Arkistoluettelo 685: Markku Lassander

Luettelo Kansalliskirjastossa olevan Markku Lassanderin arkiston sisällöstä

The Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRA.CER) trial: study design and rationale

Background The protease-activated receptor 1 (PAR-1), the main platelet receptor for thrombin, represents a novel target for treatment of arterial thrombosis, and SCH 530348 is an orally active, selective, competitive PAR-1 antagonist. We designed TRA.CER to evaluate the efficacy and safety of SCH 530348 compared with placebo in addition to standard of care in patients with non-ST-segment elevation (NSTE) acute coronary syndromes (ACS) and high-risk features. Trial design TRA.CER is a prospective, randomized, double-blind, multicenter, phase III trial with an original estimated sample size of 10,000 subjects. Our primary objective is to demonstrate that SCH 530348 in addition to standard of care will reduce the incidence of the composite of cardiovascular death, myocardial infarction (MI), stroke, recurrent ischemia with rehospitalization, and urgent coronary revascularization compared with standard of care alone. Our key secondary objective is to determine whether SCH 530348 will reduce the composite of cardiovascular death, MI, or stroke compared with standard of care alone. Secondary objectives related to safety are the composite of moderate and severe GUSTO bleeding and clinically significant TIMI bleeding. The trial will continue until a predetermined minimum number of centrally adjudicated primary and key secondary end point events have occurred and all subjects have participated in the study for at least I year. The TRA.CER trial is part of the large phase III SCH 530348 development program that includes a concomitant evaluation in secondary prevention. Conclusion TRA.CER will define efficacy and safety of the novel platelet PAR-1 inhibitor SCH 530348 in the treatment of high-risk patients with NSTE ACS in the setting of current treatment strategies. (Am Heart J 2009; 158:327-34.)

Parafoveal letter recognition at reduced contrast in normal aging and in patients with risk factors for AMD

Background Patients with early age-related maculopathy ( ARM) do not necessarily show obvious morphological signs or functional impairment. Many have good visual acuity, yet complain of decreased visual performance. The aim of this study was to investigate the aging effects on performance of parafoveal letter recognition at reduced contrast, and defects caused by early ARM and normal fellow eyes of patients with unilateral age-related macular degeneration (nfAMD). Methods Testing of the central visual field (8 radius) was performed by the Macular Mapping Test (MMT) using recognition of letters in 40 parafoveal target locations at four contrast levels (5, 10, 25 and 100%). Effects of aging were investigated in 64 healthy subjects aged 23 to 76 years (CTRL). In addition, 39 eyes (minimum visual acuity of 0.63; 20/30) from 39 patients with either no visible signs of ARM, while the fellow eye had advanced age-related macular degeneration (nfAMD; n=12), or early signs of ARM (eARM; n=27) were examined. Performance was expressed summarily as a ""field score"" (FS). Results Performance in the MMT begins to decline linearly with age in normal subjects from the age of 50 and 54 years on, at 5% and 10% contrast respectively. The differentiation between patients and CTRLs was enhanced if FS at 5% was analyzed along with FS at 10% contrast. In 8/12 patients from group nfAMD and in 18/27 from group eARM, the FS was statistically significantly lower than in the CTRL group in at least one of the lower contrast levels. Conclusion Using parafoveal test locations, a recognition task and diminished contrast increases the chance of early detection of functional defects due to eARM or nfAMD and can differentiate them from those due to aging alone.

Market timing e avaliação de desempenho dos fundos brasileiros

Este trabalho avalia o desempenho de fundos de investimento brasileiros pelo seu market timing, ou seja, pela capacidade de os gestores anteciparem diferenças de retorno das ações em relação a um ativo de renda fixa. Utilizam-se testes - paramétrico e não-paramétrico - desenvolvidos por Henriksson e Merton para a análise do desempenho de 243 fundos, no período de setembro de 1998 a outubro de 2003. Encontra-se evidência de habilidade de market timing para uma minoria de gestores de fundos, resultado que aparentemente se deve à maior facilidade de se preverem grandes diferenças de retorno entre o mercado acionário e a taxa de juros livre de risco.

Genomic rearrangements in trypanosomatids: an alternative to the "one gene" evolutionary hypotheses?

Most molecular trees of trypanosomatids are based on point mutations within DNA sequences. In contrast, there are very few evolutionary studies considering DNA (re) arrangement as genetic characters. Waiting for the completion of the various parasite genome projects, first information may already be obtained from chromosome size-polymorphism, using the appropriate algorithms for data processing. Three illustrative models are presented here. First, the case of Leishmania (Viannia) braziliensis/L. (V.) peruviana is described. Thanks to a fast evolution rate (due essentially to amplification/deletion of tandemly repeated genes), molecular karyotyping seems particularly appropriate for studying recent evolutionary divergence, including eco-geographical diversification. Secondly, karyotype evolution is considered at the level of whole genus Leishmania. Despite the fast chromosome evolution rate, there is qualitative congruence with MLEE- and RAPD-based evolutionary hypotheses. Significant differences may be observed between major lineages, likely corresponding to major and less frequent rearrangements (fusion/fission, translocation). Thirdly, comparison is made with Trypanosoma cruzi. Again congruence is observed with other hypotheses and major lineages are delineated by significant chromosome rearrangements. The level of karyotype polymorphism within that "species" is similar to the one observed in "genus" Leishmania. The relativity of the species concept among these two groups of parasites is discussed.

Liver safety assessment: required data elements and best practices for data collection and standardization in clinical trials.

A workshop was convened to discuss best practices for the assessment of drug-induced liver injury (DILI) in clinical trials. In a breakout session, workshop attendees discussed necessary data elements and standards for the accurate measurement of DILI risk associated with new therapeutic agents in clinical trials. There was agreement that in order to achieve this goal the systematic acquisition of protocol-specified clinical measures and lab specimens from all study subjects is crucial. In addition, standard DILI terms that address the diverse clinical and pathologic signatures of DILI were considered essential. There was a strong consensus that clinical and lab analyses necessary for the evaluation of cases of acute liver injury should be consistent with the US Food and Drug Administration (FDA) guidance on pre-marketing risk assessment of DILI in clinical trials issued in 2009. A recommendation that liver injury case review and management be guided by clinicians with hepatologic expertise was made. Of note, there was agreement that emerging DILI signals should prompt the systematic collection of candidate pharmacogenomic, proteomic and/or metabonomic biomarkers from all study subjects. The use of emerging standardized clinical terminology, CRFs and graphic tools for data review to enable harmonization across clinical trials was strongly encouraged. Many of the recommendations made in the breakout session are in alignment with those made in the other parallel sessions on methodology to assess clinical liver safety data, causality assessment for suspected DILI, and liver safety assessment in special populations (hepatitis B, C, and oncology trials). Nonetheless, a few outstanding issues remain for future consideration.

GateKeeper - Käyttäjienhallintaohjelma

Tämän insinöörityön tavoitteena oli suunnitella ja toteuttaa selainpohjainen käyttäjienhallintaohjelma GateKeeper Karttakeppi.com-työryhmälle. GateKeeper-ohjelma kuuluu osana laajempaan ohjelmistoprojektiin, jonka tarkoituksena on tuottaa opetusmateriaalia etäopiskelijoille Internetissä. Etäopetusmateriaalin tuottamisessa käytetään useita ohjelmia, joille on määriteltävä eritasoisia käyttäjätunnuksia ja käyttöoikeuksia. Ohjelmien käyttäjienhallintamekanismit ovat erilaisia, mikä osaltaan lisää järjestelmän ylläpitäjien työtä ja vastuuta. GateKeeper-ohjelman tavoitteena on nopeuttaa, helpottaa ja yksinkertaistaa käyttäjienhallintaan liittyviä toimintoja tietoturvallisesti. GateKeeper-ohjelma on suunniteltu siten, että uusien käyttäjien ja ohjelmien lisäämiselle ei ole asetettu rajoja. Jokaisen lisättävän ohjelman yhteydessä on kuitenkin selvitettävä kyseisen ohjelman käyttäjienhallintamekanismi. Tässä insinöörityössä tutkittiin, miten versionhallintaohjelma Subversionin, julkaisujärjestelmä Mambon, sekä oppimisalusta Moodlen käyttäjiä voidaan keskitetysti hallinnoida GateKeeper-ohjelman avulla. GateKeeper-ohjelma noudattaa arkkitehtuuriltaan kolmikerrosmallia, jossa käyttöliittymä, sovelluslogiikka ja tietovarasto on erotettu toisistaan. Ohjelma koostuu joukosta PHP-kielellä toteutettuja dynaamisia web-sivuja. Tietovarastona käytetään tietokantapalvelimella sijaitsevaa MySQL-tietokantaa.

Capacidades de Timing e Selectividade dos Gestores de Fundos de Investimento Mobiliário: Evidência Empírica para o Caso Português

Com esta investigação propomos analisar o desempenho de uma amostra de fundos de investimento mobiliário portugueses, durante o período Janeiro de 2002 a Dezembro de 2009, utilizando a medida de Jensen (1968) e a metodologia de timing proposta por Henriksson e Merton (1981). Os resultados obtidos pela medida de Jensen sugerem que, no geral, os fundos têm desempenhos inferiores ao mercado na ordem dos 0,34% ao ano. Contudo este valor não é estatisticamente significante. Os fundos internacionais conseguem “bater” o mercado, enquanto os fundos nacionais e fundos da União Europeia têm desempenhos inferiores. Tendo por base a medida de Henriksson e Merton (1981), verificamos que os gestores possuem poucas capacidades de selectividade (0,42% ao ano) e falham nas suas previsões quanto à evolução do mercado – timing. Enquanto os gestores internacionais parecem evidenciar melhores capacidades de selectividade, os gestores nacionais registam melhores capacidades de timing. Os resultados sugerem igualmente que existe uma acentuada correlação negativa entre ambas as componentes do desempenho e uma distance effect na componente timing. Os testes realizados através de metodologias não condicionais e condicionais confirmam a robustez dos resultados iniciais em relação à especificação do modelo. No entanto, sugerem que, em média, a introdução de factores de risco adicionais e sua posterior combinação com informação condicional em pouco afecta as estimativas de timing, mas melhora os coeficientes de determinação e as estimativas de selectividade, sendo, em média, os alfas condicionais maiores que os alfas não condicionais.

CAPACIDADES DE TIMING E SELECTIVIDADE DOS GESTORES DE FUNDOS DE INVESTIMENTO MOBILIÁRIO: EVIDÊNCIA EMPÍRICA PARA O CASO PORTUGUÊS

Com esta investigação propomos analisar o desempenho de uma amostra de fundos de investimento mobiliário portugueses, entre Janeiro de 2002 e Dezembro de 2009, mediante a aplicação da medida de Jensen (1968) e da metodologia de timing proposta por Henriksson e Merton (1981). Os resultados obtidos pela medida de Jensen sugerem que no geral os fundos têm desempenhos inferiores ao mercado, na ordem dos 0,34% ao ano. Contudo este valor não é estatisticamente significativo. Os fundos internacionais conseguem “bater” o mercado enquanto os fundos nacionais e fundos da União Europeia têm desempenhos inferiores. Tendo por base a medida de Henriksson e Merton (1981), verificamos que os gestores possuem poucas capacidades de selectividade (0,42% ao ano) e falham nas suas previsões quanto à evolução do mercado – timing. Enquanto os gestores internacionais parecem evidenciar melhores capacidades de selectividade, os gestores nacionais registam melhores capacidades de timing. Os resultados sugerem igualmente a existência de uma acentuada correlação negativa entre ambas as componentes do desempenho e uma distance effect na componente timing. Os testes realizados através de metodologias não condicionais e condicionais confirmam a robustez dos resultados iniciais em relação à especificação do modelo de Henriksson e Merton (1981). No entanto, sugerem que em média a introdução de factores de risco adicionais e sua posterior combinação com informação condicional em pouco afectam as estimativas de timing, mas melhoram os coeficientes de determinação e as estimativas de selectividade, sendo em média os alfas condicionais maiores que os alfas não condicionais.

Kansamme parhaaksi : rotuhygienia Suomessa vuoden 1935 sterilointilakiin asti

Summary: In our nation's best interest : eugenics in Finland until the promulgation of the sterilization law of 1935