Experimentally induced intravaginal Tritrichomonas foetus infection in a mouse model

The interest to develop research on the host-parasite relationship in bovine tritrichomonosis has accomplished the use of experimental models alternative to cattle. The BALB/c mouse became the most appropriate species susceptible to vaginal Tritrichomonas foetus infection requiring previous estrogenization. For the need of an experimental model without persistent estrogenization and with normal estrous cycles, the establishment and persistence of vaginal infection on BALB/c mouse with different concentrations of T. foetus in two experimental groups was evaluated. Group A was treated with 5mg of b-estradiol 3-benzoate to synchronize the estrous, 48 hours before the T. foetus vaginal inoculation, and Group B was inoculated in natural estrus. At 5-7 days after treatment, estrogenic effect decreased allowing all animals to cycle regularly during the experiment. From the first week post-infection, samples of vaginal mucus were taken from all animals during 34 weeks, in order to evaluate the course of infection and the stage of the estrus cycle. Group A showed 93.6% of infected animals, and Group B showed 38%. Different doses of T. foetus were assayed to establish the vaginal infection, with a persistence of 34 weeks. Although different behavior was observed in each subgroup belonging to either Group A or Group B, there were no significant differences among the infecting doses used. The b-estradiol 3-benzoate treatment had a favorable effect on the establishment of the infection (P<0.0001), but it did not influence its persistence (P=0.1097). According to the results, an experimental mouse model is presented, appropriate for further studies on mechanisms of pathogenicity, immune response, protective evaluation of immunogen and therapeutic effect of drugs.

Hedge-rahastojen menestyksen pysyvyyden empiirinen tarkastelu sijoittajan näkökulmasta

This study examines performance persistence of hedge funds from investor's point of view and look at the methods by which an investor could choose the successful hedge funds to the portfolio. This study was used the data from HFI & Tremont databases on period 1998-2007. In this study used the 36-month combination (24-month selection and 12-month prediction periods). As the research methods used the Sharpe index, raw returns, MVR (mean variance ratio), GSC-clustering, the SDI index and the new combination of metrics. The evaluation criterions of the results used the volatility, excess returns and the Sharpe index. This study compared different results from the 7 time series with each other, and commenting the problems on a portfolio loss of funds.

Hedge-rahastojen menestyksen pysyvyys ja suhteellinen suoriutuminen sijoittajan näkökulmasta

The purpose of the thesis is to examine the long-term performance persistence and relative performance of hedge funds during bear and bull market periods. Performance metrics applied for fund rankings are raw return, Sharpe ratio, mean variance ratio and strategy distinctiveness index calculated of the original and clustered data correspondingly. Four different length combinations for selection and holding periods are employed. The persistence is examined using decile and quartile portfolio formatting approach and on the basis of Sharpe ratio and SKASR as performance metrics. The relative performance persistence is examined by comparing hedge portfolio returns during varying stock market conditions. The data is gathered from a private database covering 10,789 hedge funds and time horizon is set from January 1990 to December 2012. The results of this thesis suggest that long-term performance persistence of the hedge funds exists. The degree of persistence also depends on the performance metrics employed and length combination of selection and holding periods. The best results of performance persistence were obtained in the decile portfolio analysis on the basis of Sharpe ratio rankings for combination of 12-month selection period and the holding period of equal length. The results also suggest that the best performance persistence occurs in the Event Driven and Multi strategies. Dummy regression analysis shows that a relationship between hedge funds and stock market returns exists. Based on the results, Dedicated Short Bias, Global Macro, Managed Futures and Other strategies perform well during bear market periods. The results also indicate that the Market Neutral strategy is not absolutely market neutral and the Event Driven strategy has the best performance among all hedge strategies.

Presurgical ketoprofen, but not morphine, dipyrone, diclofenac or tenoxicam, preempts post-incisional mechanical allodynia in rats

The treatment of pain before it initiates may prevent the persistent pain-induced changes in the central nervous system that amplify pain long after the initial stimulus. The effects of pre- or postoperative intraperitoneal administration of morphine (2 to 8 mg/kg), dipyrone (40 and 80 mg/kg), diclofenac (2 to 8 mg/kg), ketoprofen (10 and 20 mg/kg), and tenoxicam (10 and 20 mg/kg) were studied in a rat model of post-incisional pain. Groups of 5 to 8 male Wistar rats (140-160 g) were used to test each drug dose. An incision was made on the plantar surface of a hind paw and the changes in the withdrawal threshold to mechanical stimulation were evaluated with Von Frey filaments at 1, 2, 6 and 24 h after the surgery. Tenoxicam was given 12 or 6 h preoperatively, whereas the remaining drugs were given 2 h or 30 min preoperatively. Postoperative drugs were all given 5 min after surgery. No drug abolished allodynia when injected before or after surgery, but thresholds were significantly higher than in control during up to 2 h following ketoprofen, 6 h following diclofenac, and 24 h following morphine, dipyrone or tenoxicam when drugs were injected postoperatively. Significant differences between pre- and postoperative treatments were obtained only with ketoprofen administered 30 min before surgery. Preoperative (2 h) intraplantar, but not intrathecal, ketoprofen reduced the post-incisional pain for up to 24 h after surgery. It is concluded that stimuli generated in the inflamed tissue, rather than changes in the central nervous system are relevant for the persistence of pain in the model of post-incisional pain.

Immune factors and immunoregulation in tuberculosis

Pathogens causing tuberculosis and other chronic infectious diseases of major public health importance commonly have complex mechanisms involved in their persistence in the host despite specific and sometimes strong immune responses. These diseases are also associated with the lack of efficient vaccines, difficult therapeutics and a high mortality rate among susceptible individuals. Here, we will review features of the host immune response that contribute to the occurrence of disease. In addition, we propose that the immune responses observed in tuberculosis cannot be interpreted solely on the basis of a Th1-Th2 counter-regulatory paradigm since there is growing evidence that natural regulatory T cells may play an important role in the regulation of host immune responses against Mycobacterium tuberculosis. Thus, the development of more effective vaccines against this bacterial disease should take into account the role of natural regulatory T cells in the progression to severe disease and persistence of infection. Finally, new treatments based on manipulation of regulatory T cells should be investigated.

Asthma: where is it going?

Asthma is characterized by reversible airway obstruction, airway hyperresponsiveness, and airway inflammation. Although our understanding of its pathophysiological mechanisms continues to evolve, the relative contributions of airway hyperresponsiveness and inflammation are still debated. The first mechanism identified as important for asthma was bronchial hyperresponsiveness. In a second step, asthma was recognized also as an inflammatory disease, with chronic inflammation inducing structural changes or remodeling. However, persistence of airway dysfunction despite inflammatory control is observed in chronic severe asthma of both adults and children. More recently, a potential role for epithelial-mesenchymal communication or transition is emerging, with epithelial injury often resulting in a self-sustaining phenotype of wound repair modulation by activation/reactivation of the epithelial-mesenchymal trophic unit, suggesting that chronic asthma can be more than an inflammatory disease. It is noteworthy that the gene-environmental interactions critical for the development of a full asthma phenotype involve processes similar to those occurring in branching morphogenesis. In addition, a central role for airway smooth muscle in the pathogenesis of the disease has been explored, highlighting its secretory function as well as different intrinsic properties compared to normal subjects. These new concepts can potentially shed light on the mechanisms underlying some asthma phenotypes and improve our understanding of the disease in terms of the therapeutic strategies to be applied. How we understand asthma and its mechanisms along time will be the focus of this overview.

Issues in the Transatlantic Trade and Investment Partnership: A critical discourse analysis

Negotiating trade agreements is an important part of government trade policies, economic planning and part of the globally operating trading system of today. European Union and the United States have been active in the formation of trade agreements in global comparison. Now these two economic giants are engaged in negotiations to form their own trade agreement, the so called Transnational Trade and Investment Partnership (TTIP). The purpose of this thesis is to understand the reasons for making a trade agreement between two economic areas and understanding the issues it may include in the case of the TTIP. The TTIP has received a great deal of attention in the media. The opinions towards the partnership have been extreme, and the debate has been heated. The purpose of this study is to introduce the nature of the public discussion regarding the TTIP from Spring 2013 until 2014. The research problem is to find out what are the main issues in the agreement and what are the values influencing them. The study was conducted applying methods of critical discourse analysis to the chosen data. This includes gathering the issues from the data based on the attention each has received in the discussion. The underlying motives for raising different issues were analysed by investigating the authors’ position in the political, economic and social circuits. The perceived economic impacts of the TTIP are also under analysis with the same criteria. Some of the most respected economic newspapers globally were included in the research material as well as papers or reports published by the EU and global organisations. The analysis indicates a clear dichotomy of the attitudes towards the TTIP. Key problems include lack of transparency in the negotiations, the misunderstood investor-state dispute settlement, the constantly expanding regulatory issues and the risk of protectionism. The theory and data does suggest that the removal of tariffs is an effective tool for reaching economic gains in the TTIP and even more effective would be the reducing of non-tariff barriers, such as protectionism. Critics are worried over the rising influence of corporations over governments. The discourse analysis reveals that the supporters of the TTIP have values related to increasing welfare through economic growth. Critics do not deny the economic benefits but raise the question of inequality as a consequence. Overall they represent softer values such as sustainable development and democracy as a counter-attack to the corporate values of efficiency and the maximising of profits.

Resuming growth in Latin America: short and long term policies

The authors of this paper assert that the paralysis of the state generated by the crises of the 1970s and 1980s deprived the economies of the region of an important lever to resume and sustain growth. They thus maintain that to overcome stagnation it will be necessary to reconstruct the state's capacity to implement pro-growth policies. Following Keynes and Kalecki's ideas, but also classical development economists, the authors argue, first, that short-term macroeconomic policies, to reduce unemployment and to increase the degree of capacity utilization, should be used to promote the generation of profits to firms and to wake up entrepreneurs' animal spirits. Short-term expansionary policies should be coupled with measures to improve competitiveness and avoid balance of payments problems. They also claim that alternatives to the liberal programme will fail unless a pro-growth strategy is adopted which includes both short- and long-term policies. They thus propose that long-term policies must complete the package, signaling: a) sustained increases of effective demand in the future; and b) investment priorities to ensure that capacities will be created in strategic sectors and branches of the economy.

Talkootyön verokohtelu

Tutkimus käsittelee talkootyön verotusta, joka liittyy lähinnä aatteellisten yhdistysten toimintaan. Tutkimuksen tavoitteena on muodostaa selkeä kokonaiskuva talkootyön verokohtelusta sekä osoittaa oikeustapauksiin perehtymällä mahdollisia riskitekijöitä yhdistysten kannalta kielteisiin veroseuraamuksiin. Tutkimusmenetelmä on lainopillinen eli voimassa olevaa oikeutta tutkiva. Työn teoreettisen viitekehyksen muodostavat siten lainsäädäntö, oikeuskirjallisuus sekä Verohallinnon ohjeistus, jolla on ennakkopäätösten ohella suuri käytännön merkitys verotuksessa. Yhdistystoiminnan perusta on vapaaehtoistyövoima. Välitön, vastikkeeton työ suoraan yhdistyksen hyväksi on verotuksellisesti ongelmaton. Talkootyösuoritteet eli välillinen työ yhdistyksen nimissä kolmannen osapuolen lukuun muodostavat merkittävän osuuden yhdistysten varainhankinnasta. Talkootyötulo voi olla verotonta ainoastaan, mikäli korvauksen saaja täyttää tuloverolaissa mainitut yleishyödyllisyyskriteerit. Lisäksi verottomuuden edellytyksenä on se, ettei suoritusta pidetä yhdistyksen elinkeinotulona tai työn tekijän henkilökohtaisena palkkana. Saatu tulo on käytettävä yhdistyksen tarkoituksen mukaiseen yleishyödylliseen toimintaan, eikä hyöty saa kanavoitua työn tekijöiden hyväksi. Oikeustapausten perusteella talkootyön verollisuutta arvioitaessa merkitystä on annettu työn kestolle, toimeksiantajan johdon ja valvonnan olemassaololle, työn läheiselle liittymiselle varsinaiseen yleishyödylliseen toimintaan, kilpailuolosuhteille sekä tulojen määrälle suhteessa muihin tuloihin. Ratkaisujen valossa verotuskäytäntö vaikuttaa osittain ristiriitaiselta. Lisäksi on muistettava, että kyseessä on aina yksittäistapauksen kokonaisarviointi. Riskialttiilta vaikuttavassa tapauksessa verovelvollisen on suositeltavaa hakea ennakkokannanotto, sillä usean vuoden ajalta kumuloituvat veroseuraamukset johtavat helposti syvään talousahdinkoon, pahimmillaan jopa toiminnan lakkaamiseen.

Da economia política à política econômica: o novo-desenvolvimentismo e o governo Lula

From political economy to economic policy: The neo-developmentalism and the Lula administration. This article critically reviews the design of neo-developmentalist economic policies in Brazil, in the first half of the last decade, and their relationship with the economic policies of the Lula administration after 2006. Paradoxically, the neo-developmentalist policies were implemented jointly with the main (neoliberal) macroeconomic policies which had been introduced earlier. The article reviews the relevant literature, and examines the contradictory nature of this 'inflection' of economic policy. So far, this combination of policies has achieved an unquestionable - though provisional - success, despite the persistence of the structural macroeconomic problems due to the continuity of the neoliberal policies.

Quinze anos de rigidez monetária no Brasil pós-Plano Real: uma agenda de pesquisa

Fifteen years of monetary rigidity in Brazil after the Real Plan: a research agenda.The paper makes a review of literature and a research agenda on the anomaly of Brazilian monetary policy. Following a retrospect of the first 15 years after the Real Plan, there is a review of studies aiming to explain the high real interest rate. None of the summarized theses can completely explain the phenomenon. The main research opportunities are: deepening of empirical evidence of monetary policy efficacy loss; improvement in mensuration of its inefficacy; and improvement of alternative instruments to control inflation. The field of political economy is also fertile. One should assess the relevance of oligopolies as an explaining factor of persistence of high inflation.

A persistência da indexação no Brasil pós-Real

The paper analyzes the shortcomings of the Real Plan combining political science and economics, considering evidences on difficulties in implementing a complete plan of deindexation, namely: the distributional conflict, the corporatist relations between the State and society and the bureaucratic isolation of a highly specialized technocracy. The announcement of the plan triggered defensive reactions, fueling distributive tensions during the URV period, forcing the economic team to take measures that contradicted the overall guidelines followed. The persistence of indexation mechanisms indicate the resulting obstacles in seeking a reform of the State through a stabilization plan, even though the latter has the former as a precondition.

Cholesterol, cardiovascular disease and statin use in older persons

Older age increases the risk of developing a chronic atherosclerotic cardiovascular disease (CVD), such as coronary heart disease. Complications of CVDs, myocardial infarction or stroke often lead to loss of functional capacity or premature death. Dyslipidemia, high serum levels of total or low-density lipoprotein cholesterol (LDL-c) and low levels of high-density lipoprotein cholesterol (HDL-c), is among the most important modifiable risk factors for CVDs; it can be treated with lifestyle modifications, and with lipid-lowering drugs, primarily statins. In older persons, however, the association of cholesterol levels with cardiovascular and all-cause mortality has been inconsistent in previous studies. Furthermore, the beneficial effects of statins in older persons without previous CVD are still somewhat unclear, and older persons are more prone to adverse effects from statins. This thesis presents a prospective cohort study (TUVA), exploring associations of cholesterol levels with mortality and the changes in cholesterol levels of a 70-year-old population in long-term follow-up. Further, prevalence of CVDs, risk factors and preventive medication use in the TUVA cohort is compared with respective prevalences in another age-matched cohort (UTUVA) 20 years later in order to examine the changes in cardiovascular risk over time. Additionally, to evaluate statin use patterns among older persons, an observational register study was conducted covering the total Finnish population aged 70 and older during 2000-2008. Based on individual-level data retrieved from national health registries, the population was classified into low, moderate and high risk groups according to estimated CVD risk. The prevalence, incidence and persistence of statin use among the risk groups was then evaluated based upon yearly statin purchases tracked from the Prescription Register. The prospective cohort study demonstrated that low total cholesterol, LDL-c and HDL-c were associated with higher mortality in a cohort of home-dwelling 70-year-olds. However, after adjusting for traditional cardiovascular risk factors and cancer this association disappeared. Further, low total cholesterol seemed to be protective, whereas low HDL-c strongly predicted increased risk of CVD death. Cholesterol levels of those elderly who remained available for follow-up and were still home-dwelling at the age of 85 seemed to improve with advancing age. Compared to the TUVA cohort, the later born UTUVA cohort had less CVDs and their risk factors were better controlled, which was reflected in the higher use of preventive medications such as statins and antihypertensives. The register studies confirmed that statin use has increased significantly during 2000-2008 among older persons, especially among the oldest (80+) age groups and among those at high risk for cardiovascular events. Two-thirds of new statin users persisted with their use during the four years of follow-up; the most discontinuations were made during the first year of use. In conclusion, statins are commonly used among older age groups in Finland. Most of the older statin users had a high cardiovascular event risk, indicating that the treatment is well directed towards those who are likely to benefit from it the most. No age-limits should be put on the screening and treatment of dyslipidemia in older persons, but the benefits and adverse effects of statin treatment should be carefully weighed based on an individual assessment of the person’s general health status and functional capacity. Physicians should pay more attention to medication adherence, especially when prescribing preventive medications.

L'évaluation du rôle des facteurs génétiques dans la genèse des terreurs nocturnes chez l'enfant : étude prospective chez les jumeaux.

Depuis plusieurs années, les études ont bien démontré que les troubles du sommeil tendent à être héréditaires. Il existe de plus en plus d’évidence scientifique démontrant l’implication des facteurs génétiques dans la manifestation des terreurs nocturnes. Les études de jumeaux sont essentielles pour évaluer l’influence des facteurs génétiques et environnementaux dans les affections complexes comme les terreurs nocturnes. Cependant, la plupart des études antérieures de jumeaux sur les terreurs nocturnes sont, soient des études rétrospectives ou encore des études avec un échantillon insuffisant de patients, ce qui résulte en des résultats peu concluants. L’objectif de ce mémoire était de déterminer la contribution des facteurs génétiques et des facteurs environnementaux dans la manifestation des terreurs nocturnes d’une large cohorte de jeunes jumeaux suivis d’une façon prospective. Ce mémoire a montré que la proportion de la variance phénotypique totale des terreurs nocturnes due aux influences génétiques est plus que 40% pour les jumeaux âgés de 18 et de 30 mois. La corrélation polychorique, à l’âge de 18 mois, est de 0,63 chez les jumeaux monozygotes et de 0,36 chez les jumeaux dizygotes du même âge. À l’âge de 30 mois, cette corrélation est de 0,68 chez les monozygotes et de 0,24 chez les dizygotes. Ceci démontre que les facteurs génétiques jouent un rôle important dans la manifestation des terreurs nocturnes chez les enfants de très jeune âge. Basée sur l’héritabilité, cette étude suggère que la prédisposition génétique soit associée avec la persistance des symptômes des terreurs nocturnes jusqu’à l’âge de 30 mois.

Étude du rôle régulateur de la lamine B1 dans l’activation plaquettaire : base moléculaire de la thromboprotection chez les patients porteurs d'anticoagulant lupique et d'anti-lamine B1

Les anticorps anti-phospholipides (aPL), tels que les anticoagulants lupiques (LAC), sont associés au développement récurrent de thromboses chez les patients atteints du lupus érythémateux disséminé (LED). Il a été observé que des titres élevés d’auto-anticorps antilamine B1 (anti-LB1), chez des patients porteurs de LAC, diminuent le risque de ces manifestations thrombotiques. Toutefois, la relation existant entre la lamine B1 (LB1), les anti-LB1 et la thromboprotection n’est toujours pas expliquée. Dans cette étude, nous avons donc cherché à comprendre comment la LB1 et les anti-LB1 induisent cette thromboprotection. Nous avons testé les effets d'anti-LB1 purifiés et de LB1 recombinante sur l'activation des cellules endothéliales et des plaquettes. Nous avons été en mesure de déterminer que la LB1, contrairement aux anti-LB1, possède une activité anti-plaquettaire. En effet, la LB1 réduit l’activation et l’agrégation plaquettaires in vitro et in vivo. Cette activité est due à une liaison directe de la LB1 aux plaquettes, suivie par une internalisation rapide dans des vésicules de clathrine. Par co-immunoprécipitation, nous avons découvert que la LB1 interagit avec le récepteur de l’insuline situé sur la membrane plaquettaire. La liaison de la LB1 à ce récepteur entraîne vraisemblablement son internalisation et l'inhibition d'une des cascades de signalisation normalement induite par le récepteur de l’insuline, menant éventuellement à l’inhibition des fonctions plaquettaires. L’ajout d’anti-LB1 purifiés dans nos expériences a permis d'augmenter de façon significative la persistance de la LB1 dans les plaquettes, une observation confirmée par la détection de LB1 uniquement dans les lysats de plaquettes prélevées chez des patients anti-LB1 positifs. iv Nos résultats suggèrent que la LB1 prend part aux mécanismes régulateurs des processus d’hémostase chez des sujets sains et que la présence d’anti-LB1, chez les patients lupiques, prolonge la persistance de cet auto-antigène dans les plaquettes, les empêchant ainsi de s’activer. Ce mécanisme expliquerait la diminution du risque de thrombose chez les patients LAC positifs porteurs d’anti-LB1 circulants.