Switch to etravirine for HIV-positive patients receiving statin treatment: a prospective study.

BACKGROUND: Lifestyle changes and statins are the cornerstones in management of dyslipidaemia in patients with HIV infection. Replacement of an antiretroviral therapy (ART) component is a proposed therapeutic strategy to reduce cardiovascular risk. In dyslipidaemic patients with HIV infection, we assessed the efficacy of replacing boosted protease inhibitor (bPI) or efavirenz (EFV) by etravirine (ETR) as an alternative to statin therapy. MATERIALS AND METHODS: A prospective, open-label, multicentre, 12-week study of patients with HIV infection on ART including bPI or EFV, and statin treatment. Four weeks after statin interruption, bPI or EFV was switched to ETR (400 mg, 8 weeks) if serum low-density lipoprotein cholesterol (LDL-C) was ≥ 3 mM. The primary endpoint was the proportion of patients on ETR with no indication for statin treatment at study completion. Serum levels of HIV RNA, lipids and biomarkers of cardiovascular disease were also measured. (ClinicalTrials.gov: NCT01543035). RESULTS: The 31 included patients had a HIV-1 RNA < 50 copies/mL (median age, 52 years; median CD4, 709 cell/mL; median LDL-C, 2·89 mM), 68% were on EFV, and 32% were on bPI. At week 4, 27 patients switched to ETR. At study completion, 15 patients (56%) on ETR did not qualify for statin treatment. After the ETR switch, serum levels of the cardiovascular biomarkers sICAM and MCP1/CCL2 decreased by 11·2% and 18·9%, respectively, and those of CCL5/RANTES and tissue inhibitor of metalloproteinase-1 increased by 14·3% and 13·4%, respectively, indicating reduced cardiovascular risk. There were no notable treatment-related adverse events. CONCLUSIONS: Replacing bPI or EFV by ETR is a viable strategy to obviate primary prevention statin treatment.

A qualitative study of adolescents with medically unexplained symptoms and their parents. Part 2: How is healthcare perceived?

Medically unexplained symptoms (MUS) are common among adolescents and an important cause of clinical visits. This study sought to understand the experiences with, and perceptions of, the healthcare of adolescents who have MUS and their parents. Using a qualitative approach, six focus groups and two individual interviews were conducted with a total of ten adolescents and sixteen parents. The participants were recruited in a university hospital in Switzerland. A thematic analysis was conducted in accordance with the Grounded Theory. Six main themes emerged: needing a label for the symptoms, seeking an etiology to explain the symptoms, negotiating the medical system, medication and treatments, interactions with doctors, and the inclusion of parents during consultations. Transcending these themes, however, was the need for good communication between the adolescents, their parents and the clinicians. When explaining the symptoms, clinicians should make sure to discuss the results, investigations and lack of organic origin.

Sertifioidun puuraaka-aineen ja sertifioitujen tuotteiden tietojärjestelmän määrittely

Asiakkaiden kiinnostus tuotteiden raaka-aineiden alkuperää kohden on kasvanut. Puuraaka-aineesta tehtyjen tuotteiden alkuperä voidaan todentaa sertifikaatilla, jos puu on peräisin sertifioidusta metsästä ja sen alkuperäketju tunnetaan. Tieto sertifioidusta tuotteesta kulkeutuu asiakkaalle leimaamalla tuotteita sertifioinnista kertovin merkein tai merkitsemällä esimerkiksi tuotteen asiakirjaan sertifioinnista kertova teksti. Tutkimus tehtiin Stora Enson Imatran tehtaalle, jolla oli tarve uudelle tietojärjestelmälle. Tutkimuksen tarkoituksena oli määritellä sertifioidun puuraaka-aineen käytön ja sertifioituina myytävien tuotteiden seurannan mandollistava tietojärjestelmä. Puun alkuperäketjun hallinnan standardit määiittävät, paljonko sertifioitua puuta kohdennettava tuotteelle, jos tuotteita halutaan myydä sertifioituna. Tietojärjestelmän määrittelyn lisäksi oli tarve selvittää prosessi, kuinka tuotteisiin ja asiakirjoihin saataisiin sertifioinnista kertova leima. Tutkimusta tehdessä selvisi, että tehtaan nykyiset myyntitoiminnot ja tietojärjestelmät asettavat rajoituksia tuotteiden ja asiakirjojen leimaukselle. Prosessia kartoitettiin mm. haastatt elemalla tehtaan ti etojärj estelmi en, myynti- ja varastotoimintojen parissa työskenteleviä ihmisiä. Haastattelujen perusteella koottiin myös tietojärjestelmän asiakasvaatimukset. Vaatimusmäärittelyä tehdessä huomioitiin myös alkuperäketjun hallinnan standardien vaatimukset. Määriteltävän tietojärjestelmän toimintaa pyrittiin havainnollistamaan tehtaan edustajille prototyyppien avulla. Lisäksi tutkimuksessa on pyritty havainnollistamaan järjestelmän toimintaa erilaisin kaavioin ja kuvin. Haasteena työssä oli tulkita standardeja ja kerätä yhteen toisistaan poikkeavia asiakasvaatimuksia.

Cartographie et analyse des données disponibles pour estimer le nombre de préservatifs écoulés sur le marché suisse en une année

L'Office fédéral de la santé publique (OFSP) a mandaté la Fédération romande des consommateurs (FRC) et l'Institut universitaire de médecine sociale et préventive (IUMSP) pour réaliser une cartographie du marché des préservatifs et analyser les données disponibles pour estimer le nombre de préservatifs écoulés sur le marché suisse en une année. Les données disponibles identifiées sont les suivantes : 1. Données Verein : l'Association pour le label de qualité des préservatifs possède des données sur le nombre de préservatifs testés chaque année pour l'obtention du label OK. Ces données constituent une estimation du nombre de préservatifs ayant suivi la procédure de certification du label OK. Ces dernières années, des entreprises auraient renoncé à leur collaboration avec l'association pour le label de qualité, ce qui réduit la fiabilité de cette méthode pour suivre l'évolution du marché des préservatifs en Suisse. 2. Données douanes : l'Administration fédérale des douanes établit une statistique du commerce extérieur et met à disposition une base de données qui donne accès aux données statistiques d'importation et d'exportation de préservatifs. Etant donné que cette statistique se base sur les données indiquées par les importateurs et les exportateurs, des erreurs de déclaration peuvent être commises. 3. Données IUMSP : entre 1986 et 2011, l'IUMSP a reçu des producteurs/importateurs des données de mises sur le marché de préservatifs. Ces données, fiables car provenant directement des producteurs/importateurs, ne sont malheureusement plus complètes depuis 2012, en raison d'une difficulté croissante à obtenir de telles informations. 4. Données Nielsen et IMS Health : Nielsen et IMS HEalth sont des entreprises privées qui recensent les données de vente des préservatifs en Suisse réalisées dans les commerces de détail, ainsi que dans les drogueries et pharmacies. Ces données constituent des données de vente réelles obtenues grâce à l'enregistrement des mouvements de la marchandise lors du passage en caisse dans les magasins. La couverture des points de vente est élevée (près de 80% pour les données Nielsen) et stable dans le temps.

Classification supervisée multi-étiquette en actes de dialogue: analyse discriminante et transformations de Schoenberg

Abstract This work studies the multi-label classification of turns in simple English Wikipedia talk pages into dialog acts. The treated dataset was created and multi-labeled by (Ferschke et al., 2012). The first part analyses dependences between labels, in order to examine the annotation coherence and to determine a classification method. Then, a multi-label classification is computed, after transforming the problem into binary relevance. Regarding features, whereas (Ferschke et al., 2012) use features such as uni-, bi-, and trigrams, time distance between turns or the indentation level of the turn, other features are considered here: lemmas, part-of-speech tags and the meaning of verbs (according to WordNet). The dataset authors applied approaches such as Naive Bayes or Support Vector Machines. The present paper proposes, as an alternative, to use Schoenberg transformations which, following the example of kernel methods, transform original Euclidean distances into other Euclidean distances, in a space of high dimensionality. Résumé Ce travail étudie la classification supervisée multi-étiquette en actes de dialogue des tours de parole des contributeurs aux pages de discussion de Simple English Wikipedia (Wikipédia en anglais simple). Le jeu de données considéré a été créé et multi-étiqueté par (Ferschke et al., 2012). Une première partie analyse les relations entre les étiquettes pour examiner la cohérence des annotations et pour déterminer une méthode de classification. Ensuite, une classification supervisée multi-étiquette est effectuée, après recodage binaire des étiquettes. Concernant les variables, alors que (Ferschke et al., 2012) utilisent des caractéristiques telles que les uni-, bi- et trigrammes, le temps entre les tours de parole ou l'indentation d'un tour de parole, d'autres descripteurs sont considérés ici : les lemmes, les catégories morphosyntaxiques et le sens des verbes (selon WordNet). Les auteurs du jeu de données ont employé des approches telles que le Naive Bayes ou les Séparateurs à Vastes Marges (SVM) pour la classification. Cet article propose, de façon alternative, d'utiliser et d'étendre l'analyse discriminante linéaire aux transformations de Schoenberg qui, à l'instar des méthodes à noyau, transforment les distances euclidiennes originales en d'autres distances euclidiennes, dans un espace de haute dimensionnalité.

Imaging the time-integrated cerebral metabolic activity with subcellular resolution through nanometer-scale detection of biosynthetic products deriving from (13)C-glucose.

Glucose is the primary source of energy for the brain but also an important source of building blocks for proteins, lipids, and nucleic acids. Little is known about the use of glucose for biosynthesis in tissues at the cellular level. We demonstrate that local cerebral metabolic activity can be mapped in mouse brain tissue by quantitatively imaging the biosynthetic products deriving from [U-(13)C]glucose metabolism using a combination of in situ electron microscopy and secondary ion mass-spectroscopy (NanoSIMS). Images of the (13)C-label incorporated into cerebral ultrastructure with ca. 100nm resolution allowed us to determine the timescale on which the metabolic products of glucose are incorporated into different cells, their sub-compartments and organelles. These were mapped in astrocytes and neurons in the different layers of the motor cortex. We see evidence for high metabolic activity in neurons via the nucleus (13)C enrichment. We observe that in all the major cell compartments, such as e.g. nucleus and Golgi apparatus, neurons incorporate substantially higher concentrations of (13)C-label than astrocytes.

Correlative microscopy.

In recent years correlative microscopy, combining the power and advantages of different imaging system, e.g., light, electrons, X-ray, NMR, etc., has become an important tool for biomedical research. Among all the possible combinations of techniques, light and electron microscopy, have made an especially big step forward and are being implemented in more and more research labs. Electron microscopy profits from the high spatial resolution, the direct recognition of the cellular ultrastructure and identification of the organelles. It, however, has two severe limitations: the restricted field of view and the fact that no live imaging can be done. On the other hand light microscopy has the advantage of live imaging, following a fluorescently tagged molecule in real time and at lower magnifications the large field of view facilitates the identification and location of sparse individual cells in a large context, e.g., tissue. The combination of these two imaging techniques appears to be a valuable approach to dissect biological events at a submicrometer level. Light microscopy can be used to follow a labelled protein of interest, or a visible organelle such as mitochondria, in time, then the sample is fixed and the exactly same region is investigated by electron microscopy. The time resolution is dependent on the speed of penetration and fixation when chemical fixatives are used and on the reaction time of the operator for cryo-fixation. Light microscopy can also be used to identify cells of interest, e.g., a special cell type in tissue or cells that have been modified by either transfections or RNAi, in a large population of non-modified cells. A further application is to find fluorescence labels in cells on a large section to reduce searching time in the electron microscope. Multiple fluorescence labelling of a series of sections can be correlated with the ultrastructure of the individual sections to get 3D information of the distribution of the marked proteins: array tomography. More and more efforts are put in either converting a fluorescence label into an electron dense product or preserving the fluorescence throughout preparation for the electron microscopy. Here, we will review successful protocols and where possible try to extract common features to better understand the importance of the individual steps in the preparation. Further the new instruments and software, intended to ease correlative light and electron microscopy, are discussed. Last but not least we will detail the approach we have chosen for correlative microscopy.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism.

Possible new ways in the pharmacological treatment of bipolar disorder and comorbid alcoholism. Azorin JM, Bowden CL, Garay RP, Perugi G, Vieta E, Young AH. Source Department of Psychiatry, CHU Sainte Marguerite, Marseilles, France. Abstract About half of all bipolar patients have an alcohol abuse problem at some point of their lifetime. However, only one randomized, controlled trial of pharmacotherapy (valproate) in this patient population was published as of 2006. Therefore, we reviewed clinical trials in this indication of the last four years (using mood stabilizers, atypical antipsychotics, and other drugs). Priority was given to randomized trials, comparing drugs with placebo or active comparator. Published studies were found through systematic database search (PubMed, Scirus, EMBASE, Cochrane Library, Science Direct). In these last four years, the only randomized, clinically relevant study in bipolar patients with comorbid alcoholism is that of Brown and colleagues (2008) showing that quetiapine therapy decreased depressive symptoms in the early weeks of use, without modifying alcohol use. Several other open-label trials have been generally positive and support the efficacy and tolerability of agents from different classes in this patient population. Valproate efficacy to reduce excessive alcohol consumption in bipolar patients was confirmed and new controlled studies revealed its therapeutic benefit to prevent relapse in newly abstinent alcoholics and to improve alcohol hallucinosis. Topiramate deserves to be investigated in bipolar patients with comorbid alcoholism since this compound effectively improves physical health and quality of life of alcohol-dependent individuals. In conclusion, randomized, controlled research is still needed to provide guidelines for possible use of valproate and other agents in patients with a dual diagnosis of bipolar disorder and substance abuse or dependence.

Classifier combination for in vivo magnetic resonance spectra of brain tumours

In this paper we present a multi-stage classifier for magnetic resonance spectra of human brain tumours which is being developed as part of a decision support system for radiologists. The basic idea is to decompose a complex classification scheme into a sequence of classifiers, each specialising in different classes of tumours and trying to reproducepart of the WHO classification hierarchy. Each stage uses a particular set of classification features, which are selected using a combination of classical statistical analysis, splitting performance and previous knowledge.Classifiers with different behaviour are combined using a simple voting scheme in order to extract different error patterns: LDA, decision trees and the k-NN classifier. A special label named "unknown¿ is used when the outcomes of the different classifiers disagree. Cascading is alsoused to incorporate class distances computed using LDA into decision trees. Both cascading and voting are effective tools to improve classification accuracy. Experiments also show that it is possible to extract useful information from the classification process itself in order to helpusers (clinicians and radiologists) to make more accurate predictions and reduce the number of possible classification mistakes.

Controle de autenticidade de óleos de copaíba comerciais por cromatografia gasosa de alta resolução

Copaiba oil is a resin extracted from the trunk of trees of Copaifera species which grow in Brazil where it is widely used in popular medicine as an anti-inflammatory, antiseptic anti-bactericidal, diuretic, dermatological, expectorant, and anti-infective. The comparative study of the composition of commercial copaiba oils was carried out by high resolution gas chromatography (HRGC) and high resolution gas chromatography-mass spectrometry (HRGC-MS) analysis. The commercial oils were compared with authentic oils, collected from the southeast and northern regions of Brazil. Sixteen commercial oils were analysed and two of them revealed adulterations with fatty acids. Using the chromatographic profile of authentic copaiba species oils, it is possible to analyse commercial oils and determine the authenticity of these materials.

Determinação espectrofotométrica por injeção em fluxo de vitamina B6 (piridoxina) em formulações farmacêuticas

A flow injection (FI) spectrophotometric procedure is proposed for the determination of vitamin B6 (pyridoxine hydrochloride) in pharmaceutical preparations. Powdered samples containing from 2.5 to 4.5 mg, were previously dissolved in 0.1 mol L-1 phosphate buffer solution (pH 7.0) and a volume of 500 muL was injected directly into a carrier stream consisting of this same phosphate buffer solution, flowing at 4.4 mL min-1. The stable blue indophenol dye produced in the oxidation of pyridoxine hydrochloride by potassium hexacyanoferrate(III) and N,N-diethyl-p-phenylenediamine solution was directly measured at 684 nm. Vitamin B6 was determined in five pharmaceutical preparations in the 0.5 to 6.0 mg L-1 concentration range (calibration graph: A= -0.00499 + 0.11963 C; r= 0.9991, where A is the absorbance and C is the vitamin B6 concentration in mg L-1), with a detection limit of 0.02 mg L-1 (3 Sblank/slope). The recovery of this vitamin from three samples ranged from 97.5 to 103.3 %. The analytical frequency was 62 h-1 and r.s.d. were less than 2% for solutions containing 1.0 and 3.0 mg L-1 vitamin B6 (n= 10). The results obtained for the determination of vitamin B6 in commercial formulations were in good agreement with those obtained by a spectrophotometric procedure (r=0.9997) and also with the label values (r= 0.9998).

Alguns aspectos de imunoensaios aplicados à química analítica

In the last years, the use of antibody-antigen interactions, has earned attention not only for clinical analysis, but also for food industry and environmental control. Since the scope and diversity of immunoassay technology have shown a wide development. Continuous advances in order to analyse complex matrices, to improve reliability, simplicity (nonseparation) and to get multiple simultaneous assays, and extreme sensitivity (lower than zeptomole detection limits) are increasing. Many strategies have been investigated including chemiluminescent enzyme immunoassays, DNA as label and development of flow injection and immunosensors techniques. This subject became very usefull and important in nowadays that are taught in the undergraduate courses of chemistry in the european universities. However in our country are still ignored in the chemistry course.

Determinação espectrofotométrica de vitamina B2 (riboflavina) em formulações farmacêuticas empregando sistema de análises por injeção em fluxo

A flow injection spectrophotometric procedure exploiting merging zones is proposed for determining vitamin B2 (riboflavin) in pharmaceutical preparations. The determination is based on the red-colored complex formation between vitamin B2 and silver(I) which was measured at 520 nm. Vitamin B2 was determined in four pharmaceutical preparations in the 1.0 to 50.0 mg L-1 concentration range, with a detection limit of 0.5 mg L-1. The recovery from three samples ranged from 98.0 to 104.0 %. The analytical frequency was 42 h-1 and r.s.d. were lower than 1% for solutions containing 10.0, 30.0 and 50.0 mg L-1 vitamin B2 (n= 10). The results obtained in commercial formulations using the FIA procedure were in good agreement with those obtained by using a conventional fluorimetric procedure (r=0.9998) and also with the label values (r= 0.9997).

Nanoparticle Labels in Bioaffinity Assays

Nanoparticles offer adjustable and expandable reactive surface area compared to the more traditional solid phase forms utilized in bioaffinity assays due to the high surface to-volume ratio. The versatility of nanoparticles is further improved by the ability to incorporate various molecular complexes such as luminophores into the core. Nanoparticle labels composed of polystyrene, silica, inorganic crystals doped with high number of luminophores, preferably lanthanide(III) complexes, are employed in bioaffinity assays. Other label species such as semiconductor crystals (quantum dots) or colloidal gold clusters are also utilized. The surface derivatization of such particles with biomolecules is crucial for the applicability to bioaffinity assays. The effectiveness of a coating is reliant on the biomolecule and particle surface characteristics and the selected coupling technique. The most critical aspects of the particle labels in bioaffinity assays are their size-dependent features. For polystyrene, silica and inorganic phosphor particles, these include the kinetics, specific activity and colloidal stability. For quantum dots and gold colloids, the spectral properties are also dependent on particle size. This study reports the utilization of europium(III)-chelate-embedded nanoparticle labels in the development of bioaffinity assays. The experimental covers both the heterogeneous and homogeneous assay formats elucidating the wide applicability of the nanoparticles. It was revealed that the employment of europium(III) nanoparticles in heterogeneous assays for viral antigens, adenovirus hexon and hepatitis B surface antigen (HBsAg), resulted in sensitivity improvement of 10-1000 fold compared to the reference methods. This improvement was attributed to the extreme specific activity and enhanced monovalent affinity of the nanoparticles conjugates. The applicability of europium(III)-chelate-doped nanoparticles to homogeneous assay formats were proved in two completely different experimental settings; assays based on immunological recognition or proteolytic activity. It was shown that in addition to small molecule acceptors, particulate acceptors may also be employed due to the high specific activity of the particles promoting proximity-induced reabsorptive energy transfer in addition to non-radiative energy transfer. The principle of proteolytic activity assay relied on a novel dual-step FRET concept, wherein the streptavidin-derivatized europium(III)-chelate-doped nanoparticles were used as donors for peptide substrates modified with biotin and terminal europium emission compliant primary acceptor and a secondary quencher acceptor. The recorded sensitized emission was proportional to the enzyme activity, and the assay response to various inhibitor doses was in agreement with those found in literature showing the feasibility of the technique. Experiments regarding the impact of donor particle size on the extent of direct donor fluorescence and reabsorptive excitation interference in a FRET-based application was conducted with differently sized europium(III)-chelate-doped nanoparticles. It was shown that the size effect was minimal

Maahantuonnin logistisen prosessin analysointi ja kilpailukyvyn parantaminen

Kodintekniikka-alan kilpailutilanne on kiristynyt viime vuosina merkittävästi uusien kilpailijoiden ja myymälämäärän lisääntymisen myötä. Myös vuonna 2008 alkanut talouskriisi ja sen vaikutukset heikentävät alan näkymiä tulevina vuosina. Yritysten onkin täytynyt etsiä vaihtoehtoisia toimintatapoja kannattavuuden ja asiakasmäärien parantamisen vuoksi. Kohdeyritys on harjoittanut maahantuontia omien tuotemerkkien sekä virallisen maahantuonnin muodossa jo pitkään. Yrityksessä ei kuitenkaan ole aikaisemmin selvitetty logistisen prosessin tehokkuutta, joten yrityksessä on esiintynyt tarve selvittää prosessin kustannusrakenne ja mahdolliset heikkoudet. Tutkimuksessa tarkastellaan kohdeyrityksen oman maahantuonnin logistista prosessia sekä pyritään löytämään maahantuonnin kilpailukykyä lisääviä tekijöitä. Päätutkimustyyppinä on tapaustutkimus ja sen lisäksi tutkimusmenetelmänä käytettiin toimintatutkimusta. Tutkimuksen aineisto on sekä kvalitatiivista että kvantitatiivista. Tutkimuksen tuloksista ilmenee, että logistinen prosessi on kohdeyrityksessä monelta osin hoidettu hyvin, mutta joitain parannuskohteitakin löytyi. Myös maahantuonnin kilpailukyvyn parantamiseksi löydettiin useita keinoja. Parannustoimilla on mahdollista säästää kustannuksissa sekä parantaa maahantuonnin palveluastetta.