bluuebunny/crossref_metadata_2025_split huggingface dataset:
Observations on Three Endpoint Properties and Their Relationship to Regulatory Outcomes of European Oncology Marketing Applications
Authors: Liberti Lawrence , Stolk Pieter , McAuslane James Neil , Schellens Jan , Breckenridge Alasdair M. , Leufkens Hubert 
Published: May 2015

Abstract

Background.
Guidance and exploratory evidence indicate that the type of endpoints and the magnitude of their outcome can define a therapy's clinical activity; however, little empirical evidence relates specific endpoint properties with regulatory outcomes.

Materials and Methods.
We explored the relationship of 3 endpoint properties to regulatory outcomes by assessing 50 oncology marketing authorization applications (MAAs; reviewed from 2009 to 2013).

Results.
Overall, 16 (32%) had a negative outcome. The most commonly used hard endpoints were overall survival (OS) and the duration of response or stable disease. OS was a component of 91% approved and 63% failed MAAs. The most commonly used surrogate endpoints were progression-free survival (PFS), response rate, and health-related quality of life assessments. There was no difference (p = .3801) between the approved and failed MAA cohorts in the proportion of hard endpoints used. A mean of slightly more than four surrogate endpoints were used per approved MAA compared with slightly more than two for failed MAAs. Longer OS and PFS duration outcomes were generally associated with approvals, often when not statistically significant. The approved cohort was associated with a preponderance of statistically significant (p &lt; .05) improvements in primary endpoints (p &lt; .0001 difference between the approved and failed groups).

Conclusion.
Three key endpoint properties (type of endpoint [hard/surrogate], magnitude of an endpoint outcome, and its statistical significance) are consistent with the European Medicines Agency guidance and, notwithstanding the contribution of unique disease-specific circumstances, are associated with a predictable positive outcome for oncology MAAs.

Implications for Practice:
Regulatory decisions made by the European Medicines Agency determine which new medicines will be available to European prescribers and for which therapeutic indications. Regulatory success or failure can be influenced by many factors. This study assessed three key properties of endpoints used in preauthorization trials (type of endpoint [hard/surrogate], magnitude of endpoint outcome, and its statistical significance) and whether they are associated with a positive regulatory outcome. Clinicians can use these properties, which are described in the publicly available European public assessment reports, to help guide their understanding of the clinical effect of new oncologic therapies.
Os granitos ediacaranos no contexto dos terrenos Jaguaribeano e Rio Piranhas-Seridó no oeste do RN, Província Borborema.
Authors: Sá1 Jaziel Martins , Galindo Antonio Carlos , Legrand Jean Michel , Souza Laécio Cunha de , Maia Heitor Neves 
Published: May 2015

Volumoso magmatismo plutônico neoproterozoico está bem registrado a leste e a oeste da Zona de Cisalhamento (tipo e cinemática) Portalegre, predominantemente transcorrente e destral, que ocorre no oeste do Rio Grande do Norte. Foram identificados vários tipos litológicos com assinaturas geoquímicas distintas, desde cálcio-alcalinas de alto potássio a alcalinas tipo-A. As relações temporais/estratigráficas entre estas unidades bem como suas relações com o funcionamento das zonas de cisalhamento transcorrentes da região foram estabelecidas, gerando uma cronologia para estes plutons. Estruturalmente estes corpos apresentam desde uma foliação bem desenvolvida, em geral associada às zonas de cisalhamento, até texturas isotrópicas. Estruturas primárias tais como zoneamento magmático de feldspatos, estruturas de fluxo e entelhamento de cristais foram identificadas. Análises U-Pb em zircões e Sm-Nd em rochas total foram realizadas em rochas básicas e ácidas dos batólitos Quixaba, Pereiro (tipo Itaporanga) e Umarizal, e em um dique de diorito (vaugnerito) contendo biotitas centimétricas e ortopiroxênio + clinopiroxênio, intrusivo nos granitos Pereiro e em rochas da Suíte São João do Sabugi. Foram obtidas idades de 618 ± 9 Ma a 570 ± 5 Ma, identificando um plutonismo ativo desde condições sintectônicas a pós-tectônicas à Zona de Cisalhamento Portalegre. Análises isotópicas Sm-Nd apontam protólitos neoarqueanos (2,5-2,6 Ga) para o granito Pereiro, a estaterianas (1,8 Ga) para o granito Quixaba, todas com assinaturas de fonte crustal ou forte contaminação crustal devido aos valores de eNd negativos.
Density-Based Production-Data Analysis of Gas Wells With Significant Rock-Compressibility Effects
Authors: Zhang Miao , Ayala Luis F. 
Published: May 2015

Summary
The state-of-the-art analysis of the production performance of gas wells relies on material-balance concepts combined with pseudopressure and pseudotime for rate-time decline analysis and reserves estimations. In many cases, rock compressibility and reservoir pore-volume (PV) change are either neglected or accounted for by replacing gas compressibility with total compressibility values. In this work, we extend the applicability of a rescaled exponential and density-based decline-analysis approach (Ayala and Ye 2013a, b; Zhang and Ayala 2014a, b) for the decline analysis of gas systems experiencing significant rock-compressibility effects. We formally derive the density-based analytical techniques that rigorously capture formation-compressibility effects during the analysis of gas-well-production data during boundary-dominated flow, which proves crucially important for high-pressure and/or large-formation-compressibility gas-reservoir systems. The proposed formulation enables the calculation and correct prediction of well performance and original gas in place (OGIP) by incorporating formation compressibility and the change of reservoir PV effects, which may prove crucially important in high-pressure and/or relatively large-formation-compressibility gas reservoirs. We also present the associated straight-line analysis technique used for OGIP determination on the basis of the density approach applicable to constant-bottomhole-pressure production and variable-flow-rate/pressure-drop systems.
Twitter: A Novel Tool for Studying the Health and Social Needs of Transgender Communities
Authors: Krueger Evan A , Young Sean D 
Published: May 2015

Background
Limited research has examined the health and social needs of transgender and gender nonconforming populations. Due to high levels of stigma, transgender individuals may avoid disclosing their identities to researchers, hindering this type of work. Further, researchers have traditionally relied on clinic-based sampling methods, which may mask the true heterogeneity of transgender and gender nonconforming communities. Online social networking websites present a novel platform for studying this diverse, difficult-to-reach population.

Objective
The objective of this study was to attempt to examine the perceived health and social needs of transgender and gender nonconforming communities by examining messages posted to the popular microblogging platform, Twitter.

Methods
Tweets were collected from 13 transgender-related hashtags on July 11, 2014. They were read and coded according to general themes addressed, and a content analysis was performed. Qualitative and descriptive statistics are presented.

Results
There were 1135 tweets that were collected in total. Both “positive” and “negative” events were discussed, in both personal and social contexts. Violence, discrimination, suicide, and sexual risk behavior were discussed. There were 34.36% (390/1135) of tweets that addressed transgender-relevant current events, and 60.79% (690/1135) provided a link to a relevant news article or resource.

Conclusions
This study found that transgender individuals and allies use Twitter to discuss health and social needs relevant to the population. Real-time social media sites like Twitter can be used to study issues relevant to transgender communities.
An Evaluation of Chinese Firms' Profitability: 2005–2013
Authors: Liu Jing , Ohlson James A. , Zhang Weining 
Published: May 2015

SYNOPSIS
We empirically examine the profitability of leading Chinese firms, benchmarked against comparable U.S. firms, for the period 2005–2013. Return on invested capital (ROIC), which excludes leverage effects on performance, provides the primary metric. Averaged over firms and years, the two sets of firms have similar profitability, about 11 percent annually. Decomposing ROIC into free cash flow yield and invested capital growth, we show that the same ROIC has very different compositions: while the Chinese firms have high growth and negative free cash flows, the U.S. firms have low growth and positive free cash flows. Due to balance sheet conservatism, we infer that Chinese (U.S.) firms' free cash flow yields and the resulting ROICs have been biased downward (upward). After correcting for the bias, we show that Chinese firms have much higher profitability than their U.S. counterparts: 15.1 percent versus 8.1 percent. This result is driven by the abundance of growth opportunities in China in our sample period. When we control for the growth rates, we find U.S. firms have been more “efficient” in generating more free cash flows than Chinese firms.
Monetary Incentives, Feedback, and Recognition—Complements or Substitutes? Evidence from a Field Experiment in a Retail Services Company
Authors: Lourenço Sofia M 
Published: May 2015

ABSTRACT
This study investigates the performance effects of the combined use of three reinforcers, or incentive motivators, commonly used by companies: monetary incentives, feedback, and recognition. Using a field experiment in a retail services company, I test whether these incentives, which appeal to diverse motivation mechanisms—tangible payoffs, self-regulation, and social esteem—and, hence, have different utilities, are complements or substitutes. The results of the hard performance data collected, in the form of a ratio of sales relative to goals, show that monetary incentives and recognition are substitutes, while feedback is independent of the other incentives. The negative interaction between monetary incentives and recognition is evidence of crowding out between tangible payoffs and social esteem motivations. Individually, these two incentives have a positive impact on performance of about 13 percentage points, which corresponds to a 32.5 percent performance increase. Feedback interactions and main effects are not statistically significant, which suggests that, in this setting, providing feedback in the form of knowledge of results has no impact.
Internal Control Opinion Shopping and Audit Market Competition
Authors: Newton Nathan J. , Persellin Julie S. , Wang Dechun , Wilkins Michael S. 
Published: May 2015

ABSTRACT
This study examines the extent to which audit clients successfully engage in internal control opinion shopping activities and whether audit market competition appears to facilitate those activities. Regulators have long been concerned about the impact of both audit market competition and opinion shopping on audit quality. We adopt the framework developed in Lennox (2000) to construct a proxy to measure the tendency that clients engage in internal control opinion shopping activities. Our empirical results suggest that clients are successful in shopping for clean internal control opinions. In addition, we find evidence that internal control opinion shopping occurs primarily in competitive audit markets. Finally, our results indicate that among auditor dismissal clients, opinion shopping is more likely to occur when dismissals are made relatively late during a reporting period and when audit market competition is high. Our findings have implications for the current policy debate regarding audit quality and audit market competition.
Client Conservatism and Auditor-Client Contracting
Authors: DeFond Mark L. , Lim Chee Yeow , Zang Yoonseok 
Published: May 2015

ABSTRACT
We find that auditors of more conservative clients charge lower fees, issue fewer going concern opinions, and resign less frequently, consistent with more conservative clients imposing less engagement risk on their auditors. Using path analysis, we find evidence that both inherent risk and auditor business risk explain these associations. Also consistent with conservatism reducing auditor business risk, we find that client conservatism is associated with fewer lawsuits against auditors and with fewer client restatements. Taken together, our results are consistent with auditors viewing client conservatism as an important determinant of engagement risk that, in turn, affects auditor-client contracting decisions. Our findings should be of interest to auditors who actively manage client risk and to standard-setters who recently dropped conservatism as a desired attribute of financial reporting quality.
Data Availability: All data are publicly available from sources indicated in the text.
Accounting and Public Policy: The Importance of Credible Research
Authors: Denison Christine A. , Ravenscroft Sue P. , Williams Paul F. 
Published: May 2015

ABSTRACT
Accounting as a professional practice plays a profound, unavoidable, and often unnoticed role in the lives of all citizens. As members of the Public Interest Section of the American Accounting Association, we explicitly explore the myriad social roles of accounting and promote its use to improve the general well-being. In this forum, to say accounting matters is to state the obvious and uncontested. Accounting's important social role imposes responsibilities on those defining and studying that role; as academics we are obligated to promote the highest standards in our research on accounting practice and its social implications. However, the dominant accounting research that explores and attempts to underlay accounting practice does not consistently adhere to the basic precepts of good scientific research practice. To serve the public interest, researchers in accounting can and must do more than award and distribute status via publication in journals whose prestige is high but whose requirements fail to meet scientific standards of reproducibility. We look first at the importance of accounting's role in society. Then we evaluate existing research practices in accounting and find them inadequate to the demands of scientific standards. We provide examples accounting academics could adopt from related disciplines in pursuit of more reliable research findings.
Calcium Variously Mediates the Effect of Cytokinin on Chlorophyll and LHCPII Accumulation During Greening in Barley Leaves and Cucumber Cotyledons
Authors: Legocka Jolanta , Sobieszczuk-Nowicka Ewa 
Published: May 2015

Abstract
During greening, excised etiolated barley leaves and cucumber cotyledons that were depleted of exogenous Ca2+ by a chelating agent (ethylene glycol-bis (beta aminoethyl ether)-N,N,N`N`-tetraacetic acid, EGTA) showed ∼50% reduced chlorophyll (Chl) accumulation and ∼30% accumulation of apoprotein of the light-harvesting chlorophyll a/b-binding protein complex of photosystem II (LHCPII). The Ca2+ channel blocker lanthanum chloride (LaCl3) applied to cucumber cotyledons reduced LHCPII accumulation more than EGTA did. In both plant mate-rials, cytokinins enhanced chlorophyll accumulation by 50-60% and this effect was completely canceled by EGTA application. Hormones significantly increased LHCPII accumulation but EGTA application reduced that effect in barley leaves by ∼30% and in cucumber cotyledons by ∼80%. A similar effect was observed in LaCl3-treated cotyledons. CaCl2 application boosted chlorophyll accumulation in both plant materials. CaCl2 applied together with cytokinin reduced the hormonal effect on chlorophyll accumulation by ∼38% in barley leaves and 23% in cucumber cotyledons, but almost totally inhibited cytokinin-stimulated LHCPII accumulation. Our results indicate that calcium variously mediates the effect of cytokinin on chlorophyll and LHCPII accumulation. Cytokinin-induced enhancement of chlorophyll accumulation seems totally dependent on the exogenous pool of Ca2+, while Ca2+-dependent and Ca2+-independent pathways are involved in the hormonal effect on LHCPII accumulation. The effect of cytokinin on the increase of light-induced LHCPII accumulation appears to be sensitive to exogenously applied Ca2+, which almost totally blocked the hormonal effect. Our results give indirect evidence that the responses to cytokinin and light act on different events leading to Chl and LHCPII accumulation.
Quantitative Determination of Ellagic Acid and Gallic Acid in Geum Rivale L. and G. Urbanum L.
Authors: Owczarek Aleksandra , Olszewska Monika Anna , Gudej Jan 
Published: May 2015

Abstract
Hydrolyzable tannins and products of their hydrolysis, ellagic acid (EA) and gallic acid (GA), are important con-stituents of many medicinal plants and exhibit various biological activities. Geum rivale and G. urbanum are traditional herbal remedies rich in tannin compounds. The aim of the study was to quantitate free and total EA and GA in aerial and underground parts of G. rivale and G. urbanum. After optimization of extraction, both compounds were quantitated by reversed phase HPLC (RP-HPLC). EA was more abundant than GA in the inves-tigated material, and underground parts of G. rivale were the richest source of total EA and GA.
Comparative Anatomy of Ovules in Galinsoga, Solidago and Ratibida (Asteraceae)
Authors: Kolczyk Jolanta , Stolarczyk Piotr , Płachno Bartosz J. 
Published: May 2015

Abstract
Many Asteraceae species have been introduced into horticulture as ornamental or interesting exotic plants. Some of them, including Solidago and Galinsoga, are now aggressive weeds; others such as Ratibida are not. Special modifications of the ovule tissue and the occurrence of nutritive tissue have been described in several Asteraceae species, including invasive Taraxacum species. This study examined whether such modifications might also occur in other genera. We found that the three genera examined - Galinsoga (G. quadriradiata), Solidago (S. canadensis, S. rigida, S. gigantea) and Ratibida (R. pinnata) - differed in their nutritive tissue structure. According to changes in the integument, we identified three types of ovules in Asteraceae: “Taraxacum” type (recorded in Taraxacum, Bellis, Solidago, Chondrilla), with well-developed nutritive tissue having very swollen cell walls of spongy structure; “Galinsoga” type (in Galinsoga), in which the nutritive tissue cells have more cyto-plasm and thicker cell walls than the other integument parenchyma cells, and in which the most prominent character of the nutritive tissue cells is well-developed rough ER; and “Ratibida” type (in Ratibida), in which the nutritive tissue is only slightly developed and consists of large highly vacuolated cells. Our study and future investigations of ovule structure may be useful in phylogenetic analyses.
Interaction Between Photoreceptors and BR Signaling in Arabidopsis
Authors: Zhu Zhong Xin , Zhu Xiao Feng , Zhu Yu Ting , Yao Da Nian , Xuan Yuan Hu 
Published: May 2015

Abstract
Extensive studies have been performed to elucidate the role of brassinosteroids (BRs), an important class of phy-tohormone in plant growth, development, and photomorphogenesis. Different wavelengths of light recognized by photoreceptors play a crucial role in plant development. The role of different photoreceptors in BR signaling has not been analyzed. Here we used photoreceptor single mutants, double mutants and even a quadruple mutant to analyze BR-dependent hypocotyl growth and gene regulation. All the photoreceptor mutants differed from the controls in their response to BR, and hypocotyl elongation as well as BR marker gene regulation were inhibited by application of propiconazole (PCZ), a BR biosynthesis inhibitor. In addition, altered Phytochrome and Cryptochrome expression in brassinosteroid insensitive 1 mutant bri1-5 and brassinazole-resistant 1 dominant mutant bzr1-D indicated that BR negatively regulates photoreceptors in transcriptional levels. This is the first study to investigate the connections between BR and photoreceptors in Arabidopsis.
Growth Improvement of Nicotiana and Arabidopsis In Vitro by Microalgal Conditioned Media
Authors: Zielińska Elżbieta , Matusiak-Mikulin Krystyna , Grabski Krzysztof , Heda Anna , Krzykowska Aleksandra , Tukaj Zbigniew 
Published: May 2015

Abstract
Conditioned medium (CM) is a general term describing media in which cells have already been cultivated for some time. Such media, usually clarified by filtration, have been used by plant biotechnologists as additives sup-porting the growth of cell suspensions, organs and whole plants. This study examined the effect of CM obtained from green alga Desmodesmus subspicatus on the growth and functioning of the photosynthetic apparatus of Nicotiana tabacum and Arabidopsis thaliana in culture in vitro. Plants where cultured on CM diluted 1.25-, 2-and 5-fold with MS medium. The increase in fresh and dry weight was highest in tobacco and Arabidopsis cultured on CM/2 and CM/1.25 media. Those two concentrations also increased the amount of chlorophylls in both plants tested. CM improved parameter PI (reflecting the photosynthetic “vitality” of the organism) and electron transport efficiency, and increased the fraction of active reaction centers. Analysis of chlorophyll fluorescence in vivo suggests that the improvement of these plants grown in the presence of algal CM may result from stimulation of photosynthesis. Algal CM offers a convenient, cheap, universal supplement for stimulating the growth of higher plants in vitro.
A Comparison of Machine Learning Methods in a High-Dimensional Classification Problem
Authors: Zekić-Sušac Marijana , Pfeifer Sanja , Šarlija Nataša 
Published: May 2015

Abstract
Background: Large-dimensional data modelling often relies on variable reduction methods in the pre-processing and in the post-processing stage. However, such a reduction usually provides less information and yields a lower accuracy of the model. Objectives: The aim of this paper is to assess the high-dimensional classification problem of recognizing entrepreneurial intentions of students by machine learning methods. Methods/Approach: Four methods were tested: artificial neural networks, CART classification trees, support vector machines, and k-nearest neighbour on the same dataset in order to compare their efficiency in the sense of classification accuracy. The performance of each method was compared on ten subsamples in a 10-fold cross-validation procedure in order to assess computing sensitivity and specificity of each model. Results: The artificial neural network model based on multilayer perceptron yielded a higher classification rate than the models produced by other methods. The pairwise t-test showed a statistical significance between the artificial neural network and the k-nearest neighbour model, while the difference among other methods was not statistically significant. Conclusions: Tested machine learning methods are able to learn fast and achieve high classification accuracy. However, further advancement can be assured by testing a few additional methodological refinements in machine learning methods.