Benefits of a marketing cooperative in transition agriculture: Mórakert purchasing and service co-operative

The paper analyses the potential benefits of marketing cooperatives in Hungary, employing a transaction cost economics framework. We found that the purchased quantity, the existence of contracts, flexibility and trust are the most important factors farmers consider when selling their products via a cooperative. The most striking result is that diversification has positive influences on the share of cooperatives in farmers’ sale. Furthermore, farmers with larger bargaining power have less willingness to sell their product to the cooperative. Surprisingly, asset specificity has rather negative effects on the share of cooperatives in members’ sales

Governance and strategy of entrepreneurial networks: an introduction

This special issue focuses on empirical and theoretical papers that help us to better understand the strategy and governance of entrepreneurial networks, such as franchise chains, alliances, and cooperative networks. The following central themes are covered: (I) Which formal governance mechanisms do entrepreneurial networks use in order to reduce transaction cost/agency cost and to increase strategic value? (II) What is the role of relational governance mechanisms (such as information exchange and social ties) for the performance outcomes in franchise chains and cooperatives? (III) Which alliance strategies do entrepreneurial firms pursue to realize a competitive advantage, and what is the impact of resources and capabilities on performance outcomes of entrepreneurial firms. To address these issues, insights from organizational economics (transaction cost theory, agency theory, signaling theory), strategic management perspectives (resource-based, knowledge-based and organizational capabilities theory), entrepreneurship theory and the relational governance view are used

Clinical applications of 7T MRI in the brain

AbstractThis review illustrates current applications and possible future directions of 7Tesla (7T) Magnetic Resonance Imaging (MRI) in the field of brain MRI, in clinical studies as well as clinical practice. With its higher signal-to-noise (SNR) and contrast-to-noise ratio (CNR) compared to lower field strengths, high resolution, contrast-rich images can be obtained of diverse pathologies, like multiple sclerosis (MS), brain tumours, aging-related changes and cerebrovascular diseases. In some of these diseases, additional pathophysiological information can be gained compared to lower field strengths. Because of clear depiction of small anatomical details, and higher lesion conspicuousness, earlier diagnosis and start of treatment of brain diseases may become possible. Furthermore, additional insight into the pathogenesis of brain diseases obtained with 7T MRI could be the basis for new treatment developments. However, imaging at high field comes with several limitations, like inhomogeneous transmit fields, a higher specific absorption rate (SAR) and, currently, extensive contraindications for patient scanning. Future studies will be aimed at assessing the advantages and disadvantages of 7T MRI over lower field strengths in light of clinical applications, specifically the additional diagnostic and prognostic value of 7T MRI

Current Status of Clinical Magnetic Resonance Imaging for Plaque Characterisation in Patients with Carotid Artery Stenosis

AbstractObjectiveThe article aims to provide an overview of the literature that assessed the agreement between magnetic resonance imaging (MRI) and histology for specific carotid plaque characteristics associated with vulnerability in terms of sensitivity and specificity.MethodsA systematic search strategy was conducted in MEDLINE and EMBASE databases resulting in 1084 articles. Finally, we included 17 papers. Due to variation in presentation, especially in MRI and histology methods, a pooled analysis could not be performed.ResultsTwo studies were performed on a 3.0-T MRI scanner; all other studies were performed on a 1.5-T scanner. Most performed sequences were two-dimensional (2D) and three-dimensional (3D) T1-weighted and all histology protocols varied slightly. Our results indicate that calcification, fibrous cap, intraplaque haemorrhage and lipid-rich necrotic cores can be identified with moderate-to-good sensitivity and specificity.ConclusionsBased on current literature, it appears premature for routine application of MRI as an imaging modality to assess carotid plaque characteristics associated with plaque vulnerability. Although MRI still holds promise, clinical application for plaque characterisation would require consensus regarding MRI settings and confirmation by histology. Predefined protocols for histology and MR imaging need to be established

99mTc-sestamibi is a substrate for P-glycoprotein and the multidrug resistance-associated protein.

99mTc-sestamibi (99mTc-MIBI) is a substrate for the P-glycoprotein (P-gp) pump but it is not known whether it is a substrate for the multidrug resistance-associated protein (MRP) pump. Therefore, 99mTc-MIBI was evaluated in the GLC4 cell line and its doxorubicin-resistant MRP-, but not P-gp-, overexpressing GLC4/ADR sublines as well as in the S1 cell line and its MRP-transfected subline S1-MRP. 99mTc-MIBI concentration decreased in the GLC4/ADR sublines with increasing MRP overexpression and was lower in S1-MRP than in S1. 99mTc-MIBI plus vincristine increased 99mTc-MIBI concentration in GLC4 lines compared with 99mTc-MIBI alone. 99mTc-MIBI efflux raised with increasing MRP expression in the GLC4 lines. Glutathione depletion elevated 99mTc-MIBI concentration in GLC4/ADR150x. Cross resistance for 99Tc-MIBI, used to test cytotoxicity of the Tc compound, was observed in GLC4/ADR150x vs GLC4. 99Tc-MIBI induced a synergistic effect on vincristine cytotoxicity in GLC4/ADR150x. These results show that 99mTc-MIBI is involved in MRP-mediated efflux. The fact that 99mTc-MIBI efflux is influenced by MDR1 and MRP expression must be taken into account when this gamma-rays-emitting complex is tested for tumour efflux measurements

The association between frailty and MRI features of cerebral small vessel disease

Frailty is a common syndrome in older individuals that is associated with poor cognitive outcome. The underlying brain correlates of frailty are unclear. The aim of this study was to investigate the association between frailty and MRI features of cerebral small vessel disease in a group of non-demented older individuals. We included 170 participants who were classified as frail (n = 30), pre-frail (n = 85) or non-frail (n = 55). The association of frailty and white matter hyperintensity volume and shape features, lacunar infarcts and cerebral perfusion was investigated by regression analyses adjusted for age and sex. Frail and pre-frail participants were older, more often female and showed higher white matter hyperintensity volume (0.69 [95%-CI 0.08 to 1.31], p = 0.03 respectively 0.43 [95%-CI: 0.04 to 0.82], p = 0.03) compared to non-frail participants. Frail participants showed a non-significant trend, and pre-frail participants showed a more complex shape of white matter hyperintensities (concavity index: 0.04 [95%-CI: 0.03 to 0.08], p = 0.03; fractal dimensions: 0.07 [95%-CI: 0.00 to 0.15], p = 0.05) compared to non-frail participants. No between group differences were found in gray matter perfusion or in the presence of lacunar infarcts. In conclusion, increased white matter hyperintensity volume and a more complex white matter hyperintensity shape may be structural brain correlates of the frailty phenotype

Biomarker qualification at the European Medicines Agency: a review of biomarker qualification procedures from 2008 to 2020

Regulatory qualification of biomarkers facilitates their harmonised use across drug developers, enabling more personalised medicine. This study reviews various aspects of the European Medicines Agency's (EMA) biomarker qualification procedure, including frequency and outcome, common challenges, and biomarker characteristics. Our findings provide insights into EMA's biomarker qualification process and will thereby support future applications. All biomarker-related "Qualification of Novel Methodologies for Medicine Development" procedures that started from 2008 to 2020 were included. Procedural data were extracted from relevant documents and analysed descriptively. In total, 86 biomarker qualification procedures were identified, of which 13 resulted in qualified biomarkers. Whereas initially many biomarker qualification procedures were linked to a single company and specific drug development program, a shift was observed to qualification efforts by consortia. Most biomarkers were proposed (n=45) and qualified (n=9) for use in patient selection, stratification, and enrichment, followed by efficacy biomarkers (37 proposed, 4 qualified). Overall, many issues were raised during qualification procedures, mostly related to biomarker properties and assay validation (in 79% and 77% of all procedures, respectively). Issues related to the proposed context of use and rationale were least common, yet, were still raised in 54% of all procedures. While few qualified biomarkers are currently available, procedures focus increasingly on biomarkers for general use instead of those linked to specific drug compounds. The issues raised during qualification procedures illustrate the thorough discussions taking place between applicants and regulators - highlighting aspects that need careful consideration and underlining the importance of an appropriate validation strategy

Selection of workers and firm heterogeneity

A model based on differences between workers regarding their preferences for wage and leisure drives the heterogeneity of firms result. The more industrious workers are driven to small firms due to free riding in large firms. An industry consisting of small and large firms turns out to produce more output than an industry consisting of only large firms. Some comparative statics results are derived with respect to the size of large firms, the productivity difference between firms, and monitoring capabilities