Variation and adaptation: learning from success in patient safety-oriented simulation training

Simulation is traditionally used to reduce errors and their negative consequences. But according to modern safety theories, this focus overlooks the learning potential of the positive performance, which is much more common than errors. Therefore, a supplementary approach to simulation is needed to unfold its full potential. In our commentary, we describe the learning from success (LFS) approach to simulation and debriefing. Drawing on several theoretical frameworks, we suggest supplementing the widespread deficit-oriented, corrective approach to simulation with an approach that focusses on systematically understanding how good performance is produced in frequent (mundane) simulation scenarios. We advocate to investigate and optimize human activity based on the connected layers of any setting: the embodied competences of the healthcare professionals, the social and organizational rules that guide their actions, and the material aspects of the setting. We discuss implications of these theoretical perspectives for the design and conduct of simulation scenarios, post-simulation debriefings, and faculty development programs

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML

DNA Methylation Signatures Predict Cytogenetic Subtype and Outcome in Pediatric Acute Myeloid Leukemia (AML)

Pediatric acute myeloid leukemia (AML) is a heterogeneous disease composed of clinically relevant subtypes defined by recurrent cytogenetic aberrations. The majority of the aberrations used in risk grouping for treatment decisions are extensively studied, but still a large proportion of pediatric AML patients remain cytogenetically undefined and would therefore benefit from additional molecular investigation. As aberrant epigenetic regulation has been widely observed during leukemogenesis, we hypothesized that DNA methylation signatures could be used to predict molecular subtypes and identify signatures with prognostic impact in AML. To study genome-wide DNA methylation, we analyzed 123 diagnostic and 19 relapse AML samples on Illumina 450k DNA methylation arrays. We designed and validated DNA methylation-based classifiers for AML cytogenetic subtype, resulting in an overall test accuracy of 91%. Furthermore, we identified methylation signatures associated with outcome in t(8;21)/RUNX1-RUNX1T1, normal karyotype, and MLL/KMT2A-rearranged subgroups (p < 0.01). Overall, these results further underscore the clinical value of DNA methylation analysis in AML

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Instituutiosijoittajan sijoitustuotteet

Opinnäytetyö käsittelee eri sijoitustuotteita institutionaalisen sijoittajan näkökulmasta. Insti-tutionaalisiksi sijoittajiksi lasketaan yhteisöt, joiden tekemät sijoitukset ovat suuria. Näitä sijoittajia ovat esimerkiksi pankit, vakuutusyhtiöt, sijoitusrahastot, yritykset, pankkiiriliik-keet, julkiset yhteisöt kuten valtiot ja kunnat, eläkeyhtiöt ja muut samankaltaiset yhteisöt. Opinnäytetyössä käsitellään joukkovelkakirjalainasijoittamista, osakesijoittamista, rahastosi-joittamista, kiinteistösijoittamista sekä pääomasijoittamista instituutiosijoittajan näkökul-masta. Opinnäytetyön tavoitteena on selvittää instituutiosijoittajalle sopivimmat sijoitusmuodot eri omaisuusluokista. Parhaimmat sijoitusmuodot selvitetään keräämällä tiedot eri sijoitusmuoto-jen hyvistä ja huonoista puolista, parhaat tuottomahdollisuudet omaavista tuotteista sekä riskipitoisimmista tuotteista. Työn tarkoituksena on selvittää instituutiosijoittajien allokaa-tiopäätöksien taustat. Opinnäytetyössä kerrotaan perustiedot eri sijoitustuotteista, jotta lukija saa mahdollisimman hyvän kuvan eri tuotteiden ominaisuuksista. Jokaisen tuotteen kohdalla mainitaan perustieto-jen lisäksi sijoitustuotteeseen liittyvät riskit. Työssä esitellään myös erikseen perustiedot si-joitustuotteen valintaan vaikuttavista tekijöistä sekä instituutiosijoittajan mahdollisuuksista hallita riskejä. Opinnäytetyön tutkimus toteutetaan dokumenttianalyysinä. Tietolähteinä käytetään kirjallisia lähteitä sekä Internet-lähteitä. Päätelmien tukena käytetään eri instituutiosijoittajien vuosi-kertomuksista löytyviä tietoja sijoituskohteista ja siitä, miten sijoitukset ovat jakaantuneet prosentuaalisesti.The thesis deals with investment products from the point of view of institutional investors, here defined as communities whose investments are large. These investors can be banks, insurance companies, investment funds, companies, banking companies, pension companies, public communities such as countries and cities and other similar communities. In this thesis bonds, listed shares, funds, real estates and capital are examined from the institutional investors’ perspective. The objective of this thesis is to determine the most suitable investment forms from different property classes for the institutional investor. The best investment forms are identified by gathering information about the disadvantages and redeeming features of different investment forms: investment products that have the best chances for profit and about high-risk products. The purpose of this thesis is to clarify the background behind the allocation decisions of institutional investors. Basic information about the investment products is presented in the thesis, so that the reader will get a good understanding of their different characteristics. In addition, the risks of each product are described. Information about the factors that affect the selection of the products and the possibilities to control the risks is also presented in the thesis. The research of the thesis is executed as a document analysis. The information sources used include online and printed literature. Information from institutional investors’ annual reports regarding the allocation of investments and the different investment forms are used in sup-port of the conclusions

Varhaisen mobilisaation merkitys akuutisti sairastuneen ikääntyneen kuntoutumisessa

Opinnäytetyön tarkoituksena on kuvailla varhaisen mobilisaation merkitystä akuutisti sairastuneen ikääntyneen kuntoutumisessa. Opinnäytetyömme tavoitteena on auttaa tunnistamaan varhaisen mobilisaation merkitys akuutisti sairastuneen ikääntyneen kuntoutumisessa. Opinnäytetyön tutkimuskysymys on: Mikä merkitys varhaisella mobilisaatiolla on akuutisti sairastuneen ikääntyneen kuntoutumisessa? Työelämäkumppani on Espoon sairaalan päivystysosasto. Aihe valikoitui heidän tarjoamistaan aiheista ja tarpeesta saada lisää tietoa varhaisen mobilisaation merkityksestä akuutisti sairastuneen ikääntyneen kuntoutumisessa. Opinnäytetyö on toteutettu kuvailevana kirjallisuuskatsauksena. Tutkimusmenetelmäksi valikoitui kuvaileva kirjallisuuskatsaus, koska tutkimusmenetelmä vastaa parhaiten työelämäkumppanin tarpeeseen saada lisää tietoa varhaisen mobilisaation merkityksestä akuutisti sairastuneiden iäkkäiden kuntoutumisessa. Kuvaileva kirjallisuuskatsaus antoi myös vapaammat kädet aineiston hakuun kuin esimerkiksi systemaattinen kirjallisuuskatsaus. Aineiston haku ja opinnäytetyöhön valittavat tutkimukset ovat sellaisia, jotka vastaavat tutkimuskysymykseen. Aineiston haussa käytettiin sisäänotto- ja poissulkukriteerejä ja tarkasti valittuja hakusanoja. Tutkimusten kohderyhmä on ikääntyneet yli 65-vuotiaat potilaat ja ne käsittelevät varhaista mobilisaatiota. Aineiston haussa seitsemän tutkimusta valikoitui työhön ja ne analysoitiin kokoamalla taulukkomuotoon keskeiset asiat jokaisesta tutkimuksesta. Taulukossa esitetään jokaisen tutkimuksen keskeiset tulokset. Tutkimusten tulokset jaoteltiin kolmeen eri teemaan. Teemoja ovat varhaisen mobilisaation vaikutus toimintakykyyn, varhaisen mobilisaation vaikutus toipumisaikaan ja kotiutumiseen sekä varhaisen mobilisaation vaikutus komplikaatioihin ja kuolleisuuteen. Opinnäytetyössä analysoitujen tutkimusten tuloksista voidaan tehdä johtopäätös, että varhainen mobilisaatio on hyödyllistä ja turvallista toteuttaa akuutisti sairastuneiden iäkkäiden kuntoutuksessa.The purpose of this thesis was to describe how early mobilization affects the rehabilitation of acutely ill elderly patients. The aim of this thesis was to help to recognize the significance of early mobilization in the rehabilitation of acutely ill elderly patients. The research question is: What significance does an early mobilization have in the rehabilitation of acutely ill elderly? The working life partner was Espoo hospital emergency ward. The subject of this thesis was chosen based on the need for more information about the early mobilization’s significance on the rehabilitation in acutely ill elderly patients in Espoo hospital emergency ward. Narrative literature review was chosen as the method, because it corresponds best to the working life partner’s demand of additional information on early mobilization. This method also gives more freedom in the search for research material compared to systematic literature review. The search for the research material and the studies chosen for this thesis were those that best responded to the research question. In the selection of the research material, inclusion and exclusion criteria and carefully chosen search terms were used. The focus group of the studies were elderly patients who were over 65 years old and the studies should discuss early mobilization. Seven studies were chosen for the thesis and they were compiled into tables by choosing the most central findings of the studies, so they could be analysed. The main findings are shown in the tables. The findings of the studies were divided into three different themes. The themes are the effects of early mobilization on functional ability, the impact of early mobilization on the recovery time and length of the stay and the impact of early mobilization on complications and mortality. Based on the analysis it can be concluded that early mobilization is beneficial and safe to execute in the rehabilitation of acutely ill elderly patients

Älvkarleby, landscape character and design proposal : landscapecharacteranalysis inspired by the method Landscape Character Assessment resulting in guidelines and designporposal

Älvkarleby, landscape character and design proposal is a Graduated Thesis (30 ECCcredtis), in the subject of landscape planning at the Swedish University of Agricultural Sciences, the Department of Rural and Urban Development. This thesis is a study and implement of the method "Landscape Character Assessment" (LCA), developed in England and Scotland as tool to analyse and highlight the landscape in different planning processes. The purpose of LCA is to increase the understanding and strengthen the role of the landscape. The thesis consists of three main parts: landscape characterization, guidelines and a design proposal. The landscape characterization emphasizes the values of the landscape in different types of planning processes, a documentation to base estimations on in any kind of change in the area. Theese estimations have resulted in guidelines that give proposals to the development of the landcape, focusing at the desingproposal. The design proposal is partly based on the landscape characterization and the guidelines, but should be considered a free part of the work. The dominating river landscape in the center of Älvkarleby is the focal point for most activities in the area both historically and at present. As an exmaple of this can be mentioned tourism, scientific research, the water power station, military activities (in the past), fishing and outdoor life. A lot of different interests within this area each make small decisions that can easily result in a fragmented impression of the landscape. In October 2007 Älvkarleby will get a new train station. This will make it easier for people to commute and for tourists to visit. The purpose of the thesis, Älvkarleby landskapskaraktär och gestaltningsförslag, has been to clarify the importance of the landscape for the development of Älvkarleby and to illustrate the landscape characters in the area. The purpose is also to prevent various sorts of changes that fragments the landscape instead of enhance the local landscape characters. As a proposal of a small change I have suggested a design for a new pedestrian- and bicycle path that is partly based on the LCA but partly is to be considered an independent part of the work. The LCA method is developed in England and Scotland for a British landscape. Since the Swedish landscape is rather different it is difficult to adapt the LCA method directly to Sweden. If the method is to be used frequently in future planning processes, a translation to Swedish conditions is needed.Älvkarleby landskapskaraktär och gestaltningsförslag är ett examensarbete på 30 hp, i ämnet landskapsplanering vid Institutionen för stad och land, SLU. Examensarbetet är en studie samt tillämpning av metoden Landscape Character Assessment (LCA) utvecklad i England och Skottland. LCA är en metod som ger en arbetsstruktur som lyfter fram landskapet i olika typer av planeringsprocesser. Metodens syfte är att öka förståelsen och betydelsen av landskapet. Examensarbetet består av tre huvuddelar: landskapskaraktärisering, bedömning och gestaltningsförslag. Landskapskaraktäriseringen resulterar i landskapskaraktärsbeskrivningar som ska fungera som utgångspunkt för eventuella framtida förändringar i området. Utifrån landskapskaraktärsbeskrivningarna görs en bedömning i form av riktlinjer, som ger förslag på hur landskapet kan utvecklas med inriktning på gestaltningsförslaget. Gestaltningsförslaget tar delvis utgångspunkt i landskapsbeskrivningen och riktlinjerna, men ska uppfattas som en fristående del av examensarbetet. Jag har valt att arbeta med Älvkarleby, en ort präglad av sitt landskap som till stor del är dominerat av Dalälven. Älven är utgångspunkt för de flesta aktiviteter i området, både historiskt och idag, som turism, forskning, vattenkraft, militärverksamhet, fiske och friluftsliv. Olika aktörer inom dessa områden fattar små beslut och utför bitvis förändringar som lätt kan resultera i ett splittrat landskap. I oktober 2007 kommer Älvkarleby att få en järnvägsstation. Detta ger nya möjligheter för orten att utvecklas, både som pendlingsort och turistmål. Examensarbetet belyser landskapets betydelse för Älvkarlebys framtida utveckling och tar fram viktiga landskapskaraktärer i området. Genom att lyfta fram landskapet kan man förhindra negativa förändringar i området och istället förstärka de karaktärer som ger en positiv upplevelse av platsen. Som ett exempel på en mindre förändring i landskapet, har jag gestaltat en gång- och cykelväg. Arbetsmetoden är utvecklad i och för det engelska landskapet, detta medför att vissa delar av LCA kan vara svåra att tillämpa i Sverige, som till stora delar har en helt annan typ av landskap. En översättning till svenska förhållanden och begrepp kan behövas för att LCA ska kunna användas i större omfattning även här

Functional role of T-cell activation in viral hepatitis

Hepatitis B and C (HBV, HCV) constitute global health problems and there are approximately 350 million chronically HBV infected people around the world, most of them are found in East and South East Asia and Africa. Worldwide there are 170 million HCV infected individuals with the highest prevalence seen in Egypt. Reported cases of HBV and HCV have decreased significantly due to improvements in screening of blood donors and in particular with respect to HBV due to the introduction of a preventive vaccine. HBV and HCV are transmitted mainly by blood-to-blood contact or by sexual transmission (less efficient for HCV). There are great differences in the ability to clear the viral infection between HBV and HCV infected individuals. In HCV almost 75% develop a chronic disease, while the rate of chronicity caused by HBV is influenced by the age at infection. Thus, only 5% of adult-acquired infection leads to chronic hepatitis B (CHB) whereas the chronicity rate for perinatal infection is up to 90%. Failure to mount effective T cell responses may possibly cause both an inability to respond to HBV vaccination, as well as to CHB. Protective immunity towards HBV can be achieved by vaccination; the protection is based on the emergence of antibodies to the hepatitis B surface antigen (anti-HBs). Though a small group of individuals i.e. non-responders (5 to 10%) fail to do this. We therefore designed a study where previously nonresponders to the HBV vaccine were re-vaccinated using a double dose of the combined hepatitis A virus (HAV) and HBV vaccine in hope to improve priming of a protective HBV response. Almost all non-responders developed protective levels of anti-HBs and approximately half of the patients developed a HBs antigen (HBsAg)-speific T-cell proliferation after re-vaccination. Thus, a nonresponse to the HBV vaccine is not absolute, it most often represent a low responder satus which can be circumvented with the appropriate stimulus. We next investigated how HBV-specific T-cell responses emerged in children with different stages of CHB. In the majority of children an HBV core antigen (HBcAg) specific T-cell proliferation was detected, also in an anti-HBeAg positive group, , indicating that a continuous T-cell proliferation is important to maintain HBe antigen (HBeAg) clearance. Exogenous HBcAg is well known to be a potent activator of both B cells and T helper (TH). An intrinsic feature of HBcAg it is the binding to naïve human and mouse B-cells. Its high immunogenicity suggests that it may be a good target for immunotherapy. Essential for this binding were the residue 76 to 80 on the tip of the spike of the HBcAg.We could also note that the induced CD8+ T-cell response after immunization with endogenously expressed HBcAg was not Bcell dependent whereas priming with exogenously expressed HBcAg was. New treatment strategies are needed for both HBV and HCV infections. We have developed two DNA based vaccines, one based on HBcAg for HBV: and the other based on the non-structural protein 3/4A (NS3/4A) for HCV. Previous studies have showed that the HBcAg- and NS3/4A-vaccine induce both a strong humoral and cellular response in mice, but less is known if they are functional in the liver. We therefore developed a model to test if CD8+ T-cells could home to the liver and eliminate NS3/4A expressing hepatocytes. Transiently transgenic mice were generated using hydrodynamic injection of HBcAg- or NS3/4A-expressing plasmids. We could show that the primed peripheral CD8+ T cells indeed entered the liver and eliminated NS3/4A expressing hepatocytes. We lastly characterized the ability of HBcAg-DNA to induce CTLs. We found that HBcAg-DNA was surprisingly poor in inducing CTLs at a low DNA level when compared to the NS3/4A gene. Despite delivery by in vivo electroporation and gene codon optimization, low levels of DNA still failed to effectively prime CTLs. This is an unexpected property of HBcAg. Overall, these studies show that a poor T cell response, or poor ability to activate T cells, can effectively be overcomed by the appropriate measures, which has implications for human vaccine design

Redovisning och värdering av Goodwill enligt IFRS/IAS

Syftet med vår uppsats är att utreda var utrymme för subjektivitet finns när svenska företag skall redovisa sin goodwillpost enligt de nya IFRS/IAS reglerna. Syftet är även att undersöka hur företagen skall göra för att minska subjektiviteten och göra redovisningen mer jämförbar enligt de grundläggande principerna. Vi har i vårt tillvägagångssätt använd oss av en kvalitativ metod, denna har vi har valt för att få en djupare förståelse för ämnet. Det finns inte några befintliga teorier och därför har vi utgått från verkligheten. Vi har arbetat med en öppen ansats utifrån ett förstående och förklarande syfte, en induktiv strategi. Uppsatsen bygger på information från djupintervjuer och information hämtad från litteratur, standarder och tidskrifter. Ur ett teoretiskt perspektiv har vi arbetat utifrån internationella standarder IFRS/IAS och de grundläggande principerna. Sedan har vi arbetat med värdering till verkligt värde och utrett kritiken bakom denna värdering. Empiri; I teorin skulle man kunna utnyttja de subjektiva spelrummen i värdering av goodwill men hittills är kunskapen i företagen på de flesta håll alltför bristfällig för ett sådant strategiskt tänkande. Resultatredovisning; Balans mellan subjektivitet och objektivitet måste uppnås. Då krävs det att praxis etableras och att kunskap sprids i företagen om värdering av goodwill till verkligt värde, uppdelning av immateriella tillgångar och kassagenererande enheter