78 research outputs found
Az EU-s támogatások és a tagállamok közigazgatásának kapcsolata
Az Európai Unió regionális politikájának intézményi háttere jogszabályokban került lefektetésre. Az intézményrendszer felállÃtása és működtetése az EU-tárgyalásoknak is kiemelt témája volt. A megkövetelt végrehajtási rendszer minden tagállamban – akár régi, akár újonnan csatlakozott – a meglévÅ‘ közigazgatási rendszerre épült. Ugyanakkor nem lényegtelen, hogy mÃg az ún. régi tagállamok, és ezért maga az EU-szabályozás is már az elmúlt 25-35 évben a „New Public Management†eszméjében élt és fejlÅ‘dött, addig az újonnan csatlakozók még az ezredfordulón is inkább egy bürokratikus közigazgatást működtettek, és kevésbé volt jelen a szolgáltatói szemlélet, illetve eredményorientáció. Annak ellenére, hogy az új tagállamok jelentÅ‘s idÅ‘nyomásra állÃtották fel intézményrendszerüket, és a közigazgatási kultúra változása is folyamatosan jelen van még ma is az uniós források felhasználásában (szigorúan pénzügyileg nézve), ez nem okozott hátrányt. A V4 országok a forráslehÃvások tekintetében nem egy régi tagállamot is megelÅ‘znek. Vagyis az az állÃtás, hogy nem tudjuk az EU-s forrásokat felhasználni, megdÅ‘lni látszik (persze a programok jogi, EU általi zárása még hátra van). ----------------------------------------- The institutional background for the Community regional policy was set forth in legal regulations. Setting up and operating the institutional system was a priority topic at the accession negotiations as well. The required implementation system was built on the existing system of public administration in every country, whether old or new Member State. It needs to be pointed out, however, that while the old Member States – and the Community regulations themselves – have existed and developed in an environment infused with the theory of ‘New Public Management’ over the last 25 to 35 years, the new Member States were running a rather bureaucratic public administration system even at the turn of the millennium. The aspects of being a service provider and of focusing on goals were less prominent. Despite the fact that the new Member States were under significant time pressure when setting up their institutional systems, and the culture of public administration is still evolving, utilisation of Community subsidies – from a strictly financial perspective – was not hindered. The V4 countries are ahead of more than one old member state in terms of the proportion of funds called down. There fore the claim that we are unable to utilise the Community funds seems to be overturned (of course the legal closing of the programmes by the Community has not yet been performed).támogatás, közigazgatás, forrásfelhasználás, subsidy, public administration, utilisation of funds, Agricultural and Food Policy, International Development,
Interaction between p22(phox) and Nox4 in the endoplasmic reticulum suggests a unique mechanism of NADPH oxidase complex formation.
The p22(phox) protein is an essential component of the phagocytic- and inner ear NADPH oxidases but its relationship to other Nox proteins is less clear. We have studied the role of p22(phox) in the TGF-beta1-stimulated H2O2 production of primary human and murine fibroblasts. TGF-beta1 induced H2O2 release of the examined cells, and the response was dependent on the expression of both Nox4 and p22(phox). Interestingly, the p22(phox) protein was present in the absence of any detectable Nox/Duox expression, and the p22(phox) level was unaffected by TGF-beta1. On the other hand, Nox4 expression was dependent on the presence of p22(phox), establishing an asymmetrical relationship between the two proteins. Nox4 and p22(phox) proteins localized to the endoplasmic reticulum and their distribution was unaffected by TGF-beta1. We used a chemically induced protein dimerization method to study the orientation of p22(phox) and Nox4 in the endoplasmic reticulum membrane. This technique is based on the rapamycin-mediated heterodimerization of the mammalian FRB domain with the FK506 binding protein. The results of these experiments suggest that the enzyme complex produces H2O2 into the lumen of the endoplasmic reticulum, indicating that Nox4 contributes to the development of the oxidative milieu within this organelle
The NKCC1 ion transporter modulates microglial phenotype and inflammatory response to brain injury in a cell-autonomous manner
The NKCC1 ion transporter contributes to the pathophysiology of common neurological disorders, but its function in microglia, the main inflammatory cells of the brain, has remained unclear to date. Therefore, we generated a novel transgenic mouse line in which microglial NKCC1 was deleted. We show that microglial NKCC1 shapes both baseline and reactive microglia morphology, process recruitment to the site of injury, and adaptation to changes in cellular volume in a cell-autonomous manner via regulating membrane conductance. In addition, microglial NKCC1 deficiency results in NLRP3 inflammasome priming and increased production of interleukin-1 beta (IL-1 beta), rendering microglia prone to exaggerated inflammatory responses. In line with this, central (intracortical) administration of the NKCC1 blocker, bumetanide, potentiated intracortical lipopolysaccharide (LPS)-induced cytokine levels. In contrast, systemic bumetanide application decreased inflammation in the brain. Microglial NKCC1 KO animals exposed to experimental stroke showed significantly increased brain injury, inflammation, cerebral edema, and, worse, neurological outcome. Thus, NKCC1 emerges as an important player in controlling microglial ion homeostasis and inflammatory responses through which microglia modulate brain injury. The contribution of microglia to central NKCC1 actions is likely to be relevant for common neurological disorders.Peer reviewe
Policy instruments for managing road safety on EU-roads
Directive 2008/96/EC on road infrastructure safety management requires the establishment and implementation of procedures relating to road safety impact assessments (RSIA), road safety audits (RSA), ranking of high accident concentration sections and network safety ranking (NSR) and road safety inspections (RSI). The aim of this article is to present the outputs of BALTRIS project. The goal of the international project BALTRIS is to elaborate the road and street infrastructure safety management procedures and teaching material consistently explaining the above mentioned infrastructure management procedures. Four Baltic Sea region countries (Sweden, Estonia, Latvia, and Lithuania), represented by universities and national road administrations participate in the elaboration of these procedures and teaching material. This article describes the scope of NSR, RSA and RSI procedures prepared in the frame of BALTRIS project, also article provides detailed implementation and execution of procedures for the EU Member States. NSR means a method for identifying, analysing and classifying parts of the existing road network according to their potential for safety development and accident cost savings. Ranking of high accident concentration sectionsmeans a method to identify, analyse and rank sections of the road network which have been in operation for 3÷5 years and upon which a large number of fatal/injury accidents in proportion to the traffic flow or compared to respective conditions have occurred. RSI is a strategic comparative analysis of the impact of the new road or a substantial modification to the existing network on the safety performance of the road network. RSA is a formal safety performance examination of the existing or future road or intersection by an independent audit team
Postoperative differences between colonization and infection after pediatric cardiac surgery-a propensity matched analysis
BACKGROUND: The objective of this study was to identify the postoperative risk factors associated with the conversion of colonization to postoperative infection in pediatric patients undergoing cardiac surgery. METHODS: Following approval from the Institutional Review Board, patient demographics, co-morbidities, surgery details, transfusion requirements, inotropic infusions, laboratory parameters and positive microbial results were recorded during the hospital stay, and the patients were divided into two groups: patients with clinical signs of infection and patients with only positive cultures but without infection during the postoperative period. Using propensity scores, 141 patients with infection were matched to 141 patients with positive microbial cultures but without signs of infection. Our database consisted of 1665 consecutive pediatric patients who underwent cardiac surgery between January 2004 and December 2008 at a single center. The association between the patient group with infection and the group with colonization was analyzed after propensity score matching of the perioperative variables. RESULTS: 179 patients (9.3%) had infection, and 253 patients (15.2%) had colonization. The occurrence of Gram-positive species was significantly greater in the colonization group (p=0.004). The C-reactive protein levels on the first and second postoperative days were significantly greater in the infection group (p=0.02 and p=0.05, respectively). The sum of all the positive cultures obtained during the postoperative period was greater in the infection group compared to the colonization group (p=0.02). The length of the intensive care unit stay (p<0.001) was significantly longer in the infection group compared to the control group. CONCLUSIONS: Based on our results, we uncovered independent relationships between the conversion of colonization to infection regarding positive S. aureus and bloodstream results, as well as significant differences between the two groups regarding postoperative C-reactive protein levels and white blood cell counts
Nesfatin-1/NUCB2 as a Potential New Element of Sleep Regulation in Rats.
STUDY OBJECTIVES: Millions suffer from sleep disorders that often accompany severe illnesses such as major depression; a leading psychiatric disorder characterized by appetite and rapid eye movement sleep (REMS) abnormalities. Melanin-concentrating hormone (MCH) and nesfatin-1/NUCB2 (nesfatin) are strongly co - expressed in the hypothalamus and are involved both in food intake regulation and depression. Since MCH was recognized earlier as a hypnogenic factor, we analyzed the potential role of nesfatin on vigilance. DESIGN: We subjected rats to a 72 h-long REMS deprivation using the classic flower pot method, followed by a 3 h-long 'rebound sleep'. Nesfatin mRNA and protein expressions as well as neuronal activity (Fos) were measured by quantitative in situ hybridization technique, ELISA and immunohistochemistry, respectively, in 'deprived' and 'rebound' groups, relative to controls sacrificed at the same time. We also analyzed electroencephalogram of rats treated by intracerebroventricularly administered nesfatin-1, or saline. RESULTS: REMS deprivation downregulated the expression of nesfatin (mRNA and protein), however, enhanced REMS during 'rebound' reversed this to control levels. Additionally, increased transcriptional activity (Fos) was demonstrated in nesfatin neurons during 'rebound'. Centrally administered nesfatin-1 at light on reduced REMS and intermediate stage of sleep, while increased passive wake for several hours and also caused a short-term increase in light slow wave sleep. CONCLUSIONS: The data designate nesfatin as a potential new factor in sleep regulation, which fact can also be relevant in the better understanding of the role of nesfatin in the pathomechanism of depression
Recommendations for patient involvement in health technology assessment in Central and Eastern European countries
IntroductionMeaningful patient involvement in health technology assessment (HTA) is essential in ensuring that the interests of the affected patient population, their families, and the general public are accurately reflected in coverage and reimbursement decisions. Central and Eastern European (CEE) countries are generally at less advanced stages of implementing HTA, which is particularly true for patient involvement activities. As part of the Horizon2020 HTx project, this research aimed to form recommendations for critical barriers to patient involvement in HTA in CEE countries. MethodsBuilt on previous research findings on potential barriers, a prioritisation survey was conducted online with CEE stakeholders. Recommendations for prioritised barriers were formed through a face-to-face workshop by CEE stakeholders and HTx experts. ResultsA total of 105 stakeholders from 13 CEE countries completed the prioritisation survey and identified 12 of the 22 potential barriers as highly important. The workshop had 36 participants representing 9 CEE countries, and 5 Western European countries coming together to discuss solutions in order to form recommendations based on best practices, real-life experience, and transferability aspects. Stakeholder groups involved in both phases included HTA organisation representatives, payers, patients, caregivers, patient organisation representatives, patient experts, health care providers, academic and non-academic researchers, health care consultants and health technology manufacturers/providers. As a result, 12 recommendations were formed specified to the CEE region's context, but potentially useful for a broader geographic audience. ConclusionIn this paper, we present 12 recommendations for meaningful, systematic, and sustainable patient involvement in HTA in CEE countries. Our hope is that engaging more than a hundred CEE stakeholders in the study helped to spread awareness of the importance and potential of patient involvement and that the resulting recommendations provide tangible steps for the way forward. Future studies shall focus on country-specific case studies of the implemented recommendations
Phase 3 trials of ixekizumab in moderate-to-severe plaque psoriasis
BACKGROUND Two phase 3 trials (UNCOVER-2 and UNCOVER-3) showed that at 12 weeks of treatment, ixekizumab, a monoclonal antibody against interleukin-17A, was superior to placebo and etanercept in the treatment of moderate-to-severe psoriasis. We report the 60-week data from the UNCOVER-2 and UNCOVER-3 trials, as well as 12-week and 60-week data from a third phase 3 trial, UNCOVER-1. METHODS We randomly assigned 1296 patients in the UNCOVER-1 trial, 1224 patients in the UNCOVER-2 trial, and 1346 patients in the UNCOVER-3 trial to receive subcutaneous injections of placebo (placebo group), 80 mg of ixekizumab every 2 weeks after a starting dose of 160 mg (2-wk dosing group), or 80 mg of ixekizumab every 4 weeks after a starting dose of 160 mg (4-wk dosing group). Additional cohorts in the UNCOVER-2 and UNCOVER-3 trials were randomly assigned to receive 50 mg of etanercept twice weekly. At week 12 in the UNCOVER-3 trial, the patients entered a long-term extension period during which they received 80 mg of ixekizumab every 4 weeks through week 60; at week 12 in the UNCOVER-1 and UNCOVER-2 trials, the patients who had a response to ixekizumab (defined as a static Physicians Global Assessment [sPGA] score of 0 [clear] or 1 [minimal psoriasis]) were randomly reassigned to receive placebo, 80 mg of ixekizumab every 4 weeks, or 80 mg of ixekizumab every 12 weeks through week 60. Coprimary end points were the percentage of patients who had a score on the sPGA of 0 or 1 and a 75% or greater reduction from baseline in Psoriasis Area and Severity Index (PASI 75) at week 12. RESULTS In the UNCOVER-1 trial, at week 12, the patients had better responses to ixekizumab than to placebo; in the 2-wk dosing group, 81.8% had an sPGA score of 0 or 1 and 89.1% had a PASI 75 response; in the 4-wk dosing group, the respective rates were 76.4% and 82.6%; and in the placebo group, the rates were 3.2% and 3.9% (P<0.001 for all comparisons of ixekizumab with placebo). In the UNCOVER-1 and UNCOVER-2 trials, among the patients who were randomly reassigned at week 12 to receive 80 mg of ixekizumab every 4 weeks, 80 mg of ixekizumab every 12 weeks, or placebo, an sPGA score of 0 or 1 was maintained by 73.8%, 39.0%, and 7.0% of the patients, respectively. Patients in the UNCOVER-3 trial received continuous treatment of ixekizumab from weeks 0 through 60, and at week 60, at least 73% had an sPGA score of 0 or 1 and at least 80% had a PASI 75 response. Adverse events reported during ixekizumab use included neutropenia, candidal infections, and inflammatory bowel disease. CONCLUSIONS In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known
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