Levetiracetam circulating concentrations and response in status epilepticus.

Intravenous levetiracetam (LEV) is broadly used in the treatment of status epilepticus (SE). A loading dose is usually infused, aiming to reach quickly the range of plasma concentrations considered as therapeutic (12-46 mg/l). The aim of the study was to evaluate the response to LEV in SE, correlated exposure assessed by plasma concentration monitoring, as well as calculated exposure parameters. We retrospectively analyzed a SE registry, including patients since 2015 with at least one available LEV plasma level measured less than 36 h after loading. A Bayesian maximum likelihood approach based on a population pharmacokinetic model was used to estimate LEV exposure parameters. We compared plasma levels and pharmacokinetics parameter estimates between responders and nonresponders. Therapeutic response was defined as SE cessation within 24 h following LEV introduction without a need for additional antiepileptic drug (AED). We included 29 patients (45 plasma levels). Variability was salient in LEV loading doses (ranging between 17 and 38 mg/kg) and monitoring practice. There was no difference in median plasma concentrations (19.5 versus 21.5 mg/l; p = 0.71), median estimated LEV exposure (25.8 versus 37.0 mg/l; p = 0.61), peak (30.4 versus 41.5 mg/l; p = 0.36), or residual levels after loading dose (14.4 versus 20.5 mg/l; p = 0.07) between responders and nonresponders. Levetiracetam exposure does not seem to differ significantly between responders and nonresponders; greater exposure was not associated with better outcome. Loading doses of 30 mg/kg seem, however, appropriate to quickly reach the target exposure level. The short LEV half-life makes standardized sampling measurement necessary to obtain directly interpretable LEV levels

Studying changes in the practice of two teachers developing assessment for learning

This paper describes changes in the practice of two teachers, observed over an eighteen month period, who were participating in a study intended to support teachers in developing their use of assessment in support of learning. The design of the intervention allowed each teacher to choose for themselves which aspects of their practice to develop. Analysis of lesson observations, journal entries and interviews indicate that both teachers were keen to change their practice, but were concerned about the disruption to their established routines, and in particular about the potential for loss of control of their classes. Both teachers did effect significant changes in their classrooms, but these tended to be developments of existing preferred ways of working, rather than radical innovations. In conclusion, it is suggested that to be most effective, teacher professional development needs to be structured strongly enough to afford teacher growth, but flexible enough to allow different teachers to take their practice in different ways

Antidoping programme and biological monitoring before and during the 2014 FIFA World Cup Brazil.

BACKGROUND: The FIFA has implemented an important antidoping programme for the 2014 FIFA World Cup. AIM: To perform the analyses before and during the World Cup with biological monitoring of blood and urine samples. METHODS: All qualified players from the 32 teams participating in the World Cup were tested out-of-competition. During the World Cup, 2-8 players per match were tested. Over 1000 samples were collected in total and analysed in the WADA accredited Laboratory of Lausanne. RESULTS: The quality of the analyses was at the required level as described in the WADA technical documents. The urinary steroid profiles of the players were stable and consistent with previously published papers on football players. During the competition, amphetamine was detected in a sample collected on a player who had a therapeutic use exemption for attention deficit hyperactivity disorder. The blood passport data showed no significant difference in haemoglobin values between out-of-competition and postmatch samples. CONCLUSIONS: Logistical issues linked to biological samples collection, and the overseas shipment during the World Cup did not impair the quality of the analyses, especially when used as the biological passport of football players

Intravenous lacosamide in status epilepticus: Correlation between loading dose, serum levels, and clinical response.

Intravenous lacosamide (LCM) is increasingly used in the treatment of status epilepticus (SE), but optimal loading dose and target serum levels are unclear. We analysed the correlation between LCM serum levels after intravenous loading dose and clinical response. Retrospective study in two centres from December 2014 to May 2016 including consecutive SE patients treated with LCM, in which trough serum levels after intravenous loading dose were available. Trough levels were correlated with the loading dose and the clinical response, defined as LCM introduction terminating SE without the need of further treatment. Correlations were adjusted for other SE characteristics. Among 40 patients, 16 (40%) responded to LCM. LCM serum concentrations within the reference interval (10-20mg/l) were associated with loading doses of >9mg/kg (p=0.003; χ2). However, we observed no difference between LCM serum levels in responders (median 10.4mg/l) versus non-responders (median 9.5mg/l; p=0.36; U test), even after adjusting for other predictors of clinical outcome (SE severity, aetiology, and number of previous treatment). High intravenous LCM loading doses (>9mg/kg) were associated with serum levels within the reference interval, there was however no correlation with the clinical response. Prospective studies are needed to evaluate the benefit of increasing the LCM loading dose in SE

Antibodies to TRIM46 are associated with paraneoplastic neurological syndromes.

Paraneoplastic neurological syndromes (PNS) are often characterized by the presence of antineuronal antibodies in patient serum or cerebrospinal fluid. The detection of antineuronal antibodies has proven to be a useful tool in PNS diagnosis and the search for an underlying tumor. Here, we describe three patients with autoantibodies to several epitopes of the axon initial segment protein tripartite motif 46 (TRIM46). We show that anti-TRIM46 antibodies are easy to detect in routine immunohistochemistry screening and can be confirmed by western blotting and cell-based assay. Anti-TRIM46 antibodies can occur in patients with diverse neurological syndromes and are associated with small-cell lung carcinoma

Fluorescent nanopigments: Quantitative assessment of their quantum yield

In the last few years, an intense research effort has focused on the synthesis of fluorescent nanopigments for functional inks, light harvesting, tagging, tracing, (bio)labeling, imaging, and lighting applications. Moreover, combined with dielectric matrices, these fluorescent nanoparticles may open the way to the realization of novel optophotonic devices. In particular, due to the large variety of available organic fluorescent dyes, their encapsulation into either an inorganic or an organic host is a very promising approach to synthesize a large palette of new fluorescent nanopigments. However, since the dye encapsulation may affect the fluorescence efficiency, measuring the quantum yield of fluorescent nanopigments is of paramount importance for the development of any connected application. In this article, we present a diffuse reflectance (DR) technique that enables the quantitative assessment of the quantum yield of fluorescent nanoparticles such as zeolite L nanocrystals and poly(methyl methacrylate) nanospheres both loaded with fluorescent perylene molecules. Our method is validated by measuring a well known fluorescence standard and by comparing the results obtained for a model zeolite nanopigment with those provided by an alternative DR technique. Reliable and reproducible quantum yield values are obtained for both low- and high-efficiency fluorescent nanoparticles. Our technique can thus enable systematic and quantitative studies that may yield an important insight in the mechanisms affecting the fluorescence efficiency of a large variety of nanopigments