2,897 research outputs found
Особенности социальной ответственности малых и средних предприятий
Рассмотрены особенности деятельности малых и средних предприятий, их отличия от крупных предприятий, особенности и проблемы развития социальной ответственности малого и среднего бизнеса в Украине.Розглянуто особливості діяльності малих і середніх підприємств, їх відмінності від великих підприємств, особливості та проблеми розвитку соціальної відповідальності малого і середнього бізнесу в Україні.The paper examines features of small and middle enterprises activities and their distinction from big enterprises. The problems concerning development of social responsibility of small and middle business in Ukraine are also considered in the article
Safety and effectiveness of edoxaban in a real-world clinical setting: Two-year follow-up of the ETNA-AF-Europe study
Abstract
Funding Acknowledgements
Type of funding sources: Private company. Main funding source(s): Daiichi Sankyo Europe
OnBehalf
ETNA-AF-Europe investigators
Background
Oral anticoagulation (OAC) for stroke prevention is essential in the management of patients with atrial fibrillation (AF). The assessment of OAC use in routine clinical care and the effects of this therapy on outcomes and safety are important. Purpose: We analysed two-year outcome data with adjudicated follow-up results in 13,417 patients with AF treated with edoxaban. Methods: ETNA-AF-Europe (Clinicaltrials.gov: NCT02944019) enrolled 13,417 consecutive patients with AF treated with edoxaban in 825 centres in 10 European countries and 2-year prospectively collected, real world data is presented. Results: Edoxaban was prescribed according to licence recommendations in 83.1% (n = 11,146) of patients (Table). Whilst three quarters of patients were prescribed edoxaban 60 mg (n = 10,248, 76.4%), the quarter prescribed edoxaban 30 mg were older (79.5 versus 71.8 years), had a higher stroke risk (CHA2DS2-VASc score: 3.9 versus 3.0) and a higher bleeding risk (HAS-BLED score: 2.9 versus 2.4). Thromboembolic and bleeding events were more common in patients receiving edoxaban 30 mg OD without differences in intracranial haemorrhage (ICH) (Figure). Patients prescribed a non-recommended dose of edoxaban had a numerically higher stroke risk (CHA2DS2-VASc score: 3.6 versus 3.1) with subsequent higher rates of ischemic stroke and mortality, however they also had higher bleeding rates, with the exception of ICH (table) despite a similar initial bleeding risk (HAS-BLED score: 2.7 versus 2.5). Conclusions: In this large, European data set reporting two-year outcomes on edoxaban therapy, no additional safety signals were observed and event rates were in line with those observed in ETNA-AF after 1 year and in ENGAGE AF-TIMI 48, re-affirming the safety and effectiveness of edoxaban licence recommendations in a real world setting of patients with AF. All key events of interest, other than intracranial haemorrhage, were numerically lower in patients prescribed the licenced recommended dose. Outcomes with rec. vs non-rec. dosesn (%/year [95%CI])Recommended dose (n = 11,146; 83.1%)Non-recommended dose (n = 2271; 16.9%)Any stroke/SEE138 (0.68 [0.57;0.80])31 (0.76 [0.51;1.07])Ischaemic stroke99 (0.48 [0.39;0.59])26 (0.63 [0.41; 0.93])Major bleeding189 (0.93 [0.80;1.07])49 (1.20 [0.89;1.59])Intracranial haemorrhage43 (0.21 [0.15;0.28])7 (0.17 [0.07;0.35])All-cause mortality729 (3.55 [3.30;3.82])208 (5.04 [4.38;5.78])CV mortality405 (1.97 [1.79;2.18])113 (2.74 [2.26;3.30])CI, confidence interval; CV, cardiovascular; rec., recommended; SEE, systemic embolic event.Abstract Figure. Annualised event rates at 2-year F
Beyond humanization and de-immunization: tolerization as a method for reducing the immunogenicity of biologics
Immune responses to some monoclonal antibodies (mAbs) and biologic proteins interfere with their efficacy due to the development of anti-drug antibodies (ADA). In the case of mAbs, most ADA target ‘foreign’ sequences present in the complementarity determining regions (CDRs). Humanization of the mAb sequence is one approach that has been used to render biologics less foreign to the human immune system. However, fully human mAbs can also drive immunogenicity. De-immunization (removing epitopes) has been used to reduce biologic protein immunogenicity. Here, we discuss a third approach to reducing the immunogenicity of biologics: introduction of Treg epitopes that stimulate Treg function and induce tolerance to the biologic protein. Supplementing humanization (replacing xenosequences with human) and de-immunization (reducing T effector epitopes) with tolerization (introducing Treg epitopes) where feasible, as a means of improving biologics ‘quality by design’, may lead to the development of ever more clinically effective, but less immunogenic, biologics
Verified and potential pathogens of predatory mites (Acari: Phytoseiidae)
Several species of phytoseiid mites (Acari: Phytoseiidae), including species of the genera Amblyseius, Galendromus, Metaseiulus, Neoseiulus, Phytoseiulus and Typhlodromus, are currently reared for biological control of various crop pests and/or as model organisms for the study of predator¿prey interactions. Pathogen-free phytoseiid mites are important to obtain high efficacy in biological pest control and to get reliable data in mite research, as pathogens may affect the performance of their host or alter their reproduction and behaviour. Potential and verified pathogens have been reported for phytoseiid mites during the past 25 years. The present review provides an overview, including potential pathogens with unknown host effects (17 reports), endosymbiotic Wolbachia (seven reports), other bacteria (including Cardinium and Spiroplasma) (four reports), cases of unidentified diseases (three reports) and cases of verified pathogens (six reports). From the latter group four reports refer to Microsporidia, one to a fungus and one to a bacterium. Only five entities have been studied in detail, including Wolbachia infecting seven predatory mite species, other endosymbiotic bacteria infecting Metaseiulus (Galendromus, Typhlodromus) occidentalis (Nesbitt), the bacterium Acaricomes phytoseiuli infecting Phytoseiulus persimilis Athias-Henriot, the microsporidium Microsporidium phytoseiuli infecting P. persimilis and the microsporidium Oligosproridium occidentalis infecting M. occidentalis. In four cases (Wolbachia, A. phytoseiuli, M. phytoseiuli and O. occidentalis) an infection may be connected with fitness costs of the host. Moreover, infection is not always readily visible as no obvious gross symptoms are present. Monitoring of these entities on a routine and continuous basis should therefore get more attention, especially in commercial mass-production. Special attention should be paid to field-collected mites before introduction into the laboratory or mass rearing, and to mites that are exchanged among rearing facilities. However, at present general pathogen monitoring is not yet practical as effects of many entities are unknown. More research effort is needed concerning verified and potential pathogens of commercially reared arthropods and those used as model organisms in research
Metabolic pathway alignment between species using a comprehensive and flexible similarity measure
Comparative analysis of metabolic networks in multiple species yields important information on their evolution, and has great practical value in metabolic engineering, human disease analysis, drug design etc. In this work, we aim to systematically search for conserved pathways in two species, quantify their similarities, and focus on the variations between themElectrical Engineering, Mathematics and Computer Scienc
Nutri-RecQuest: a web-based search engine on current micronutrient recommendations
Background: The EURRECA (EURopean micronutrient RECommendations Aligned) Network of Excellence collated current micronutrient recommendations. A user-friendly tool, Nutri-RecQuest, was developed to allow access to the collated data and to create a database source for use in other nutritional software tools. Methods: Recommendations, that is, intakes of micronutrients sufficient to meet the requirements of the majority of healthy individuals of that population, from 37 European countries/organizations and eight key non-European countries/regions comprising 29 micronutrients were entered into a database. General information on the source of the recommendations, as well scientific background information, was added. Results: A user-friendly web-based interface was developed to provide efficient search, comparison, display, print and export functions. Conclusion: Easy access to existing recommendations through the web-based tool may be valuable for bodies responsible for setting recommendations, as well as for users of recommendations including scientists, policy makers, health professionals and industry. Adding related dietary reference values such as average nutrient requirements and upper limits may extend the utility of the tool. European Journal of Clinical Nutrition (2010) 64, S43-S47; doi:10.1038/ejcn.2010.6
Fluctuations in granular gases
A driven granular material, e.g. a vibrated box full of sand, is a stationary
system which may be very far from equilibrium. The standard equilibrium
statistical mechanics is therefore inadequate to describe fluctuations in such
a system. Here we present numerical and analytical results concerning energy
and injected power fluctuations. In the first part we explain how the study of
the probability density function (pdf) of the fluctuations of total energy is
related to the characterization of velocity correlations. Two different regimes
are addressed: the gas driven at the boundaries and the homogeneously driven
gas. In a granular gas, due to non-Gaussianity of the velocity pdf or lack of
homogeneity in hydrodynamics profiles, even in the absence of velocity
correlations, the fluctuations of total energy are non-trivial and may lead to
erroneous conclusions about the role of correlations. In the second part of the
chapter we take into consideration the fluctuations of injected power in driven
granular gas models. Recently, real and numerical experiments have been
interpreted as evidence that the fluctuations of power injection seem to
satisfy the Gallavotti-Cohen Fluctuation Relation. We will discuss an
alternative interpretation of such results which invalidates the
Gallavotti-Cohen symmetry. Moreover, starting from the Liouville equation and
using techniques from large deviation theory, the general validity of a
Fluctuation Relation for power injection in driven granular gases is
questioned. Finally a functional is defined using the Lebowitz-Spohn approach
for Markov processes applied to the linear inelastic Boltzmann equation
relevant to describe the motion of a tracer particle. Such a functional results
to be different from injected power and to satisfy a Fluctuation Relation.Comment: 40 pages, 18 figure
European micronutrient recommendations aligned: a general framework developed by EURRECA
Background: In Europe, micronutrient recommendations have been established by (inter)national committees of experts and are used by public health-policy decision makers to monitor and assess the adequacy of the diets of population groups. Current micronutrient recommendations are, however, heterogeneous, whereas the scientific basis for this is not obvious. Alignment of setting micronutrient recommendations is necessary to improve the transparency of the process, the objectivity and reliability of recommendations that are derived by diverse regional and (inter)national bodies. Objective: This call for alignment of micronutrient recommendations is a direct result of the current sociopolitical climate in Europe and uncovers the need for an institutional architecture. There is a need for evidence-based policy making, transparent decision making, stakeholder involvement and alignment of policies across Europe. Results: In this paper, we propose a General Framework that describes the process leading from assessing nutritional requirements to policy applications, based on evidence from science, stakeholder interests and the sociopolitical context. The framework envisions the derivation of nutrient recommendations as scientific methodology, embedded in a policy-making process that also includes consumer issues, and acknowledges the influences of the wider sociopolitical context by distinguishing the principal components of the framework: (a) defining the nutrient requirements for health, (b) setting nutrient recommendations, (c) policy options and (d) policy applications. Conclusion: The General Framework can serve as a basis for a systematic and transparent approach to the development and review of micronutrient requirements in Europe, as well as the decision making of scientific advisory bodies, policy makers and stakeholders involved in this process of assessing, developing and translating these recommendations into public health nutrition policy. European Journal of Clinical Nutrition (201 0) 64, S2-510; doi:10.1038/ejcn.2010.5
Gender perspectives on views and preferences of older people on exercise to prevent falls: a systematic mixed studies review
Background: To offer fall prevention exercise programs that attract older people of both sexes there is a need to understand both womens and mens views and preferences regarding these programs. This paper aims to systematically review the literature to explore any underlying gender perspectives or gender interpretations on older peoples views or preferences regarding uptake and adherence to exercise to prevent falls. Methods: A review of the literature was carried out using a convergent qualitative design based on systematic searches of seven electronic databases (PubMed, CINAHL, Amed, PsycINFO, Scopus, PEDro, and OTseeker). Two investigators identified eligible studies. Each included article was read by at least two authors independently to extract data into tables. Views and preferences reported were coded and summarized in themes of facilitators and barriers using a thematic analysis approach. Results: Nine hundred and nine unique studies were identified. Twenty five studies met the criteria for inclusion. Only five of these contained a gender analysis of mens and womens views on fall prevention exercises. The results suggests that both women and men see women as more receptive to and in more need of fall prevention messages. The synthesis from all 25 studies identified six themes illustrating facilitators and six themes describing barriers for older people either starting or adhering to fall prevention exercise. The facilitators were: support from professionals or family; social interaction; perceived benefits; a supportive exercise context; feelings of commitment; and having fun. Barriers were: practical issues; concerns about exercise; unawareness; reduced health status; lack of support; and lack of interest. Considerably more women than men were included in the studies. Conclusion: Although there is plenty of information on the facilitators and barriers to falls prevention exercise in older people, there is a distinct lack of studies investigating differences or similarities in older womens and mens views regarding fall prevention exercise. In order to ensure that fall prevention exercise is appealing to both sexes and that the inclusion of both men and women are encouraged, more research is needed to find out whether gender differences exists and whether practitioners need to offer a range of opportunities and support strategies to attract both women and men to falls prevention exercise.Funding Agencies|Swedish Research Council [2015-03481]; Strategic Research Programme in Care Sciences, Umea University; Karolinska Institute, Sweden; Umea University</p
Cleavage of von Willebrand Factor by Granzyme M Destroys Its Factor VIII Binding Capacity
Von Willebrand factor (VWF) is a pro-hemostatic multimeric plasma protein that promotes platelet aggregation and stabilizes coagulation factor VIII (FVIII) in plasma. The metalloproteinase ADAMTS13 regulates the platelet aggregation function of VWF via proteolysis. Severe deficiency of ADAMTS13 is associated with thrombotic thrombocytopenic purpura, but does not always correlate with its clinical course. Therefore, other proteases could also be important in regulating VWF activity. In the present study, we demonstrate that VWF is cleaved by the cytotoxic lymphocyte granule component granzyme M (GrM). GrM cleaved both denaturated and soluble plasma-derived VWF after Leu at position 276 in the D3 domain. GrM is unique in that it did not affect the multimeric size and pro-hemostatic platelet aggregation ability of VWF, but instead destroyed the binding of VWF to FVIII in vitro. In meningococcal sepsis patients, we found increased plasma GrM levels that positively correlated with an increased plasma VWF/FVIII ratio in vivo. We conclude that, next to its intracellular role in triggering apoptosis, GrM also exists extracellularly in plasma where it could play a physiological role in controlling blood coagulation by determining plasma FVIII levels via proteolytic processing of its carrier VWF
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