Quantitative assessment of the pharmacotherapy of biopolar disorder and schizophrenia

The work present in this thesis was aimed at assessing the efficacy of lithium in the acute treatment of mania and for the prophylaxis of bipolar disorder, and investigating the value of plasma haloperidol concentration for predicting response to treatment in schizophrenia. The pharmacogenetics of psychotropic drugs is critically appraised to provide insights into interindividual variability in response to pharmacotherapy, In clinical trials of acute mania, a number of measures have been used to assess the severity of illness and its response to treatment. Rating instruments need to be validated in order for a clinical study to provide reliable and meaningful estimates of treatment effects, Eight symptom-rating scales were identified and critically assessed, The Mania Rating Scale (MRS) was the most commonly used for assessing treatment response, The advantage of the MRS is that there is a relatively extensive database of studies based on it and this will no doubt ensure that it remains a gold standard for the foreseeable future. Other useful rating scales are available for measuring mania but further cross-validation and validation against clinically meaningful global changes are required. A total of 658 patients from 12 trials were included in an evaluation of the efficacy of lithium in the treatment of acute mania. Treatment periods ranged from 3 to 4 weeks. Efficacy was estimated using (i) the differences in the reduction in mania severity scores, and (ii) the ratio and difference in improvement response rates. The response rate ratio for lithium against placebo was 1.95 (95% CI 1.17 to 3.23). The mean number needed to treat was 5 (95% CI 3 to 20). Patients were twice as likely to obtain remission with lithium than with chlorpromazine (rate ratio = 1.96, 95% CI 1.02 to 3.77). The mean number needed to treat (NNT) was 4 (95% CI 3 to 9). Neither carbamazepine nor valproate was more effective than lithium. The response rate ratios were 1.01 (95% CI 0.54 to 1.88) for lithium compared to carbarnazepine and 1.22 (95% CI 0.91 to 1.64) for lithium against valproate. Haloperidol was no better than lithium on the basis of improvement based on assessment of global severity. The differences in effects between lithium and risperidone were -2.79 (95% CI -4.22 to -1.36) in favour of risperidone with respect to symptom severity improvement and -0.76 (95% CI -1.11 to -0,41) on the basis of reduction in global severity of disease. Symptom and global severity was at least as well controlIed with lithium as with verapamil. Lithium caused more side-effects than placebo and verapamil, but no more than carbamazepine or valproate. A total of 554 patients from 13 trials were included in the statistical analysis of lithium's efficacy in the prophylaxis of bipolar disorder. The mean follow-up period was 5-34 months. The relapse risk ratio for lithium versus placebo was 0.47 (95% CI 0.26 to 0.86) and the NNT was 3 (95% CI 2 to 7). The relapse risk ratio for lithium versus imipramine was 0.62 (95% CI 0.46 to 0.84) and the NNT was 4 (951% Cl 3 to 7), The combination of lithium and imipramine was no more effective than lithium alone. The risk of relapse was greater with lithium alone than with the lithium-divalproate combination. A risk difference of 0.60 (95% CI 0.21 to 0.99) and an NNT of 2 (95% CI 1 to 5) were obtained. Lithium was as effective as carbamazepine. Based on individual data concerning plasma haloperidol concentration and percent improvement in psychotic symptoms, our results suggest an acceptable concentration range of 11.20-30.30 ng/mL A minimum of 2 weeks should be allowed before evaluating therapeutic response. Monitoring of drug plasma levels seems not to be necessary unless behavioural toxicity or noncompliance is suspected. Pharmacokinetics and pharmacodynamics, which are mainly determined by genetic factors, contribute to interindividual and interethnic variations in clinical response to drugs. These variations are primarily due to differences in drug metabolism. Variability in pharmacokinetics of a number of drugs is associated with oxidation polymorphism. Debrisoquine/sparteine hydroxylase (CYP2D6) and the S-mephenytoin hydroxylase (CYP2C19) are polymorphic P450 enzymes with particular importance in psychopharmacotherapy. The enzymes are responsible for the metabolism of many commonly used antipsychotic and antidepressant drugs. The incidence of poor metabolisers of debrisoquine and S-mephenytoin varies widely among populations. Ethnic variations in polymorphic isoenzymes may, at least in part, explain ethnic differences in response to pharmacotherapy of antipsychotics and antidepressant drugs.

Multinational Performance and the Geography of FDI:evidence from 46 countries

The literature on multinationality and firm performance has generally disregarded the role of geography. However, the location of FDI assumes particular importance in terms of the link between multinationality at the firm level. The purpose of this paper is to consider the multinationality-performance relationship within the context of greater emphasis on the importance of location, but also emphasising the importance of the location decision. This paper draws on firm-level data covering over 16,000 multinationals from 46 countries over the period of 1997-2007 and allows for different effects upon the performance of the multinational firm depending on the level of development of the host economy. In our results, we find a clear positive relation between multinationality and firm performance. However, investment in developing countries is associated with larger effects on performance than in the case of investment in developed countries. We also find that the return to investing in developing countries is U-shaped. This indicates that multinationals are likely to face losses in the early stage of their investment in developing countries before the positive returns are realized. Overall, our results suggest that the net gains for multinationals from greater geographical diversification have not yet been fully explored. Geographical diversification into developing countries may be an important source of competitive advantages that deserves more serious consideration from business leaders and academics alike. © 2013 Springer-Verlag Berlin Heidelberg.

Medical School Donor Recognition Reception Photo 46

http://digitalcommons.fiu.edu/com_images/1051/thumbnail.jpg

Fragm. lat. VI 46 - Tropar

Trägerband: Inc. qu. 526; Vorbesitzer: Hinricus Sticz; Peter Heidenreich; Dominikanerkloster Frankfurt am Main

O ciclo Slopiewnie opus 46 bis de Karol Szymanowski: uma abordagem de estudo e performance

This text presents a discussion about the song cycle Slopiewnie Opus 46 bis of Karol Szymanowski, one of the most important Polish composers of the 20th century. Slopiewnie was composed on texts of Julian Tuwim, poet born in 1894 in Łódź, who used ancient roots to create new words and search for special sonorities. First, this text introduces a brief biographical sketch about Szymanowski, in order to contextualize Slopiewnie in relation to the composer’s works. Afterwards, the text provides an analysis of the songs and their texts, which may serve as a study tool for future perfomers. Interpretative suggestions are offered, based on the experience of learning these songs and on references. The text also presents the phonetic transcription of the poems, as well as a suggested translation to Portuguese, making it easier for Brazilian singers to learn the cycle’s text and prosody.

Compilation of 220 sediment core d13C data from the glacial Atlantic Ocean

We compare a compilation of 220 sediment core d13C data from the glacial Atlantic Ocean with three-dimensional ocean circulation simulations including a marine carbon cycle model. The carbon cycle model employs circulation fields which were derived from previous climate simulations. All sediment data have been thoroughly quality controlled, focusing on epibenthic foraminiferal species (such as Cibicidoides wuellerstorfi or Planulina ariminensis) to improve the comparability of model and sediment core carbon isotopes. The model captures the general d13C pattern indicated by present-day water column data and Late Holocene sediment cores but underestimates intermediate and deep water values in the South Atlantic. The best agreement with glacial reconstructions is obtained for a model scenario with an altered freshwater balance in the Southern Ocean that mimics enhanced northward sea ice export and melting away from the zone of sea ice production. This results in a shoaled and weakened North Atlantic Deep Water flow and intensified Antarctic Bottom Water export, hence confirming previous reconstructions from paleoproxy records. Moreover, the modeled abyssal ocean is very cold and very saline, which is in line with other proxy data evidence.

3.46 Ga Apex chert 'microfossils' reinterpreted as mineral artefacts produced during phyllosilicate exfoliation

We acknowledge the facilities, scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at: Centre for Microscopy Characterisation and Analysis, The University of Western Australia; Electron Microscopy Unit, The University of New South Wales. These facilities are funded by the Universities, State and Commonwealth Governments. DW was funded by the European Commission and the Australian Research Council (FT140100321). This is ARC CCFS paper number XXX. We acknowledge Martin van Kranendonk, Owen Green, Cris Stoakes, Nicola McLoughlin, the late John Lindsay and the Geological Survey of Western Australia for fieldwork assistance, Thomas Becker for assistance with Raman microspectroscopy, Anthony Burgess from FEI for the preparation of one of the TEM wafers, and Russell Garwood, Tom Davies, Imran Rahman & Stephan Lautenschlager for training and advice on the SPIERS and AVIZO software suites. We thank Chris Fedo and an anonymous reviewer for comments that improved the manuscript.

3.46 Ga Apex chert 'microfossils' reinterpreted as mineral artefacts produced during phyllosilicate exfoliation

We acknowledge the facilities, scientific and technical assistance of the Australian Microscopy & Microanalysis Research Facility at: Centre for Microscopy Characterisation and Analysis, The University of Western Australia; Electron Microscopy Unit, The University of New South Wales. These facilities are funded by the Universities, State and Commonwealth Governments. DW was funded by the European Commission and the Australian Research Council (FT140100321). This is ARC CCFS paper number XXX. We acknowledge Martin van Kranendonk, Owen Green, Cris Stoakes, Nicola McLoughlin, the late John Lindsay and the Geological Survey of Western Australia for fieldwork assistance, Thomas Becker for assistance with Raman microspectroscopy, Anthony Burgess from FEI for the preparation of one of the TEM wafers, and Russell Garwood, Tom Davies, Imran Rahman & Stephan Lautenschlager for training and advice on the SPIERS and AVIZO software suites. We thank Chris Fedo and an anonymous reviewer for comments that improved the manuscript.

2 nocturnes pour le piano: op. 46

par Léopoldine Blahetka.

Saothair Oideachais an Ghúim 1926-46

Ceann de phrionsabail bhunaidh An Ghúim téacsleabhair agus leabhair ghinearálta a sholáthar do dhaltaí scoile is do lucht léitheoireachta na Gaeilge. Ábhair a bhaineann le curaclam na scoile, cuir i gcás, eolaíocht is tíos, oideachas, saoránaíocht, spórt, na teangacha Clasaiceacha, tíreolaíocht, taisteal agus an nádúr, creideamh is stair, a roghnaítear don taighde seo. Tugtar Aguisín (921 lch) le bheith ina threoir do phríomh-bhunachar sonraí na dochtúireachta seo (an chiall ghinearálta mar bhailiúchán eolais atá i gceist le “bunachar” sa tráchtas seo in ionad brí theicniúil ar leith). Trí phríomhchuid atá sa staidéar: “buneolas”, “anailís” is “toradh”. Sa “Bhuneolas”, tugtar cuntas beathaisnéiseach ar na bunúdair, soláthraítear achoimre ar na foilseacháin faoi staidéar, mar aon le faisnéis bhibleagrafaíochta i dtaobh na n- aistritheoirí, agus eolas faoi na comhlachtaí foilsitheoireachta a bhí páirteach sna tograí. Pléann “Anailís” brainsí de chuid an státchórais mar an Roinn Oideachais agus an Roinn Airgeadais i gcúrsaí maoinithe, nó gníomhairí lasmuigh de, cosúil le lucht deartha is clóchuradóireachta; moladh is coimisiúnú na saothar; sonraí cóipchirt na bhfoilseachán; roghnú, monatóireacht is díolaíocht na n-aistritheoirí, mar aon le breithniú inmheánach is seachtrach. Sa chuid dheireanach, féachtar le “Toradh” na hiarrachta a mheas, ag tagairt den líon cóipeanna de na leabhair a díoladh. Faightear eolas ar fhiosrú léitheoirí; praghas na leabhar; a ndíolachán is a n- athchló. Tugtar léirmheasanna a scríobhadh ar na haistriúcháin Ghaeilge agus na cúiseanna nár tháinig tograí ar leith chun críche. Is é aidhm na hoibre thar aon ní eile gné lárnach chasta d’eisint An Ghúim atá ligthe i ndíchuimhne a thabhairt ar ais chugainn go beo beathaíoch faoi mar a bhí lena ré saoil féin.

Implications of FIN 46 for Accruals Quality and Investment Efficiency

The Financial Accounting Standards Board (FASB) issued Interpretation No. 46 (FIN 46), Consolidation of Variable Interest Entities – An Interpretation of ARB No. 51, in January 2003 and revised it in December 2003, with the objective to improve the transparency of financial information. Under FIN 46, companies are required to consolidate variable interest entities (VIEs) on financial statements if they are the primary beneficiaries of the VIEs. This dissertation empirically examines whether the implementation of this new financial reporting guidance affects firms’ accruals quality and investment efficiency. A manually collected sample comprised of firms affected by FIN 46 and firms disclosing no material impact from FIN 46 is used in the empirical analyses.The first part of the dissertation investigates the effects of FIN 46 on accruals quality. By using different accrual quality measures in prior studies, this study found that firms affected by FIN 46 experienced a decrease in accrual quality compared to firms reporting no material impact from FIN 46. Among the firms affected by FIN 46, firms consolidating VIEs were compared with firms terminating or restructuring VIEs. The accruals quality of firms consolidating VIEs was found to be lower than that of firms terminating or restructuring VIEs. These results are consistent in tests using alternative control samples.The second part of this dissertation examines the effects of FIN 46 on investment efficiency. Mixed results were found from using two different proxies used in prior literature. Using the investment-cash flow sensitivity to proxy for investment efficiency, firms affected by FIN 46 experienced a decrease in investment efficiency compared to firms reporting no material impact. It was also found that higher investment-cash flow sensitivity for firms consolidating VIEs during post-FIN 46 periods compared to both the no-impact firms and the matched pair control sample. Contrasting results were found when the deviation from expected investment is used as another proxy for investment efficiency. Empirical analyses show that FIN 46 firms experienced improved investment efficiency measured by the deviation from expected investment after their adoption of FIN 46. This study also provides explanations for the opposite results from the two different proxies.

Seasonal variations in surface metabolite composition of Fucus vesiculosus and Fucus serratus sampled at outer Kiel Fjord (August 2012 - July 2013)

The chemical composition of surface associated metabolites of two Fucus species (Fucus vesiculosus and Fucus serratus) was analysed by means of gas chromatography-mass spectrometry (GC-MS) to describe temporal patterns in chemical surface composition. Method: The two perennial brown macroalgae F. vesiculosus and F. serratus were sampled monthly at Bülk, outer Kiel Fjord, Germany (54°27'21 N / 10°11'57 E) over an entire year (August 2012 - July 2013). Per month and species six non-fertile Fucus individuals were collected from mixed stands at a depth of 0.5 m under mid water level. For surface extraction approx. 50 g of the upper 5-10 cm apical thalli tips were cut off per species. The surface extraction of Fucus was performed according to the protocol of de Nys and co-workers (1998) with minor modifications (see Rickert et al. 2015). GC/EI-MS measurements were performed with a Waters GCT premier (Waters, Manchester, UK) coupled to an Agilent 6890N GC equipped with a DB-5 ms 30 m column (0.25 mm internal diameter, 0.25 mM film thickness, Agilent, USA). The inlet temperature was maintained at 250°C and samples were injected in split 10 mode. He carrier gas flow was adjusted to 1 ml min-1. Alkanes were used for referencing of retention times. For further details (GC-MS sample preparation and analysis) see the related publication (Rickert et al. submitted to PLOS ONE).