bluuebunny/crossref_metadata_2025 huggingface dataset:
Creating Value Through Best‐In‐Class Capital Allocation1
Authors: Zenner Marc , Berkovitz Tomer , Clark John H.S.
Published: December 2009

With the economy showing signs of recovery, companies are shifting their focus from liquidity and balance sheet concerns back towards capital allocation and value creation. This article provides a comprehensive framework to examine shareholder value creation through capital allocation, and discusses important capital allocation lessons that have re‐emerged over the last few years.

Notable among the key lessons are the following:

Growth alone does not guarantee value creation, which suggests that companies should allocate capital based on the economic value of each investment opportunity.

The limits of diversification in a financial crisis should be considered when allocating capital and managing liquidity.

Companies should be conservative with base‐case cash flow projections and incorporate the possibility of downside scenarios into their projections.

It is important to incorporate all forms of capital when managing liquidity.

Whether using a long‐term or current‐market approach, companies should be consistent throughout the cycle in their cost of capital methodology.

Companies should continually rethink investments and allocate capital in an attempt to maintain a competitive advantage.

Evaluate returns relative to risk and cost of capital, and not against the company's average ROIC.

Comparing the IRR of share repurchases to new investments is not an apples‐to‐apples comparison.

Finally, companies should concentrate on the strategic uses and value of particular assets and not allow their decisions to be driven by the value they might receive relative to their initial cost.
Extended Mechanical Circulatory Support With a Continuous‐Flow Rotary Left Ventricular Assist Device
Authors: Harris Scott , Tepper David , Ip Randy
Published: December 2009

Abstract.  Objectives.  This study sought to evaluate the use of a continuous‐flow rotary left ventricular assist device (LVAD) as a bridge to heart transplant

Background LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous‐flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism.

Methods In a prospective multicenter study, 281 patients urgently listed (United Network for Organ Sharing status 1A or 1B) for heart transplant underwent implant of a continuous‐flow LVAD. Survival and transplant rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months.

Results Of 281 patients, 222 (79%) underwent transplant or LVAD removal for cardiac recovery or had ongoing LVAD support at 18‐month follow‐up. Actuarial survival on support was 72% (95% confidence interval, 65%–79%) at 18 months. At 6 months, there were significant improvements in functional status and 6‐minute walk test results (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6‐minute walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients.

Conclusions A continuous‐flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplant, with improved functional status and quality of life.
Permanent Genetic Resources added to Molecular Ecology Resources Database 1 August 2009–30 September 2009
Authors:   Molecular Ecology Resources Primer Development Consortium, ABDOULLAYE DOUKARY , ACEVEDO I. , ADEBAYO ABISOLA A. , BEHRMANN‐GODEL JASMINCA , BENJAMIN R. C. , BOCK DAN G. , BORN CÉLINE , BROUAT CARINE , CACCONE ADALGISA , CAO LING‐ZHEN , CASADO‐AMEZÚA P. , CATANÉO J. , CORREA‐RAMIREZ M. M. , CRISTESCU MELANIA E. , DOBIGNY GAUTHIER , EGBOSIMBA EMMANUEL E. , ETCHBERGER LIANNA K. , FAN BIN , FIELDS PETER D. , FORCIOLI D. , FURLA P. , GARCIA de LEON F. J. , GARCÍA‐JIMÉNEZ R. , GAUTHIER PHILIPPE , GERGS RENÉ , GONZÁLEZ CLEMENTINA , GRANJON LAURENT , GUTIÉRREZ‐RODRÍGUEZ CARLA , HAVILL NATHAN P. , HELSEN P. , HETHER TYLER D. , HOFFMAN ERIC A. , HU XIANGYANG , INGVARSSON PÄR K. , ISHIZAKI S. , JI HEYI , JI X. S. , JIMENEZ M. L. , KAPIL R. , KARBAN R. , KELLER STEPHEN R. , KUBOTA S. , LI SHUZHEN , LI WANSHA , LIM DOUGLAS D. , LIN HAORAN , LIU XIAOCHUN , LUO YAYAN , MACHORDOM A. , MARTIN ANDREW P. , MATTHYSEN E. , MAZZELLA MAXWELL N. , McGEOCH MÉLODIE A. , MENG ZINING , NISHIZAWA M. , O’BRIEN PATRICIA , OHARA M. , ORNELAS JUAN FRANCISCO , ORTU M. F. , PEDERSEN AMY B. , PRESTON L. , REN QIN , ROTHHAUPT KARL‐OTTO , SACKETT LOREN C. , SANG QING , SAWYER G. M. , SHIOJIRI K. , TAYLOR DOUGLAS R. , Van DONGEN S. , Van VUUREN BETTINE JANSEN , VANDEWOESTIJNE S. , WANG H. , WANG J. T. , WANG LE , XU XIANG‐LI , YANG GUANG , YANG YONGPING , ZENG Y. Q. , ZHANG QING‐WEN , ZHANG YONGPING , ZHAO Y. , ZHOU YAN
Published: December 2009

This article documents the addition of 238 microsatellite marker loci and 72 pairs of Single Nucleotide Polymorphism (SNP) sequencing primers to the Molecular Ecology Resources Database. Loci were developed for the following species: Adelges tsugae, Artemisia tridentata, Astroides calycularis, Azorella selago, Botryllus schlosseri, Botrylloides violaceus, Cardiocrinum cordatum var. glehnii, Campylopterus curvipennis, Colocasia esculenta, Cynomys ludovicianus, Cynomys leucurus, Cynomys gunnisoni, Epinephelus coioides, Eunicella singularis, Gammarus pulex, Homoeosoma nebulella, Hyla squirella, Lateolabrax japonicus, Mastomys erythroleucus, Pararge aegeria, Pardosa sierra, Phoenicopterus ruber ruber and Silene latifolia. These loci were cross‐tested on the following species: Adelges abietis, Adelges cooleyi, Adelges piceae, Pineus pini, Pineus strobi, Tubastrea micrantha, three other Tubastrea species, Botrylloides fuscus, Botrylloides simodensis, Campylopterus hemileucurus, Campylopterus rufus, Campylopterus largipennis, Campylopterus villaviscensio, Phaethornis longuemareus, Florisuga mellivora, Lampornis amethystinus, Amazilia cyanocephala, Archilochus colubris, Epinephelus lanceolatus, Epinephelus fuscoguttatus, Symbiodinium temperate‐A clade, Gammarus fossarum, Gammarus roeselii, Dikerogammarus villosus and Limnomysis benedeni. This article also documents the addition of 72 sequencing primer pairs and 52 allele specific primers for Neophocaena phocaenoides.
Exciting Structures
Authors: Foley John F.
Published: December 2009

The solution to the structure of the AMPA receptor reveals clues about the general mechanisms of action of ionotropic glutamate receptors.
SEMIGROUPS WITH if–then–else AND HALTING PROGRAMS
Authors: JACKSON MARCEL , STOKES TIM
Published: December 2009

The "if–then–else" construction is one of the most elementary programming commands, and its abstract laws have been widely studied, starting with McCarthy. Possibly, the most obvious extension of this is to include the operation of composition of programs, which gives a semigroup of functions (total, partial, or possibly general binary relations) that can be recombined using if–then–else. We show that this particular extension admits no finite complete axiomatization and instead focus on the case where composition of functions with predicates is also allowed (and we argue there is good reason to take this approach). In the case of total functions — modeling halting programs — we give a complete axiomatization for the theory in terms of a finite system of equations. We obtain a similar result when an operation of equality test and/or fixed point test is included.
Early exposure of the pregestational intrauterine and postnatal growth-restricted female offspring to a peroxisome proliferator-activated receptor-γ agonist
Authors: Garg Meena , Thamotharan Manikkavasagar , Pan Gerald , Lee Paul W. N. , Devaskar Sherin U.
Published: December 2009

Prenatal nutrient restriction with intrauterine growth restriction (IUGR) alters basal and glucose-stimulated insulin response and hepatic metabolic adaptation. The effect of early intervention with insulin-sensitizing peroxisome proliferator-activated receptor γ agonists was examined in the metabolically maladapted F1 pregestational IUGR offspring with a propensity toward pregnancy-induced gestational diabetes. The effect of rosiglitazone maleate [RG; 11 μmol/day from postnatal day (PN) 21 to PN60] vs. placebo (PL) on metabolic adaptations in 2-mo-old F1 female rats subjected to prenatal (IUGR), postnatal (PNGR), or pre- and postnatal (IUGR + PNGR) nutrient restriction was investigated compared with control (CON). RG vs. PL had no effect on body weight or plasma glucose concentrations but increased subcutaneous white and brown adipose tissue and plasma cholesterol concentrations in all three experimental groups. Glucose tolerance tests with a 1:1 mixture of [2-2H2]- and [6,6-2H2]glucose in RG IUGR vs. PL IUGR revealed glucose tolerance with a lower glucose-stimulated insulin release (GSIR) and suppressed endogenous hepatic glucose production (HGP) with no difference in glucose clearance (GC) and recycling (GR). RG PNGR, although similar to PL CON, was hyperglycemic vs. PL PNGR with reduced GR but no difference in the existent low GSIR, HGP, and GC. RG IUGR + PNGR overall was no different from the PL counterpart. Insulin tolerance tests revealed perturbed recovery to baseline from the exaggerated hypoglycemia in RG vs. the PL groups with the only exception being RG PNGR where further worsening of hypoglycemia over PL PNGR was minimal with full recovery to baseline. These observations support that early intervention with RG suppressed HGP in IUGR vs. PL IUGR, without increasing GSIR similar to that seen in CON. Although RG reversed PNGR to the PL CON metabolic state, no such insulin-sensitizing effect was realized in IUGR + PNGR.
Overexpression of Foxf2 in adipose tissue is associated with lower levels of IRS1 and decreased glucose uptake in vivo
Authors: Westergren Rickard , Nilsson Daniel , Heglind Mikael , Arani Zahra , Grände Mats , Cederberg Anna , Ahrén Bo , Enerbäck Sven
Published: December 2009

Many members of the forkhead genes family of transcription factors have been implicated as important regulators of metabolism, in particular, glucose homeostasis, e.g., Foxo1, Foxa3, and Foxc2. The purpose of this study was to exploit the possibility that yet unknown members of this gene family play a role in regulating glucose tolerance in adipocytes. We identified Foxf2 in a screen for adipose-expressed forkhead genes. In vivo overexpression of Foxf2 in an adipose tissue-restricted fashion demonstrated that such mice display a significantly induced insulin secretion in response to an intravenous glucose load compared with wild-type littermates. In response to increased Foxf2 expression, insulin receptor substrate 1 (IRS1) mRNA and protein levels are significantly downregulated in adipocytes; however, the ratio of serine vs. tyrosine phosphorylation of IRS1 seems to remain unaffected. Furthermore, adipocytes overexpressing Foxf2 have a significantly lower insulin-mediated glucose uptake compared with wild-type adipocytes. These findings argue that Foxf2 is a previously unrecognized regulator of cellular and systemic whole body glucose tolerance, at least in part, due to lower levels of IRS1. Foxf2 and its downstream target genes can provide new insights with regard to identification of novel therapeutic targets.
Glucose transporters in the 21st Century
Authors: Thorens Bernard , Mueckler Mike
Published: December 2009

The ability to take up and metabolize glucose at the cellular level is a property shared by the vast majority of existing organisms. Most mammalian cells import glucose by a process of facilitative diffusion mediated by members of the Glut (SLC2A) family of membrane transport proteins. Fourteen Glut proteins are expressed in the human and they include transporters for substrates other than glucose, including fructose, myoinositol, and urate. The primary physiological substrates for at least half of the 14 Glut proteins are either uncertain or unknown. The well-established glucose transporter isoforms, Gluts 1–4, are known to have distinct regulatory and/or kinetic properties that reflect their specific roles in cellular and whole body glucose homeostasis. Separate review articles on many of the Glut proteins have recently appeared in this journal. Here, we provide a very brief summary of the known properties of the 14 Glut proteins and suggest some avenues of future investigation in this area.
Dynamic convergence and divergence of renal genomic and biological pathways in protection from Dahl salt-sensitive hypertension
Authors: Lu Limin , Li Peigang , Yang Chun , Kurth Terry , Misale Michael , Skelton Meredith , Moreno Carol , Roman Richard J. , Greene Andrew S. , Jacob Howard J. , Lazar Jozef , Liang Mingyu , Cowley Allen W.
Published: December 2009

Chromosome 13 consomic and congenic rat strains were analyzed to investigate the pattern of genomic pathway utilization involved in protection against salt-sensitive hypertension and renal injury. Introgression of the entire Brown-Norway chromosome 13 (consomic SS-13BN) or nonoverlapping segments of this chromosome (congenic strains, 16 Mbp in D13Rat151–D13Rat197 or 14 Mbp in D13Rat111–D13Got22) into the genome of the Dahl salt-sensitive rat attenuated salt-induced hypertension and proteinuria. mRNA abundance profiles in the renal cortex and the renal medulla from rats receiving 0.4% or 8% NaCl diets revealed two important features of pathway recruitment in these rat strains. First, the two congenic strains shared alterations in several pathways compared with Dahl salt-sensitive rats, despite the fact that the genomic segments introgressed in the two congenic strains did not overlap. Second, even though the genomic segment introgressed in each congenic strain was a part of the chromosome introgressed in the consomic strain, pathways altered in each congenic strain were not simply a subset of those altered in the consomic. Supporting the relevance of the mRNA data, differential expression of oxidative stress-related genes among the four strains of rats was associated with differences in urinary excretion of lipid peroxidation products. The findings suggest that different genetic alterations might converge to influence shared pathways in protection from hypertension, and that, depending on the genomic context, the same genetic alteration might diverge to affect different pathways.
Pole to Pole Intraocular Transit of Tarantula Hairs—An Intriguing Cause of Red Eye
Authors: Sheth Hiten G. , Pacheco Patricio , Sallam Ahmed , Lightman Sue
Published: December 2009

This intriguing case report provides novel images and a description of the anterior and rarer posterior segment findings seen in ocular inflammation associated with tarantula spider hair exposure. We present an interventional case report of a 9-year-old boy who presented with a red, sore eye. Slit lamp examination revealed right eye injection, multiple small hairs at differing levels of the cornea with associated opacities and inflammation within the anterior and posterior segments of the eye. Only after detailed and repeated questioning did the aetiology become apparent. Conservative management in the form of topical steroid and antibiotics was commenced and he did well with no obvious sequelae in the medium term. Healthcare personnel (and indeed pet shop owners, arachnid enthusiasts and even parents) should be aware of the potential ocular complications of tarantula hair exposure and clinicians should perhaps specifically ask about pet-keeping when presented with an unusual red eye.
Constructive Field Theory in Zero Dimension
Authors: Rivasseau V.
Published: December 2009

Constructive field theory can be considered as a reorganization of perturbation theory in a convergent way. In this pedagogical note we propose to wander through five different methods to compute the number of connected graphs of the zero‐dimensional ϕ4 field theory, in increasing order of sophistication and power.
Successful Surgical Resection for Peritoneal Implantation of Hepatocellular Carcinoma at the Paracardial Portion
Authors: Sanada Yuichi , Osada Shinji , Tokuyama Yasuharu , Tanaka Yoshihiro , Takahashi Takao , Yamaguchi Kazuya , Yoshida Kazuhiro
Published: December 2009

Peritoneal implantation from hepatocellular carcinoma has been rarely reported. It may occur at various sites. Here we present a surgically resected case of peritoneal implantation to the diaphragm from hepatocellular carcinoma. A 50-year-old woman underwent right hemihepatectomy extended to a medial part of Couinaud segment IV for hepatocellular carcinoma in May 2000. In December 2008, the elevation of alpha-phetoprotein and the appearance of a heterogeneously enhanced mass, with dimensions of  cm, and adjacent to the remnant liver and pericardium suggested intrahepatic recurrence with markedly enhanced growth. After transcatheter arterial embolization, surgical resection under laparotomy combined with median sternotomy was selected. Samples of pericardial fluid showed no malignancy after cytological examination. At the superior border of the tumor, the confluence of pericardium and diaphragm was displaced, but the tumor itself showed a generally expanding but not invasive growth. The resected tumor showed moderately differentiated hepatocellular carcinoma whose pathology revealed a peritoneal implantation to the diaphragm. The patient is in good health without any postoperative complications or any further sign of recurrence.
Osteotomy and Autograft Lengthening for Intra-Articular Malunion of the Proximal Ulna: A Case Report
Authors: Doornberg Job N. , Marti René K.
Published: December 2009

An osteotomy with interposition of iliac crest bone graft and lengthening of the proximal ulna can be used to restore ulnohumeral congruency after a malunited comminuted olecranon fracture treated with figure-of-eight tension band wiring.
Attenuation of Acute Lung Inflammation and Injury by Whole Body Cooling in a Rat Heatstroke Model
Authors: Yang Hsi-Hsing , Chang Ching-Ping , Cheng Juei-Tang , Lin Mao-Tsun
Published: December 2009

Whole body cooling is the current therapy of choice for heatstroke because the therapeutic agents are not available. In this study, we assessed the effects of whole body cooling on several indices of acute lung inflammation and injury which might occur during heatstroke. Anesthetized rats were randomized into the following groups and given (a) no treatment or (b) whole body cooling immediately after onset of heatstroke. As compared with the normothermic controls, the untreated heatstroke rats had higher levels of pleural exudates volume and polymorphonuclear cell numbers, lung myloperoxidase activity and inducible nitric oxide synthase expression, histologic lung injury score, and bronchoalveolar proinflammatory cytokines and glutamate, and PaCO2. In contrast, the values of mean arterial pressure, heart rate, PaO2, pH, and blood HCO3 − were all significantly lower during heatstroke. The acute lung inflammation and injury and electrolyte imbalance that occurred during heatstroke were significantly reduced by whole body cooling. In conclusion, we identified heat‐induced acute lung inflammation and injury and electrolyte imbalance could be ameliorated by whole body cooling.
MEL-IRIS: An Online Tool for Audio Analysis and Music Indexing
Authors: Margounakis Dimitrios , Politis Dionysios , Mokos Konstantinos
Published: December 2009

Chroma is an important attribute of music and sound, although it has not yet been adequately defined in literature. As such, it can be used for further analysis of sound, resulting in interesting colorful representations that can be used in many tasks: indexing, classification, and retrieval. Especially in Music Information Retrieval (MIR), the visualization of the chromatic analysis can be used for comparison, pattern recognition, melodic sequence prediction, and color-based searching. MEL-IRIS is the tool which has been developed in order to analyze audio files and characterize music based on chroma. The tool implements specially designed algorithms and a unique way of visualization of the results. The tool is network-oriented and can be installed in audio servers, in order to manipulate large music collections. Several samples from world music have been tested and processed, in order to demonstrate the possible uses of such an analysis.
Design for Motor Controller in Hybrid Electric Vehicle Based on Vector Frequency Conversion Technology
Authors: Lian Jing , Zhou Yafu , Ma Teng , Wang Wei
Published: December 2009

Motor and its control technology are one of the main components of Hybrid Electric Vehicle (HEV). To meet HEV′s fast torque response, vector control algorithm based on rotor flux‐oriented and simulation model is concerned and modular designs for controller′s hardware and software are presented in the paper in order to build a platform to achieve the vector control of asynchronous induction motor. Analyze the controller′s electromagnetic compatibility, introduce the corresponding antijamming measures to assure the normal operation of the electromagnetic sensitive devices such as CAN bus; experiment proves that the measure is practical and feasible. On the basis of the control logic correct, such as improving CAN bus communication reliability, assuring power‐on sequence and fault treatment, carry on the motor bench experiment, test its static properties, and adjust the controller parameters. The experimental results show that the designed driving system has the performance of low speed and high torque, a wide range of variable speed and high comprehensive efficiency.
Hepatocyte Growth Factor Reduces Susceptibility to an Irreversible Epidermal Growth Factor Receptor Inhibitor in EGFR-T790M Mutant Lung Cancer
Authors: Yamada Tadaaki , Matsumoto Kunio , Wang Wei , Li Qi , Nishioka Yasuhiko , Sekido Yoshitaka , Sone Saburo , Yano Seiji
Published: December 2009

Purpose: The secondary T790M mutation in epidermal growth factor receptor (EGFR) is the most frequent cause of acquired resistance to the reversible EGFR tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib, in lung cancer. Irreversible EGFR-TKIs are expected to overcome the reversible EGFR-TKI resistance of lung cancer harboring T790M mutation in EGFR. However, it is clear that resistance may also develop to this class of inhibitors. We showed previously that hepatocyte growth factor (HGF) induced gefitinib resistance of lung cancer harboring EGFR-activating mutations. Here, we investigated whether HGF induced resistance to the irreversible EGFR-TKI, CL-387,785, in lung cancer cells (H1975) harboring both L858R activating mutation and T790M secondary mutation in EGFR.

Experimental Design: CL-387,785 sensitivity and signal transduction in H1975 cells were examined in the presence or absence of HGF or HGF-producing fibroblasts with or without HGF-MET inhibitors.

Results: HGF reduced susceptibility to CL-387,785 in H1975 cells. Western blotting and small interfering RNA analyses indicated that HGF-induced hyposensitivity was mediated by the MET/phosphoinositide 3-kinase/Akt signaling pathway independent of EGFR, ErbB2, ErbB3, and ErbB4. Hyposensitivity of H1975 cells to CL-387,785 was also induced by coculture with high-level HGF-producing lung fibroblasts. The hyposensitivity was abrogated by treatment with anti-HGF neutralizing antibody, HGF antagonist NK4, or MET-TKI.

Conclusions: We showed HGF-mediated hyposensitivity as a novel mechanism of resistance to irreversible EGFR-TKIs. It will be clinically valuable to investigate the involvement of HGF-MET–mediated signaling in de novo and acquired resistance to irreversible EGFR-TKIs in lung cancer harboring T790M mutation in EGFR. Clin Cancer Res; 16(1); 174–83
Senescence of Cultured Porcine Coronary Arterial Endothelial Cells Is Associated with Accelerated Oxidative Stress and Activation of NFĸB
Authors: Lee Mary Y.K. , Wang Yu , Vanhoutte Paul M.
Published: December 2009

Aims: Endothelial dysfunction occurs following multiple passaging in vitro,but the molecular mechanisms involved remain unidentified. The present study defined the genomic changes related to dysfunction in cultured senescent endothelial cells. Methods and Results: Senescent cells were produced by multiple passaging of porcine coronary arterial endothelial cells for up to 4 weeks. Genomic and proteomic studies on cultured cells at the first passage (P1) and the fourth passage (P4) were performed. Senescence and decreased NO production were observed in cells and several signaling pathways – such as IFN/STAT, IGF, TGF-β, cytoskeleton rearrangement and lipid metabolism – were altered at P4, as judged from the microarray analysis. The basal and stimulated (by TNF-α) levels of NFĸB were augmented in senescent cells in electrophoretic mobility shift assays in association with increased oxidative stress, increased p53 protein stability, and activated apoptotic pathways. The increased oxidative stress was alleviated by treatment with the superoxide dismutase mimetic MnTMPyP. Conclusions: After multiple passaging in vitro, porcine coronary endothelial cells exhibited dysfunction and senescence associated with reduced proliferative capacity, increased oxidative stress, and activation of the NFĸB and p53 signaling pathways.
Alterations in the Renin-Angiotensin System in a Rat Model of Human Preeclampsia
Authors: Uddin Mohammad Nasir , Agunanne Enoch , Horvat Darijana , Puschett Jules B.
Published: December 2009

Background/Aims: Preeclampsia is a hypertensive disorder unique to pregnancy in which elevated levels of marinobufagenin (MBG) have been reported. The renin-angiotensin system (RAS) may also play a role in the pathogenesis of preeclampsia. The aim of our study was to evaluate the status of the RAS in a rat model of preeclampsia characterized by hypertension, proteinuria, excessive weight gain and intrauterine growth restriction. Methods: We evaluated the components of the RAS in 5 groups of animals: nonpregnant control; normal pregnant (NP); pregnant rats which received injections of desoxycorticosterone acetate and 0.9% saline as their drinking water (PDS); normal pregnant rats injected with MBG (NPM), and PDS rats to which resibufogenin (RBG) had been administered (PDSR). RBG is an antagonist of MBG differing in structure from MBG only in the absence of a hydroxyl group in the β-5 position. Results: Plasma levels of active renin, renin and Ang II were significantly lower in PDS and NPM compared to NP and PDSR rats (p < 0.05). However, placental levels of these components were increased significantly in PDS and NPM compared to NP and PDSR rats (p < 0.05). Placental AT1 receptor expression was significantly higher in PDS and NPM compared to NP and PDSR rats (p < 0.05). Conclusions: (1) The peripheral RAS is downregulated, and the uteroplacental RAS is upregulated in this rat model of preeclampsia; (2) MBG is involved in the causation of these alterations, and (3) RBG prevents these changes.
Clinical Effectiveness of Implantable Cardioverter-Defibrillators Among Medicare Beneficiaries With Heart Failure
Authors: Hernandez Adrian F. , Fonarow Gregg C. , Hammill Bradley G. , Al-Khatib Sana M. , Yancy Clyde W. , O'Connor Christopher M. , Schulman Kevin A. , Peterson Eric D. , Curtis Lesley H.
Published: December 2009

Background—

The clinical effectiveness of implantable cardioverter-defibrillators (ICDs) in older patients with heart failure has not been established, and older patients have been underrepresented in previous studies.

Methods and Results—

We identified patients with heart failure who were aged 65 years or older and were eligible for an ICD, had left ventricular ejection fraction of 35% or less, and were discharged alive from hospitals participating in the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients With Heart Failure and the Get With the Guidelines–Heart Failure quality-improvement programs during the period January 1, 2003, through December 31, 2006. We matched the patients to Medicare claims to examine long-term outcomes. The main outcome measure was all-cause mortality over 3 years. The study population included 4685 patients who were discharged alive and were eligible for an ICD. Mean age was 75.2 years, 60% of the patients were women, mean ejection fraction was 25%, and 376 (8.0%) patients received an ICD before discharge. Mortality was significantly lower among patients who received an ICD compared with those who did not (19.8% versus 27.6% at 1 year, 30.9% versus 41.9% at 2 years, and 38.1% versus 52.3% at 3 years;
P
<0.001 for all comparisons). The inverse probability-weighted adjusted hazard of mortality at 3 years for patients receiving an ICD was 0.71 (95% CI, 0.56 to 0.91).

Conclusions—

Medicare beneficiaries hospitalized with heart failure and left ventricular ejection fraction of 35% or less who were selected for ICD therapy had lower risk-adjusted long-term mortality compared with those who did not receive an ICD.

Clinical Trial Registration—

clinicaltrials.gov. Identifier: NCT00344513.
The “Shoulds” and “Should Nots” of Moral Emotions: A Self-Regulatory Perspective on Shame and Guilt
Authors: Sheikh Sana , Janoff-Bulman Ronnie
Published: December 2009

A self-regulatory framework for distinguishing between shame and guilt was tested in three studies. Recently, two forms of moral regulation based on approach versus avoidance motivation have been proposed in the literature. Proscriptive regulation is sensitive to negative outcomes, inhibition based, and focused on what we should not do. Prescriptive regulation is sensitive to positive outcomes, activation based, and focused on what we should do. In the current research, consistent support was found for shame’s proscriptive and guilt’s prescriptive moral underpinnings. Study 1 found a positive association between avoidance orientation and shame proneness and between approach orientation and guilt proneness. In Study 2, priming a proscriptive orientation increased shame and priming a prescriptive orientation increased guilt. In Study 3, transgressions most apt to represent proscriptive and prescriptive violations predicted subsequent judgments of shame and guilt, respectively. This self-regulatory perspective provides a broad interpretive framework for understanding and extending past research findings.
State Housing Finance Agencies Forty Years Later
Authors: Scally Corianne P.
Published: December 2009

The gradual withdrawal of federal leadership in affordable housing has required states to step into an ever-widening gap in housing policy and finance. Much of this responsibility falls upon state housing finance agencies (HFAs). This article compares historical HFA roles with contemporary national trends and case study data and identifies five major roles played by HFAs today: financer, administrator/ monitor, planner, convener/coordinator, and policy innovator. HFA roles have been expanded through top-down political mandates, bottom-up interest group pressures, and complex institutional structures. The article also identifies several challenges to further change, including financial risk, interagency coordination, and agency transparency and accountability. HFAs have become major players in state affordable housing policy and suggests that planners, policy makers and advocates make better use of these agencies in implementing state affordable housing solutions.
Academics and Auditors
Authors: Siemiatycki Matti
Published: December 2009

How common are cost overruns during the delivery of transportation infrastructure projects such as roads, bridges, and public transit facilities, and what explains their occurrence? This article compares the findings of studies by academics and independent government auditors, two groups that have different mandates, objectives, and access to data. There is a high level of consistency in the finding that transportation projects regularly experience escalating costs. Yet there are sharp divergences between the technical and managerial explanations prioritized by the auditors and the political, economic, and psychological explanations prioritized in much of the academic literature. The differences in explanations point to diverse remedies for the challenge of cost overruns.
The Stress Process in Palliative Cancer Care: A Qualitative Study on Informal Caregiving and its Implication for the Delivery of Care
Authors: Brazil Kevin , Bainbridge Daryl , Rodriguez Christine
Published: December 2009

Objective: The primary objective of this study was to examine how the comprehensive nature of the Stress Process Model could elucidate on the stressors associated with caring for a palliative cancer patient.

Method: A qualitative research strategy involving home-based face-to-face interviews with 12 bereaved family caregivers was used to examine the caregiving experience.

Results: The primary stressors associated with caring for the palliative cancer care patients stemmed from care recipient symptoms and personal care needs. The absence of adequate support from the formal health care delivery system was a consistent message from all participants. There was evidence of financial stress primarily associated with the purchase of private home care to supplement formal care. In contrast, the resources that family caregivers relied on to moderate the stressful effects of caregiving included extended family, friends, and neighbors. While the stress of direct caregiving was high, the study revealed that formal care was also a significant source of stress for family caregivers.

Conclusion: It was concluded that an appropriately financed, integrated system of care that followed a person-centered philosophy of care would best meet the needs of the patient and his or her family.
Law, Language, and Land: A Multimethod Analysis of the General Allotment Act and Its Discourses
Authors: Lawrence Adrea , Cooke Brec
Published: December 2009

This study emerges from a professional development workshop the authors conducted with elementary, middle, and high school teachers. The article highlights of responses of workshop participants, particularly their response that the law was about assimilation, in the context of The General Allotment Act of 1887 and the Hopi Indian response to it. This article investigates that claim by pairing critical dialogist and poststructural analyses. Through the critical dialogist’s tools of microanalysis—meaning fields and reconstructive horizon analyses—the authors uncover possible explicit and implicit assumptions of the General Allotment Act and the Hopi response. The authors then employ a macrolevel poststructural analysis using the analytic frames of governmentality and performativity to interrogate the discursive assumptions underwriting the law and its framers’ failure to acknowledge the polyvocality of American Indian groups. By coupling the critical dialogist and poststructural analytic techniques, the authors produce a comprehensive critique that problematizes the narrative of assimilation and develops new means of historical analysis.
Assessing the Causes and Effects of Political Trust Among U.S. Latinos
Authors: Abrajano Marisa A. , Alvarez R. Michael
Published: December 2009

This article examines why Latinos are more trusting of the federal government than Anglos and Blacks. We address this puzzle by turning to previous research on racial politics and political trust. Consistent with previous research, discrimination and generational status are important predictors of Latinos’ political trust, with first-generation Latinos more trusting than later-generation Latinos. Encounters with racial discrimination also make Latinos and Blacks less trusting of government. In contrast, Anglos’ political trust can be explained by their economic evaluations as well as their partisanship. Although these findings are insightful, they do not directly address why intergroup differences arise when it comes to their trust in government. We argue that combined with generational distinctions among Latinos in their trust of government, the heavy flow of Latino immigration in the past 30 years has changed the Latino population in such a way that the views of the foreign-born are disproportionately represented in survey questions related to trust in government. This is producing a Latino population that is more inclined to trust government than Anglos or Blacks. We then examine the impact of political trust on individuals’ opinions toward redistributive policies. Political trust has a strong and positive effect on Latinos’ attitudes toward such policies.
A Matter of Distinction
Authors: Hayes Danny , Turgeon Mathieu
Published: December 2009

Because Republican and Democratic elites have polarized in recent decades, American voters increasingly face choices between candidates who hold divergent policy positions. Such a development has potential implications for the way voters process information during campaigns and choose between candidates on election day. Drawing on research in political psychology and using a nationally representative survey-experiment, we argue and find that levels of candidate polarization—the convergence or divergence of candidates’ issue positions—affect voter information consumption, recall of campaign information, and the balance of on-line and memory-based processing employed in the vote decision. In showing that voters faced with more similar candidates rely more heavily on memory-based processing, we provide further support for hybrid models of political information processing and suggest that candidate polarization has consequences for voter attitude strength and resistance to persuasion.
Games for Civic Learning: A Conceptual Framework and Agenda for Research and Design
Authors: Raphael Chad , Bachen Christine , Lynn Kathleen-M. , Baldwin-Philippi Jessica , McKee Kristen A.
Published: December 2009

Scholars, educators, and media designers are increasingly interested in whether and how digital games might contribute to civic learning. However, there are three main barriers to advancing understanding of games’ potential for civic education: the current practices of formal schooling, a dearth of evidence about what kinds of games best inspire learning about public life, and divergent paradigms of civic engagement. In response, this article develops a conceptual framework for how games might foster civic learning of many kinds. The authors hypothesize that the most effective games for civic learning will be those that best integrate game play and content, that help players make connections between their individual actions and larger social structures, and that link ethical and expedient reasoning. This framework suggests an agenda for game design and research that could illuminate whether and how games can be most fruitfully incorporated into training and education for democratic citizenship and civic leadership.
The Role of Resistance Training in the Prevention and Treatment of Chronic Disease
Authors: Ciccolo Joseph T. , Carr Lucas J. , Krupel Katie L. , Longval Jaime L.
Published: December 2009

Recent research suggests that resistance training (RT) in adults has the potential to prevent, treat, and possibly even reverse the impact of several chronic diseases. A properly designed progressive program can have profound effects on the musculoskeletal system, resulting in enhanced physical and mental health. In this review, the authors summarize recent research detailing the numerous benefits gained from participating in an RT program in those with or at risk for chronic disease. This includes increases in muscle mass and strength; enhanced physical function; reduced risks for osteoporosis and cardiovascular and metabolic diseases; improved management of cancer, neuromuscular disorders, HIV, and chronic obstructive pulmonary disease; and reductions in negative mood states. Given these benefits, numerous national organizations, including the committee commissioned to create the National Physical Activity Guidelines for Americans, have endorsed the participation in RT as a necessary component of maintaining health. Fortunately, the most current estimates show that a growing number of individuals are participating in RT, but these national estimates still fall below the goal of 30% set by Healthy People 2010. Future research will therefore need to focus on increasing the adoption and adherence of RT, as it carries the potential to dramatically affect public health.
Evidence of uneven selective pressure on different subsets of the conserved human genome; implications for the significance of intronic and intergenic DNA
Authors: Davidson Scott , Starkey Andrew , MacKenzie Alasdair
Published: December 2009

Background

Human genetic variation produces the wide range of phenotypic differences that make us individual. However, little is known about the distribution of variation in the most conserved functional regions of the human genome. We examined whether different subsets of the conserved human genome have been subjected to similar levels of selective constraint within the human population. We used set theory and high performance computing to carry out an analysis of the density of Single Nucleotide Polymorphisms (SNPs) within the evolutionary conserved human genome, at three different selective stringencies, intersected with exonic, intronic and intergenic coordinates.

Results

We demonstrate that SNP density across the genome is significantly reduced in conserved human sequences. Unexpectedly, we further demonstrate that, despite being conserved to the same degree, SNP density differs significantly between conserved subsets. Thus, both the conserved exonic and intronic genomes contain a significantly reduced density of SNPs compared to the conserved intergenic component. Furthermore the intronic and exonic subsets contain almost identical densities of SNPs indicating that they have been constrained to the same degree.

Conclusion

Our findings suggest the presence of a selective linkage between the exonic and intronic subsets and ascribes increased significance to the role of introns in human health. In addition, the identification of increased plasticity within the conserved intergenic subset suggests an important role for this subset in the adaptation and diversification of the human population.
Characterization of Intrinsic Properties of Cingulate Pyramidal Neurons in Adult Mice after Nerve Injury
Authors: Cao Xiao-Yan , Xu Hui , Wu Long-Jun , Li Xiang-Yao , Chen Tao , Zhuo Min
Published: December 2009

The anterior cingulate cortex (ACC) is important for cognitive and sensory functions including memory and chronic pain. Glutamatergic excitatory synaptic transmission undergo long-term potentiation in ACC pyramidal cells after peripheral injury. Less information is available for the possible long-term changes in neuronal action potentials or intrinsic properties. In the present study, we characterized cingulate pyramidal cells in the layer II/III of the ACC in adult mice. We then examined possible long-term changes in intrinsic properties of the ACC pyramidal cells after peripheral nerve injury. In the control mice, we found that there are three major types of pyramidal cells according to their action potential firing pattern: (i) regular spiking (RS) cells (24.7%), intrinsic bursting (IB) cells (30.9%), and intermediate (IM) cells (44.4%). In a state of neuropathic pain, the population distribution (RS: 21.3%; IB: 31.2%; IM: 47.5%) and the single action potential properties of these three groups were indistinguishable from those in control mice. However, for repetitive action potentials, IM cells from neuropathic pain animals showed higher initial firing frequency with no change for the properties of RS and IB neurons from neuropathic pain mice. The present results provide the first evidence that, in addition to synaptic potentiation reported previously, peripheral nerve injury produces long-term plastic changes in the action potentials of cingulate pyramidal neurons in a cell type-specific manner.
Plasma Membrane Expression of Gonadotropin-Releasing Hormone Receptors: Regulation by Peptide and Nonpeptide Antagonists
Authors: Finch Ann R. , Caunt Christopher J. , Armstrong Stephen P. , McArdle Craig A.
Published: December 2009

Gonadotropin-releasing hormone acts via cell surface receptors but most human (h) GnRH receptors (GnRHRs) are intracellular. A membrane-permeant nonpeptide antagonist [(2S)-2-[5-[2-(2-axabicyclo[2.2.2]oct-2-yl)-1,1-dimethy-2-oxoethyl]-2-(3,5-dimethylphenyl)-1H-indol-3-yl]-N-(2-pyridin-4-ylethyl)propan-1-amine (IN3)] increases hGnRHR expression at the surface, apparently by facilitating its exit from the endoplasmic reticulum. Here we have quantified GnRHR by automated imaging in HeLa cells transduced with adenovirus expressing hemagglutinin-tagged GnRHR. Consistent with an intracellular site of action, IN3 increases cell surface hGnRHR, and this effect is not blocked or mimicked by membrane-impermeant peptide antagonists [Ac-D2Nal-D4Cpa-D3Pal-Ser-Tyr-d-Cit-Leu-Arg-Pro-d-Ala-NH2 (cetrorelix) and antide]. However, when the C-terminal tail of a Xenopus (X) GnRHR was added (h.XGnRHR) to increase expression, both peptides further increased cell surface GnRHR. Cetrorelix also synergized with IN3 to increase expression of hGnRHR and a G-protein coupling-deficient mutant (A261K-hGnRHR). Cetrorelix also increased cell surface expression of hGnRHR, h.XGnRHR, and mouse GnRHR in gonadotrope-lineage LβT2 cells, and in HeLa cells it slowed h.XGnRHR internalization (measured by receptor-mediated antihemagglutinin uptake). Thus cetrorelix has effects other than GnRHR blockade; it acts as an inverse agonist in internalization assays, supporting the potential importance of ligand-biased efficacy at GnRHR. We also developed an imaging assay for GnRH function based on Ca2+-dependent nuclear translocation of a nuclear factor of activated T cells reporter. Using this in HeLa and LβT2 cells, IN3 and cetrorelix behaved as competitive antagonists when coincubated with GnRH, and long-term pretreatment (16 h) with IN3 reduced its effectiveness as an inhibitor whereas pretreatment with cetrorelix increased its inhibitory effect. This distinction between peptide and nonpeptide antagonists may prove important for therapeutic applications of GnRH antagonists.
Should We Trust Intellectuals?
Authors: Cohen Mitchell
Published: December 2009

This article explores the problem of the political responsibilities of intellectuals and philosophers through an appraisal of Michael Walzer's work on the idea of “connected criticism.” The author elaborates the main elements of this theory, shows how it approaches various thinkers, like Herbert Marcuse and Jean-Paul Sartre, and shows where it fits into American intellectual life, particularly the intellectual history of Dissent Magazine and the democratic Left. Walzer's idea of a connected social critic contrasts to Sartre's idea of an “engaged critic.” The article also examines Walzer's theory in light of some of the arguments made by “commonsense” moral philosophy, such as those of Irving Howe, John Rawls, Theodor Adorno, and Leo Strauss. Cohen defines Walzer's theory as part of a social democratic approach that also can serve in part as an antidote to intellectual hubris. Finally, this article presents a critique of Edward Said's understanding of intellectuals in his Representations of the Intellectual. The author argues that Said's book misrepresents Turgenev's novel Fathers and Sons. Cohen suggests that there are radical differences between Said's description of this novel's central character, Bazarov, and the world in which he lives, and those created by Turgenev. Said's approach is evaluated in relation to the notion of connected criticism and some criticisms of connected criticism are offered.