bluuebunny/crossref_metadata_2025 huggingface dataset:
Coactivation of AKT and β-Catenin in Mice Rapidly Induces Formation of Lipogenic Liver Tumors
Authors: Stauffer Jimmy K. , Scarzello Anthony J. , Andersen Jesper B. , De Kluyver Rachel L. , Back Timothy C. , Weiss Jonathan M. , Thorgeirsson Snorri S. , Wiltrout Robert H.
Published: February 2011

Obesity is a risk factor for development of certain cancers but the basis for this risk is unclear. In this study, we developed a novel mouse model that demonstrates directly how lipogenic phenotypes commonly associated with diet-induced metabolic syndromes can influence hepatic cancer development. Activated AKT and β-catenin (AKT/CAT) genes were hydrodynamically codelivered using the Sleeping Beauty transposon to initiate liver tumorigenesis. AKT/CAT and MET/CAT combination induced microscopic tumor foci by 4 weeks, whereas no tumorigenesis resulted from delivery of AKT, MET, or CAT alone. Primary AKT/CAT tumor cells were steatotic (fatty) hepatocellular adenomas which progressed to hepatocellular carcinomas (HCC) upon in vivo passage, whereas primary MET/CAT tumors emerged directly as frank HCC. Conversion of AKT/CAT tumor cells to frank HCC during passage was associated with induction of the human HCC marker α-fetoprotein and the stem cell marker CD133. Using hierarchical clustering and gene set enrichment analysis, we compared the primary murine AKT/CAT and MET/CAT tumors to a panel of 53 human HCCs and determined that these two mouse models could be stratified as distinct subtypes associated in humans with poor clinical prognosis. The chief molecular networks identified in primary and passaged AKT/CAT tumors were steatosis and lipid metabolic pathways, respectively. Our findings show how coactivation of the AKT and CAT pathways in hepatocytes can efficiently model development of a lipogenic tumor phenotype. Furthermore, we believe that our approach could speed the dissection of microenvironmental factors responsible for driving steatotic-neoplastic transformation to frank carcinoma, through genetic modification of existing immunodefined transgenic models. Cancer Res; 71(7); 2718–27. ©2011 AACR.
Sphingosine Kinase-1 Enhances Resistance to Apoptosis through Activation of PI3K/Akt/NF-κB Pathway in Human Non–Small Cell Lung Cancer
Authors: Song Libing , Xiong Huaping , Li Jun , Liao Wenting , Wang Lan , Wu Jueheng , Li Mengfeng
Published: February 2011

Purpose: The present study was to examine the effect of sphingosine kinase-1 (SPHK1) on chemotherapeutics-induced apoptosis in non–small cell lung cancer (NSCLC) cells, which is relatively insensitive to chemotherapy, and its clinical significance in NSCLC progression.

Experimental Design: The correlation of SPHK1 expression and clinical features of NSCLC was analyzed in 218 paraffin-embedded archived NSCLC specimens by immunohistochemical analysis. The effect of SPHK1 on apoptosis induced by chemotherapeutics was examined both in vitro and in vivo, using Annexin V staining and TUNEL (terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling) assays. Western blotting and luciferase analysis were performed to examine the impact of SPHK1 on the PI3K/Akt/NF-κB signaling.

Results: The expression of SPHK1 was markedly increased in NSCLC and correlated with tumor progression and poor survival of patients with NSCLC. Upregulation of SPHK1 significantly inhibited doxorubicin- or docetaxel-induced apoptosis, associated with induction of antiapoptotic proteins Bcl-xl, c-IAP1, c-IAP2, and TRAF1. In contrast, silencing SPHK1 expression or inhibiting SPHK1 activity with specific inhibitor, SK1-I, significantly enhanced the sensitivity of NSCLC cells to apoptosis induced by chemotherapeutics both in vitro and in vivo. Moreover, we demonstrated that upregulation of SPHK1 activated the PI3K/Akt/NF-κB pathway, and that inhibition of the PI3K/Akt/NF-κB pathway abrogated the antiapoptotic effect of SPHK1 on NSCLC cells.

Conclusions: Our results suggest that SPHK1 is a potential pharmacologic target for the treatment of NSCLC and inhibition of SPHK1 expression or its kinase activity might represent a novel strategy to sensitize NSCLC to chemotherapy. Clin Cancer Res; 17(7); 1839–49. ©2011 AACR.
A Multilocus Technique for Risk Evaluation of Patients with Neuroblastoma
Authors: Ambros Inge M. , Brunner Bettina , Aigner Gerhard , Bedwell Clare , Beiske Klaus , Bénard Jean , Bown Nick , Combaret Valerie , Couturier Jerome , Defferrari Raffaella , Gross Nicole , Jeison Marta , Lunec John , Marques Barbara , Martinsson Tommy , Mazzocco Katia , Noguera Rosa , Schleiermacher Gudrun , Speleman Frank , Stallings Ray , Tonini Gian Paolo , Tweddle Deborah A. , Valent Alexander , Vicha Ales , Roy Nadine Van , Villamon Eva , Ziegler Andrea , Preuner Sandra , Drobics Mario , Ladenstein Ruth , Amann Gabriele , Schuit Robert J.L. , Pötschger Ulrike , Ambros Peter F.
Published: February 2011

Purpose: Precise and comprehensive analysis of neuroblastoma genetics is essential for accurate risk evaluation and only pangenomic/multilocus approaches fulfill the present-day requirements. We present the establishment and validation of the PCR-based multiplex ligation-dependent probe amplification (MLPA) technique for neuroblastoma.

Experimental Design: A neuroblastoma-specific MLPA kit was designed by the SIOP Europe Neuroblastoma Biology Committee in cooperation with MRC-Holland. The contained target sequences cover 19 chromosomal arms and reference loci. Validation was performed by single locus and pangenomic techniques (n = 174). Dilution experiments for determination of minimal tumor cell percentage were performed and testing of reproducibility was checked by interlaboratory testing (n = 15). Further 156 neuroblastomas were used for establishing the amplification cutoff level.

Results: The MLPA technique was tested in 310 neuroblastomas and 8 neuroblastoma cell lines (including validation and amplification cutoff level testing). Intertechnique validation showed a high concordance rate (99.5%). Interlaboratory MLPA testing (κ = 0.95, P < 0.01) revealed 7 discrepant of 1,490 results (0.5%). Validation by pangenomic techniques showed a single discordance of 190 consensus results (0.5%). The test results led to formulation of interpretation standards and to a kit revision. The minimal tumor cell percentage was fixed at 60%.

Conclusions: The recently designed neuroblastoma-specific MLPA kit covers all chromosomal regions demanded by the International Neuroblastoma Risk Group for therapy stratification and includes all hitherto described genetic loci of prognostic interest for future studies and can be modified or extended at any time. Moreover, the technique is cost effective, reliable, and robust with a high interlaboratory and intertechnique concordance. Clin Cancer Res; 17(4); 792–804. ©2011 AACR.
Antitumor Efficacy of PKI-587, a Highly Potent Dual PI3K/mTOR Kinase Inhibitor
Authors: Mallon Robert , Feldberg Larry R. , Lucas Judy , Chaudhary Inder , Dehnhardt Christoph , Santos Efren Delos , Chen Zecheng , dos Santos Osvaldo , Ayral-Kaloustian Semiramis , Venkatesan Aranapakam , Hollander Irwin
Published: February 2011

Purpose: The aim of this study was to show preclinical efficacy and clinical development potential of PKI-587, a dual phosphoinositide 3-kinase (PI3K)/mTOR inhibitor.

Experimental Design: In vitro class 1 PI3K enzyme and human tumor cell growth inhibition assays and in vivo five tumor xenograft models were used to show efficacy.

Results: In vitro, PKI-587 potently inhibited class I PI3Ks (IC50 vs. PI3K-α = 0.4 nmol/L), PI3K-α mutants, and mTOR. PKI-587 inhibited growth of 50 diverse human tumor cell lines at IC50 values of less than 100 nmol/L. PKI-587 suppressed phosphorylation of PI3K/mTOR effectors (e.g., Akt), and induced apoptosis in human tumor cell lines with elevated PI3K/mTOR signaling. MDA-MB-361 [breast; HER2+, PIK3CA mutant (E545K)] was particularly sensitive to this effect, with cleaved PARP, an apoptosis marker, induced by 30 nmol/L PKI-587 at 4 hours.

In vivo, PKI-587 inhibited tumor growth in breast (MDA-MB-361, BT474), colon (HCT116), lung (H1975), and glioma (U87MG) xenograft models. In MDA-MB-361 tumors, PKI-587 (25 mg/kg, single dose i.v.) suppressed Akt phosphorylation [at threonine(T)308 and serine(S)473] for up to 36 hours, with cleaved PARP (cPARP) evident up to 18 hours. PKI-587 at 25 mg/kg (once weekly) shrank large (∼1,000 mm3) MDA-MB-361 tumors and suppressed tumor regrowth. Tumor regression correlated with suppression of phosphorylated Akt in the MDA-MB-361 model. PKI-587 also caused regression in other tumor models, and efficacy was enhanced when given in combination with PD0325901 (MEK 1/2 inhibitor), irinotecan (topoisomerase I inhibitor), or HKI-272 (neratinib, HER2 inhibitor).

Conclusion: Significant antitumor efficacy and a favorable pharmacokinetic/safety profile justified phase 1 clinical evaluation of PKI-587. Clin Cancer Res; 17(10); 3193–203. ©2011 AACR.
Identification of Soluble Candidate Biomarkers of Therapeutic Response to Sunitinib in Medullary Thyroid Carcinoma in Preclinical Models
Authors: Broutin Sophie , Ameur Nabahet , Lacroix Ludovic , Robert Thomas , Petit Benoit , Oumata Nassima , Talbot Monique , Caillou Bernard , Schlumberger Martin , Dupuy Corinne , Bidart Jean-Michel
Published: February 2011

Purpose: Medullary thyroid carcinoma (MTC), an aggressive rare tumor due to activating mutations in the proto-oncogene RET, requires new therapeutic strategies. Sunitinib, a potent inhibitor of RET, VEGF receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and platelet-derived growth factor receptor (PDGFR)α/β, has been reported as clinically effective in some patients with advanced MTC. In this study, we examine molecular mechanisms of action of sunitinib and identify candidate soluble biomarkers of response.

Experimental Design: Both in vitro and in vivo assays, using the human TT RETC634W MTC cell line, were done to assess the activity of sunitinib. Kinetic microarray studies were used to analyze molecular pathways modified by sunitinib and to identify candidate biomarkers that were subsequently investigated in the serum of patients.

Results: Sunitinib displayed antiproliferative and antiangiogenic activities and inhibited RET autophosphorylation and activation of downstream signaling pathways. We showed that sunitinib treatment induced major changes in the expression of genes involved in tissue invasion and metastasis including vimentin (VIM), urokinase plasminogen (PLAU), tenascin-C (TN-C), SPARC, and CD44. Analyzing downregulated genes, we identified those encoding secreted proteins and, among them, interleukin (IL)-8 was found to be modulated in the serum of xenografted mice under sunitinib treatment. Furthermore, we demonstrated that metastatic MTC patients presented increased serum levels of IL-8 and TGF-β2.

Conclusions: Experimental models confirm the clinical efficacy of sunitinib observed in a few studies. Molecular pathways revealed by genomic signatures underline the impact of sunitinib on tissue invasion. Selected soluble candidate biomarkers could be of value for monitoring sunitinib response in metastatic MTC patients. Clin Cancer Res; 17(7); 2044–54. ©2011 AACR.
Large-Scale Analysis of KIT Aberrations in Chinese Patients with Melanoma
Authors: Kong Yan , Si Lu , Zhu Yanyan , Xu Xiaowei , Corless Christopher L. , Flaherty Keith T. , Li Li , Li Haifu , Sheng Xinan , Cui Chuanliang , Chi Zhihong , Li Siming , Han Mei , Mao Lili , Lu Aiping , Guo Jun
Published: February 2011

Purpose: KIT aberrations were described in acral and mucosal melanomas in largely Caucasian populations. Asian populations are more prone to develop acral and mucosal than cutaneous melanomas, and may harbor a high frequency of KIT aberrations.

Experimental Design: Melanoma subtypes (n = 502) were analyzed histologically to determine melanoma subtype. Tissue samples were analyzed for mutations in exons 9, 11, 13, 17, and 18 of KIT gene in genomic DNA by PCR amplification and Sanger sequencing. The copy numbers of the KIT gene were analyzed by quantitative PCR, and protein expression levels of KIT (CD117) were determined by immunohistochemistry.

Results: The most common melanoma subtypes were acral (38.4%) and mucosal (33.3%) melanomas in this population. The overall incidence of somatic mutations within the KIT gene was 10.8% (54/502), and all subtypes of melanoma contained KIT mutations. Increases in KIT gene copy numbers were correlated to CD117 overexpression. The genetic mutations of KIT were unrelated to the age, gender, stage, thickness, and ulceration of primary melanomas. Importantly, the overall survival of melanoma patients with KIT mutations (P = 0.001) or with KIT aberrations (mutation plus amplification, P = 0.0002) was significantly shorter than that of patients without such alterations.

Conclusion: In China, the prevalent melanomas are acral and mucosal melanomas. KIT mutations are detected in all melanoma subtypes. Our study suggests that increases in KIT gene copy numbers, but not KIT mutations, may be correlated to CD117 overexpression. For the first time, our study suggests that genetic KIT aberration is an adverse prognostic factor for melanoma. Clin Cancer Res; 17(7); 1684–91. ©2011 AACR.
Stromal LRP1 in Lung Adenocarcinoma Predicts Clinical Outcome
Authors: Meng He , Chen Guoan , Zhang Xiaojie , Wang Zhuwen , Thomas Dafydd G. , Giordano Thomas J. , Beer David G. , Wang Michael M.
Published: February 2011

Purpose: LRP1 (low-density lipoprotein receptor–related protein 1) is a broadly expressed receptor that binds multiple extracellular ligands and participates in protein clearance. It is expressed in numerous cancers, but its role in lung cancer has not been characterized. Here, we investigate the relationship between LRP1 and lung cancer.

Experimental Design: LRP1 mRNA levels were determined in lung tumors from several large, multicenter studies. LRP1 protein localization was determined by immunohistochemical analysis of lung tumor microarrays. Normal fibroblasts, fibroblasts treated with the LRP1 inhibitor RAP (receptor-associated protein), and Lrp1 null fibroblasts were cocultured with 3 independent lung cancer cell lines to investigate the role of LRP1 on tumor cell proliferation.

Results: LRP1 mRNA levels are significantly decreased in lung tumors relative to nontumorous lung tissue. Lower expression of LRP1 in lung adenocarcinomas correlates with less favorable clinical outcome in a cohort of 439 patients. Immunohistochemical analysis shows that LRP1 is primarily expressed in stromal cells in 94/111 lung cancers, with very little protein found in cancer cells. A growth-suppressive function of mouse embryonic fibroblast (MEF) cells was observed in 3 lung cancer cell lines tested (H460, H2347, and HCC4006 cells); growth suppression was blocked by the LRP1 inhibitor RAP. Lrp1 deletion in fibroblasts reduced the ability of MEF cells to suppress tumor cell mitosis. In a validation set of adenocarcinomas, we confirmed a significant, positive correlation between both LRP1 mRNA and protein levels and favorable clinical outcomes.

Conclusions: LRP1 expression is associated with improved lung cancer outcomes. Mechanistically, stromal LRP1 may non–cell autonomously suppress lung tumor cell proliferation. Clin Cancer Res; 17(8); 2426–33. ©2011 AACR.
Leukocytes and the Natural History of Deep Vein Thrombosis
Authors: Saha Prakash , Humphries Julia , Modarai Bijan , Mattock Katherine , Waltham Matthew , Evans Colin E. , Ahmad Anwar , Patel Ashish S. , Premaratne Sobath , Lyons Oliver T.A. , Smith Alberto
Published: February 2011

Observational studies have shown that inflammatory cells accumulate within the thrombus and surrounding vein wall during the natural history of venous thrombosis. More recent studies have begun to unravel the mechanisms that regulate this interaction and have confirmed that thrombosis and inflammation are intimately linked. This review outlines our current knowledge of the complex relationship between inflammatory cell activity and venous thrombosis and highlights new areas of research in this field. A better understanding of this relationship could lead to the development of novel therapeutic targets that inhibit thrombus formation or promote its resolution.
The Role of Thrombolysis in the Clinical Management of Deep Vein Thrombosis
Authors: Popuri Radha Krishna , Vedantham Suresh
Published: February 2011

The cornerstones of current management of deep vein thrombosis (DVT) are the routine use of anticoagulant therapy, graduated elastic compression stockings, and early ambulation. Thrombolytic therapy was previously reserved only for patients with life-, limb-, or organ-threatening complications. However, the postthrombotic syndrome has been increasingly recognized as a frequent and serious long-term complication of DVT. In parallel, endovascular thrombolytic methods have evolved considerably in recent years, prompting discussion and controversy as to whether they should be more liberally used. In some centers, pharmacomechanical catheter–directed thrombolysis is now routinely used in the treatment of acute iliofemoral DVT. Randomized trials are currently under way to determine when the use of pharmacomechanical catheter–directed thrombolysis is appropriate in patients presenting with acute proximal DVT.
Predictors of Short-Term Complications After Implantable Cardioverter-Defibrillator Replacement
Authors: Krahn Andrew D. , Lee Douglas S. , Birnie David , Healey Jeffrey S. , Crystal Eugene , Dorian Paul , Simpson Christopher S. , Khaykin Yaariv , Cameron Douglas , Janmohamed Amir , Yee Raymond , Austin Peter C. , Chen Zhongliang , Hardy Judy , Tu Jack V.
Published: February 2011

Background—

Complications after implantable cardioverter-defibrillator (ICD) replacement are often clinically devastating, particularly when infection or reoperation occurs. Identifying factors contributing to complications may permit identification of high-risk individuals that warrant incremental monitoring and therapy to attenuate risk. In addition, replacement may be a discretionary decision in the context of an advisory or borderline device performance and patient, device, and implanter factors that predict adverse outcome may assist in clinical decision-making.

Methods and Results—

In a prospective, multicenter, population-based registry of all ICD patients at 18 centers in Ontario, Canada, we examined 45-day complication and all-cause mortality rates from February 2007 to August 2009 in patients undergoing ICD generator replacement. Complications were determined longitudinally and were categorized as major or minor. ICD replacement was performed in 1081 of 5176 patients (20.8%) undergoing ICD implantation (age, 64.3±12.7 years; 78.5% men). In patients undergoing ICD replacement, 47 patients (4.3%) had a complication within 45 days, with 47 major complications in 28 patients (2.6%), most commonly infection (n=23), lead revision (n=35), electrical storm (n=14), and pulmonary edema (n=13). Minor complications occurred in 2.3% of patients, most commonly incisional infection (n=10) and pocket hematoma (n=10). On multivariable analysis, risk factors associated with major complications were Canadian Cardiovascular Society angina class (adjusted hazard ratio [HR], 3.70 for class 2 to 4 versus 0 to 1;
P
=0.027) and multiple previous procedures on the pocket (adjusted HR, 3.35 for >1 versus 1;
P
=0.058). Risk factors associated with any complication were the use of antiarrhythmic therapy (adjusted HR, 6.29;
P
=0.001), implanter volume (adjusted HR 10.4 for <60/y versus >120/y,
P
=0.026), and Canadian Cardiovascular Society angina class (adjusted HR, 3.00 for class 2 to 4 versus 0 to 1;
P
=0.031). In a Cox model with a time-dependent variable of major complication within 45 days after replacement, major complications after ICD replacement were associated with an increased risk of mortality at 45, 90, and 180 days (adjusted HR, 9.61, 12.69, and 6.41, respectively;
P
=0.002 to 0.039).

Conclusions—

Risk factors associated with complications after ICD replacement include the presence of angina, antiarrhythmic therapy, increased number of previous procedures, and low implanter volume. Major complications may be associated with increased risk of subsequent mortality.
Luminal Esophageal Temperature Monitoring With a Deflectable Esophageal Temperature Probe and Intracardiac Echocardiography May Reduce Esophageal Injury During Atrial Fibrillation Ablation Procedures
Authors: Leite Luiz R. , Santos Simone N. , Maia Henrique , Henz Benhur D. , Giuseppin Fábio , Oliverira Anderson , Zanatta André R. , Peres Ayrton K. , Novakoski Clarissa , Barreto Jose R. , Vassalo Fabrício , d'Avila Andre , Singh Sheldon M.
Published: February 2011

Background—

Luminal esophageal temperature (LET) monitoring is one strategy to minimize esophageal injury during atrial fibrillation ablation procedures. However, esophageal ulceration and fistulas have been reported despite adequate LET monitoring. The objective of this study was to assess a novel approach to LET monitoring with a deflectable LET probe on the rate of esophageal injury in patients undergoing atrial fibrillation ablation.

Methods and Results—

Forty-five consecutive patients undergoing an atrial fibrillation ablation procedure followed by esophageal endoscopy were included in this prospective observational pilot study. LET monitoring was performed with a 7F deflectable ablation catheter that was positioned as close as possible to the site of left atrial ablation using the deflectable component of the catheter guided by visualization of its position on intracardiac echocardiography. Ablation in the posterior left atrial was limited to 25 W and terminated when the LET increased 2°C from baseline. Endoscopy was performed 1 to 2 days after the procedure. All patients had at least 1 LET elevation >2°C necessitating cessation of ablation. Deflection of the LET probe was needed to accurately measure LET in 5% of patients when ablating near the left pulmonary veins, whereas deflection of the LET probe was necessary in 88% of patients when ablating near the right pulmonary veins. The average maximum increase in LET was 2.5±1.5°C. No patients had esophageal thermal injury on follow-up endoscopy.

Conclusions—

A strategy of optimal LET probe placement using a deflectable LET probe and intracardiac echocardiography guidance, combined with cessation of radiofrequency ablation with a 2°C rise in LET, may reduce esophageal thermal injury during left atrial ablation procedures.
“The Artist is Present”: Artistic Re-enactments and the Impossibility of Presence
Authors: Jones Amelia
Published: February 2011

Springing off from the recent obsession over performance histories in the performance and art domains, “The Artist is Present” takes on claims for authenticity and “presence” by examining the series of recent re-enactments and events featuring Marina Abramović.
Peculiar Voices
Authors: Goebbels Heiner
Published: February 2011

The experimental work with the human voice in contemporary compositions often simply ignores the genuine connection of the voice to expression and to the body. The voice is not a “neutral” instrument, but always intertwined with its very character of impartation and its physical body.
Memory Walking with Urban Bush Women'sBatty Moves
Authors: Aduonum Ama Oforiwaa
Published: February 2011

Like the childhood songs and butt-shaking contests of Ghana, Batty Moves by the Brooklyn-based dance company Urban Bush Women celebrates the African American female form. The choreographer and the dancers share their memories of butt-tucking ballet classes, and the author shares her memory walk from Ghana to black America.
Gray Matter: Daniel Arsham, Jonah Bokaer, and Judith Sánchez Ruíz's REPLICA
Authors: England Betsy
Published: February 2011

In REPLICA, Daniel Arsham, Jonah Bokaer, and Judith Sánchez Ruíz attempt to replicate the capacities of the human brain through movement, highlighting the intertwined layers of perception and memory.
Colonialism and the Environment in India: Railways and Deforestation in 19th Century Punjab
Authors: Das Pallavi
Published: February 2011

Much of the deforestation seen in the Himalayas today can be traced back to the second half of the 19th century when railway construction began in colonial India. In this paper I argue that the construction and expansion of railways promoted by the British colonial state was designed to enable efficient resource extraction from India and that this process itself depleted India’s natural resources such as forests. In analysing the temporal and spatial unevenness of this deforestation in the specific context of the Punjab province I have drawn on government records of various departments, Parliamentary reports, books, scientific journals and newspapers as primary sources.
Assessing the Risk of Bullet Ricochet from Waves
Authors: Mirshak Ramzi
Published: February 2011

In both littoral environments and the open ocean, assessing the risk of bullet ricochet from the water surface is important as friendly assets and possibly civilian infrastructure may be in close proximity to operations. Bullet ricochet from water is usually examined in a laboratory environment where bullets are fired at a level water surface. While this set-up is appropriate for replicating ricochet from ponds, puddles, or small water containers, it is less applicable to ricochet from large bodies of water that support a rich surface wave field. Here, a method is proposed to extend results of flat-water experiments to consider bullet ricochet from a wavy surface. It is shown that the critical angle above which ricochet does not occur and the likelihood of stable or tumbling ricochets depend on whether waves are present and in what direction those waves are traveling relative to the path of the incoming bullet. Modeling suggests that the risk of ricochet is reduced when wave crests are perpendicular to the direction of fire but waves also increase the variability of ricochet characteristics. It is therefore suggested that, when possible, wave effects be considered when assessing the risk of bullet ricochet from water.
The Neoliberal State and the Penalization of Misery
Authors: Jinkings Isabella
Published: February 2011

The strategy adopted by the neoliberal state to maintain social order and safeguard private property in a context of economic deregulation and social precariousness has destroyed the welfare state and aggravated poverty, depriving the masses of any form of social protection while subjecting them to repression. The reinforcement of the repressive state apparatus is associated with the social instability provoked by the lack of social policies, the degradation of living conditions for the great majority of the population, and the amplification of income and property inequalities both in the so-called capitalist periphery and in the richest industrialized countries. The penalization of misery is revealed as a new expression of class domination.
Interregional Brain Interactions in Children with Unilateral Hearing Loss
Authors: Tibbetts Kathleen , Ead Banan , Umansky Amy , Coalson Rebecca , Schlaggar Bradley L. , Firszt Jill B. , Lieu Judith E. C.
Published: February 2011

Objective

To determine whether patterns of functional connectivity of cortical regions responsible for auditory processing and executive functions differ in children with unilateral hearing loss (UHL) versus their normal‐hearing (NH) siblings.

Study Design

Prospective observational study.

Setting

Academic medical center.

Subjects and Methods

Children with severe‐to‐profound UHL (9 right UHL, 7 left UHL) and 10 NH sibling controls were imaged using resting state functional connectivity magnetic resonance imaging (rs‐fcMRI). All MRI images were transformed to a single common atlas; regions of interest (ROI) were chosen based on previous literature and unpublished results. Mean regionwise correlations and conjunction analyses were performed across 34 seed ROIs to identify temporally synchronized, low‐frequency spontaneous fluctuations in the resting state blood oxygenation level–dependent signal that reveal functionally related regions.

Results

Mean regionwise Student t tests found a left posterior opercular region with more correlated resting state activity with the inferior parietal lobule seed in the children with both left and right UHL than NH. In conjunction analysis, 4 regions showed different resting‐state functional interactions between the NH and both UHL groups. These differences were in left medial globus pallidus, left middle temporal gyrus, right parahippocampal gyrus, and mid‐cingulate cortex. These regions include areas associated with auditory processing, executive function, and memory formation.

Conclusions

Resting state fcMRI identified differences in brain network interconnections between children with UHL and NH and may inform further investigation into the educational and behavioral difficulties experienced by children with UHL.
Intraoperative Parathyroid Hormone Assay
Authors: Gill Matthew T. , Dean Marc , Karr Jacob , Aultman Donnie F. , Nathan Cherie‐Ann O.
Published: February 2011

Objectives

The aims were to: (1) evaluate whether failure of intraoperative parathyroid hormone (ioPTH) to decrease by the Miami criterion is a more specific indicator of multiglandular disease (MGD) than sestamibi scan and (2) determine an adequate cutoff value for decrease in ioPTH in MGD.

Study Design

Case series with chart review.

Setting

Louisiana State University Health Sciences Center–Shreveport.

Subjects and Methods

Review of subjects undergoing parathyroidectomy using ioPTH and sestamibi for suspected parathyroid adenoma between 2005 and 2009. Patients with MGD were identified by pathology and operative reports.

Results

Eighty‐three subjects were identified (68 single adenomas, 11 double adenomas, and 4 multiple‐gland hyperplasias). Sestamibi predicted MGD in only 4 of 15 cases (27%). Five of the 11 double adenomas (DAs) were identified during initial surgery; the rest required reoperation for cure. ioPTH was useful in predicting MGD in 7 of 10 cases (70%) when a postexcisional value was drawn after removal of the first enlarged gland. Using the Miami criterion of 50% decrease in ioPTH over 15 minutes would have resulted in 1 unnecessary neck exploration and 3 missed DAs. Requiring both a 50% decrease in ioPTH over 15 minutes and normalization of the postexcisional value would have missed only 1 DA and resulted in a single unnecessary neck exploration.

Conclusion

Sestamibi alone fails to identify MGD 73% of the time, but the success rate increases significantly when combined with ioPTH. The “50% and normal” criterion worked best to increase the success rate in our study population, but larger trials are needed to confirm the utility of this criterion.
Dural Scalp and Intracranial Hemangiomas Causing Hydrocephalus and Venous Sinus Thrombosis in an Infant
Authors: Nahed Brian V. , Ferreira Manuel , Babu Maya A. , Terry Anna R. , Walcott Brian P. , Kahle Kristopher T. , Smith Edward R.
Published: February 2011

Cutaneous scalp hemangiomas may herald the presence of occult intracranial hemangiomas. A previously healthy 4-month-old girl presented with a bleeding scalp hemangioma, a bulging fontanel, and anemia. Magnetic resonance imaging (MRI) of the brain revealed hydrocephalus along with multiple intracranial hemangiomas. These lesions compressed the jugular foramina, resulting in venous sinus thrombosis involving the right transverse sinus, the left sigmoid sinus, and the torcular herophili. The patient had no family history of phakomatoses or other genetic abnormalities. A thrombophilia work-up result was unremarkable. The patient was treated with prednisolone (10 mg twice daily) and low molecular weight heparin (1 mg/kg/dose) twice daily. This treatment decreased the size of her cutaneous and intracranial hemangiomas and led to the resolution of her venous sinus thromboses and hydrocephalus. Innocuous scalp hemangioma in an infant may herald more concerning intracranial pathology, which can be treated effectively if diagnosed with appropriate imaging studies.
Jointly Navigating the Reclamation of the ‘‘Woman I Used to Be’’: Negotiating Concerns About the Postpartum Body Within the Marital Dyad
Authors: Paff Ogle Jennifer , Tyner Keila E. , Schofield-Tomschin Sherry
Published: February 2011

This interpretive study explored the marital dyad as a context for the negotiation of concerns relative to the postpartum body, and in particular, the reconfiguration of this body so as to more closely approximate the pre-pregnant body/self. The research was guided by symbolic interactionism and the work of Erving Goffman. Data were collected via in-depth interviews with 14 married couples expecting their first child. Analyses revealed that wives and husbands negotiated meanings relative to recapturing, redefining, and reclaiming wives’ bodies after childbirth in a way that suggested a repertoire of possible selves, including the Woman I/My Wife Used to Be (before pregnancy), the Woman I Fear I/My Wife Could Become (i.e., a woman who cannot get her old shape back), and the Women I/My Wife Hope(s) to Become (i.e., a woman who can get her old shape back) (cf. Guy & Banim, 2000). Within this general system of meanings, three overarching themes emerged: (a) aspirations for the postpartum body, (b) the navigation of concerns relative to the appearance of the postpartum body, and (c) reclamation projects planned and/or undertaken by wives. In varied ways, interactions within the marital dyad shaped the wives’ efforts to navigate their concerns about the postpartum body and to plan or undertake bodily reclamation projects. Generally speaking, husband-wife interactions were described by wives as a source of reassurance in the journey back to The Women They Used to Be. Findings provide support for interactionist proposition that the people come to understand the body through others’ eyes.
Border Health: Its Hidden Issues and Implications for Nursing Care
Authors: Kohlbry Pamela
Published: February 2011

The purpose of this article is to enhance nursing care for populations living on the U.S.—Mexico border by broadening nursing knowledge of related health issues. The health status of the individuals and families who reside on the border are negatively affected by many factors. These include population growth, health care access, poverty, high chronic disease rates, environment-related problems, and communicable diseases. Binational efforts, projects, and attention over the last 15 years have begun to acknowledge and attend to issues causing health challenges. Nursing’s contribution in the literature has focused on environmental health problems, such as childhood lead exposure. This article will review the status of border health, barriers to health care, and issues related to health care utilization. Implications for nursing practice and nursing research related to border health of individuals and families will be identified. Knowledge of these factors is the first step for nurses to address the unique problems of this population, which on the U.S. side of the border typically involves the uninsured and immigrant populations.
Daylighting metrics based on illuminance, distribution, glare and directivity
Authors: Cantin F. , Dubois M-C.
Published: February 2011

A method is presented for assessing daylighting quality based on metrics related to illuminance, distribution, glare and directivity. The calculations are done using the programs RADIANCE and DAYSIM for a south-west and a north-west oriented offices in the CDP building in Montreal (latitude 45° 30'N). The results indicate that the following set of metrics is the most useful for assessing the daylighting quality of architectural spaces: Useful Daylight Illuminance (UDI), Daylight Glare Probability and Vector/Scalar illuminance ratio. The results also suggest that the daylight factor should be replaced by the UDI and that more empirical research is needed to establish appropriate criteria for acceptable luminance ratios in the case of well daylit buildings.
When to Befriend the Court? Examining State Amici Curiae Participation Before the U.S. Supreme Court
Authors: Provost Colin
Published: February 2011

Over the past 30 years, the U.S. states have increased their participation as amici curiae significantly, in addition to winning more of their cases as direct parties. However, little attention has been paid to the factors that cause amici participation rates to vary among the states. The author examines the decision of state attorneys general (AGs) to initiate or join amicus curiae briefs in all 253 U.S. Supreme Court criminal procedure cases from 1990 through 2001. He hypothesizes that AGs are motivated largely by their own policy preferences and by their motivation to get reelected. Because amicus briefs are not particularly high-profile policy tools, reelection motivations ought to be demonstrated through responsiveness to elites in state government. The findings provide less support for this idea and more support for the idea that state AGs follow their own policy preferences through amicus participation.
Radioimmunotherapy-based conditioning for hematopoietic cell transplantation in children with malignant and nonmalignant diseases
Authors: Schulz Ansgar S. , Glatting Gerhard , Hoenig Manfred , Schuetz Catharina , Gatz Susanne A. , Grewendorf Simon , Sparber-Sauer Monika , Muche Rainer , Blumstein Norbert , Kropshofer Gabriele , Suttorp Meinolf , Bunjes Donald , Debatin Klaus-Michael , Reske Sven N. , Friedrich Wilhelm
Published: February 2011

Targeted irradiation of the bone marrow with radiolabeled monoclonal antibodies (radioimmunotherapy) represents a novel therapeutic approach with both myeloablative and antileukemic potential. In an open-label, single-center pilot study, 30 pediatric and adolescent patients undergoing hematopoietic cell transplantation for malignant (n = 16) and nonmalignant (n = 14) disorders received treatment with a 90Y-labeled anti-CD66 monoclonal antibody. Patients with a high risk of relapse (n = 7) received additional treatment with standard conditioning based on either total body irradiation or busulfan to intensify the antileukemic effect. In patients with comorbidities (n = 23), radioimmunotherapy was combined with a reduced-intensity conditioning regimen to reduce systemic toxicity. Preferential irradiation of the bone marrow was achieved in all patients. Nonrelapse mortality was 4 (13%) of 30 patients. In patients with malignant diseases, the probabilities of overall and disease-free survival at 2 years were 0.69 (95% confidence interval 0.37-0.87) and 0.46 (95% confidence interval 0.19-0.70), respectively. In patients with nonmalignant diseases, the probability of both overall and disease-free survival at 2 years was 0.94 (95% confidence interval 0.63-0.99). This pilot study demonstrates that radioimmunotherapy is effective in achieving myeloablation with low additional toxicity when used in combination with standard or reduced-intensity conditioning in young patients.
The incidence, risk factors, and outcome of transfusion-related acute lung injury in a cohort of cardiac surgery patients: a prospective nested case-control study
Authors: Vlaar Alexander P. J. , Hofstra Jorrit J. , Determann Rogier M. , Veelo Denise P. , Paulus Frederique , Kulik Wim , Korevaar Johanna , de Mol Bas A. , Koopman Marianne M. W. , Porcelijn Leendert , Binnekade Jan M. , Vroom Margreeth B. , Schultz Marcus J. , Juffermans Nicole P.
Published: February 2011

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related morbidity and mortality. Both antibodies and bioactive lipids that have accumulated during storage of blood have been implicated in TRALI pathogenesis. In a single-center, nested, case-control study, patients were prospectively observed for onset of TRALI according to the consensus definition. Of 668 patients, 16 patients (2.4%) developed TRALI. Patient-related risk factors for onset of TRALI were age and time on the cardiopulmonary bypass. Transfusion-related risk factors were total amount of blood products (odds ratio [OR] = 1.2; 95% confidence interval [CI], 1.03-1.44), number of red blood cells stored more than 14 days (OR = 1.6; 95% CI, 1.04-2.37), total amount of plasma (OR = 1.2; 95% CI, 1.03-1.44), presence of antibodies in donor plasma (OR = 8.8; 95% CI, 1.8-44), and total amount of transfused bioactive lipids (OR = 1.0; 95% CI, 1.00-1.07). When adjusted for patient risk factors, only the presence of antibodies in the associated blood products remained a risk factor for TRALI (OR = 14.2; 95% CI, 1.5-132). In-hospital mortality of TRALI was 13% compared with 0% and 3% in transfused and nontransfused patients, respectively (P < .05). In conclusion, the incidence of TRALI is high in cardiac surgery patients and associated with adverse outcome. Our results suggest that cardiac surgery patients may benefit from exclusion of blood products containing HLA/HNA antibodies.
Predicting fadeout versus persistence of paratuberculosis in a dairy cattle herd for management and control purposes: a modelling study
Authors: Marcé Clara , Ezanno Pauline , Seegers Henri , Pfeiffer Dirk Udo , Fourichon Christine
Published: February 2011

Epidemiological models enable to better understand the dynamics of infectious diseases and to assessex-antecontrol strategies. ForMycobacterium aviumsubsp.paratuberculosis(Map), possible transmission routes have been described, butMapspread in a herd and the relative importance of the routes are currently insufficiently understood to prioritize control measures. We aim to predict early afterMapintroduction in a dairy cattle herd whether infection is likely to fade out or persist, when no control measures are implemented, using a modelling approach. Both vertical transmission and horizontal transmission via the ingestion of colostrum, milk, or faeces present in the contaminated environment were modelled. Calf-to-calf indirect transmission was possible. Six health states were represented: susceptible, transiently infectious, latently infected, subclinically infected, clinically affected, and resistant. The model was partially validated by comparing the simulated prevalence with field data. Housing facilities and contacts between animals were specifically considered for calves and heifers. After the introduction of one infected animal in a naive herd, fadeout occurred in 66% of the runs. WhenMappersisted, the prevalence of infected animals increased to 88% in 25 years. The two main transmission routes were via the farm's environment and in utero transmission. Calf-to-calf transmission was minor. Fadeout versusMappersistence could be differentiated with the number of clinically affected animals, which was rarely above one when fadeout occurred. Therefore, early detection of affected animals is crucial in preventingMappersistence in dairy herds.
Imputation strategies for missing binary outcomes in cluster randomized trials
Authors: Ma Jinhui , Akhtar-Danesh Noori , Dolovich Lisa , Thabane Lehana ,   the CHAT investigators
Published: February 2011

Background

Attrition, which leads to missing data, is a common problem in cluster randomized trials (CRTs), where groups of patients rather than individuals are randomized. Standard multiple imputation (MI) strategies may not be appropriate to impute missing data from CRTs since they assume independent data. In this paper, under the assumption of missing completely at random and covariate dependent missing, we compared six MI strategies which account for the intra-cluster correlation for missing binary outcomes in CRTs with the standard imputation strategies and complete case analysis approach using a simulation study.

Method

We considered three within-cluster and three across-cluster MI strategies for missing binary outcomes in CRTs. The three within-cluster MI strategies are logistic regression method, propensity score method, and Markov chain Monte Carlo (MCMC) method, which apply standard MI strategies within each cluster. The three across-cluster MI strategies are propensity score method, random-effects (RE) logistic regression approach, and logistic regression with cluster as a fixed effect. Based on the community hypertension assessment trial (CHAT) which has complete data, we designed a simulation study to investigate the performance of above MI strategies.

Results

The estimated treatment effect and its 95% confidence interval (CI) from generalized estimating equations (GEE) model based on the CHAT complete dataset are 1.14 (0.76 1.70). When 30% of binary outcome are missing completely at random, a simulation study shows that the estimated treatment effects and the corresponding 95% CIs from GEE model are 1.15 (0.76 1.75) if complete case analysis is used, 1.12 (0.72 1.73) if within-cluster MCMC method is used, 1.21 (0.80 1.81) if across-cluster RE logistic regression is used, and 1.16 (0.82 1.64) if standard logistic regression which does not account for clustering is used.

Conclusion

When the percentage of missing data is low or intra-cluster correlation coefficient is small, different approaches for handling missing binary outcome data generate quite similar results. When the percentage of missing data is large, standard MI strategies, which do not take into account the intra-cluster correlation, underestimate the variance of the treatment effect. Within-cluster and across-cluster MI strategies (except for random-effects logistic regression MI strategy), which take the intra-cluster correlation into account, seem to be more appropriate to handle the missing outcome from CRTs. Under the same imputation strategy and percentage of missingness, the estimates of the treatment effect from GEE and RE logistic regression models are similar.
Study design and participant characteristics of a randomized controlled trial of directly administered antiretroviral therapy in opioid treatment programs
Authors: Mullen Bernadette Anna , Cook Katie , Moore Richard D , Rand Cynthia , Galai Noya , McCaul Mary E , Glass Sheldon , Oursler Krisann K , Lucas Gregory M
Published: February 2011

Background

HIV-infected drug users are at higher risk of non-adherence and poor treatment outcomes than HIV-infected non-drug users. Prior work from our group and others suggests that directly administered antiretroviral therapy (DAART) delivered in opioid treatment programs (OTPs) may increase rates of viral suppression.

Methods/Design

We are conducting a randomized trial comparing DAART to self-administered therapy (SAT) in 5 OTPs in Baltimore, Maryland. Participants and investigators are aware of treatment assignments. The DAART intervention is 12 months. The primary outcome is HIV RNA < 50 copies/mL at 3, 6, and 12 months. To assess persistence of any study arm differences that emerge during the active intervention, we are conducting an 18-month visit (6 months after the intervention concludes). We are collecting electronic adherence data for 2 months in both study arms. Of 457 individuals screened, a total of 107 participants were enrolled, with 56 and 51 randomly assigned to DAART and SAT, respectively. Participants were predominantly African American, approximately half were women, and the median age was 47 years. Active use of cocaine and other drugs was common at baseline. HIV disease stage was advanced in most participants. The median CD4 count at enrollment was 207 cells/mm3, 66 (62%) had a history of an AIDS-defining opportunistic condition, and 21 (20%) were antiretroviral naïve.

Conclusions

This paper describes the rationale, methods, and baseline characteristics of subjects enrolled in a randomized clinical trial comparing DAART to SAT in opioid treatment programs.

Trial Registration

ClinicalTrials.gov: NCT00279110