Use of the dried blood spot sampling process coupled with fast gas chromatography and negative-ion chemical ionization tandem mass spectrometry: application to fluoxetine, norfluoxetine, reboxetine, and paroxetine analysis.

The objective of this work was to combine the advantages of the dried blood spot (DBS) sampling process with the highly sensitive and selective negative-ion chemical ionization tandem mass spectrometry (NICI-MS-MS) to analyze for recent antidepressants including fluoxetine, norfluoxetine, reboxetine, and paroxetine from micro whole blood samples (i.e., 10 microL). Before analysis, DBS samples were punched out, and antidepressants were simultaneously extracted and derivatized in a single step by use of pentafluoropropionic acid anhydride and 0.02% triethylamine in butyl chloride for 30 min at 60 degrees C under ultrasonication. Derivatives were then separated on a gas chromatograph coupled with a triple-quadrupole mass spectrometer operating in negative selected reaction monitoring mode for a total run time of 5 min. To establish the validity of the method, trueness, precision, and selectivity were determined on the basis of the guidelines of the "Société Française des Sciences et des Techniques Pharmaceutiques" (SFSTP). The assay was found to be linear in the concentration ranges 1 to 500 ng mL(-1) for fluoxetine and norfluoxetine and 20 to 500 ng mL(-1) for reboxetine and paroxetine. Despite the small sampling volume, the limit of detection was estimated at 20 pg mL(-1) for all the analytes. The stability of DBS was also evaluated at -20 degrees C, 4 degrees C, 25 degrees C, and 40 degrees C for up to 30 days. Furthermore, the method was successfully applied to a pharmacokinetic investigation performed on a healthy volunteer after oral administration of a single 40-mg dose of fluoxetine. Thus, this validated DBS method combines an extractive-derivative single step with a fast and sensitive GC-NICI-MS-MS technique. Using microliter blood samples, this procedure offers a patient-friendly tool in many biomedical fields such as checking treatment adherence, therapeutic drug monitoring, toxicological analyses, or pharmacokinetic studies.

Trace element monitoring in the ICU: quality and economic impact of a change in sampling practice.

BACKGROUND & AIMS: Trace elements (TE) are involved in the immune and antioxidant defences which are of particular importance during critical illness. Determining plasma TE levels is costly. The present quality control study aimed at assessing the economic impact of a computer reminded blood sampling versus a risk guided on-demand monitoring of plasma concentrations of selenium, copper, and zinc. METHODS: Retrospective analysis of 2 cohorts of patients admitted during 6 months periods in 2006 and 2009 to the ICU of a University hospital. INCLUSION CRITERIA: to receive intravenous micronutrient supplements and/or to have a TE sampling during ICU stay. The TE samplings were triggered by computerized reminder in 2006 versus guided by nutritionists in 2009. RESULTS: During the 2 periods 636 patients met the inclusion criteria out of 2406 consecutive admissions, representing 29.7% and 24.9% respectively of the periods' admissions. The 2009 patients had higher SAPS2 scores (p = 0.02) and lower BMI compared to 2006 (p = 0.007). The number of laboratory determinations was drastically reduced in 2009, particularly during the first week, despite the higher severity of the cohort, resulting in à 55% cost reduction. CONCLUSIONS: The monitoring of TE concentrations guided by a nutritionist resulted in a reduction of the sampling frequency, and targeting on the sickest high risk patients, requiring a nutritional prescription adaptation. This control leads to cost reduction compared to an automated sampling prescription.

Procurement and inventory management in product ramp down

Tuotteiden elinkaaret elektroniikkateollisuudessa ovat lyhentyneet entisestään. Paineet uusien kehittyneempien tuotteiden lanseeraamiselle ovat kasvaneet. Huonosti hoidettu tuotevaihto voi aiheuttaa merkittäviä kustannuksia yritykselle mikäli alasajon kustannusvaikutusta tulokseen aliarvioidaan. Työ käsittelee markkinoilta poistuvan tuotteen materiaalivirtojen hallintaa tuotevaihdon aikana. Lähtökohtana työssä oli kehittää toimintatapa miten tuotteen alasajon aikana tulisi toimia sekä mallintaa hankintaketju riskien ja pullonkaulojen löytämiseksi. Päätavoitteena oli materiaalivaraston arvon minimoiminen sekä ylijäämämateriaalien hyödyntäminen. Työn merkittävimpiä tuloksia oli hankintaketjun materiaalivirtojen seurantaan kehitetty Excel työkalu sekä alasajon liittyvien työvaiheiden kuvaaminen.

DOPPLERVELOCIMETRIA DO DUTO VENOSO NO CÁLCULO DE RISCO PARA SÍNDROME DE DOWN NO PRIMEIRO TRIMESTRE DA GRAVIDEZ

OBJETIVO: Investigar a validade da Dopplervelocimetria do duto venoso em detectar a síndrome de Down entre 10 e 14 semanas de gestação e propor novo cálculo de risco. PACIENTES E MÉTODOS: Foram estudados 491 fetos, consecutivamente. Em 132 casos realizou-se estudo citogenético no material obtido por biópsia de vilosidade coriônica e em 359 o resultado baseou-se no fenótipo do recém-nascido. Em todos os fetos realizaram-se, além da ultra-sonografia de rotina, a medida da translucência nucal e a Dopplervelocimetria do duto venoso. Na análise estatística foram utilizados o teste paramétrico T de "student", a análise de variância e a regressão linear. Posteriormente, calcularam-se: sensibilidade, especificidade, valores preditivos positivo e negativo, probabilidade de falso-positivo e razões de probabilidades. RESULTADOS: Ocorreram 21 casos de trissomia do cromossomo 21. Desses casos, o fluxo no duto venoso durante a contração atrial foi ausente em três casos e reverso em 17 - sensibilidade de 95,2%. No grupo de fetos normais (470 casos), oito avaliações mostraram alterações do Doppler do duto venoso (especificidade de 98,2%, valores preditivos positivo e negativo de 71,4% e 99,8%, respectivamente, e razões de probabilidades positiva e negativa de 56 e 0,1, respectivamente). CONCLUSÕES: Nossos resultados preliminares sugerem que a presença de síndrome de Down pode ser fortemente suspeitada se houver fluxo reverso ou ausente no duto venoso. Especulamos a possibilidade de cálculo de novo risco para trissomia do 21 com base no Doppler do duto venoso. Utilizando o programa de risco da Fetal Medicine Foundation como risco basal, teríamos um fator multiplicador de aproximadamente 0,1 (razão de probabilidade negativa), caso duto normal, ou de 50 (razão de probabilidade positiva), caso duto reverso ou ausente, e assim, teremos novo risco corrigido.

The down-regulation of disgust by implementation intentions: experiential and physiological concomitants

Emotion regulation plays a key role in mental health and psychopathology. Therefore, it seems important to develop effective forms of emotion regulation. Implementation intentions are if-then plans that help people attain their self-regulatory goals. Perspective-taking and response-focused implementation intentions have been shown to reduce feelings of unpleasantness and arousal, respectively, in response to briefly presented disgusting pictures. The present study addressed the open research questions whether forming these types of implementation intentions is effective in regulating affect during prolonged presentation of disgusting pictures, and whether it is associated with changes in physiological arousal. Eighty-one participants viewed disgusting, neutral, and pleasant pictures of 6 s duration under four instructions: the goal intention to not get disgusted, this goal intention furnished with a perspective-taking or a response-focused implementation intention, and no emotion regulation instructions. The dependent variables were ratings of disgust, valence, arousal, and electrodermal activity. Only perspective-taking implementation intention participants significantly reduced their disgust and unpleasantness as compared to goal-intention and control participants. Arousal and skin conductance did not significantly differ between conditions. The effectiveness of response-focused but not perspective-taking implementation intentions seems to be substantially reduced during sustained exposure duration.

From the Olympic dream to a down to earth approach: Lausanne's sports events hosting strategy

In the context of globalized competition among territories, cities, regions and countries have to find new ways to be attractive to companies, investors, tourists and residents. In that perspective, major sports events (such as the Olympic Games or the FIFA World Cup) are often seen as a lever for territorial development. Based on that idea, many sports events hosting strategies have emerged in the 1980s and 1990s. However, the growing competition in the sports events' market and the gigantism of those major events, forced some territories to turn to smaller events. This necessary resize of their strategy raises the question of their capacity to meet the initial objectives, which aim usually at developing the economy and promoting the image of the host destination. This essay sketches out the evolution of a sports events hosting strategy in a city that does not have the resources (either financial, human or in terms of infrastructures) to attract major international sports events. The challenges they have to face and a possible solution based on the event portfolio perspective are discussed through the article.

Anxiety, depression, and attachment before and after the first-trimester screening for Down syndrome: comparing couples who undergo ART with those who conceive spontaneously.

OBJECTIVES: This study's aim was to describe the emotional status of parents to be before and after the first-trimester combined prenatal screening test. METHODS: One hundred three couples participated, of which 52 had undergone an in vitro fertilization/intracytoplasmic sperm injection treatment [assisted reproductive technology (ART)] and 51 had conceived spontaneously. Participants completed the state scale of the State-trait Anxiety Inventory, the Edinburgh Depression Scale, and the Maternal and Paternal Antenatal Attachment Questionnaire before the first-trimester combined prenatal screening test at around 12 weeks of gestational age (T1) and just after receiving the results at approximately 14 weeks of gestational age (T2). RESULTS: We observed a significant decrease in anxiety and depression symptoms and a significant increase in attachment from T1 to T2. Results showed no differences between groups at either time point, which suggests that ART parents are more similar to than different from parents conceiving spontaneously. Furthermore, given the importance of anxiety during pregnancy, a subsample of women with clinical anxiety was identified. They had significantly higher rates of clinical depression and lower attachment. CONCLUSIONS: These results indicate that, regardless of whether conception was through ART or spontaneous, clinical anxiety in women over the prenatal testing period is associated with more vulnerability during pregnancy (i.e. clinical depression and less attachment to fetus). © 2015 John Wiley & Sons, Ltd.

Caveolin-1 down-regulates inducible nitric oxide synthase via the proteasome pathway in human colon carcinoma cells.

To investigate whether caveolin-1 (cav-1) may modulate inducible nitric oxide synthase (iNOS) function in intact cells, the human intestinal carcinoma cell lines HT29 and DLD1 that have low endogenous cav-1 levels were transfected with cav-1 cDNA. In nontransfected cells, iNOS mRNA and protein levels were increased by the addition of a mix of cytokines. Ectopic expression of cav-1 in both cell lines correlated with significantly decreased iNOS activity and protein levels. This effect was linked to a posttranscriptional mechanism involving enhanced iNOS protein degradation by the proteasome pathway, because (i) induction of iNOS mRNA by cytokines was not affected and (ii) iNOS protein levels increased in the presence of the proteasome inhibitors N-acetyl-Leu-Leu-Norleucinal and lactacystin. In addition, a small amount of iNOS was found to cofractionate with cav-1 in Triton X-100-insoluble membrane fractions where also iNOS degradation was apparent. As has been described for endothelial and neuronal NOS isoenzymes, direct binding between cav-1 and human iNOS was detected in vitro. Taken together, these results suggest that cav-1 promotes iNOS presence in detergent-insoluble membrane fractions and degradation there via the proteasome pathway.