Niobium and rare earth minerals from the Virulundo carbonatite, Namibe, Angola

The Virulundo carbonatite in Angola, one of the biggest in the world, contains pyrochlore as an accessory mineral in all of the carbonatite units (calciocarbonatites, ferrocarbonatites, carbonatite breccias, trachytoids). The composition of the primary pyrochlore crystals is very close to fluornatrocalciopyrochlore in all these units. High-temperature hydrothermal processes caused the pseudomorphic replacement of the above crystals by a second generation of pyrochlore, characterized by lower F and Na contents. Low-temperature hydrothermal replacement of the above pyrochlores, associated with production of quartz-carbonates-fluorite veins, controled the development of a third generation of pyrochlore, characterized by high Sr contents. Finally, supergene processes produced the development of a secondary paragenesis in the carbonatite, consisting in late carbonates, goethite, hollandite and REE minerals (mainly synchysite-(Ce), britholite-(Ce), britholite-(La), cerite-(Ce)). Separation of Ce from the other REE was allowed by oxidizing conditions. Therefore, Ce4+ was also incorporated into a late generation of pyrochlore, which is also strongly enriched in Ba and strongly depleted in Ca and Na

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

Malaria chemoprophylaxis recommendations for immigrants to Europe, visiting relatives and friends--a Delphi method study.

BACKGROUND: Numbers of travellers visiting friends and relatives (VFRs) from Europe to malaria endemic countries are increasing and include long-term and second generation immigrants, who represent the major burden of malaria cases imported back into Europe. Most recommendations for malaria chemoprophylaxis lack a solid evidence base, and often fail to address the cultural, social and economic needs of VFRs. METHODS: European travel medicine experts, who are members of TropNetEurop, completed a sequential series of questionnaires according to the Delphi method. This technique aims at evaluating and developing a consensus through repeated iterations of questionnaires. The questionnaires in this study included questions about professional experience with VFRs, controversial issues in malaria prophylaxis, and 16 scenarios exploring indications for prescribing and choice of chemoprophylaxis. RESULTS: The experience of participants was rather diverse as was their selection of chemoprophylaxis regimen. A significant consensus was observed in only seven of 16 scenarios. The analysis revealed a wide variation in prescribing choices with preferences grouped by region of practice and increased prescribing seen in Northern Europe compared to Central Europe. CONCLUSIONS: Improving the evidence base on efficacy, adherence to chemoprophylaxis and risk of malaria and encouraging discussion among experts, using techniques such as the Delphi method, may reduce the variability in prescription in European travel clinics.

Politique fédérale des agglomérations dans les domaines des transports et de l'urbanisation

La croissance de la population, de l'économie et des transports individuels motorisés, particulièrement depuis la seconde moitié du 20ème siècle, ont notamment comme corollaire le développement urbanistique hors des frontières de la ville-centre et la formation des agglomérations. Ces zones urbaines sont stratégiques puisqu'elles accueillent une part toujours plus importante de la population et représentent le moteur de l'économie nationale. Toutefois, le développement des agglomérations et de la mobilité individuelle motorisée ne va pas sans poser de nombreux problèmes, dont la résolution nécessite de les aborder à l'échelle de l'agglomération, en coordonnant les transports et l'urbanisation. Notre système politique fédéral se définit notamment par une répartition des compétences dans une multitude de domaines entre les trois niveaux institutionnels de la Confédération, des cantons et des communes. Cette réalité est particulièrement vraie en matière d'aménagement du territoire. Il est à noter que les plus petites unités institutionnelles (les communes) conservent encore aujourd'hui des prérogatives importantes dans ce domaine. Au début des années 2000, la Confédération a développé une politique publique en faveur de ces zones stratégiques. Au moyen du fonds d'infrastructure, la politique fédérale des agglomérations dans les domaines des transports et de l'urbanisation est une politique publique incitative. Le dépôt, par les agglomérations, d'un projet respectant un cahier des charges précis et proposant des mesures de coordination entre les transports et l'urbanisation, permet d'obtenir un cofinancement fédéral du transport d'agglomération. Parmi les projets d'agglomération de première génération présentés à la Confédération, certains ont obtenu le cofinancement, d'autres pas. Le dimensionnement trop généreux des surfaces à bâtir fut notamment un facteur d'échec du projet d'agglomération de Fribourg, alors que la capacité à développer l'urbanisation à l'intérieur de l'agglomération fut un facteur de succès du projet Lausanne-Morges. L'analyse des projets d'agglomération Riviera et Monthey-Aigle, qui sont des projets de deuxième génération, confrontée à des entretiens avec des urbanistes et des responsables politiques, permet d'identifier leurs faiblesses et leurs atouts. Le projet d'agglomération Riviera présente une complémentarité des territoires et un grand potentiel de développement, mais aussi un manque de cohésion des partenaires du projet. Quant au projet Monthey-Aigle, il existe une réelle volonté politique de trouver des solutions aux conflits, mais les possibilités de développer les transports publics sont faibles. Dans le cadre de l'examen fédéral de ces deux projets d'agglomération, les éléments précités pourraient être des facteurs d'échec ou de succès. La politique publique fédérale invite les agglomérations à penser le développement de leurs transports et de leur urbanisation à un niveau global. La prise de hauteur et la coordination politique que cela suppose sont à même d'améliorer le lieu de vie des trois-quarts de la population suisse et de préserver le moteur de l'économie nationale. The growth of population, economy and personal motorised transportation, most particularly since the second half of the 20th century, has, as a consequence, induced an expansion of urban areas outside the borders of cities and encouraged the formation of urban agglomerations. These urban zones are of strategic importance as they attract an increasingly large population and represent a real driver of the national economy. However, the development of these agglomerations and the motorised mobility of their inhabitants cause numerous problems which require solutions to be adopted at the level of the agglomeration involving the interconnection of transport and urbanisation. Our federal political system is characterised by a distribution of responsibilities in many domains among the three institutional levels, namely the Confederation, the cantons and the communes. This is particularly the case of territorial developments. It should be noted that the smallest institutional units, the communes, still hold today important responsibilities in this area. At the beginning of the years 2000, the Confederation has developed a public policy in favour of these strategic zones. Through the establishment of an infrastructure fund, the federal policy in favour of urban agglomerations in the areas of transport and urbanisation aims at providing incentives to agglomerations. The submission by the agglomeration of a project containing a clear description of tasks and measures to integrate transport and urbanisation can result in a cofinancing participation by the Confederation in this project. Among the projects of first generation which had been submitted to the Confederation, some have received the cofinancing, others have not. The too generous dimension of the building areas in the project submitted by the agglomeration of Fribourg was a factor of its failure, while the capacity to develop urbanisation within the agglomeration was a factor of success for the Lausanne-Morges project. The analysis of the projects of the agglomerations Riviera and Monthey-Aigle which are projects of the second generation, as well as the interviews of urbanists and concerned officials have allowed us to identify their strengths and weaknesses. The Riviera project provides a complementary approach and a high potential of territorial developments, but at the same time denotes a lack of cohesion among partners of the project. With respect to the project Monthey-Aigle, there is a real political willingness to resolve conflicts, but the potential for the development of public transports is small. In the consideration by the Confederation of these two projects, the factors mentioned above may bring success or failure. The federal public policy incites the agglomerations to conceive the development of their transportation and urbanisation plans at a global level. The elevation of interests and the political coordination that this requires can improve the place of living of ¾ of the Swiss population and preserve the engine of growth of the national economy.

Ensimmäisen ja toisen sukupolven nestemäisten liikennebiopolttoaineiden kasvihuonekaasupäästöjenvertailu

Elinkaariarviointia voidaan käyttää ensimmäisen ja toisensukupolven nestemäisten liikennebiopolttoaineiden kasvihuonekaasupäästöjen ja primäärienergian kulutuksen vertailuun. Elinkaariarviointia käyttämällä pyritään tuottamaan luotettavaa tietoa koko elinkaaren ajalta. Nestemäisiä liikennebiopolttoaineita käsittelevissä tutkimuksissa elinkaari jaetaan yleensä kahteen osaan,joista suurempi painoarvo on elinkaaren alkuosalla. Tässä diplomityössä tehdään yksinkertaistettu elinkaariarviointi selluloosaetanolin ja Fischer-Tropsch-dieselin elinkaaren alkuosalle ja verrataan niitä sitten ohraetanoliin ja rypsimetyyliesteriin. Tässä työssä keskitytään primäärienergian kulutukseen sekä hiilidioksidi-, metaani- ja dityppioksidipäästöihin. Selluloosaetanolin raaka-aineena tarkasteltiin ruokohelpeä, Fischer-Tropsch-dieselin raaka-aineena metsätähdettä. Diplomityö osoitti, että toisen sukupolven nestemäisten liikennebiopolttoaineiden tuotannossa kuluu vähemmän primäärienergiaa ja syntyy vähemmän kasvihuonekaasupäästöjä kuin ensimmäisen sukupolven nestemäisten liikennebiopolttoaineiden tuotannossa. Sama tulos on saatu myös muissa aihetta käsittelevissä tutkimuksissa.

Antipsychotic polypharmacy in a regional health service: a population-based study

Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine. Background To analyse the extent and profile of outpatient regular dispensation of antipsychotics, both in combination and monotherapy, in the Barcelona Health Region (Spain), focusing on the use of clozapine and long-acting injections (LAI). Methods Antipsychotic drugs dispensed for people older than 18 and processed by the Catalan Health Service during 2007 were retrospectively reviewed. First and second generation antipsychotic drugs (FGA and SGA) from the Anatomical Therapeutic Chemical classification (ATC) code N05A (except lithium) were included. A patient selection algorithm was designed to identify prescriptions regularly dispensed. Variables included were age, gender, antipsychotic type, route of administration and number of packages dispensed. Results A total of 117,811 patients were given any antipsychotic, of whom 71,004 regularly received such drugs. Among the latter, 9,855 (13.9%) corresponded to an antipsychotic combination, 47,386 (66.7%) to monotherapy and 13,763 (19.4%) to unspecified combinations. Of the patients given antipsychotics in association, 58% were men. Olanzapine (37.1%) and oral risperidone (36.4%) were the most common dispensations. Analysis of the patients dispensed two antipsychotics (57.8%) revealed 198 different combinations, the most frequent being the association of FGA and SGA (62.0%). Clozapine was dispensed to 2.3% of patients. Of those who were receiving antipsychotics in combination, 6.6% were given clozapine, being clozapine plus amisulpride the most frequent association (22.8%). A total of 3.800 patients (5.4%) were given LAI antipsychotics, and 2.662 of these (70.1%) were in combination. Risperidone was the most widely used LAI. Conclusions The scant evidence available regarding the efficacy of combining different antipsychotics contrasts with the high number and variety of combinations prescribed to outpatients, as well as with the limited use of clozapine.

Neuropeptide Y and corticotropin-releasing hormone in CSF mark response to antidepressive treatment with citalopram.

Neuropeptides appear to play a role in the pathophysiology of depression and electroconvulsive treatment and lithium affect these compounds in human cerebrospinal fluid (CSF) and rodent brain. Consequently, we investigated whether long-term treatment with the selective serotonin reuptake inhibitor (SSRI) citalopram (Cit) would also affect neuropeptides in CSF of depressed patients. Changes in CSF monoamine metabolites were also explored. CSF concentrations of corticotropin-releasing hormone (CRH)-like immunoreactivity (-LI), neuropeptide Y (NPY)-LI, and Cit were determined in 21 patients with major depression. Lumbar puncture was performed in the morning at baseline and was repeated after at least 4 wk of Cit treatment (40 mg/d). The severity of depression was assessed by the Hamilton Rating Scale for Depression (HAMD). Cit treatment was associated with a significant increase in NPY-LI and decrease in CRH-LI. An evaluation of the relationship between changes in concentrations of NPY-LI, CRH-LI, and the clinical response showed significant correlations between these parameters. Significant NPY and CRH changes in CSF following treatment as well as correlations to changes in HAMD support the hypothesis that these two peptides play a role in affective disorders and are markers of therapeutic response.

L'immunoscintigraphie par les anticorps monoclonaux radiomarqués. Evolution d'une méthode de diagnostic du cancer et espoir d'une nouvelle forme de thérapie [Immunoscintigraphy using radio-labeled monoclonal antibodies. Development of a method of cancer diagnosis and hopes for a new form of therapy].

Personal results are presented to illustrate the development of immunoscintigraphy for the detection of cancer over the last 12 years, from the early experimental results in nude mice grafted with human colon carcinoma to the most modern form of immunoscintigraphy applied to patients, using I123 labeled Fab fragments from monoclonal anti-CEA antibodies detected by single photon emission computerized tomography (SPECT). The first generation of immunoscintigraphy used I131 labeled, immunoadsorbent purified, polyclonal anti-CEA antibodies and planar scintigraphy, as the detection system. The second generation used I131 labeled monoclonal anti-CEA antibodies and SPECT, while the third generation employed I123 labeled fragments of monoclonal antibodies and SPECT. The improvement in the precision of tumor images with the most recent forms of immunoscintigraphy is obvious. However, we think the usefulness of immunoscintigraphy for routine cancer management has not yet been entirely demonstrated. Further prospective trials are still necessary to determine the precise clinical role of immunoscintigraphy. A case report is presented on a patient with two liver metastases from a sigmoid carcinoma, who received through the hepatic artery a therapeutic dose (100 mCi) of I131 coupled to 40 mg of a mixture of two high affinity anti-CEA monoclonal antibodies. Excellent localisation in the metastases of the I131 labeled antibodies was demonstrated by SPECT and the treatment was well tolerated. The irradiation dose to the tumor, however, was too low at 4300 rads (with 1075 rads to the normal liver and 88 rads to the bone marrow), and no evidence of tumor regression was obtained. Different approaches for increasing the irradiation dose delivered to the tumor by the antibodies are considered.

Mapping HIV/STI behavioural surveillance in Europe.

BACKGROUND: Used in conjunction with biological surveillance, behavioural surveillance provides data allowing for a more precise definition of HIV/STI prevention strategies. In 2008, mapping of behavioural surveillance in EU/EFTA countries was performed on behalf of the European Centre for Disease prevention and Control. METHOD: Nine questionnaires were sent to all 31 member States and EEE/EFTA countries requesting data on the overall behavioural and second generation surveillance system and on surveillance in the general population, youth, men having sex with men (MSM), injecting drug users (IDU), sex workers (SW), migrants, people living with HIV/AIDS (PLWHA), and sexually transmitted infection (STI) clinics patients. Requested data included information on system organisation (e.g. sustainability, funding, institutionalisation), topics covered in surveys and main indicators. RESULTS: Twenty-eight of the 31 countries contacted supplied data. Sixteen countries reported an established behavioural surveillance system, and 13 a second generation surveillance system (combination of biological surveillance of HIV/AIDS and STI with behavioural surveillance). There were wide differences as regards the year of survey initiation, number of populations surveyed, data collection methods used, organisation of surveillance and coordination with biological surveillance. The populations most regularly surveyed are the general population, youth, MSM and IDU. SW, patients of STI clinics and PLWHA are surveyed less regularly and in only a small number of countries, and few countries have undertaken behavioural surveys among migrant or ethnic minorities populations. In many cases, the identification of populations with risk behaviour and the selection of populations to be included in a BS system have not been formally conducted, or are incomplete. Topics most frequently covered are similar across countries, although many different indicators are used. In most countries, sustainability of surveillance systems is not assured. CONCLUSION: Although many European countries have established behavioural surveillance systems, there is little harmonisation as regards the methods and indicators adopted. The main challenge now faced is to build and maintain organised and functional behavioural and second generation surveillance systems across Europe, to increase collaboration, to promote robust, sustainable and cost-effective data collection methods, and to harmonise indicators.

Vuelos de la defoliadora de maíz, pastos y céspedes, Mythimna (Pseudaletia) unipuncta (Haworth) en la zona de Lleida

Mythimna unipuncta causa daños en gramíneas cultivadas (principalmente maíz) y céspedes cuya importancia ha ido aumentando los últimos años. En nuestra región presenta cuatro vuelos de adultos. Los daños causados por la descendencia del primer y cuarto vuelo no han sido apreciables, mientras que la descendencia del segundo vuelo ha causado daños de consideración en algunos campos de maíz y la del tercero en céspedes públicos. Se han calculado los grados -día necesarios para completar cada generación en campo y en el laboratorio. Se ha observado que casi todas las hembras capturadas del cuarto vuelo estaban apareadas y habían depositado sus huevos.

Efficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis.

Randomized, controlled trials have demonstrated efficacy for second-generation antipsychotics in the treatment of acute mania in bipolar disorder. Despite depression being considered the hallmark of bipolar disorder, there are no published systematic reviews or meta-analyses to evaluate the efficacy of modern atypical antipsychotics in bipolar depression. We systematically reviewed published or registered randomized, double-blind, placebo-controlled trials (RCTs) of modern antipsychotics in adult bipolar I and/or II depressive patients (DSM-IV criteria). Efficacy outcomes were assessed based on changes in the Montgomery-Asberg Depression Rating Scale (MADRS) during an 8-wk period. Data were combined through meta-analysis using risk ratio as an effect size with a 95% confidence interval (95% CI) and with a level of statistical significance of 5% (p<0.05). We identified five RCTs; four involved antipsychotic monotherapy and one addressed both monotherapy and combination with an antidepressant. The two quetiapine trials analysed the safety and efficacy of two doses: 300 and 600 mg/d. The only olanzapine trial assessed olanzapine monotherapy within a range of 5-20 mg/d and olanzapine-fluoxetine combination within a range of 5-20 mg/d and 6-12 mg/d, respectively. The two aripiprazole placebo-controlled trials assessed doses of 5-30 mg/d. Quetiapine and olanzapine trials (3/5, 60%) demonstrated superiority over placebo (p<0.001). Only 2/5 (40%) (both aripiprazole trials) failed in the primary efficacy measure after the first 6 wk. Some modern antipsychotics (quetiapine and olanzapine) have demonstrated efficacy in bipolar depressive patients from week 1 onwards. Rapid onset of action seems to be a common feature of atypical antipsychotics in bipolar depression. Comment in The following popper user interface control may not be accessible. Tab to the next button to revert the control to an accessible version.Destroy user interface controlEfficacy of modern antipsychotics in placebo-controlled trials in bipolar depression: a meta-analysis--results to be interpreted with caution.

Digitaalisen television soveltuvuus tietoyhteiskunnan tarpeisiin, case Kuopion Kaapelitelevisio Oy

Tutkielmassa selvitetään Kuopion Kaapelitelevisio Oy:n toteuttaman digitaalisen television ominaisuuksia ja niiden sopivuutta tietoyhteiskunnan vaatimuksiin. Tietoyhteiskunnassa tiedosta on tullut tärkein yritysten pääoma. Yritysten välinen toiminta on tiedon siirtämistä palvelun tuottajalta palvelun kuluttajalle. Jotta edellä mainitut asiat ovat mahdollista, tarvitaan tiedon valtatie, joka koostuu tieto-, perus-, varus-, liityntä ja siirtopalvelusta sekä palvelun tuottajista palvelimineen että käyttäjistä päätelaitteineen. Itse tieto liikkuu siirtotietä pitkin. Kuopion Kaapelitelevisio Oy:n ensimmäisen sukupolven digitaalinen televisio täyttää tiedon valtatien ominaisuudet vain varuspalveluiden osalta. Kaikki muut internetistä tutut peruspalvelut eivät ole mahdollisia. Tuleva toisen sukupolven digitaalinen televisio, jossa on mukana MHP-palvelualusta, MHP-digisovittimet ja interaktiivisuuden tuova paluukanava mahdollisuuden tehdä digitaalisesta televisiosta internetin ja mobiiliverkkojen kaltainen monipalveluverkko. Uuden toisen sukupolven digitaalisen television palveluiden tuottamisen suurin este on digisovittimien tulevat myyntiin vasta syksyllä 2003. Tällä hetkellä ainut MHP-digisovitin, Sony Wega NX100, on hinnaltaan noin 4000 €. Tutkimuksen tuloksia tullaan hyödyntämään digitaalisen television kehitystyössä Kuopion Kaapelitelevisio Oy.ssä

Piikarbidipuolijohdekomponentit tehoelektroniikassa

Piikarbidi (SiC) on tunnettu korkealuokkaisena hioma-aineena ja hiekkapaperin pin-noitteena yli 100 vuoden ajan. Nykyisin ainetta käytetään pääasiassa puolijohteiden raaka-aineena. Piikarbidi on puolijohteena ylivoimainen tavanomaiseen piihin (Si) verrattuna lähes joka suhteessa johtuen sen kiderakenteesta, mutta sen valmistus on osoittautunut erittäin monimutkaiseksi johtuen pääasiassa vaikeudesta kasvattaa riittävän suuria ja laadukkaita SiC-kiteitä. Siksi tehoelektroniikan SiC-puolijohdekomponenttien laajamittaista käyttöä joudutaan yhä odottamaan. Tässä diplomityössä tehdään perusteellinen selvitys, miten piikarbidin valmistuspro-sessit eroavat normaaleista piin valmistusprosesseista, mitä etuja piikarbidin käytöllä saavutetaan ja vastaavasti mitä varjopuolia sillä on. Työssä selvitetään tällä hetkellä markkinoilla olevien SiC-tehopuolijohdekomponenttien ominaisuuksia, ketkä ovat teh-neet tutkimusta alalla, sekä esitetään arvioita SiC-tekniikan tulevaisuuden näkymistä.

Accessory phases as a tool to investigate magmatic underplating in polymetamorphic metasediments : an example from a fossil lower crust : Ivrea Verbano zne, NW Italy

The Ivrea and the Strona-Ceneri zones, NW italy and S Switzerland, offer the possibility to study the continental crust of the Southern Alps. Because of its high metamorphic degree and the abundant Permo- Carboniferous mafic intrusions, the Ivrea Zone is classically interpreted an exposed section trough the Permian lower crust. The present work is focused here on metasedimentary slices (septa) intercalated within Permian gabbro (mafic complex). In particular I studied the evolution of accessory phases such as rutile and zircon and the chemistry of the metasediments. The septa build an irregular and discontinuous band that cut obliquely the mafic complex from its deepest part (N) to its roof (S). The chemistry of the metasediments evolves along the band and the chemical evolution can be compared with that observed in the country-rock surrounding the mafic intrusion to the NE and overprinted by a main regional metamorphic event. This suggests that the degree of chemical depletion of the septa was mainly established during the same regional metamorphic event. Moreover it suggests that incorporation of the septa within the gabbro did not modify their original stratigraphie distribution within the crust. It implies that the mafic complex has been emplaced following a dynamic substantially different from the classic model of « gabbro glacier » (Quick et al., 1992; Quick et al., 1994). It is more likely that it has been emplaced by repeated injections of sills at different depths during a protracted period of time. Zircon trace elements and U-Pb ages suggest that regional metamorphism occurred 330-320Ma, the first sills in the deepest part of the Mafic Complex are injected at ~300Ma, the mafic magmas reached higher levels in the crust at 285Ma and the magmatic activity continued locally until 275Ma. The ages of detrital cores in zircons fix the maximal sedimentation age at ~370Ma, this age corresponds therefore with the maximal age of the incorporation of the Ivrea zone within the lower crust. I propose that the Ivrea zone has been accreted to the lower crust during the Hercynian orogeny sensu lato. The analysis of detrital ages suggests that the source terrains for the Ivrea zone and those for the Strona-Ceneri zone have a completely different Palaeozoic history. The systematic analysis of rutile in partially molten metasediments of the Ivrea zone reveals the occurrence of two generations. The two generations are characterized by a different chemistry and textural distribution. A first generation is formed during pro-grade metamorphism in the restitic counterpart. The second generation is formed in the melts during cooling at the same time that part of the first generation re-equilibrate. Re-equilibration of the first generation seems to be spatially controlled by the presence of fluids. Locally the second generation forms overgrowths on the first generation. Considered the different diffusivity of U and Pb in rutile, U heterogeneities have important implication for U-Pb dating of rutile. ID-TIMS and LA-ICPMS dating coupled with a careful textural investigation (SEM) suggest that rutile grains are characterized by multiple path along which Pb diffusion can occur: volume diffusion is an important process, but intragrain and subgrain boundaries provide additional high diffusivity pathways for Pb escape and reduce drastically the effective diffusion length. -- La zone d'Ivrea et la zone de Strona-Ceneri, en Italie nord-occidentale et Suisse méridionale, offrent la possibilité d'étudier la croûte continentale des Alpes du Sud. En raison du haut degré métamorphique et l'abondance d'intrusions mafiques d'âge Permo-Carbonifère [complexe mafique), la zone d'Ivrea est interprétée classiquement comme de la croûte inférieure permienne. Ce travail ce concentre sur des bandes metasédimentaires (septa) incorporées dans les magmas mafiques lors de l'intrusion. Les septa forment une bande irrégulière qui coupe obliquement le complexe mafique du bas (N) vers le haut (S). La chimie des septa évolue du bas vers le haut et l'évolution chimique se rapproche de l'évolution observé dans la roche encaissante l'intrusion affecté par un événement métamorphique régionale. Cette relation suggère que le degré d'appauvrissement chimique des septa a été établit principalement lors de l'événement métamorphique régional. De plus l'incorporation dans les gabbros n'a pas perturbée la distribution stratigraphique originelle des septa. Ces deux observations impliquent que le métamorphisme dans la roche encaissante précède la mise en place du gabbro et que cette dernière ne se fait pas selon le modèle classique (« gabbro glacier » de Quick et al., 1992, 1994), mais se fait plutôt par injections répétées de sills a différentes profondeurs. Les âges U-Pb et les éléments traces des zircons suggèrent que le métamorphisme régionale a eu lieu 330-320Ma, alors que les premiers sills dans la partie profonde du Mafic Complex s'injectent à ~300Ma, le magmatisme mafique atteigne des niveaux supérieurs à 285Ma et continue localement jusqu'à 270Ma. Les âges des coeurs détritiques des zircons permettent de fixer l'âge maximale de sédimentation à ~370Ma ce qui correspond donc à l'âge maximale de l'incorporation de la zone d'Ivrea dans la croûte inférieur. L'analyse systématique des rutiles, nous a permit de montrer l'existence de plusieurs générations qui ont une répartition texturale et une chimie différente. Une génération se forme lors de l'événement UHT dans les restites, une autre génération se forme dans les liquides lors du refroidissement, au même temps qu'une partie de la première génération se rééquilibre au niveau du Zr. Localement la deuxième génération peut former des surcroissances autour de la première génération. Dans ces cas, des fortes différences en uranium entre les deux générations ont des importantes implications pour la datation U-Pb sur rutile. Classiquement les ratios Pb/U dans le rutile sont interprétés comme indiquant l'âges du refroidissement du minéral sous une température à la quelle la diffusion du Pb dans le minéral n'est plus détectable et la diffusion à plus hautes températures est assumée se faire par «volume diffusion» dans le grain (Mezger et al., 1989). Par des datations ID-TIMS (sur grain entier) et LA-ICPMS (in-situ) et une analyse texturale (MEB) approfondie nous montrons que cette supposition est trop simpliste et que le rutile est repartie en sous-domaines. Chacun de ces domaines a ça propre longueur ou chemin de diffusion spécifique. Nous proposons donc une nouvelle approche plus cohérente pour l'interprétation des âges U-Pb sur rutile.

Pharmacogenetic and clinical study on adverse effects induced by psychotropic drugs

Second-generation antipsychotics (SGAs) have become the first-line antipsychotic treatment for psychotic disorders due to their better overall tolerance compared to classical antipsychotics. However, metabolic side effects such as weight gain are frequently described during treatment with SGAs and/or other psychotropic drugs including some antidepressants and mood stabilizers, which may also result in poor adherence to treatment. The aim of this work was to investigate different methods to predict common side effects, in particular weight gain during treatment with weight gain inducing psychotropic drugs. Firstly, clinical data were used to determine the potential predictive power of a one month weight gain on weight increase after three and 12 months of treatment (n=351 patients). A fast and strong weight gain of >5% after a period of one month (>5%WG) was found to be the best predictor for an important weight gain at three (>15%) and 12 months (>20%). Similar analyses in an independent cohort of psychiatric adolescents (n=42), showed that a comparable >4% weight gain at one month is the best predictor for an important weight gain at three months (>15%). Secondly, we aimed to determine whether an extensive analysis of genes could be used, in addition to clinical factors, to predict patients at risk for >5%WG or for type 2 diabetes (T2D). Adding genetic markers to clinical variables to predict >5%WG increased significantly the area under the curve (AUC) of the analysis (AUCfinai:0.92, AUCdmicai:0.75, pcO.OOOl, n=248). Conversely, genetic risk scores were found to be associated with T2D (OR: 2.5, p=0.03, n=285) but without a significant increase of AUC'when compared to the prediction based to clinical factors alone. Finally, therapeutic drug monitoring was used to predict extrapyramidal symptoms during risperidone treatment (n=150). Active moiety (sum of risperidone and of its active metabolite 9- hydroxyrisperidone plasma concentrations) of >40 ng/ml should be targeted only in case of insufficient response. These results highlight different approaches for personalizing psychotropic treatments in order to reduce related side effects. Further research is needed, in particular on the identification of genetic markers, to improve the implementation of these results into clinical practice. Résumé Les antipsychotiques atypiques (APA) sont devenus le traitement antipsychotique de première intention pour le traitement des psychoses, grâce à un profil d'effets secondaires plus favorables comparé aux antipsychotiques typiques. Néanmoins, d'autres effets indésirables d'ordre métabolique (ex. prise pondérale) sont observés sous APA, stabilisateurs de l'humeur et/ou certains antidépresseurs, pouvant aussi limiter l'adhérence au traitement. L'objectif de ce travail est d'explorer différentes méthodes permettant de prédire des effets secondaires courants, en particulier la prise de poids durant un traitement avec des psychotropes pouvant induire un tel effet. Dans une première partie, des données cliniques ont été évaluées pour leurs potentiels prédictifs d'une prise de poids à un mois sur une prise de poids à trois et 12 mois de traitement (n=351 patients). Une prise de poids rapide et forte >5% à un mois (PP>5%) s'est avérée être le meilleur prédicteur pour une prise pondérale importante à trois (>15%) et 12 (>20%) mois de traitement. Des analyses similaires dans une cohorte pédiatrique (n=42) ont indiqué une prise de poids >4% à un mois comme le meilleur prédicteur pour une prise pondérale importante (>15%) à trois mois de traitement. Dans une deuxième partie, des marqueurs génétiques, en complément aux données cliniques, ont été analysés pour leur contribution potentielle à la prédiction d'une PP>5% et au dépistage du diabète de type 2 (DT2). L'ajout de variants génétiques aux données cliniques afin de prédire une PP>5% a augmenté significativement l'aire sous la courbe (ASC) de l'analyse (ASCflnai:0.92, ASCC|inique:0.75, p<0.0001, n=248). Concernant le DT2, un score génétique est associé au DT2 (OR: 2.5, p=0.03, n=285), néanmoins aucune augmentation significative de l'ASC n'a été observée par rapport à l'analyse avec les données cliniques seules. Finalement, des mesures de concentrations plasmatiques de médicaments ont été utilisées pour prédire la survenue de symptômes extrapyramidaux sous rispéridone (n=150). Cette analyse nous a permis d'établir qu'une concentration plasmatique de rispéridone associée à son métabolite actif >40 ng/ml ne devrait être recherchée qu'en cas de réponse clinique insuffisante. Ces différents résultats soulignent différentes approches pour personnaliser la prescription de psychotropes afin de réduire la survenue d'effets secondaires. Des études supplémentaires sont néanmoins nécessaires, en particulier sur l'identification de marqueurs génétiques, afin d'améliorer l'implémentation de ces résultats en pratique clinique. Résumé large publique Les antipsychotiques atypiques et autres traitements psychotropes sont couramment utilisés pour traiter les symptômes liés à la schizophrénie et aux troubles de l'humeur. Comme pour tout médicament, des effets secondaires sont observés. L'objectif de ce travail est d'explorer différentes méthodes qui permettraient de prédire la survenue de certains effets indésirables, en particulier une prise de poids et la survenue d'un diabète. Dans une première partie, nous avons évalué l'effet d'une prise de poids précoce sur une prise de poids au long terme sous traitement psychotrope. Les analyses ont mis en évidence dans une population psychiatrique qu'une prise de poids à un mois >5% par rapport au poids initial permettait de prédire une prise pondérale importante après trois (>15%) et 12 (>20%) mois de traitement. Un résultat semblable a. été observé dans un autre groupe de patients exclusivement pédiatriques. Dans une deuxième partie, nous avons évalué la contribution potentielle de marqueurs génétiques à la prédiction d'une prise pondérale de >5% après un mois de traitement ainsi que dans la survenue d'un diabète de type 2. Pour la prise de poids, la combinaison des données génétiques aux données cliniques a permis d'augmenter de 17% la précision de la prédiction, en passant de 70% à 87%. Concernant la survenue d'un diabète, les données génétiques n'ont pas amélioré la prédiction. Finalement, nous avons analysé la relation possible entre les concentrations sanguines d'un antipsychotique atypique couramment utilisé, la rispéridone, et la survenue d'effets secondaires (ici les tremblements). Il est ressorti de cette étude qu'une concentration plasmatique du médicament supérieure à 40 ng/ml ne devrait être dépassée qu'en cas de réponse thérapeutique insuffisante, au risque de voir augmenter la survenue d'effets secondaires du type tremblements. Ces résultats démontrent la possibilité de prédire avec une bonne précision la survenue de certains effets secondaires. Cependant, en particulier dans le domaine de la génétique, d'autres études sont nécessaires afin de confirmer les résultats obtenus dans nos analyses. Une fois cette étape franchie, il serait possible d'utiliser ces outils dans la pratique clinique. A terme, cela pourrait permettre au prescripteur de sélectionner les traitements les mieux adaptés aux profils spécifiques de chaque patient.