Focus on Users – The National Digital Library of Finland

Heli Kautosen esitys Digital Humanities 2012 -konferenssissa Hampurissa 20.7.2012

Leukocyte trafficking: a special focus on VAP-1 and CLEVER-1

It is crucial that lymphocytes patrol the body against foreign intruders and that leukocytes invade inflamed tissues to ameliorate the infection or injury. The adhesion molecules in leukocytes and endothelial cells play an essential role in the immune response by directing the traffic of leukocytes. However, the same molecules that guide leukocyte traffic under physiological conditions are also involved in pathological situations, when an overly excessive or harmful inflammatory response leads to tissue destruction and organ dysfunction or tumor growth. Vascular adhesion protein-1 (VAP-1) and Common lymphatic endothelial and vascular endothelial receptor-1 (CLEVER-1) are endothelial molecules that participate in the adhesion of leukocytes to the endothelia. This study was designed to elucidate, using different inflammation models, the role of VAP-1 and CLEVER-1 in leukocyte migration to the inflamed tissue, and to evaluate the use of antibodies against these molecules as an anti-adhesive therapy. Also, the role of CLEVER-1 during tumorigenesis was studied. Blocking the function of VAP-1 with antibodies significantly decreased the accumulation of leukocytes in the inflamed tissue. Targeting CLEVER-1 prevented cell migration via lymphatic vessels, as well as leukocyte traffic during inflammation. Following the anti-CLEVER-1 antibody treatment the number of immune regulating leukocytes in tumors was reduced, which led to a decrease in tumor growth. However, the normal immune response towards immunization or bacterial infection was not compromised. Thus, VAP-1 and CLEVER-1 are both potential targets for antiinflammatory therapies for preventing the harmful accumulation of leukocytes in inflamed areas. Targeting CLEVER-1 may also inhibit tumor growth by reducing immunosuppressive leukocytes in tumors

Containment Measures in Adolescent Psychiatric Care - Focus on Mechanical Restrain

Rajoitetoimet, erityisesti sitominen, nuorisopsykiatrisessa hoitotyössä Tutkimuksen tavoitteena oli kuvata ja syventää tietoa rajoitetoimien, erityisesti sitomisen, käytöstä nuorisopsykiatrisessa vastentahtoisessa osastohoidossa. Tutkimuksen tavoitteena oli kuvata hoitajien, lääkäreiden ja potilaiden asenteita eri rajoittamiskeinoja kohtaan nuorisopsykiatrisessa osastohoidossa, kerätä tietoa yhden vuoden aikana tapahtuneiden sitomisten määrästä ja luonteesta sekä kuvata potilaiden kokemuksia sitomisesta nuorisopsykiatrisen osastohoidon aikana. Tutkimus tuottaa arvokasta tietoa korkeatasoisten sitomiskäytäntöjen kehittämiseen nuorisopsykiatrisessa osastohoidossa, sekä sitomisten määrää vähentämällä että sitomistapoja kehittämällä. Tavoitteena on parantaa sidottujen potilaiden kliinistä hoitoa. Tutkimusaineisto kerättiin suomalaisilla, pääkaupunkiseudulle sijoittuvilla, nuorisopsykiatrisilla osastoilla neljässä vaiheessa lokakuun 2009 ja huhtikuun 2012 välisenä aikana. Helsingin ja Uudenmaan sairaanhoitopiirin (HUS) nuorisopsykiatrian erikoisalan seitsemän suljetun osaston hoitohenkilökunta sekä lääkärit suhtautuivat myönteisesti rajoittamistoimenpiteisiin. Nuorisopsykiatriset potilaat suhtautuivat rajoittamistoimenpiteisiin kriittisemmin kuin henkilökunta. Nuoret suhtautuivat myönteisimmin tarvittaessa annettavaan lääkitykseen, ajoittaiseen tarkkailuun ja kulun rajoittamiseen. Vähiten hyväksytty menetelmä oli verkkosänky. Nuoret arvioivat sitomisen kolmen vähiten hyväksytyn menetelmän joukkoon. Sitomisen esiintyvyys ja pitkien sitomisten määrä olivat korkeita tutkimukseen valituissa yksiköissä. Useimmat sidotut nuoret tiesivät syyn sitomiseensa, suhtautuivat siihen ambivalentisti nähden siinä sekä hyötyä että haittaa, pitäen sitä kuitenkin rangaistuksena. Huolimatta tästä, suurin osa haastatelluista nuorista koki, että joissain tilanteissa sitomista tarvitaan nuorisopsykiatrisessa osastohoidossa. Nuorilla oli monia ehdotuksia, kuinka parantaa sitomista käytännön osastohoidossa. Tämä väitöskirja tuottaa uutta tietoa eri rajoittamistoimenpiteiden ja sitomisen toteuttamisesta nuorisopsykiatrisessa osastohoidossa. Käytännön hoitotyön parantamiseksi nuorisopsykiatrisilla osastoilla tarvitaan laaja-alaista ja syvälle luotaavaa koulutusta, jotta rajoittamis-toimenpiteiden määrää voidaan vähentää. Myös kriisitilanteiden hallintaan tarvitaan uusia keinoja. Tietoa, kuvausta toimenpiteistä ja tilanteiden käsittelyä jälkikäteen tulee tarjota ala-ikäiselle potilaalle hänen kehitystasonsa huomioiden. Sitomisten määrää tulee vähentää ja niiden kestoa lyhentää. Nuorten tulee olla aktiivisesti mukana kehittämässä aggression hallintamenetelmiä suomalaisessa nuorisopsykiatrisessa osastohoidossa.

Perspectives on narrative discourse markers : focus on Old English þa

Ett element som har intresserat forskarna av fornengelska sedan början av filologiska studier är adverbet þa ’då’, som är högfrekvent i många berättande texter. Utöver ordföjldsregeln enligt vilken satsinitialt þa följs av omvänd ordföljd, finns det redan tidigt kommentarer om användningen av þa för emfas, livlighet och konnektivitet. Även om sådana karakteriseringar tar den textuella kontexten i beaktande, är deras fokus inte på diskursfunktioner utan på satsgrammatik. Denna avhandling betraktar användningen av þa från diskursstrukturens perspektiv och undersöker dess funktioner i markeringen av berättelsens huvudlinje (eng. grounding), kohesiva kontinuiter (eng. continuities), samt vändpunkter och spänning (eng. peak, tension) i texten. I stället för att fokusera på bara en funktion som har associerats med þa, undersöks denna frekventa element från olika perspektiv. Genom både kvantitativa och kvalitativa analyser av narrativt material, visar de inkluderade delstudierna att detta ord spelar en viktig roll i struktureringen av fornengelska berättelser. Parallellt med kärnfunktionen att markera berättelsens huvudlinje, används þa i samspel med andra strukturerande element för att uttrycka den hierarkiska strukturen och spänning i berättelsen. Jämförelser med andra uttryck av temporal kontinuitet visar att þa skiljer sig från dem i sina användningsmönster, vilket vidare bekräftar dess status som en narrativ diskursmarkör.

Software development methods and quality assurance: Special focus on South Korea

The purpose of this study was to explore software development methods and quality assurance practices used by South Korean software industry. Empirical data was collected by conducting a survey that focused on three main parts: software life cycle models and methods, software quality assurance including quality standards, the strengths and weaknesses of South Korean software industry. The results of the completed survey showed that the use of agile methods is slightly surpassing the use of traditional software development methods. The survey also revealed an interesting result that almost half of the South Korean companies do not use any software quality assurance plan in their projects. For the state of South Korean software industry large number of the respondents thought that despite of the weakness, the status of software development in South Korea will improve in the future.

Focus on the user: perception, expectations and needs

Esitys KDK-käytettävyystyöryhmän järjestämässä seminaarissa: Miten käyttäjien toiveet haastavat metatietokäytäntöjämme? / How users' expectations challenge our metadata practices? 30.9.2014.

Analysis of trophic responses in lesioned brain: focus on basic fibroblast growth factor mechanisms

The actions of fibroblast growth factors (FGFs), particularly the basic form (bFGF), have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair

Wood biochemicals for the protection of health. Focus on hemicellulose, stilbenoids and lignans

Trees produce an enormous amount of compounds that are still scantly utilized.However, the results obtained from structurally similar biochemicals suggest that wood-derived compounds could be used for the protection of health in various applications. Polyphenols, for instance, could be extracted from wood in high quantities. Similar polyphenols to those in wood include resveratrol, found in grapes, and secoisolariciresinol, present in flaxseeds. Their consumption has been inversely associated with the incidence of various diseases, especially certain cancers and obesity-related disorders. The aim of this study was to determine the health-promoting effects of woodderived biochemicals. The effect of spruce hemicellulose on the growth of probiotic intestinal bacteria was studied. The results suggest that the bifidobacteria and lactobacilli can utilize hemicellulose and thus it has potential as a prebiotic compound. In particular, the efficacy of pine polyphenols to inhibit the growth of prostate cancer was our main interest. It was found that stilbenoids and lignans inhibited the proliferation of various cancer cells, and reduced the growth of prostate cancer xenografts in mice. The polyphenol rich pine knot extract was well tolerated in diet and extract-derived polyphenols were rapidly absorbed after intake. Furthermore, we determined the effect of the dietary pine knot extract on the weight gain and the expression of aromatase gene in reporter mouse expressing the promoter region of a human aromatase gene. It was found that dietary pine knot extract alleviated the obesity-induced inflammation in adipose tissue and downregulated the expression of a human aromatase gene. Taken together, several components of spruce and pine may have a future role as health-promoting compounds.

Intensive chemotherapy as salvage treatment for solid tumors: focus on germ cell cancer

Germ cell tumors present contrasting biological and molecular features compared to many solid tumors, which may partially explain their unusual sensitivity to chemotherapy. Reduced DNA repair capacity and enhanced induction of apoptosis appear to be key factors in the sensitivity of germ cell tumors to cisplatin. Despite substantial cure rates, some patients relapse and subsequently die of their disease. Intensive doses of chemotherapy are used to counter mechanisms of drug resistance. So far, high-dose chemotherapy with hematopoietic stem cell support for solid tumors is used only in the setting of testicular germ cell tumors. In that indication, high-dose chemotherapy is given as the first or late salvage treatment for patients with either relapsed or progressive tumors after initial conventional salvage chemotherapy. High-dose chemotherapy is usually given as two or three sequential cycles using carboplatin and etoposide with or without ifosfamide. The administration of intensive therapy carries significant side effects and can only be efficiently and safely conducted in specialized referral centers to assure optimum patient care outcomes. In breast and ovarian cancer, most studies have demonstrated improvement in progression-free survival (PFS), but overall survival remained unchanged. Therefore, most of these approaches have been dropped. In germ cell tumors, clinical trials are currently investigating novel therapeutic combinations and active treatments. In particular, the integration of targeted therapies constitutes an important area of research for patients with a poor prognosis.

Averting the legacy of kidney disease - focus on childhood

World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood.

Players of Th-cell differentiation and immune dysregulation – focus on GIMAP family genes

The balance of T helper (Th) cell differentiation is the fundamental process that ensures that the immune system functions correctly and effectively. The differentiation is a fine tuned event, the outcome of which is driven by activation of the T-cell in response to recognition of the specific antigen presented. The co-stimulatory signals from the surrounding cytokine milieu help to determine the outcome. An impairment in the differentiation processes may lead to an imbalance in immune responses and lead to immune-mediated pathologies. An over-representation of Th1 type cytokine producing cells leads to tissue-specific inflammation and autoimmunity, and excessive Th2 response is causative for atopy, asthma and allergy. The major factors of Th-cell differentiation and in the related disease mechanisms have been extensively studied, but the fine tuning of these processes by the other factors cannot be discarded. In the work presented in this thesis, the association of T-cell receptor costimulatory molecules CTLA4 and ICOS with autoimmune diabetes were studied. The underlying aspect of the study was to explore the polymorphism in these genes with the different disease rates observed in two geographically close populations. The main focus of this thesis was set on a GTPase of the immunity associated protein (GIMAP) family of small GTPases. GIMAP genes and proteins are differentially regulated during human Th-cell differentiation and have been linked to immune-mediated disorders. GIMAP4 is believed to contribute to the immunological balance via its role in T-cell survival. To elucidate the function of GIMAP4 and GIMAP5 and their role in human immunity, a study combining genetic association in different immunological diseases and complementing functional analyses was conducted. The study revealed interesting connections with the high susceptibility risk genes. In addition, the role of GIMAP4 during Th1-cell differentiation was investigated. A novel function of GIMAP4 in relation to cytokine secretion was discovered. Further assessment of GIMAP4 and GIMAP5 effect for the transcriptomic profile of differentiating Th1-cells revealed new insights for GIMAP4 and GIMAP5 function.