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Álagseinkenni í handknattleik karla á Íslandi: Leit að áhættuþáttum álagseinkenna í hnjám, mjóbaki og öxlum
No full textThe aims of this project were: 1) to provide data regarding the physical abilities of Icelandic male handball players, by using 9+ screening test. 2) to register prevalence of overuse problems in the knee, low-back and dominant shoulder and to investigate if 9+ screening test score could predict for overuse problems. 3) to record the players training load during pre-season, to register prevalence of overuse problems in the knee, low back and dominant shoulder and assess the possible association between the training volume and overuse problems.
Several physical factors from players from 13 handball teams were tested using a 9+ screening test with players earning score according to their performance. The players answered the Oslo Sport Trauma Research Centre (OSTRC) overuse questionnaire regarding overuse problems in the knee, low-back and shoulder during one competitive season. During a 6-week pre-season, players from 10 teams answered the OSTRC overuse questionnaire weekly. The coaches recorded their teams training volume and training types.
The main results were that age-related differences were observed. Junior players displayed lower scores than senior players in tests measuring abdominal strength and stability, but higher in tests measuring trunk and shoulder mobility. About 30% of the players reported overuse problems (OP) in the knee, low-back or shoulder at any given time during the research period. Ten percent reported substantial overuse problems (SOP), affecting their performance and/or participation. No association was found between overuse problems and the 9+ screening test score. The prevalence of OP and SOP was higher in the shoulder in the pre-season compared to the competitive season, but lower in SOP in the low-back. The knees were most susceptible for OP during the pre-season, with running exercises and shooting practice as the main risk factors. Jumping was associated with OP in the low-back.Markmið verkefnisins var: 1) Að afla gagna um líkamlegt atgervi íslenskra handknattleiksmanna með 9+ skimunarprófi. 2) Að skrá algengi og alvarleika álagseinkenna í hnjám, mjóbaki og ríkjandi öxl og kanna hvort skor úr 9+ skimunarprófi hefði forspárgildi fyrir álagseinkenni. 3) Að skrásetja æfingaálag leikmanna, ásamt algengi og alvarleika álagseinkenna í hnjám, mjóbaki og ríkjandi öxl á undirbúningstímabili og kanna hvort samband sé þar á milli.
Nokkrir þættir líkamlegrar getu leikmanna frá 13 íslenskum handknattleiksliðum voru prófaðir með 9+ skimunarprófi að og hlutu leikmenn einkunn miðað við frammistöðu. Leikmenn svöruðu Oslo Sport Trauma Research Centre (OSTRC) álagseinkenna spurningalista um breytingar á þátttöku, æfingamagni, frammistöðu og verkjum tengt álagseinkennum yfir heilt keppnistímabil. Á sex vikna undirbúningstímabili svöruðu leikmenn frá 10 íslenskum liðum OSTRC spurningalistanum vikulega ásamt því sem þjálfarar liðanna skráðu æfingaálag og tegundir æfinga.
Helstu niðurstöður voru þær að ungir leikmenn hlutu lægri einkunn en þeir eldri í prófunum er mældu stöðugleika og styrk í bol, en hærri einkunn í prófum sem mældu liðleika í öxlum og bol. Um 30% leikmanna voru með óþægindi (OP) í hnjám, mjóbaki eða öxlum á hverjum tíma og um 10% leikmanna voru með umtalsverð óþægindi (SOP), sem höfðu áhrif á iðkun og frammistöðu. Algengi álagseinkenna í móbaki var hærra en í sambærilegum rannsóknum. Engin tengsl fundust á milli einkunnar á 9+ skimunarprófinu og álagstengdra einkenna. Algengi álagseinkenna var hærra í öxlum á undirbúningstímabili en á keppnistímabili, en lægra í SOP í mjóbaki. Hné voru mest útsett fyrir álagseinkennum og voru hlaup og skotæfingar líklegustu orsakavaldarnir. Hopp orsökuðu OP frá mjóbaki
Young learner’s lexical proficiency and motivation to learn English in Iceland
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Globalization and technological development contribute to an increased demand for English skills in daily recreational activity in Iceland. This phenomenon, and a steadily growing exposure, has changed the status of English in Iceland from being a foreign language towards being closer to a second language (Birna Arnbjörnsdóttir 2007). This study aims to explore 4th-grade students’ attitudes towards English and examine which contributing factors affect their motivation for learning English, specifically learning English vocabulary. Four research questions explore the relationships between context-specific variables and whether gender or onset of instruction affects context-oriented English use or vocabulary size. The study used a quantitative method approach. First, a survey was administered based, on the one hand, on Dörnyei’s “L2 Motivational Self-System” (2005) and, on the other hand, seven context-specific factors. These are TV/Music, Computers, Education, Peers, Family, Texts and Lingua Franca. Secondly, two vocabulary tests were administered to determine students’ lexical knowledge at the onset of formal English instruction; a Yes-No test and a VKS test measured students’ vocabulary size and dimension of knowledge. Participants were 378 primary school students in the 4th-grade (190 girls and 188 boys). The quantitative methods of analysis of the survey responses and vocabulary tests include descriptive statistics, factor analysis, and stepwise multiple regression analysis to examine the relationship between motivating factors, English context-based exposure, and vocabulary test results.
The study's findings are that the participants’ vocabulary knowledge is acquired largely extramurally and is motivated by a need to use English during leisure time in their daily lives. Additionally, the results indicate that the children in this study visualize how and where they need to use English in the future.Ágrip
Hnattvæðing og tækniþróun í samskiptum kalla á aukna enskukunnáttu í daglegu lífi á Íslandi. Ljóst er að enskuáreiti í daglegu lífi Íslendinga er mikið. Því hefur staða ensku á Íslandi breyst úr því að vera erlent tungumál, sem var aðallega kennt í skólum, í að vera líkara öðru tungumáli sem lærist bæði innan og utan skóla (Birna Arnbjörnsdóttir, 2007). Rannsóknin sem greint er frá hér skoðar viðhorf til ensku og enskunotkun íslenskra barna við upphaf formlegrar enskukennslu í 4. bekk og áhrif þessara þátta á orðaforðaþekkingu þeirra og hvata til að læra ensku. Rannsóknarspurningarnar leitast við að skoða tengsl milli enskuáreitis og enskunotkunar í umhverfi barnanna og stærð orðaforða þeirra, en einnig að skoða áhrif kyns og upphafs enskukennslu á orðaforða þátttakenda. Fyrst var lögð fyrir spurningakönnun um hvata barnanna til námsins sem er byggð á hvatakerfi Dörnyei „L2 Motivational Self-System” (Dörnyei, 2005). Könnunin beinir sjónum að m.a. hvort og þá hvernig sjö umhverfisþættir, Sjónvarp/tónlist, Tölvur, Menntun, Vinir, Fjölskylda, Textar og Samskipti (Lingua Franca), hafa áhrif á enskan orðaforða barnanna. Tilgangurinn var að kortleggja hvaðan börnin lærðu enskan orðaforða. Síðan voru lögð fyrir tvö orðaforðapróf sem meta grunnþekkingu og vídd þekkingar við upphaf formlegs náms í ensku í grunnskóla. Þátttakendur voru 378 nemendur í 4. bekk grunnskóla haustið 2010 (190 stúlkur og 188 drengir). Megindleg greining á könnunum og prófum var framkvæmd með lýsandi tölfræði, greiningu á áhrifum umhverfisþátta auk raðbundnar fjölbreytu-aðhvarfsgreiningar til að skoða tengsl umhverfisþátta, notkunar og orðaforðaþekkingar. Niðurstöður benda til að orðaforði nemenda kemur að mestu leyti úr daglegu umhverfi utan skóla og er tengdur áhugasviði þeirra. Niðurstöður sýna einnig að þessi 9 ára börn átta sig á nauðsyn þess að læra ensku til framtíðarnotkunar í skóla og við lestur. Þetta eru svið þar sem enska var almennt ekki notuð þegar rannsóknin var framkvæmd. Það að börnin gera sér grein fyrir því að þau ættu að kunna að nota ensku í skóla og við lestur bendir til að þau túlka framtíðarhlutverk enskunnar og notkun þess sem veigarmikinn hluta af námi og lífi þeirra út frá hagnýtu sjónarhorni
Millivefslungnabreytingar og öldrunartengdir þættir
No full textIntroduction: Interstitial lung diseases (ILD), such as idiopathic pulmonary fibrosis (IPF), are diseases of elderly people that are characterised by pulmonary deposition of fibrous tissue and often have a poor prognosis. Interstitial lung abnormalities (ILA) are radiologic changes that are similar in appearance to ILD but are characterised in cohort study participants without known ILD. Prior research findings, including risk factors parallels such as advanced age, suggest that ILA are likely a precursor to ILD in some cases and are themselves associated with poor health outcomes. Due to the strong links that ILA and ILD share with advanced aging, the aims of the thesis were to assess the relationship of ILA with aging-related biological markers and outcomes in four papers. These were functional status, pulmonary and extra-pulmonary malignancies, a variety of blood proteins and leukocyte telomere length.
Methods: Data from three cohort studies, the Age/Gene-Environment Susceptibility-Reykjavik (AGES-Reykjavik) study, the Genetic epidemiology of COPD (COPDGene) study and the Framingham Heart study were used. CT images of participants had been manually read with regards to ILA status. Outcomes were ascertained from the cohorts’ phenotyping data and from electronic medical records. The associations of three self-reported measures of health and functional status with ILA were assessed with logistic regression. The relationship of ILA with diagnoses of and mortality from pulmonary and non-pulmonary malignancies was assessed with Gray’s tests and proportional hazards models. The associations of ILA, ILA progression and single nucleotide polymorphisms associated with pulmonary fibrosis with protein markers were assessed with adjusted regression models of single proteins. Adaptive LASSO modelling of bootstrap data samples was used to find sets of proteins predictive of ILA and ILA progression. The relations of ILA with leukocyte telomere length and telomere length with mortality among those with ILA were modelled with regression and Cox proportional hazards models.
Results: In the AGES-Reykjavik cohort, participants with ILA were less likely to be independent in activities of daily living (odds ratio (OR) 0.70, 95% confidence interval (CI) 0.55-0.90), to perceive their health as good or better (OR 0.66, CI 0.52-0.82) and to be regularly physically active (OR 0.72, CI 0.56-0.91). The cumulative incidences of lung cancer diagnoses and lung cancer mortality were higher among participants with ILA than others (p < 0.001), but such differences were not found for other cancers. In adjusted Cox proportional hazards models, ILA were associated with diagnoses of lung cancer (hazard ratio (HR) 2.77, CI 1.76-4.36) and mortality from lung cancer (HR 2.89, CI 1.80-4.66) but not with diagnoses of, or mortality from, cancers excluding lung cancer. In adjusted analyses of single serum proteins and ILA in AGES-Reykjavik, 287 proteins were significantly associated with ILA. The most significant associations were for Surfactant protein B (SFTPB), Secretoglobin family 3A member 1 (SCGB3A1) and WAP four-disulfide core domain protein 2 (WFDC2). An eight-protein model of ILA status was created based on inclusion in 200 adaptive LASSO models in bootstrap data samples which had an area under the receiving operator characteristic curve (AUROC) value of 0.880 after bootstrap validation. Single-protein results for SFTPB, SCGB3A1 and WFDC2 and the eight-protein model were validated in COPDGene (validated AUROC 0.826). Similarly, 121 proteins were associated with ILA progression in single protein models in AGES-Reykjavik and multi-protein modelling yielded a four-protein model which had a validated AUROC of 0.824. In analyses of fibrosis-associated genetic polymorphisms, the rs35705950 polymorphism near the MUC5B gene was found to be associated with levels of SFTPB (β 0.26, p = 8×10-18). As for analyses of ILA and leukocyte telomere length, shorter telomere length was associated with increased odds of ILA in COPDGene (OR 2.2, CI 1.5-3.4) and AGES-Reykjavik (OR 2.6, CI 1.4-4.9) and ILA was associated with shorter telomere length in FHS (β -767 base pairs, CI -76 - -1584). Adjusted Cox proportional hazards models did not demonstrate a significant association of telomere length with mortality among those with ILA in COPDGene nor in AGES-Reykjavik.
Conclusions: These cohort study-based data demonstrate the associations of ILA with several aging-related markers and outcomes. These are subjective markers of functional status, diagnoses of and mortality from pulmonary malignancies and telomere length in leukocytes. Additionally, many novel protein biomarkers of ILA are proposed, some of them previously related to aging. These findings improve knowledge of biological markers and epidemiological outcomes associated with ILA as a possible marker of early pulmonary fibrosis.Eimskipasjóður Háskóla Ísland
In Foreign Hands: Jón Sigurðsson and manuscript collecting in Iceland 1840–1880
No full textÍ þessari ritgerð er fjallað um handritasöfnun Jóns Sigurðssonar forseta. Markmið hennar er þríþætt. Í fyrsta lagi að varpa ljósi á tilgang söfnunarinnar og þá hvata er lágu þar að baki, í öðru lagi að skoða þær deilur er spruttu í kjölfar hennar og loks að kanna viðbrögð við þeim eins og þau birtust á opinberum vettvangi, í bréfaskiptum Jóns Sigurðssonar og samferðarmanna hans, og í aðbúnaði varðveislustofnana á Íslandi.
Stuðst er við ævisögulega nálgun (e. biographical approach) og til greiningar er notast við kenningar Pierre Bourdieu um menningarlegt auðmagn (e. cultural capital), hið svokallaða þriggja þrepa líkans Miroslavs Hroch um þróun þjóðernishreyfinga (e. three-phase model of national movements), líkan Joeps Leerssen um ræktun menningar (e. cultivation of culture) og kenningar um atbeini (e. agency).
Heimildir ritgerðarinnar samanstanda af bréfasöfnum Jóns og samferðamanna hans, skjalasöfnum Alþingis, Hins íslenska bókmenntafélags, Landsbókasafns og Forngripasafns, fundargerðabókum Kvöldfélagsins og annarra félaga, Alþingistíðindum, ferðabókum og frásögnum erlendra aðila er komu hingað til lands á átjándu og nítjándu öld, greinum, ræðum og ritverkum Jóns og blöðum og tímaritum er komu út á rannsóknartímabili ritgerðarinnar sem miðast við tímabilið 1840–1880.
Í inngangskafla er gerð grein fyrir aðferðum og efnistökum ritgerðarinnar, kenningaramma hennar, fyrri rannsóknum og heimildum. Í öðrum kafla er fjallað um sögulegan bakgrunn ritgerðarinnar, sem mótaðist einkum af viðamiklum handritasöfnunum Dana og Svía á Íslandi á sautjándu öld og Árna Magnússonar í aldarlok og upphafi þeirrar átjándu. Mikill afrakstur þeirra safnana mótaði þá skoðun að íslensk miðaldahandrit hefðu flest verið komin í erlendar hendur þegar í lok sautjándu aldar, sem hafði umtalsverð áhrif á umræðuna um handritasöfnun á Íslandi um miðbik nítjándu aldar.
Í þriðja kafla er fjallað um þá hvata er lágu að baki handritasöfnun Jóns Sigurðssonar sem má einkum rekja til andstöðu hans við flutning handrita frá Íslandi og nauðsyn þess að tryggja varðveislu þeirra og aðgengi innanlands. Sú skoðun er í skýru samhengi við uppgang þjóðernisrómantíkur í Evrópu á sama tíma og áherslu á söfnun, varðveislu og skráningu menningarverðmæta þjóða og þjóðarbrota er kom þá víða fram um álfuna. Jón og samferðamenn hans töldu jafnframt mikið óhagræði fólgið í því að varðveita íslensk skjöl og handrit í erlendum söfnum þar sem það hamlaði rannsóknum á sögu og samtíma þjóðarinnar auk þess sem þau væru iðulega illa skráð og lítt aðgengileg. Jón hóf þó sjálfur að viða að sér handritum til Kaupmannahafnar, ýmist í sitt persónulega safn frá 1840 eða í safn Kaupmannahafnardeildar Hins íslenska bókmenntafélags frá 1854, sem hann veitti forstöðu. Með þessum söfnunum taldi Jón að hægt væri að nýta handritin í fræðilegu tilliti með betra móti en á Íslandi, en halda þeim þó í eigu Íslendinga.
Í fjórða kafla er handritasöfnun Jóns tekin til nánari skoðunar. Söfnunarstefna hans var afar víðfeðm og safnaði hann hvers kyns gömlum og nýjum handritum og skjölum sem hann fékk frá löndum sínum sem þóknun fyrir ýmis konar útréttingar í Kaupmannahöfn. Vinir hans og kunningjar söfnuðu jafnframt handritum fyrir hann á Íslandi með markvissum hætti og fengu aðra til liðs við sig víða um land. Þá lét Jón einnig skrifa upp fyrir sig fjölda handrita úr söfnum á Íslandi, Bretlandseyjum og á Norðurlöndum og varðveitti jafnframt eigin gögn er lutu að hans fræða-, félags- og stjórnmálastörfum. Loks keypti hann önnur handritasöfn Íslendinga, stór og smá.
Í fimmta kafla er fjallað um þær deilur er risu um handritasöfnun Jóns um miðja öldina en töluverð eftirspurn var þá eftir íslenskum handritum. Fornfræðafélagið í Kaupmannahöfn hóf handritasöfnun árið 1846, handritasafni var komið á fót innan Landsbókasafns sama ár, og Reykjavíkurdeild Bókmenntafélagsins óskaði eftir handritum árið 1856 líkt og Kaupmannahafnardeildin hafði gert tveimur árum fyrr. Þá fjölgaði erlendum ferðamönnum til landsins til muna eftir 1858 sem margir hverjir föluðust eftir íslenskum handritum, bókum og forngripum. Í bréfaskiptum Jóns og samferðamanna hans um þetta leyti kom þessi eftirspurn skýrt fram og má þar greina andstöðu við flutning handrita úr landi, jafnvel þótt þeim væri stefnt til íslenskra aðila á borð við Jón eða Kaupmannahafnardeildar Bókmenntafélagsins. Í þessum deilum toguðust einkum á sjónarmið þeirra er vildu halda handritum á Íslandi og byggja þar upp innlent fræðasamfélag og annarra er töldu best að varðveita handrit í Kaupmannahöfn, þar sem þau kæmu að betri notum í fræðilegu tilliti. Þar komu einnig fram sjónarmið þeirra sem vildu síður senda handrit sín til Reykjavíkur vegna andúðar á eflingu bæjarins. Sjá má að margir litu á handritin sem menningarverðmæti sem ekki ætti að flytja úr landi og hélst sú skoðun í hendur við ríka þjóðernisvitund á sama tíma.
Í sjötta kafla er kannað hvernig brugðist var við deilunum um flutning handrita úr landi. Með athugun á þingmálum, bænaskrám, umræðu í blöðum og tímaritum og aðgerðum félagasamtaka má sjá að þrátt fyrir háværa umræðu í bréfaskiptum Jóns Sigurðssonar og samferðamanna hans um flutning handrita úr landi, náði hún ekki nægilegum styrk til að verða að formlegu baráttumáli. Hvorki Jón Sigurðsson né aðrir beittu sér fyrir þingmálum er sneru að söfnun og varðveislu handrita eða rituðu greinar um það málefni nema að mjög litlu leyti og Jón nýtti málefnið ekki í þjóðernislegum tilgangi í ræðu eða riti. Önnur mál voru landsmönnum ofar í huga. Þessi viðbrögð eru könnuð enn frekar í sjöunda kafla með því að rannsaka hvernig búið var að Landsbókasafni og Forngripasafni, enda söfnuðu þau og varðveittu handrit og skjöl, þótt í mismiklum mæli væri. Fundargerðir, bréfaskipti og blaðagreinar umsjónarmanna þeirra og yfirlit yfir safnkost benda til þess að yfirvöld og almenningur hafi sýnt þeim lítinn áhuga og skilning. Töluverð andúð ríkti gagnvart auknum álögum og eflingu nýrra stofnana og deildar meiningar voru um hvort söfnun og varðveisla handrita væru í verkahring ríkisvaldsins. Handritakostur Landsbókasafns óx margfalt hægar en söfn Jóns Sigurðssonar og Kaupmannahafnardeildar Bókmenntafélagsins sem gefur til kynna að þrátt fyrir áberandi umræðu í bréfaskiptum Jóns og samferðamanna hans um andstöðu við flutning handrita úr landi gripu samt margir til þess ráðs að senda handrit sín til Jóns eða Bókmenntafélagsins í Kaupmannahöfn.
Sagan af handritasöfnun Jóns Sigurðssonar varpar þannig fyrst og fremst ljósi á deilur og ólík sjónarmið er víða komu fram meðal Íslendinga varðandi söfnun og varðveislu handrita fram á síðari hluta nítjándu aldar, rétt í þann mund er fræðamiðja þjóðarinnar var að færast frá Danmörku til Íslands og auknar kröfur fóru að koma fram um skil handrita og skjala úr dönskum söfnum.The subject of this thesis is the collecting of manuscripts by Jón Sigurðsson (1811–1879). Its objective comprises three parts: firstly, to throw light on the purpose of his collecting, and the motivations behind it; secondly, to examine the disputes that arose on the subject among Icelanders, and to analyse their background and viewpoints; and finally to explore the response to those disputes as it was manifested in parliament and in the discourse of newspapers, periodicals and associations, and in Jón Sigurðsson’s correspondence with his associates, as well as in the conditions of the bodies responsible for collecting and preserving manuscripts in Iceland.
A biographical approach is applied, and the analysis employs Pierre Bourdieu’s theory of cultural capital, Miroslav Hroch’s three-phase model of national movements, Joep Leerssen’s model of cultivation of culture, and theories of agency.
The sources of the thesis are drawn from archives of correspondence between Jón Sigurðsson and his associates, the archives of Alþingi (parliament), the Icelandic Literary Society, the National Library of Iceland and the Antiquarian Collection (precursor of the National Museum), minutes books of Kvöldfélagið (the Evening Society) and other associations, Alþingistíðindi (Parliamentary Gazette), travel books and other accounts written by foreign visitors to Iceland in the eighteenth and nineteenth centuries, Jón Sigurðsson’s articles, speeches and other writings, and newspapers and periodicals published during the period covered by the thesis, which is based on the period 1840–1880.
The introductory chapter discusses the methods and approaches, theoretical framework, previous studies, and sources. Chapter two is concerned with the historical background, which was largely informed by extensive collecting of manuscripts by Danes and Swedes in Iceland in the seventeenth century, and by Árni Magnússon at the end of that century and the early eighteenth. As a result the view was widely held that most of Iceland’s manuscripts had been lost from the country; and that viewpoint influenced the predominant attitude to manuscript collections in the nineteenth century. Chapter three addresses the motivations behind Jón Sigurðsson’s collecting of manuscripts, which are mainly attributable to his opposition to the removal of manuscripts from Iceland, and the necessity of ensuring their preservation and accessibility in the country. That hostility has a clear relationship with the rise of romantic nationalism in Europe at that time, and the focus on collection, preservation and cataloguing of the cultural heritage of nations and ethnic groups which emerged at the time all over the continent. Jón and his associates also felt that it was impractical to preserve Icelandic documents and manuscripts in foreign collections, as it hindered study of Iceland in past and present – since the documents were, in addition, invariably poorly catalogued and not easily accessible.
In the middle of the century, however, Jón himself started to accumulate manuscripts in Copenhagen – both for his private collection from 1840, and for the Copenhagen branch of the Icelandic Literary Society, from 1854. Through this collecting, Jón was of the view that better use could be made of the manuscripts for scholarly purposes than in Iceland, while keeping them in Icelandic ownership.
Chapter four examines Jón’s collecting activities more closely. His collection principles were catholic, and he collected a wide range of manuscripts, old and new, many of which he acquired in return for favours carried out in Copenhagen on behalf of Icelanders. His friends and acquaintances also systematically collected manuscripts for him in Iceland, commissioning others to collect for him around the country. In addition, he had copies made of many manuscripts in collections in Iceland, the United Kingdom and Scandinavia, while also preserving his own documents regarding his scholarly, social and political activities. Finally, he purchased other collections, large and small.
Chapter five is concerned with disputes that arose regarding Jón’s manuscript collection in the middle of the century, when Icelandic manuscripts were in some demand. Det Kongelige Nordiske Oldskriftselskab (the Royal Nordic Society of Antiquaries) started to collect manuscripts in 1846; in that same year a manuscript collection was founded at the National Library of Iceland; and in 1856 the Reykjavík branch of the Icelandic Literary Society requested manuscripts, as did the Copenhagen branch. Numbers of foreign tourists in Iceland rose sharply from 1858, and many of them sought out Icelandic manuscripts, books and antiquities for purchase. In Jón’s correspondence with his associates at that time, this demand for heritage goods is discussed, and opposition is expressed to the removal of manuscripts from Iceland, even when they were intended for Icelandic parties such as Jón Sigurðsson or the Copenhagen branch of the Literary Society. These disputes reflected mainly the conflict between the perspective of those who wished to keep the manuscripts in Iceland, and to develop an Icelandic academic environment, and those who felt that the manuscripts were best kept in Copenhagen, where they would be more useful in a scholarly sense. In addition, views expressed included those of people who were unwilling to send their manuscripts to Reykjavík due to their opposition to the rise of the town. Many saw the manuscripts as objects of cultural heritage which should not be removed from Iceland; and that view went hand-in-hand with the rising national consciousness of the time.
Chapter six examines the response to disputes about the removal of manuscripts from Iceland. An examination of parliamentary proceedings, petitions, discourse in newspapers and periodicals, and actions taken by associations reveals that, despite the intense debate about the removal of manuscripts from the country in Jón Sigurðsson’s correspondence with his associates, it never reached the point of becoming a formal campaigning issue. Neither Jón Sigurðsson nor others undertook parliamentary actions regarding the collection and preservation of manuscripts, nor did they write articles on the subject, except to a very minor degree; and Jón did not make use of it for nationalistic purposes, neither in speeches nor in writing. Other issues were regarded as more important by Icelanders.
These responses are explored further in chapter seven, by examining the circumstances of the National Library and Antiquarian Collection, both of which collected and kept manuscripts and documents – though not in the same quantity. Minutes books, correspondence and press articles by their directors, and overviews of their collections, indicate that the government and public showed them little interest or understanding. Additional taxation and the development of new institutions met with general antipathy, and the involvement of government in the collection and preservation of manuscripts was a controversial issue. The National Library’s manuscript collection grew at a fraction of the speed of Jón Sigurdsson’s collection and that of the Copenhagen branch of the Icelandic Literary Society, and that implies that, despite the vociferous debate in correspondence between Jón and his associates about opposition to the removal of manuscripts from Iceland, people commonly resorted to sending their manuscripts to Copenhagen, either to Jón or to the Literary Society.
The story of Jón Sigurðsson’s manuscript-collecting thus primarily throws light on the disputes and differing viewpoints widely expressed by Icelanders about the collection and preservation of manuscripts, until the late 19th century, around the time when Iceland’s scholarly focus was moving from Denmark to Iceland, and demands increased for the restitution of manuscripts and documents from Danish collections
Augnlyfjaferjur byggðar á -sýklódextríni
No full textgamma-Cyclodextrin (gCD) has been recently used as pharmaceutical excipient in topical formulation for ocular delivery. The high corticosteroid concentration in various ocular tissues has been reported after topical application of aqueous eye drops, especially achieving therapeutic level in the posterior segment of the eyes. This draws attention to expand on the gCD application in ocular corticosteroid delivery and discover new use of gCD as drug carrier for drug candidates in eye disease. It is well known that physicochemical properties of lipophilic drug, e.g., solubility, can be changed when they form complex with gCD without covalent bond involved in the complexation. Most complex formations result in improvement of the drug´s solubility or stability or both in water leading to the enhancement of the drug bioavailability at target organ after administration. Normally, aqueous mucus layer covering epithelium of many organs hampers lipophilic drug to dissolve and partition in this layer. When the aqueous solubility of poorly water-soluble drugs is improved, availability of the drug molecule is greater at mucus-epithelium interface. Similarly, the aqueous-mucin layer of tear film covering ocular epithelium is the frontline physical barrier of the lipophilic drug. In ophthalmic formulation development, not only solubilizing property of excipient but the ability of vehicle to enhance drug permeability is also important for drug delivery system to overcome complicated barriers of the eyes. Therefore, this project will explore into the foundation of the gCD application as a drug carrier for topical delivery to the eye and seek feasibility of incorporation of new drug candidate in gCD-based carrier platform.
The objectives of this study were to improve water solubility of the lipophilic drug, dovitinib free base using gCD; to examine physicochemical properties of the drug in the presence of gCD and other pharmaceutical excipients; to determine the effect of gCD on drug permeation; as well as to investigate the factors affecting drug permeation through lipophilic membrane and drug release from gCD-based carrier.
Phase-solubility technique was used to form complex of the lipophilic model-drugs (dovitinib and dexamethasone) in gCD aqueous media, determine the aqueous solubility of the drugs in relevant studied condition, and prepare sample solutions for the permeation studies. To improve the aqueous solubility of dovitinib, single technique such as gCD complexation and salt formation, and combination techniques of gCD complexation and ionization were evaluated. Five acids were used to investigate salt formation and ionization of dovitinib base by pH-solubility studies. In optimization, three different concentrations of each acid were added to the complexing media containing two different gCD concentrations and the enhanced solubility was determined. Lipophilicity and stability were also examined in the presence and absence of pharmaceutical excipients, i.e., gCD, counterions, buffers. Furthermore, the solid fraction found in spontaneous suspensions of the dovitinib/acid/high gCD concentration was characterized in terms of the contents of dovitinib and gCD, size of solid particles, and form of dovitinib and gCD using high performance liquid chromatography, laser scattering technique, and Fourier-transform infrared spectroscopy, respectively. Finally, in-vitro permeation studies were carried out using vertical Franz diffusion cells, artificial lipophilic membranes, and a single layer of cellulose dialysis membranes. A particularly experimental condition was designed to separately investigate the gCD effect on drug permeation, formulation factors affecting drug permeation, and drug release from gCD-based carrier.
Solubility studies showed that salt formation with counterions increased the aqueous solubility of dovitinib greatly rather than complexation with gCD. Lactic acid improved the solubility up to many ten-thousand folds and its solubility enhancement was the highest among other acids used. When the combined techniques were used, the total solubility, i.e., the intrinsic solubility of the pure drug and solubility of the drug/gCD complex, was increased due to the improvement of apparent intrinsic solubility as expected. Surprisingly, a synergistic effect of solubilization was found when dovitinib was dissolved in the acidic aqueous solutions containing lactic/gCD, phosphoric/gCD and maleic/gCD at low concentration of gCD (38.6 mM). At high gCD concentration (154.2 mM), the dissolved dovitinib and dovitinib/gCD complex increased with increasing acid concentration. In contrast, some samples containing relatively low acid concentration were suspension. Thus, the contents of dovitinib and gCD in solid fraction were determined and two suspensions obtained from lactic acid and phosphoric acid were characterized. The results revealed that solid fraction contained gCD content more than dovitinib content. The solid particles in those suspensions were in a few micrometers of size and in a complex form with gCD. This indicated that spontaneous suspension of dovitinib/acid/154.2 mM gCD obtained from lactic acid and phosphoric acid contained self-assembled microparticles of dovitinib/gCD complexes. Moreover, lipophilicity of dovitinib in the presence of acidic counterions was determined at different pH and described with log10 of distribution coefficient, log D. It was found that the pH was the main factor influencing the log D of the ionizable dovitinib. The counterions can affect the log D of the ionized dovitinib but have a negligible impact on the log D of the unionized drug. The stability studies also showed that gCD could stabilize dovitinib at relatively low pH. The stabilizing effect of gCD was more noticeable than the buffer effect.
The drug permeation studies through the artificial lipophilic membrane were performed to investigate the gCD effect on permeation of dexamethasone and the impact of formulation factor on dovitinib permeation. The results of dexamethasone permeation showed that drug flux increased with increasing dissolved dexamethasone and gCD concentration. The dexamethasone flux increased until reaching the maximum at the highest solubility of the drug then decreased dramatically when excess gCD was found in the dexamethasone-saturated solution. This indicated that the highest permeation was obtained when both the thermodynamic activity of the drug and the soluble drug concentration were at maximum. However, the results from dovitinib permeation showed different phenomenon. The dovitinib flux and apparent permeability coefficient (Papp) decreased when the self-assembled nanoparticles existed. In addition, the flux and Papp further decreased when the nanoparticle was larger in size and concentration. Therefore, the formulation factor such as particle size should be considered during formulation design.
The study of drug release was performed using a single layer of cellulose dialysis membrane. Original intention of this study was to investigate the effect of alpha-amylase enzyme, which has been found in tear fluid, on dexamethasone release from gCD-based carrier under mimic tear pH and ocular surface temperature. However, unexpected factor was found with additive influence on the alpha-amylase effect. From the observation in the release studies, it can explain that the faster release of dexamethasone from aqueous solution containing relatively low gCD, i.e., 1–4 mM and alpha-amylase enzyme was due to the additive effect of dilution and alpha-amylase catalysis.
In conclusion, gCD showed functional flexibility as an excipient depending upon its concentration and the presence of additives. It could both solubilize and stabilize the lipophilic drug of interest, dovitinib through forming complex and self-assembled gCD particles. gCD-based carrier can either enhance or hamper the drug permeation, but the effect can be optimized. Furthermore, drug release can be enhanced when alpha-amylase is present in diluted gCD solution. These findings suggest that gCD can be used as a drug carrier for lipophilic drug in topical delivery to the eyes.-sýklódextrín (CD) hefur nýlega verið notað sem hjálparefni fyrir lyf til
staðbundinnar notkunar í auga. Greint hefur verið frá mikilli þéttni barkstera í
ýmsum augnvefjum eftir staðbundna notkun augndropa, einkum eftir að
meðferðarþéttni hefur verið náð í aftari hluta augna. Þetta gefur tilefni til að
kanna frekari notkun CD við gjöf barkstera í auga og uppgötva nýja
notkunarmöguleika CD sem lyfjalosunarkerfis fyrir önnur hugsanleg lyf við
augnsjúkdómum. Það er vel þekkt að eðlisefnafræðilegir eiginleikar
gestasameindar, til dæmis fitusækið lyf og/eða CD, geta breyst þegar þau
mynda flóka. Þetta gerist þrátt fyrir að ekkert samgilt tengi taki þátt í myndun
efnaflókans milli lyfsins og CD. Flestir efnaflókar leiða til aukinnar leysni
og/eða aukins stöðugleika lyfsins í vatni, sem aftur leiðir til aukins aðgengis
lyfsins að marklíffærinu eftir gjöf. Vatnskennda slímlagið sem liggur yfir
þekjuvef margra líffæra hindrar yfirleitt upplausn fitusækna lyfsins og
dreifingu þess í slímlaginu. Með því að bæta vatnsleysni lyfja sem leysast illa
upp í vatni eykst enn fremur aðgengi að lyfjasameindinni á mótum slímlags
og þekju. Á svipaðan hátt myndar vatnskennt slímlag tárahimnunnar sem
þekur augnþekjuna helstu efnislegu hindrunina fyrir fitusækna lyfið. Við þróun
augnlyfja er ekki aðeins mikilvægt að auka leysnieiginleika hjálparefna heldur
einnig að bæta gegndræpi lyfja til að lyfjalosunarkerfið komist fram hjá
flóknum hindrunum í augum. Þar af leiðandi felur þetta verkefni í sér
rannsókn á notkun CD sem lyfjaferju fyrir staðbundna notkun í augum og að
leita hagkvæmra leiða fyrir ný hugsanleg lyf sem CD getur flutt með sama
hætti.
Markmið rannsóknarinnar var að bæta vatnsleysni fitusækna lyfsins
dóvitiníbs, sem er óbundinn basi, með því að nota CD til að rannsaka
eðlisefnafræðilega eiginleika lyfsins samhliða CD og öðrum hjálparefnum
með það fyrir augum að ákvarða áhrif CD á gegndræpi lyfja. Enn fremur var
markmiðið að rannsaka þá þætti sem hafa áhrif á gegndræpi lyfja í gegnum
fitusæknar himnur og losun lyfs frá CD-lyfjaferju. Fasaleysniaðferð (e.
phase-solubility technique) var notuð á vatnslausn með CD til að mynda
flóka úr fitusæknum lyfjum í líkani (e. model-drugs) (dóvitiníb og
dexametasón), ákvarða vatnleysni lyfjanna á viðkomandi rannsóknarformi og
að undirbúa sýnislausnir fyrir gegndræpirannsóknir. Metin var virkni stakra
aðferða, svo sem myndun CD-flóka og myndun salta, og samsettra aðferða
með myndun CD-flóka og jónun til að bæta vatnsleysni dóvitiníbs. Fimm
sýrur voru notaðar til að rannsaka saltmyndun og jónun dóvitiníb-basa með
rannsóknum á leysanleika tengdum sýrustigi (e. pH-solubility). Fimm
iv
mótjónum með þremur mismunandi þéttnigildum var bætt við flókalausnina
sem innihélt CD með tveimur mismunandi þéttnigildum og aukin leysni var
svo ákvörðuð út frá því. Auk þess voru fitusækni og stöðugleiki skoðuð bæði
með og án hjálparefna, þ.e. CD, mótjóna, jafnalausna. Enn fremur var
eiginleikum brota á föstu formi sem fundust í dreifu með dóvitiníbi/sýru/CD í
mikilli þéttni lýst með hliðsjón af magni dóvitiníbs og CD með því að nota
háþrýstivökvaskiljun, stærð föstu agnanna var lýst með ljósdreifigreiningu
með leysigeisla og formi dóvitiníbs og CD var lýst með Fouriervörpunarlitrófsgreiningu með innrauðu ljósi. Að lokum var in vitro prófun á
gegndræpi framkvæmd í lóðréttu Franz dreifihólfi (e. Franz diffusion cell) með
efnasmíðaðri fitusækinni himnu og stöku lagi af skilunarhimnu úr sellulósa.
Sérstakar tilraunaaðstæður voru hannaðar til að rannsaka sérstaklega áhrif
CD á gegndræpi lyfs, myndunarþætti sem hafa áhrif á gegndræpi lyfs og
losun lyfs frá CD-lyfjaferju.
Rannsóknir á leysni sýndu að saltmyndun með mótjón eykur vatnsleysni
dóvitiníbs mun meira en myndun efnaflóka með CD. Mjólkursýra bætti leysni
allt að tugþúsundfalt og var leysniaukning hennar mest af þeim sýrum sem
voru notaðar. Þegar tvær aðferðir voru notaðar samhliða jókst leysnin vegna
bættrar sýnilegrar og eðlislægrar leysni, eins og búist var við í sumum
kerfum. Hins vegar kom á óvart að samverkandi leysniáhrif komu fram þegar
dóvitiníb var leyst upp í súrum vatnslausnum sem innihéldu fosfór-/CD og
malín-/CD þar sem CD var í lágri þéttni (38,6 mM). Á sama tíma bætti
þrígilda kerfið með dóvitiníbi, mjólkursýru og CD (38,6 mM) leysni gegnum
viðbótaráhrif. Við mikla þéttni CD (154,2 mM) jókst upplausn dóvitiníbs og
dóvitiníb-/CD-flóka í takt við aukna sýruþéttni. Aftur á móti voru nokkur sýni
sem innihéldu tiltölulega lága sýruþéttni dreifur. Því var magn dóvitiníbs og
CD í föstu broti ákvarðað og tvær dreifur sem fengust úr mjólkursýru og
fosfórsýru voru greindar með hliðsjón af eiginleikum. Niðurstöðurnar leiddu í
ljós að fasta brotið innihélt meira af CD en dóvitiníbi. Föstu agnirnar í
þessum dreifum voru nokkrir míkrómetrar að stærð og á formi flóka með CD.
Þetta benti til þess að dreifa með dóvitiníbi, sýru og CD (154,2 mM) sem
fékkst úr mjólkursýru og fosfórsýru innihélt sjálfraðaðar (e. self-assemble)
öragnir af dóvitiníb-/CD-flókum. Auk þess var fitusækni dóvitiníbs ákvörðuð
þegar súrar mótjónir voru til staðar við mismunandi sýrustig og henni lýst með
log10 af dreifistuðli, log D. Í ljós kom að sýrustigið var helsti þátturinn sem
hafði áhrif á log D í jónanlegu dóvitiníbi. Mótjónirnar geta haft áhrif á log D
jónaðs dóvitiníbs en þær hafa óveruleg áhrif á log D í ójónaða lyfinu.
Rannsóknir á stöðugleika sýndu einnig að CD getur haldið dóvitiníbi stöðugu
við tiltölulega lágt sýrustig. Stöðugleikaáhrif CD voru greinilegri en áhrif
jafnalausnarinnar.
Rannsóknir á gegndræpi lyfsins í gegnum efnasmíðaða fitusækna himnu
voru gerðar til að kanna áhrif CD á gegndræpi dexametasóns og áhrif
v
myndunarþáttarins á gegndræpi dóvitiníbs. Niðurstöður fyrir gegndræpi
dexametasóns sýndu að flæði lyfsins jókst með aukinni upplausn
dexametasóns og aukinni þéttni CD. Flæðið minnkaði verulega eftir að
hámarksleysni dexametasóns var náð en hins vegar sást umframmagn af
CD. Þetta benti til þess að mesta gegndræpi hafi komið fram þegar bæði
varmafræðileg virkni lyfsins og þéttni uppleysts lyfs voru í hámarki. Hins
vegar voru niðurstöðurnar fyrir gegndræpi dóvitiníbs ólíkar. Flæði dóvitiníbs
minnkaði og sýnilegur gegndræpistuðull (Papp) þess lækkaði þegar
sjálfröðuðu nanóagnirnar voru til staðar. Auk þess minnkaði flæðið og Papp
lækkaði enn frekar þegar nanóagnir voru stærri. Þar af leiðandi skal hafa í
huga myndunarþætti á borð við stærð agna við hönnun lyfjasamsetningar.
Rannsóknin á losun lyfsins var framkvæmd með því að nota eitt lag af
skilunarhimnu úr sellulósa. Upphaflegur tilgangur þessarar rannsóknar var að
kanna áhrif -amýlasaensíms, sem fundist hefur í táravökva, á losun
dexametasóns frá CD-lyfjaferju við aðstæður sem líkja eftir sýrustigi tára og
yfirborðshita augans. Hins vegar fannst óvæntur þáttur sem hefur
viðbótaráhrif á virkni -amýlasa. Samkvæmt niðurstöðum úr
losunarrannsóknunum getur þetta skýrt hraðari losun dexametasóns úr
vatnslausn sem inniheldur CD í tiltölulega lágri þéttni, þ.e. 1–4 mM og -
amýlasaensím á þann veg að hraðari losun er tilkomin vegna viðbótaráhrifa
þynningar og hvötunar -amýlasa.
Lokaniðurstaðan er sú að CD hefur sveigjanlega virkni sem fer eftir þéttni
þess og því hvort aukefni eru til staðar eða ekki. Það getur bæði gert
fitusækna lyfið dóvitiníb leysanlegt og haldið því stöðugu með því að mynda
flóka og sjálfraðaðar CD-agnir. Jafnvel þó CD-lyfjaferja geti bæði aukið eða
hindrað gegndræpi lyfsins er hægt að hámarka áhrifin. Enn fremur er hægt
að auka losun lyfs þegar -amýlasi er til staðar í þynntri CD-lausn. Þessar
niðurstöður benda til þess að hægt sé að nota CD sem lyfjaferju fyrir
fitusækin lyf til staðbundinnar notkunar í auga
A provisional seismic source zonation of Iceland for the ESHM20 based on new physics-based bookshelf fault system models and a new revised earthquake catalogue
No full textThe earthquake hazard in Iceland is highest in its two transform zones, the South
Iceland Seismic Zone in the South and the Tjörnes Fracture Zone in the North and the reliable probabilistic seismic hazard assessment (PSHA) is the prerequisite for the codified aseismic design of structures and mitigation of seismic risk. The three fundamental aspects of a reliable PSHA, the proper specification of the seismic sources, in particular in the transform zones, their activity rates, and the use of acceptable forms of ground motion models that characterize the rapid attenuation of Icelandic strong-motion, need to be based on the latest state-of-the-art information and methods. In this study, we present a new and provisional subdivision of Iceland into seismic area-source zones on the basis of new physics-based fault system models as well as parameter set for each zone based on new revised and harmonised earthquake catalogue for Iceland. The zonation is guided by the systematic spatial distribution of the predominant types of earthquake faulting mechanisms in Iceland, consistent with the volcanic and transform zones in the country. Moreover, the new physics-based estimates of activity rates in the transform zones effectively explain the historical seismicity and allow the specification of subzone activity rates. On the basis of this new zonation finite-fault earthquake catalogues can be simulated for long-time intervals that are consistent with the time-independent estimates of seismicity. The provisional seismic zonation model can therefore both serve as the basis for the revision of the PSHA of Iceland using conventional engineering approaches and lays the foundation for physics-based earthquake rupture simulation approaches to the time-independent PSHA. For the time being however, this provisional model has been provided to the harmonized efforts of PSHA in Europe (ESHM20).The Iceandic Centre for Research (Grant no. 196089).Peer Reviewe
Sjálfvirkni þunglyndisþanka í daglegu lífi: Rannsóknir á vanabundnu eðli þunglyndisþanka í úrtökum háskólanema og fólks með endurtekið þunglyndi. Innsýn úr snjallsímamælingum
Get PDFBackground: Major depression is the most common psychiatric disorder, associated with the highest disease burden worldwide when it comes to years lost to disability. Efforts to identify indicators of depression risk have strongly implicated depressive rumination, a negative thinking style characterized by repetitive and passive thoughts about the causes, meanings, and consequences of one's feelings and distress. An increasingly popular theoretical perspective posits that over time depressive rumination becomes a mental habit that is initiated automatically without conscious awareness or intent in response to downward shifts in mood, making it persistent and difficult to control. However, the rumination as-a-habit account has rarely been directly tested and it is still unknown whether depression vulnerability is characterized by elevated levels of mood-reactive habitual rumination at the level of short-term dynamics.
Aims: The aim of the current research project was to address gaps in the current knowledge on depression vulnerability by utilizing a combination of experimental and novel mobile in-the-moment assessment strategies to better understand the dynamic interplay between mood and ruminative thinking and its habitual characteristics. Three studies were designed to test specific hypotheses involving: a) effects that fluctuations in mood have on subsequent ruminative thinking, b) the degree to which habitual characteristics of negative thinking predict such mood-reactive rumination, and c) whether mood-reactive rumination varies according to the depression-risk spectrum in line with theoretical accounts of depression vulnerability.
Methods: In study 1, a total of 115 university students completed self-report measures and participated in an experimental rumination-induction task and outcome-devaluation task measuring habit vs. goal-directed behaviour control. In study 2, a total of 97 participants recorded affect and rumination ten times daily over six days using Ecological Momentary Assessment, after completing measures of trait ruminative brooding and habitual characteristics of negative thinking (e.g., automaticity, lack of conscious awareness, intent, and control). In study 3, formerly depressed individuals with a recurrent history of depression (n = 94) and non-clinical controls (n = 55) recorded in-the-moment affect and rumination ten times daily over six days, after completing baseline measures of trait ruminative brooding, habitual characteristics of negative thinking, and early-life stress.
Results: In study 1, greater habitual characteristics of negative thinking were associated with ruminative brooding but not ruminative reflection, and predicted more persistent dysphoric mood following rumination-induction. Rumination was not, however, consistently associated with an imbalance in habit vs. goal-directed behaviour control. In study 2, momentary fluctuations in negative (increased) and positive (decreased) affect was prospectively associated with greater rumination at the next sampling occasion. The degree to which affect triggered a subsequent ruminative response was moderated by habitual characteristics of negative thinking in a theoretically consistent way. Stronger temporal pairing of negative affect and rumination was also associated with greater emotional inertia but less carry-over of rumination from one moment to the next. In study 3, momentary fluctuations in negative affect were prospectively associated with greater rumination at the next sampling occasion in formerly depressed participants whereas this pattern of mood-reactive rumination was not observed in healthy never-depressed participants. In formerly depressed participants, habitual characteristics of negative thinking were associated with greater mood-reactivity of rumination, particularly among those with a history of early-life stress. Mood-reactive rumination was not, however, associated with depression course nor trait ruminative brooding.
Conclusions: The findings of the studies demonstrate that fluctuations in affect can trigger ruminative thinking as a function of habit consistent with recent theoretical frameworks of depression vulnerability. Mood-reactive rumination may be a potential vulnerability marker for depression, with rumination being habitually triggered in response to momentary fluctuations in negative affect with a high degree of automaticity, and with a deleterious effect on mood. The current thesis suggests ways depression vulnerability may emerge as a dynamic relationship between negative affect and rumination across time, not captured by traditional trait measures of rumination frequency. Ecological momentary assessment may be a valuable measurement paradigm to test predictions derived from habit-accounts of depressive rumination, that have rarely been investigated until now, and might provide new insights into research on depression risk.This research was sponsored by the Icelandic Center for Research and the Eimskip Fund of The University of Iceland (Rannís Grant 173803-052, 173803-053)
Dissociative ionization and electron beam induced deposition of tetrakis(dimethylamino)silane, a precursor for silicon nitride deposition
Get PDFMotivated by the use of tetrakis(dimethylamino)silane (TKDMAS) to produce silicon nitride-based deposits and its potential as a precursor for Focused Electron Beam Induced Deposition (FEBID), we have studied its reactivity towards low energy electrons in the gas phase and the composition of its deposits created by FEBID. While no negative ion formation was observed through dissociative electron attachment (DEA), significant fragmentation was observed in dissociative ionization (DI). Appearance energies (AEs) of fragments formed in DI were measured and are compared to the respective threshold energies calculated at the DFT and coupled cluster (CC) levels of theory. The average carbon and nitrogen loss per DI incident is calculated and compared to its deposit composition in FEBID. We find that hydrogen transfer reactions and new bond formations play a significant role in the DI of TKDMAS. Surprisingly, a significantly lower nitrogen content is observed in the deposits than is to be expected from the DI experiments. Furthermore, a post treatment protocol using water vapour during electron exposure was developed to remove the unwanted carbon content of FEBIDs created from TKDMAS. For comparison, these were also applied to FEBID deposits formed with tetraethyl orthosilicate (TEOS). In contrast, effective carbon removal was achieved in post treatment of TKDMAS. This approach only marginally affected the composition of deposits made with TEOS.The Icelandic Centre of Research (RANNIS), grant no. 13049305(1−3). MC acknowledges a doctoral grant from the University of Iceland Research Fund.Peer Reviewe
Flutningur lyfja með augndropum inn í auga
No full textFyrir marga lyfjaflokka þykir staðbundin lyfjagjöf í augndropaformi ákjósanlegasta leiðin
vegna einfaldleika við lyfjagjöf. Eru augndropar algengasta aðferðin til að meðhöndla
augnsjúkdóma í fremri hluta augans. Staðbundin lyfjagjöf í augndropaformi yfir
hornhimnu er hinsvegar óhagkvæm þegar meðhöndla þarf aftari hluta augans.
Hefðbundin lyfjameðferð fyrir aftari hluta augans felur í sér að lyfinu er dælt í glerhlaup
augans en með tilheyrandi áhættu á fylgikvillum ásamt tilheyrandi óþægindum fyrir
sjúklinga. Sýnt hefur verið fram á að leiðin í gegnum augnslímhúð og augnhvítu hefur
hlutfallslega hærra gegndræpi fyrir risasameindir, stærra aðgengilegt yfirborð og meiri
nálægð við sjónhimnu samanborið við hornhimnu. Fyrir vikið hafa verið kenningar um
að augnslímhúð og augnhvíta sé mögulega leið lyfja í augndropaformi yfir í aftari hluta
augans. Meginmarkmið þessarar ritgerðar eru (1) að kanna hversu vel ákveðin lyf í sýklódextrín augndropaformi flytjast yfir í fremri og aftari hluta augans, (2) að ákvarða lyfjafræðileg áhrif angíótensínviðtaka-hamlara á augnþrýsting eftir augndropagjöf, (3) að meta og bera saman in vitro gegndræpi í gegnum hornhimnu og í gegnum augnslímhúð og augnhvítu fyrir staðbundna augndropalyfjagjöf í aftari hluta augans og (4) að bera
kennsl á helstu eðlisefnafræðilega eiginleika sem hafa áhrif á gegndræpi lyfja yfir
hornhimnu í fullri þykkt og leiðina frá augnslímhúð, í gegnum augnhvítu og æðahimnu
að sjónhimnu (augnslímhúð-augnhvítu-æðahimnu-sjónhimnu leið). Aðferðir
1. Framkvæmdar voru tvær in vivo rannsóknir á kanínum þar sem mældur var
lyfjastyrkur í augnvefjum eftir stakan skammt af augnlyfjum í sýklódextrín
nanóögnum. Í fyrri rannsókninni voru tveir mismunandi
angíótensínviðtakahamlarar, 1.5% irbesartan og 0.15% candesartan, gefnir 49
kanínum. Styrkur lyfjanna var mældur í hornhimnu og augnvökva eftir 1, 2, 3, 6
og 12 klukkustundir frá lyfjagjöf. Í seinni rannsókninni var ný γ-sýklódextrín
öragna augnlyfjaferja með cediranib maleate (öflugur VEGF hamlari) prófuð á
26 kanínum. Styrkur cediranib maleate var mældur í vefjum fremri og aftari
hluta augans eftir 1, 3, og klukkustundir frá lyfjagjöf.
2. Augnþrýstingslækkandi áhrif irbesartan og candesartan voru mæld í 10
kanínum. Algengt glákuaugndropalyf, 0.5% timolol, var síðan notað til samanburðar. Augnþrýstingur var mældur með sérstökum augnþrýstingsmæli á
tíma 0, 2 og 4 klukkustundum eftir stakan lyfjaskammt.
3. Framkvæmd var in vitro rannsókn á augnvef úr svínum með Franz-sveimklefa til
að bera saman gegndræpi 27 mismunandi efnasambanda yfir hornhimnu og
augnslímhúð – augnhvítu – æðahimnu og sjónhimnu. Reiknað var út flæði lyfja
og gegndræpisstuðlar fyrir hvert efnasamband og vef. Lýsing á 39 sameindum
fyrir efnasamböndin sem voru notuð, voru fengin frá ákveðnum gagnagrunnum
á alnetinu og notuð til að reikna út fylgni við gegndræpisstuðul með Spearmans
rho fylgnistuðul. Niðurstöður 1. Styrkur irbesartan í augnvökva meðferðarauga fór upp í 282 ± 159 ng/g (meðaltal ± SD, n = 26) og fyrir candesartan 70 ± 73 ng/g. Hæsti styrkur í
hornhimnu var 3662,6 ± 987,7 ng/g fyrir irbesartan og 3503,9 ± 801,5 ng/g
fyrir candesartan. Cediranib maleate mældist í sjónhimnu í styrkleika 1070 ±
1404 nM og í glerhlaupi 19 ± 9 nM (n = 6). 2. Candesartan hafði mest lækkandi áhrif á augnþrýsting, með breytingu upp á 5,6 mmHg fjórum klukkustundum eftir lyfjagjöf samanborið við 4,0 mmHg fyrir irbesartan og 4,6 mmHg fyrir timolol.
3. 22 af 27 efnasamböndum (81%) sýndu hærra gegndræpi í gegnum
augnslímhúð-augnhvítu-æðahimnu-sjónhimnu leiðina, samanborið við
hornhimnu. Meðalgegndræpi fyrir augnslímhúð-augnhvítu-æðahimnu-sjónhimnu
vefina var 2,9 sinnum hærra en gegndræpi hornhimnunnar. Fylgni var á milli
aukins vatnsleysnis og meira gegndræpis yfir bæði hornhimnu í fullri þykkt og
augnslímhúð-augnhvítu-æðahimnu-sjónhimnu-leiðina, á meðan hærri fitusækni,
mólmassi og fjöldi hringa leiddi til lægri gegndræpisstuðla.
Umræða
Irbesartan, candesartan og cediranib mældust í styrk af tilætluðum lyfjafræðilegum
áhrifum í fremri og aftari hluta augans eftir lyfjagjöf með sýklódextrin augnlyfjaferjum.
Niðurstöðurnar gefa til kynna staðbundna dreifingu lyfjanna sem gæti komið í veg fyrir
þörf á inngripsmiklum lyfjagjöfum. Irbesartan og candesartan í augndropaformi lækkuðu augnþrýsting hjá kanínum með góðum árangri, sem gæti bent til nýs flokks glákulyfja.
In vitro gögn okkar benda til þess að fyrir mörg efnasambönd gæti augnslímhúðaugnhvítu leiðin verið áhrifameiri og mögulega eina leiðin til að skila lyfjum í vefi í
aftari hluta augans með staðbundinni augndropalyfjagjöf.Purpose: Topical ocular administration is the preferred route for many classes of drugs
because of its ease of administration. It is the most common way of treating eye
diseases in the anterior segment. Topical administration through the cornea, however,
is inefficient for drug delivery to the back of the eye. Intravitreal injections are the
standard drug treatment for posterior segment disorders but are associated with the risk
of complications and patient discomfort. The conjunctiva-sclera route has shown a relatively higher permeability to macromolecules, a larger surface of exposed tissue and a closer location to the retina when compared to the cornea. Consequently, it has been suggested as an alternative route for topical drug delivery to the posterior segment.
The main goals of this thesis are (1) to test the efficacy of cyclodextrin-based eye drop
formulations in delivering certain drugs to the anterior and posterior segments of the
eye, (2) to determine the pharmacological effect of angiotensin receptor blockers on
intraocular pressure after topical administration, (3) to evaluate and compare the in vitro
permeabilities of the corneal and noncorneal routes for topical drug delivery to the
posterior segment and (4) to identify the main physicochemical properties affecting the
permeation of drugs across full-thickness cornea and conjunctiva-sclera-choroid-retina.
Methods: 1. Two separate in vivo studies were performed in rabbits to measure the drug
concentration in the intraocular tissues after a single dose administration of
cyclodextrin-based nanosuspension eye drops. In the first study, two different
angiotensin receptor blockers, 1.5% irbesartan and 0.15% candesartan, were
administered to 49 rabbits and the drug concentrations in the cornea and
aqueous humour were quantified at 1, 2, 3, 6 and 12 hours after
administration. In the second study, a novel γ-cyclodextrin nanoparticle eye
drops formulation containing cediranib maleate, was applied to 26 rabbits. The
concentration of cediranib maleate in the tissues of both anterior and posterior
segments was quantified at 1, 3 and 6 hours after administration.
2. The potential lowering effect of irbesartan and candesartan on intraocular
pressure was investigated in 10 rabbits. The IOP was measured at 0, 2 and 4
hours after a single-dose administration using a rebound tonometer and
compared with a commercial 0.5% timolol solution.
3. In vitro studies were performed using porcine ocular tissues mounted on Franzdiffusion cells to compare the permeability of 27 different compounds across
vi full-thickness cornea and conjunctiva-sclera-choroid-retina. The drug fluxes and
permeability coefficients were calculated for each compound and tissue. 39
molecular descriptors were obtained for our compounds from different online
databases and correlated with their permeability coefficient using Spearman’s
rho. Results: 1. Irbesartan and candesartan reached maximum concentrations in the aqueous humour of the treated eyes three hours after administration. Cediranib maleate
was found in all studied tissues, and the highest concentrations in the retina
and vitreous were found 1 hour after the administration. 2. Irbesartan and candesartan showed an IOP lowering effect that was equivalent to that of timolol four hours after the administration. 3. Regarding the in vitro permeability data, 22 out of 27 compounds (81%)
showed a higher permeability across conjunctiva-sclera-choroid-retina
compared with the full-thickness cornea. The mean permeability of the
noncorneal route was 2.9 times higher than the cornea. The correlation
analysis showed that charge, mass and size, lipophilicity, and the ability to
form hydrogen bonds were the most relevant properties for corneal
permeability, while lipophilicity and the number of rings and rotatable bonds
were more important for the noncorneal route.
Discussion: The drugs were found at pharmacologically relevant concentrations in both
anterior and posterior segments of the eye after topical administration of cyclodextrinbased formulations. These results indicate a local delivery that could contribute to minimizing systemic drug absorption while replacing the need for invasive drug delivery techniques. Irbesartan and candesartan successfully lowered the IOP in rabbits when topically administered, suggesting the potential for a new class of glaucoma drugs. Our in vitro data suggest that, for many compounds, the noncorneal route could
represent a more effective, and possibly the only way of drug delivery to the posterior
segment following topical administration
Stjórnun á fordæmalausri áhættu: Óstöðugar fjallshlíðar á Íslandi og Grænlandi
No full textClimate change is contributing to shifts in the magnitude and scale of hazards, and the emergence of environmental risks in areas where they were previously unknown. In the Öræfi district of south-east Iceland, a fracture discovered by farmers gathering sheep on the Svínafellsheiði mountainside was the first indication that a large section of the slope was unstable. If the slope fails, the resulting landslide is predicted to contain 60 million cubic
metres of bedrock. The debris may remain deposited on the surface of the Svínafellsjökull glacier below; however, there is a chance that the landslide could incorporate ice from the glacial surface, and cause flooding or a tsunami in the proglacial lake. The potential flooding or tsunami represents the main risk for people and infrastructure downhill. The area is a nature tourism hub with approximately 30,000 tourists visiting the glacier each year.
An estimated 1,500 people spent time in the at-risk area each day in 2018.
This thesis aims to increase our understanding of how disaster risk management is conducted for unprecedented climate change-related hazards. This was done by examining the social dimensions of the unstable Svínafellsheiði slope from different angles including the contribution of local knowledge to newly emerging hazards, the effects of risk mitigation
measures on psychosocial wellbeing, risk communication with affected demographics, and planning for relocation. Using grounded theory ethnography, the study incorporates semi-structured interviews, participant observation, complete participation, document analysis, and a review of the literature. Comparisons are also made with landslide-triggered tsunami risk
management in Karrat and Uummannaq Fjords of Greenland. The research was conducted between September 2018 and May 2022.
This research highlights the need for official risk management processes to engage affected people as decision-makers, mitigate the psychosocial impacts of risk management policies, and ensure that all people living and working in exposed areas are informed about the risk and emergency response protocols. A key recommendation is that government authorities
pivot from determining risk management and relocation options, to providing a structure to underpin and support community agency. By identifying complex patterns of exposure and vulnerability, this research establishes a nuanced understanding of the risk that can help guide the risk management and community resilience to the unstable slope. The findings can inform risk management and relocation processes in other societies facing unprecedented
potentially-fatal climate change-related hazards.Loftslagsbreytingar valda sífellt fleiri og alvarlegri tegundum náttúruvár og
umhverfistengdar hættur koma nú betur í ljós á landsvæðum sem hafa jafnvel
aldrei áður þurft að kljást við slíkt. Í Öræfasveit, í heiðinni fyrir ofan
Svínafellsjökul, uppgötvuðu bændur í fjárleit sprungu í berggrunninum sem
var fyrsta vísbending um að stór hluti hlíðarinnar væri óstöðugur. Skríði
hlíðin af stað getur það valdið framhlaupi af allt að 60 milljónum rúmmetra
af efni. Framhlaupið gæti stöðvast fyrir neðan, á jöklinum sjálfum, en það er
líka hugsanlegt að það hrífi með sér ís af yfirborði jökulsins, ýti við
framhlaupi frá neðrihluta hans eða valdi flóðbylgju frá jökullóninu, sem allt
myndi hafa mikil áhrif á fólk og mannvirki á áhrifasvæðinu fyrir neðan.
Svæðið er vinsæll ferðamannastaður og árlega koma um 30.000 manns til að
skoða jökulinn. Árið 2018 komu um 1.500 manns daglega þangað sem
hættan er mest.
Doktorsritgerð þessi hefur það markmið að auka skilning á því hvernig
viðbragðsáætlanir og aðgerðir eru framkvæmdar þegar um er að ræða
óþekktar loftslagstengdar hættur. Rannsóknin felst í því að kanna hinar ýmsu
félagslegu hliðar þeirrar vár sem stafar af sprungunni í Svínafellsheiði, m.a.
út frá staðbundinni þekkingu á nýjum hættum af þessu tagi, kanna áhrif
viðbragðsáætlana á sálfélagslega líðan, skoða þau samskipti um vána sem
eiga sér stað milli ólíkra hópa og að varpa ljósi á áætlanir um brottflutning
fólks af hættusvæðinu. Notuð var etnógrafísk aðferð, með aðferðafræðilegri
nálgun grundaðrar kenningar, og var gögnum safnað með hálfopnum
viðtölum, þátttökuathugunum, skjalarýni, sem og víðtækri könnun á
heimildum á viðkomandi rannsóknasviði. Einnig var gerður samanburður á
því tilviki sem er í brennidepli rannsóknarinnar við annað sambærilegt tilvik,
þ.e. viðbrögð og áætlanir sem gripið var til þegar flóðbylgjur af völdum
framhlaups urðu í Karrat- og Uummannaqfjörðum á Grænlandi. Rannsóknin
var gerð frá september 2018 til maí 2022.
Í ritgerðinni eru færð rök fyrir því að við gerð viðbragðsáætlana og í
aðgerðum hins opinbera verði að hafa það fólk sem er í hættu með í ráðum,
að það þurfi að leitast við að milda þau sálfélagslegu áhrif sem stefna hins
opinbera í gerð viðbragðsáætlana hefur, og að ganga verði úr skugga um að
öllum sem búa og starfa á áhrifasvæði tiltekinnar náttúruvár sé gerð ljós sú
hætta sem af henni stafar og hvað neyðar- og viðbragðsáætlanir þar að
lútandi fela í sér. Ein af lykilniðurstöðunum er að hlutverk yfirvalda ætti
frekar að snúist um að efla íbúana sem virkan geranda í viðbrögðum og
aðgerðum en einblína eingöngu á viðbragðsáætlanir og brottflutning sem slík.
Rannsókn þessi sýnir fram á hve flókið það er fyrir samfélag að verav
berskjaldað fyrir náttúruvá og framlag hennar er blæbrigðaríkur skilningur á
þessari stöðu sem nýst gæti til áhættustjórnunar og aukinnar seiglu
samfélagsins á áhrifasvæði sprungunnar í Svínafellsheiði í Öræfasveit.
Rannsóknin er einnig framlag til áhættustjórnunar og áætlana um
brottflutning fólks á öðrum svæðum í heiminum þar sem í auknum mæli er
tekist á við náttúruvár af völdum loftslagsbreytinga, sem oft stofna lífi fjölda
fólks í hættu.This work was kindly supported by the Doctoral Grants of the University of Iceland Research Fund (Rannsóknasjóður Háskóla Íslands), Iceland [grant number 1010–101343, 2019–2022]