Publikationer från Umeå universitet
Not a member yet
55455 research outputs found
Sort by
Policy enactment in Swedish preschools : preschool principals’ perspectives on the new curriculum and municipal support structures
No full textPrincipals are important actors in enacting national educational policy, so it is important to elicit their views of curricular change. Thus, this study explores Early childhood education and care (ECEC) principals’ perspectives of a new ECEC curriculum and its interpretation in a Swedish municipality. Using a contextual lens with cultural, structural and material filters, I examine the principals’ views of the reformulated curriculum and an Implementation Project that the municipality organized to provide support. Empirically, it is based on non-participant observations of group discussions and activities that were parts of the implementation project and in-depth interviews with 16 principals who participated in the project. The findings reveal a positive set of attitudes towards the new curriculum and the concept of ‘teaching’ it has introduced, both as highly valued ideas and for the increase in status it will bring to preschools. At the same time, the principals recognize that it also introduces challenges for preschool education and professional staff associated with complex webs of interactions between actors, activities, contextual factors and new concepts. Although the principals view the municipality’s support very positively, they raise concerns about its organization and timing. The findings have important implications for future support initiatives of municipalities
Insights into cardiac function by echocardiography in advanced heart failure and heart transplantation
No full textBackground: Heart failure (HF) is defined as a clinical syndrome with typical symptoms and signs determined by congenital or acquired abnormalities of the structure or the function of the heart. Several therapeutic options have improved the quality of life and the outcome of patients with HF in recent years. However, also because an increasing number of individuals survives longer, up to the 10% of HF population reaches the advanced stage of the disease. Advanced HF (AdHF) is characterized by persistent severe symptoms despite optimal HF medical and electrical therapy with very poor functional capacity and episodes of unplanned hospitalizations or visits to reduce congestion or improve cardiac output. AdHF patients periodically undergo invasive right heart catheterization (RHC) to estimate pulmonary pressure and vascular resistance. Heart transplantation (HTX) remains the gold standard treatment for AdHF, allowing patients good mid- and long-term survival rates. Main complications after HTX include rejection, more common within the first year after surgery, and cardiac allograft vasculopathy (CAV) in the long term. Echocardiography is a key first line tool for the routine assessment of cardiac function in AdHF and HTX, to monitor effectiveness of therapies and to stratify prognosis. Second level echocardiography techniques, especially Speckle Tracking-derived Myocardial work, are promising in assessing with more sensibility changes in left ventricular function, especially when associated with biomarkers as natriuretic peptides. Objectives: This thesis is focused on the added role of echocardiography in AdHF and HTX patients and the main aims include: to study the reliability of echocardiography in the estimation of pulmonary arterial pressures (PAP) and the diagnosis of pulmonary hypertension when compared to gold standard method (i.e. RHC, paper I); to estimate prognostic value of myocardial work in AdHF (paper II); to determine normal reference value of myocardial work indices in the transplanted heart compared to general healthy population (paper III); to describe the trend of NT-viproBNP (the most used natriuretic peptide in HF) after HTX, assessing its possible predictors among pre- and post-operative echocardiographic and clinical variables (paper IV). Materials and methods: We retrospectively screened patients with AdHF in regular follow up at our University Hospital. For paper I, we selected all individuals with available RHC data and echocardiographic images recorded on the same day, excluding those with diseases which could represent biases, as chronic obstructive pulmonary disease, and those with poor acoustic window or undetectable tricuspid regurgitation; all patients underwent accurate echocardiographic analysis for the estimation of pulmonary pressures including peak tricuspid regurgitation velocity (TRV) and mean right ventricular–right atrial (RV–RA) pressure gradient. For paper II we included all patients with good acoustic windows and brachial artery cuff systemic blood pressure measured at the same time as the echocardiographic exam, for the calculation of myocardial work indices, excluding those with more than mild heart valve disease or atrial fibrillation. Applying dedicated software, myocardial work indices, including global constructive work (GCW), global work efficiency (GWE); global work index (GWI) and global wasted work (GWW) were calculated in each patient which was then followed up for the development of major events (all-cause mortality, HTX, left ventricular assist devices implantation – primary endpoint – or acute HF hospitalization – secondary endpoint). A population of HTX patients without history of CAV or rejection were screened for paper III and included if the acoustic window was good and brachial artery cuff systemic blood pressure was measured at the same time as the echocardiographic examination. Patients were excluded also in the presence of donor-specific antibodies or atrial fibrillation, more than mild mitral or aortic regurgitation, or abnormal left ventricular function. Myocardial work indices were calculated and compared to general population with similar age and no comorbidities, derived from the European Association of Cardiovascular Imaging (EACVI) NORRE study. Lastly, for paper IV, a wider population of HTX patients with available long term follow up and pre-surgical information were screened and described in terms of NT-proBNP values at 10 different time points including 1 month, 3 months, 6 months and 1 year after theviiHTX. Continuous variables were reported as either mean with standard deviation or median with interquartile range according to normal distribution. Receiver Operating Characteristic (ROC) curves were used to evaluate the ability of echocardiographic parameters to predict outcome (PH for Paper I, adverse events for paper II). Pearson's correlation coefficient was utilized to examine the strength of the association between echocardiographic measures and RHC findings in Paper I or NT-proBNP values in paper IV. Univariate and multivariate Cox proportional hazard regression analyses were applied to assess predictors of outcomes in paper II where Kaplan–Meier analysis estimated event-free survival. Linear regression was applied to test possible association with MW indices and population characteristics in paper III. Results: Paper I: in the 41 patients enrolled, peak TRV was superior in terms of area under the curve by ROC analysis to mean RV–RA gradient in predicting increased mean PAP at RHC, both when using 20 or 25 mmHg as pathological cut off value. In particular, a peak TRV >2.4 m/s had 65% sensitivity and 100% positive predictive value for predicting PH according to the new guidelines’ definition. Paper II: among 138 enrolled individuals, 35 patients developed at least 1 event at follow up. While myocardial work parameters were not associated with primary endpoint occurrence, the hazard ratio for each increase in GWI by 50 mmHg% was 0.90 (p = 0.025) and for each increase in GCW by 50 mmHg% was 0.90 (p = 0.022) when estimating the risk of acute HF hospitalization. Patients with GWI ≥ 369 mmHg% had a better event-free survival at Kaplan–Meier analysis. Paper III: 82 HTx patients, 68.3% male with a median age of 53 (46–62) years were included in a median time lapse for HTX of 5 (2–22) months. No significant differences were described in terms of gender in HTX patients. On the contrary, all the myocardial work indices significantly differed from those reported in the EACVI NORRE study (all P-value <0.001), in particular with lower GWI, GCW, and GWE and higher GWW values in the HTX population.viii Paper IV: in a population of 71 HTX patients, major reduction of NT-proBNP was described at month 3 after surgery, with further reduction at 6 months and 1 year after which it tended to remain stable. Among predictors of NT-proBNP values, at regression analysis, 1-year NT-proBNP values was related to RHC measured pulmonary wedge pressure and ischemic etiology but also to post-HTX kidney function and tricuspid regurgitation severity; long term NT-proBNP values were instead predicted by positive Human Leucocyte Antigen (HLA) antibodies, age at HTX and mitral and tricuspid regurgitation severity. Conclusions: Standard and advanced echocardiography is confirmed to be an essential and non-invasive tool to describe pathological conditions in AdHF, to determine the best follow up timing to avoid major events or HF hospitalizations but also to early diagnose modification of physiological deformation in case of CAV of rejection or to predict an 0increase of NT-proBNP
Estimation of the postoperative fatality window in colorectal cancer surgery
No full textBackground: Postoperative death measured 30 days after surgery is a conventional quality metric, whereas intervals up to 90 days are increasingly used, although data-driven time windows have scarcely been investigated. Methods: The Swedish Colorectal Cancer Registry was used to identify all patients subjected resection for colorectal cancer between 2007 and 2020. All patients were followed up until 180 days after surgery. A join-point statistical hazard model was used to model a declining hazard to a transition point, followed by a stable death rate. This method was subsequently applied to describe postoperative deaths for the entire cohort and subgroups according to tumour location (colon and rectum). Results: Some 56 096 patients electively operated on for colorectal cancer during the study interval were included, with a 30-day and 90-day fatality of 805 (1.43%) and 1458 (2.60%) patients respectively. The derived postoperative fatality window, after which the death rate transitioned to a stable rate, was 23.8 (95% c.i. 21.5 to 28.2) days after surgery. There was no significant difference in the time window between rectal cancer (22.9 days; 95% c.i. 15.1 to 28.4) and colon cancer (27.3 days; 95% c.i. 21.4 to 31.8) patients (P = 0.455). However, postoperative fatality time windows were extended in patients aged at least 80 years and with American Society of Anesthesiologists’ grade III or IV. Conclusion: The traditional postoperative time window of 30 days was confirmed to be an appropriate metric in elective colorectal cancer surgery when evaluated with a hazards-based statistical framework. Importantly, this time window is influenced by older age and advanced co-morbidity, which could prompt increased vigilance for these patient groups
Identifiering och karakterisering av värdfaktorer som bidrar till orthoflavivirus infektion
No full textOrthoflaviviruses are arthropod borne single stranded RNA viruses that cause mild to severe illness in humans, affecting millions of people each year with no antivirals currently available. This viral genus includes viruses such as tick-borne encephalitis virus (TBEV), West Nile virus (WNV) and Zika virus (ZIKV). Orthoflavivirus have their own viral proteins, yet like other viruses they also recruit and utilize several cellular proteins to fulfill their life cycle. While some of these host factors have been identified or characterized, most of them remain unknow. In this thesis, I have used different tools to identify and characterize novel proteins involved in orthoflavivirus infection. Understanding the function of cellular proteins in the viral life cycle is important to comprehend the disease mechanism of the virus and to develop antivirals that target these. In the first part, we implemented proteomic phage display (ProP-PD) to identify short linear motif (SLIM) interaction between viral and cellular proteins, and this method identified Polyadenylate-binding protein 1 (PABP1) as a pro viral factor for many RNA viruses. In the second part of this thesis, we identified proteins involved in TBEV infection by performing an ascorbate peroxidase (APEX) 2-screen to identify proteins found in the vicinity of TBEV NS4B. Using this approach we identified Acyl-CoA Binding Domain Containing 3 (ACBD3). This protein is found in close proximity of TBEV NS4B affecting both viral replication and assembly in TBEV and Langat virus (LGTV) infection, by modifying the trafficking between the endoplasmic reticulum (ER) and Golgi. In the third part of the thesis, we explored the role of the nucleoporins (NUPs) in orthoflavivirus infection. NUPs are the building blocks of the nuclear pore complex, which is the complex responsible for the transport of RNA and proteins between the nucleus and cytoplasm. By implementing a variety of different molecular biology techniques, we identified NUP153 and NUP98 to be of importance in the viral life cycle. We observed that during orthoflavivirus infection, NUP153 and NUP98 are upregulated and recruited from the nucleus to the cytosolic region where they bind viral RNA (vRNA). We found that NUP153 regulates viral translation, while NUP98 is important for viral replication, showing the importance and different functions of this protein family in orthoflavivirus infection. Furthermore, in this thesis we also evaluated the use of peptides to block these specific virus-host protein interactions as potential antivirals. We show that peptides targeting and binding to PABP1 and NUP98 are antivirally active against several orthoflaviviruses. Taken together, the findings presented in this thesis have led to a better understanding of specific host factors required for the viral life cycle. This knowledge can be used in the development of new antivirals
A qualitative study on sex as self-injury among young people
No full text Självskadande beteende ansågs inte alltför länge sedan som ett tämligen sällsynt fenomen. Synen på självskadande beteende är däremot förändrad och idag finns det flera typer av självskadebeteende. Sexuellt självskadebeteende är en typ av självskada, som det sällan pratas om. Syftet med studien är att undersöka när ett sexuellt beteende övergår till att betraktas som självskada enligt socionomer på Ungdomsmottagningen (UMO) och Barn- och ungdomspsykiatrin (BUP). Till grund för studien återfinns tidigare forskning som belyser sexuellt självskadebeteende, dess definition och bakomliggande faktorer som kan ligga till grund för självskadebeteendet. Studien har en teoretisk utgångspunkt i teorin om Stigma, utvecklad av Erving Goffman. För att samla in data har kvalitativa semistrukturerade intervjuer genomförts med fyra socionomer från olika regioner i Sverige. Det insamlade materialet transkriberades och analyserades sedan genom en tematisk analys. Resultatet visar att begreppet sexuellt självskadebeteende saknar en entydig definition då det finns flera sätt att definiera det på. Resultatet visar att ett sexuellt beteende kan anses vara en sexuell självskada när handlingen utförs för att dämpa bakomliggande känslor kopplade till ångest och andra svårigheter. Att ungdomen tänjer på sina gränser och utsätter sig för sexuella risker kan även definieras som självskada. Vidare visar resultatet att bakomliggande faktorer, så som ångest och tidigare trauman, är vanligt hos personer med ett sexuellt självskadebeteende. Resultatet visar även att ungdomar sällan är medvetna om sitt självskadebeteende.
Långdistansgenreglering och 3D-organisation av glioblastomgenomet
No full textAlterations in 3D chromatin organization and epigenetic regulation drivecancer progression. Here I use glioblastoma (GB) as a model to understandthe broad impact of epigenetic changes on tumour biology. By mapping the promoter-enhancer interactome and chromatin states in GB, we uncovered extensive rewiring of chromatin architecture that leads to the activation of gene networks associated with synaptic communication, axonogenesis, axon guidance, and chromatin remodelling. Central to these networks are transcription factors (TFs) such as SMAD3 and PITX1, identified as keyplayers in gene regulatory networks (GRNs) mediating neuron-to-gliomasynaptic communication. Moreover, we showed that tumour growth can be affected by modulating the activity of TFs, such as SMAD3, which mediates neuron-to-glioma synapses. These findings highlight how epigenetic changes and reorganization of 3D genome topology enable GB cells to integrate neural signals and translate them into a proliferative response. Through epigenetic perturbation of novel EGFR (Epidermal Growth Factor Receptor) enhancers, we observed a reduction in GB cell proliferation and invasion, alongside increased sensitivity to the chemotherapeutic agent temozolomide (TMZ). Therefore, targeting specific regulatory regions canalso influence tumour cell behaviour, though to a lower extent than targeting complete GRNs via TF modulation. Additionally, using Multi-Omics Binary Integration via Lasso Ensembles (MOBILE), a Machine Learning (ML)-based tool, we identified novel GRNs impacted by the rewiring of GB’s epigenetic landscape and critical for GB pathogenesis. Among them, GABA signalling emerged as a previously unrecognized driver of GB tumour progression. In summary, this work advances our understanding of how epigenetic regulation and 3D chromatin architecture shape the gene expression landscape of glioblastoma tumours. It paves the way for novel therapeutic strategies targeting chromatin regulators and GRNs to tackle difficult-to-treat cancers, such as glioblastoma.Förändringar i 3D-kromatinorganisation och epigenetisk reglering driver cancerprogression. Här använder vi glioblastom (GB) som en modell för att förstå den bredare effekten av epigenetiska förändringar på tumörbiologi. Genom att kartlägga promotor-enhancerinteraktomet och kromatintillstånd i GB, upptäckte vi omfattande omkoppling av kromatinarkitektur. Detta leder till aktivering av gennätverk associerade med synaptisk kommunikation, axonogenes, axonvägledning och kromatinstrukturering. Centrala i dessa nätverk är transkriptionsfaktorer (TF) som SMAD3 och PITX1, identifierade som nyckelspelare i genreglerande nätverk (GRN) som förmedlar neuron-till-gliom synaptisk kommunikation. Dessa fynd belyser hur neuronal aktivitet främjar gliomcellproliferation via epigenetiskt drivna förändringar i 3D-genomtopologi. Dessutom visade vi att tumörtillväxt kan påverkas genom att modulera aktiviteten hos TF:er, som SMAD3, som förmedlar neuron-till-gliom synaptisk kommunikation. Genom epigenetisk störning av nya EGFR (Epidermal Growth Factor Receptor)-enhancers observerade vi en minskning av GB-cellproliferation och invasion, samt ökad känslighet för det kemoterapeutiska medlet temozolomid (TMZ). Därför kan inriktning på specifika regulatoriska regioner också påverka tumörcellsbeteende, även om det sker i mindre utsträckning än genom att rikta in sig på kompletta GRN via TF-modulering. Dessutom, med hjälp av Multi-Omics binär integration via Lasso Ensembles (MOBILE), ett maskininlärningsbaserat verktyg (ML), identifierade vi nya GRN:er som påverkas av omkopplingen av GB epigenetiska landskap ochsom är kritiska för GB patogenes. Bland dessa framträdde GABA-signaleringsom en tidigare okänd drivkraft för GB-tumörprogression. Sammanfattningsvis främjar detta arbete vår förståelse av hur epigenetisk reglering och 3D-kromatinarkitektur formar genuttryckslandskapet i glioblastomtumörer. Det banar väg för nya terapeutiska strategier som rikta rsig mot kromatinregulatorer och GRNs för att tackla svårbehandlade cancerformer, såsom glioblastom
When the help feels inadequate : Nurses' Experiences of Caring for Patients with Self-Harm – A literature study
No full textBakgrund: Självskadebeteende och psykisk ohälsa är ett växande problem i samhället. Självskadebeteende är ofta kopplat till svårigheter att hantera negativa känslor, traumatiska upplevelser eller en upplevd förlust av kontroll. Sjuksköterskor har en nyckelroll i omhändertagandet av dessa patienter, där det är centralt att skapa trygghet, ge stöd och säkerställa patientens fysiska välbefinnande. Syfte: Syftet med litteraturstudien var att beskriva sjuksköterskors upplevelse av att vårda patienter med självskadebeteende. Metod: Litteraturstudien är baserad på kvalitativa studier. Databassökning genomfördes i Cinahl och Pubmed. För att analysera studierna användes Fribergs femstegsmodell. Resultat: Analysen resulterade i tre kategorier och tio underkategorier. De tre kategorierna var: “Kompetens”, “Arbetsmiljö” och “Bemötande”. Konklusion: Sjuksköterskor upplever ett flertal utmaningar i mötet med personer med självskadebeteende. Brist på tid, resurser, och utbildning är några av dem. Attityderna till patienterna varierar och många upplever en stor frustration i mötet. Ökad utbildning och stöd för sjuksköterskor kan förbättra både vården och arbetsmiljön.Background: Self Harm and mental illness are increasing issues in society. Self-Harm is often caused by difficulties in managing emotions, past trauma, or a perceived loss of control. Nurses play an important role in the care of these patients by focusing on safety, offering support, and ensuring their physical wellbeing. Aim: The aim of this review was to describe registered nurses’ experiences of caring for patients with self-harm. Methods: The literature review is based on qualitative studies. Searches were conducted in databases Cinahl and Pubmed. Friberg’s five-step model was used to analyze the studies. Results: The analysis resulted in three categories which were divided into subcategories. The three main categories were: “Competence”, “Work Environment” and “Approach”. Conclusion: Nurses face multiple challenges while working with patients who self-harm. Lack of time, resources and education are some of them. Attitudes towards these patients vary, and many nurses’ express frustration during these encounters. An increased education and support for nurses has the potential to enhance both patient care and the work environment.
Intratumoural expression of dihydropyrimidine dehydrogenase is an independent prognostic factor in resected pancreatic ductal adenocarcinoma treated with adjuvant gemcitabine
No full textPancreatic ductal adenocarcinoma (PDAC) is associated with a poor prognosis, and biomarkers to guide treatment decisions in PDAC are generally lacking. Intratumoural expression of dihydropyrimidine dehydroge- nase (DPD) is a potential prognostic parameter in patients with PDAC undergoing surgical resection and postoperative chemotherapy. In the present study, DPD was analysed by immunohistochemistry of a tissue microarray platform including a real-world cohort of 495 patients with PDAC who had undergone resection with curative intent at any of three tertiary centres, including Northern, Western and Southeastern regions of Sweden, between 1993 and 2019. DPD level (high/low) was analysed and overall survival associations were assessed in treatment subgroups using a multivariate Cox regression model accounting for potential confounders. In patients who had not received adjuvant chemotherapy (n=182), the median overall survival time was 11.6 months (95% CI 9.6-13.5), compared with 28.8 months (25.0-32.6) among those who had (n=313; log-rank P<0.001). The most common type of chemotherapy was gemcitabine single agent (Gem, n=239) followed by gemcitabine plus capecitabine (GemCape, n=39). Tumour-Node-Metastasis (TNM) stage and DPD expression were statistically significant prognostic parameters in the Gem group (HR 1.19, 95% CI 1.01-1.41, P=0.036), with high expres- sion of DPD linked with worse survival. In addition, tumour grade and TNM stage were statistically significant prognostic factors in the group that did not receive any chemotherapy (P≤0.001). No statistically significant parameters were iden- tified in the GemCape group. Taken together, intratumoural expression of DPD may be considered a prognostic marker for patients with PDAC treated with adjuvant gemcitabine following surgical resection, with low expression levels predicting better survival. Further studies in larger cohorts of patients receiving multi-drug or non-gemcitabine based regimens are warranted
Reason and emotion in engineering ethics education
No full textThis chapter discusses the relationship between reason and emotion in engineering ethics education (EEE), focusing on psychological and sociological perspectives. It identifies some factors that have led to emotions not being adequately considered alongside reasoning in the research on, or practice of, engineering ethics education. The chapter argues that reason and emotion are essential to consider at multiple levels of social analysis, including the individual, interpersonal, and societal. To aid researchers and ethics teachers in better reflecting emotion alongside reason in EEE and better conceptualizing these connections, the chapter draws upon several integrating concepts. Ultimately, it suggests that EEE must engage more with sociology – and with moral and social psychology – to better incorporate emotions into research and practice
'Constructing the test to the teaching' – and the complexities of assessing learning in ethics education
No full textThis study draws on a research project where a model of fiction- based ethics education was developed and put into practice during a school year in five classes in compulsory school, two in grade 5 and three in grade 8. A test was constructed with the purpose of evaluating a multi-dimensional ethical competence. The test was given at the beginning and the end of the school year to the students in the five classes, but also to students in five other classes who received the ordinary form of ethics education. The test was constructed by using tasks from earlier Swedish national tests on ethics education, but in this study new assessment instructions were developed. According to this test, almost no significant differences were found between the classes with fiction-based ethics education and the other classes. However, this contrasts with the fruitfulness of the fiction-based model, as identified through other forms of evaluation. The findings raise questions about whether and how ethics education can be meaningfully tested, which in this article is self-critically reflected on. A concluding discussion on target competence, teaching intervention and ways of evaluation – in relation to each other – ends the article.“Refining the Ethical Eye and Ethical Voice – The Possibilities and Challenges of a Fiction-based Approach to Ethics Educatio