Bubble Universe Dynamics After Free Passage

We consider bubble collisions in single scalar field theories with multiple vacua. Recent work has argued that at sufficiently high impact velocities, collisions between such bubble vacua are governed by 'free passage' dynamics in which field interactions can be ignored during the collision, providing a systematic process for populating local minima without quantum nucleation. We focus on the time period that follows the bubble collision and provide evidence that, for certain potentials, interactions can drive significant deviations from the free-passage bubble profile, thwarting the production of bubbles with different field values.Comment: 21pages, 8 figures, Revised version modified to include Acknowledgements sectio

Pullosällien verkkokaupan tarina : kuinka se rakentui ja minkälaisia valintoja eri vaihtoehtojen välillä on matkan varrella tehty?

Tämä opinnäytetyö on toteutettu toiminnallisessa muodossa. Oppimisympäristönä opiskelujen aikana on toiminut Salon BisnesAkatemia, joka on oppimisympäristönä tavanomaisesta poikkeava. Siellä rohkaistaan opiskelijoita yrittämään ja siitä myös opinnäytetyöni kertoo. Opinnäytetyöni käsittelee Pullosällit-nimistä brändiä, ja tarkemmin ottaen Pullosällien verkkokauppaa ja sitä, minkälaisia valintoja matkalla on tullut tehtyä ja kuinka niihin on päädytty. Pullosällit on kolmen opiskelijakaveruksen projekti, jonka tavoiteena on antaa käytetyille lasipulloille uusi elämä. Kaikki toimintamme on pyritty tekemään mahdollisimman ammattimaisesti, sillä haluamme olla jonain päivänä tulevaisuudessa menestyviä yrittäjiä. Matka kohti valmistumista on ollut palkitseva ja ikimuistoinen.In this final project of my studies I'll present a concept, how anyone can create a workable e-commerce with a little knowledge and expenses. I am telling you about our project called Pullosällit which is new recycling brand made by few business students whose aim is to be entrepreneurs someday in the future. Our ambition was to create a practical e-commerce where we could sell our self-made products. None of us had experience of this kind of work before. I’m also explaining why we made the decisions that we made and which meaning these decisions had on our journey. We have tried to do all our actions as well as possible for we want to be professionals in the future. It is important to know how trade in the world of internet. We all have learned a lot about entrepreneurship during this journey and this has been a important final step towards our graduations from BisnesAkatemia

Validering och implementering av EliA Calprotectin 2 för mätning av fekalt kalprotektin med immunanalysatorn Phadia 250

Abstrakt Kalprotektin är ett protein som förekommer rikligt i neutrofila granulocyter, som utsöndrar kalprotektin i tarmlumen vid inflammatoriska tarmsjukdomar (IBD, inflammatory bowel disease). Den ökade kalprotektinutsöndringen innebär högre kalprotektinhalt i avföringen och tyder på tarminflammation. Fekal kalprotektinundersökning (F-Calpro) kan användas för särskiljning mellan IBD och funktionell tarmsjukdom (IBS, irritable bowel syndrome), vid uppföljningen och behandlingen av IBD samt att förutspå aktivare sjukdomsperioder hos IBD-patienter. Examensarbetets syfte var att validera och implementera kalprotektinanalysmetoden EliA Calprotectin 2 med immunanalysatorn Phadia 250. Metoden som användes med Phadia 250 för att mäta kalprotektinhalten benämns EliA och är en fluorescens-enzymimmunometod (FEIA). De uppmätta kalprotektinhalterna som erhölls med EliA Calprotectin och EliA Calprotectin 2 jämfördes. EliA Calprotectin 2 hade uppdaterade reagens jämfört med EliA Calprotectin, men båda analyserna utfördes med samma EliA-metod. För examensarbetet samlades 67 avföringsprover. Avföringsproverna späddes med reagens från EliA Calprotectin och EliA Calprotectin 2, varefter kalprotektinhalten i de två olika spädningarna analyserades med Phadia 250. EliA Calprotectin 2 har enligt tillverkaren en bättre känslighet än EliA Calprotectin, vilket kan antydas från detta examensarbete. EliA Calprotectin och EliA Calprotectin 2 jämfördes och en högre kalprotektinhalt uppmättes oftare med EliA Calprotectin 2. EliA Calprotectin 2 bedömdes pålitlig att ersätta EliA Calprotectin. En skillnad fanns i de uppmätta kalprotektinhalterna, som troligen berodde på den bättre känsligheten hos EliA Calprotectin 2. Implementeringen av EliA Calprotectin 2 för Phadia 250 genomfördes efter valideringen.Tiivistelmä Neutrofiilisissä granulosyyteissä on runsaasti proteiinia, varsinkin kalprotektiinia. Neutrofiilit vapauttavat kalprotektiinia suoliston luumeniin tulehduksellisissa suolistosairauksissa (IBD, inflammatory bowel disease). Lisääntynyt kalprotektiinieritys tarkoittaa korkeampaa kalprotektiinipitoisuutta ulosteessa ja viittaa mahdolliseen suolistotulehdukseen. Ulosteen kalprotektiinitutkimusta (F-Calpro) voidaan käyttää IBD:n ja ärtyvän suoliston oireyhtymän (IBS, irritable bowel syndrome) erotusdiagnostiikassa, IBD-potilaiden seurannassa ja hoidossa, sekä IBD-potilaiden aktiivisen sairausvaiheen ennustamisessa. Opinnäytetyön tarkoitus oli validoida ja ottaa käyttöön kalprotektiinianalyysimenetelmä, EliA Calprotectin 2, Phadia 250 -immunoanalysaattorilla. Kalprotektiinipitoisuuden määritykseen Phadia 250 -immunoanalysaattorilla käytettyä fluoroentsyymi-immunomenetelmää (FEIA) kutsutaan EliA-mentelmäksi. EliA Calprotectin 2 -analyysipaketin reagenssit on uudistettu. Opinnäytetyössä verrattiin EliA-menetelmällä mitattuja kalprotektiinipitoisuuksia alkuperäisillä (EliA Calprotectin) ja uudistetuilla (EliA Calprotectin 2) reagensseilla. Opinnäytetyössä kerättiin 67 ulostenäytettä. Ulostenäytteet laimennettiin alkuperäisillä (EliA Calprotectin) ja uudistetuilla (EliA Calprotectin 2) reagensseilla, minkä jälkeen kalprotektiinipitoisuus analysoitiin molemmista laimennuksista Phadia 250 -immunoanalysaattorilla. EliA Calprotectin 2 -analyysilla on valmistajan mukaan aiempaa parempi herkkyys, mikä myös ilmenee tässä opinnäytetyössä. Vertailussa EliA Calprotectin 2 antoi useammin korkeampia kalprotektiinipitoisuuksia kuin EliA Calprotectin. EliA Calprotectin 2 hyväksyttiin luotettavana EliA Calprotectin -analyysin korvaajana. Mitatuissa kalprotektiinipitoisuuksissa oli ero, joka luultavasti riippui EliA Calprotectin 2 -analyysin paremmasta herkkyydestä. EliA Calprotectin 2 -analyysin käyttöönotto Phadia 250 -immunoanalysaattorilla toteutettiin validoinnin jälkeen.Abstract Calprotectin is an abundant protein in neutrophilic granulocytes and is released from neutrophilic granulocytes into the intestinal lumen during inflammatory bowel disease (IBD). The increased release of calprotectin causes a higher calprotectin level in faeces and is an indication of intestinal inflammation. Faecal calprotectin analysis (F-Calpro) can be used to differentiate between IBD and irritable bowel syndrome (IBS), to monitor and treat IBD patients and to predict a more active disease period in IBD patients. The aim of this thesis was to validate and implement the EliA Calprotectin 2 assay for measurement of calprotectin levels with the Phadia 250 immunoanalyser. The method used with Phadia 250 to measure the calprotectin level is called EliA and is a fluorescence enzyme immunoassay (FEIA). The measured calprotectin levels with EliA Calprotectin and EliA Calprotectin 2 were compared. EliA Calprotectin 2 had updated reagents compared to EliA Calprotectin, however, both assays used the same EliA method. For the thesis 67 faecal samples were collected. The faecal samples were diluted with reagents from EliA Calprotectin and EliA Calprotectin 2, and the calprotectin level was analysed from the two different dilutions with the Phadia 250 immunoanalyser. EliA Calprotectin 2 has a higher sensitivity than EliA Calprotectin according to the manufacturer, which can be indicated from this thesis. EliA Calprotectin and EliA Calprotectin 2 were compared, and a higher calprotectin level was more often measured with EliA Calprotectin 2. EliA Calprotectin 2 was approved as reliable to replace EliA Calprotectin. There was a difference between the measured calprotectin levels, which probably was due to the higher sensitivity of EliA Calprotectin 2. The implementation of EliA Calprotectin 2 for Phadia 250 was done after the validation

The role of the deubiquitinating enzyme CYLD and its substrate BCL-3 in solid tumors

The tumor suppressor CYLD and the proto-oncogene BCL-3 are known to be deregulated in various cancer types. The molecular background of how these genes participate in carcinogenesis is not fully understood. CYLD is a deubiquitinating enzyme known to specifically target lysine 63 linked ubiquitin chains, which can negatively regulate the BCL-3, NF-κB and JNK signaling pathways, leading to a decrease of cell survival or proliferation. BCL-3 is an alternative IκB family member that is needed for activation (or repression) of target genes by homodimeric p50 and p52. The aim of this thesis was to further investigate the molecular mechanisms behind CYLD and BCL-3 regulation and how they might contribute to carcinogenesis. In particular, the role of BCL-3 in prostate cancer (PCa), and the role of CYLD in hepatocellular carcinoma (HCC) were studied. In PCa we found up-regulation of BCL-3 in human prostate cancers with abundant infiltration of inflammatory cells. Using PCa cell lines we found that interleukin-6 (IL-6) could activate STAT3 mediated up-regulation of BCL-3, which in turn could elevate Id-1 and Id-2 expression. Knockdown of BCL-3 increased the sensitivity for anticancer drug-induced apoptosis. PCa cells with reduced BCL-3 levels that were subcutaneously injected into NUDE mice formed smaller tumors due to a higher percentage of apoptotic cells. In other tissues Bcl-3 has been shown to regulate proliferation through expression of its target gene CYCLIN D1, a process that is negatively regulated by CYLD. We found that CYLD knockout MEF cells have significantly increased proliferation rates and increased levels of CYCLIND1 in a serum dependent manner when compared with wild type MEF cells. The reduced proliferation in wild type cells was mediated through up-regulation of CYLD by transcription factor serum response factor (SRF) in a p38 mitogen-activated protein kinase (p38MAPK) dependent manner. Knockdown of SRF by siRNA or inhibition of p38MAPK reduced the expression of CYLD and increased cell proliferation rate. These results suggest that SRF is a positive regulator of CYLD expression, which in turn reduces the mitogenic activation of wild type MEF cells. For further investigation of the molecular mechanisms of CYLD in cancer we performed a tissue microarray, comparing benign liver tissue with HCC. We found that CYLD is significantly down-regulated in human (HCC) and that CYLD expression was inversely correlated with the expression of proliferation marker Ki67. In vivo experiments showed that CYLD deficient mice were more susceptible to the chemical carcinogen DEN-induced HCC. Furthermore, HCC isolated from CYLD knockout mice had elevated cell proliferation compared to wild type mice. This effect was mediated via TRAF-2 ubiquitination, JNK activation and c-MYC expression. In correlation to this result, transient transfection of CYLD into a HCC cell line restricted cell proliferation and reduced the activation of JNK. Together these results suggest that CYLD down-regulation is a risk factor for development and progression of HCC mediated through activation of JNK

Hoitajien kokemuksia perehdyttämisestä

Hoitajien kokemuksia saamastaan perehdytyksestä on tutkittu Suomessa melko vähän. Kyse on kuitenkin koko työyhteisöä koskettavasta ilmiöstä, jonka tärkeys korostuu henkilöstön suuren vaihtuvuuden ja eläköitymisen vuoksi. Tämän opinnäytetyön tarkoituksena oli kartoittaa hoitohenkilökunnan kokemuksia perehdyttämisestä erään eteläsuomalaisen kunnan sairaalassa ja perusterveydenhuollon yksikössä. Tutkimuksen tavoitteena oli tuottaa tietoa, jota voidaan käyttää perehdytyksen kehittämiseen. Tutkimusmenetelmä oli kvalitatiivinen ja aineistonkeruumenetelmänä käytettiin nauhoitettua teemahaastattelua. Tutkimukseen osallistui yhteensä kymmenen perus-, lähi-, sairaan- ja terveydenhoitajaa. Tutkimusaineisto analysoitiin induktiivisella sisällönanalyysillä ja sen tuloksena syntyi kuvaus hoitajien kokemuksista saadusta perehdytyksestä. Tutkimuksen päätuloksena on, että perehdytys koetaan puutteelliseksi. Tutkittavat kokevat perehdytyksen olevan pääosin riittämätöntä sekä sen suunnitteluvaiheessa että sen varsinaisessa toteuttamisessa. Tutkimustulosten lisäksi opinnäytetyössä tuodaan esille haastateltavien omia kehittämisehdotuksia perehdytyksen kehittämiseksi. Tämän opinnäytetyön tuloksia voidaan hyödyntää perehdytystyön arvioinnissa ja kehittämisessä. Tulosten pohjalta jatkossa voisi tutkia perehdytyksen vaikutusta työsuhteiden pituuksiin, esimiesten ja lähiesimiesten kokemuksia perehdytyksestä ja sitä, miten perehdyttäjät itse kokevat antamansa perehdytyksen.In Finland, relatively little research has been conducted on the experiences of nurses regarding work orientation. However, work orientation has an impact on the entire work community. High employee turnover and retirement rates in health care make it all the more important. The purpose of this study was to describe the experiences of nurses regarding the work orientation they had received while working in a southern Finland hospital and a unit of primary health care. The aim of the study was to produce information and knowledge for further assessment and improvement of work orientation. The research method was qualitative and the data was collected by using voice recorded theme interviews. Ten nurses participated in the study. The data was analyzed by inductive content analysis and resulted in a description of how the nurses experience the received work orientation. The main result of this study showed that the received work orientation was mainly experienced as inadequate. Work orientation was found lacking in both the planning and implementation phases. In addition to the study results, the participants’ own development proposals are being brought out in this thesis. The results of this study can be utilized in evaluation and improvement of work orientation. Further ideas for studying include assessing the connection between work orientation and the length of employment, studying how the superiors and immediate superiors experience the work orientation and how the mentors themselves experience the orientation they give

Methodological challenges in pregnancy pharmacoepidemiology : the case of antiseizure medication and offspring neurodevelopment

This thesis is driven by the overarching aim of elucidating methodological challenges inherent in pharmacoepidemiology during pregnancy, with a particular focus on antiseizure medications. In Study I, a substantial surge in antiseizure medication use in the United Kingdom is observed, notably linked to increases in psychiatric indications. This shift in the medication landscape raises questions about the predominant contributors to this rise and underscores the necessity of understanding evolving patterns in drug utilization during pregnancy. In Study II, a large-scale examination of associations between specific antiseizure medications and neurodevelopmental conditions across Sweden and the United Kingdom emphasizes the importance of considering drug classes and shared confounders, providing valuable insights into the possible causal effect of these drugs. Study III explores the intricate interplay between epilepsy and psychiatric conditions, unveiling a heightened risk of neurodevelopmental conditions in individuals diagnosed with epilepsy. These findings shed light on the complex within-individual links between these conditions, potentially explaining the observed higher likelihood of neurodevelopmental diagnoses in children of women using antiseizure medications in pregnancy. In Study IV, a critical evaluation of drug safety studies warns against indication-based sampling, advocating for comprehensive regression adjustments to mitigate biases. Finally, Study V introduces the marginalized between-within model, a novel approach to derive absolute measures of occurrence in sibling analysis, enhancing the interpretability of findings. This thesis, collectively, calls for a concerted effort to improve the methodology of pharmacoepidemiology during pregnancy, fostering a more nuanced understanding of medication risks, and ultimately enhancing maternal and fetal health outcomes