bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Breakfast on the Exposure of the Once-Daily Tacrolimus Formulation in Stable Kidney Transplant Recipients
Authors: Stifft Frank , Undre Nasrullah , van Hooff Johannes P. , Christiaans Maarten H. L.
Published: April 2016

Background:

The once-daily Tacrolimus formulation (Tac ONCE-DAILY) has to be taken on an empty stomach. This is inconvenient for patients and may hamper compliance. The influence of food intake on the exposure of Tac ONCE-DAILY is unknown in transplant recipients. We compared the pharmacokinetics (PKs) of Tac ONCE-DAILY in stable kidney transplant recipients under fasted and fed conditions.

Methods:

In an open-label, single-center, cross-over PK study, 27 stable kidney white transplant recipients (17 male, 10 female) treated with Tac ONCE-DAILY under fasted conditions were enrolled. Two 10-point 24-hour blood concentration time profiles [area under the blood concentration time curve from time 0 to 24 hours (AUC0–24)] were collected under steady state conditions. The primary objective was to investigate the effect of food on the PKs and relative bioavailability of Tac ONCE-DAILY.

Results:

Twenty-seven stable renal transplant patients provided 1 AUC0–24 under fasted and fed conditions, respectively. AUC0–24, C24, and Cmax, were lower in the fed state and Tmax was 1 hour postponed. The 90% confidence interval ratio (fed: fasted) for AUC0–24 was 0.81–0.91 and for C24 0.82–0.92 (both P < 0.001). The majority (60%) had no significant change, but the change in AUC0–24 ranged from −38% to +29%. One trough level was below the target range after fed intake.

Conclusions:

When Tac ONCE-DAILY is ingested with standard continental breakfast, AUC0–24 and C24 decrease overall, with C24 in the therapeutic range in almost all patients. The convenient fed intake could promote therapy adherence. Given the possible significant change in exposure, we advise monitoring of the tacrolimus trough level 1 week after fed ingestion of Tac ONCE-DAILY.
Considerations in Evaluating Treatment Options for Patellofemoral Cartilage Pathology
Authors: Pinkowsky Gregory J. , Farr Jack
Published: April 2016

Patellofemoral (PF) pain, a subset of anterior knee pain, presents a particularly challenging diagnosis due to the multifactorial etiology. Within this group, assigning the patient’s symptoms to a patellofemoral cartilage lesion is indirect; that is, a diagnosis by exclusion as hyaline cartilage is aneural. In addition, these PF compartment lesions are often in conjunction with various comorbidities, for example, malalignment and/or instability. In light of these factors and the high shear and compression stresses at the PF compartment, patellar and trochlear chondral lesions require unique treatment considerations from the tibiofemoral compartments. A thorough understanding of the various cartilage restoration techniques available is necessary to select the best option for the individual patient/knee/lesion noting that there is overlap of techniques’ applications. In addition, failure to address and correct associated comorbidities may jeopardize the outcome of any cartilage restoration procedure. That is, the key to achieving optimal outcomes with PF cartilage restoration is to select the best cartilage treatment for the particular setting and to concomitantly optimize the PF biomechanical environment and stability.
Diseases of Subchondral Bone 1
Authors: Lerebours Frantz , ElAttrache Neal S. , Mandelbaum Bert
Published: April 2016

The subchondral zone plays an important role in both the structural and biochemical maintenance of articular cartilage. Knowledge of the structure, function, and pathophysiology of the normal subchondral bone/articular surface interface is essential for an understanding of the pathogenesis of many of the disease entities that we will review in this chapter.
Ecology, molecules and colour: Multivariate species delimitation and conservation of Harlequin poison frogs
Authors: Posso-Terranova Andres , Andres Jose A.
Published: April 2016

Abstract

We propose a iterative protocol for delimiting species under the generalized lineage concept (GLC) based on the multivariate clustering of morphological, ecological, and genetic data. Our rationale is that the resulting groups should correspond to evolutionarily independent metapopulation lineages because they reflect the common signal of different secondary defining properties (ecological and genetic distinctiveness, morphological diagnosability, etc.), implying the existence of barriers preventing or limiting gene exchange. We applied this method to study a group of highly endangered poison frogs, theOophaga histrionicacomplex. In our study case, we use next generation targeted amplicon sequencing to obtain a robust genetic dataset that we then combined with patterns of morphological and ecological divergence. Our analyses revealed the existence of at least five different species in the histrionica complex (three of them new to science) occurring in very small isolated populations outside any protected areas. More broadly, our study exemplifies how transcriptome-based reduction of genomic complexity and multivariate statistical techniques can be integrated to successfully identify species and their boundaries.

In memoriam

“I propose that each species has a distinctive life history, which include a series of stages that correspond to some of the named species concepts”

Richard G. Harrison

1945-2016
The pluripotency factor Nanog regulates pericentromeric heterochromatin organization in mouse embryonic stem cells
Authors: Novo Clara Lopes , Tang Calvin , Ahmed Kashif , Djuric Ugljesa , Fussner Eden , Mullin Nicholas P. , Morgan Natasha P. , Hayre Jasvinder , Sienerth Arnold R. , Elderkin Sarah , Nishinakamura Ryuichi , Chambers Ian , Ellis James , Bazett-Jones David P. , Rugg-Gunn Peter J.
Published: April 2016

An open and decondensed chromatin organization is a defining property of pluripotency. Several epigenetic regulators have been implicated in maintaining an open chromatin organization, but how these processes are connected to the pluripotency network is unknown. Here, we identified a new role for the transcription factor NANOG as a key regulator connecting the pluripotency network with constitutive heterochromatin organization in mouse embryonic stem cells. Deletion of Nanog leads to chromatin compaction and the remodeling of heterochromatin domains. Forced expression of NANOG in epiblast stem cells is sufficient to decompact chromatin. NANOG associates with satellite repeats within heterochromatin domains, contributing to an architecture characterized by highly dispersed chromatin fibers, low levels of H3K9me3, and high major satellite transcription, and the strong transactivation domain of NANOG is required for this organization. The heterochromatin-associated protein SALL1 is a direct cofactor for NANOG, and loss of Sall1 recapitulates the Nanog-null phenotype, but the loss of Sall1 can be circumvented through direct recruitment of the NANOG transactivation domain to major satellites. These results establish a direct connection between the pluripotency network and chromatin organization and emphasize that maintaining an open heterochromatin architecture is a highly regulated process in embryonic stem cells.
Food-derived sensory cues modulate longevity via distinct neuroendocrine insulin-like peptides
Authors: Artan Murat , Jeong Dae-Eun , Lee Dongyeop , Kim Young-Il , Son Heehwa G. , Husain Zahabiya , Kim Jinmahn , Altintas Ozlem , Kim Kyuhyung , Alcedo Joy , Lee Seung-Jae V.
Published: April 2016

Environmental fluctuations influence organismal aging by affecting various regulatory systems. One such system involves sensory neurons, which affect life span in many species. However, how sensory neurons coordinate organismal aging in response to changes in environmental signals remains elusive. Here, we found that a subset of sensory neurons shortens Caenorhabditis elegans’ life span by differentially regulating the expression of a specific insulin-like peptide (ILP), INS-6. Notably, treatment with food-derived cues or optogenetic activation of sensory neurons significantly increases ins-6 expression and decreases life span. INS-6 in turn relays the longevity signals to nonneuronal tissues by decreasing the activity of the transcription factor DAF-16/FOXO. Together, our study delineates a mechanism through which environmental sensory cues regulate aging rates by modulating the activities of specific sensory neurons and ILPs.
Crystal structures of tetramethylammonium (2,2′-bipyridine)tetracyanidoferrate(III) trihydrate and poly[[(2,2′-bipyridine-κ2N,N′)di-μ2-cyanido-dicyanido(μ-ethylenediamine)(ethylenediamine-κ2N,N′)cadmium(II)iron(II)] monohydrate]
Authors: Chanthee Songwuit , Punyain Wikorn , Namuangrak Supawadee , Chainok Kittipong
Published: April 2016

The crystal structures of the building block tetramethylammonium (2,2′-bipyridine-κ2N,N′)tetracyanidoferrate(III) trihydrate, [N(CH3)4][Fe(CN)4(C10H8N2)]·3H2O, (I), and a new two-dimensional cyanide-bridged bimetallic coordination polymer, poly[[(2,2′-bipyridine-κ2N,N′)di-μ2-cyanido-dicyanido(μ-ethylenediamine-κ2N:N′)(ethylenediamine-κ2N,N′)cadmium(II)iron(II)] monohydrate], [CdFe(CN)4(C10H8N2)(C2H8N2)2]·H2O, (II), are reported. In the crystal of (I), pairs of [Fe(2,2′-bipy)(CN)4]−units (2,2′-bipy is 2,2′-bipyridine) are linked together through π–π stacking between the pyridyl rings of the 2,2′-bipy ligands to form a graphite-like structure parallel to theabplane. The three independent water molecules are hydrogen-bonded alternately with each other, forming a ladder chain structure withR44(8) andR66(12) graph-set ring motifs, while the disordered [N(CH3)4]+cations lie above and below the water chains, and the packing is stabilized by weak C—H...O hydrogen bonds. The water chains are further linked with adjacent sheets into a three-dimensional networkviaO—H...O hydrogen bonds involving the lattice water molecules and the N atoms of terminal cyanide groups of the [Fe(2,2′-bipy)(CN)4]−building blocks, forming anR44(12) ring motif. Compound (II) features a two-dimensional {[Fe(2,2′-bipy)(CN)4Cd(en)2]}nlayer structure (en is ethylenediamine) extending parallel to (010) and constructed from {[Fe(2,2′-bipy)(CN)4Cd(en)]}nchains interlinked by bridging en ligands at the Cd atoms. Classical O—H...N and N—H...O hydrogen bonds involving the lattice water molecule and N atoms of terminal cyanide groups and the N—H groups of the en ligands are observed within the layers. The layers are further connectedviaπ–π stacking interactions between adjacent pyridine rings of the 2,2′-bipy ligands, completing a three-dimensional supramolecular structure.
6-Chloro-1H-indole-2,3-dione
Authors: Golen James A. , Manke David R.
Published: April 2016

The molecule of the title compound, C8H4ClNO2, is planar, with the non-H atoms possessing an r.m.s. deviation from planarity of 0.062 Å. In the crystal, molecules are linked through N—H...O hydrogen bonds, forming chains along [010]. The chains are further linked through C—H...O hydrogen bonds, forming layers parallel to (001).
1,6-Diacetyl-2-isopropyl-4,7-dimethylnaphthalene
Authors: Benharref Ahmed , Oukhrib Abdelouhed , Ait Elhad Mustapha , El Ammari Lahcen , Saadi Mohamed , Berraho Moha
Published: April 2016

The title compound, C19H22O2, was synthesized in three steps from a mixture of α-, β- and γ-himachalene, which was isolated from an essential oil of the Atlas cedar (Cedrus atlantica). In the crystal, molecules are linked by C—H...O hydrogen bonds into chains running parallel to thebaxis.
Corporate governance mechanisms and agency costs: cross-country analysis
Authors: Garanina Tatiana , Kaikova Elina
Published: April 2016

Purpose

The purpose of this paper is to investigate whether specific corporate governance mechanisms, such as board size, board composition, leverage and firm size, tend to mitigate agency cost occurrence in the USA, Russia and Norway.

Design/methodology/approach

The authors analyze the sample of 243 US, 196 Russian and 175 Norwegian joint stock companies for the period 2004-2012. The regression analysis is applied to test the models.

Findings

It is revealed that larger boards increase agency costs (measured by asset utilization ratio and asset liquidity ratio) in all sample companies. The proportion of female members has a very slight positive effect in US companies, a negative influence on agency costs in the Norwegian sample and is not significant in the Russian market. The authors find that the big Russian and US companies in the samples of this paper have lower agency costs.

Practical implications

The results of this paper show which agency-mitigation mechanisms work more effectively in companies operating in the analyzed countries characterized by specific corporate governance models.

Originality/value

The main contribution of this paper to the empirical literature is that it extends the stream of agency research by introducing new, emerging markets: represented by Scandinavian (depicted by the Norwegian sample) and Russian companies. Considering that each market – US, Norwegian and Russian – represents significant distinguishing features in their institutional framework, the paper provides an important research setting in which corporate governance mechanisms can be analyzed from the perspective of a country’s peculiar characteristics. Unlike other agency cost studies, this paper accounts for the gender diversity component in the companies and contributes to gender diversity issues.
On the impact of outside blockholders’ voting power
Authors: Hugo Wang Zhonghui
Published: April 2016

Purpose

The purpose of this paper is to complement existing research of the relationship between concentrated ownership and firm performance by theoretically exploring the impact of outside blockholders on the firm, primarily from the perspective of voting power.

Design/methodology/approach

This paper proposes theoretical propositions based on analyses and logical extension of results of the existing theoretical and empirical studies.

Findings

This paper proposes three theoretical predictions: First, voting power provides outside blockholders a necessary condition to pursue shared and private benefits of control, and it is positively correlated with blockholders’ capability of influencing firm value. Second, everything else being equal, an outside blockholder is more (less) likely to pursue private benefits than shared benefits when the equity market is efficient and when the blockholder’s voting power is less (more) than 50 per cent. Third, controlling outside blockholders can capitalize on their voting power to appoint managerial delegates and board representatives to the invested firms for the purpose of pursuing private benefits of control.

Originality/value

This paper tries to make two contributions to the corporate governance literature. First, this research relies on a new perspective to explore the relationship between ownership structure and firm value. Second, this paper presents the first theoretical argument which states that controlling outside blockholders rely on their managerial delegates and board representatives to pursue their private benefits of control.
A multi-methodology on building a corporate governance index from the perspectives of academics and practitioners for firms in Greece
Authors: Nerantzidis Michail
Published: April 2016

Purpose

The purpose of this paper is to look inside the “black box” in corporate governance (CG) measurement, and shed some light on how to construct a transparent, reliable and valid index, considering equally both the academics and practitioners’ perspectives.

Design/methodology/approach

A synthesized literature review is presented and a CG index is developed combining the strengths of three different methodologies: the Delphi method, the classical test theory (CTT) and the analytic hierarchy process (AHP). This approach helps authors to break the process into separate steps and to select the appropriate techniques to support their decision regarding the norms, the criteria, the variables and the weights that someone should use to construct a CG index.

Findings

The authors’ analysis indicates that a well-designed CG index requires a combination of research methods to identify the best options to solve several methodological issues in index construction. For the application of this multi-methodology in Greece, the authors used two equal and independent samples to explore the different perspectives regarding the importance of the index criteria and sub-criteria. This process provides evidence that the opinion of academics and practitioners in Greece tend to converge. Moreover, it is found that this multi-methodology produces the highest variation in CG scores and ranking orders, as opposed to a traditional approach, in measuring CG disclosure, an important issue with econometric implications.

Research limitations/implications

The limitations of this study are associated with the methods used.

Practical implications

This paper provides practical implications for investors and commercial vendors. For the former, it highlights the need to be more cautious and/or suspicious when they use CG ratings, meaning that they should comprehend the base of the ratings models, and for the latter, it demonstrates the importance of enhancing the transparency in CG indices construction.

Originality/value

The value of the paper lies in improved understanding of the methodological issues in constructing CG indices. This is quite interesting because this approach could serve as a roadmap for other researchers.
Corporate governance: the impact of director and board structure, ownership structure and corporate control on the performance of listed companies on the Ghana stock exchange
Authors: Darko Josephine , Aribi Zakaria Ali , Uzonwanne Godfrey C.
Published: April 2016

Purpose

The purpose of this paper is to examine the relationship between corporate governance and firm performance of listed Ghanaian companies.

Design/methodology/approach

The paper adopts a longitudinal and cross-sectional data set of 20 sampled companies over a period of five years. The data were analyzed using a panel regression and ANOVA analysis to establish the relationship between corporate governance and firm performance. Corporate governance is defined in terms of three indices – board structure, ownership structure and corporate control, while firm performance is measured by return on assets, return on equity, net profit margin and Tobin’s Q.

Findings

The empirical results show that ownership concentration and female representation on board have a positive impact on performance. Although the results revealed no evidence to support the impact of board size and audit committee size on performance, there is significant evidence to support the fact that independent directors and audit committee frequency both adversely affect firm performance.

Research limitations/implications

The scope of this paper can be expanded to include non-listed firms. In addition, other corporate governance mechanisms could be considered to broaden the scope of the paper.

Originality/value

This paper contributes to the scarce literature on corporate governance and firm performance in developing countries, especially in sub-Saharan Africa. The paper provides useful information that is of great value to policymakers, academics and other stakeholders.
Examining the key dimensions of mobile banking service quality: an exploratory study
Authors: Jun Minjoon , Palacios Sergio
Published: April 2016

Purpose

– The purpose of this paper is to identify the key dimensions of mobile banking (m-banking) service quality.

Design/methodology/approach

– The authors employ the critical incident technique to unveil the key dimensions of m-banking service quality as perceived by m-banking customers, and to identify critical satisfiers/dissatisfiers among the identified dimensions.

Findings

– The analysis reveals a total of 17 dimensions of m-banking service quality: m-banking application quality (content, accuracy, ease of use, speed, aesthetics, security, diverse mobile application service features, and mobile convenience), and m-banking customer service quality (reliability, responsiveness, competence, courtesy, credibility, access, communication, understanding the customer, and continuous improvement). Of these, five dimensions, such as mobile convenience, accuracy, diverse mobile application service features, ease of use, and continuous improvement, are considered as the main sources of customer satisfaction/dissatisfaction.

Practical implications

– M-bankers, based on the identified 17 dimensions, can develop a comprehensive service quality management system, which helps them identify and overcome key obstacles to the delivery of high quality m-banking customer services.

Originality/value

– This study focusses on uncovering the key dimensions of m-banking service quality and their associated sub-dimensions specific to the context of m-banking. Theoretically, the identified dimensions and their related sub-items can serve as building blocks for further research in customer relationship management in m-banking.
WIF4InL: Web-based integration framework for Indoor location
Authors: Niu Long , Saiki Sachio , Matsumoto Shinsuke , Nakamura Masahide
Published: April 2016

Purpose

The purpose of this paper is to establish an application platform that addresses expensive development cost and effort of indoor location-aware application (InL-Apps) problems caused by tightly coupling between InL-App and indoor positioning systems (IPSs).

Design/methodology/approach

To achieve this purpose, in this paper, the authors proposes a Web-based integration framework called Web-based Integration Framework for Indoor Location (WIF4InL). With a common data model, WIF4InL integrates indoor location data obtained from heterogeneous IPS. It then provides application-neutral application programming interface (API) for various InL-Apps.

Findings

The authors integrate two different IPS (RedPin and BluePin) using WIF4InL and conduct a comparative study which is based on sufficiency of essential capabilities of location-dependent queries among three systems: RedPin, BluePin and WIF4InL. WIF4InL supports more capabilities for the location-dependent queries. Through the data and operation integration, WIF4InL even enriches the existing proprietary IPS.

Originality/value

As WIF4InL allows the loose coupling between IPS and InL-Apps, it significantly improves reusability of indoor location information and operation.
A study on individual mobility patterns based on individuals’ familiarity to visited areas
Authors: Han Jungkyu , Yamana Hayato
Published: April 2016

Purpose

The purpose of this paper is to clarify the correlations between amount of individual’s knowledge of a specific area and his/her visit pattern to point of interest (POI, interested places) located in the area.

Design/methodology/approach

This paper proposes a visit-frequency-based familiarity estimation method that estimates individuals’ knowledge of areas in a quantitative manner. Based on the familiarity degree, individuals’ visit logs to POIs are divided into a set of groups followed by analyzing the differences among the groups from various points of view, such as user preference, POI categories/popularity, visit time/date and subsequent visits.

Findings

Existence of statistically significant correlations between individuals’ familiarity to areas and their visit patterns is observed by our analysis using 1.4-million POI visit logs collected from a popular location-based social network (LBSN), Foursquare. There exist different skewness of the visit time and visited POI distribution/popularity with regard to the familiarity. For instance, users go to unfamiliar areas on weekends and visit POIs for cultural experiences, such as museums. A notable point is that the correlations can be detected even in the areas in home city, which have not been known so far.

Originality/value

This is the first in-depth work that studies both estimation of individuals’ familiarity and correlations between the familiarity and individuals’ mobility patterns by analyzing massive LBSN data. The methodologies used and the findings of this work can be applicable not only to human mobility analysis for sociology, but also to POI recommendation system design.
Local government transparency index: determinants of municipalities’ rankings
Authors: Araujo Joaquim Filipe Ferraz Esteves de , Tejedo-Romero Francisca
Published: April 2016

Purpose

– Cases of corruption, embezzlement, theft and fraud, abuse of discretion, favoritism, nepotism, clientelism, and abuse of power in governments have led to a growing demand from society to access public information. In response to this demand, governments have been forced to be more transparent in the conduct of their activities. The information transparency index (TI) may be conditioned by economic and political characteristics of local governments affecting the information provided. What factors influenced the index of municipal transparency? Literature about transparency is largely based on the explanations of the agency theory and the legitimacy theory. Based on the postulates of both theories, the purpose of this paper is twofold. First, study the index transparency in Spanish municipalities, and, second, determine the main features that are affecting the index of transparency.

Design/methodology/approach

– Data were collected from Transparency International Spain ranking and from official sources. Univariate and multivariate analysis are performed for the treatment of data.

Findings

– The results shows that political factors like electoral turnout, political ideology, and political competition have a significant effect on the index of transparency. Gender has no significant effect on the index of transparency.

Originality/value

– This study is a contribution to the growing body literature of transparency in order to understand what explains the variations of the TI among municipalities.
Effects of organisational culture on organisational innovation performance in family firms
Authors: Laforet Sylvie
Published: April 2016

Purpose

– The purpose of this paper is to examine the effects of organisational culture (OC) on organisational innovation performance (OIP) in family small and medium-sized enterprises (SMEs). It seeks to establish the type of culture that lead to high innovation performance in family firms.

Design/methodology/approach

– A postal survey of family SMEs across sectors in the UK is conducted. The study employs multiple regression analyses to test which family business culture has an effect on OIP. Among the family business cultures tested are: an external cultural orientation, a flexible and open OC as well as an organisational climate based on open communication and trust, the founder culture, and a long-term cultural orientation.

Findings

– The findings show that a paternalistic and founder culture type do not have a positive effect on family firm innovation performance, but an entrepreneurial-like culture does, i.e. one that is externally oriented, flexible, proactive (refer to an open culture) and long-term oriented. Similarly, an inward focus culture such as, the founder culture impedes innovation; while an outward focus culture such as, an external orientation culture has a positive effect on family firm innovation performance.

Originality/value

– This study makes valuable contributions to the understanding of theory and practices of innovation in family businesses. It provides future research directions.
Determinants of innovation decision in small and medium-sized family enterprises
Authors: Lopez-Fernandez Maria Concepción , Serrano-Bedia Ana Maria , Gómez-López Raquel
Published: April 2016

Purpose

– The purpose of this paper is to contribute to the understanding of the factors that influence small to medium-sized family enterprises (SMFEs) innovation decision.

Design/methodology/approach

– This paper utilises an original data set of 73 SMFEs employing 5-249 people to run binomial logistic regression model which considers the joint effect of both internal and external factors.

Findings

– The results confirm, on the one hand, a significant and positive relationship between the long chief executive officer (CEO) tenure, the prospector and analyser strategic orientation, and the innovation decision in the Spanish family firms. On the other hand, the results confirm a significant and negative relationship between the risk taking, the cost of innovation, the lack of qualified personnel, a customer indifference towards innovation, and the innovation decision in the Spanish SMFEs.

Research limitations/implications

– The results contribute to the development of theoretical and knowledge bases, as well as offering results that will be of interest to research and policy communities. The results are limited to a small sample size, single survey, using cross-sectional data.

Practical implications

– The findings have a bearing on business innovation strategy for policy makers. The results suggest that policy measures that promote long CEO tenures, and the prospector and analyser strategic orientation may have the greatest impact in terms of helping to facilitate innovation decision.

Originality/value

– A novel feature of the model is the consideration of the joint effect of both internal and external factors in SMFEs.
Venture capital funds in transition countries
Authors: Hisrich Robert D. , Petković Saša , Ramadani Veland , Dana Léo-Paul
Published: April 2016

Purpose

– The purpose of this paper is to focus on the possibilities and limitations of venture capital formation in Bosnia and Herzegovina and Macedonia where there has been a lack of success and benefits of small- and medium-sized enterprises (SMEs) from this type of financing.

Design/methodology/approach

– The paper provides a rationale for specific methodological choices and justifies its choice. Both quantitative and qualitative methods were employed. The methods section (research design) explains the entry criteria for the study population, specific imaging techniques and methods of data analysis.

Findings

– Venture capital invest in companies in the beginning to achieve an above average return on investment. Unfortunately, there are no officially registered venture capital funds in Bosnia and Herzegovina. For the venture capital funds to operate, it is necessary to adopt regulations governing this area, to create a favorable tax system and introduce a cash basis for VAT calculation for SMEs. The majority of respondents in the research believe that in the establishment of venture capital funds would provide one of the greatest supports by the governments of these countries, analyzing the economic situation in these countries, it is apparent that there is an under-developed legal and tax system, which does not support SMEs. In order to attract foreign and domestic investors, and form venture capital funds, it is necessary to create a favorable business environment.

Originality/value

– The paper contains novel information and insight into VC funds in two transition economies of Bosnia and Herzegovina and Macedonia.
On Confidence Intervals for the Hazard Ratio in Randomized Clinical Trials
Authors: Lin Dan-Yu , Dai Luyan , Cheng Gang , Sailer Martin Oliver
Published: April 2016

The log-rank test is widely used to compare two survival distributions in a randomized clinical trial, while partial likelihood (Cox, 1975) is the method of choice for making inference about the hazard ratio under the Cox (1972) proportional hazards model. The Wald 95% confidence interval of the hazard ratio may include the null value of 1 when the p-value of the log-rank test is less than 0.05. Peto et al. (1977) provided an estimator for the hazard ratio based on the log-rank statistic; the corresponding 95% confidence interval excludes the null value of 1 if and only if the p-value of the log-rank test is less than 0.05. However, Peto's estimator is not consistent, and the corresponding confidence interval does not have correct coverage probability. In this article, we construct the confidence interval by inverting the score test under the (possibly stratified) Cox model, and we modify the variance estimator such that the resulting score test for the null hypothesis of no treatment difference is identical to the log-rank test in the possible presence of ties. Like Peto's method, the proposed confidence interval excludes the null value if and only if the log-rank test is significant. Unlike Peto's method, however, this interval has correct coverage probability. An added benefit of the proposed confidence interval is that it tends to be more accurate and narrower than the Wald confidence interval. We demonstrate the advantages of the proposed method through extensive simulation studies and a colon cancer study.
Joint Latent Class Model for Longitudinal Data and Interval-Censored Semi-Competing Events: Application to Dementia
Authors: Rouanet Anaïs , Joly Pierre , Dartigues Jean-François , Proust-Lima Cécile , Jacqmin-Gadda Hélène
Published: April 2016

Joint models are used in ageing studies to investigate the association between longitudinal markers and a time-to-event, and have been extended to multiple markers and/or competing risks. The competing risk of death must be considered in the elderly because death and dementia have common risk factors. Moreover, in cohort studies, time-to-dementia is interval-censored since dementia is assessed intermittently. So subjects can develop dementia and die between two visits without being diagnosed. To study predementia cognitive decline, we propose a joint latent class model combining a (possibly multivariate) mixed model and an illness–death model handling both interval censoring (by accounting for a possible unobserved transition to dementia) and semi-competing risks. Parameters are estimated by maximum-likelihood handling interval censoring. The correlation between the marker and the times-to-events is captured by latent classes, homogeneous sub-groups with specific risks of death, dementia, and profiles of cognitive decline. We propose Markovian and semi-Markovian versions. Both approaches are compared to a joint latent-class model for competing risks through a simulation study, and applied in a prospective cohort study of cerebral and functional ageing to distinguish different profiles of cognitive decline associated with risks of dementia and death. The comparison highlights that among subjects with dementia, mortality depends more on age than on duration of dementia. This model distinguishes the so-called terminal predeath decline (among healthy subjects) from the predementia decline.
Robustifying Bayesian Nonparametric Mixtures for Count Data
Authors: Canale Antonio , Prünster Igor
Published: April 2016

Our motivating application stems from surveys of natural populations and is characterized by large spatial heterogeneity in the counts, which makes parametric approaches to modeling local animal abundance too restrictive. We adopt a Bayesian nonparametric approach based on mixture models and innovate with respect to popular Dirichlet process mixture of Poisson kernels by increasing the model flexibility at the level both of the kernel and the nonparametric mixing measure. This allows to derive accurate and robust estimates of the distribution of local animal abundance and of the corresponding clusters. The application and a simulation study for different scenarios yield also some general methodological implications. Adding flexibility solely at the level of the mixing measure does not improve inferences, since its impact is severely limited by the rigidity of the Poisson kernel with considerable consequences in terms of bias. However, once a kernel more flexible than the Poisson is chosen, inferences can be robustified by choosing a prior more general than the Dirichlet process. Therefore, to improve the performance of Bayesian nonparametric mixtures for count data one has to enrich the model simultaneously at both levels, the kernel and the mixing measure.
Agreeing the content of a patient‐reported outcome measure for primary care: a Delphi consensus study
Authors: Murphy Mairead , Hollinghurst Sandra , Salisbury Chris
Published: April 2016

Background

As the first contact for any health‐related need, primary care clinicians often address multiple patient problems, with a range of possible outcomes. There is currently no patient‐reported outcome measure (PROM) which covers this range of outcomes. Therefore, many research studies into primary care services use PROMs that do not capture the full impact of these services.

Objective

The study aim was to identify outcomes sought by primary care patients which clinicians can influence, thus providing the basis for a new primary care PROM.

Methods

We used a Delphi process starting with an outcomes list inductively derived in a prior qualitative study. Thirty‐five experts were recruited into patient, clinician and academic panels. Participants rated each outcome on whether it was (i) relevant to health, (ii) influenced by primary care and (iii) detectable by patients. In each round, outcomes which passed/failed preset levels of agreement were accepted/rejected. Remaining outcomes continued to the next round.

Results

The process resulted in a set of outcomes occupying the domains of health status, health empowerment (internal and external), and health perceptions. Twenty‐six of 36 outcomes were accepted for inclusion in a PROM. Primary care having insufficient influence was the main reason for exclusion.

Conclusions

To our knowledge, this is the first time PROM outcomes have been agreed through criteria which explicitly exclude outcomes less relevant to health, uninfluenced by primary care or undetected by patients. The PROM in development covers a unique set of outcomes and offers an opportunity for enhanced research into primary care.
Zircon U–Pb ages of plutonic rocks in the southern Abukuma Mountains: Implications for Cretaceous geotectonic evolution of the Abukuma Belt
Authors: Takahashi Yutaka , Mikoshiba Masumi , Kubo Kazuya , Iwano Hideki , Danhara Tohru , Hirata Takafumi
Published: April 2016

Plutonic rocks in the southern Abukuma Mountains include gabbro and diorite, fine‐grained diorite, hornblende–biotite granodiorite (Ishikawa, Samegawa, main part of Miyamoto and Tabito, Kamikimita and Irishiken Plutons), biotite granodiorite (the main part of Hanawa Pluton and the Torisone Pluton), medium‐ to coarse‐grained biotite granodiorite and leucogranite, based on the lithologies and geological relations. Zircon U–Pb ages of gabbroic rocks are 112.4 ±1.0 Ma (hornblende gabbro, Miyamoto Pluton), 109.0 ±1.1 Ma (hornblende gabbro, the Hanawa Pluton), 102.7 ±0.8 Ma (gabbronorite, Tabito Pluton) and 101.0 ±0.6 Ma (fine‐grained diorite). As for the hornblende–biotite granodiorite, zircon U–Pb ages are 104.2 ±0.7 Ma (Ishikawa Pluton), 112.6 ±1.0 Ma (Tabito Pluton), 105.2 ±0.8 Ma (Kamikimita Pluton) and 105.3±0.8 Ma (Irishiken Pluton). Also for the medium‐ to fine‐grained biotite granodiorite, zircon U–Pb ages are 106.5±0.9 Ma (Miyamoto Pluton), 105.1 ±1.0 Ma (Hanawa Pluton) and the medium‐ to coarse‐grained biotite granodiorite has zircon U–Pb age of 104.5 ±0.8 Ma. In the case of the leucogranite, U–Pb age of zircon is 100.6 ±0.9 Ma. These data indicate that the intrusion ages of gabbroic rocks and surrounding granitic rocks ranges from 113 to 101 Ma. Furthermore, K–Ar ages of biotite and or hornblende in the same rock samples were dated. Accordingly, it is clear that these rocks cooled down rapidly to 300 °C (Ar blocking temperature of biotite for K–Ar system) after their intrusion. These chronological data suggest that the Abukuma plutonic rocks in the southern Abukuma Mountains region uplifted rapidly around 107 to 100 Ma after their intrusion.
Persistent bone marrow depression following short-term treatment with temozolomide
Authors: Vandraas Kathrine , Tjønnfjord Geir Erland , Johannesen Tom Børge , Brandal Petter
Published: April 2016

Temozolomide (TMZ) is, in combination with radiotherapy (RT), the treatment of choice for glioblastoma multiforme. Although generally well tolerated, haematological side effects are observed in approximately 1–10% of patients receiving TMZ. We report a case of a patient who developed severe bone marrow failure (BMF) after only 3 weeks of concomitant TMZ. The BMF was grave with no signs of improvement for 12 months, resulting in more than 100 transfusions of blood cells.
Evaluation of the correlation between type 1 diabetes and cognitive function in children and adolescents, and comparison of this correlation with structural changes in the central nervous system: a study protocol
Authors: Pourabbasi Ata , Tehrani-Doost Mehdi , Ebrahimi Qavam Soqra , Larijani Bagher
Published: April 2016

Introduction

Diabetes mellitus type 1 (T1DM) affects nearly 15 million children worldwide and failure to achieve and maintain good glycaemic control in this group can lead to diabetes-related complications. Children with T1DM can experience impairment in cognitive function such as memory, attention and executive function. This study is designed to evaluate the correlation between diabetes and cognitive dysfunction as well as to clarify whether this correlation can be linked to neurological structural changes in 6–11-year-old children with diabetes.

Methods and analysis

310 eligible children with diabetes will be divided into two groups based on glycaemic control according to their HbA1c index. The control group will include 150 children aged 6–11 without diabetes. The following parameters will be measured and investigated: duration of the disease since diagnosis, required daily insulin dose, frequency of insulin administration, hospital admissions due to diabetes, hypoglycaemic episodes during the last year, and episodes of diabetic ketoacidosis. The following components of cognitive function will be evaluated: memory, attention, executive function, decision-making and academic performance. Cognitive function and subsequent subtests will be assessed using Cambridge Neuropsychological Test Automated Battery (CANTAB) tools. Brain structural indices such as intracranial vault (ICV), as well as cerebrospinal fluid (CSF), ventricle, hippocampus, total intracranial, total brain, grey matter and white matter volume will be measured using MRI. ANOVA, correlational tests (Spearman) and regression models will be used to evaluate the hypothesis.

Ethics and dissemination

This study is approved by the ethics committee of the Endocrinology and Metabolism Research Institute (EMRI) of Tehran University of Medical Sciences (TUMS) under reference number 00300. Our findings are to be published in a peer-reviewed journal and disseminated both electronically and in print.
Effect of FTY720 (fingolimod) on graft survival in renal transplant recipients: a systematic review protocol
Authors: Gholamnezhadjafari Reza , Falak Reza , Tajik Nader , Aflatoonian Reza , Ali Keshtkar Abbas , Rezaei Abbas
Published: April 2016

Introduction

Studies have shown that FTY720 has inconsistent effects in kidney transplant recipients. Several review articles on FTY720 have been published, but most have focused on the mechanism of action of FTY720. Therefore, this review aims to evaluate and determine the beneficial and harmful effects of FTY720 therapy in kidney transplant recipients.

Methods and analysis

We electronically searched the following databases: PubMed, Scopus, the Web of Sciences, EMBASE, Cochrane databases and the Cochrane Central Registry of Controlled Trials. Any clinical, randomised controlled trials relating to FTY720 for treating kidney transplant recipients were included without publication status or language restriction. Study selection, data extraction and assessment of study quality were performed independently by two researchers. Data were synthesised by either the fixed effects or the random effects model according to a heterogeneity test. If the extracted data were suitable for meta-analysis, STATA software was used to combine the relative risks for dichotomous outcomes, and the mean differences for continuous outcomes with 95% CIs were measured. Death, loss of function and incidence of acute kidney rejection were assessed as the primary outcomes. Renal graft function, malignancy, delayed graft function and infection were evaluated as secondary outcomes.

Ethics/dissemination

This review does not require formal ethics approval because the data are not individualised. The resulting review article will be submitted for publication in a peer-reviewed journal.

Trial registration number

CRD42015024648.
Primary care-led survivorship care for patients with colon cancer and the use of eHealth: a qualitative study on perspectives of general practitioners
Authors: Duineveld Laura A M , Wieldraaijer Thijs , Wind Jan , Verdonck-de Leeuw Irma M , van Weert Henk C P M , van Uden-Kraan Cornelia F
Published: April 2016

Objectives

The aim of this study was to explore the perspectives of general practitioners (GPs) regarding their current and future role in survivorship care of patients with colon cancer, and to assess their perspectives on patients’ self-management capacities and the value of the eHealth application Oncokompas2.0used by patients.

Setting

GPs from the central part of the Netherlands were interviewed at their location of preference.

Participants

20 GPs participated (10 men, 10 women, age range 34–65 years, median age 49.5 years). The median years of experience as a GP was 14.5 years (range 3–34 years).

Results

GPs indicated attempting to keep in contact with patients after colon cancer treatment and mentioned being aware of symptoms of recurrent disease. Most participants would have liked to be more involved and expected to be able to provide survivorship care of colon cancer. Requirements mentioned were agreements with secondary care and a protocol. GPs considered Oncokompas2.0, which stimulates patients to structure their own survivorship care, as a useful additional tool for a specific group of patients (ie, young and highly-educated patients).

Conclusions

Based on the perspectives of the GPs, survivorship care of colon cancer in primary care is deemed feasible and the use of an eHealth application such as Oncokompas2.0is expected to benefit specific groups of patients after colon cancer treatment.
Pathogens in otitis externa: diagnostic techniques to identify secondary causes of ear disease
Authors: Shaw Stephen
Published: April 2016

This article describes the diagnostic techniques needed in the approach to otitis externa in the dog with particular emphasis on the correct identification of microbes causing secondary and perpetuating features of the disease. The common organisms are described, along with the numbers and features that determine whether treatment is necessary, with the emphasis on the correct use of the microscope and cytological interpretation.