The Role of social institutions in inter-generational mobility

In this study we examine the role of institutions in shaping inter-generational mobility behavior. Research has traditionally emphasized the role of educational systems but cummulative evidence suggests that variations in their design offer only a very limited explanation for observed mobility differences. We examine the impact of welfare states and, in particular, how early childhood and family policies may influence the impact of economic and cultural characteristics of origin families on child outcomes.

Asymmetries in the opportunity structure. Intergenerational mobility trends in Europe

It remains unclear whether social mobility is increasing in the advancednations. The answer may depend on mobility patterns within very recentbirth cohorts. We use the inter-generational module in the 2005 EUSILCwhich allows us to include more recent cohorts. Comparingacross two Nordic and three Continental European countries, weestimate inter-generational mobility trends for sons both indirectly, viasocial origin effects on educational attainment, and directly in terms ofadult income attainment. In line with other studies we find substantiallymore mobility in Scandinavia, but also that traditionally less mobilesocieties, like Spain, are moving towards greater equality. We focusparticularly on non-linear relations. Most interestingly, we revealevident asymmetries in the process of equalizing life chances, inDenmark. The disadvantages associated with low social class originshave largely disappeared, but the advantages related to privilegedorigins persist.

Panorama des environs de Londres / Par A. M. Perrot ; Ad. Hocquart Dir[ec]t[ion]

Échelle(s) : [ca 1:365 000], échelle de 4 lieues de poste de France [= 4,7 cm]

Subtype-specific Modulation of Acid-sensing Ion Channel (ASIC) Function by 2-Guanidine-4-methylquinazoline.

Acid-sensing ion channels (ASICs) are neuronal Na(+)-selective channels that are transiently activated by extracellular acidification. ASICs are involved in fear and anxiety, learning, neurodegeneration after ischemic stroke, and pain sensation. The small molecule 2-guanidine-4-methylquinazoline (GMQ) was recently shown to open ASIC3 at physiological pH. We have investigated the mechanisms underlying this effect and the possibility that GMQ may alter the function of other ASICs besides ASIC3. GMQ shifts the pH dependence of activation to more acidic pH in ASIC1a and ASIC1b, whereas in ASIC3 this shift goes in the opposite direction and is accompanied by a decrease in its steepness. GMQ also induces an acidic shift of the pH dependence of inactivation of ASIC1a, -1b, -2a, and -3. As a consequence, the activation and inactivation curves of ASIC3 but not other ASICs overlap in the presence of GMQ at pH 7.4, thereby creating a window current. At concentrations >1 mm, GMQ decreases maximal peak currents by reducing the unitary current amplitude. Mutation of residue Glu-79 in the palm domain of ASIC3, previously shown to be critical for channel opening by GMQ, disrupted the GMQ effects on inactivation but not activation. This suggests that this residue is involved in the consequences of GMQ binding rather than in the binding interaction itself. This study describes the mechanisms underlying the effects of a novel class of ligands that modulate the function of all ASICs as well as activate ASIC3 at physiological pH.

Simultaneous determination of plasma levels of fluvoxamine and of the enantiomers of fluoxetine and norfluoxetine by gas chromatography-mass spectrometry.

A gas chromatographic-mass spectrometric method is presented which allows the simultaneous determination of the plasma concentrations of fluvoxamine and of the enantiomers of fluoxetine and norfluoxetine after derivatization with the chiral reagent, (S)-(-)-N-trifluoroacetylprolyl chloride. No interference was observed from endogenous compounds following the extraction of plasma samples from six different human subjects. The standard curves were linear over a working range of 10 to 750 ng/ml for racemic fluoxetine and norfluoxetine and of 50 to 500 ng/ml for fluvoxamine. Recoveries ranged from 50 to 66% for the three compounds. Intra- and inter-day coefficients of variation ranged from 4 to 10% for fluvoxamine and from 4 to 13% for fluoxetine and norfluoxetine. The limits of quantitation of the method were found to be 2 ng/ml for fluvoxamine and 1 ng/ml for the (R)- and (S)-enantiomers of fluoxetine and norfluoxetine, hence allowing its use for single dose pharmacokinetics. Finally, by using a steeper gradient of temperature, much shorter analysis times are obtained if one is interested in the concentrations of fluvoxamine alone.

Determination of oseltamivir and oseltamivir carboxylate in human plasma by liquid chromatography-tandem mass spectrometry

Introduction: Oseltamivir phosphate (OP), the prodrug of oseltamivir carboxylate (OC; active metabolite), is marketed since 10 years for the treatment of seasonal influenza flu. It has recently received renewed attention because of the threat of avian flu H5N1 in 2006-7 and the 2009-10 A/H1N1 pandemic. However, relatively few studies have been published on OP and OC clinical pharmacokinetics. The disposition of OC and the dosage adaptation of OP in specific populations, such as young children or patients undergoing extrarenal epuration, have also received poor attention. An analytical method was thus developed to assess OP and OC plasma concentrations in patients receiving OP and presenting with comorbidities or requiring intensive care. Methods: A high performance liquid chromatography coupled to tandem mass spectrometry method (HPLC-MS/MS) requiring 100-µL aliquot of plasma for quantification within 6 min of OP and OC was developed. A combination of protein precipitation with acetonitrile, followed by dilution of supernant in suitable buffered solvent was used as an extraction procedure. After reverse phase chromatographic separation, quantification was performed by electro-spray ionization-triple quadrupole mass spectrometry. Deuterated isotopic compounds of OP and OC were used as internal standards. Results: The method is sensitive (lower limit of quantification: 5 ng/mL for OP and OC), accurate (intra-/inter-assay bias for OP and OC: 8.5%/5.5% and 3.7/0.7%, respectively) and precise (intra-/inter-assay CV%: 5.2%/6.5% and 6.3%/9.2%, respectively) over the clinically relevant concentration range (upper limits of quantification 5000 ng/mL). Of importance, OP, as in other previous reports, was found not to be stable ex vivo in plasma on standard anticoagulants (i.e. EDTA, heparin or citrate). This poor stability of OP has been prevented by collecting blood samples on commercial fluoride/oxalate tubes. Conclusions: This new simple, rapid and robust HPLC-MS/MS assay for quantification of OP and OC plasma concentrations offers an efficient tool for concentration monitoring of OC. Its exposure can probably be controlled with sufficient accuracy by thorough dosage adjustment according to patient characteristics (e.g. renal clearance). The usefulness of systematic therapeutic drug monitoring in patients appears therefore questionable. However, pharmacokinetic studies are still needed to extend knowledge to particular subgroups of patients or dosage regimens.

Increased mobility of major histocompatibility complex I-peptide complexes decreases the sensitivity of antigen recognition.

CD8(+) cytotoxic T lymphocytes (CTL) can recognize and kill target cells expressing only a few cognate major histocompatibility complex (MHC) I-peptide complexes. This high sensitivity requires efficient scanning of a vast number of highly diverse MHC I-peptide complexes by the T cell receptor in the contact site of transient conjugates formed mainly by nonspecific interactions of ICAM-1 and LFA-1. Tracking of single H-2K(d) molecules loaded with fluorescent peptides on target cells and nascent conjugates with CTL showed dynamic transitions between states of free diffusion and immobility. The immobilizations were explained by association of MHC I-peptide complexes with ICAM-1 and strongly increased their local concentration in cell adhesion sites and hence their scanning by T cell receptor. In nascent immunological synapses cognate complexes became immobile, whereas noncognate ones diffused out again. Interfering with this mobility modulation-based concentration and sorting of MHC I-peptide complexes strongly impaired the sensitivity of antigen recognition by CTL, demonstrating that it constitutes a new basic aspect of antigen presentation by MHC I molecules.

Geochemistry and stable isotope composition of fresh alkaline porphyry copper tailings: Implications on sources and mobility of elements during transport and early stages of deposition

Prevention of acid mine drainage (AMD) in sulfide-containing tailings requires the identification of the geochemical processes and element pathways in the early stages of tailing deposition. However, analyses of recently deposited tailings in active tailings impoundments are scarce because mineralogical changes occur near the detection limits of many assays. This study shows that a detailed geochemical study which includes stable isotopes of water (delta H-2, delta O-18), dissolved sulfates (delta S-34, delta O-18) and hydrochernical parameter (pH, Eh, DOC, major and trace elements) from tailings samples taken at different depths in rainy and dry seasons allows the understanding of weathering (oxidation, dissolution, sorption, and desorption), water and element pathways, and mixing processes in active tailings impoundments. Fresh alkaline tailings (pH 9.2-10.2) from the Cu-Mo porphyry deposit in El Teniente, Chile had low carbonate (0.8-1.1 Wt-% CaCO3 equivalent) and sulfide concentrations (0.8-1.3 wt.%, mainly as pyrite). In the alkaline tailings water, Mo and Cu (up to 3.9 mg/L Mo and 0.016 mg/L Cu) were mobile as MoO42- and Cu (OH)(2)(0). During the flotation, tailings water reached equilibrium with gypsum (up to 738 mg/L Ca and 1765 mg/ L SO4). The delta S-34 VS. delta O-18 covariations of dissolved sulfate (2.3 to 4.5% delta S-34 and 4.1 to 6.0 % delta O-18) revealed the sulfate sources: the dissolution of primary sulfates (12.0 to 13.2%. delta S-34, 7.4 to 10.9%.delta O-18) and oxidation of primary sulfides (-6.7 to 1.7%. delta S-34). Sedimented tailings in the tailings impoundment can be divided into three layers with different water sources, element pathways, and geochemical processes. The deeper sediments (> 1 m depth) were infiltrated by catchment water, which partly replaced the original tailings water, especially during the winter season. This may have resulted in the change from alkaline to near-neutral pH and towards lower concentrations of most dissolved elements. The neutral pH and high DOC (up to 99.4 mg/L C) of the catchment water mobilized Cu (up to 0.25 mg/L) due to formation of organic Cu complexes; and Zn (up to 130 mg/L) due to dissolution of Zn oxides and desorption). At I m depth, tailings pore water obtained during the winter season was chemically and isotopically similar to fresh tailings water (pH 9.8-10.6, 26.7-35.5 mg/L Cl, 2.3-6.0 mg/L Mo). During the summer, a vadose zone evolved locally and temporarily up to 1.2 m depth. resulting in a higher concentration of dissolved solids in the pore water due to evaporation. During periodical new deposition of fresh tailings, the geochemistry of the surface layer was geochemically similar to fresh tailings. In periods without deposition, sulfide oxidation was suggested by decreasing pH (7.7-9.5), enrichment of MoO42- and SO42-, and changes in the isotopic composition of dissolved sulfates. Further enrichment for Na, K, Cl, SO4, Mg, Cu, and Mo (up to 23.8 mg/L Mo) resulted from capillary transport towards the surface followed by evaporation and the precipitation of highly soluble efflorescent salts (e.g., mirabilite, syngenite) at the tailing surface during summer. (C) 2008 Elsevier B.V. All rights reserved.

Temporary help agencies and workers' occupational mobility

This paper focuses on the occupational mobility of temporary helpagency workers by studying their job-to-job upgrading chances as opposedto those who have not been hired through these intermediaries. A screeningapproach to the role of those labor brokers suggests that agency workersmay expect greater chances of upgrading from one occupation to another.Results obtained with a sample of Spanish workers show that workingthrough those intermediaries comparatively offers stronger prospects ofoccupational upgrading for workers of a medium qualification level. Thisbasic result is reinforced when the existence of self-selection into thistype of intermediated work is appropriately taken into account.

Simultaneous determination of antidementia drugs by HPLC-MS: validation data of the method and plasma level determinations in 300 patients

Aims: A rapid and simple HPLC-MS method was developed for the simultaneousdetermination of antidementia drugs, including donepezil, galantamine, rivastigmineand its major metabolite NAP 226 - 90, and memantine, for TherapeuticDrug Monitoring (TDM). In the elderly population treated with antidementiadrugs, the presence of several comorbidities, drug interactions resulting frompolypharmacy, and variations in drug metabolism and elimination, are possiblefactors leading to the observed high interindividual variability in plasma levels.Although evidence for the benefit of TDM for antidementia drugs still remains tobe demonstrated, an individually adapted dosage through TDM might contributeto minimize the risk of adverse reactions and to increase the probability of efficienttherapeutic response. Methods: A solid-phase extraction procedure with amixed-mode cation exchange sorbent was used to isolate the drugs from 0.5 mL ofplasma. The compounds were analyzed on a reverse-phase column with a gradientelution consisting of an ammonium acetate buffer at pH 9.3 and acetonitrile anddetected by mass spectrometry in the single ion monitoring mode. Isotope-labeledinternal standards were used for quantification where possible. The validatedmethod was used to measure the plasma levels of antidementia drugs in 300patients treated with these drugs. Results: The method was validated accordingto international standards of validation, including the assessment of the trueness(-8 - 11 %), the imprecision (repeatability: 1-5%, intermediate imprecision:2 - 9 %), selectivity and matrix effects variability (less than 6 %). Furthermore,short and long-term stability of the analytes in plasma was ascertained. Themethod proved to be robust in the calibrated ranges of 1 - 300 ng/mL for rivastigmineand memantine and 2 - 300 mg/mL for donepezil, galantamine and NAP226 - 90. We recently published a full description of the method (1). We found ahigh interindividual variability in plasma levels of these drugs in a study populationof 300 patients. The plasma level measurements, with some preliminaryclinical and pharmacogenetic results, will be presented. Conclusion: A simpleLC-MS method was developed for plasma level determination of antidementiadrugs which was successfully used in a clinical study with 300 patients.

A new way of quantifying dominant upper-limb mobility in healthy and painful shoulders

Introduction: Quantification of daily upper-limb activity is determinant in the evaluation of shoulder surgery. For a number of shoulder diseases, roblems in performing daily activities have been expressed in terms of upper-limb usage. Althought many instruments measure upper-limb movements, there is no accepted standard or widely used objective measure and no device to differenciate left or right shoulder usage. We present an objective method to measure the mobility and quantify the usage of dominant and healthy or painfull shoulder movement during daily life. Methods: 12 patients with unilateral pathological shoulder (rotator cuff disease) are compared to 18 control subjects (10 right and 8 left handed). Both SST and DASH questionnaires were completed by each one. Three inertial miniature modules including triaxial gyroscopes and accelerometers were fixed on the dorsal side of both humerus, and on the thorax. An ambulatory datalogger have recorded the signals during one day. Results: We observed that right handed healthy subjects used 18% and 26% more their dominant shoulder during respectively stand and sit postures while left handed subjects used 8% and 18% more their left side. In walking periods, shoulder mobility was quite alike for both sides. Patients affected on their dominant arm (PD group) mostly used their non-dominant side (respectively 5% and 9% during stand and sit). For the patients affected on their non-dominant shoulder (PND group), this difference is respectively 28% and 26%. Moreover, we can note that, during walking periods, a difference can be observed (on the contrary to controls). Patients used 13% and 15% more their nonpathologic side respectively for PD and PND groups. Conclusion: Inertial sensors, during long-term ambulatory monitoring of upper limbs, can quantify the difference between dominant and nondominant sides. Patients used more their non affected shoulder during daily life. For the PD group, the difference with control can be shown during walking. These results are very encouraging for future evaluation of patients with shoulder injuries since it can provide an objective evaluation of the shoulder mobility and of the treatment outcome during daily life.