bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeting CEA in Pancreas Cancer Xenografts with a Mutated scFv-Fc Antibody Fragment
Authors: Girgis Mark D , Olafsen Tove , Kenanova Vania , McCabe Katelyn E , Wu Anna M , Tomlinson James S 
Published: November 2011

AbstractBackgroundSensitive antibody-based tumor targeting has the potential not only to image metastatic and micrometastatic disease, but also to be the basis of targeted therapy. The vast majority of pancreas cancers express carcinoembryonic antigen (CEA). Thus, we sought to evaluate the potential of CEA as a pancreatic cancer target utilizing a rapidly clearing engineered anti-CEA scFv-Fc antibody fragment with a mutation in the Fc region [anti-CEA scFv-Fc H310A].MethodsImmunohistochemistry (IHC) with the antibody fragment was used to confirm expression of CEA on human pancreas cancer specimens.In vivotumor targeting was evaluated by tail vein injection of I124-labeled anti-CEA scFv-Fc(H310A) into mice harboring CEA-positive and -negative xenografts. MicroPET/CT imaging was performed at successive time intervals. Radioactivity in blood and tumor was measured after the last time point. Additionally, unlabeled anti-CEA scFv-Fc(H310A) was injected into CEA-positive tumor bearing mice andex vivoIHC was performed to identify the presence of the antibody to define the microscopic intratumoral pattern of targeting.ResultsModerate to strong staining by IHC was noted on 84% of our human pancreatic cancer specimens and was comparable to staining of our xenografts. Pancreas xenograft imaging with the radiolabeled anti-CEA scFv-Fc(H310A) antibody demonstrated average tumor/blood ratios of 4.0. Immunolocalization demonstrated peripheral antibody fragment penetration of one to five cell diameters (0.75 to 1.5 μm).ConclusionsWe characterized a preclinical xenograft model with respect to CEA expression that was comparable to human cases. We demonstrated that the anti-CEA scFv-Fc(H310A) antibody exhibited antigen-specific tumor targeting and shows promise as an imaging and potentially therapeutic agent.
Phase II Study of the Mammalian Target of Rapamycin Inhibitor Ridaforolimus in Patients With Advanced Bone and Soft Tissue Sarcomas
Authors: Chawla Sant P. , Staddon Arthur P. , Baker Laurence H. , Schuetze Scott M. , Tolcher Anthony W. , D'Amato Gina Z. , Blay Jean-Yves , Mita Monica M. , Sankhala Kamalesh K. , Berk Lori , Rivera Victor M. , Clackson Tim , Loewy John W. , Haluska Frank G. , Demetri George D. 
Published: November 2011

PurposeRidaforolimus is an inhibitor of mammalian target of rapamycin, an integral component of the phosphatidyl 3-kinase/AKT signaling pathway, with early evidence of activity in sarcomas. This multicenter, open-label, single-arm, phase II trial was conducted to assess the antitumor activity of ridaforolimus in patients with distinct subtypes of advanced sarcomas.Patients and MethodsPatients with metastatic or unresectable soft tissue or bone sarcomas received ridaforolimus 12.5 mg administered as a 30-minute intravenous infusion once daily for 5 days every 2 weeks. The primary end point was clinical benefit response (CBR) rate (complete response or partial response [PR] or stable disease ≥ 16 weeks). Safety, progression-free survival (PFS), overall survival (OS), time to progression, and duration of response were also evaluated.ResultsA total of 212 patients were treated in four separate histologic cohorts. In this heavily pretreated population, 61 patients (28.8%) achieved CBR. Median PFS was 15.3 weeks; median OS was 40 weeks. Response Evaluation Criteria in Solid Tumors (RECIST) confirmed response rate was 1.9%, with four patients achieving confirmed PR (two with osteosarcoma, one with spindle cell sarcoma, and one with malignant fibrous histiocytoma). Archival tumor protein markers analyzed were not correlated with CBR. Related adverse events were generally mild or moderate and consisted primarily of stomatitis, mucosal inflammation, mouth ulceration, rash, and fatigue.ConclusionSingle-agent ridaforolimus in patients with advanced and pretreated sarcomas led to PFS results that compare favorably with historical metrics. A phase III trial based on these data will further define ridaforolimus activity in sarcomas.
Midregional Proadrenomedullin for Prediction of Cardiovascular Events in Coronary Artery Disease: Results from the AtheroGene Study
Authors: Wild Philipp S , Schnabel Renate B , Lubos Edith , Zeller Tanja , Sinning Christoph R , Keller Till , Tzikas Stergios , Lackner Karl J , Peetz Dirk , Rupprecht Hans J , Bickel Christoph , Morgenthaler Nils G , Papassotiriou Jana , Tiret Laurence , Münzel Thomas , Blankenberg Stefan 
Published: November 2011

Abstract

BACKGROUND
Midregional proadrenomedullin (MR-proADM) is a newly identified prognostic marker in heart failure. We evaluated the prognostic impact of MR-proADM in a cohort of patients with symptomatic coronary artery disease according to their clinical presentation.

METHODS
We measured baseline MR-proADM concentrations in 2240 individuals from the prospective AtheroGene study and evaluated the prognostic impact on future fatal and nonfatal cardiovascular events during a follow-up period of 3.6 (1.6) years.

RESULTS
The sample comprised 1355 individuals with stable angina pectoris (SAP) and 885 with acute coronary syndrome (ACS). A cardiovascular event occurred in 192 people. Individuals presenting with SAP had only slightly lower plasma MR-proADM concentrations than those with ACS (0.53 vs 0.55 nmol/L, P = 0.006). MR-proADM showed a moderate association with age, serum N-terminal pro–B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, serum C-reactive protein, hypertension, diabetes, and prevalent multivessel disease (all P &lt; 0.0005). Individuals suffering from a cardiovascular event had higher MR-proADM concentrations at baseline in both groups (SAP 0.63 vs 0.53 nmol/L and ACS 0.65 nmol/L vs 0.55 nmol/L, both P &lt; 0.0005). Cox regression analysis incorporating various variables of cardiovascular risk and NT-proBNP revealed a hazard ratio of 1.4 (95% CI 1.2–1.6; P &lt; 0.0005) per increment of MR-proADM by 1SD. In risk models for secondary prevention, MR-proADM provided information comparable to that of NT-proBNP.

CONCLUSIONS
MR-proADM is an independent predictor for future cardiovascular events in patients with symptomatic coronary artery disease, providing information comparable to NT-proBNP for secondary risk stratification.
Rosuvastatin, Proprotein Convertase Subtilisin/Kexin Type 9 Concentrations, and LDL Cholesterol Response: the JUPITER Trial
Authors: Awan Zuhier , Seidah Nabil G , MacFadyen Jean G , Benjannet Suzanne , Chasman Daniel I , Ridker Paul M , Genest Jacques 
Published: November 2011

Abstract

BACKGROUND
Although statin therapy is known to increase concentrations of PCSK9, whether this effect is related to the magnitude of LDL reduction is uncertain. This study was undertaken to understand the extent of this effect and examine the relationship between PCSK9 and LDL cholesterol (LDL-C) reduction.

METHODS
We measured plasma PCSK9 concentrations by ELISA at baseline and at 1 year in 500 men and 500 women participating in the Justification for Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial that randomly allocated participants to rosuvastatin 20 mg daily or placebo. We also evaluated rs11591147, a single nucleotide polymorphism known to have an impact on plasma PCSK9 concentrations.

RESULTS
At baseline, median (interquartile range) PCSK9 concentrations were higher in women [73 (62–90)] ng/mL than in men [69 (57–81) ng/mL] (P &lt; 0.005). During 1 year, there was no change in PCSK9 concentrations in the placebo arm, suggesting stability in time. In contrast, the rosuvastatin increased PCSK9 by 35% in women [101 (82–117) ng/mL] and 28% in men [89 (71–109) ng/mL] (P &lt; 0.0001). Among those allocated to rosuvastatin, greater reductions in LDL-C were associated with greater increases in PCSK9 on both absolute and relative scales (r = −0.15, P &lt; 0.0005). Furthermore PCSK9 (rs11591147) did not alter the magnitude of LDL-C reduction associated with rosuvastatin use.

CONCLUSIONS
In this randomized trial, rosuvastatin increased plasma concentration of PCSK9 in proportion to the magnitude of LDL-C reduction; the LDL-C response to statin could not be inferred by PCSK9 concentrations.
Entwicklung eines Bewertungssystems für Virtual Reality-Simulatoren in der Chirurgie
Authors: Boll Marie-Theres , Maaß Heiko , Cakmak Hüseyin Kemal , Kühnapfel Uwe , Bretthauer Georg 
Published: November 2011

Zusammenfassung
Chirurgische Fertigkeiten im Bereich der minimal invasiven Chirurgie können an Virtual Reality-Simulatoren geübt werden. Für ein zielgerichtetes Training ist die Bewertung der Übungsausführung wichtig. Deshalb werden neue Methoden zur Entwicklung eines Bewertungssystems für die automatisierte Beurteilung von Trainierenden eingeführt. Zwei Studien haben die Eignung des neuen Konzeptes gezeigt.
Undernutrition, Poor Feeding Practices, and Low Coverage of Key Nutrition Interventions
Authors: Lutter Chessa K. , Daelmans Bernadette M. E. G. , de Onis Mercedes , Kothari Monica T. , Ruel Marie T. , Arimond Mary , Deitchler Megan , Dewey Kathryn G. , Blössner Monika , Borghi Elaine 
Published: November 2011

OBJECTIVE:
To estimate the global burden of malnutrition and highlight data on child feeding practices and coverage of key nutrition interventions.

METHODS:
Linear mixed-effects modeling was used to estimate prevalence rates and numbers of underweight and stunted children according to United Nations region from 1990 to 2010 by using surveys from 147 countries. Indicators of infant and young child feeding practices and intervention coverage were calculated from Demographic and Health Survey data from 46 developing countries between 2002 and 2008.

RESULTS:
In 2010, globally, an estimated 27% (171 million) of children younger than 5 years were stunted and 16% (104 million) were underweight. Africa and Asia have more severe burdens of undernutrition, but the problem persists in some Latin American countries. Few children in the developing world benefit from optimal breastfeeding and complementary feeding practices. Fewer than half of infants were put to the breast within 1 hour of birth, and 36% of infants younger than 6 months were exclusively breastfed. Fewer than one-third of 6- to 23-month-old children met the minimum criteria for dietary diversity, and only ∼50% received the minimum number of meals. Although effective health-sector–based interventions for tackling childhood undernutrition are known, intervention-coverage data are available for only a small proportion of them and reveal mostly low coverage.

CONCLUSIONS:
Undernutrition continues to be high and progress toward reaching Millennium Development Goal 1 has been slow. Previously unrecognized extremely poor breastfeeding and complementary feeding practices and lack of comprehensive data on intervention coverage require urgent action to improve child nutrition.
A Primer on the Economics of Prescription Pharmaceutical Pricing in Health Insurance Markets
Authors: Berndt Ernst R. , McGuire Thomas , Newhouse Joseph P. 
Published: November 2011

Abstract
The pricing of medical products and services in the U.S. is notoriously complex. In health care, supply prices (those received by the manufacturer) are distinct from demand prices (those paid by the patient) due to health insurance. The insurer, in designing the benefit, decides what prices patients pay out-of-pocket for drugs and other products. In this primer we characterize cost and supply conditions in markets for generic and branded drugs, and apply basic tools of microeconomics to describe how an insurer, acting on behalf of its enrollees, would set demand prices for drugs. Importantly, we show how the market structure on the supply side, characterized alternatively by monopoly (unique brands), Bertrand differentiated product markets (therapeutic competition) and competition (generics), influences the insurer’s choices about demand prices. This perspective sheds light on the choice of coinsurance versus copayments, the structure of tiered formularies, and developments in the retail market.
Selection Models in Accounting Research
Authors: Lennox Clive S. , Francis Jere R. , Wang Zitian 
Published: November 2011

ABSTRACT
This study explains the challenges associated with the Heckman (1979) procedure to control for selection bias, assesses the quality of its application in accounting research, and offers guidance for better implementation of selection models. A survey of 75 recent accounting articles in leading journals reveals that many researchers implement the technique in a mechanical way with relatively little appreciation of important econometric issues and problems surrounding its use. Using empirical examples motivated by prior research, we illustrate that selection models are fragile and can yield quite literally any possible outcome in response to fairly minor changes in model specification. We conclude with guidance on how researchers can better implement selection models that will provide more convincing evidence on potential selection bias, including the need to justify model specifications and careful sensitivity analyses with respect to robustness and multicollinearity.
Data Availability: Data used are available from public sources identified in the study.
Customer-Base Concentration: Implications for Firm Performance and Capital Markets
Authors: Patatoukas Panos N. 
Published: November 2011

ABSTRACT
This study investigates whether and how customer-base concentration affects supplier firm fundamentals and stock market valuation. I compile a comprehensive sample of supply chain relationships and develop a measure (CC) to capture the extent to which a supplier's customer base is concentrated. In contrast to the conventional view of customer-base concentration as an impediment to supplier firm performance, I document a positive contemporaneous association between CC and accounting rates of return, suggesting that efficiencies accrue to suppliers with concentrated customer bases. Consistent with a cause-and-effect link between customer-base concentration and supplier firm performance, analysis of intertemporal changes demonstrates that CC increases predict efficiency gains in the form of reduced operating expenses per dollar of sales and enhanced asset utilization. Using stock returns tests, I find that investors underreact to the implications of changes in customer-base concentration for future firm fundamentals when setting stock prices. A trading strategy that exploits investors' underreaction yields abnormal stock returns over the 30-year period studied.
JEL Classifications: M41; L25; G14.
Data Availability: Data are available from the sources indicated in the text.
Falls, Older Adults, and the Impact of the Neighborhood Environment
Authors: Chippendale Tracy , Bear-Lehman Jane 
Published: November 2011

Abstract
Almost half of falls occur outdoors; yet, the emphasis in fall prevention has been on intrinsic factors and the indoor environment. In this article we argue that the neighborhood environment and its impact on falls warrants further attention. Occupational therapy is best suited to address these issues in collaboration with urban planners and public health professionals. Both practice and policy changes are suggested to meet the health and wellness needs of community-dwelling older adults going forward.
Manualization of Occupational Therapy Interventions: Illustrations From the Pressure Ulcer Prevention Research Program
Authors: Blanche Erna Imperatore , Fogelberg Donald , Diaz Jesus , Carlson Mike , Clark Florence 
Published: November 2011

Abstract
The manualization of a complex occupational therapy intervention is a crucial step in ensuring treatment fidelity for both clinical application and research purposes. Toward the latter end, intervention manuals are essential for ensuring trustworthiness and replicability of randomized controlled trials that aim to provide evidence of the effectiveness of occupational therapy. In this article, we review the literature on the process of intervention manualization. We then illustrate the prescribed steps through our experience in implementing the University of Southern California/Rancho Los Amigos National Rehabilitation Center’s collaborative Pressure Ulcer Prevention Project. In this research program, qualitative research provided the initial foundation for manualization of a multifaceted occupational therapy intervention designed to reduce the incidence of medically serious pressure ulcers in adults with spinal cord injury.
Returning Genius to the Place
Authors: Lazarus Mary Ann , Crawford Chip 
Published: November 2011

AbstractAdvocates of sustainable design since the early 1990s, HOK are intent on disseminating new research, resources and tools across their global design teams. Mary Ann Lazarus, Sustainable Design Director at HOK, and Chip Crawford, Planning Group Director at HOK, describe a particularly innovative project that the two groups have collaborated on with the essential input of the Biomimicry Guild (see p 44). Addressing critical environmental issues at the habitat scale and performance standards, they have developed ecological design tools that have been employed on masterplans for Lavasa, India, and Langfang, China. Copyright © 2011 John Wiley & Sons, Ltd.
Recyclicity: A Toolbox for Resource‐Based Design
Authors: Jongert Jan , Nelson Nels , Goosens Fabienne 
Published: November 2011

AbstractArchitect Jan Jongert, urban ecologist Nels Nelson and chemical engineer Fabienne Goosens of 2012Architecten are all part of a shifting cast of specialists, undertaking research and design in this Rotterdam‐based practice. Here they describe how a focus on recycling has led them to develop research tools, such as harvest maps, urban metabolism studies, material flow analyses and Sankey diagrams. These provide essential information for designers. Harvest maps, for instance, enable them to locate locally available recyclable materials and resources. Copyright © 2011 John Wiley & Sons, Ltd.
Adaptive Strategies for an Ecological Architecture
Authors: Yannas Simos 
Published: November 2011

AbstractSimos Yannas, Director of the Environment & Energy Studies Programme at the Architectural Association (AA) School of Architecture in London, calls for a rethink of architectural processes. Presently, architecture is conceived as an inanimate material system, but to become truly bioclimatic it needs to become adaptive in tune with the behaviour and the comfort of occupiers. Shifting from an emphasis on providing fixed interior conditions, it requires a dynamic approach to building performance and the resultant interactions between occupants, buildings and engineering appliances. Copyright © 2011 John Wiley & Sons, Ltd.
Sub‐Picosecond Processes of Ferroelectric Domain Switching from Field and Temperature Experiments
Authors: Jiang An Quan , Lee Hyun Ju , Hwang Cheol Seong , Scott James F. 
Published: November 2011

AbstractAfter calculations of various domain‐switching current transients under the pulse from electrical circuit parameters, the field dependence of domain‐switching speeds is accurately estimated over five orders of magnitude in a wide temperature range of 5.4–280 K from the height of domain‐switching current in Pb(Zr0.4Ti0.6)O3 thin films. These estimations are extended following Merz's equation [W. J. Merz, Phys. Rev. 1954, 95, 690] and an ultimate domain‐switching current density of 1.4 × 108 A cm−1 is extracted at the highest field of 0.20 MV cm−1. From classical domain‐nucleation models with thermal fluctuations, an ultimate (asymptotic high‐field) nucleation time of 0.47 ps is derived when the domain sideways motion is kink‐nucleation‐rate limited.
Optical Gating of Photosensitive Synthetic Ion Channels
Authors: Ali Mubarak , Nasir Saima , Ramirez Patricio , Ahmed Ishtiaq , Nguyen Quoc Hung , Fruk Ljiljana , Mafe Salvador , Ensinger Wolfgang 
Published: November 2011

Abstract4‐oxo‐4‐(pyren‐4‐ylmethoxy) butanoic acid is used as a photolabile protecting group to show the optical gating of nanofluidic devices based on synthetic ion channels. The inner surface of the channels is decorated with monolayers of photolabile hydrophobic molecules that can be removed by irradiation, which leads to the generation of hydrophilic groups. This process can be exploited in the UV‐light‐triggered permselective transport of ionic species in aqueous solution through the channels. The optical gating of a single conical nanochannel and multichannel polymeric membranes is characterised experimentally and theoretically by means of current–voltage and selective permeation measurements, respectively. It is anticipated that the integration of nanostructures into multifunctional devices is feasible and can readily find applications in light‐induced controlled release, sensing, and information processing.
Opioid use and dosing in the workers' compensation setting. A comparative review and new data from Ohio
Authors: Dembe Allard , Wickizer Thomas , Sieck Cynthia , Partridge Jamie , Balchick Robert 
Published: November 2011

AbstractBackgroundMany authorities are concerned about the rising use and the potential overuse of opioid pain medications. A study of opioid prevalence and dosage in Ohio's workers' compensation (WC) system was conducted, with comparisons made to opioid use in other WC and non‐WC settings.MethodsSystematic literature reviews of WC and non‐WC opioid use and dosage nationally were conducted. Two years of Ohio WC data (2008–2009) were analyzed to determine average daily morphine equivalent dose (MED), opioid costs, pharmacies used per claimant, and extent of long‐duration cases.ResultsNearly one‐fifth (19.2%) of Ohio WC claims involved opioid use, compared to 31.8% in other WC systems and 17.9% in non‐WC settings. Mean MED was 57.5 mg, compared to 47.8 mg in other WC systems, and 41.8 mg among non‐WC populations. Nearly 10% of WC claims involved relatively high MED exceeding 120 mg/day.ConclusionPolicy makers need to develop strategies for addressing high opioid use in WC systems. Am. J. Ind. Med. 55:313–324, 2012. © 2011 Wiley Periodicals, Inc.
Increased rates of asthma among World Trade Center disaster responders
Authors: Kim Hyun , Herbert Robin , Landrigan Philip , Markowitz Steven B. , Moline Jacqueline M. , Savitz David A. , Todd Andrew C. , Udasin Iris G. , Wisnivesky Juan P. 
Published: November 2011

AbstractBackgroundStudies have documented high rates of asthma symptoms among responders to the World Trade Center (WTC) disaster. However, whether there are increased rates of asthma among responders compared to the general population is unknown.MethodsThe study population consisted of a prospective cohort of 20,834 responders participating in the WTC Medical Monitoring and Treatment Program between July 2002 and December 2007. We calculated prevalence and standardized morbidity ratios (SMRs) of lifetime asthma and 12‐month asthma (defined as ≥1 attacks in the prior 12 months) among WTC responders. The comparison population consisted of >200,000 adults who completed the National Health Interview Survey in 2000 (for pre‐9/11 comparisons) and between 2002 and 2007 (for post‐9/11 comparisons).ResultsWTC responders were on average 43 ± 9 years old, 86% male, 59% white, and 42% had an occupation in protective services. The lifetime prevalence of asthma in the general population was relatively constant at about 10% from 2000 to 2007. However, among WTC responders, lifetime prevalence increased from 3% in 2000, to 13% in 2002, and 19% in 2007. The age‐adjusted overall SMR for lifetime asthma among WTC responders was 1.8 (95% CI: 1.8–1.9) for men and 2.0 (95% CI: 1.9–2.1) for women. Twelve‐month asthma was also more frequent among WTC responders compared to the general population (SMR 2.4, 95% CI: 2.2–2.5) for men and 2.2 (95% CI: 2.0–2.5) for women.ConclusionsWTC responders are at an increased risk of asthma as measured by lifetime prevalence or active disease. Am. J. Ind. Med. 55:44–53, 2012. © 2011 Wiley Periodicals, Inc.