Tiagabine add‐on for drug‐resistant partial epilepsy

Cochrane Database Syst Rev. 2002;(3):CD001908. Tiagabine add-on for drug-resistant partial epilepsy. Pereira J, Marson AG, Hutton JL. Servico de Neurologia, Hospital de Santo Antonio, Largo Prof. Abel Salazar, 4099-001 Porto, Portugal. [email protected] Abstract BACKGROUND: Epilepsy is a common neurological condition, affecting almost 0.5 to 1 per cent of the population. Nearly 30 per cent of people with epilepsy are resistant to currently available drugs. Tiagabine is one of the newer antiepileptic drugs and its effects as an adjunct (add-on) to standard drugs is assessed in this review. OBJECTIVES: To evaluate the effects of add-on treatment with tiagabine upon seizures, side effects, cognition and quality of life for people with drug-resistant localization related seizures. SEARCH STRATEGY: We searched the Cochrane Epilepsy Group trials register (28 March 2002), the Cochrane Controlled Trials Register (Cochrane Library Issue 1, 2002), MEDLINE (1966 to November 2001). In addition, we contacted Sanofi~Synthelabo (makers of tiagabine) and experts in the field to seek any unpublished or ongoing studies. SELECTION CRITERIA: Randomized placebo controlled add-on trials of people of any age with localization related seizures, in which an adequate method of concealment of randomization was used. The studies could be double, single or unblinded and be of parallel or crossover design. They had to have a minimum treatment period of eight weeks. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted data. Any disagreements were resolved by discussion. Outcomes investigated included 50 per cent or greater reduction in seizure frequency; treatment withdrawal; side effects; effects on cognition and quality of life. The primary analyses were by intention-to-treat. Worst case and best case analyses were also calculated for seizure outcomes. Dose response was evaluated in regression models. MAIN RESULTS: Three parallel group and two crossover group trials were included. The overall relative risk (RR) for a 50 per cent or greater reduction in seizure frequency (tiagabine versus placebo) was 3.16(95% confidence interval 1.97 to 5.07). Due to differences in response rates among trials, regression models were unable to provide reliable estimates of responses to individual doses. The RR for treatment withdrawal was 1.81(95% confidence interval 1.25 to 2.62). The 99% confidence interval for the following side effects: dizziness; fatigue; nervousness and tremor did not include unity, indicating that they are significantly associated with tiagabine. For cognitive and quality of life outcomes the limited data available suggested that there were no significant effects on cognition and mood and adjustment. REVIEWER'S CONCLUSIONS: Tiagabine reduces seizures frequency but is associated with some side effects when used as an add-on for people with drug-resistant localization related seizures. PMID: 12137637 [PubMed - indexed for MEDLINE] Publication Types, MeSH Terms, SubstancesPublication Types: Review MeSH Terms: Anticonvulsants/adverse effects Anticonvulsants/therapeutic use* Drug Resistance Epilepsies, Partial/drug therapy* Humans Nipecotic Acids/adverse effects Nipecotic Acids/therapeutic use* Substances: Anticonvulsants Nipecotic Acids tiagabine LinkOut - more resource

Lean Six Sigma Approach to Improve the Production Process in the Mould Industry: a Case Study

Purpose: The purpose of this article is to explore the optimization of internal process is assumed as a critical factor to be capable of answering to the moulds industries. Consequently, it has been considered essential to adopt high-valued methodologies to support tooling industry in order to achieve global competitive advantages. For that purpose, this work aims to apply LEAN principles and techniques to support mould design and manufacturing processes. Methodology/Approach: The methodology used was based on PDCA/DMAIC, with the following stages: Define, Measure, Analyze, Improve and Control. For each stages was taken some of Lean Six Sigma techniques, such as Continuous Improvement, Value Stream Mapping, Pareto analysis and Overall Equipment Effectiveness. Findings: This study results was revealed that there are many areas on the organizations in the Mould Industry, when they utilize otimizations tools obtain hugt successes. With the Pareto analysis was carried out to show that events that contributes the most to the stops. The results were: unavailability of the operator (16.4%), programming the machine (14.4%) and tool exchange (12.4%) In the case of this Mould Industry study was obtained for the CNC machines studies, with the implementation of Lean Six Sigma tools as obtained a improvement about 20% of global OEE. Research Limitation/implication: This research was revealed that there the moulds are Project unique and difficult to analyze. Moreover, this paper reports that the approach LEAN Six Sigma is very interesting for the continuous improvement of processes and profitability of moulds industry. Originality/Value of paper: This research highlight areas of future research using of quality management methods and Lean Six Sigma tools to analyse and optimize production in the moulds industry. Therefore this research It is considered to promote and adopt high-valued methodologies to support tooling industry in order to achieve global competitive advantages.info:eu-repo/semantics/publishedVersio

Use of a total traffic count metric to investigate the impact of roadways on asthma severity: A case-control study

Background: This study had two principal objectives: (i) to investigate the relationship between asthma severity and proximity to major roadways in Perth, Western Australia; (ii) to demonstrate a more accurate method of exposure assessment for traffic pollutants using an innovative GIS-based measure that fully integrates all traffic densities around subject residences. Methods. We conducted a spatial case-control study, in which 'cases' were defined as individuals aged under 19 years of age with more severe asthma (defined here as two or more emergency department contacts with asthma in a defined 5-year period) versus age- and gender-matched 'controls' with less severe asthma (defined here as one emergency department contact for asthma). Traffic exposures were measured using a GIS-based approach to determine the lengths of the roads falling within a buffer area, and then multiplying them by their respective traffic counts. Results: We examined the spatial relationship between emergency department contacts for asthma at three different buffer sizes: 50 metres, 100 metres and 150 metres. No effect was noted for the 50 metre buffer (OR = 1.07; 95% CI: 0.91-1.26), but elevated odds ratios were observed with for crude (unadjusted) estimates OR = 1.21 (95% CI: 1.00-1.46) for 100 metre buffers and OR = 1.25 (95% CI: 1.02-1.54) for 150 metre buffers. For adjusted risk estimates, only the 150 metre buffer yielded a statistically significant finding (OR = 1.24; 95% CI:1.00-1.52). Conclusions: Our study revealed a significant 24% increase in the risk of experiencing multiple emergency department contacts for asthma for every log-unit of traffic exposure. This study provides support for the hypothesis that traffic related air pollution increases the frequency of health service contacts for asthma. This study used advanced GIS techniques to establish traffic-weighted buffer zones around the geocoded residential location of subjects to provide an accurate assessment of exposure to traffic emissions, thereby providing a quantification of the ranges over which pollutants may exert a health effect

Experimental tests and numerical simulation of fire fighter clothing exposed to radiant heat

Neste artigo é apresentado um estudo de avaliação do comportamento de um conjunto muito significativo, de tecidos para proteção individual de segurança de bombeiros, quando submetidos a uma fonte de calor radiante. São apresentados ensaios experimentais desenvolvidos na Universidade de Tsinghua (TU, China) e no Instituto Politécnico de Bragança (IPB, Portugal). São apresentados os resultados de 84 ensaios experimentais no IPB, sendo 72 ensaios realizados para baixos níveis de fluxo de calor incidente (5 [kW/m2]) e 12 ensaios realizados para níveis médios de fluxo de calor incidente (20 kW/m2]). Estes ensaios permitiram determinar qual a melhor combinação de proteção para diferentes conjuntos de materiais com 3 camadas (camada exterior com 6 tecidos diferentes, barreira térmica com 4 tecidos diferentes e camada interior com 3 tecidos diferentes). A melhor combinação foi determinada pelo conjunto de material que apresentava menor densidade de fluxo de calor transmitido (TB3/BT2/F1 para baixos níveis de densidade de fluxo radiante e TB1/BT2/F1 para níveis médios de densidade de fluxo radiante). É ainda apresentado um estudo numérico 2D, não linear transiente, para baixos e médios níveis de densidades de fluxo de calor incidente. O modelo numérico foi validado com os ensaios realizados na Universidade de Tsinghua. Estes resultados permitiram concluir que existe uma relação não linear entre o fluxo de calor incidente e o fluxo de calor transmitido, tendo em consideração o estudo paramétrico.This paper presents the results of a very significant number of radiant heat tests on different fabrics assemblies for individual fire safety protection. Experimental tests developed at Tsinghua University (TU, China) and at the Polytechnic Institute of Bragança (IPB, Portugal) are presented. A total of 84 experimental tests were carried out at IPB, of which 72 were performed for low incident heat flux level (5 [kW/m2]) and 12 tests for medium incident heat flux level (20 [kW/m2]). These tests allowed to determine the best combination of protection for different assemblies of materials with 3 layers (outer layer with 6 different fabrics, thermal barrier with 4 different fabrics and inner layer with 3 different fabrics). The best combination was determined by the assembly with the lowest transmitted heat flux density (TB3/BT2/F1 for low radiation level and TB1/BT2/F1 for the medium radiation level). A two-dimensional nonlinear transient numerical model for low and medium incident heat flux is also presented. The numerical model was validated with the experimental tests performed at Tsinghua University. These results led to the conclusion that there is a nonlinear relationship between the incident heat flux and the transmitted heat flux, based on the parametric study.info:eu-repo/semantics/publishedVersio

Generalised second law of thermodynamics for interacting dark energy in the DGP brane world

In this paper, we investigate the validity of the generalized second law of thermodynamics (GSLT) in the DGP brane world when universe is filled with interacting two fluid system: one in the form of cold dark matter and other is holographic dark energy. The boundary of the universe is assumed to be enclosed by the dynamical apparent horizon or the event horizon. The universe is chosen to be homogeneous and isotropic FRW model and the validity of the first law has been assumed here

Untargeted metabolomics and in vitro functional analysis unravel the intraspecific bioactive potential of flowers from underexplored Camellia japonica cultivars facing their industrial application

The Camellia genus comprises a vast array of underexplored medicinal plants that merit a systematic valorization to exploit their potential as natural sources of phytochemicals with associated health-promoting properties. In this work, flower extracts from eight poorly characterized Camellia japonica L. cultivars were subjected to polyphenol profiling through untargeted metabolomics combined with in vitro functional analysis. Anthocyanins, mostly represented by cyanidin 3-O-glycosides, flavones, and flavonols, were found as the major constituents of C. japonica flowers, together with hydroxycinnamic acids, tyrosols, alkylphenols, and stilbenes, which were detected for the first time in this species. The application of multivariate statistics revealed a flower colordependent fingerprint of C. japonica cultivars, featuring anthocyanins and other flavonoids as metabolite markers associated with color-flowered cultivars with respect to white-flowered ones. The accumulation of anthocyanins, especially reported in ‘Eugenia de Montijo’ flowers, was highly correlated with the cytotoxic and anti-inflammatory properties of the derived extracts, including AGS, Caco-2, and MCF7 cancer cell lines. Moreover, the flavones accumulation reported in ‘Carolyn Tuttle’ extracts was also associated with high rates of free-radical scavenging activity, as well as a potent cytotoxicity against the Caco-2 cell line. In general, C. japonica anthocyanin-enriched flower extracts were revealed as promising candidates for the industrial production of polyphenols with associated biological activities of high interest for critical sectors in the food, pharmaceutical, and cosmetic industries.The research leading to these results was supported by MICINN supporting the Ramón y Cajal grant for M.A.-P. (RYC-2017–22891) and the Juan de la Cierva Formación grant for T.-O. (FJC2019–042549-I). The authors acknowledge Xunta de Galicia for funding the post-doctoral grant of L. C. (ED481B-2021/152) and the program EXCELENCIAED431F 2020/12, which supported the work by F.C. The authors are also grateful to the Foundation for Science and Technology (FCT, Portugal) for financial support through national funds FCT/MCTES (PIDDAC) to CIMO (UIDB/00690/2020 and UIDP/00690/2020) and SusTEC (LA/P/0007/2020), and national funding by FCT, P.I., through the institutional scientific employment program contract for L.-B. and R. C.-C. The work by P.G.-P. was financed by the Spanish Ministry of Universities under the application 33.50.460A.752 and by the European Union NextGenerationEU/PRTR through a Margarita Salas contract by the Universidade de Vigo.info:eu-repo/semantics/publishedVersio

Validity of the Generalized Second Law of Thermodynamics of the Universe Bounded by the Event Horizon in Holographic Dark Energy Model

In this letter, we investigate the validity of the generalized second law of thermodynamics of the universe bounded by the event horizon in the holographic dark energy model. The universe is chosen to be homogeneous and isotropic and the validity of the first law has been assumed here. The matter in the universe is taken in the form of non-interacting two fluid system- one component is the holographic dark energy model and the other component is in the form of dust.Comment: 8 page

The transcription factor Snf1p is involved in a Tup1p-independent manner in the glucose regulation of the major methanol metabolism genes of Hansenula polymorpha

Hansenula polymorpha is a methylotrophic yeast widely employed in biotechnology as a ''protein factory''. Most promoters used for heterologous protein expression, like MOX (methanol oxidase) and DAS (di-hydroxy acetone synthase), are involved in the peroxisomal methanol metabolism (C1 metabolism) and are under strong glucose repression. Interestingly, the MOX promoter is subjected to glucose regulation also in Saccharomyces cerevisiae, a non-methylotrophic yeast in which this phenomenon is well studied. In this species, the transcription factor Tup1p plays an essential role in glucose repression of several genes. This effect is counteracted by the activator Snf1p when glucose is exhausted from medium. Therefore, to test whether this regulatory circuit has been conserved in H. polymorpha, HpTUP1 and HpSNF1 were partially cloned and disrupted. Deletion of HpTUP1 did not affect glucose repression of the major C1 metabolism genes (MOX, DAS). Thus, though conserved, HpTUP1 does not seem to take part in a general glucose repression in H. polymorpha. In contrast, the deletion of HpSNF1 led to significant decreases in the activation of these genes in the absence of glucose. Therefore, the effect of HpSNF1 in transcriptional activation may be through an HpTUP1- independent circuit.521528Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP

Klein tunneling in graphene: optics with massless electrons

This article provides a pedagogical review on Klein tunneling in graphene, i.e. the peculiar tunneling properties of two-dimensional massless Dirac electrons. We consider two simple situations in detail: a massless Dirac electron incident either on a potential step or on a potential barrier and use elementary quantum wave mechanics to obtain the transmission probability. We emphasize the connection to related phenomena in optics, such as the Snell-Descartes law of refraction, total internal reflection, Fabry-P\'erot resonances, negative refraction index materials (the so called meta-materials), etc. We also stress that Klein tunneling is not a genuine quantum tunneling effect as it does not necessarily involve passing through a classically forbidden region via evanescent waves. A crucial role in Klein tunneling is played by the conservation of (sublattice) pseudo-spin, which is discussed in detail. A major consequence is the absence of backscattering at normal incidence, of which we give a new shorten proof. The current experimental status is also thoroughly reviewed. The appendix contains the discussion of a one-dimensional toy model that clearly illustrates the difference in Klein tunneling between mono- and bi-layer graphene.Comment: short review article, 18 pages, 14 figures; v3: references added, several figures slightly modifie