Wyniki leczenia topiramatem padaczki u osób w podeszłym wieku

Cele. Ocena skuteczności, tolerancji i jakości życia u starszych pacjentów z padaczką, leczonych topiramatem. Metody. Otwarte, trwające rok badanie kliniczne z elastycznym dawkowaniem. Wyniki. Przebadano 107 pacjentów (średni wiek 69 lat; 53% mężczyzn) przez okres 273 &#177; 141 dni. Średnia dawka, którą osiąga- no ostatecznie w monoterapii, wynosiła 98 mg/dobę - w porównaniu z 153 mg/dobę w ramach leczenia wspomagającego. Średnia skumulowana miesięczna częstość napadów padaczkowych zmniejszyła się z 3,7 &#177; 15 do 1,6 &#177; 7,7 (n = 101; p < 0,0001). U 78% pacjentów z napadami padaczkowymi w momencie rozpoczęcia badania (n = 102) osiągnięto przynajmniej 50-procentową redukcję częstości napadów, 44% nie miało napadów w okresie badania. Całkowita punktacja w skali jakości &#348;ycia osób z padaczką (QOLIE-31) poprawiła się z 57 &#177; 17 na 68 &#177; 18 (n = 64; p < 0,0001). Najczęściej zgłaszanymi zdarzeniami niepożądanymi były drgawki, zawroty głowy i zmęczenie. Wnioski. Pacjenci w starszym wieku leczeni topiramatem osiągali wyraźne zmniejszenie liczby napadów padaczkowych i istotną poprawę w zakresie licznych aspektów jakości życia przy dobrej tolerancji leku

The Roles of Standardization, Certification and Assurance Services in Global Commerce

In this article we examine the rapid emergence and expansion of standardized product and process frameworks and a private-sector compliance and enforcement infrastructure that we believe may increasingly be providing a substitute for public and legal regulatory infrastructure in global commerce. This infrastructure is provided by a proliferation of performance codes and standards, many of which define acceptable social and environmental behavior, and a rapidly-growing number of privately-trained and authorized inspectors and certifiers that we call the third-party assurance industry. We offer reasons for this development, evidence of its scope and scale, and then describe the phenomenon in more detail by examining supply chain arrangements in two industries, food products and apparel, where the use of third-party standards and assurance services has expanded especially rapidly. We conclude with a discussion of the implications for the make or buy decision at the core of the theory of the firm. We argue that as quasi-regulatory standards are developed within various industries, and as performance to these standards can be systematically evaluated using third-party inspectors and certifiers, the costs of moving production outside of vertical firm hierarchies drop. We believe this may be an important factor in accelerating the shift to outsourcing that has been observed over the last two decades

Overview of ASDEX upgrade results in view of ITER and DEMO

Experiments on ASDEX Upgrade (AUG) in 2021 and 2022 have addressed a number of critical issues for ITER and EU DEMO. A major objective of the AUG programme is to shed light on the underlying physics of confinement, stability, and plasma exhaust in order to allow reliable extrapolation of results obtained on present day machines to these reactor-grade devices. Concerning pedestal physics, the mitigation of edge localised modes (ELMs) using resonant magnetic perturbations (RMPs) was found to be consistent with a reduction of the linear peeling-ballooning stability threshold due to the helical deformation of the plasma. Conversely, ELM suppression by RMPs is ascribed to an increased pedestal transport that keeps the plasma away from this boundary. Candidates for this increased transport are locally enhanced turbulence and a locked magnetic island in the pedestal. The enhanced D-alpha (EDA) and quasi-continuous exhaust (QCE) regimes have been established as promising ELM-free scenarios. Here, the pressure gradient at the foot of the H-mode pedestal is reduced by a quasi-coherent mode, consistent with violation of the high-n ballooning mode stability limit there. This is suggestive that the EDA and QCE regimes have a common underlying physics origin. In the area of transport physics, full radius models for both L- and H-modes have been developed. These models predict energy confinement in AUG better than the commonly used global scaling laws, representing a large step towards the goal of predictive capability. A new momentum transport analysis framework has been developed that provides access to the intrinsic torque in the plasma core. In the field of exhaust, the X-Point Radiator (XPR), a cold and dense plasma region on closed flux surfaces close to the X-point, was described by an analytical model that provides an understanding of its formation as well as its stability, i.e., the conditions under which it transitions into a deleterious MARFE with the potential to result in a disruptive termination. With the XPR close to the divertor target, a new detached divertor concept, the compact radiative divertor, was developed. Here, the exhaust power is radiated before reaching the target, allowing close proximity of the X-point to the target. No limitations by the shallow field line angle due to the large flux expansion were observed, and sufficient compression of neutral density was demonstrated. With respect to the pumping of non-recycling impurities, the divertor enrichment was found to mainly depend on the ionisation energy of the impurity under consideration. In the area of MHD physics, analysis of the hot plasma core motion in sawtooth crashes showed good agreement with nonlinear 2-fluid simulations. This indicates that the fast reconnection observed in these events is adequately described including the pressure gradient and the electron inertia in the parallel Ohm’s law. Concerning disruption physics, a shattered pellet injection system was installed in collaboration with the ITER International Organisation. Thanks to the ability to vary the shard size distribution independently of the injection velocity, as well as its impurity admixture, it was possible to tailor the current quench rate, which is an important requirement for future large devices such as ITER. Progress was also made modelling the force reduction of VDEs induced by massive gas injection on AUG. The H-mode density limit was characterised in terms of safe operational space with a newly developed active feedback control method that allowed the stability boundary to be probed several times within a single discharge without inducing a disruptive termination. Regarding integrated operation scenarios, the role of density peaking in the confinement of the ITER baseline scenario (high plasma current) was clarified. The usual energy confinement scaling ITER98(p,y) does not capture this effect, but the more recent H20 scaling does, highlighting again the importance of developing adequate physics based models. Advanced tokamak scenarios, aiming at large non-inductive current fraction due to non-standard profiles of the safety factor in combination with high normalised plasma pressure were studied with a focus on their access conditions. A method to guide the approach of the targeted safety factor profiles was developed, and the conditions for achieving good confinement were clarified. Based on this, two types of advanced scenarios (‘hybrid’ and ‘elevated’ q-profile) were established on AUG and characterised concerning their plasma performance

A Study of the Implementation of ISO 14001 Environmental Management Systems in Hong Kong

The ISO 14001 environmental management system (EMS) standard has been adopted in many parts of the world. In order to evaluate current implementation in Hong Kong, a questionnaire survey was conducted of more than 200 local companies. ISO 14001 EMS adoption is still slow in Hong Kong, particularly for small and medium-sized enterprises (SMEs). The majority of SMEs do not have plans to implement the standard in the near future. However, the EMS standard has brought many advantages to the local ISO 14001 EMS certified companies, including the reduction of operating costs and the improvement of working efficiency. Recommendations are made for EMS standard implementation in local organizations, particularly SMEs.

Variants in the neuronal nitric oxide synthase (nNOS, NOS1) gene are associated with restless legs syndrome.

Sixty percent of the patients with restless legs syndrome (RLS) report a positive family history. To date five loci have been mapped on chromosome 12q, 14q, 9p, 2q, and 20p (RLS1-5) but no gene has been identified so far. To identify genes related to RLS, we performed a three-stage association study (explorative study, replication study, high-density mapping) in two Caucasian RLS case-control samples of altogether 918 independent cases and controls. In the explorative study (367 cases and controls, respectively), we screened 1536 SNPs in 366 genes in a 21 Mb region encompassing the RLS1 critical region on chromosome 12. Armitage trend test revealed three genomic regions that were significant (P &lt; 0.05). In the replication study (551 cases and controls, respectively) we genotyped the most significant SNPs of Stage 1. After correction for multiple testing, association was observed with SNP rs7977109 (P(nominal) = 0.00175, P(Westfall-Young) = 0.04895, OR = 0.76228, 95% CI = 0.64310-0.90355), which is in the neuronal nitric oxide synthase (NOS1) gene. High-density mapping using altogether 34 tagging and coding SNPs of the NOS1 gene in both case-control samples further confirmed the significant association results to NOS1. Ten more SNPs revealed significance with nominal P-values from 0.0001 to 0.0482 (genotypic test and Armitage test). Altogether, this study provides evidence for an association of variants in the NOS1 gene and RLS, and suggests the involvement of the NO/arginine pathway in the pathogenesis of RLS. Potential usage of NO modulating agents as new treatment options for RLS have become a challenging aspect for future research of this disorder