K'cidade : um modo de viver a intervenção comunitária

Relatório de estágio de mestrado, Ciências da Educação (Formação de Adultos), Universidade de Lisboa, Instituto de Educação, 2011

Cost-Effectiveness of Non-Vitamin K Antagonist Oral Anticoagulants for Atrial Fibrillation in Portugal

INTRODUCTION AND OBJECTIVES:Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS: A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS:Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS:Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.

Toyota RAV4 model year marketing plan for the U.K

NSBE - UNL

The fourth extracellular loop of the alpha subunit of Na,K-ATPase. Functional evidence for close proximity with the second extracellular loop.

Na,K-ATPase is the main active transport system that maintains the large gradients of Na(+) and K(+) across the plasma membrane of animal cells. The crystal structure of a K(+)-occluding conformation of this protein has been recently published, but the movements of its different domains allowing for the cation pumping mechanism are not yet known. The structure of many more conformations is known for the related calcium ATPase SERCA, but the reliability of homology modeling is poor for several domains with low sequence identity, in particular the extracellular loops. To better define the structure of the large fourth extracellular loop between the seventh and eighth transmembrane segments of the alpha subunit, we have studied the formation of a disulfide bond between pairs of cysteine residues introduced by site-directed mutagenesis in the second and the fourth extracellular loop. We found a specific pair of cysteine positions (Y308C and D884C) for which extracellular treatment with an oxidizing agent inhibited the Na,K pump function, which could be rapidly restored by a reducing agent. The formation of the disulfide bond occurred preferentially under the E2-P conformation of Na,K-ATPase, in the absence of extracellular cations. Using recently published crystal structure and a distance constraint reproducing the existence of disulfide bond, we performed an extensive conformational space search using simulated annealing and showed that the Tyr(308) and Asp(884) residues can be in close proximity, and simultaneously, the SYGQ motif of the fourth extracellular loop, known to interact with the extracellular domain of the beta subunit, can be exposed to the exterior of the protein and can easily interact with the beta subunit.

Purification and characterization of (Na+ + K+)-ATPase from toad kidney

This report describes the partial purification and the characteristics of (Na+ + K+)-ATPase (ATP phosphohydrolase, EC 3.6.1.3) from an amphibian source. Toad kidney microsomes were solubilized with sodium deoxycholate and further purified by sodium dodecyl sulphate treatment and sucrose gradient centrifugation, according to the methods described by Lane et al. [(1973) J. Biol. Chem. 248, 7197--7200], Jørgensen [(1974) Biochim. Biophys. Acta 356, 36--52] and Hayashi et al. [(1977) Biochim. Biophys. Acta 482, 185--196]. (Na+ + K+)-ATPase preparations with specific activities up to 1000 mumol Pi/mg protein per h were obtained. Mg2+-ATPase only accounted for about 2% of the total ATPase activity. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis revealed three major protein bands with molecular weights of 116 000, 62 000 and 26 000. The 116 000 dalton protein was phosphorylated by [gamma-32P]ATP in the presence of sodium but not in the presence of potassium. The 62 000 dalton component stained for glycoproteins. The Km for ATP was 0.40 mM, for Na+ 12.29 mM and for K+ 1.14 mM. The Ki for ouabain was 35 micron. Temperature activation curves showed two activity peaks at 37 degrees C and at 50 degrees C. The break in the Arrhenius plot of activity versus temperature appeared at 15 degrees C.

TACI, unlike BAFF-R, is solely activated by oligomeric BAFF and APRIL to support survival of activated B cells and plasmablasts.

The cytokine BAFF binds to the receptors TACI, BCMA, and BAFF-R on B cells, whereas APRIL binds to TACI and BCMA only. The signaling properties of soluble trimeric BAFF (BAFF 3-mer) were compared with those of higher-order BAFF oligomers. All forms of BAFF bound BAFF-R and TACI, and elicited BAFF-R-dependent signals in primary B cells. In contrast, signaling through TACI in mature B cells or plasmablasts was only achieved by higher-order BAFF and APRIL oligomers, all of which were also po-tent activators of a multimerization-dependent reporter signaling pathway. These results indicate that, although BAFF-R and TACI can provide B cells with similar signals, only BAFF-R, but not TACI, can respond to soluble BAFF 3-mer, which is the main form of BAFF found in circulation. BAFF 60-mer, an efficient TACI agonist, was also detected in plasma of BAFF transgenic and nontransgenic mice and was more than 100-fold more active than BAFF 3-mer for the activation of multimerization-dependent signals. TACI supported survival of activated B cells and plasmablasts in vitro, providing a rational basis to explain the immunoglobulin deficiency reported in TACI-deficient persons.

Structural organization of alpha-subunit from purified and microsomal toad kidney (Na+ + K+)-ATPase as assessed by controlled trypsinolysis

The membrane organization of the alpha-subunit of purified (Na+ + K+)-ATPase ((Na+ + K+)-dependent adenosine triphosphate phosphorylase, EC 3.6.1.3) and of the microsomal enzyme of the kidney of the toad Bufo marinus was compared by using controlled trypsinolysis. With both enzyme preparations, digestions performed in the presence of Na+ yielded a 73 kDa fragment and in the presence of K+ a 56 kDa, a 40 kDa and small amounts of a 83 kDa fragment from the 96 kDa alpha-subunit. In contrast to mammalian preparations (Jørgensen, P.L. (1975) Biochim. Biophys. Acta 401, 399-415), trypsinolysis of the purified amphibian enzyme led to a biphasic loss of (Na+ + K+)-ATPase activity in the presence of both Na+ and K+. These data could be correlated with an early rapid cleavage of 3 kDa from the alpha-subunit in both ionic conditions and a slower degradation of the remaining 93 kDa polypeptide. On the other hand, in the microsomal enzyme, a 3 kDa shift of the alpha-subunit could only be produced in the presence of Na+. Our data indicate that (1) purification of the amphibian enzyme with detergent does not influence the overall topology of the alpha-subunit but produces a distinct structural alteration of its N-terminus and (2) the amphibian kidney enzyme responds to cations with similar conformational transitions as the mammalian kidney enzyme. In addition, anti alpha-serum used on digested enzyme samples revealed on immunoblots that the 40 kDa fragment was better recognized than the 56 kDa fragment. It is concluded that the NH2-terminal of the alpha-subunit contains more antigenic sites than the COOH-terminal domain in agreement with the results of Farley et al. (Farley, R.A., Ochoa, G.T. and Kudrow, A. (1986) Am. J. Physiol. 250, C896-C906).

Lounais-Suomen pohjavesien toimenpideohjelma vuoteen 2015

Kaikissa EU-maissa on laadittu ensimmäiset vesienhoitosuunnitelmat, joiden avulla tavoitellaan pinta- ja pohjavesien hyvää tilaa vuonna 2015. Pohjavesin osalta tavoitteena on pohjavesien hyvä kemiallinen ja määrällinen tila. Vesienhoito on osa koko Euroopan laajuista, vesipolitiikan puitedirektiiviin pohjautuvaa työtä. Kokemäenjoen-Saaristomeren-Selkämeren vesienhoitoalueelle laaditussa vesienhoitosuunnitelmassa asetettujen tavoitteiden saavuttamiseksi on Lounais-Suomen alueen pohjavesille laadittu toimenpideohjelma. Lisäksi alueelle on laadittu kaksi pintavesien hoidon toimenpideohjelmaa, joista toinen Varsinais-Suomeen ja toinen Satakuntaan. Lounais-Suomen pohjavesien toimenpideohjelmaan vuoteen 2015 on koottu tiedot pohjavettä heikentävistä toiminnoista, riskipohjavesialueista ja selvityskohteista sekä pohjavesien määrällisestä ja kemiallisesta tilasta. Toimenpideohjelmassa esitetään myös tärkeimmät toimenpiteet, joiden avulla pohjavesien määrällinen ja kemiallinen hyvä tila pyritään saavuttamaan ja ylläpitämään vuoteen 2015 mennessä. Pohjavesien osalta tarkastelu kohdistuu vedenhankinnan kannalta tärkeisiin pohjavesialueisiin (luokka I) ja vedenhankintaan soveltuviin pohjavesialueisiin (luokka II). Lounais-Suomessa pohjavesialueita on yhteensä 295, joista I-luokan alueita on 219 kappaletta ja II-luokan alueita 76 kappaletta. Toimenpideohjelmassa tarkastellaan tarkemmin pohjavesialueita, joilla pohjaveden tila on heikentynyt tai hyvä tila on uhattuna ihmistoiminnasta johtuen. Lounais-Suomen alueella merkittävimmät pohjavettä vaarantavat ja muuttavat toiminnot ovat teollisuus ja yritystoiminta, pilaantuneet maa-alueet, liikenne ja tienpito sekä asutus ja maankäyttö. Myös maa-ainesten otolla, maa- ja metsätaloudella sekä vedenotolla ja tekopohjaveden muodostamisella voi olla pohjaveden laatua heikentäviä vaikutuksia. Riskialueiksi nimettiin 34 pohjavesialuetta, selvityskohteiksi 48 ja seurantakohteiksi 5 pohjavesialuetta. Huonoon tilaan on kemiallisen tilan arvioinnin kautta luokiteltu 9 pohjavesialuetta, joiden ongelmat johtuvat mm. torjunta-aineista, kloridista, liuottimista, polttonesteiden lisäaineista ja raskasmetalleista. Pohjavesien määrällinen tila on kaikilla Lounais-Suomen pohjavesialueilla hyvä. Kemiallisen hyvän tilan saavuttaminen ja sen ylläpitäminen vaativat toimenpiteitä, joista tärkeimpiä ovat riskitoimintojen ohjaaminen pohjavesialueiden ulkopuolelle, pohjavesien suojelusuunnitelmat, pilaantuneiden maa-alueiden tutkimukset ja kunnostukset sekä tiealueiden pohjavesisuojausten rakentaminen. Pohjavesien hyvää kemiallista tilaa ei saavuteta kaikilla pohjavesialueilla vuoteen 2015 mennessä, vaikka esitetyt toimenpiteet toteutettaisiin. Toimenpideohjelma tarkistetaan kuuden vuoden välein, jolloin arvioidaan uudestaan pohjavesien tila ja toimet pohjavesien hyvän tilan saavuttamiseksi.

Karta öfver storfurstendömet Finland sammandragen, med stöd af de tillförlitligaste kartor uti general landtmäteri kontoret samt särskildte benäget meddelade upplysningar, uppå K. E. Holms förlag, af A. W. Eklund /

1 kartta :, vär. ;, lehti 88,7 x 58 cm

Теченїе Невы рѣки изъ Ладожскаго озера къ Ст. Петербургу / Tetšenïe Nevy rěki iz Ladožskago ozera k St. Peterburgu = Fluvius Newa a Lacu Ladoga Petropolin versus procurrens

Mittakaava 1:105000

Nieuwe paskaart voor een gedeelte van de Oost-Zee = Nouvelle carte hydrographique d'une partie de la Mer Baltique = Nya pass cort öfwer yen dehl af Oster-Siöön = The new sea map of the second of the East-Sea

Sisältää myös kartakkeet: Pastkaartje van de Noord Bodem, Suomenlahden itäosa ja Laatokka

Nieuwe paskaart voor een gedeelte van de Oost-Zee = Nouvelle carte hydrographique d'une partie de la Mer Baltique = Nya pass cort öfwer yen dehl af Oster-Siöön = The new sea map of the second of the East-Sea

Sisältää myös kartakkeet: Pastkaartje van de Noord Bodem, Suomenlahden itäosa ja Laatokka

Revue française d'histoire d'outre-mer / Société française d'histoire d'outre-mer

1926/04 (A14)-1926/06.

Revue française d'histoire d'outre-mer / Société française d'histoire d'outre-mer

1917 (A5).