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Now showing items 852-871 of 25281
  • Tynjälä, Pirjo (Helsingin yliopisto, 2008)
    Juvenile idiopathic arthritis (JIA) is a heterogeneous group of childhood chronic arthritides, associated with chronic uveitis in 20% of cases. For JIA patients responding inadequately to conventional disease-modifying anti-rheumatic drugs (DMARDs), biologic therapies, anti-tumor necrosis factor (anti-TNF) agents are available. In this retrospective multicenter study, 258 JIA-patients refractory to DMARDs and receiving biologic agents during 1999-2007 were included. Prior to initiation of anti-TNFs, growth velocity of 71 patients was delayed in 75% and normal in 25%. Those with delayed growth demonstrated a significant increase in growth velocity after initiation of anti-TNFs. Increase in growth rate was unrelated to pubertal growth spurt. No change was observed in skeletal maturation before and after anti-TNFs. The strongest predictor of change in growth velocity was growth rate prior to anti-TNFs. Change in inflammatory activity remained a significant predictor even after decrease in glucocorticoids was taken into account. In JIA-associated uveitis, impact of two first-line biologic agents, etanercept and infliximab, and second-line or third-line anti-TNF agent, adalimumab, was evaluated. In 108 refractory JIA patients receiving etanercept or infliximab, uveitis occurred in 45 (42%). Uveitis improved in 14 (31%), no change was observed in 14 (31%), and in 17 (38%) uveitis worsened. Uveitis improved more frequently (p=0.047) and frequency of annual uveitis flares was lower (p=0.015) in those on infliximab than in those on etanercept. In 20 patients taking adalimumab, 19 (95%) had previously failed etanercept and/or infliximab. In 7 patients (35%) uveitis improved, in one (5%) worsened, and in 12 (60%) no change occurred. Those with improved uveitis were younger and had shorter disease duration. Serious adverse events (AEs) or side-effects were not observed. Adalimumab was effective also in arthritis. Long-term drug survival (i.e. continuation rate on drug) with etanercept (n=105) vs. infliximab (n=104) was at 24 months 68% vs. 68%, and at 48 months 61% vs. 48% (p=0.194 in log-rank analysis). First-line anti-TNF agent was discontinued either due to inefficacy (etanercept 28% vs. infliximab 20%, p=0.445), AEs (7% vs. 22%, p=0.002), or inactive disease (10% vs. 16%, p=0.068). Females, patients with systemic JIA (sJIA), and those taking infliximab as the first therapy were at higher risk for treatment discontinuation. One-third switched to the second anti-TNF agent, which was discontinued less often than the first. In conclusion, in refractory JIA anti-TNFs induced enhanced growth velocity. Four-year treatment survival was comparable between etanercept and infliximab, and switching from first-line to second-line agent a reasonable therapeutic option. During anti-TNF treatment, one-third with JIA-associated anterior uveitis improved.
  • Häkkinen, Hanna (2004)
    Horizontal restrictions of competition can take different forms – the most obvious being a price cartel, where producers directly agree on the prices of their products. Through a contractual agreement the cartel members are able to increase their joint market power, which leads to higher prices, lower output and, eventually, decreased consumer welfare (the conventional argument against monopolies). It has been estimated that the magnitude of the harm from cartels is many billions of dollars annually. The first part of this thesis presents the most important economic contribution made to the analysis of oligopolistic coordination, which includes among others the articles from Green and Porter (1984) and Rotemberg and Saloner (1986). The analysis begins by identifying structural factors that affect the stability and sustainability of collusion. These factors include industry concentration, entry barriers and demand fluctuations. The analysis shows that collusive behaviour is more likely in industries where concentration ratios and entry barriers are high. However, collusion is more difficult to sustain if demand is unstable. The role played by the presence of large levels of inventories and excess capacities is shown to be more ambiguous, which holds true also for product homogeneity. The end of the first part emphasises the role of price transparency and information exchange in sustaining collusive outcomes. The second part of the thesis is about antitrust enforcement against cartels. Since competition authorities rarely have reliable data on firms’ costs, the detection of cartels is difficult. To overcome this problem of asymmetric information, the authorities in both US and EU have adopted so-called leniency programs that grant reduced fines for cartel members that cooperate with the authority, thus helping to reveal the illegal cartel. The analysis follows Motta and Polo (2003), showing that fine reductions may make antitrust enforcement more effective, but only if the authority’s resources are scarce. Since fine reductions also reduce the cost of collusive behaviour, they may – under certain combinations of policy parameters – make collusion even more attractive.
  • Kanerva, Kristiina (Helsingin yliopisto, 2010)
    Polyamines are organic polycations that participate in various physiological functions, including cell proliferation, differentiation and apoptosis. Cellular polyamines originate from endogenous biosynthesis and exogenous sources. Their subcellular pool is under strict control, achieved by regulating their uptake and metabolism. Polyamine-induced proteins called antizymes (AZ) act as key regulators of intracellular polyamine concentration. They regulate both the transport of polyamines and the activity and degradation of ornithine decarboxylase (ODC), the rate-limiting enzyme in polyamine biosynthesis. AZs themselves are negatively regulated by antizyme inhibitor (AZIN). AZIN functions as a positive regulator of cellular polyamine homeostasis, which by binding to AZs reactivates ODC and induces the uptake of polyamines. In various pathological conditions, including cancer, polyamine levels are misregulated. Polyamine homeostasis has therefore become an attractive target for therapeutic interventions and it is thus crucial to characterize the molecular basis underlying the homeostatic regulation. A novel human AZIN-resembling protein was previously identified in our group. The purpose of this study was to elucidate the function and distribution of this protein, termed as an antizyme inhibitor 2 (AZIN2). According to my results, AZIN2 functions as a novel regulator of polyamine homeostasis. It shows no enzymatic activity, but instead it binds AZs and negates their activity, which subsequently leads to reactivation of ODC and inhibition of its degradation. Expression of AZIN2 is restricted to terminally differentiated cells, such as mast cells (MC) and neurosecretory cells. In these actively secreting cell types, AZIN2 localizes to subcellular vesicles or granules where its function is important for the vesicle-mediated secretion. In MCs, AZIN2 localizes to the serotonin-containing subset of MC granules, and its expression is coupled to MC activation. The functional role of polyamines as potential mediators of MC activity was also investigated, and it was observed that the secretion of serotonin is selectively dependent on activation of ODC. In neurosecretory cells, AZIN2-positive vesicles localize mainly to the trans-Golgi network (TGN). Depletion of AZIN2 or cellular polyamines causes selective fragmentation of the TGN and retards secretion of proteins. Since addition of exogenous polyamines reverses these effects, the data indicate that AZIN2 and its downstream effectors, polyamines, are functionally implicated in the regulation of secretory vesicle transport. My studies therefore reveal a novel function for polyamines as modulators of both constitutive and regulated secretion. Based on the results, I propose that the role of AZIN2 is to act as a local in situ activator of polyamine biosynthesis.
  • Korpinen, Kasperi Nikolai (2005)
    Opinnäytetyössä on analysoitu pankkiryhmien yrityksille ja elinkeinonharjoittajille toimialoittain myöntämien lainojen korkoja. Korkoja on mallinnettu kovarianssianalyysin avulla. Estimointimenetelminä on käytetty pienimmän neliösumman ja painotetun pienimmän neliösumman menetelmiä. Korkoaineistolle estimoiduista paneeliaineistomalleista on johdettu aggregoimalla makromallit ja verrattu näitä suoraan aggregaattitasolla estimoituihin tavanomaisiin makromalleihin. Heterogeenisista paneeliaineistomalleista saadaan johdettua makromallit, joiden kertoimien keskivirheet ovat pienimmät. Kun painoina käytettiin uusien lainojen määrien neliöjuurimuunnoksia, painotetun pienimmän neliösumman menetelmällä päästiin paneeliaineistomalleissa parempiin aggregaattitason sovitteisiin. Muutokset eri pankkiryhmien eri toimialoille myöntämien uusien lainojen määrissä vaikuttavat aggregaattikorkoon. Tavanomaiset makromallit eivät sisällä informaatiota näissä markkinaosuuksissa tapahtuvista muutoksista. Selittävinä tekijöinä käytettiin konkurssialttiutta, keskuspankin ohjauskorkoa, kuluttajabarometriä, toimi-aloittaisia liikevaihto- ja arvonlisätietoja, Herfindahl-indeksiä, uusien lainojen osuuksia toimialan lainoista yhteensä sekä kokonaistuotannon kuukausikuvaajaa. Toimialakohtaiset muuttujat osoittautuivat epästabiileiksi ja aiheuttivat multikollineaarisuusongelmia. Merkitsevimmiksi ja vakaimmiksi selittäviksi tekijöiksi osoittautuivat ohjauskorko, uusien lainojen osuus toimialan uusista lainoista, kuluttajabarometri ja vuosivakiot. Tutkimuksessa todetaan, että korot vaihtelevat pankkiryhmittäin ja toimialoittain. Korkojen erot ovat vähentyneet koko tarkasteluperiodin aikana vuoden 1997 alusta vuoden 2002 loppuun. Lainamarkkinoiden keskittyneisyys on laskenut kaikilla toimialoilla paitsi maa- ja kalataloustoimialoilla. Samoin korkojen poikkeamat keskuspankin ohjauskorosta ovat pienentyneet. Korkojen ja ohjauskoron välisten erojen pieneneminen on tapahtunut eri vauhtia.
  • Lietsala, Leena (Helsingin yliopisto, 2010)
  • Salokannel, Juhani (1971)
  • Pelkonen, L. ((191)
  • Otava, T. K. (Tunt)
  • Toivola, Impi Siviä (1935)
  • Halila, Aimo Oskari ((193)
  • Julkunen, Asta-Maija (1985)