Os linfócitos T CD4+ orquestram a resposta imune adaptativa, auxiliando os macrófagos, os linfócitos T CD8+ e os linfócitos B na resposta mais eficiente frente a um antígeno. As etapas que caracterizam uma resposta imune adaptativa são: apresentação do antígeno, ativação e diferenciação dos linfócitos T, expansão clonal e morte celular para retorno à homeostasia via AICD. Este tipo de morte ocorre via FAS/FASL. Tendo em vista que o mecanismo pelo qual a PGE2 inibe a expressão de fasl ainda não é conhecido, o presente trabalho tem como objetivo compreender o mecanismo molecular de atuação da PGE2 sobre os linfócitos T CD4+ na inibição gênica do FASL, tendo como hipótese o envolvimento do repressor transcricional ICER. Foi verificado que PGE2 10-8 M é capaz de proteger as DO11.10 da AICD e que, nesta concentração, ela induz a expressão de icer. Este repressor apresenta uma expressão transiente e observa-se seu aumento concomitantemente à inibição da expressão de fasl. Sendo assim, sugere-se a participação de ICER na via de inibição do fasl pela PGE2. / CD4+ T lymphocytes orchestrate the adaptive immune response, helping the macrophages, CD8+ T lymphocytes and B lymphocytes to reach an efficient antigen-specific immune response. The adaptive immune response is characterized by different phases: antigen, T lymphocyte activation and differentiation, clonal expansion and, finally, clonal cell death to return to homeostasis via AICD. This cell death occurs via FAS/FASL. Since the mechanism by which PGE2 inhibits fasl expression is not known, our aim is to understand the molecular mechanism responsible for PGE2 inhibition of fasl in CD4+ lymphocytes. Our hypothesis is that the transcriptional repressor ICER, which binds to CRE sites on gene promoters, is involved in this process. We verified that PGE2 10-8 M protects DO11.10 cells from AICD, and in that concentration, PGE2 increases icer expression. This repressor has a transient expression and we observed that its expression is increased in the same time that fasl expression is inhibited. Thus, we suggest the involvement of ICER in fasl inhibition pathway by PGE2.

Os linfócitos T CD4+ orquestram a resposta imune adaptativa, auxiliando os macrófagos, os linfócitos T CD8+ e os linfócitos B na resposta mais eficiente frente a um antígeno. As etapas que caracterizam uma resposta imune adaptativa são: apresentação do antígeno, ativação e diferenciação dos linfócitos T, expansão clonal e morte celular para retorno à homeostasia via AICD. Este tipo de morte ocorre via FAS/FASL. Tendo em vista que o mecanismo pelo qual a PGE2 inibe a expressão de fasl ainda não é conhecido, o presente trabalho tem como objetivo compreender o mecanismo molecular de atuação da PGE2 sobre os linfócitos T CD4+ na inibição gênica do FASL, tendo como hipótese o envolvimento do repressor transcricional ICER. Foi verificado que PGE2 10-8 M é capaz de proteger as DO11.10 da AICD e que, nesta concentração, ela induz a expressão de icer. Este repressor apresenta uma expressão transiente e observa-se seu aumento concomitantemente à inibição da expressão de fasl. Sendo assim, sugere-se a participação de ICER na via de inibição do fasl pela PGE2. / CD4+ T lymphocytes orchestrate the adaptive immune response, helping the macrophages, CD8+ T lymphocytes and B lymphocytes to reach an efficient antigen-specific immune response. The adaptive immune response is characterized by different phases: antigen, T lymphocyte activation and differentiation, clonal expansion and, finally, clonal cell death to return to homeostasis via AICD. This cell death occurs via FAS/FASL. Since the mechanism by which PGE2 inhibits fasl expression is not known, our aim is to understand the molecular mechanism responsible for PGE2 inhibition of fasl in CD4+ lymphocytes. Our hypothesis is that the transcriptional repressor ICER, which binds to CRE sites on gene promoters, is involved in this process. We verified that PGE2 10-8 M protects DO11.10 cells from AICD, and in that concentration, PGE2 increases icer expression. This repressor has a transient expression and we observed that its expression is increased in the same time that fasl expression is inhibited. Thus, we suggest the involvement of ICER in fasl inhibition pathway by PGE2.

No description available.

Yes / Although highway runoff has historically been extensively studied, the increasing complexity of stormwater management means that there are still significant gaps regarding the reduction of soluble metals. The work reported in this paper addresses these challenges by analysing the presence and behaviour of iron, copper and zinc in runoff from junction 24 of the M1 motorway in the UK (peak traffic flow: 30,000 vehicles per hour) and comparing it with other urban sources of metals found in the same catchment (a local brook and sewage treatment works). The sampling site included an interceptor and a treatment lagoon and the event monitoring indicated a trend by which the metals did not change their concentration or particulate soluble proportion immediately, hence showing that pre- and post-storm conditions are important factors when analysing the solubility of metals and their behaviour. The data provided further evidence of the important influence of storm characteristics on metal concentrations in highway runoff, in particular the effects of an antecedent dry weather period (ADWP). In addition, this study also helped us to better understand how the release of sodium the application of de-icer for road maintenance in winter affects the availability of zinc.

Background: All treatments, especially funded by social means, should be subject to cost-effectiveness studies to ensure that the best possible optimization decision it taken between different treatment options. Within the health care area this is a well-developed area. For odontology in general, and orthodontic treatment in specific, this is an unknown territory and cost-effectiveness studies are rare. Malocclusion can be treated with several different systems. The sales pitch from system providers for braces - such as self-ligated brackets (SLB) promises e.g. shorten treatment duration, shorter chairtime, fewer visits, but the purchase cost of SLB systems is higher. Due to lack of results from unbiased RCT there is no guidelines. It is up to the dentist to use the treatment method/system of their own choice. Purpose: The purpose of this thesis is to estimate the cost-effectiveness of SLB compared to conventional brackets (CB) to determine which of the two systems that should be considered as the preferred choice of treatment in a publicly funded system. Method: Through an incremental cost-effectiveness ratio (ICER) calculate the most costeffective system from a societal perspective which includes all costs. To estimate the health care cost, the Reference price list will be used as baseline for production cost for CB. With the use of secondary resources examine the cost driving components to estimate the production cost of SLB. To estimate the non-health care cost a matrix with downtime from work and travel costs was estimated accounting for travel to disclose the magnitude of these cost. The Outcome of the different treatment alternatives will be measured from different perspectives, such as state specific and general profiles. Treatment duration and foregone education will also be investigated. Conclusions: When all production costs for SLB has been adjusted it shows that the total cost of SLB is slightly cheaper. The reduced number of visits required, less chairtime and shorter treatment period are the positive sides of the higher purchase cost of the SLB. Most of the outcome results are not statistically significant, but there is a tendency, with better average values for SLB. SLB seems to be the cheaper and with more effective outcome though not to the extent the provider promises. The difference of treatment duration is minimal and has no significant advantage. The foregone education for the patient is not possible to quantify in monetary terms but could have significant impact depending on different geographical areas but will small differences between the systems. Hence, in lack of unbiased studies and just focusing on average values, SLB dominates CB and should be the preferred choice of treatment until new long-term studies has been published. / Bakgrund: Alla behandlingar, särskilt de som är offentligt finansierade, borde ha genomgått kostnadseffektivitetsbedömningar för att kunna fatta bästa möjliga beslut. Inom sjukhälsovård är detta ett välutvecklat område. Inom tandvård generellt, men kanske ortodonti i synnerhet, är detta ett outforskat område och kostnadseffektivitetsstudier är sällsynta. Malocklusion kan behandlas med flera olika system. Säljargument från olika tandställningsleverantörer, som t.ex. självligerande brackets (SLB) ger löften om t.ex. kortare behandlingsperiod, kortare tid i tandläkarstolen, färre besök men till en högre inköpskostnad. I brist på resultat från oberoende RCT saknas riktlinjer. Det är upp till den enskilda tandläkaren att välja den behandlingsmetod/system som hen finner bäst. Syfte: Syftet med uppsatsen är att undersöka kostnadseffektiviteten mellan SLB jämfört med konventionella brackets (CB) för att avgöra vilket av dessa två system borde anses vara föredraget behandlingsalternativ i ett offentligt finansierat system Metod: Med kostnadseffektivitetskvoten (incremental cost-effectiveness ratio, ICER) beräkna det mest kostnadseffektiva systemet från ett samhällsperspektiv som inkluderar alla kostnader. För att uppskatta direkta behandlingskostnaden kommer Referensprislistan att användas som produktionskostnadsbas. Med hjälp av sekundära källor som undersöker de kostnadsdrivande komponenterna, uppskatta produktionskostnaden för SLB. För att mäta de indirekta behandlingskostnaderna skapas en matris för att påvisa kostnaden med ställtid från arbete och resekostnader. Resultatet av de olika behandlingsalternativen kommer att mätas från olika perspektiv, såsom generella hälsoprofiler och tillståndsspecifika. Behandlingsperiod och missad utbildnings kommer också att undersökas. Slutsats: Efter det att produktionskostnaderna har blivit justerade visas att totalkostnaden för SLB är något billigare. Färre antal besök, kortare tid i behandlingsrummet är det positiva sidorna av det högre inköpspriset för SLB. De flesta av resultaten är inte statistiskt signifikanta men det finns en tendens mot bättre effekt med SLB. SLB tycks vara det billigare och mest effektiva systemet om än inte i den utsträckning som säljargumenten hävdar. Skillnaden i behandlingsperiod är minimal och har igen avgörande betydelse. Den missade utbildningen är svårligen kvantifierbar i monetära termer men kan ha en avgörande betydelse beroende på olika geografiska platser men med små skillnader mellan systemen. Följaktligen, i brist på oberoende studier och med ett fokus på medelvärde är SLB det dominerande valet över CB och borde vara det föredragna behandlingsalternativet fram till dess att nya långsiktiga forskningsrön har blivit publicerade.

In my thesis, in the theoretical part I deal with atrial fibrillation. I also deal with management of atrial fibrillation treatment. In the paper I explain the basic principles of pharmaco-economic evaluation in the Czech Republic, on the basis of which laws these pharmacological interventions are evaluated and who are in the Czech Republic. In the work I present cost breakdown and what are the most commonly used pharmaco-economic analyzes. In the practical part I will apply the theoretical knowledge. I have developed cost utility analysis based on available clinical evidence - randomized clinical trials ARISTOTLE (Granger, 2011), RE-LY (Connolly, 2009), ROCKET AF (Patel, 2011). I made an indirect comparison of the total benefits of NOACs. In the baseline scenario, I have calculated QALY to evaluate the benefits of effectiveness, safety and reduction of mortality. I have also dealt with a bleeding-related scenario. The ICER's greatest contribution to the public healthcare system has shown the active substance apixaban in both scenarios. I added the results and confirmed the clinical results of a recent, robust, retrospective study by Mayo Clinic (Yao, 2016).

I Sverige har vårdköerna varit hett debatterade under större delen av 2000-talet. Detta berorpå att vårdköerna har blivit långa, vilket har lett till att politikerna stiftat lagar som stipulerarhur lång tid en patient ska få vänta på vård. Detta är den så kallade Vårdgarantin, som innebärbland annat att patienten inte ska behöva vänta längre än 90 dagar på kirurgisk vård efterfastställd diagnos. Trots Vårdgarantin har vårdköerna inte minskat, utan snarare ökat. Utifrån denna problematik är syftet att undersöka alternativkostnaden för samhället av att inteprioritera vårdkön. Vi gör detta genom att analysera operationer som har längre väntetid änvad Vårdgarantin föreskriver, och undersöker hur kostnadseffektiva operationerna är för attberäkna hur många år i full hälsa som går förlorade på grund av väntetiderna. Slutligendiskuterar vi vad regionens kostnader blir av att inte prioritera vårdköerna. För att svara på frågeställningarna gör vi en litteratursökning likt en tidigare studie nyligengenomförd i Irland för att undersöka kostnadseffektiviteten av kirurgiska behandlingar, ochdärefter jämföra kostnadseffektiviteten mot ett tröskelvärde för kostnadseffektivitet på 300000 SEK. Resultatet visar att en större investering i den svenska vårdkön vore mycketkostnadseffektivt, då operationernas kostnadseffektivitet är betydligt lägre än tröskelvärdet på300 000 SEK. I studien visar vi exempelvis att ingen av de sex interventionerna somundersöks kostar mer än 50 000 SEK per år i full hälsa, medan svenska beslutsfattare inomvårdsektorn är villiga att acceptera en kostnad uppemot 2 miljoner SEK under vissaförutsättningar. Det ska dock tilläggas att patienterna som står i vårdkö får vård till slut, ävenom det kan dröja flera år tills de får det. Vår slutsats är att patienter som väntar på vård är en nedprioriterad grupp i sjukvården, ochatt de representerar en alternativkostnad som beslutsfattare bör ta i beaktande vid andrainvesteringsmöjligheter gällande hälsa- och sjukvård. Vidare forskning bör bland annatutreda möjligheterna att förkorta väntetiderna. / The waiting lists for healthcare have been heavily debated in Sweden during the 21st century.It has been so because patients have been waiting for healthcare much longer than expected,which has led politicians to change the healthcare laws, promising to decrease the queuingtime for patients. This is the so-called Vårdgarantin (Healthcare Warranty), which, amongother things, says that a patient should not have to wait longer than 90 days for surgery, afterreferral. Despite Vårdgarantin, the waiting lists have not decreased, but rather increased. Based on this problem we have chosen to examine the opportunity cost for society of notprioritizing the healthcare waiting lists by analyzing which surgeries have longer waiting liststhan the Vårdgaranti prescribes. We will also examine how cost effective each surgery is andcalculate how many years at full health is lost in the population when society does notprioritize addressing the queues. Furthermore, we will discuss the Swedish regions’ (which isthe administrative unit in Sweden that is responsible for providing health care to its citizens)opportunity costs by not prioritizing the waiting list. To answer these issues, have we done a literature study, in the same fashion as researchers inIreland recently, to examine the cost effectiveness of surgeries and compare it to a 300 000SEK cost-effectiveness threshold. Our results show that it would be cost effective forSwedish regions to invest in reducing their waiting lists, due to relatively low costs per yearwith full health of surgeries with long waiting lists. In our study, all of the six includedinterventions cost less than 50 000 SEK per year in full health. This can be compared to theSwedish decision makers who sometimes are willing to pay up to 2 million SEK per year atfull health for the very ill under extraordinary circumstances. It should be noted that thepatients who are in the healthcare queue receive care in the end, even if it can take severalyears until the patients receive it. Conclusively, patients waiting for care is a deprioritized group in the healthcare sector andcan be seen as an opportunity cost when considering new investment opportunities. Furtherresearch should investigate the possibilities of how waiting times can be reduced.

Leucodepletion, the removal of leucocytes from blood products improves the safety of blood transfusion by reducing adverse events associated with the incidental non-therapeutic transfusion of leucocytes. Leucodepletion has been shown to have clinical benefit for immuno-suppressed patients who require transfusion. The selective leucodepletion of blood products by bed side filtration for these patients has been widely practiced. This study investigated the economic consequences in Queensland of moving from a policy of selective leucodepletion to one of universal leucodepletion, that is providing all transfused patients with blood products leucodepleted during the manufacturing process. Using an analytic decision model a cost-effectiveness analysis was conducted. An ICER of $16.3M per life year gained was derived. Sensitivity analysis found this result to be robust to uncertainty in the parameters used in the model. This result argues against moving to a policy of universal leucodepletion. However during the course of the study the policy decision for universal leucodepletion was made and implemented in Queensland in October 2008. This study has concluded that cost-effectiveness is not an influential factor in policy decisions regarding quality and safety initiatives in the Australian blood sector.

Background: In the ‘Arimidex’, Tamoxifen Alone or in Combination (ATAC) trial, the aromatase inhibitor (AI) anastrozole had a ignificantly better efficacy and safety profile than tamoxifen as initial adjuvant therapy for hormone receptor-positive (HR+) early breast cancer (EBC) in postmenopausal patients. To compare the combined long-term clinical and economic benefits, we carried out a cost-effectiveness analysis (CEA) of anastrozole versus tamoxifen based on the data of the 100- month analysis of the ATAC trial from the perspective of the German public health insurance. Patients and Methods: A Markov model with a 25-year time horizon was developed using the 100-month analysis of the ATAC trial as well as data obtained from published literature and expert opinion. Results: Adjuvant treatment of EBC with anastrozole achieved an additional 0.32 quality-adjusted life-years (QALYs) gained per patient compared with tamoxifen, at an additional cost of D 6819 per patient. Thus, the incremental cost effectiveness of anastrozole versus tamoxifen at 25 years was D 21,069 ($ 30,717) per QALY gained. Conclusions: This is the first CEA of an AI that is based on extended follow-up data, taking into account the carryover effect of anastrozole, which maintains the efficacy benefits beyond therapy completion after 5 years. Adjuvant treatment with anastrozole for postmenopausal women with HR+ EBC is a cost-effective alternative to tamoxifen. / Hintergrund: Bei der adjuvanten Therapie von postmenopausalen Patientinnen mit Hormonrezeptor-positivem (HR+) Mammakarzinom belegen die ATAC-100-Monatsdaten (ATAC-Studie: ‘Arimidex’, Tamoxifen Alone or in Combination) einen signifikanten Vorteil von Anastrozol gegenüber Tamoxifen in Bezug auf Rezidivrisiko und Verträglichkeit. Es wurde eine Kosten-Nutzwert-Analyse von Anastrozol im Vergleich zu Tamoxifen aus der Sicht des deutschen Gesundheitssystems durchgeführt. Material und Methoden: Als Berechnungsbasis wurde ein Markov- Modell zur Abschätzung der Kosteneffektivität entwickelt. Der Modellierungszeitraum umfasste 25 Jahre. Die Daten wurden anhand der ATAC-100-Monatsdaten, vorliegender Literatur und durch ein interdisziplinäres Expertenteam ermittelt. Ergebnisse: Eine adjuvante Therapie mit Anastrozol erzielte 0,32 quality-adjusted life-years (QALYs) pro Patientin mehr, verglichen mit einer adjuvanten Tamoxifentherapie. Die zusätzlichen Kosten der Therapie mit Anastrozol lagen bei 6819 D pro Patientin. Im Vergleich mit Tamoxifen erzielte Anastrozol einen ICER (Incremental Cost-Effectiveness Ratio) von 21 069 D (30 717 $)/QALY über den gesamten Modellierungszeitraum. Schlussfolgerung: Diese Kosten- Nutzwert-Analyse eines Aromatasehemmers basiert erstmals auf einer Datenanalyse, die auch das Follow-Up und den sogenannten Carryover- Effekt nach einer abgeschlossenen 5-Jahres-Therapie beinhaltet. Anastrozol ist auch nach dieser Analyse aus der Sicht des deutschen Gesundheitssystems eine kosteneffektive Therapieoption für postmenopausale Patientinnen mit einem HR+ frühen Mammakarzinom. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The standard ASTM C672 de-icer salt scaling resistance test has been found to be overly aggressive to concretes containing slag cement. It was compared to the newly proposed ASTM WK9367 method, based on the Quebec BNQ test, as well as several modifications, including use of an accelerated curing regime developed in Virginia (VADOT). Sixteen concrete mixtures were studied using high-alkali cement, low-alkali cement, grade 100 slag and grade 120 slag with slag contents of 0%, 20%, 35% and 50%. Vinsol resin air-entraining admixture was compared to Micro Air®. Reducing the water cement ratio from 0.42 to 0.38 had the biggest impact on improving scaling resistance of slag concretes. In general, increased slag contents increased scaling regardless of the test method used. The Micro Air® admixture provided a lower air void actor and higher hardened air content compared to Vinsol resin.