Designing national electronic services in the public healthcare sector.

Papers 2 and 5 of this thesis are not available in Munin 2. Larsen, E. and LK. Johannessen (2014), 'Top-down or bottom-up? Building information system for healthcare', (manuscript) 5. Larsen, E. and G. Ellingsen (2014) 'Nothing free about free market', Rossitto, C. et al. (eds.), COOP Proceedings of the 11th International Conference on the Design of Cooperative Systems: COOP 2014 Nice, France, May 27 – 30, Proceedings of the 11th International Conference on the Design of Cooperative Systems, Springer: 69-85. Available at http://dx.doi.org/10.1007/978-3-319-06498-7_5This thesis deals with a socio-technical approach towards the development of inter-organisational ICT tools in healthcare. My overall case is Norwegian healthcare, and I investigated how national inter-organisational ICT tools were developed and why good results were difficult to achieve. Three public projects make up the basis of my data collection in which the main categories of data are interviews, participant observations and document studies. The data collection period spanned 2005 to the completion of this thesis. The main contribution of this thesis is the empirical insight into the long-standing establishment of inter-organisational health care services in Norway, a country that is characterised primarily by a publicly funded healthcare system. Studying this domain have demanded an inter-disciplinary approach because of the need to understand work practices, the implications of development and the complexities of information infrastructures, financing, project management, political governance and political philosophies. This study demonstrates how the strategies adopted by Norwegian authorities have changed. These strategies began as measures for invigorating the sector through the funding of public projects that establish specifications which vendors can use in developing new services. The strategies have transitioned into a top-down approach, with the Directorate of Health as the dominant stakeholder in a dedicated and specialised market. The recent strategy represents an approach that prioritises projects in a political process instead of basing such projects in extensive discussions in the healthcare sector. On the basis of the results, I suggest that a middle position be adopted in organising large-scale projects on integrated information systems. Such a strategy will give more power to the users of the information system. I believe that in real-world settings, a step-by-step strategy is favourable but requires good conditions for continued growth. Critical tasks are to break down large projects into a series of smaller ones, prioritise direct business value and assemble stable, full-time and cross-functional teams that execute these projects along a disciplined agile and optimisation approach

Pygmy resonance and low-energy enhancement in the γ\gamma-ray strength functions of Pd~isotopes

An unexpected enhancement in the $\gamma$-ray strength function, as compared to the low energy tail of the Giant Dipole Resonance (GDR), has been observed for Sc, Ti, V, Fe and Mo isotopes for $E_\gamma<4$ MeV. This enhancement was not observed in subsequent analyses on Sn isotopes, but a Pygmy Dipole Resonance (PDR) centered at $E_\gamma\approx8$ MeV was however detected. The $\gamma$-ray strength functions measured for Cd isotopes exhibit both features over the range of isotopes, with the low-energy enhancement decreasing- and PDR strength increasing as a function of neutron number. This suggests a transitional region for the onset of low-energy enhancement, and also that the PDR strength depends on the number of neutrons. The $\gamma$-ray strength functions of $^{105-108}$Pd have been measured in order to further explore the proposed transitional region. Experimental data were obtained at the Oslo Cyclotron Laboratory by using the charged particle reactions ($^{3}$He, $^{3}$He$^{\prime}\gamma$) and ($^{3}$He, $\alpha$$\gamma$) on $^{106,108}$Pd target foils. Particle$-\gamma$ coincidence measurements provided information on initial excitation energies and the corresponding $\gamma$-ray spectra, which were used to extract the level densities and $\gamma$-ray strength functions according to the Oslo method. The $\gamma$-ray strength functions indicate a sudden increase in magnitude for $E_{\gamma}>4$ MeV, which is interpreted as a PDR centered at $E_{\gamma}\approx8$ MeV. An enhanced $\gamma$-ray strength at low energies is also observed for $^{105}$Pd, which is the lightest isotope measured in this work. Further, the results correspond and agree very well with the observations from the Cd isotopes, and support the suggested transitional region for the onset of low-energy enhancement with decreasing mass number. The neutron number dependency of the PDR strength is also evident

Methodology for Health Care Process Modelling: Bringing the Health Care Complexity into Health IT System Development

Abstrac

Factors associated with coronary heart disease in COPD patients and controls

Background: COPD and coronary heart disease (CHD) frequently co-occur, yet which COPD phenotypes are most prone to CHD is poorly understood. The aim of this study was to see whether COPD patients did have a true higher risk for CHD than subjects without COPD, and to examine a range of potential factors associated with CHD in COPD patients and controls. Methods: 347 COPD patients and 428 non-COPD controls, were invited for coronary computed tomography angiography (CCTA) and pulmonary CT. Arterial blood gas, bioelectrical impedance and lung function was measured, and a detailed medical history taken. The CCTA was evaluated for significant coronary stenosis and calcium score (CaSc), and emphysema defined as >10% of total area <-950 Hounsfield units. Results: 12.6% of the COPD patients and 5.7% of the controls had coronary stenosis (p100 compared to 31.6% of the controls (p100 was 1.68 (1.12–2.53) in COPD patients compared with controls. Examining the risk of significant stenosis and CaSc>100 among COPD patients, no variable was associated with significant stenosis, whereas male sex [OR 2.85 (1.56–5.21)], age [OR 3.74 (2.42–5.77)], statin use [OR 2.23 (1.23–4.50)] were associated with CaSc>100, after adjusting for body composition, pack-years, C-reactive protein, use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), diabetes, emphysema score, GOLD category, exacerbation frequency, eosinophilia, and hypoxemia. Conclusion: COPD patients were more likely to have CHD, but neither emphysema score, lung function, exacerbation frequency, nor hypoxemia predicted presence of either coronary stenosis or CaSc>100.publishedVersio

Kommunen som pådriver for alternative boligløsninger. Rapport fra forskningsprosjektet Bopilot

Dagens boligsektor styres av private utbyggingsinteresser med kortsiktige mål og ivaretar i liten grad samfunnets langsiktige mål om boligløsninger som støtter sosialt inkluderende nabolag og et hverdagsliv som gir redusert klimagassutslipp. Derfor er det behov for nytenking i boligproduksjonen og tilbudet av boliger i norske byer, spesielt når det gjelder boliger for grupper som faller utenfor det kommersielle markedet. Kommunene spiller en sentral rolle som planleggingsinstans, godkjenningsmyndighet og grunneier, og som bestiller, utbygger og eier av kommunale utleieboliger og oppretter av kommunale stiftelser. I det forskningsdrevne innovasjonsprosjektet “Kommunen som pådriver for alternative boligløsninger (Bopilot)” har vi prøvd ut nye arbeidsmåter og samarbeidsmodeller som kan påvirke tilbudet i markedet og etterspørselen i boligsektoren. Det har også vært et mål å bidra til å realisere pilotprosjekter som kan vise alternative boligløsninger. Pilotprosjektene skal støtte opp under målsettingen om et mer klimavennlig og sosialt bærekraftig hverdagsliv ved å gjøre det mulig å bo og leve på mer miljøvennlige måter og i alternative sosiale fellesskap. De to kommunene som har deltatt i prosjektet, Bergen og Trondheim, har hatt ulike tilnærminger til utfordringene, og tidlig i prosessen definerte de hva de konkret ville jobbe med. I Bergen kommune var det et mål at Bopilot skulle bidra til å utvikle nye metoder å jobbe på for å få realisert byboliger som tilrettelegger for barnefamilier i by. Deling av arealer og funksjoner er en del av løsningen. De identifiserte to delmål: (1) Gjøre markedet interessert i deleboliger (påvirke/mobilisere markedet) og (2) Være en pådriver (internt i kommunen) for at deleløsninger blir realisert i utviklingen av Grønneviken. Bopilot i Trondheim kommune ønsket å se på alternative måter å bidra til å få realisert rimelige utleieboliger med forutsigbare leieforhold i tredje boligsektor. I første fase ønsket man å undersøke om selvbygging og gjenbruk kunne være en del av løsningen. Partnerne fra kommunen identifiserte følgende delmål: (1) Utvikle/undersøke Trondheim kommunes rolle som pådriver for etablering av rimelige utleieboliger med forutsigbare leieforhold og (2) bidra til realisering av pilotbygg på Svartlamoen med selvbygging og gjenbruk. I løpet av prosessen ble delmål 2 omformulert til å handle om hva den tredje boligsektor kan være i Trondheim i bredere forstand, og her ble det trukket inn to nye pilotprosjekter i samarbeid med Boligstiftelsen i Trondheim. Kommunene har prøvd ut en rekke metoder for å nå målene de har satt seg. Begge kommuner har gjennomført en digital spørreundersøkelse for å undersøke innbyggernes behov og interesse for alternative boligløsninger (deleløsninger og tredje boligsektor) og for å komme i kontakt med interesserte innbyggere. I Bergen ble det gjennomført Design Sprint for få fram nye romlige/arkitektoniske løsninger for boliger med deling og fellesskap, deretter en Hackaton for å utvikle en ny digital møteplass for innbyggere og utbyggere som vil bo og bygge boliger med deleløsninger. I Trondheim ble det gjennomført en rekke verksteder der bransjeaktører og representanter for boligstiftelser møtte folk fra kommunen og innbyggere rundt temaer som selvbygging, gjenbruk og boligstiftelser. Begge kommuner gjennomførte i tillegg en rekke seminarer og deltok i ulike sammenhenger både lokalt og nasjonalt med innlegg og foredrag om temaer relatert til Bopilot. I Bergen ble Bopilot avsluttet med en større boligutstilling gjennomført i samarbeid med KODE museer, med et omfattende program med kveldsmøter der aktuelle temaer ble tatt opp og debattert. I tillegg til Helen & Hards 1:1 utstillingsmodell basert på bofellesskapet Vindmøllebakken i Stavanger, var det utstilt over 20 utviklingsprosjekter som på ulike måter tester ut deleløsninger. Også i Trondheim ble det laget en utstilling hvor 18 plansjer som belyste tredje boligsektor og boligstiftelsenes rolle, ble stilt ut utendørs i Trondheim sentrum. Den utadrettede virksomheten førte til mye oppmerksomhet rundt prosjektet og flere medieoppslag. Prosjektet ble avsluttet med en sluttkonferanse som foregikk fysisk i Trondheim og Bergen samtidig, og som ble overført på nett for hele landet. Når denne rapporten skrives, er det for tidlig å si om Bopilot har lykkes med å styrke kommunenes innovasjonsarbeid med hensyn til boligutvikling – både når det gjelder realiseringen av pilotprosjektene (om og hvordan pilotene blir realisert) og om de nye måtene å jobbe på har bidratt til å endre arbeidsmåter på lengre sikt. Samtidig viser Bopilot at boligfeltet er sammensatt og angår mange ulike etater i kommunen. Derfor er det behov for et pådriverarbeid dersom en mer sosial bærekraftig boligutvikling skal settes tydeligere på dagsorden og bidra til en samlet satsing og realisering av nye løsninger. Aktivitetene som er gjennomført, har bidratt til å synliggjøre at det må jobbes på tvers av sektorer og etater i kommunen. Til tross for at overordnede mål er godt forankret i politiske føringer og overordnede plandokumenter, gjenstår det fortsatt mye for å realisere nye løsninger. Aktivitetene i begge kommunene har bidratt til å løfte fram nye problemstillinger i boligsektoren og satt i gang debatter om hvilke roller kommunene kan ha for å bidra til å realisere løsningene. Dette krever nye måter å arbeide på både innad i kommunene og utad mot markedet. Prosjektet har dessuten vist at det kan være hensiktsmessig å organisere en slik pådriverrolle på tvers av flere enheter og på utsiden av den tradisjonelle “linja” i kommuneadministrasjonen.publishedVersio

CosmoDC2: A Synthetic Sky Catalog for Dark Energy Science with LSST

This paper introduces cosmoDC2, a large synthetic galaxy catalog designed to support precision dark energy science with the Large Synoptic Survey Telescope (LSST). CosmoDC2 is the starting point for the second data challenge (DC2) carried out by the LSST Dark Energy Science Collaboration (LSST DESC). The catalog is based on a trillion-particle, 4.225 Gpc^3 box cosmological N-body simulation, the `Outer Rim' run. It covers 440 deg^2 of sky area to a redshift of z=3 and is complete to a magnitude depth of 28 in the r-band. Each galaxy is characterized by a multitude of properties including stellar mass, morphology, spectral energy distributions, broadband filter magnitudes, host halo information and weak lensing shear. The size and complexity of cosmoDC2 requires an efficient catalog generation methodology; our approach is based on a new hybrid technique that combines data-driven empirical approaches with semi-analytic galaxy modeling. A wide range of observation-based validation tests has been implemented to ensure that cosmoDC2 enables the science goals of the planned LSST DESC DC2 analyses. This paper also represents the official release of the cosmoDC2 data set, including an efficient reader that facilitates interaction with the data

Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure

Heart failure (HF) claims 250,000 lives per year in the US, and nearly half of these deaths are sudden and presumably due to ventricular tachyarrhythmias. QT interval and action potential (AP) prolongation are hallmark proarrhythmic changes in the failing myocardium, which potentially result from alterations in repolarizing potassium currents. Thus,we aimed to examinewhether decreased expression of the rapid delayed rectifier potassiumcurrent, IKr, contributes to repolarization abnormalities in human HF. Tomap functional IKr expression across the left ventricle (LV), we optically imaged coronary-perfused LV free wall from donor and end-stage failing human hearts. The LV wedge preparation was used to examine transmural AP durations at 80% repolarization (APD80), and treatment with the IKr-blocking drug, E-4031, was utilized to interrogate functional expression. We assessed the percent change in APD80 post-IKr blockade relative to baseline APD80 (&#916;APD80) and found that &#916;APD80s are reduced in failing versus donor hearts in each transmural region, with 0.35-, 0.43-, and 0.41-fold reductions in endo-, mid-, and epicardium, respectively (p = 0.008, 0.037, and 0.022). We then assessed hERG1 isoform gene and protein expression levels using qPCR and Western blot. While we did not observe differences in hERG1a or hERG1b gene expression between donor and failing hearts, we found a shift in the hERG1a:hERG1b isoform stoichiometry at the protein level. Computer simulations were then conducted to assess IKr block under E-4031 influence in failing and nonfailing conditions. Our results confirmed the experimental observations and E-4031-induced relative APD80 prolongationwas greater in normal conditions than in failing conditions, provided that the cellularmodel of HF included a significant downregulation of IKr. In humanHF, the response to IKr blockade is reduced, suggesting decreased functional IKr expression. This attenuated functional response is associated with altered hERG1a:hERG1b protein stoichiometry in the failing human LV, and failing cardiomyoctye simulations support the experimental findings. Thus, of IKr protein and functional expression may be important determinants of repolarization remodeling in the failing human LV.We thank the Translational Cardiovascular Biobank & Repository (TCBR) at Washington University for provision of donor/patient records. The TCBR is supported by the NIH/CTSA (UL1 TR000448), Children's Discovery Institute, and Richard J. Wilkinson Trust. We also thank the laboratory of Dr. Sakiyama-Elbert for the use of the StepOnePlus equipment We appreciate the critical feedback on the manuscript by Dr. Jeanne Nerbonne. This work has been supported by the National Heart, Lung & Blood Institute (NHLBI, R01 HL114395). K. Holzem has been supported by the American Heart Association (12PRE12050315) and the NHLBI (F30 HL114310).Holzem, KM.; Gómez García, JF.; Glukhov, AV.; Madden, EJ.; Koppel, AC.; Ewald, GA.; Trénor Gomis, BA.... (2016). Reduced response to IKr blockade and altered hERG1a/1b stoichiometryin human heart failure. Journal of Molecular and Cellular Cardiology. 96:82-92. https://doi.org/10.1016/j.yjmcc.2015.06.008S82929

Area of exposure and treatment challenges of malaria in Eritrean migrants: a GeoSentinel analysis

Background: Recent reports highlight malaria as a frequent diagnosis in migrants who originate from Eritrea. A descriptive analysis of GeoSentinel cases of malaria in Eritrean migrants was done together with a literature review to elucidate key attributes of malaria in this group with a focus on possible areas of acquisition of malaria and treatment challenges.Results: A total of 146 cases were identified from the GeoSentinel database from 1999 through September 2017, with a marked increase in 2014 and 2015. All patients originated from Eritrea and the main reporting GeoSentinel sites were in Norway, Switzerland, Sweden, Israel and Germany. The majority of patients (young adult males) were diagnosed with malaria following arrival in the host country. All patients had a possible exposure in Eritrea, but may have been exposed in documented transit countries including Ethiopia, Sudan and possibly Libya in detention centres. Most infections were due to Plasmodium vivax (84.2%), followed by Plasmodium falciparum (8.2%). Two patients were pregnant, and both had P. vivax malaria. Some 31% of the migrants reported having had malaria while in transit. The median time to onset of malaria symptoms post arrival in the host country was 39days. Some 66% of patients were hospitalized and nine patients had severe malaria (according to WHO criteria), including five due to P. vivax.Conclusion: sThe 146 cases of mainly late onset, sometimes severe, P. vivax malaria in Eritrean migrants described in this multi-site, global analysis reflect the findings of single-centre analyses identified in the literature search. Host countries receiving asylum-seekers from Eritrea need to be prepared for large surges in vivax and, to a lesser extent, falciparum malaria, and need to be aware and prepared for glucose-6-phosphate dehydrogenase deficiency testing and primaquine treatment, which is difficult to procure and mainly unlicensed in Europe. There is an urgent need to explore the molecular epidemiology of P. vivax in Eritrean asylum-seekers, to investigate the area of acquisition of P. vivax along common transit routes and to determine whether there has been re-introduction of malaria in areas, such as Libya, where malaria is considered eliminated, but where capable vectors and Plasmodium co-circulate

α-Synuclein Expression Selectively Affects Tumorigenesis in Mice Modeling Parkinson's Disease

Alpha Synuclein (α-Syn) is a protein implicated in mechanisms of neuronal degeneration in Parkinson's disease (PD). α-Syn is primarily a neuronal protein, however, its expression is found in various tumors including ovarian, colorectal and melanoma tumors. It has been hypothesized that neurodegeneration may share common mechanisms with oncogenesis. We tested whether α-Syn expression affects tumorigenesis of three types of tumors. Specifically, B16 melanoma, E0771 mammary gland adenocarcinoma and D122 Lewis lung carcinoma. For this aim, we utilized transgenic mice expression the human A53T α-Syn form. We found that the in vivo growth of B16 and E0771 but not D122 was enhanced in the A53T α-Syn mice. The effect on tumorigenesis was not detected in age-matched APP/PS1 mice, modeling Alzheimer's disease (AD), suggesting a specific effect for α-Syn- dependent neurodegeneration. Importantly, transgenic α-Syn expression was detected within the three tumor types. We further show uptake of exogenously added, purified α-Syn, by the cultured tumor cells. In accord, with the affected tumorigenesis in the young A53T α-Syn mice, over- expression of α-Syn in cultured B16 and E0771 cells enhanced proliferation, however, had no effect on the proliferation of D122 cells. Based on these results, we suggest that certain forms of α-Syn may selectively accelerate cellular mechanisms leading to cancer