High-Throughput Qualitative and Quantitative Drug Checking by MALDI HRMS.

Illicit drugs are a global health problem, since both their acute and chronic consumption have negative impacts on the drug user's health. Drug checking facilities are receiving growing interest as they allow drug users to chemically analyze their product prior to consumption to assess the presence of adulterants or other non-expected substances. Such harm reduction programs allow the reduction of the risks associated with drug consumption without encouraging it. In particular, the emergence of new psychoactive substances (NPS) emphasizes the risk for the population increasing the diversity and the lability of illicit drugs on the market. Analytical developments are required to catch up with this rapid evolution and reduce the potential harm caused by such consumption. In this study, we developed a matrix-assisted laser desorption/ionization (MALDI) high-resolution mass spectrometry (HRMS) strategy for the high-throughput qualitative and quantitative analysis of drug checking samples. The use of online-based m/z cloud library for untargeted compound search improved the ability to identify unknown compounds. Sixty-seven drug checking samples were analyzed using this analytical strategy, allowing the detection of 10 designer drugs and several classical drugs of abuse (mainly cocaine and MDMA) as well as adulterants and contaminants. The results were then compared with routine analyses of the same samples using conventional approaches showing similar performance while removing the use of chromatographic separation thus resulting in a significant reduction of the time required for sample preparation and analysis. This study enlightens the potential of MALDI-HRMS as a high-throughput approach allowing to speed-up up to six times the identification and quantification of substances enabling to catch the fast changes on the drug of abuse market. This strategy could be an interesting alternative analytical approach, allowing better prevention and harm reduction for drug users

Income Taxes, Sorting, and the Costs of Housing: Evidence from Municipal Boundaries in Switzerland

This paper provides novel evidence on the role of income taxes for residential rents and spatial sorting. Drawing on comprehensive apartment-level data, we identify the effects of tax differentials across municipal boundaries in Switzerland. The boundary discontinuity design (BDD) corrects for unobservable location characteristics such as environmental amenities or the access to public goods and thereby reduces the estimated response of housing prices by one half compared to conventional estimates: we identify an income tax elasticity of rents of about 0.26. We complement this approach with census data on local sociodemographic characteristics and show that about one third of this effect can be traced back to a sorting of high-income households into low-tax municipalities. These findings are robust to a matching approach (MBDD) which compares identical residences on opposite sides of the boundary and a number of further sensitivity checks

Riksdagsmotioner om kulturmiljövård

Antalet motioner avgivna un­der den allmänna motionsti­den i januari 1991 var 3723. De flesta av dessa, 398 stycken, läm­nades till utbildningsutskottet. Spridningen av motioner med an­knytning till kulturmiljövården är stor. De har lämnats in till en rad olika utskott. Här nedan följer ett antal exempel dock utan en när­mare redogörelse för innehållet

Riksdagsmotioner om kulturmiljövård

Antalet motioner avgivna un­der den allmänna motionsti­den i januari 1991 var 3723. De flesta av dessa, 398 stycken, läm­nades till utbildningsutskottet. Spridningen av motioner med an­knytning till kulturmiljövården är stor. De har lämnats in till en rad olika utskott. Här nedan följer ett antal exempel dock utan en när­mare redogörelse för innehållet

Feeling and showing : A new conceptualization of dispositional teacher enthusiasm and its relation to students' interest

Although teacher enthusiasm is a relevant variable in the teaching context, a clear definition is still lacking. Research on teacher enthusiasm is characterized by ambiguous conceptualizations of enthusiasm as either an affective characteristic of teachers or behaviors of expressiveness. Integrating these two notions, a new conceptualization of dispositional teacher enthusiasm, defined by teachers' positive affect and positive emotional expressivity, was developed. It was hypothesized that dispositional teacher enthusiasm would relate to students' interest, mediated by students' perceived teacher enthusiasm. Based on a correlational study design, secondary teachers (N = 75) from Switzerland reported on their enthusiasm, complemented by student ratings (N = 1523) on perceived enthusiasm and interest. Multilevel structural equation modeling revealed that dispositional teacher enthusiasm positively predicted students' interest, which was fully mediated by students' perceived enthusiasm, providing the basis of a valid definition of teacher enthusiasm. Based on this integrative definition, implications for future research are discussed

Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 2: cytodiagnosis, pathogenesis, therapy, and prognostic aspects

The second part of the present review article presents and discusses the current literature regarding cytodiagnostic aspects, pathogenesis, therapy, incidence of recurrence, and malignant transformation rate of oral erythroplakia (OE) and oral erythroleukoplakia (OEL). Oral cytopathology, eventually in combination with DNA cytometry, can add valuable information to conventional histopathology, but is not able yet to replace the aforementioned. Numerous molecular genetic variants have been studied in precancerous lesions to gain knowledge about the prognosis of these lesions. Still, there are no evidence-based parameters available to safely detect precursor lesions that will undergo malignant transformation in the future. Excision of OE and OEL should be performed with a margin of safety using the CO2 laser or a scalpel. Data about incidence of recurrence and malignant tranformation rates of OE are mostly based upon case reports or case series. The OEL has a significantly higher risk of malignant transformation than oral leukoplakias.Link_to_subscribed_fulltex

[Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 2: cytodiagnosis, pathogenesis, therapy, and prognostic aspects]

The second part of the present review article presents and discusses the current literature regarding cytodiagnostic aspects, pathogenesis, therapy, incidence of recurrence, and malignant transformation rate of oral erythroplakia (OE) and oral erythroleukoplakia (OEL). Oral cytopathology, eventually in combination with DNA cytometry, can add valuable information to conventional histopathology, but is not able yet to replace the aforementioned. Numerous molecular genetic variants have been studied in precancerous lesions to gain knowledge about the prognosis of these lesions. Still, there are no evidence-based parameters available to safely detect precursor lesions that will undergo malignant transformation in the future. Excision of OE and OEL should be performed with a margin of safety using the CO2 laser or a scalpel. Data about incidence of recurrence and malignant tranformation rates of OE are mostly based upon case reports or case series. The OEL has a significantly higher risk of malignant transformation than oral leukoplakias

[Oral erythroplakia and erythroleukoplakia: red and red-white dysplastic lesions of the oral mucosa--part 1: epidemiology, etiology, histopathology and differential diagnosis]

Oral erythroplakia (OE) and oral erythroleukoplakia (OEL; synonym: speckled leukoplakia) are working diagnoses for red and red-white lesions of the oral mucosa after exclusion of all other possible diagnoses for lesions with a similar clinical appearance. A good knowledge of oral medicine and possible differential diagnoses of oral mucosal pathologies is mandatory to correctly detect OE and OEL on this exclusion basis. In the present review article in a series of two, epidemiologic data, etiologic factors, possible differential diagnoses, and the histopathologic characteristics of OE and OEL will be presented and discussed regarding the current literature. A thorough histopathologic examination of these epithelial precursor lesions is mandatory to recognise the presence and the severity of epithelial dysplasia, which is a decisive factor for the subsequent treatment planning