bluuebunny/crossref_metadata_2025_split huggingface dataset:
Semiparametric estimation for measurement error models with validation data
Authors: Xu Yuhang , Kim Jae Kwang , Li Yehua 
Published: March 2017

AbstractWe consider regression problems where error‐prone surrogates of true predictors are collected in a primary data set while accurate measurements of the predictors are available only in a relatively small validation data set. We propose a new class of semiparametric estimators for the regression coefficients based on expected estimating equations, where the relationship between the surrogates and the true predictors is modelled nonparametrically using a kernel smoother trained with the validation data. The new methods are developed under two different scenarios where the response variable is either observed or not observed in the validation data set. The proposed estimators have a natural connection with the fractional imputation method. They are consistent, asymptotically unbiased, and normal in both scenarios. Our simulation studies show that the proposed estimators are superior to competitors in terms of bias and mean squared error and are quite robust against the misspecification of the regression model and bandwidth selection. A real data application to the Korean Longitudinal Study of Aging is presented for illustration.The Canadian Journal of Statistics45: 185–201; 2017 © 2017 Statistical Society of Canada
Pharmacokinetic Considerations for Combining Antiretroviral Therapy, Direct‐Acting Antiviral Agents for Hepatitis C Virus, and Addiction Treatment Medications
Authors: Bednasz Cindy J. , Venuto Charles S. , Ma Qing , Morse Gene D. 
Published: March 2017

AbstractThere are many factors that can affect the pharmacokinetics (PK) of drugs. Pathophysiological changes from disease states can alter the mechanisms that control the PK of antiretrovirals (ARVs), direct‐acting antivirals (DAAs), and addiction treatment medications. Drug–drug interaction pathways of certain ARVs and DAAs can be very complex, with agents being substrates, inhibitors, or inducers of multiple metabolic and transporter pathways. Buprenorphine and methadone may be used in HIV‐ and hepatitis C virus (HCV)–infected patients and may also be affected by drug interactions. Current research is focused on novel PK analyses, which aim to describe the PK of agents within organs that host the infection of interest, such as within hepatocytes during treatment for HCV. Modeling techniques allow for the prediction of drug PK in specific organs and the plasma compartment. This review will provide a summary of these areas while exploring PK considerations for ARVs, DAAs, and addiction treatment medications.
Asunaprevir: An HCV Protease Inhibitor With Preferential Liver Distribution
Authors: Eley Timothy , Garimella Tushar , Li Wenying , Bertz Richard J. 
Published: March 2017

AbstractAsunaprevir is an inhibitor of the hepatitis C virus (HCV) NS3/4A protease, demonstrating efficacy in clinical studies in patients infected with HCV genotype 1 or 4, with either peginterferon/ribavirin or combinations of direct‐acting antivirals. Because of preferential distribution of asunaprevir to the liver via organic anion‐transporting polypeptide (OATP)–mediated transport, asunaprevir demonstrates high apparent oral clearance and very low plasma concentrations. Asunaprevir plasma concentrations are markedly increased by single‐dose rifampin (an OATP inhibitor) and in subjects with moderate to severe hepatic impairment. In addition, modestly higher plasma concentrations of asunaprevir have been noted in subjects infected with HCV relative to healthy subjects and in Asian subjects relative to whites. At the marketed dose, infrequent hepatic transaminase abnormalities were poorly predicted by plasma concentrations. For a compound with these characteristics, hepatic concentrations may have provided an improved understanding of the in vivo pharmacokinetic and pharmacodynamic data to support decision making during development.
Cure Strategies for Hepatitis B Virus: The Promise of Immunotherapy
Authors: Shire Norah J. 
Published: March 2017

AbstractChronic hepatitits B virus remains a public health challenge, infecting more than 240 million people globally and causing 600,000 deaths per year from end‐stage liver disease and/or hepatocellular carcinoma. Current antiviral therapeutic agents are highly effective at blocking viral replication, but discontinuation of therapy prior to loss of hepatitis B surface antigen generally leads to relapse. New modalities that target host factors of viral persistence such as immune response pathway inhibition hold promise. Other experimental approaches may target virally related persistence factors, including covalently closed circular DNA. All these approaches will require creative new means of assessing proof of biology and proof of mechanism, particularly in the relevant compartment of liver tissue. Furthermore, it is likely to require combinations of modalities in defined patient populations to achieve optimal response. A precompetitive consortium approach may enable companies, regulators, and academic researchers to share best practices and evaluate preclinical and clinical pathways for these novel approaches.
Assessment of Hepatic Impairment and Implications for Pharmacokinetics of Substance Use Treatment
Authors: Talal Andrew H. , Venuto Charles S. , Younis Islam 
Published: March 2017

AbstractAlthough the liver is the primary site of metabolism and biliary excretion for many medications, data are limited on the liver's pharmacokinetic abilities in cirrhosis. Cirrhosis develops through collagen deposition, eventually culminating in end‐stage liver disease that compromises hepatic drug metabolism. Consequently, the US Food and Drug Administration (FDA) recommends evaluating the pharmacokinetics of medications in subjects with hepatic impairment if hepatic metabolism constitutes more than 20% of their elimination or if they have a narrow therapeutic range. A variety of noninvasive indices and radiologic procedures can be employed to assess hepatic drug metabolism and excretion. The Child‐Pugh score is the most commonly used scale for assessing hepatic impairment among drugs submitted for US FDA approval. The score, originally developed to guide operative mortality in patients undergoing hepatic resection, has not been modified since its inception 5 decades ago. Furthermore, the score was not originally intended to be a guide for potential dose modification in patients with hepatic impairment. These reasons, in combination with the availability of a variety of new imaging modalities and an enhanced understanding of hepatic biology, should foster the development of novel methods to assess the effect of hepatic impairment on liver drug metabolism.
Bicyclo[6.3.0]undeca‐1(11),2,4,6,8‐pentaen‐10‐ylidene: An Aromatic Carbene with Ambiphilic Properties
Authors: Ishikawa Hiroyuki , Nishida Jun‐ichi , Jones John W. , Scott Lawrence T. , Kawase Takeshi 
Published: March 2017

AbstractThe title carbene (4) was generated as a highly reactive species in solution by photoirradiation of 10‐diazobicyclo[6.3.0]undecapentaene (5) using a high‐pressure mercury lamp. Carbene 4 reacts with benzene to afford two isomeric adducts, 10‐phenylbicyclo[6.3.0]undecapentaene (10) and tricyclo[9.3.03, 10.0]heptadeca‐1,3(10),4,6,8,12,14,16‐octaene (11). The reactivity toward benzene is a characteristic of an electrophilic aromatic carbene analogous to cyclopentadienylidene 1. In contrast, the reaction of 4 with methanol produces 7‐methoxybicyclo[6.3.0]undeca‐1,3,5,8,10‐pentaene (15). When [D1]methanol was employed as a reactant, the 10‐deuterated analogue was formed. The results clearly indicate the formation of bicyclo[6.3.0]undecapentaenyl cation (7) as a novel 10 π‐electronic compound by protonation of 4. Theoretical calculations indicate that the 2‐ and 7‐positions of the cation have the largest positive charge in the cation. Moreover, the carbene was generated in the presence of tert‐butyl hydroperoxide in aqueous tetrahydrofuran to afford azulene through oxidation of 7, followed by decarbonylation. The nucleophilic property of carbene 3 is similar to that of cycloheptatrienylidene 2. Thus, 4 can be regarded as a novel ambiphilic aromatic carbene.
Systematic Investigation of Resorcin[4]arene‐Based Cavitands as Affinity Materials on Quartz Crystal Microbalances
Authors: Ryvlin Dimitrij , Dumele Oliver , Linke Alexander , Fankhauser Daniel , Schweizer W. Bernd , Diederich François , Waldvogel Siegfried R. 
Published: March 2017

AbstractResorcin[4]arene cavitands are well‐known supramolecular hosts, and their outstanding guest‐binding abilities in solution have been studied in detail in recent decades. In a systematic approach, different resorcin[4]arene cavitands and container molecules are characterized as affinity materials for gravimetric sensing using high‐fundamental‐frequency quartz crystal microbalances. Analysis of their affinity toward a series of various analytes reveals a remarkable dependence of both selectivity and sensitivity on the shape, accessibility, and size of the cavity, along with their supramolecular interactions with the host molecules.
What Drives Successful Implementation of Product Stewardship Strategy? The Role of Absorptive Capability
Authors: Bhupendra Kumar Verma , Sangle Shirish 
Published: March 2017

AbstractImplementation of Product Stewardship Strategy (PSS) requires integration of ‘voices of stakeholders’ in business decisions to create ‘differentiation’ in the market place. Considering that absorptive capability (AC) is a critical aspect of organizational learning, it may deliver dynamic integration of stakeholder's expectations and know‐how in decision making. This paper attempts to link the attributes of AC with the features of PSS and presents outcomes of an empirical study of sixty Indian firms from several industry sectors. The result shows that firms demonstrating the traits of AC are in better position to implement PSS. This study also expands the scope of AC by including the additional source of knowledge as societal‐stakeholders to provide a comprehensive view that this type of knowledge is complimentary to technological and market knowledge for sustainable commercial success. Based on the research findings, the paper proposes some important managerial implications and suggests direction for future research. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Corporate Social Responsibility Reporting and Varieties of Capitalism: an International Analysis of State‐Led and Liberal Market Economies
Authors: Gallego‐Álvarez Isabel , Quina‐Custodio Ivo Alexandre 
Published: March 2017

AbstractDifferent studies carried out to date in the corporate social responsibility (CSR) field have focused on analysing certain explanatory factors of CSR reporting in different countries or individual factors, such as firm size, activity sector, good corporate governance, economic and financial profitability, and the cost of equity capital, among others. In contrast, other aspects of national cultures and institutions that make up the macroeconomic, legal, and political context of a country have been addressed to a lesser extent. This paper analyses how aspects of national institutions affect CSR reporting on an international level using the varieties of the capitalism approach. This approach is concerned with companies and the ways in which they interact strategically to solve the coordination problems that arise from their activities. The study uses data from the Thomson Reuters Eikon database and the Global Reporting Initiative (G3.1) for a sample of firms from countries classified as state‐led market economies (France, Portugal, and Spain) and countries considered liberal market economies (the USA and the UK). The results obtained by linear regression show those companies in state‐led market economies disclose more concerning CSR than companies in liberal market economies. Moreover, firms in state‐led market economies disclose more on stakeholder aspects such as social, environmental and business behaviour than companies in liberal market economies. This may be due to coercive pressure, that is, the existence of a significant and well‐developed legal system that seeks to protect stakeholders and is not exclusively oriented towards shareholder interests. Copyright © 2017 John Wiley & Sons, Ltd and ERP Environment
Effects of ultrasound irradiation on enzymatic hydrolysis of protein and application for the determination of tetracyclines in complex matrices
Authors: Zhou Qian , Wang Hong , Zhu Kuanzheng , Zhu Lihua , Zhou Shengyin , Peng Jin , Lu Xiya 
Published: March 2017

The widespread use of tetracyclines (TCs) in food animals has led to concerns regarding unsafe residue levels in feed, food and manure. The determination of TCs in such matrices suffers from interference by the interactions between proteins and TCs. Three deproteination methods were compared in this study. In contrast with acid deproteination, which caused a large loss of TCs due to the strong adsorption of TCs on protein precipitates, a normal enzymatic hydrolysis was confirmed to have a merit of effectively releasing TCs from protein matrices, but required treatment time as long as 16 h. The adoption of ultrasound irradiation was proposed to shorten the enzymatic hydrolysis time. After investigating the effects of ultrasound power and irradiation time, the conditions of the ultrasound‐enhanced enzymatic hydrolysis were optimized as ultrasound power of 100 W and irradiation time of 6 min. The ultrasound‐enhanced enzymatic hydrolysis treatment of 6 min yielded recovery of TCs (from protein‐containing matrices) as high as that obtained by the normal enzymatic hydrolysis treatment of 16 h. The acceleration effect of ultrasound irradiation was attributed to ultrasound‐induced cavitation, which increased exposure of both the functional groups of trypsin and the C‐terminal amino acid in the protein that was a cleavage site for trypsin attack. When the ultrasound‐enhanced enzymatic hydrolysis method was used to determine TCs in complex matrices, it was found that this new method achieved recoveries of 89.5, 117.7, 110.4 and 100.0% for oxytetracycline, tetracycline, chlortetracycline and doxycycline, being much higher than those (29.6–39.4%) obtained using the common acid deproteination process. Copyright © 2017 John Wiley & Sons, Ltd.
Modelling moose–forest interactions under different predation scenarios at Isle Royale National Park, USA
Authors: De Jager Nathan R. , Rohweder Jason J. , Miranda Brian R. , Sturtevant Brian R. , Fox Timothy J. , Romanski Mark C. 
Published: March 2017

AbstractLoss of top predators may contribute to high ungulate population densities and chronic over‐browsing of forest ecosystems. However, spatial and temporal variability in the strength of interactions between predators and ungulates occurs over scales that are much shorter than the scales over which forest communities change, making it difficult to characterize trophic cascades in forest ecosystems. We applied the LANDIS‐II forest succession model and a recently developed ungulate browsing extension to model how the moose population could interact with the forest ecosystem of Isle Royale National Park, USA, under three different wolf predation scenarios. We contrasted a 100‐yr future without wolves (no predation) with two predation scenarios (weak, long‐term average predation rates and strong, higher than average rates). Increasing predation rates led to lower peak moose population densities, lower biomass removal rates, and higher estimates of forage availability and landscape carrying capacity, especially during the first 40 yr of simulations. Thereafter, moose population density was similar for all predation scenarios, but available forage biomass and the carrying capacity of the landscape continued to diverge among predation scenarios. Changes in total aboveground live biomass and species composition were most pronounced in the no predation and weak predation scenarios. Consistent with smaller‐scale studies, high browsing rates led to reductions in the biomass of heavily browsed Populus tremuloides, Betula papyrifera, and Abies balsamea, and increases in the biomass of unbrowsed Picea glauca and Picea mariana, especially after the simulation year 2050, when existing boreal hardwood stands at Isle Royale are projected to senesce. As a consequence, lower predation rates corresponded with a landscape that progressively shifted toward dominance by Picea glauca and Picea mariana, and lacking available forage biomass. Consistencies with previously documented small‐scale successional shifts, and population estimates and trends that approximate those from this and other boreal forests that support moose provide some confidence that these dynamics represent a trophic cascade and therefore provide an important baseline against which to evaluate long‐term and large‐scale effects of alternative predator management strategies on ungulate populations and forest succession.
Full annual cycle climate change vulnerability assessment for migratory birds
Authors: Culp Leah A. , Cohen Emily B. , Scarpignato Amy L. , Thogmartin Wayne E. , Marra Peter P. 
Published: March 2017

AbstractClimate change is a serious challenge faced by all plant and animal species. Climate change vulnerability assessments (CCVAs) are one method to assess risk and are increasingly used as a tool to inform management plans. Migratory animals move across regions and continents during their annual cycles where they are exposed to diverse climatic conditions. Climate change during any period and in any region of the annual cycle could influence survival, reproduction, or the cues used to optimize timing of migration. Therefore, CCVAs for migratory animals best estimate risk when they include climate exposure during the entire annual cycle. We developed a CCVA incorporating the full annual cycle and applied this method to 46 species of migratory birds breeding in the Upper Midwest and Great Lakes (UMGL) region of the United States. Our methodology included background risk, climate change exposure × climate sensitivity, adaptive capacity to climate change, and indirect effects of climate change. We compiled information about migratory connectivity between breeding and stationary non‐breeding areas using literature searches and U.S. Geological Survey banding and re‐encounter data. Climate change exposure (temperature and moisture) was assessed using UMGL breeding season climate and winter climate from non‐breeding regions for each species. Where possible, we focused on non‐breeding regions known to be linked through migratory connectivity. We ranked 10 species as highly vulnerable to climate change and two as having low vulnerability. The remaining 34 species were ranked as moderately vulnerable. In general, including non‐breeding data provided more robust results that were highly individualistic by species. Two species were found to be highly vulnerable throughout their annual cycle. Projected drying will have the greatest effect during the non‐breeding season for species overwintering in Mexico and the Caribbean. Projected temperature increases will have the greatest effect during the breeding season in UMGL as well as during the non‐breeding season for species overwintering in South America. We provide a model for adaptive management of migratory animals in the face of projected climate change, including identification of priority species, research needs, and regions within non‐breeding ranges for potential conservation partnerships.
Evaluating the effects of herbicide drift on nontarget terrestrial plants: A case study with mesotrione
Authors: Brain Richard A. , Perine Jeff , Cooke Catriona , Ellis Clare Butler , Harrington Paul , Lane Andrew , O'Sullivan Christine , Ledson Mark 
Published: March 2017

Abstract

Nature of exposure is a fundamental driver in nontarget terrestrial plant risk assessment for pesticides; consequently a novel study was designed to generate field-based drift exposure and evaluate corresponding biological effects of the herbicide mesotrione. The approach used a combination of US guideline drift reduction technology and vegetative vigor approaches. In each of 3 independent replicate spray application trials, 10 pots each of lettuce and tomato were placed at distances of 10, 20, 30, 40, and 50 ft (∼3, 6, 9, 12, and 15 m) from the downwind edge of the spray boom. Each application was conducted using a commercial 60-ft (18-m) boom sprayer fitted with TeeJet® Technologies TTI110025 nozzles, with a nominal application rate of 0.2 lb a.i./A (224 g a.i./ha). The environmental conditions required by the protocol (air temperature 10–30 °C and wind perpendicular to the swath (±30°) blowing toward the plants at a mean wind speed of ≥10 mph [≥4.5 m/s] measured at 2.0 m above the ground) were met for each application. Following exposure, plants were transferred to a greenhouse for the 21-d vegetative vigor phase of the study. Symptoms of phytotoxicity and plant height were assessed at 7, 14, and 21 d after treatment. On completion of the 21-d after treatment assessment, all plants were harvested and dried in an oven to determine shoot dry weight. The biological data indicated that no statistically significant effects were observed at a distance of 30 ft (∼9 m) from mesotrione drift at wind speeds of ≥10 mph (10.9–12.4 mph); this endpoint (30 ft) is defined as the no observed effects distance (NOED). Environ Toxicol Chem 2017;36:2465–2475. © 2017 SETAC
Reirradiation of head and neck cancer: Long‐term disease control and toxicity
Authors: Bots Wouter T. C. , van den Bosch Sven , Zwijnenburg Ellen M. , Dijkema Tim , van den Broek Guido B. , Weijs Willem L. J. , Verhoef Lia C. G. , Kaanders Johannes H. A. M. 
Published: March 2017

ABSTRACTBackgroundThe purpose of this study was to report long‐term disease control and late radiation toxicity for patients reirradiated for head and neck cancer.MethodsWe conducted a retrospective analysis of 137 patients reirradiated with a prescribed dose ≥45 Gy between 1986 and 2013 for a recurrent or second primary malignancy. Endpoints were locoregional control, overall survival (OS), and grade ≥4 late complications according to European Organization for Research and Treatment of Cancer (EORTC)/Radiation Therapy Oncology Group (RTOG) criteria.ResultsFive‐year locoregional control rates were 46% for patients reirradiated postoperatively versus 20% for patients who underwent reirradiation as the primary treatment (p < .05). Sixteen cases of serious (grade ≥4) late toxicity were seen in 11 patients (actuarial 28% at 5 years). In patients reirradiated with intensity‐modulated radiotherapy (IMRT), a borderline improved locoregional control was observed (49% vs 36%; p = .07), whereas late complication rates did not differ.ConclusionReirradiation should be considered for patients with a recurrent or second primary head and neck cancer, especially postoperatively, if indicated. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1122–1130, 2017