Online test purchased new psychoactive substances in 5 different European countries; a snapshot study of chemical composition and price

Background: New psychoactive substances (NPS) are on offer worldwide online, in order to shed light on the purity and price of these substances in the European Union, a research collaboration was set up involving France, United Kingdom (UK), the Netherlands, Czech Republic and Poland. Methods: Per country, around 10 different NPS were test purchased from different webshops. Then, chemical analysis of NPS was done with according reference standards to identify and quantify the contents. Results: In contrast to what is generally advertised on the webshops (>99%), purity varied considerably per test purchased NPS. Several NPS were mislabelled, some containing chemical analogues (e.g. 25B/C-NBOMe instead of 25I-NBOMe, pentedrone instead of 3,4- DMMC). But in some cases NPS differed substantially from what was advertised (e.g. pentedrone instead of AMT or 3-FMC instead of 5-MeO-DALT). Per gram, purity-adjusted prices of cathinones differed substantially between three countries of test purchase, with Poland being the least expensive. Synthetic cannabinoids were relatively the most expensive in the Czech Republic and least expensive in the UK. Conclusions: The current findings provides a snapshot of the price and chemical contents of NPS products purchased by different countries and in different webshops. There is a potential danger of mislabelling of NPS. The great variety in price and purity of the delivered products might be the result of the market dynamics of supply and demand and the role of law enforcement in different European countries

Fractional Euler-Lagrange differential equations via Caputo derivatives

We review some recent results of the fractional variational calculus. Necessary optimality conditions of Euler-Lagrange type for functionals with a Lagrangian containing left and right Caputo derivatives are given. Several problems are considered: with fixed or free boundary conditions, and in presence of integral constraints that also depend on Caputo derivatives.Comment: This is a preprint of a paper whose final and definite form will appear as Chapter 9 of the book Fractional Dynamics and Control, D. Baleanu et al. (eds.), Springer New York, 2012, DOI:10.1007/978-1-4614-0457-6_9, in pres

Fractional variational calculus of variable order

We study the fundamental problem of the calculus of variations with variable order fractional operators. Fractional integrals are considered in the sense of Riemann-Liouville while derivatives are of Caputo type.Comment: Submitted 26-Sept-2011; accepted 18-Oct-2011; withdrawn by the authors 21-Dec-2011; resubmitted 27-Dec-2011; revised 20-March-2012; accepted 13-April-2012; to 'Advances in Harmonic Analysis and Operator Theory', The Stefan Samko Anniversary Volume (Eds: A. Almeida, L. Castro, F.-O. Speck), Operator Theory: Advances and Applications, Birkh\"auser Verlag (http://www.springer.com/series/4850

Mephedrone pharmacokinetics after intravenous and oral administration in rats: relation to pharmacodynamics

Fe d'errates disponible a: http://​dx.​doi.​org/​10.​1007/​s00213-013-3283-6Rationale Mephedrone (4-methylmethcathinone) is a still poorly known drug of abuse, alternative to ecstasy or cocaine. Objective The major aims were to investigate the pharmacokineticsa and locomotor activity of mephedrone in rats and provide a pharmacokinetic/pharmacodynamic model. Methods Mephedrone was administered to male Sprague-Dawley rats intravenously (10 mg/kg) and orally (30 and 60 mg/kg). Plasma concentrations and metabolites were characterized using LC/MS and LC-MS/MS fragmentation patterns. Locomotor activity was monitored for 180-240 min. Results Mephedrone plasma concentrations after i.v. administration fit a two-compartment model (α=10.23 h−1, β=1.86 h−1). After oral administration, peak mephedrone concentrations were achieved between 0.5 and 1 h and declined to undetectable levels at 9 h. The absolute bioavailability of mephedrone was about 10 % and the percentage of mephedrone protein binding was 21.59±3.67%. We have identified five phase I metabolites in rat blood after oral administration. The relationship between brain levels and free plasma concentration was 1.85±0.08. Mephedrone induced a dose-dependent increase in locomotor activity, which lasted up to 2 h. The pharmacokinetic-pharmacodynamic model successfully describes the relationship between mephedrone plasma concentrations and its psychostimulant effect. Conclusions We suggest a very important first-pass effect for mephedrone after oral administration and an easy access to the central nervous system. The model described might be useful in the estimation and prediction of the onset, magnitude,and time course of mephedrone pharmacodynamics as well as to design new animal models of mephedrone addiction and toxicity

Protocol of the baseline assessment for the Environments for Healthy Living (EHL) Wales cohort study

Background Health is a result of influences operating at multiple levels. For example, inadequate housing, poor educational attainment, and reduced access to health care are clustered together, and are all associated with reduced health. Policies which try to change individual people's behaviour have limited effect when people have little control over their environment. However, structural environmental change and an understanding of the way that influences interact with each other, has the potential to facilitate healthy choices irrespective of personal resources. The aim of Environments for Healthy Living (EHL) is to investigate the impact of gestational and postnatal environments on health, and to examine where structural change can be brought about to optimise health outcomes. The baseline assessment will focus on birth outcomes and maternal and infant health. Methods/Design EHL is a longitudinal birth cohort study. We aim to recruit 1000 pregnant women in the period April 2010 to March 2013. We will examine the impact of the gestational environment (maternal health) and the postnatal environment (housing and neighbourhood conditions) on subsequent health outcomes for the infants born to these women. Data collection will commence during the participants' pregnancy, from approximately 20 weeks gestation. Participants will complete a questionnaire, undergo anthropometric measurements, wear an accelerometer, compile a food diary, and have environmental measures taken within their home. They will also be asked to consent to having a sample of umbilical cord blood taken following delivery of their baby. These data will be complemented by routinely collected electronic data such as health records from GP surgeries, hospital admissions, and child health and development records. Thereafter, participants will be visited annually for follow-up of subsequent exposures and child health outcomes. Discussion The baseline assessment of EHL will provide information concerning the impact of gestational and postnatal environments on birth outcomes and maternal and infant health. The findings can be used to inform the development of complex interventions targeted at structural, environmental factors, intended to reduce ill-health. Long-term follow-up of the cohort will focus on relationships between environmental exposures and the later development of adverse health outcomes, including obesity and diabetes

Intermediate filament cytoskeleton of the liver in health and disease

Intermediate filaments (IFs) represent the largest cytoskeletal gene family comprising ~70 genes expressed in tissue specific manner. In addition to scaffolding function, they form complex signaling platforms and interact with various kinases, adaptor, and apoptotic proteins. IFs are established cytoprotectants and IF variants are associated with >30 human diseases. Furthermore, IF-containing inclusion bodies are characteristic features of several neurodegenerative, muscular, and other disorders. Acidic (type I) and basic keratins (type II) build obligatory type I and type II heteropolymers and are expressed in epithelial cells. Adult hepatocytes contain K8 and K18 as their only cytoplasmic IF pair, whereas cholangiocytes express K7 and K19 in addition. K8/K18-deficient animals exhibit a marked susceptibility to various toxic agents and Fas-induced apoptosis. In humans, K8/K18 variants predispose to development of end-stage liver disease and acute liver failure (ALF). K8/K18 variants also associate with development of liver fibrosis in patients with chronic hepatitis C. Mallory-Denk bodies (MDBs) are protein aggregates consisting of ubiquitinated K8/K18, chaperones and sequestosome1/p62 (p62) as their major constituents. MDBs are found in various liver diseases including alcoholic and non-alcoholic steatohepatitis and can be formed in mice by feeding hepatotoxic substances griseofulvin and 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC). MDBs also arise in cell culture after transfection with K8/K18, ubiquitin, and p62. Major factors that determine MDB formation in vivo are the type of stress (with oxidative stress as a major player), the extent of stress-induced protein misfolding and resulting chaperone, proteasome and autophagy overload, keratin 8 excess, transglutaminase activation with transamidation of keratin 8 and p62 upregulation

Search for High-Mass Resonances Decaying to τν in pp Collisions at √s=13 TeV with the ATLAS Detector

A search for high-mass resonances decaying to τν using proton-proton collisions at √s=13 TeV produced by the Large Hadron Collider is presented. Only τ-lepton decays with hadrons in the final state are considered. The data were recorded with the ATLAS detector and correspond to an integrated luminosity of 36.1 fb−1. No statistically significant excess above the standard model expectation is observed; model-independent upper limits are set on the visible τν production cross section. Heavy W′ bosons with masses less than 3.7 TeV in the sequential standard model and masses less than 2.2–3.8 TeV depending on the coupling in the nonuniversal G(221) model are excluded at the 95% credibility level

Search for the direct production of charginos and neutralinos in final states with tau leptons in √s=13 TeV collisions with the ATLAS detector

A search for the direct production of charginos and neutralinos in final states with at least two hadronically decaying tau leptons is presented. The analysis uses a dataset of pp collisions corresponding to an integrated luminosity of 36.1 fb−1, recorded with the ATLAS detector at the Large Hadron Collider at a centre-of-mass energy of 13TeV.Nosignificant deviation from the expected Standard Model background is observed. Limits are derived in scenarios of ˜χ+1 ˜χ−1 pair production and of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 production in simplified models where the neutralinos and charginos decay solely via intermediate left-handed staus and tau sneutrinos, and the mass of the ˜ τL state is set to be halfway between the masses of the ˜χ±1 and the ˜χ01. Chargino masses up to 630 GeV are excluded at 95% confidence level in the scenario of direct production of ˜χ+1 ˜χ−1 for a massless ˜χ01. Common ˜χ±1 and ˜χ02 masses up to 760 GeV are excluded in the case of production of ˜χ±1 ˜χ02 and ˜χ+1 ˜χ−1 assuming a massless ˜χ01. Exclusion limits for additional benchmark scenarios with large and small mass-splitting between the ˜χ±1 and the ˜χ01 are also studied by varying the ˜ τL mass between the masses of the ˜χ±1 and the ˜χ01

Combined measurement of differential and total cross sections in the H → γγ and the H → ZZ* → 4ℓ decay channels at s=13 TeV with the ATLAS detector

A combined measurement of differential and inclusive total cross sections of Higgs boson production is performed using 36.1 fb−1 of 13 TeV proton–proton collision data produced by the LHC and recorded by the ATLAS detector in 2015 and 2016. Cross sections are obtained from measured H→γγ and H→ZZ*(→4ℓ event yields, which are combined taking into account detector efficiencies, resolution, acceptances and branching fractions. The total Higgs boson production cross section is measured to be 57.0−5.9 +6.0 (stat.) −3.3 +4.0 (syst.) pb, in agreement with the Standard Model prediction. Differential cross-section measurements are presented for the Higgs boson transverse momentum distribution, Higgs boson rapidity, number of jets produced together with the Higgs boson, and the transverse momentum of the leading jet. The results from the two decay channels are found to be compatible, and their combination agrees with the Standard Model predictions