bluuebunny/crossref_metadata_2025 huggingface dataset:
The Impact of Business Strategies on Online Sustainability Disclosures
Authors: Amran Azlan , Ooi Say Keat , Mydin Riduan Toani , Devi S. Susela
Published: December 2013

With increasing attention being paid to corporate sustainability, pressure from stakeholders, especially customers, is forcing companies to implement sustainability strategies and practices that express their commitment to sustainable development, and engage with stakeholders through voluntary sustainability disclosure. To better understand the sustainability disclosure mechanisms from a business strategy perspective, this study investigates the influence of business strategy, formulated by customer groups, on online sustainability disclosure. It provides empirical observation of Malaysian public‐listed companies based on the combined lens of stakeholder and legitimacy theory. Despite the comparatively low level of corporate sustainability disclosure in Malaysia, this content analysis of online sustainability information disclosure reveals that the companies with more diversified product lines disclose more sustainability information, and that the corporate sustainability effort is significantly related to brand name. Hence, companies should be encouraged to proactively improve their sustainability performance and disclose more sustainability information in order to strengthen their brand names. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Capacity planning for batch and perfusion bioprocesses across multiple biopharmaceutical facilities
Authors: Siganporia Cyrus C. , Ghosh Soumitra , Daszkowski Thomas , Papageorgiou Lazaros G. , Farid Suzanne S.
Published: December 2013

Production planning for biopharmaceutical portfolios becomes more complex when products switch between fed‐batch and continuous perfusion culture processes. This article describes the development of a discrete‐time mixed integer linear programming (MILP) model to optimize capacity plans for multiple biopharmaceutical products, with either batch or perfusion bioprocesses, across multiple facilities to meet quarterly demands. The model comprised specific features to account for products with fed‐batch or perfusion culture processes such as sequence‐dependent changeover times, continuous culture constraints, and decoupled upstream and downstream operations that permit independent scheduling of each. Strategic inventory levels were accounted for by applying cost penalties when they were not met. A rolling time horizon methodology was utilized in conjunction with the MILP model and was shown to obtain solutions with greater optimality in less computational time than the full‐scale model. The model was applied to an industrial case study to illustrate how the framework aids decisions regarding outsourcing capacity to third party manufacturers or building new facilities. The impact of variations on key parameters such as demand or titres on the optimal production plans and costs was captured. The analysis identified the critical ratio of in‐house to contract manufacturing organization (CMO) manufacturing costs that led the optimization results to favor building a future facility over using a CMO. The tool predicted that if titres were higher than expected then the optimal solution would allocate more production to in‐house facilities, where manufacturing costs were lower. Utilization graphs indicated when capacity expansion should be considered. © 2013 The Authors Biotechnology Progress published by Wiley Periodicals, Inc. on behalf of American Institute of Chemical Engineers Biotechnol. Prog., 30:594–606, 2014
Antigen‐responsive regulation of Cell motility and migration via the signalobodies based on c‐Fms and c‐Mpl
Authors: Kawahara Masahiro , Hitomi Azusa , Nagamune Teruyuki
Published: December 2013

Since cell migration plays critical roles in development and homeostasis of the body, artificial control of cell migration would be promising for the treatment of various diseases related to migration. To this end, we previously developed single‐chain Fv (scFv)/receptor chimeras, named signalobodies, which can control cell fates via a specific antigen that is different from natural cytokines. Although a conventional chemotaxis chamber assay revealed that several signalobodies based on receptor tyrosine kinases transduced antigen‐dependent migration signals, we have never performed direct observation of the cells to obtain more information on overall properties of cell motility and migration. In this study, we utilized murine pro‐B Ba/F3 cells expressing either a scFv‐Fms or scFv‐Mpl signalobody, and compared their migratory characteristics. We employed a lipid–polyethylene glycol conjugate to softly immobilize the suspension cells on a slide, which facilitated direct observation of chemokinetic activity of the cells. Consequently, both cells markedly exhibited chemokinesis in response to a specific antigen. In addition, the cells were subjected to a stable antigen‐concentration gradient to observe horizontal directional cell migration in real time. The results showed that the cells expressing scFv‐Fms underwent directional migration toward a positive antigen‐concentration gradient. Taken together, we successfully demonstrated antigen‐responsive regulation of cell motility and migration via the signalobodies. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:411–417, 2014
Preparation of a novel hydrophobic affinity cryogel for adsorption of lipase and its utilization as a chromatographic adsorbent for fast protein liquid chromatography
Authors: Ünlüer Özlem Biçen , Özcan Ayça , Uzun Lokman
Published: December 2013

In this study, we have prepared a hydrophobic cryogel for the chromatographic separation of lipase from its aqueous solutions including single protein and protein mixture and also Yarrowia lipolytica cell extract. N‐methacryloyl‐(l)‐phenylalanine methyl ester was used as a monomer to provide the hydrophobic character to the prepared cryogels. The highest adsorption capacity was observed at pH 5.0 at 0.5 mL min−1 flow rate. The chromatographic separation of lipase was achieved from a binary mixture of lipase:bovine serum albumin (BSA) and lipase:lysozyme, and was also achieved from triple‐mixture of lipase:lysozyme:BSA by using fast protein liquid chromatography. Finally, lipase purification was performed from Yarrowia lipolytica cell extract used as a natural source. These studies have shown that the hydrophobic cryogel has good chromatographic performance for the separation and purification of lipase not only from aqueous solution, but also from cell extract as a natural source of lipase. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:376–382, 2014
Understanding the effects of adolescent girls' social positions within peer groups on exchange practices
Authors: Gentina Elodie
Published: December 2013

Most adolescent consumer research focuses on individual variables (e.g. susceptibility to peers' influence), without studying the peer group structure. This research investigates the role of adolescent girls' social position within their networks in exchange practices with friends. By using several different methods (social network method, participant observations and semi‐structured interviews), this study reveals that different forms of clothing exchanges (sharing, lending and borrowing) associated with different social motives (needs for socialising, experiencing, belonging, distinguishing and influencing) evolve differently, depending on adolescent girls' social positions (clique member, liaison and isolate). Whereas clique members engage in sharing practices to socialise and share experiences with their friends, isolated adolescent girls engage in other activities (e.g. asking to borrow clothes) as a way to cope with feelings of loneliness. Some liaisons limit their exchange practices to loans, to emphasise their leadership, but most of them avoid sharing clothes in an attempt to preserve their uniqueness. These results suggest an extended view of materialism, with greater emphasis on use and social motives than on acquisition and its utility. Accordingly, this study proposes a new conceptualisation of materialism, as the extent to which adolescents engage in exchange practices to construct and maintain their social identities. Copyright © 2013 John Wiley & Sons, Ltd.
A star in the eye: cat scratch neuroretinitis
Authors: Gajula Viswanath , Kamepalli Ravi , Kalavakunta Jagadeesh K.
Published: December 2013

Key Clinical Message

Neuroretinitis is one of the atypical presentations of Cat scratch disease (CSD). Fundoscopy showed star pattern macular exudates. CSD should be considered in patients who present with blurry vision and typical fundoscopic findings.
The influence of complications on the costs of complex cancer surgery
Authors: Short Marah N. , Aloia Thomas A. , Ho Vivian
Published: December 2013

BACKGROUND

It is widely known that outcomes after cancer surgery vary widely, depending on interactions between patient, tumor, neoadjuvant therapy, and provider factors. Within this complex milieu, the influence of complications on the cost of surgical oncology care remains unknown. The authors examined rates of Patient Safety Indicator (PSI) occurrence for 6 cancer operations and their association with costs of care.

METHODS

The Agency for Healthcare Research and Quality (AHRQ) PSI definitions were used to identify patient safety‐related complications in Medicare claims data. Hospital and inpatient physician claims for the years 2005 through 2009 were analyzed for 6 cancer resections: colectomy, rectal resection, pulmonary lobectomy, pneumonectomy, esophagectomy, and pancreatic resection. Risk‐adjusted regression analyses were used to measure the association between each PSI and hospitalization costs.

RESULTS

Overall PSI rates ranged from a low of 0.01% for postoperative hip fracture to a high of 2.58% for respiratory failure. Death among inpatients with serious treatable complications, postoperative respiratory failure, postoperative thromboembolism, and accidental puncture/laceration were >1% for all 6 cancer operations. Several PSIs—including decubitus ulcer, death among surgical inpatients with serious treatable complications, and postoperative thromboembolism—raised hospitalization costs by ≥20% for most cancer surgery types. Postoperative respiratory failure resulted in a cost increase >50% for all cancer resections.

CONCLUSIONS

The consistently higher costs associated with cancer surgery PSIs indicate that substantial health care savings could be achieved by targeting these indicators for quality improvement. Cancer 2014;120:1035–1041. © 2013 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
Comparative effectiveness study of patient‐reported outcomes after proton therapy or intensity‐modulated radiotherapy for prostate cancer
Authors: Hoppe Bradford S. , Michalski Jeff M. , Mendenhall Nancy P. , Morris Christopher G. , Henderson Randal H. , Nichols Romaine C. , Mendenhall William M. , Williams Christopher R. , Regan Meredith M. , Chipman Jonathan J. , Crociani Catrina M. , Sandler Howard M. , Sanda Martin G. , Hamstra Daniel A.
Published: December 2013

BACKGROUND

Data continue to emerge on the relative merits of different treatment modalities for prostate cancer. The objective of this study was to compare patient‐reported quality‐of‐life (QOL) outcomes after proton therapy (PT) and intensity‐modulated radiation therapy (IMRT) for prostate cancer.

METHODS

A comparison was performed of prospectively collected QOL data using the Expanded Prostate Cancer Index Composite (EPIC) questionnaire. QOL data were collected during the first 2 years after treatment for men who received PT and IMRT. PT was delivered to 1243 men at a single center at doses from 76 grays (Gy) to 82 Gy. IMRT was delivered to 204 men who were included in the Prostate Cancer Outcomes and Satisfaction with Treatment Quality Assessment (PROSTQA) study in doses from 75.6 Gy to 79.4 Gy. The Wilcoxon rank‐sum test was used to compare EPIC outcomes by modality using baseline‐adjusted scores at different time points. Individual questions were assessed by converting to binary outcomes and testing with generalized estimating equations.

RESULTS

No differences were observed in summary score changes for bowel, urinary incontinence, urinary irritative/obstructive, and sexual domains between the 2 cohorts. However, more men who received IMRT reported moderate/big problems with rectal urgency (P = 0.02) and frequent bowel movements (P = 0.05) than men who received PT.

CONCLUSIONS

There were no differences in QOL summary scores between the IMRT and PT cohorts during early follow‐up (up to 2‐years). Response to individual questions suggests possible differences in specific bowel symptoms between the 2 cohorts. These outcomes highlight the need for further comparative studies of PT and IMRT. Cancer 2014;120:1076–1082. © 2013 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.
National trends in pancreatic cancer outcomes and pattern of care among Medicare beneficiaries, 2000 through 2010
Authors: Wang Yun , Schrag Deborah , Brooks Gabriel A. , Dominici Francesca
Published: December 2013

BACKGROUND

Pancreatic cancer is a major cause of morbidity and mortality in the Medicare population. Whether the health care burden of pancreatic cancer has changed over the last decade is unknown.

METHODS

The authors used Medicare data from 2000 to 2010 to identify beneficiaries aged ≥ 65 years who were hospitalized for the management of pancreatic cancer. Annual trends were estimated for the age‐sex‐race–adjusted initial hospitalization rate, the age‐sex‐race‐comorbidity–adjusted 1‐year mortality rate after initial hospitalization, age‐sex‐race‐comorbidity–adjusted procedure rates, 1‐year all‐cause rehospitalizations after initial pancreatic cancer hospitalization, and mean inflation‐adjusted Medicare payment for initial hospitalization.

RESULTS

A total of 130,728 patients had ≥ 1 hospitalizations for pancreatic cancer and were identified from 56,642,071 beneficiaries during the study period. The age‐sex‐race–adjusted rate of initial hospitalization for pancreatic cancer was 50 per 100,000 person‐years in 2010, representing a 0.5% annual increase since 2000 (95% confidence interval [95% CI], 0.3%‐0.7%). In the same period, the age‐sex‐race‐comorbidity–adjusted 1‐year mortality rate decreased by 4.4% (95% CI, 3.9%‐4.9%), and the age‐sex‐race‐comorbidity–adjusted surgical resection rate increased by 6.9% (95% CI, 6.4%‐7.5%). The mean inflation‐adjusted Medicare payment for the initial hospitalization decreased, from $14,118 in 2000 to $13,318 in 2010, and the number of 1‐year all‐cause rehospitalizations after the initial hospitalization increased from 0.75 per patient in 2000 to 0.82 per patient in 2009 (all P < .001).

CONCLUSIONS

For Medicare fee‐for‐service beneficiaries, initial pancreatic cancer hospitalization, surgical resection, and rehospitalization rates increased, but 1‐year mortality rates declined over the last decade. Cancer 2014;120:1050–1058. © 2013 American Cancer Society.
Coexpression of three opsins in cone photoreceptors of the salamander Ambystoma tigrinum
Authors: Isayama Tomoki , Chen Ying , Kono Masahiro , Fabre Eduard , Slavsky Michael , DeGrip Willem J. , Ma Jian‐Xing , Crouch Rosalie K. , Makino Clint L.
Published: December 2013

Although more than one type of visual opsin is present in the retina of most vertebrates, it was thought that each type of photoreceptor expresses only one opsin. However, evidence has accumulated that some photoreceptors contain more than one opsin, in many cases as a result of a developmental transition from the expression of one opsin to another. The salamander UV‐sensitive (UV) cone is particularly notable because it contains three opsins (Makino and Dodd [1996] J Gen Physiol 108:27–34). Two opsin types are expressed at levels more than 100 times lower than the level of the primary opsin. Here, immunohistochemical experiments identified the primary component as a UV cone opsin and the two minor components as the short wavelength‐sensitive (S) and long wavelength‐sensitive (L) cone opsins. Based on single‐cell recordings of 156 photoreceptors, the presence of three components in UV cones of hatchlings and terrestrial adults ruled out a developmental transition. There was no evidence for multiple opsin types within rods or S cones, but immunohistochemistry and partial bleaching in conjunction with single‐cell recording revealed that both single and double L cones contained low levels of short wavelength‐sensitive pigments in addition to the main L visual pigment. These results raise the possibility that coexpression of multiple opsins in other vertebrates was overlooked because a minor component absorbing at short wavelengths was masked by the main visual pigment or because the expression level of a component absorbing at long wavelengths was exceedingly low. J. Comp. Neurol. 522:2249–2265, 2014. © 2013 Wiley Periodicals, Inc.
Differential distribution and energy status–dependent regulation of the four CART neuropeptide genes in the zebrafish brain
Authors: Akash G. , Kaniganti Tarun , Tiwari Neeraj Kumar , Subhedar Nishikant K. , Ghose Aurnab
Published: December 2013

The cocaine‐ and amphetamine‐regulated transcript (CART) neuropeptide has been implicated in the neural regulation of energy homeostasis across vertebrate phyla. By using gene‐specific in situ hybridization, we have mapped the distribution of the four CART mRNAs in the central nervous system of the adult zebrafish. The widespread neuronal expression pattern for CART 2 and 4 suggests a prominent role for the peptide in processing sensory information from diverse modalities including olfactory and visual inputs. In contrast, CART 1 and 3 have a much more restricted distribution, predominantly located in the nucleus of the medial longitudinal fasciculus (NMLF) and entopeduncular nucleus (EN), respectively. Enrichment of CART 2 and 4 in the preoptic and tuberal areas emphasizes the importance of CART in neuroendocrine functions. Starvation resulted in a significant decrease in CART‐positive cells in the nucleus recessus lateralis (NRL) and nucleus lateralis tuberis (NLT) hypothalamic regions, suggesting a function in energy homeostasis for these neurons. Similarly, the EN emerges as a novel energy status–responsive region. Not only is there abundant and overlapping expression of CART 2, 3, and 4 in the EN, but also starvation induced a decrease in CART‐expressing neurons in this region. The cellular resolution mapping of CART mRNA and the response of CART‐expressing nuclei to starvation underscores the importance of CART neuropeptide in energy processing. Additionally, the regional and gene‐specific responses to energy levels suggest a complex, interactive network whereby the four CART gene products may have nonredundant functions in energy homeostasis. J. Comp. Neurol. 522:2266–2285, 2014. © 2013 Wiley Periodicals, Inc.
Lateral habenula and the rostromedial tegmental nucleus innervate neurochemically distinct subdivisions of the dorsal raphe nucleus in the rat
Authors: Sego Chemutai , Gonçalves Luciano , Lima Leandro , Furigo Isadora C. , Donato Jose , Metzger Martin
Published: December 2013

The lateral habenula (LHb) is an epithalamic structure differentiated in a medial (LHbM) and a lateral division (LHbL). Together with the rostromedial tegmental nucleus (RMTg), the LHb has been implicated in the processing of aversive stimuli and inhibitory control of monoamine nuclei. The inhibitory LHb influence on midbrain dopamine neurons has been shown to be mainly mediated by the RMTg, a mostly GABAergic nucleus that receives a dominant input from the LHbL. Interestingly, the RMTg also projects to the dorsal raphe nucleus (DR), which also receives direct LHb projections. To compare the organization and transmitter phenotype of LHb projections to the DR, direct and indirect via the RMTg, we first placed injections of the anterograde tracer Phaseolus vulgaris leucoagglutinin into the LHb or the RMTg. We then confirmed our findings by retrograde tracing and investigated a possible GABAergic phenotype of DR‐projecting RMTg neurons by combining retrograde tracing with in situ hybridization for GAD67. We found only moderate direct LHb projections to the DR, which mainly emerged from the LHbM and were predominantly directed to the serotonin‐rich caudal DR. In contrast, RMTg projections to the DR were more robust, emerged from RMTg neurons enriched in GAD67 mRNA, and were focally directed to a distinctive DR subdivision immunohistochemically characterized as poor in serotonin and enriched in presumptive glutamatergic neurons. Thus, besides its well‐acknowledged role as a GABAergic control center for the ventral tegmental area (VTA)–nigra complex, our findings indicate that the RMTg is also a major GABAergic relay between the LHb and the DR. J. Comp. Neurol. 522:1454–1484, 2014. © 2013 Wiley Periodicals, Inc.
Evolutionary Pathways of Environmental Management in UK Companies
Authors: Ormazabal M. , Sarriegi J. M. , Barkemeyer R. , Viles E. , McAnulla F.
Published: December 2013

This research focuses on the evolution of environmental management within firms. It is based on a survey and semi‐structured interviews conducted among UK companies. Building on an evolutionary conceptual model, consisting of several maturity stages, we identify ‘milestones’, i.e. common practices companies engage in when progressing through specific maturity stages. Whilst clear commonalities can be identified, most notably linked to the order of maturity stages they progressed through and the emergence of commonly acknowledged practices linked to the individual maturity stages, the results also reveal a number of within‐sample patterns regarding the companies’ progression through the different maturity stages. It can be concluded that the maturity stages and practices identified in this research can provide valuable guidance for firms aiming to make progress in environmental matters, as they help them to identify in which maturity stage they are and sets out steps that they can take to move forward. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment.
Combination of in ovo electroporation and time‐lapse imaging to study migrational events in chicken embryos
Authors: Masyuk Maryna , Morosan‐Puopolo Gabriela , Brand‐Saberi Beate , Theiss Carsten
Published: December 2013

Background: During embryonic development cell migration plays a principal role in several processes. In past decades, many studies were performed to investigate migrational events, occurring during embryonic organogenesis, neurogenesis, gliogenesis or myogenesis, just to name a few. Although different common techniques are already used for this purpose, one of their major limitations is the static character. However, cell migration is a sophisticated and highly dynamic process, wherefore new appropriate technologies are required to investigate this event in all its complexity. Results and Conclusions: Here we report a novel approach for dynamic analysis of cell migration within embryonic tissue. We combine the modern transfection method of in ovo electroporation with the use of tissue slice culture and state‐of‐the‐art imaging techniques, such as confocal laser scanning microscopy or spinning disc confocal microscopy, and thus, develop a method to study live the migration of myogenic precursors in chicken embryos. The conditions and parameters used in this study allow long‐term imaging for up to 24 hr. Our protocol can be easily adapted for investigations of a variety of other migrational events and provides a novel conception for dynamic analysis of migration during embryonic development. Developmental Dynamics 243:690–698, 2014. © 2013 Wiley Periodicals, Inc.
The Significance of the Non‐Timber Forest Products Policy for Forest Ecology Management: A Case Study in West Bengal, India
Authors: Ghosal Somnath
Published: December 2013

A precise non‐timber forest products (NTFPs) policy can play an important role in the preservation of the forest resource base. By promoting systematic and sustainable harvesting of forest products, the exploitation of forest resources can be reduced and the socio‐economic status of marginal forest dwellers can also be improved, which will subsequently reduce illegal timber harvesting. In India, brief guidelines for the harvesting of NTFPs are placed in the Joint Forest Management resolution. However, these guidelines are not equally effective in all states because of micro‐level geophysical variances, forest–human relationships and the characteristics of the forests. Therefore, some south Indian states such as Tamil Nadu, Orissa and Andhra Pradesh have developed their own NTFP harvesting policy for the sustainable management of forests through the socio‐economic enhancement of forest dwellers. However, in West Bengal the central government's guidelines are still followed. This paper examines the need for a precise NTFP harvesting policy for the management of forests in West Bengal through the socio‐economic improvement of forest fringe tribal communities. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Environmental Commitment and Economic Performance – Short‐Term Pain for Long‐Term Gain
Authors: Teng Mei‐Jane , Wu Shih‐Ying , Chou Stephen Jui‐Hsien
Published: December 2013

Although an increasing number of studies have begun to investigate the relationship between firms' environmental practices and economic performance, one of the issues that have been neglected involves the time lag between environmental investment and economic performance, as well as the tradeoff between short‐term costs and long‐term benefits. By utilizing a sample of publicly listed corporations in Taiwan over the period 1996–2008, we find that the relationship between economic performance and ISO certification is neither strictly negative nor strictly positive, but is instead U shaped. The evidence suggests that, although a firm bears costs for environmental management in the short term, the benefits of environmental management accumulate over time after environmental certification, and a firm benefits from environmental management in the long term. The result also provides an explanation for the mixed evidence on the relationship between proactive environmental strategies and economic performance by documenting a non‐monotonic relationship between environmental management and firm performance. The finding thus implies that government subsidies for ISO certification can be rationalized, since they help firms to overcome the barrier associated with the costs of certification, and encourage them to obtain ISO certification. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Central‐Local Relations in French Energy Policy‐Making: Towards a New Pattern of Territorial Governance
Authors: Poupeau François‐Mathieu
Published: December 2013

After a long period of centralization, local authorities have been taking a new place in the French energy sector. This revival began in the 1990s with the process of deregulation, which gave them new room for manoeuvre. This continued into the 2000s, when energy efficiency and climate change issues were set on the political agenda. This process led many practitioners and academic researchers to consider these two last decades as a turning point, which initiates a new model of governance, one that is far more decentralized than in the past. Here, we discuss this hypothesis and show that this recent ‘activism’ at local level associated with a change in State intervention has been leading to a new pattern of territorial governance in France that is not at odds with the past but rather is in continuity with it. Using the neo‐institutional approach developed by James Mahoney and Kathleen Thelen, we focus on three main dimensions that play a ‘homeostatic’ role: the production structure, ideas and institutional arrangements. This leads us to develop an interpretation of ongoing changes in terms of an ‘aggiornamento’ of the former pattern of governance, rather than any real breakdown. Copyright © 2013 John Wiley & Sons, Ltd and ERP Environment
Long‐Run and Cyclical Dynamics in the US Stock Market
Authors: Caporale Guglielmo Maria , Gil‐Alana Luis
Published: December 2013

This paper uses fractional integration to examine the long‐run dynamics and cyclical structure of US inflation, real risk‐free rate, real stock returns, equity premium and price/dividend ratio, annually from 1871 to 2000. It implements a procedure which allows consideration of unit roots with possibly fractional orders of integration both at zero (long‐run) and cyclical frequencies. When focusing exclusively on the former, the estimated order of integration varies considerably, and non‐stationarity is found only for the price/dividend ratio. When the cyclical component is also taken into account, the series appear to be stationary but to exhibit long memory with respect to both components in almost all cases. The exception is the price/dividend ratio, whose order of integration is higher than 0.5 but smaller than 1 for the long‐run frequency, and is between 0 and 0.5 for the cyclical component. Also, mean reversion occurs in all cases. Finally, six different criteria are applied to compare the forecasting performance of the fractional (at both zero and cyclical frequencies) models with others based on fractional and integer differentiation only at the zero frequency. The results, based on a 15‐year horizon, show that the former outperforms the others in a number of cases. Copyright © 2013 John Wiley & Sons, Ltd.
USING POLICY INTERVENTION TO IDENTIFY FINANCIAL STRESS
Authors: Carlson Mark , Lewis Kurt , Nelson William
Published: December 2013

This paper describes the construction of a financial stress index (FSI). Our index incorporates the level, volatility and comovement of a variety of financial series, rather than a single dimension of the data. To determine which time periods are ones of notable financial stress and thus the relevant ones for determining the role of the level, volatility and comovement of our financial series, we use actions taken by policymakers. In addition to describing the construction of our FSI, we discuss issues relevant to the general construction of stress indexes such as how an FSI differs from a financial conditions index, the challenges of combining different financial series into a single measure and the role historical experience plays in index construction. Copyright © 2013 John Wiley & Sons, Ltd.
A SINGLE COMPOSITE FINANCIAL STRESS INDICATOR AND ITS REAL IMPACT IN THE EURO AREA
Authors: Islami Mevlud , Kurz‐Kim Jeong‐Ryeol
Published: December 2013

In this paper, we construct a single composite financial stress indicator (FSI), which aims to predict developments in the real economy in the euro area. Our FSI was shown to perform better than the Euro STOXX 50 volatility index for the recent banking crisis and the euro‐area sovereign debt crisis and to be able to serve as an early warning indicator for negative impacts of financial stress on the real economy. Copyright © 2013 John Wiley & Sons, Ltd.
Bidirectional (Negative/Positive) Interference of Oleandrin and Oleander Extract on a Relatively New LOCI Digoxin Assay Using Vista 1500 Analyzer
Authors: Dasgupta Amitava , Welsh Kerry J. , Hwang Shen‐An , Johnson Myrtle , Actor Jeffrey K.
Published: December 2013

Background

Oleander interferes with serum digoxin measurements using various immunoassays. The potential interference of oleander and its active ingredient, oleandrin, with a relatively new homogenous sequential chemiluminescent digoxin assay based on luminescent oxygen channeling technology (LOCI digoxin assay, Siemens Diagnostics) has not been previously reported.

Methods

Aliquots of a digoxin‐free serum pool were supplemented with increasing concentrations of oleandrin, or with oleander extract, followed by measuring the apparent digoxin concentrations using the LOCI digoxin assay using Vista 1500 analyzer. Mice were fed oleandrin or oleander extract, and their blood digoxin levels at 1 and 2 h were measured with the LOCI digoxin assay. In addition, two digoxin serum pools were prepared by combining sera of patients receiving digoxin; aliquots of both pools were supplemented with oleandrin or oleander extract and digoxin concentrations were again measured. Attempts to overcome this interference were made by measuring free digoxin concentration using a third digoxin pool.

Results

Significant apparent digoxin concentrations were observed after supplementing aliquots of the drug‐free serum pool with oleandrin or oleander extract. Mice fed with oleandrin or oleander extract also showed apparent digoxin levels 1 and 2 h after feeding. Digoxin values were also falsely lower or elevated (bidirectional interference) when aliquots of digoxin serum pools were further supplemented with oleandrin or oleander extract depending on concentration; this interference was not eliminated by free digoxin monitoring.

Conclusions

Oleandrin interferes with LOCI digoxin assay.
Anticyclic Citrullinated Peptide Antibody and Rheumatoid Factor in South Tunisian Patients With Rheumatoid Arthritis: Association With Disease Activity and Severity
Authors: Hamad Mariem Ben , Marzouk Sameh , Kaddour Neila , Masmoudi Hatem , Fakhfakh Faiza , Rebai Ahmed , Bahloul Zouhir , Maalej Abdellatif
Published: December 2013

Objective

To explore relationships between immunological status, clinical features, radiographic damage, disease activity, and functional disability in Tunisian patients with rheumatoid arthritis (RA).

Materials and Methods

The study was carried out in 112 patients with RA. Demographic characteristics, disease duration, disease activity score 28 (DAS28), the Health Assessment Questionnaire (HAQ), and the Sharp/van der Heijde score were collected. Anticyclic citrullinated peptide antibody (anti‐CCP) and rheumatoid factor (RF) were performed.

Results

We found that anti‐CCP positivity was associated with longer disease duration (P = 0.001), presence of RF (P = 4.89 × 10−8), and night pain positivity (P = 0.025). Patients with positive RF had more night pain and higher anti‐CCP positivity (for all P ≤ 0.05). Anti‐CCP titer was correlated with disease duration (P = 0.034) and Sharp total score (P = 1.2 × 10−4). Moreover, there was a significant correlation between RF and anti‐CCP antibodies titers (P = 0.011). Indeed, DAS28 correlated with HAQ (P = 1.8 × 10−7) and morning stiffness duration (P = 0.045). In multivariate regression analysis, the main factors associated with anti‐CCP titers were radiographic damage (P = 1.625 × 10−4) and RF (P = 0.013). For DAS28, only HAQ (P = 2.9 × 10−4) was associated.

Conclusion

These findings suggest that anti‐CCP antibodies are associated with RF and more severe joint damage. Moreover, disease activity is associated with functional disability.
Neutrophil to Lymphocyte Ratio Predicts Poor Prognosis in Ischemic Cerebrovascular Disease
Authors: Celikbilek Asuman , Ismailogullari Sevda , Zararsiz Gokmen
Published: December 2013

Background

Inflammation plays a role in the pathogenesis of carotid atherosclerosis. Although previous data demonstrated an association between inflammatory biomarkers and stroke, there is no publication reporting the relation of neutrophil to lymphocyte (N/L) ratio with ischemic stroke. We aimed to analyze the predictive ability of N/L ratio in acute ischemic cerebrovascular disease.

Methods

A total of 190 patients including 70 patients with first‐ever atherothrombotic acute ischemic stroke (AAIS), 50 patients with transient ischemic attack, and 70 healthy subjects were enrolled in this study. We analyzed the values of white blood cell (WBC), N/L ratio, C‐reactive protein (CRP), gamma‐glutamyltransferase (GGT), homocysteine (HCY), mean platelet volume (MPV) in patients with ischemic group and compared those with control individuals.

Results

WBC, CRP, HCY, N/L ratio were found to increase significantly in AAIS patients than the controls (P < 0.001). With respect to mortality, there were no significant differences between the values of CRP, GGT, HCY, and MPV in patients with AAIS. However, WBC and N/L ratio values were found to increase significantly in dead patients (P = 0.024 and P = 0.029, respectively). A comparison of receiver operating characteristic curves among WBC, CRP, GGT, HCY, MPV, and N/L ratio variables was made. No significant differences were obtained between area under curve values (P > 0.05). A cut‐off value of 4.1 for N/L ratio was detected in predicting mortality with a sensitivity of 66.7% and a specificity of 74.1% (κ = 0.299, P = 0.006).

Conclusions

These findings support the role of N/L ratio as a simple inexpensive and readily available marker of prognosis in acute ischemic stroke.
High False‐Positive Rate for Monoclonal Gammopathy Using Capillary Electrophoresis (CAPILLARYS 2) Alone
Authors: Huang Richard Sheng Poe , Oleske Deanna Alicia , Tholpady Ashok , Chang Brian N. , Dasgupta Amitava , Nguyen Andy , Wahed Amer
Published: December 2013

Background

Capillary zone electrophoresis (CZE) is a newer method of performing serum protein electrophoresis and is considered to be faster and more efficient than agarose gel method. We decided to evaluate CZE as an efficient screening tool for monoclonal gammopathies, and we began recommending immunofixation studies in cases with such minor/subtle distortions to avoid missing monoclonal gammopathies.

Methods

We evaluated 163 serum protein agarose gel electrophoresis (SPAGE) samples between October and November 2011, and 447 serum protein CZE (SPCZE) samples between January 2012 to February 2012 and August 2012 to September 2012.

Results

Immunofixation studies were recommended in 51 of 163 cases (31.3%) performed by SPAGE, and in 274 of 447 cases (61.3%) performed by SPCZE. While using SPAGE, of the 51 cases recommended for immunofixation (24 were performed to date), six cases (25.0%) were positive for monoclonal gammopathy. In contrast, while using SPCZE, of the 274 cases recommended for immunofixation (118 were performed to date), 18 cases (15.2%) were positive for monoclonal gammopathy. Using the SPCZE method, of these 18 cases, five (27.8%) had minor/subtle distortions without obvious peaks. Our recommendation rate for immunofixation studies has thus almost doubled (61.3% vs. 31.3%) with the adoption of SPCZE. Yet, using SPCZE has not translated to detecting more cases of true monoclonal gammopathies.

Conclusion

Therefore, we conclude that there is a high false‐positive rate for monoclonal gammopathy using CE alone.
Molecular Epidemiologic Trends of Diarrhea‐Causing Virus Infection From Clinical Specimens in Cheonan, Korea, in 2010–2012
Authors: Kim Jae Kyung , Kim Jong Wan
Published: December 2013

Background

The enteric viruses have high health significance in humans, ranging from poliomyelitis, hepatitis, and gastroenteritis to innocuous infections, and the human enteric viral infection is the one of the most common diseases during early childhood. This study was conducted from July 2010 to October 2012.

Methods

We subjected 788 stool specimens using multiplex polymerase chain reaction (mPCR) tests that could simultaneously detect five enteric viruses, group A rotavirus (GAR), enteric adenovirus (EAdV), norovirus GI (NoV‐GI), norovirus GII (NoV‐GII), and human astrovirus (HAstV). The data were analyzed according to seasonality and patient age and sex.

Results

Two hundred and seventy specimens (34.3%) were positive, 276 viruses were detected in the 788 sample. The prevalence of GAR, EAdV, NoV‐GI, NoV‐GII, and HAstV infections in the 270 mPCR‐positive specimens was 101 (36.6%), 28 (10.1%), 4 (1.4%), 132 (47.8%), and 11 (4.0%), respectively; six specimens (2.2%) contained double infections. NoV‐GII and GAR infections occurred mainly in the winter and spring.

Conclusion

We described the epidemiological analytic data of the diarrhea‐causing viruses in the population of local society of Korea. These results could be helpful for the diagnosis and subsequent epidemiological surveillance of enteric viral infections.
Technical considerations in the development of circulating peptides as pharmacodynamic biomarkers for angiogenesis inhibitors
Authors: Thomeas Vasiliki , Chow Selina , Gutierrez Jose O. , Karovic Sanja , Wroblewski Kristen , Kistner‐Griffin Emily , Karrison Theodore G. , Maitland Michael L.
Published: December 2013

To determine the biological reproducibility and estimate relevant covariates for candidate circulating biomarkers of angiogenesis, we conducted 3 sub‐studies with ≤15 subjects each. In study 1, 6 healthy subjects provided 13 blood samples across 14–24 days. In study 2, 15 advanced solid tumor patients provided single blood samples before, and approximately 8 and 40 days after sorafenib treatment. In study 3, 4 healthy subjects provided blood samples on 3 occasions over 14 days, processed simultaneously in 2 different laboratories at a single institution. Vascular endothelial growth factor (VEGFA), soluble VEGF receptor‐2 (sVEGFR2), and angiopoietin‐2 (Ang2) concentrations in plasma and serum were determined by standard immunoassays. Ang2 and sVEGFR2 demonstrated low variance within and high variance across individuals reflected by the high intraclass correlation coefficient (for Ang2: 0.86 for plasma, 0.89 for serum; for sVEGFR2: 0.91 for plasma, 0.87 for serum). Repeated measures linear modeling from 15 patients demonstrated increased Ang2 (P ≤ 0.05) and decreased sVEGFR2 (P ≤ 0.05) after exposure to sorafenib. VEGFA had high intraindividual variance, and study 3 demonstrated the laboratory to have significant effects on plasma measurements (P ≤ 0.05). The biological reproducibility of sVEGFR2 and Ang2 support further use of these markers in studies of vasculature‐targeted therapeutics.
Pharmacokinetics of cobicistat boosted‐elvitegravir administered in combination with rosuvastatin
Authors: Custodio Joseph M. , Wang Hui , Hao Jia , Lepist Eve‐Irene , Ray Adrian S. , Andrews Jessica , Ling Kah Hiing J. , Cheng Andrew , Kearney Brian P , Ramanathan Srinivasan
Published: December 2013

Statins are commonly used medications by HIV‐1 patients. Elvitegravir/cobicistat/emtricitabine/tenofovir DF is a single tablet regimen for the treatment of HIV. The pharmacokinetic interaction between cobicistat‐boosted elvitegravir (EVG/co) and rosuvastatin was evaluated. Breast cancer resistance protein (BCRP) and organic anion transporting polypeptide (OATP) 1B1 and 1B3 inhibition were assessed in vitro. Healthy subjects (N = 12) received a single dose of rosuvastatin 10 mg alone and in combination with EVG/co. Intensive pharmacokinetic sampling was conducted and safety was assessed throughout the study. Rosuvastatin pharmacokinetic exposure parameters were evaluated using 90% confidence intervals (CI) of the geometric mean ratio (GMR) of the test (combination) versus reference (rosuvastatin alone) using equivalence boundaries of 70–143% for AUCinf and 70–175% for Cmax. Elvitegravir and cobicistat inhibited BCRP and OATP in vitro, emtricitabine and TDF did not. Clinically, study treatments were well tolerated, with adverse events generally mild. Upon coadministration, rosuvastatin plasma concentrations increased (Cmax 89% higher), while AUCinf changes were modest (38% higher) and clinically nonrelevant, potentially driven by moderate inhibition of intestinal efflux by BCRP, and/or hepatic uptake by OATPs by EVG/co. Elvitegravir and cobicistat pharmacokinetics were comparable to historical data. Rosuvastatin may be coadministered with EVG/COBI/FTC/TDF without dose adjustment.
Loxapine delivered as a thermally generated aerosol does not prolong QTc in a thorough QT/QTc study in healthy subjects
Authors: Spyker Daniel A. , Voloshko Polina , Heyman Eugene R. , Cassella James V.
Published: December 2013

The objective of this study was to establish effects of inhaled loxapine on the QTc interval in this randomized, placebo‐controlled, double‐blind crossover study. Forty‐eight healthy volunteers received a single inhaled placebo or 10 mg loxapine. Plasma concentrations of loxapine increased with a median Tmax of 1 minute and a mean Cmax of 312 ng/mL. After an initial rapid distribution phase, plasma concentrations of loxapine declined with a terminal half‐life of 8 hours. Exposure to the active metabolite 7‐OH‐loxapine was 15% of the parent compound based on mean AUCinf and its terminal half‐life was 12 hours. Inhaled loxapine did not increase QT intervals, as demonstrated by the upper bound of the 1‐sided 95% CIs placed on the point estimate of the placebo‐subtracted change of QTcI (ΔΔQTcI) being less than 10 milliseconds at all 11 post‐dose times. The maximum ΔΔQTcI occurred at 1 hour post‐dose (LSmean 5.42 milliseconds, upper confidence bound 7.75 milliseconds). The study outcome was validated by the demonstrated assay sensitivity using the positive control moxifloxacin maximum ΔΔQTcI occurred at 3 hour post‐dose (LSmean 8.36 milliseconds, lower confidence bound 5.82 milliseconds). The analyses of QTc outliers, and the lack of emergent diagnostic findings for QTcI, QTcB, and QTcF; and simple mean placebo‐subtracted changes of QTcI and QTcF supported the primary QT analysis conclusion that this is a negative finding and there is no apparent QT prolongation associated with the therapeutic dose of inhaled loxapine.
The use of Oxaliplatin or Mitomycin C in HIPEC treatment for peritoneal carcinomatosis from colorectal cancer: A comparative study
Authors: Hompes D. , D'Hoore A. , Wolthuis A. , Fieuws S. , Mirck B. , Bruin S. , Verwaal V.
Published: December 2013

Background

Oxaliplatin and Mitomycin C (MMC) are both suitable as intraperitoneal chemotherapy agents in HIPEC for peritoneal carcinomatosis (PC) of colorectal cancer (CRC).

Methods

Patient cohorts from two different HIPEC‐centers underwent cytoreductive surgery and HIPEC with Oxaliplatin (39 patients) and MMC (56 patients), respectively. They were compared for toxicity and survival data. The extent of PC was assessed using the Dutch 7‐region count.

Results

The median 7‐region count was 4 [range 0–7] for Oxaliplatin‐patients versus 2.5 [range 1–6] for MMC‐patients (P = 0.004). Median intra‐operative blood loss was 650 ml [0–6,000 ml] in Oxaliplatin‐patients versus 1,230 ml [range 0–5,300 ml] in MMC‐patients (P < 0.001). Only MMC‐patients developed neutropenia/leucopenia (26.8%, P < 0.001). After statistical correction for the extent of PC, the overall postoperative complication rate was significantly higher in MMC‐patients (OR = 2.68 (95% CI: 1.04–6.91), P = 0.04), with a comparable intra‐abdominal complication (IAC) rate (OR = 0.78 (95% CI: 0.30–2.03), P = 0.61), but a tendency towards more extra‐abdominal complications (EAC) in MMC‐patients (OR = 2.23 (95% CI: 0.91–5.43), P = 0.079).

Median follow‐up was significantly shorter for Oxaliplatin‐patients (2.8 years) than for MMC‐patients (5.1 years). Median RFS was 12.2 months [IQR: 7.2‐undefined] in the Oxaliplatin‐group and 13.8 months [IQR: 7.0–25.8] in the MMC‐group (P = 0.87). Median OS is 37.1 months [IQR: 22.4–52.8] for Oxaliplatin‐patients and 26.5 months [IQR: 16.9–64.8] for MMC‐patients (P = 0.45). Logistic regression analysis (corrected for extent of PC) shows RFS (HR = 1.24 (95% CI: 0.75–2.05), P = 0.39) and OS (HR = 1.37 (95% CI: 0.74–2.54), P = 0.32) are not significantly different.

Conclusions

No clear benefit in RFS and OS for HIPEC with Oxaliplatin or MMC could be demonstrated in patients with PC from CRC. J. Surg. Oncol. 2014 109:527–532. © 2013 Wiley Periodicals, Inc.