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Deep Learning Forecasts a Strained Turbulent Flow Velocity Field in Temporal Lagrangian Framework: Comparison of LSTM and GRU
Get PDFThe subject of this study presents an employed method in deep learning to create a model and predict the following period of turbulent flow velocity. The applied data in this study are extracted datasets from simulated turbulent flow in the laboratory with the Taylor microscale Reynolds numbers in the range of 90 < Rλ< 110. The flow has been seeded with tracer particles. The turbulent intensity of the flow is created and controlled by eight impellers placed in a turbulence facility. The flow deformation has been conducted via two circular flat plates moving toward each other in the center of the tank. The Lagrangian particle-tracking method has been applied to measure the flow features. The data have been processed to extract the flow properties. Since the dataset is sequential, it is used to train long short-term memory and gated recurrent unit model. The parallel computing machine DEEP-DAM module from Juelich supercomputer center has been applied to accelerate the model. The predicted output was assessed and validated by the rest of the data from the experiment for the following period. The results from this approach display accurate prediction outcomes that could be developed further for more extensive data documentation and used to assist in similar applications. The mean average error and R2 score range from 0.001–0.002 and 0.9839–0.9873, respectively, for both models with two distinct training data ratios. Using GPUs increases the LSTM performance speed more than applications with no GPUs.Peer Reviewe
Empirical vulnerability curves for Icelandic low-rise buildings based on zero-inflated beta regression model
Get PDFIn June 2000, two earthquakes of ~Mw6.5 struck in South Iceland, and in May
2008 the same region was hit again further west, with Mw6.3 event. Almost 5000 residential buildings were affected in each of these two seismic events. To fulfil insurance claims, detailed, and complete loss data were collected in each case, and the 2000 dataset and 2008 dataset were established. Having access to two high quality loss datasets from different size earthquakes, affecting the same building typologies in the same region, is rare to find in the literature. An advanced empirical vulnerability model based on zero-inflated beta regression was fitted to five building typologies, classified according to the GEM taxonomy system, independently for the 2000 dataset and the 2008 dataset. Status of seismic codes was considered when defining the building typologies. PGA was used as intensity measure. For all the five building typologies, the calibrated vulnerability functions and the fragility curves are substantially different from these two datasets. This indicates that PGA is not alone an adequate intensity measure to predict losses. The results also show that status of seismic code affects the performance of the buildings as one would like to see.The authors thank the Natural Catastrophe Insurance of Iceland for placing the earthquake damage database and other relevant information at their disposal. This work was partly financed by the SERICE project funded by a Grant of Excellence from the Icelandic Centre for Research (RANNIS), Grant Number: 218149-051. We also acknowledge support from the University of Iceland Research Fund
Strong ground motion in the epicentral area of the 2020-2021 earthquake swarm in the Reykjanes Peninsula, Iceland
Get PDFThe Geldingadalur eruption in the Reykjanes Peninsula on 19 March 2021 was
preceded by several earthquakes of volcano-tectonic origin throughout 2020 and 2021.
Seven earthquakes with magnitude M≥5 took place during the swarm, all of them recorded by the Icelandic Strong Motion Network operated by the Earthquake Engineering Research Centre of the University of Iceland. In this paper we present salient features of strong ground motion in the epicentral area caused by the swarm. Interestingly, earthquakes as small as M5.0 caused peak ground acceleration (PGA) larger than the 475-year return period PGA at a town near the epicentral area. At two recording stations, unusually high energy content at vibration periods <0.3s was detected, with spectral accelerations exceeding the design values. The largest recorded horizontal PGA was ~0.4g at Krýsuvík, station, which is the strongest PGA recorded in Iceland since the MW6.3 2008 Ölfus Earthquake. For this station we present horizontal-to-vertical spectral ratios indicating likely site-effects. We also compare the attenuation of PGA of the largest event of the sequence with two groundmotion prediction equations (GMPEs). The recorded PGA attenuation is well captured by a local GMPE.This work was partly financed by the SERICE project funded by a Grant of Excellence from the Icelandic Centre for Research (RANNIS), Grant number: 218149-051. The authors also acknowledge support from the University of Iceland Research Fund.
The authors wish to thank the Icelandic Meteorological Office for access to the earthquake catalogue.Peer Reviewe
Ground deformation caused by viscoelastic relaxation and its role in the 2015-2021 post-eruptive period at the Bárðarbunga volcanic system, Iceland
Get PDFPost-eruptive deformation following volcanic eruptions may originate from continued magma movements, or reflect delayed and continued Earth adjustment due to co-eruptive events, often referred to as viscoelastic relaxation. Post-eruptive deformation can continue for years, and it is challenging to reveal the details of the underlying processes. In this PhD project, the ground deformation in a post-eruptive period at the Bárðarbunga volcanic system is mapped using Global Navigation Satellite System (GNSS) geodesy and Interferometric analysis of Synthetic Aperture Radar satellite images (InSAR).
The Bárðarbunga volcanic system is a laboratory area for this study because of the large-scale magma transfer during an eruption in 2014-2015, lasting six months. Magma flowed laterally along a 48-km-long dike from a magma body below the Bárðarbunga caldera. An eruption occurred at the northern end of the dike. During this time, the Bárðarbunga caldera collapsed 65 m.
Data collected using GNSS and InSAR techniques provide information on the post-rifting ground deformation both in the area near the Bárðarbunga caldera and the northernmost segment of the Bárðarbunga-Holuhraun dike north of the Vatnajökull ice cap. The background deformation signal in the area includes plate spreading (18-19 mm/yr in the horizontal direction) and glacial isostatic adjustment (GIA, less than 7 mm/yr in the horizontal direction and up to 33 mm/yr in the vertical direction). Velocities from the plate spreading and GIA are subtracted from the observed deformation field, to isolate the movements caused by other processes, referred to as corrected average velocity.
The corrected average velocity field has horizontal movements away from the caldera and the dike in the post-eruptive period. The surface close to the caldera and near the dike uplifted. Around the caldera, the GNSS station closest to the caldera has maximum corrected uplift velocity of about 20 mm/yr and maximum corrected horizontal velocity away from the caldera of about 111 mm/yr between 2015 and 2018. Other stations show smaller average velocities. A GNSS station 16 km away from the caldera shows corrected subsidence up to about 12 mm/yr. Around the dike, the maximum corrected uplift rate between 2015-2020 measured by InSAR is ~12 mm/yr. Two GNSS stations that are 20 km apart on different sides of the dike experience baseline lengthening at a corrected rate of ~19 mm/yr in the direction perpendicular to the strike of the dike.
A two-layer model with an elastic layer on top of a viscoelastic half-space is used to model viscoelastic relaxation. Three possible explanations are explored for the corrected post-eruptive deformation around the Bárðarbunga caldera: viscoelastic relaxation, renewed magma inflow, or a combination of the processes. Our study suggests that viscoelastic relaxation and/or renewed magma inflow can explain the observed deformation. It is hard to tell the difference between the processes by only comparing the average velocity field.
The post-eruptive deformation around the Bárðarbunga-Holuhraun dike is also modeled with the two-layer viscoelastic model. The best fitting model has a 4 x 10^18 Pa s viscoelastic half-space below 18 km thick elastic layer. A comparable fit is found for a 2 km thick elastic layer, underlain by a viscoelastic half-space with viscosity 12 x 10^18 Pa s.
The study of the deformation around the Bárðarbunga caldera suggests viscoelastic relaxation generates a similar average velocity field as magma inflow in the post-eruptive period. To better understand the difference between the two processes, it is explored if stress field and displacement time series differ. Modeling results suggest that the stress fields generated by these two processes are similar, and it is hard to distinguish them. The temporal variation of the horizontal surface displacement from the viscoelastic relaxation decays with time, comparable to exponential decay. The decay constant that describes the decay rate varies with distance from the source in the viscoelastic relaxation model. For magma inflow into a source of constant geometry, the rate of magma inflow may decay with time, causing time-dependent surface displacement. However, the decay constant is then the same over the study area. At the Bárðarbunga volcano, the continuous GNSS stations show decay of horizontal displacement. The decay constants differ somewhat at different locations but are all less than five years. A viscoelastic model with the viscosity 1-6 x 10^18 Pa s has a decay constant larger than ten years. Using a model with different source geometry or a different type of viscoelastic relaxation model may better explain the post-eruptive deformation at the Bárðarbunga volcano.Jarðskorpuhreyfingar á eldfjöllum eftir eldgos geta orsakast af mörgum ferlum, m.a.
áframhaldandi kvikuhreyfingum, eða verið svörun jarðar við fyrri atburðum og kvikhreyfingum í eldgosi, með taftíma. Slík síðbúin svörun jarðskorpunnar með taftíma
getur orsakast af seigfjaðrandi efnishegðun jarðar. Jarðskorpuhreyfingar eftir eldgos
geta varað árum saman og erfitt getur reynst að varpa skýru ljósi á ferlin sem stjórna
slíkum hreyfingum. Í þessu doktorsverkefni eru jarðskorpuhreyfingar í eldstöðvakerfi
Bárðarbungu eftir meiriháttar eldsumbrot metnar með GNSS (Global Navigation Satellite System) og InSAR (Interferometric analysis of Synthetic Aperture Radar satellite
images) mælingum á jarðskorpuhreyfingum.
Eldstöðvakerfið er valið sem rannsóknasvæði vegna mikillar tilfærslu kviku í eldgosi 2014-2015, sem stóð í 6 mánuði. Kvika streymdi lárett eftir um 48 km löngum
kvikugangi úr kvikueiningu undir öskju Bárðarbungu, og eldgos varð við norðurenda
gangsins. Bárðarbunguaskjan seig um 65 m.
Gögn sem safnað var með GNSS og InSAR mælingum veita upplýsingar um jarðskorpuhreyfingar á árabilinu eftir eldgos og kvikuinnskot, bæði á svæðinu næst Bárðarbunguöskjunni og eins við norðurenda kvikugangsins, norðan Vatnajökuls. Bakgrunnsjarðskorpuhreyfingar á rannsóknarsvæðunum stafa af flekareki (18-19 mm/ári lárétt
gliðnun) og vegna svörun jarðar við þynningu jökla (færslur minni en 7 mm/ári í lárétta
stefnu, en allt að 33 mm/ári lóðrétt). Leiðrétt hraðasvið er metið því að draga frá færslur
vegna þessara hreyfinga, til að meta jarðskorpuhreyfingar af öðrum ástæðum.
Leiðrétt meðal-hraðasvið sýnir láréttar færslu í átt frá Bárðarbunguöskjunni og
kvikuganginum á árunum eftir gos. Svæði næst öskjunni og ganginum rísa. GNSS stöð
sem liggur næst öskjunni hefur hæstan meðalrishraða, eða um 20 mm/ári, og hæstan
láréttan færsluhraða, eða um 111 mm/ári, á árunum frá 2015 til 2018. Aðrar stöðvar
sýna miklu lægri meðalhraða. GNSS stöð 16 km frá öskjunni sýnir leiðréttan sighraða
um 12 mm/ári. Í nágrenni kvikugangsins er leiðréttur meðalrishraði metin með InSAR
um 12 mm/ári. Tvær GNSS stöðvar sitt hvoru megin við kvikuganginn sýna að leiðrétt
fjarlægð milli þeirra lengist um 19 mm/ári.
Tvískipt jarðlagalíkan, með láréttu lagi af fjaðrandi efni ofan á seigfjaðrandi undirlagi er notað til að líkja eftir seigfjaðrandi hreyfingum. Þrjár mögulegar orsakir hreyfinga
í kringum Bárðarbunguöskjuna eru metnar: seigfjaðrandi efnishegðun, kvikuinnstreymi
eftir eldgos, eða samblanda þessara ferla. Ef hreyfisviðið er skýrt sem afleiðing af seigfjaðrandi svörun, þá passar seigjan 3 × 1018 Pa s best við niðurstöður. Líkanreikningar
sýna að seigfjaðrandi svörun og/eða kvikuinnflæði getur útskýrt niðurstöðurnar, en erfitt
er að greina á milli þessara ferla eingöngu með því að nota meðalhraða.
Jarðskorpuhreyfingar á tímabilinu eftir eldgos og kvikuinnskot í nágrenni við kvikuganginn voru notaðar til að skorða sambærilegt líkan fyrir það svæði. Það líkan sem
v
fellur best að mæligögnum þar er með 4 × 1018 Pa s seigju undir 18 km þykku lagi með
fjaðrandi hegðun. Sambærilegt samræmi við mælingar fæst þó með líkani sem er með 2
km þykkt lag af fjaðrandi efni, með undirlagi með seigjuna 12 × 1018 Pa s.
Rannsóknin á aflögun jarðskorpunnar í kringum Bárðarbunguöskjuna sýnir að seigfjaðrandi svörun jarðskorpunnar býr til meðal-hraðasvið mjög líkt því sem getur orsakast af kvikuinnstreymi í rætur eldstöðvar á árum eftir gos. Til að meta frekar mismuninn á þessum ferlum, þá voru kannaðar spennubreytingar samfara þeim, sem og hvernig færslur á yfirborði jarðar breytast með tíma. Líkanreikningar sýna að spennusvið vegna þessara ferla geta verið mjög sambærileg og erfitt að greina á milli þeirra. Láréttar
færslur á yfirborði vegna seigfjaðrandi svörunar dvína með tíma líkt og veldisfall, og
þá er stuðullinn sem lýsir dvínuninni breytilegur með fjarlægð frá uppsprettunni. Fyrir
kvikuinnflæði í kvikueiningu sem breytir ekki um geometríu, þá kann kvikuinnflæði
einnig að að dvína með tíma. Stuðull sem lýsir dvínandi jarðskorpuhhreyfingum verður
í því tilviki hins vegar sá sami í öllum fjarlægðum frá uppsprettunni. Samfelldar GNSS
stöðvar næst Bárðarbungu sýna dvínun hreyfinga sem hægt er að fella að veldisfalli.
Dvínunarstuðlarnir eru aðeins breytilegir eftir fjarlægð, en í öllum tilvikum lægri en
5 ár. Seigfjaðrandi líkan með seigju 1-6 × 1018 Pa s seigju hefur hinsvegar dvínunarstuðla hærri en 10 ár. Líkan með annari geometríu fyrir uppsprettu hreyfinganna eða
önnur tegund af seigfjaðrandi líkani en hér könnuð getur e.t.v. úskýrt betur færslur
jarðskorpunnar á árunum eftir eldgos.This PhD project was funded by the Research Fund of University of Iceland, and the European Commission, through H2020 EUROVOLC project
Lyfjalosun úr lyfjagjafarbúnaði: Útleiðsla og notkun á margsvæða smábútalíkani
No full textThe effectiveness of a drug treatment regimen relies on the efficient delivery to afflicted target areas. Drug delivery devices aim to achieve a sustained release and maintain a steady drug concentration level that falls within a therapeutic range. Polymeric delivery systems are widely studied for the local treatment of brain tumors, vascular diseases, ocular diseases, reproductive health, and wound healing. Controlled release systems are developed to control drug exposure over time, to facilitate drug penetration of physiological barriers, to minimize drug loss from premature elimination, and to target the desired site of action while decreasing drug exposure elsewhere. It is decisive to know which device properties are crucial to provide the desired system performance, especially considering that challenges encountered during production can more efficiently be addressed if there is a thorough understanding of how drug release is controlled.
This thesis describes the derivation of a finite element drug transport model that provides a framework for simulating drug release from drug delivery devices. The combined effects of different drug solute mechanisms affecting transport, including diffusion, dissolution, binding, mass transfer resistance and partitioning between phases were incorporated. The framework was verified with purpose built models to compare against data from experiments and to deduce physical parameter values. Simulations of Franz diffusion cell experiments were conducted using one dimensional multi-layer models but simulations of release experiments involving lenses relied on three dimensional models with rotational symmetry, which resulted in two dimensional multi-region models. The numerical model maintains important aspects of the mathematical model regarding mass conservation and distribution of eigenvalues. In the case of hydrogels, it was shown how polymer-solute interactions, which influence partitioning, affect the interface driving force, emphasising the necessity of properly modelling interface mass transfer.Árangur lyfjameðferðar er háður því að skilvirkur lyfjaflutningur verði til þeirra líkamshluta sem lyfjunum er ætlað að verka á. Markmið lyfjagjafarbúnaðar er að ná fram viðvarandi lyfjalosun til að viðhalda þeim styrkleika sem fellur innan meðferðarramma. Rannsóknir hafa verið gerðar á fjölliðalyfjagjafakerfum til meðferðar við heilaæxli, æðaskjúkdómum, augnsjúkdómum og við sáragræðslu. Stýrð losunarkerfi eru þróuð til að halda langtíma neikveiðum áhrifum í skefjum, að greiða fyrir flutningi í gegnum lífeðlisfræðilegar hindranir, að lágmarka lyfjatap vegna ótímabærs brottfalls og til að flytja lyf á tilætlaðan stað meðan skaðleg áhrif annars staðar eru lágmörkuð. Það skiptir sköpum að þekkja hvaða eðliseiginleikar kerfis hafa mest áhrif á flutning til að losunarkerfi nái tilætluðum árangri, en einnig til að takast á við áskoranir á framleiðslustigi með skilvirkari hætti.
Ritgerðin lýsir útleiðslu á almennu lyfjaflutningsbútalíkani til að herma lyfjalosun frá lyfjagjafarbúnaði. Tekið er tillit til samverkandi áhrifa mismunandi þátta sem hafa áhrif á flutning lyfs sem uppleysts efnis, þar á meðal sveimis, upplausnar fastra efna, efnabindingar, skiptingar og mótstöðuáhrifa efna milli fasa. Almenna líkanið var sannreynt með smíði sértækra líkana af tilraunum, þá sérstaklega til að bera saman við tilraunagögn og til að stika líkanabreytur. Hermun Franz flæðisellu tilrauna var byggð á einvíðum marglaga líkönum en hermun losunartilrauna með linsum bygðist á þrívíðum líkönum með snúningssamhverfu, sem verða þá í reynd tvívið margsvæða líkön, þar sem sýnt er fram á að tölulega líkanið viðhaldi mikilvæga eiginleika stærðfæðilíkansins eins og massavarðveislu og dreifingu eigingilda. Sérstakt tillit var tekið til fjölliðukerfa, sýnt var framm á hvernig víxlverkandi áhrif lyfs við fjölliðu, þar á meðal skiptistuðulsáhrif, höfðu áhrif á efnaflutning yfir jaðar.This work was financially supported by the Technical Development Fund (grant no. 13-1309) as part of the jointly funded European M-Era-Net project SurfLenses (M-ERA.NET/0005/2012) as well as University of Iceland Research Fund
Plotkin's call-by-value λ-calculus as a modal calculus
Get PDFIn the authors' previous analysis of the calling paradigms call-by-name and call-by-value through Girard's and Gödel's embeddings into the S4 modal logic, an asymmetry remains: the two paradigms are unified by the call-by-box paradigm of the modal target, but only for call-by-name can one say that the paradigm exists, up to isomorphism, inside the modal target. In this paper, we show that, by pushing further the modal analysis, a symmetric situation is revealed, in that ordinary and Plotkin's λ-calculi are shown to truly co-exist inside a simple modal calculus.The first and second authors were partially financed by Portuguese Funds through FCT (Fundação para a Ciência e Tecnologia) within the projects UIDB/00013/2020 and UIDP/00013/2020. The third author was supported by the Estonian Ministry of Education and Research institutional research grant IUT33-13 and the Estonian Research Council team grant PRG1210. All the three authors were supported by the EU COST action
CA15123 EUTYPES.Peer Reviewe
Focusing on metabolic modelling and engineering of Rhodothermus marinus and Lactobacillus reuteri
Get PDFThe current climate crisis and human overpopulation demands more sustainable technologies for industrial chemical synthesis, such as biorefineries. The aim of this project was to study the potential of two non-model microorganisms to produce industrially relevant chemicals from renewable biomass, through metabolic modelling and engineering. Model organisms are often used for these applications, but due to extreme environments that can occur in biorefineries, this is not always optimal. Rhodothermus marinus is a thermophilic bacterium that can use polysaccharides from complex biomass and produces carotenoids. Lactobacillus reuteri is a bacterium that has a wide growth temperature range compared to other LAB and is a native producer of 1,3-propanediol and B12-vitamin.
Genome-scale metabolic models of the two species were reconstructed, manually curated and validated. The L. reuteri model was used to predict how a gene deletion and different carbon sources affected the flux of main metabolites in central metabolism, and to suggest strategies for 1-propanol production. Different aspects of the R. marinus metabolism were reviewed and subsequently, both cell densities and carotenoid production were investigated under different growth and genotype conditions.
Native R. marinus strains produce γ-carotenoids in large quantities. The carotenoid biosynthetic genes and pathway in R. marinus were studied with the aim of making a platform strain for production of carotenoids of industrial interest. Subsequently, a mutant was obtained that produced lycopene, which is a common precursor to the synthesis of a variety of carotenoids. This is the first R. marinus strain that produces an industrially relevant carotenoid, which in turn is a vital step towards obtaining a robust R. marinus strain that can be used in industry.
Genetic engineering of R. marinus is currently limited by marker selection, which are difficult to reuse for further genetic manipulation. A thermostable CRISPR-Cas9 system was developed, which gives hope for more advanced and easier genetic engineering of R. marinus in the future. This work strengthened our understanding on the metabolism of R. marinus and L. reuteri, it produced metabolic models that increase their utility as cell factories and it provided a thermophilic platform strain for industrial carotenoid production.Ranní
Studies on temporal trends in epidemiology, cancer, elective surgery and local infectious outbreaks
Get PDFSepsis is a leading cause of admission to intensive care units (ICU) worldwide and mortality rates remain high despite advances in organ support. Awareness of the syndrome has increased substantially in the past 20 years, after the publication of several studies that showed improved outcome with relatively simple measures, such as early administration of fluid and antibiotics. These studies were the impetus for an educational treatment campaign with the goal of reducing mortality from sepsis. Several studies in recent years have shown an increasing incidence of sepsis, and declining mortality rates. Many of those are based on diagnosis codes with risk of bias due to increased use of sepsis codes as a result of this heightened awareness of sepsis. Medical care may contribute to the development of sepsis, not only by weakening host defences with immunosuppressive therapy and surgical procedures, but also on rarer occasions by contamination, highlighting the importance of scrutinous observation of hospital-acquired infections.
The overall aim of this thesis was to create a broad overview of sepsis requiring admission to intensive care units in a nationwide cohort in Iceland, with a special focus on several patient groups. Trends in incidence, treatment and outcome were assessed, with special consideration given to cancer patients with sepsis, patients developing sepsis after surgery and the detection of nosocomial infection clusters and their impact.
The four studies (I-IV) were retrospective cohort studies using two cohorts of patients. For the first cohort, all ICU admissions in Iceland were screened for the presence of severe sepsis or septic shock on admission during calendar years 2006, 2008, 2010, 2012, 2014 and 2016 using clinical criteria and chart review. This database of sepsis patients (971 patients) was used in studies I,II and III. Additionally, for study III, the number and type of all surgical procedures performed at the largest hospital in Iceland, Landspitali, during the same study years were collected. For study IV, a second database was constructed for all patients who underwent open-heart surgery in Iceland from 2013-2017 (973 patients).
In study I the population incidence of sepsis requiring intensive care did not change over the 11-year study period and mortality rates remained stable as well. Changes in treatment observed over the study period included earlier measurements of serum lactate and a reduction in the use of colloids and blood products, but no change was seen in the timing of antibiotic administration.
In study II it was observed that 24% of all sepsis patients admitted to the ICU had an underlying malignancy and the prevalence of such admissions was higher in the latter half of the study period. Patient characteristics and outcome varied between cancer types. Patients with metastatic disease were less likely to receive invasive mechanical ventilation, had a short duration of stay in the ICU and high mortality.
In study III, the overall incidence of sepsis requiring intensive care after elective surgery was low (0.19%) at Landspitali, but varied considerably between surgical procedures. The highest incidence was observed after pancreaticoduodenectomy and oesophageal resections, but the largest number of patients had undergone colorectal surgery. ICU length of stay was long, with similar mortality rates as in other sepsis patients. The rates of insufficient initial empirical antimicrobial therapy were high.
In study IV, two nosocomial clusters of infections are described that were related to the use of surface-damaged TEE (transoesophageal echocardiography) probes used during cardiac surgery. Clinical presentation was most often postoperative pneumonia but fulminant septic shock and cases of endocarditis were seen as well. The overall incidence of postoperative infections after cardiac surgery in Iceland was 20%, most frequently pneumonia and superficial wound infections.
From these studies it is concluded that by using clinical criteria in a nationwide cohort, the incidence and outcome of sepsis requiring admission to intensive care units did not change over an 11-year period. Recent treatment campaigns had limited effect on sepsis management. Cancer is a frequent comorbidity in sepsis patients but the extent of intensive care was limited in patients with advanced disease. Major oncological procedures are the most common cause of postoperative sepsis following elective surgery, and the choice of empirical antimicrobial therapy needs careful consideration in this setting. Examples of nosocomial outbreaks of infections are described which emphasize the importance of continuous infection surveillance systems.Sýklasótt (sepsis) er ein algengasta ástæða innlagna á gjörgæsludeildir í heiminum og er dánartíðnin há þrátt fyrir framfarir í stuðningsmeðferð. Mikil vitundarvakning hefur verið um heilkennið á síðastliðnum 20 árum í kjölfar birtinga fjölda rannsókna sem sýndu fram á betri lifun með tiltölulega einfaldri meðferð, til dæmis skjótri gjöf vökva og sýklalyfja. Þessi vitneskja varð hvatinn að alþjóðlegu átaki í meðferð sýklasóttar sem hafði það að markmiði að draga úr dánartíðni vegna sjúkdómsins. Nokkur fjöldi rannsókna á síðastliðnum árum hefur sýnt vaxandi nýgengi sýklasóttar, ásamt lækkandi dánarhlutfalli. Þessar rannsóknir hafa margar verið byggðar á greiningarkóðum í sjúkraskrám, en talið er að hin nýlega vitundarvakning um sýklasótt geti skekkt niðurstöður slíkra rannsókna vegna bættrar skráningar. Sýklasótt er þekktur fylgikvilli ýmissa læknismeðferða sem hafa áhrif á varnir líkamans, til dæmis krabbameinslyfjameðferða og skurðaðgerða. Sjaldgæft er að sjúklingar veikist af völdum mengaðra áhalda, íhluta eða lyfja en stöðug árvekni gagnvart sýkingum er nauðsynleg til að uppgötva slík tilfelli fljótt.
Heildarmarkmið þessa verkefnis var að lýsa faraldsfræði sýklasóttar sem leiðir til innlagna á gjörgæsludeildir hjá heilli þjóð hér á Íslandi og skoða sérstaklega nokkra undirhópa. Metið var hvort breytingar hefðu orðið á nýgengi, meðferð og afdrifum sjúklinga yfir tíma, auk þess að lýsa nánar krabbameinssjúklingum með sýklasótt, sjúklingum sem fengu sýklasótt í kjölfar valskurðaðgerða og áhrifum hópsýkinga tengdum vélindaómtæki.
Rannsóknirnar fjórar (I-IV) sem ritgerð þessi byggir á voru allar aftursæjar áhorfsrannsóknir á tveimur stórum hópum sjúklinga. Farið var yfir gögn allra sjúklinga sem lögðust inn á gjörgæsludeildir á Íslandi og metið hvort þeir uppfylltu skilyrði fyrir alvarlegri sýklasótt eða sýklasóttarlosti við innlögn. Rannsóknartímabilið voru árin 2006, 2008, 2010, 2012, 2014 og 2016 og var stuðst við gögn í sjúkraskrám sjúklinga. Þessi gagnagrunnur tók til 971 sýklasóttarsjúklings og var notaður í rannsóknum I-III. Fyrir rannsókn III var að auki fenginn listi yfir allar skurðaðgerðir sem framkvæmdar voru á Landspítala sömu ár. Fyrir rannsókn IV voru fundnir allir sjúklingar sem gengist höfðu undir opna hjartaaðgerð á Íslandi á árunum 2013-2017 og voru þeir 973.
Í rannsókn I voru helstu niðurstöður þær að nýgengi sýklasóttar á íslenskum gjörgæsludeildum breyttist ekki yfir 11 ára rannsóknartímabilið og dánarhlutfall var einnig stöðugt. Nokkrar breytingar sáust í meðferð sjúklinga yfir rannsóknartímann, svo sem skjótari mælingar á mjólkursýru í blóði eftir komu á bráðamóttöku og minni notkun sterkjulausna og blóðhluta, en engin breyting varð hins vegar á tímalengd að gjöf sýklalyfja eftir komu á bráðamóttöku.
Niðurstöður rannsóknar II sýndu að 24% allra sýklasóttarsjúklinga á gjörgæsludeildum hafa undirliggjandi krabbamein og innlögnum krabbameinssjúklinga með sýklasótt fjölgaði á seinni hluta rannsóknartímabilsins. Eðli sýkinga og afdrif sjúklinga voru mismunandi eftir tegundum krabbameina. Sjúklingar með meinvörp voru síður líklegri til að fá meðferð með öndunarvél, legutími þeirra á gjörgæsludeild var stuttur og dánartíðni há.
Í rannsókn III reyndist tíðni sýklasóttar eftir valaðgerðir á Landspítala vera lág, eða 0,19%, en hún var mjög breytileg milli aðgerðartegunda. Hæst var tíðnin eftir bris- og skeifugarnarbrottnám (Whipple aðgerð) og brottnám á vélinda en mesti fjöldi sjúklinga í rannsóknarhópnum hafði gengist undir brottnám á ristli. Dvalartími á gjörgæsludeild var langur og dánartíðni sambærileg við aðra sýklasóttarsjúklinga. Tíðni ófullnægjandi fyrstu sýklalyfjameðferðar var há.
Tilefni rannsóknar IV voru tvær hópsýkingar sem tengdar voru lækningatæki, ómhaus sem notaður er við hjartaómskoðun um vélinda í öllum hjartaaðgerðum. Í örfínum sprungum á tækinu lifðu bakteríur af hefðbundna sótthreinsun og bárust í sjúklinga. Birtingarmynd þessara sýkinga var oftast lungnabólga á fyrstu dögum eftir aðgerð en sýklasóttarlost og hjartaþelsbólga komu einnig upp. Til að meta áhrif þessara hópsýkinga var tekinn saman gagnagrunnur yfir allar opnar hjartaaðgerðir yfir fimm ára tímabil. Tíðni sýkinga eftir hjartaaðgerðir á Íslandi var 20%, algengastar voru lungnabólgur og grunnar skurðsárasýkingar.
Af þessum rannsóknum, sem byggja á vönduðum faraldsfræðigögnum fyrir heila þjóð, má álykta að faraldsfræði sýklasóttar sem leiðir til innlagna á gjörgæsludeildir hefur ekki breyst yfir 11 ára tímabil. Nýlegt átak í meðferð leiddi ekki til mikilla breytinga. Krabbamein eru algeng hjá sýklasóttar-sjúklingum en takmarkaðri gjörgæslumeðferð var beitt hjá sjúklingum með langt genginn sjúkdóm. Stærri kviðarholsaðgerðir vegna krabbameina voru algengasta orsök sýklasóttar eftir valaðgerðir og vanda þarf val fyrstu sýklalyfja hjá þessum sjúklingahópi. Hópsýkingar eftir hjartaaðgerðir sýna fram á mikilvægi þess að vera vakandi fyrir óvanalegu mynstri sýkinga.Vísindasjóður Landspítal
Samanburður á virkni, öryggi og meðferðarheldni blóðþynningarlyfja um munn
No full textOral anticoagulants (OACs) are among the most commonly used medication worldwide. Vitamin K antagonists, such as warfarin, were the only available oral anticoagulants for over 60 years. However, in the 2010s, novel direct oral anticoagulants (DOACs) were approved that act by directly inhibiting either factor II (dabigatran) or factor X (apixaban, rivaroxaban, and edoxaban). The results of the initial randomized controlled trials demonstrated that DOACs were associated with similar thromboembolic rates and lower major bleeding rates compared to warfarin. As a result, DOACs are currently considered first-line therapy for patients with atrial fibrillation and venous thromboembolism. However, randomized controlled trials comparing DOACs head-to-head are currently lacking, and previous observational studies have important limitations. Additionally, data are largely lacking on other outcomes such as rates of upper and lower gastrointestinal bleeding (GIB) and epistaxis event rates. Similarly, it is still unknown whether medication adherence differs between warfarin and DOACs.
The aims of this thesis were to compare the efficacy, safety, and adherence of different oral anticoagulants. Therefore, 5 studies were designed and are presented in 5 distinct papers. Specifically, the aim of paper I was to compare rates of thromboembolism and major bleeding between different DOACs, the aim of paper II was to compare rates of any clinically relevant GIB between DOACs, the aim of paper III was to compare rates of upper and lower GIB between warfarin and DOACs, the aim of paper IV was to compare rates of epistaxis between warfarin and DOACs, and the aims of paper V was to compare the likelihood of nonadherence between different OACs.
A study outcome database was created that included all patients in Iceland who filled a prescription for an OAC from 1 March 2014 to 28 February 2019. The database combined data from the Icelandic Medicine Registry; the electronic healthcare databases of Landspitali University Hospital and the regional hospitals of Akranes, Akureyri, Ísafjörður, and Neskaupsstaður; the electronic healthcare databases of the primary healthcare centers around the country; and the Icelandic death registry. All thromboembolic and major bleeding events were manually verified by chart review. The study population included new users of apixaban, dabigatran, rivaroxaban, and warfarin (for papers III-V). Inverse probability weighting was used to yield balanced study groups and bleeding and thromboembolic events were compared using Cox regression. Kaplan-Meier curves were used to visualize the data. Nonadherence, defined as proportion of days covered below 80%, was compared between groups using logistic regression. Similarly, logistic regression was used to estimate patient characteristics associated with nonadherence.
Rivaroxaban was associated with lower rates of any thromboembolism and myocardial infarction (MI) compared to dabigatran. Similarly, apixaban was associated with lower rates of MI compared to dabigatran, although this comparison did not reject the null hypothesis. Meanwhile, rivaroxaban was associated with higher rates of any major bleeding, any clinically relevant GIB, and any clinically relevant epistaxis compared to apixaban and dabigatran. Rates of stroke and all-cause mortality were similar between patients receiving different DOACs. Warfarin was associated with higher rates of upper but not lower or overall GIB compared to DOACs. Warfarin was also associated with higher epistaxis rates compared to DOACs. Dabigatran was associated with higher nonadherence compared to apixaban, rivaroxaban, and warfarin. Meanwhile, the odds of nonadherence was similar between apixaban, rivaroxaban, and warfarin. Apart from OAC type, female gender, hypertension, history of cerebrovascular accident, and concomitant statin use were all associated with lower odds of nonadherence.
In summary, rivaroxaban was associated with higher rates of bleeding compared to other DOACs but lower rates of any thromboembolism and MI compared to dabigatran. Warfarin was associated with high rates of upper GIB and epistaxis compared to DOACs. Dabigatran was associated with poorer adherence than other oral anticoagulants.RANNÍS (207113-051
Auðkenning efnaskiptabreytinga samfara EMT í brjóstaþekjuvef
No full textBreast cancer is the leading cause of cancer deaths among women in Iceland and worldwide. Epithelial-mesenchymal transition (EMT) is a cellular developmental process where epithelial cells assume mesenchymal-like phenotypes through degradation of the extracellular matrix, loss of adhesions, and increased mobility. It is believed that dissemination of cancer cells occurs partly following EMT. EMT contains a spectrum of epithelial-mesenchymal intermediate cell states that impart different degrees of malignancy. The ability of cells to assume these states is termed epithelial-mesenchymal plasticity (EMP). This project aimed at characterizing the metabolic phenotypes of EMT and EMP to obtain knowledge of breast cancer progression and to identify biomarkers and potential therapeutic targets for breast cancer treatment.
Proteomics analysis of cell models of EMT and EMP revealed changes to enzymes involved in glycan metabolism. UDP-glucose dehydrogenase (UGDH) and glutamine-fructose-6-phosphate transaminase 2 (GFPT2) were identified as the topmost altered glycan metabolic enzymes in EMT and EMP, respectively. UGDH converts UDP-glucose into UDP-glucuronic acid and is involved in the formation of hyaluronan in the extracellular matrix. GFPT2 influences the downstream formation of UDP-N-acetylglucosamine (UDP-GlcNAc) and protein O-GlycNAcylation. UGDH was associated with patient survival, affected cell proliferation, cell invasion, and the expression of the EMT marker SNAI1. siRNA-mediated knockdown of UGDH influenced glycerophosphocholine (GPC) and increased N-acetylaspartate (NAA) levels. GFPT2 similiarly influenced cell proliferation, migration, invasion, and expression of the EMT marker vimentin and was associated with claudin-low breast cancer. GFPT2 was shown to be a marker of oxidative stress, and knockdown of GFPT2 affected cystathionine levels and the mitochondrial enzyme sulfide quinone oxidoreductase (SQOR). Phosphoproteomics analysis indicated distinct phosphorylation profiles of epithelial versus mesenchymal cells. Specifically, pyruvate dehydrogenase kinases (PDHKs), serine/threonine-protein kinase (PAK1), and protein kinase A catalytic subunit α (PKACA) were differentially regulated across the mesenchymal cell lines tested.
In conclusion, these results suggest that UGDH and GFPT2 are central to changes that occur within glycan metabolism following EMT and EMP, respectively. Both enzymes were associated with cancer progression and GFPT2, specifically, may serve as a biomarker for cellular oxidative stress and claudin-low breast cancer. The work furthermore implicates UGDH in GPC and NAA metabolism.The Icelandic Center for Research (RANNÍS), Göngum Saman, and the doctoral grant from the University of Iceland (Doktorsstyrkir