patterns across the entire brain volume using a spherical‐searchlight approach. In addition, we assessed directional sensitivity in three predefined brain areas that have been associated with auditory motion perception in previous neuroimaging studies. These were the primary auditory cortex, the planum temporale and the visual motion complex (hMT/V5+). Our whole‐brain analysis revealed that the direction of sound‐source movement could be decoded from fMRI response patterns in the right auditory cortex and in a high‐level visual area located in the right lateral occipital cortex. Our region‐of‐interest‐based analysis showed that the decoding of the direction of auditory motion was most reliable with activation patterns of the left and right planum temporale. Auditory motion direction could not be decoded from activation patterns in hMT/V5+. These findings provide further evidence for the planum temporale playing a central role in supporting auditory motion perception. In addition, our findings suggest a cross‐modal transfer of directional information to high‐level visual cortex in healthy humans. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.
Brain structure anomalies in autism spectrum disorder—a meta‐analysis of VBM studies using anatomic likelihood estimation
Authors: Nickl‐Jockschat Thomas , Habel Ute , Maria Michel Tanja , Manning Janessa , Laird Angela R. , Fox Peter T. , Schneider Frank , Eickhoff Simon B.
Published: June 2011

Autism spectrum disorders (ASD) are pervasive developmental disorders with characteristic core symptoms such as impairments in social interaction, deviance in communication, repetitive and stereotyped behavior, and impaired motor skills. Anomalies of brain structure have repeatedly been hypothesized to play a major role in the etiopathogenesis of the disorder. Our objective was to perform unbiased meta‐analysis on brain structure changes as reported in the current ASD literature. We thus conducted a comprehensive search for morphometric studies by Pubmed query and literature review. We used a revised version of the activation likelihood estimation (ALE) approach for coordinate‐based meta‐analysis of neuroimaging results. Probabilistic cytoarchitectonic maps were applied to compare the localization of the obtained significant effects to histological areas. Each of the significant ALE clusters was analyzed separately for age effects on gray and white matter density changes. We found six significant clusters of convergence indicating disturbances in the brain structure of ASD patients, including the lateral occipital lobe, the pericentral region, the medial temporal lobe, the basal ganglia, and proximate to the right parietal operculum. Our study provides the first quantitative summary of brain structure changes reported in literature on autism spectrum disorders. In contrast to the rather small sample sizes of the original studies, our meta‐analysis encompasses data of 277 ASD patients and 303 healthy controls. This unbiased summary provided evidence for consistent structural abnormalities in spite of heterogeneous diagnostic criteria and voxel‐based morphometry (VBM) methodology, but also hinted at a dependency of VBM findings on the age of the patients. Hum Brain Mapp, 2011. © 2011 Wiley‐Liss, Inc.
Multivariable analysis of risk factors for enlargement of the tracheoesophageal puncture after total laryngectomy
Authors: Hutcheson Katherine A. , Lewin Jan S. , Sturgis Erich M. , Risser Jan
Published: June 2011

Background

Enlarged tracheoesophageal puncture (TEP) is a challenging complication of surgical prosthetic voice restoration. Prevention of this complication requires identification of high‐risk individuals, and surgical and prosthetic correlates of TEP enlargement.

Methods

Multivariable logistic regression methods were used to analyze preoperative, perioperative, and postoperative risk factors for enlarged TEP in a 5‐year retrospective cohort.

Results

Enlarged TEP only occurred in irradiated patients. Adjusting for length of follow‐up and timing of TEP, advanced (N2 or N3) nodal disease (odds ratio [OR]adjusted, 4.3; 95% confidence interval [CI], 1.0–19.1), postoperative stricture (ORadjusted, 3.2; 95% CI, 1.2–8.6), and diagnosis of locoregional recurrence or distant metastasis after laryngectomy (ORadjusted, 6.2; 95% CI, 2.3–16.4) increased risk of enlarged TEP. Extended resection and preoperative nutritional status were also significantly associated with enlarged TEP. Prosthetic parameters did not significantly correlate with enlargement.

Conclusion

Development of enlarged TEP is a multifactorial process related to both baseline and postoperative factors. © 2011 Wiley Periodicals, Inc. Head Neck, 2012
The use of liver biopsy evaluation in discrimination of idiopathic autoimmune hepatitis versus drug-induced liver injury
Authors: Suzuki Ayako , Brunt Elizabeth M. , Kleiner David E. , Miquel Rosa , Smyrk Thomas C. , Andrade Raul J. , Lucena Isabel M. , Castiella Agustin , Lindor Keith , Björnsson Einar
Published: June 2011

Distinguishing drug-induced liver injury (DILI) from idiopathic autoimmune hepatitis (AIH) can be challenging. We performed a standardized histologic evaluation to explore potential hallmarks to differentiate AIH versus DILI. Biopsies from patients with clinically well-characterized DILI [n = 35, including 19 hepatocellular injury (HC) and 16 cholestatic/mixed injury (CS)] and AIH (n = 28) were evaluated for Ishak scores, prominent inflammatory cell types in portal and intra-acinar areas, the presence or absence of emperipolesis, rosette formation, and cholestasis in a blinded fashion by four experienced hepatopathologists. Histologic diagnosis was concordant with clinical diagnosis in 65% of cases; but agreement on final diagnosis among the four pathologists was complete in only 46% of cases. Interface hepatitis, focal necrosis, and portal inflammation were present in all evaluated cases, but were more severe in AIH

(P

< 0.05) than DILI (HC). Portal and intra-acinar plasma cells, rosette formation, and emperiopolesis were features that favored AIH

(P

< 0.02). A model combining portal inflammation, portal plasma cells, intra-acinar lymphocytes and eosinophils, rosette formation, and canalicular cholestasis yielded an area under the receiver operating characteristic curve (AUROC) of 0.90 in predicting DILI (HC) versus AIH. All Ishak inflammation scores were more severe in AIH than DILI (CS)

(P

≤ 0.05). The four AIH-favoring features listed above were consistently more prevalent in AIH, whereas portal neutrophils and intracellular (hepatocellular) cholestasis were more prevalent in DILI (CS)

(P

< 0.02). The combination of portal inflammation, fibrosis, portal neutrophils and plasma cells, and intracellular (hepatocellular) cholestasis yielded an AUC of 0.91 in predicting DILI (CS) versus AIH.

Conclusion:

Although an overlap of histologic findings exists for AIH and DILI, sufficient differences exist so that pathologists can use the pattern of injury to suggest the correct diagnosis. (Hepatology 2011;)
Role of ethnicity in overweight and obese patients with nonalcoholic steatohepatitis
Authors: Lomonaco Romina , Ortiz-Lopez Carolina , Orsak Beverly , Finch Joan , Webb Amy , Bril Fernando , Louden Christopher , Tio Fermin , Cusi Kenneth
Published: June 2011

The role of ethnicity in determining disease severity in nonalcoholic steatohepatitis (NASH) remains unclear. We recruited 152 patients with biopsy-proven NASH, 63% of whom were Hispanic and 37% of whom were Caucasian. Both groups were well matched for age, sex, and total body fat. We measured: (1) liver fat by magnetic resonance imaging and spectroscopy; (2) fasting plasma glucose, fasting plasma insulin (FPI), and free fatty acid (FFA) levels; (3) total body fat by dual energy x-ray absorptiometry (DXA); (4) liver and muscle insulin sensitivity (insulin clamp with 3-[3H] glucose); (5) insulin resistance at the level of the liver (fasting endogenous glucose production derived from 3-[3H] glucose infusion × FPI) and adipose tissue (fasting FFA × FPI). Liver fat was slightly, but not significantly, higher in Hispanic vs. Caucasian patients (27 ± 2% vs. 24 ± 2%,

p

= 0.16). However, this trend did not translate into worse liver steatosis, necroinflammation or fibrosis. Patients with NASH had severe hepatic, adipose tissue and muscle insulin resistance versus healthy subjects without NASH nonalcoholic fatty liver disease, but there were no differences between both ethnic groups on these parameters. However, Hispanics versus Caucasians with type 2 diabetes mellitus (T2DM) had a trend for worse hepatic/adipose tissue insulin resistance and fibrosis.

Conclusion:

When Hispanic and Caucasian patients with NASH are well matched for clinical parameters, particularly for adiposity, slightly higher liver fat content is not associated with worse hepatic insulin resistance or more severe NASH on histology. Hispanic ethnicity does not appear to be a major determinant of disease severity in NASH, although those with diabetes may be at greater risk of fibrosis. Given the higher risk of T2DM in Hispanics, long-term studies are needed to define their risk of disease progression. (HEPATOLOGY 2011;)
Tumor-secreted lysophostatidic acid accelerates hepatocellular carcinoma progression by promoting differentiation of peritumoral fibroblasts in myofibroblasts
Authors: Mazzocca Antonio , Dituri Francesco , Lupo Luigi , Quaranta Michele , Antonaci Salvatore , Giannelli Gianluigi
Published: June 2011

Hepatocellular carcinoma (HCC) occurs in fibrotic liver as a consequence of underlying cirrhosis. The goal of this study was to investigate how the interaction between HCC cells and stromal fibroblasts affects tumor progression. We isolated and characterized carcinoma-associated fibroblasts (CAFs) and paired peritumoral tissue fibroblasts (PTFs) from 10 different patients with HCC and performed coculture experiments. We demonstrated a paracrine mechanism whereby HCC cells secrete lysophostatidic acid (LPA), which promotes transdifferentiation of PTFs to a CAF-like myofibroblastic phenotype. This effect is mediated by up-regulation of specific genes related to a myo/contractile phenotype. After transdifferentiation, PTFs expressed α-smooth muscle actin (α-SMA) and enhanced proliferation, migration, and invasion of HCC cells occur. A pan-LPA inhibitor (α-bromomethylene phosphonate [BrP]-LPA), or autotaxin gene silencing, inhibited this PTF transdifferentiation and the consequent enhanced proliferation, migration, and invasion of HCC cells.

In vivo,

PTFs coinjected with HCC cells underwent transdifferentiation and promoted tumor progression. Treatment with BrP-LPA blocked transdifferentiation of PTFs, down-regulated myofibroblast-related genes, and slowed HCC growth and progression. Patients with larger and metastatic HCC and shorter survival displayed higher serum levels of LPA. Analysis of microdissected tissues indicated that stroma is the main target of the LPA paracrine loop in HCC. As a consequence, α-SMA–positive cells were more widespread in tumoral compared with paired peritumoral stroma.

Conclusion:

Our data indicate that LPA accelerates HCC progression by recruiting PTFs and promoting their transdifferentiation into myofibroblasts. Inhibition of LPA could prove effective in blocking transdifferentiation of myofibroblasts and tumor progression. (HEPATOLOGY 2011;)
Interleukin-22 promotes human hepatocellular carcinoma by activation of STAT3
Authors: Jiang Runqiu , Tan Zhongming , Deng Lei , Chen Yun , Xia Yongxiang , Gao Yun , Wang Xuehao , Sun Beicheng
Published: June 2011

Interleukin-22 (IL-22), one of the cytokines secreted by T helper 17 (Th17) cells, was recently reported to be a novel inflammation driver through STAT3 signaling activation. We aimed to investigate the role of IL-22 expression in hepatocellular carcinoma (HCC). We demonstrated significant up-regulation of IL-22 in human HCC tumor infiltrated leukocytes (TILs) compared to peripheral lymphocytes. Moreover, IL-22 expression was significantly higher in Edmondson Grade III-IV HCC patients versus Grade I-II, confirmed by both real-time polymerase chain reaction and immunohistochemistry. Both IL-22 receptor α and IL-23 were highly expressed in HCC and adjacent cirrhotic tissues compared to normal controls. Enhanced tumor growth and metastasis was found in mice that underwent subrenal transplantation of MHCC-97H cells cotransplanted with IL-22+ TILs cells. STAT3 phosphorylation and up-regulation of downstream genes

Bcl-2, Bcl-XL, CyclinD1,

and vascular endothelial growth factor

(VEGF)

promoted tumor growth and metastasis.

In vitro

studies confirmed the tumor-promoting and antiapoptotic effect of IL-22, as well as IL-6. In the mouse chronic hepatitis and HCC model, sustained and increased IL-22 expression and STAT3 activation were found in liver tissues. A linear correlation was demonstrated between IL-22 expression and hepatic complementary proliferation. An

in vivo

diethyl-nitrosamine-induced mouse HCC model verified that tumor formation was significantly decreased in IL-22 knockout mice.

Conclusion:

Excessive IL-22 can be found in the HCC microenvironment, leading to tumor growth, inhibition of apoptosis, and promotion of metastasis due to STAT3 activation. (HEPATOLOGY 2011;)
Utility of serum immunoglobulin G4 in distinguishing immunoglobulin G4-associated cholangitis from cholangiocarcinoma
Authors: Oseini Abdul M. , Chaiteerakij Roongruedee , Shire Abdirashid M. , Ghazale Amaar , Kaiya Joseph , Moser Catherine D. , Aderca Ileana , Mettler Teresa A. , Therneau Terry M. , Zhang Lizhi , Takahashi Naoki , Chari Suresh T. , Roberts Lewis R.
Published: June 2011

Elevated serum immunoglobulin G4 (sIgG4) is a feature of autoimmune pancreatitis (AIP) and IgG4-associated cholangitis (IAC); a >2-fold increase in sIgG4 is considered highly specific for these disorders. Many patients with IAC present with biliary strictures and obstructive jaundice, making cholangiocarcinoma (CCA) an important differential diagnosis. We determined the value of sIgG4 in distinguishing IAC from CCA. sIgG4 levels were measured in a test cohort of 126 CCA and 50 IAC patients. The results were confirmed in a validation cohort of 161 CCA and 47 IAC patients. Of the 126 CCA patients in the test cohort, 17 (13.5%) had elevated sIgG4 (>140 mg/dL) and four (3.2%) had a >2-fold (>280 mg/dL) increase. Primary sclerosing cholangitis (PSC) was present in 31/126 CCA patients, of whom seven (22.6%) had elevated sIgG4 and two (6.5%) had a >2-fold elevation. Of the 50 IAC patients, 39 (78.0%) had elevated sIgG4 and 25 (50.0%) had a >2-fold increase. The results in the validation cohort were consistent with those of the test cohort.

Conclusion:

Although elevated sIgG4 levels are characteristic of IAC, some patients with CCA, particularly with PSC, have elevated sIgG4 levels, including a small percentage with a more than a 2-fold increase in sIgG4. Therefore, sIgG4 elevation alone does not exclude the diagnosis of CCA. Depending on the prevalence of the two diagnoses, the use of a 2-fold cutoff for sIgG4 may not reliably distinguish IAC from CCA. At a cutoff of 4 times the upper limit of normal, sIgG4 is 100% specific for IAC. (HEPATOLOGY 2011;)
Efficient production of Fah -null heterozygote pigs by chimeric adeno-associated virus-mediated gene knockout and somatic cell nuclear transfer
Authors: Hickey Raymond D. , Lillegard Joseph B. , Fisher James E. , McKenzie Travis J. , Hofherr Sean E. , Finegold Milton J. , Nyberg Scott L. , Grompe Markus
Published: June 2011

Hereditary tyrosinemia type I (HT1) results in hepatic failure, cirrhosis, and hepatocellular carcinoma (HCC) early in childhood and is caused by a deficiency in the enzyme fumarylacetoacetate hydrolase (FAH). In a novel approach we used the chimeric adeno-associated virus DJ serotype (AAV-DJ) and homologous recombination to target and disrupt the porcine

Fah

gene. AAV-DJ is an artificial chimeric AAV vector containing hybrid capsid sequences from three naturally occurring serotypes (AAV2, 8, and 9). The AAV-DJ vector was used to deliver the knockout construct to fetal pig fibroblasts with an average knockout targeting frequency of 5.4%. Targeted

Fah

-null heterozygote fibroblasts were used as nuclear donors for somatic cell nuclear transfer (SCNT) to porcine oocytes and multiple viable

Fah

-null heterozygote pigs were generated.

Fah

-null heterozygotes were phenotypically normal, but had decreased

Fah

transcriptional and enzymatic activity compared to wildtype animals. Conclusion: This study is the first to use a recombinant chimeric AAV vector to knockout a gene in porcine fibroblasts for the purpose of SCNT. In using the AAV-DJ vector we observed targeting frequencies that were higher than previously reported with other naturally occurring serotypes. We expect that the subsequent generation of FAH-null homozygote pigs will serve as a significant advancement for translational research in the areas of metabolic liver disease, cirrhosis, and HCC. (Hepatology 2011;)
Genetic variants in DNA repair genes and the risk of cutaneous malignant melanoma in melanoma‐prone families with/without CDKN2A mutations
Authors: Liang Xueying Sharon , Pfeiffer Ruth M. , Wheeler William , Maeder Dennis , Burdette Laurie , Yeager Meredith , Chanock Stephen , Tucker Margaret A. , Goldstein Alisa M. , Yang Xiaohong R.
Published: June 2011

Cutaneous malignant melanoma (CMM) is an etiologically heterogeneous disease with genetic, environmental (sun exposure) and host (pigmentation/nevi) factors and their interactions contributing to risk. Genetic variants in DNA repair genes may be particularly important since their altered function in response to sun exposure‐related DNA damage maybe related to risk for CMM. However, systematic evaluations of genetic variants in DNA repair genes are limited, particularly in high‐risk families. We comprehensively analyzed DNA repair gene polymorphisms and CMM risk in melanoma‐prone families with/without CDKN2A mutations. A total of 586 individuals (183 CMM) from 53 families (23 CDKN2A (+), 30 CDKN2A (−)) were genotyped for 2964 tagSNPs in 131 DNA repair genes. Conditional logistic regression, conditioning on families, was used to estimate trend p‐values, odds ratios and 95% confidence intervals for the association between CMM and each SNP separately, adjusted for age and sex. p‐Values for SNPs in the same gene were combined to yield gene specific p‐values. Two genes, POLN and PRKDC, were significantly associated with melanoma after Bonferroni correction for multiple testing (p = 0.0003 and 0.00035, respectively). DCLRE1B showed suggestive association (p = 0.0006). 28 ∼ 56% of genotyped SNPs in these genes had single SNP p < 0.05. The most significant SNPs in POLN and PRKDC had similar effects in CDKN2A (+) and CDKN2A (−) families. Our finding suggests that polymorphisms in DNA repair genes, POLN and PRKDC, were associated with increased melanoma risk in melanoma families with and without CDKN2A mutations.
An American founder mutation in MLH1
Authors: Tomsic Jerneja , Liyanarachchi Sandya , Hampel Heather , Morak Monika , Thomas Brittany C. , Raymond Victoria M. , Chittenden Anu , Schackert Hans K. , Gruber Stephen B. , Syngal Sapna , Viel Alessandra , Holinski‐Feder Elke , Thibodeau Stephen N. , de la Chapelle Albert
Published: June 2011

Mutations in the mismatch repair genes cause Lynch syndrome (LS), conferring high risk of colorectal, endometrial and some other cancers. After the same splice site mutation in the MLH1 gene (c.589‐2A>G) had been observed in four ostensibly unrelated American families with typical LS cancers, its occurrence in comprehensive series of LS cases (Mayo Clinic, Germany and Italy) was determined. It occurred in 10 out of 995 LS mutation carriers (1.0%) diagnosed in the Mayo Clinic diagnostic laboratory. It did not occur among 1,803 cases tested for MLH1 mutations by the German HNPCC consortium, while it occurred in three probands and an additional five family members diagnosed in Italy. In the U.S., the splice site mutation occurs on a large (∼4.8 Mb) shared haplotype that also harbors the variant c.2146G>A, which predicts a missense change in codon 716 referred to here as V716M. In Italy, it occurs on a different, shorter shared haplotype (∼2.2 Mb) that does not carry V716M. The V716M variant was found to be present by itself in the U.S., German and Italian populations with individuals sharing a common haplotype of 280 kb, allowing us to calculate that the variant arose around 5,600 years ago (225 generations; 95% confidence interval 183–272). The splice site mutation in America arose or was introduced some 450 years ago (18 generations; 95% confidence interval 14–23); it accounts for 1.0% all LS in the Unites States and can be readily screened for.
Adjuvant and neoadjuvant imatinib therapy: Current role in the management of gastrointestinal stromal tumors
Authors: Eisenberg Burton L. , Trent Jonathan C.
Published: June 2011

Although surgery remains the mainstay for the treatment of primary gastrointestinal stromal tumors (GIST), a significant number of patients experience disease recurrence within 5 years of surgery. The emergence of imatinib therapy for the treatment of patients with advanced GIST has offered unprecedented improvements in clinical outcomes for these patients. Prospective clinical trials have supported the efficacy and safety of imatinib before and after surgical resection of GIST. The American College of Surgeons Oncology Group Z9001 pivotal trial revealed that 1 year of adjuvant imatinib therapy provides significantly superior recurrence‐free survival in patients with GIST after surgical resection, when compared to placebo. Additional trials and case studies have also begun to define the potential clinical benefit of imatinib in the neoadjuvant setting. Optimized risk stratification paradigms will be required to ensure the appropriate selection of patients to undergo treatment with imatinib in these settings. Risk stratification schemes are evolving that potentially will include mutation status and tumor rupture, and predictive nomograms have recently been proposed. The recent European Society of Medical Oncology and National Comprehensive Cancer Network guidelines mention use of adjuvant imatinib for ≥1 year in patients with KIT+, resectable GIST at high risk of recurrence. Moreover, the guidelines support the use of neoadjuvant imatinib in cases of limited disease if it would facilitate less extensive surgery and organ sparing. This article reviews pivotal efficacy and safety data for adjuvant imatinib and explores the potential clinical benefit of neoadjuvant imatinib in patients with GIST.
B7‐H3 contributes to the metastatic capacity of melanoma cells by modulation of known metastasis‐associated genes
Authors: Tekle Christina , Nygren Marit Kveine , Chen Yih‐Wen , Dybsjord Indrejit , Nesland Jahn Marthin , Mælandsmo Gunhild Mari , Fodstad Øystein
Published: June 2011

B7‐H3, an immunoregulatory protein, is known to play a role in tumor progression. In many cancer types, observed correlations between high B7‐H3 expression and poor prognosis have been attributed to involvement in antitumor immunity. However, here we demonstrate a nonimmunological alternative function of B7‐H3 in cancer metastasis. Since advanced malignant melanoma is a disease with a poor survival rate and a broad pattern of metastasis, we used this disease as a model in our studies. We found that shRNA silencing of B7‐H3 reduced the in vitro migratory potential and matrigel invasiveness of MDA‐MB‐435 and FEMX‐I melanoma cells. In an experimental metastasis model in vivo, B7‐H3 silencing of MDA‐MB‐435 cells resulted in reduced metastatic capacity and significantly increased the median symptom‐free survival of nude mice (147 vs. 65 days, p < 0.001) and rats (53 vs. 42 days, p = 0.025) injected with MDA‐MB‐435 cells. Furthermore, a smaller fraction of mice had microscopically detectable metastases compared to control animals, and the pattern of metastases was slightly different between the two groups but with the brain as the predominant organ. Immunohistochemistry on samples from two melanoma patients showed strong B7‐H3 staining in both a primary tumor and metastases. Notably, the metastasis‐associated proteins, matrix metalloproteinase (MMP)‐2, signal transducer and activator of transcription 3 (Stat3), and the level of secreted interleukin‐8 (IL‐8) were reduced in the B7‐H3 knock‐down cell variants, whereas tissue inhibitor of metalloproteinase (TIMP)‐1 and‐2 levels were increased. Taken together, our findings indicate a novel role for B7‐H3 in the regulation of the metastatic capacity of melanoma cells and it might be a potential therapeutic target for anti‐metastasis therapy.
Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen‐induced cellular senescence
Authors: Tuttle Rebecca , Miller Kelly R. , Maiorano J. Nicholas , Termuhlen Paula M. , Gao Yongping , Berberich Steven J.
Published: June 2011

Estrogen signaling plays an important role in breast carcinogenesis. An increased understanding of estrogen gene targets and their effects will allow for more directed and effective therapies for individuals with breast cancer, particularly those with estrogen receptor positive tumors resistant to tamoxifen therapy. Here, we identify YPEL3 as a growth suppressive protein downregulated by estrogen in estrogen receptor positive breast cancer cell lines. Estrogen repression of YPEL3 expression was found to be independent of p53 but dependent on estrogen receptor alpha expression. Importantly, YPEL3 expression, which is induced by the removal of estrogen or treatment with tamoxifen triggers cellular senescence in MCF‐7 cells while loss of YPEL3 increases the growth rate of MCF‐7 cells. Taken together these findings suggest that YPEL3 may represent a potential target for directed hormonal therapy for estrogen receptor positive breast cancer patients.
Psychology and my gallbladder: an insider's account
Authors: Hoyt Michael F.
Published: June 2011

The subjective experience of the psychologist‐author when addressing and undergoing a surgical procedure is described, including—consistent with his own theoretical and technical orientation‐—the use of various brief therapy and hypnotherapy methods. A narrative of events is presented with interspersed comments about internal processes and reflections. A discussion of “Lessons Learned and Offered,” including various comments about personal therapy (therapist as patient), then completes the article. © 2011 Wiley Periodicals, Inc. J Clin Psychol: In Session 67:1–10, 2011.
Statistical optimization of process parameters for the production of vanillic acid by solid‐state fermentation of groundnut shell waste using response surface methodology
Authors: Gadhe Abhijit , Mudliar Sandeep , Pandey Ramavatar , Elumalai S , Satpute Dewanand
Published: June 2011

BACKGROUND: Vanillic acid is a flavoring agent and also serves as precursor for vanillin production. Culture medium and fermentation condition for the single step production of vanillic acid from Phanerochaete chrysosporium using lignocellulosic waste as a substrate under solid state fermentation (SSF) were optimized using response surface methodology.

RESULTS: The process parameters were chosen by borrowing methodology, and L‐asparagine, pH and moisture content of the solid medium during SSF were identified as the most significant variables. The optimum value of selected variable and their mutual interactions were determined by response surface methodology. The result demonstrated that a yield of 73.58 mg vanillic acid g−1 substate was predicted under optimum conditions (L‐asparagine 5.98 mmol L−1 (2.37 mg g−1 groundnut shell), pH of solid medium 4.51 and moisture content 74.83%). The predicted response was experimentally validated and resulted in a maximum vanillic acid yield of 73.69 mg g−1 after 8 days of SSF.

CONCLUSION: The optimization of fermentation variables resulted in a maximum 10‐fold increase in vanillic acid yield compared with that observed under sub‐optimal conditions (from 7.2 mg g−1 to 73.69 mg g−1). Copyright © 2011 Society of Chemical Industry
Optimization of biodiesel production from crude palm oil using ultrasonic irradiation assistance and response surface methodology
Authors: Worapun Ittipon , Pianthong Kulachate , Thaiyasuit Prachasanti
Published: June 2011

BACKGROUND: Production of biodiesel from crude palm oil (CPO) with 6 wt% of free fatty acid (FFA) using a low‐frequency ultrasonic irradiation (40 kHz) technique was investigated in the present work. The objective of this study was to determine the relationship between various important parameters of the alkaline catalyzed transesterification process to obtain a high conversion to biodiesel. Response surface methodology (RSM) was used to statistically analyze and optimize the operating parameters of the process. A central composite design (CCD) was adopted to study the effects of the methanol to oil molar ratio, the catalyst concentration, reaction temperature, and irradiation time on conversion to biodiesel.

RESULTS: The result from the RSM analysis indicated that the methanol to oil molar ratio, catalyst concentration and irradiation time have the most significant effects on the conversion to biodiesel. Moreover, a coefficient of determination (R2) value of 0.93 shows the fitness of a second‐order model for the present study. Based on this second‐order model, the optimum conditions for alkaline catalyzed transesterification of CPO were found to be a methanol to oil molar ratio of 6.44:1, catalyst concentration 1.25 wt%, reaction temperature 38.44 °C and irradiation time 25.96 min. At the calculated optimum condition, the conversion to biodiesel reached 97.85%. Under these same conditions, the experimental value was 98.02 ± 0.6%.

CONCLUSIONS: The mathematical model developed has been proven to adequately describe the range of the experimental parameters studied and provide a statistically accurate prediction of the optimum conversion to biodiesel. Copyright © 2011 Society of Chemical Industry
Evaluation of focal hepatic lesions with ultrasound contrast agents
Authors: Sutherland Tom , Temple Faye , Lee Wai‐Kit , Hennessy Oliver
Published: June 2011

Ultrasound contrast agents have gained wide acceptance for the detection and characterization of focal liver lesions. This pictorial essay reviews the growing body of evidence that supports the use of modern ultrasound contrast agents and illustrates the enhancement characteristics of commonly encountered focal liver lesions. Pathologies discussed include metastases, hepatocellular carcinomas, focal nodular hyperplasia, hepatocellular adenomas, hemangiomas, abscesses, complex cysts, and focal fatty deposition. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound, 2011
Prenatal diagnosis of scalp cyst with spontaneous regression
Authors: Bae Jin Young , Seong Won Joon , Lee Taek Hoo , Park Il Soo
Published: June 2011

Fetal scalp cysts are rare, and they may be easily misdiagnosed as meningoceles or encephaloceles. A 38‐year‐old pregnant woman was referred to our hospital for ultrasound examination, which revealed a small cyst above the skull with no defect in the skull. The cyst could not be seen on follow‐up ultrasound examinations. After delivery, a three‐dimensional CT scan of the head revealed no defect in skull and scalp. Fetal scalp cysts usually require surgical excision after birth, but can regress without any treatment. © 2011 Wiley Periodicals, Inc. J Clin Ultrasound 39:484–486, 2011
Factors predicting prolonged hospital stay for infants with bronchiolitis
Authors: Weisgerber Michael C. , Lye Patricia S. , Li Shun‐Hwa , Bakalarski Deborah , Gedeit Rainer , Simpson Pippa , Gorelick Marc H.
Published: June 2011

BACKGROUND:

Prior prediction models for length of stay (LOS) in bronchiolitis have focused more on birth‐ and disease‐related risk factors than on early hospital course factors, particularly common clinical markers including respiratory status and caloric intake.

OBJECTIVES:

1) Study the associations of various clinical markers and LOS; and 2) develop a LOS prediction model.

DESIGN:

Retrospective cohort study.

SETTING:

Children's Hospital of Wisconsin.

PATIENTS:

Inclusion criteria were: age <365 days old; admission between November 1, 2004 and April 15, 2005; final diagnosis of bronchiolitis; placement on the bronchiolitis treatment protocol; and lack of concurrent condition impacting LOS.

RESULTS:

During the study period, 272/347 infants admitted with bronchiolitis met inclusion criteria. On hospital day 2, infants in the prolonged LOS group (≥108 hours) had a significantly greater number of hours on supplemental oxygen, maximum supplemental oxygen use, minimum supplemental oxygen use, maximum respiratory rate, mean respiratory score, and number of times suctioned. They had significantly lower minimum oxygen saturation and caloric intake. Recursive partitioning demonstrated five variables (hours of supplemental oxygen, maximum respiratory rate, minimum supplemental oxygen use, gestation, and caloric intake) to predict short or prolonged LOS with an area under the receiver‐operator characteristic curve of 0.89/0.72 in the learning/test trees; sensitivity, 0.85; and specificity, 0.82.

CONCLUSIONS:

There are important differences between infants with bronchiolitis having short and prolonged hospital stays, including several clinical markers identifiable on hospital day 2. This model may be a useful prediction tool for targeting early interventions for high‐risk infants. Journal of Hospital Medicine 2011. © 2011 Society of Hospital Medicine
Leadership conceptual ambiguities
Authors: Brocato Billy , Jelen Jonatan , Schmidt Thomas , Gold Stuart
Published: June 2011

The authors propose a postmodern critique of modernist leadership traits research and offer a robust theoretical and methodological alternative to overcome the ambiguous conceptual use of transformational and charismatic leadership traits. A content analysis of leadership studies from 1999 to 2008 in peer‐reviewed journals and management texts was conducted to identify those salient characteristics often associated with leadership traits. Given the evasive nature of the researched phenomenon and the lack of typical quantitative rigor, our quasi‐meta‐analysis revealed 10 distinctive intrapersonal and interpersonal referents or social perceptions used by researchers when describing leadership traits and the effects of those traits on workers in general. Based on the 10 organizational and social icons deduced from the content analysis, the authors offered a postmodern leadership evaluation matrix as a substitute performance metric in an organizational setting, thus eliminating modernist conceptual ambiguities tied to the leader–worker dyadic in varying organizational contexts. The findings suggest that leadership researchers should consider complex behavioral decision‐making processes that result in emergent group performances instead of focusing on a leader's ephemeral behavioral traits.
Peak performance for the political leader
Authors: Brill Pamela , Sloan Karlin
Published: June 2011

In the corporate world, leadership development programs are standard fare. Such programs often include well‐defined competencies and performance metrics, as well as regularly scheduled feedback and mentoring sessions, especially for those employees designated “high potential” performers.

Not so in the public sphere. There are no defined career paths or standardized training curricula for heads of
state. There are, however, requisite competencies for effective public sector leadership. As Gardner (1990) observed, “Leadership is not a mysterious activity. It is possible to describe the tasks that leaders perform....[But] we have barely scratched the surface in our efforts toward leadership development” (p. xix).

The learning curve is steep for a newly elected leader, and fraught with potential landmines. Speaking with
the candor of someone no longer seeking public office, former UK Prime Minister Tony Blair said recently, “When I came to office, prime minister was the only job I'd ever held; I'd never been a government minister before....The business of running a government is like anything else: You get better the longer you do it. And there are lessons out there that, had they come to me in an identifiable form, would have been useful to know” (talk given on December 16, 2010b).

Both Gardner and Blair are emphatic that leadership is not something one is born with but something learned
over time. And as Blair (2010a) put it, “Government is a race between expectations and capability.”

In the essays that follow, several leadership coaches discuss the unique challenges and effective approaches
they are using to help government leaders build the competencies that will enable them to govern effectively—and win that race between their constituents's expectations and their own capabilities.
Political leadership and relationship systems intelligence
Authors: Pew Alfred De
Published: June 2011

In the corporate world, leadership development programs are standard fare. Such programs often include well‐defined competencies and performance metrics, as well as regularly scheduled feedback and mentoring sessions, especially for those employees designated “high potential” performers.

Not so in the public sphere. There are no defined career paths or standardized training curricula for heads of
state. There are, however, requisite competencies for effective public sector leadership. As Gardner (1990) observed, “Leadership is not a mysterious activity. It is possible to describe the tasks that leaders perform....[But] we have barely scratched the surface in our efforts toward leadership development” (p. xix).

The learning curve is steep for a newly elected leader, and fraught with potential landmines. Speaking with
the candor of someone no longer seeking public office, former UK Prime Minister Tony Blair said recently, “When I came to office, prime minister was the only job I'd ever held; I'd never been a government minister before....The business of running a government is like anything else: You get better the longer you do it. And there are lessons out there that, had they come to me in an identifiable form, would have been useful to know” (talk given on December 16, 2010b).

Both Gardner and Blair are emphatic that leadership is not something one is born with but something learned
over time. And as Blair (2010a) put it, “Government is a race between expectations and capability.”

In the essays that follow, several leadership coaches discuss the unique challenges and effective approaches
they are using to help government leaders build the competencies that will enable them to govern effectively—and win that race between their constituents's expectations and their own capabilities.
Development and validation of LC‐HRMS and GC‐NICI‐MS methods for stereoselective determination of MDMA and its phase I and II metabolites in human urine
Authors: Schwaninger Andrea E. , Meyer Markus R. , Huestis Marilyn A. , Maurer Hans H.
Published: June 2011

3,4‐Methylenedioxymethamphetamine (MDMA) is a racemic drug of abuse and its R‐ and S‐enantiomers are known to differ in their dose‐response curve. The S‐enantiomer was shown to be eliminated at a higher rate than the R‐enantiomer most likely explained by stereoselective metabolism that was observed in various in vitro experiments. The aim of this work was the development and validation of methods for evaluating the stereoselective elimination of phase I and particularly phase II metabolites of MDMA in human urine. Urine samples were divided into three different methods. Method A allowed stereoselective determination of the 4‐hydroxy‐3‐methoxymethamphetamine (HMMA) glucuronides and only achiral determination of the intact sulfate conjugates of HMMA and 3,4‐dihydroxymethamphetamine (DHMA) after C18 solid‐phase extraction by liquid chromatography–high‐resolution mass spectrometry with electrospray ionization. Method B allowed the determination of the enantiomer ratios of DHMA and HMMA sulfate conjugates after selective enzymatic cleavage and chiral analysis of the corresponding deconjugated metabolites after chiral derivatization with S‐heptafluorobutyrylprolyl chloride using gas chromatography–mass spectrometry with negative‐ion chemical ionization. Method C allowed the chiral determination of MDMA and its unconjugated metabolites using method B without sulfate cleavage. The validation process including specificity, recovery, matrix effects, process efficiency, accuracy and precision, stabilities and limits of quantification and detection showed that all methods were selective, sensitive, accurate and precise for all tested analytes. Copyright © 2011 John Wiley & Sons, Ltd.
Hydrogen rearrangement and ring cleavage reactions study of progesterone by triple quadrupole mass spectrometry and density functional theory
Authors: Jeilani Yassin A. , Cardelino Beatriz H. , Ibeanusi Victor M.
Published: June 2011

The fragmentation mechanisms of progesterone have been studied by triple quadrupole tandem mass spectrometry (MSMS) and density functional theory (DFT). Mechanisms leading to major product ions are proposed. The data suggest that progesterone fragments preferentially via hydrogen and other rearrangements lead to neutral losses. These fragmentations are quite complex and are preceded by σ‐bond cleavages in most cases. Four major pathways for progesterone fragmentation are proposed involving: (1) cleavage of ring B at C9C10, (2) cleavage of C6C7 bond in ring B through m/z 191, (3) two types of cleavages of ring D, and (4) ketene elimination in ring A. Pathways (1)–(3) proceed via charge‐remote fragmentations while pathway (4) proceeds via charge‐site initiated mechanism. The geometry of product ions in these pathways were optimized using DFT at the B3LYP/6‐311G(d,p) level of theory from which the free energies of the pathways were calculated. The effect that the choice of basis sets and density functionals has on the results was tested by performing additional calculations using B3LYP/6‐31G(d) and B3PW91/6‐311G(d,p). Copyright © 2011 John Wiley & Sons, Ltd.
Totally implantable central venous access ports. Analysis of 700 cases
Authors: Barbetakis Nikolaos , Asteriou Christos , Kleontas Athanassios , Tsilikas Christodoulos
Published: June 2011

Background and Objectives

Vascular access has great importance in the treatment of patients submitted to prolonged chemotherapy. Purpose of this study is to assess the efficacy and safety of the percutaneous insertion and use of totally implantable central venous access ports (TICVAP).

Methods

During a 10‐year period, 700 TICVAP were inserted into cancer patients for chemotherapy. Early and late complications and their management were recorded and analyzed.

Results

Of the 700 catheters implanted, 126 (18%) presented one or more types of early and late complication. Removal of 262 catheters was performed, of which 216 (82.4%) were elective indications due to the termination of the treatment and 46 (17.6%) resulted from complications that could not be controlled using clinical measures. In 280 patients (40%), the catheter remained functional until the patient's death, and 158 patients (22.5%) are still making use of their catheters for clinical treatment.

Conclusions

The low rate of complications according to this study confirms the safety and convenience of the percutaneous insertion and use of TICVAP in patients undergoing prolonged chemotherapy regimens and explains the increasing use of these devices in current medical oncology practice. J. Surg. Oncol. 2011; 104:654–656. © 2011 Wiley Periodicals, Inc.