Effect of booster vaccination against Delta and Omicron SARS-CoV-2 variants in Iceland

Publisher Copyright: © 2022, The Author(s).By the end of July 2021, the majority of the Icelandic population had received vaccination against COVID-19. In mid-July a wave of SARS-CoV-2 infections, dominated by the Delta variant, spread through the population, followed by an Omicron wave in December. A booster vaccination campaign was initiated to curb the spread of the virus. We estimate the risk of infection for different vaccine combinations using vaccination data from 276,028 persons and 963,557 qPCR tests for 277,687 persons. We measure anti-Spike-RBD antibody levels and ACE2-Spike binding inhibitory activity in 371 persons who received one of four recommended vaccination schedules with or without an mRNA vaccine booster. Overall, we find different antibody levels and inhibitory activity in recommended vaccination schedules, reflected in the observed risk of SARS-CoV-2 infections. We observe an increased protection following mRNA boosters, against both Omicron and Delta variant infections, although BNT162b2 boosters provide greater protection against Omicron than mRNA-1273 boosters.Peer reviewe

Whole genome characterization of sequence diversity of 15,220 Icelanders

Understanding of sequence diversity is the cornerstone of analysis of genetic disorders, population genetics, and evolutionary biology. Here, we present an update of our sequencing set to 15,220 Icelanders who we sequenced to an average genome-wide coverage of 34X. We identified 39,020,168 autosomal variants passing GATK filters: 31,079,378 SNPs and 7,940,790 indels. Calling de novo mutations (DNMs) is a formidable challenge given the high false positive rate in sequencing datasets relative to the mutation rate. Here we addressed this issue by using segregation of alleles in three-generation families. Using this transmission assay, we controlled the false positive rate and identified 108,778 high quality DNMs. Furthermore, we used our extended family structure and read pair tracing of DNMs to a panel of phased SNPs, to determine the parent of origin of 42,961 DNMs.Peer Reviewe

Histopathology and levels of proteins in plasma associate with survival after colorectal cancer diagnosis

Funding Information: The authors thank the subjects who have donated their time and their samples that were used in this research. Publisher Copyright: © 2023, The Author(s).Background: The TNM system is used to assess prognosis after colorectal cancer (CRC) diagnosis. Other prognostic factors reported include histopathological assessments of the tumour, tumour mutations and proteins in the blood. As some of these factors are strongly correlated, it is important to evaluate the independent effects they may have on survival. Methods: Tumour samples from 2162 CRC patients were visually assessed for amount of tumour stroma, severity of lymphocytic infiltrate at the tumour margins and the presence of lymphoid follicles. Somatic mutations in the tumour were assessed for 2134 individuals. Pre-surgical levels of 4963 plasma proteins were measured in 128 individuals. The associations between these features and prognosis were inspected by a Cox Proportional Hazards Model (CPH). Results: Levels of stroma, lymphocytic infiltration and presence of lymphoid follicles all associate with prognosis, along with high tumour mutation burden, high microsatellite instability and TP53 and BRAF mutations. The somatic mutations are correlated with the histopathology and none of the somatic mutations associate with survival in a multivariate analysis. Amount of stroma and lymphocytic infiltration associate with local invasion of tumours. Elevated levels of two plasma proteins, CA-125 and PPP1R1A, associate with a worse prognosis. Conclusions: Tumour stroma and lymphocytic infiltration variables are strongly associated with prognosis of CRC and capture the prognostic effects of tumour mutation status. CA-125 and PPP1R1A may be useful prognostic biomarkers in CRC.Peer reviewe

Genetics and epidemiology of mutational barcode-defined clonal hematopoiesis

Publisher Copyright: © 2023, The Author(s).Clonal hematopoiesis (CH) arises when a substantial proportion of mature blood cells is derived from a single hematopoietic stem cell lineage. Using whole-genome sequencing of 45,510 Icelandic and 130,709 UK Biobank participants combined with a mutational barcode method, we identified 16,306 people with CH. Prevalence approaches 50% in elderly participants. Smoking demonstrates a dosage-dependent impact on risk of CH. CH associates with several smoking-related diseases. Contrary to published claims, we find no evidence that CH is associated with cardiovascular disease. We provide evidence that CH is driven by genes that are commonly mutated in myeloid neoplasia and implicate several new driver genes. The presence and nature of a driver mutation alters the risk profile for hematological disorders. Nevertheless, most CH cases have no known driver mutations. A CH genome-wide association study identified 25 loci, including 19 not implicated previously in CH. Splicing, protein and expression quantitative trait loci were identified for CD164 and TCL1A.Peer reviewe

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2

Funding Information: We thank all of the participants that contributed samples for this study for their invaluable contribution to the research. We also thank our research staff at the Patient Recruitment Center for their thorough work. Publisher Copyright: © 2022, The Author(s).Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.Peer reviewe

Rare variants with large effects provide functional insights into the pathology of migraine subtypes, with and without aura

Publisher Copyright: © 2023, The Author(s).Migraine is a complex neurovascular disease with a range of severity and symptoms, yet mostly studied as one phenotype in genome-wide association studies (GWAS). Here we combine large GWAS datasets from six European populations to study the main migraine subtypes, migraine with aura (MA) and migraine without aura (MO). We identified four new MA-associated variants (in PRRT2, PALMD, ABO and LRRK2) and classified 13 MO-associated variants. Rare variants with large effects highlight three genes. A rare frameshift variant in brain-expressed PRRT2 confers large risk of MA and epilepsy, but not MO. A burden test of rare loss-of-function variants in SCN11A, encoding a neuron-expressed sodium channel with a key role in pain sensation, shows strong protection against migraine. Finally, a rare variant with cis-regulatory effects on KCNK5 confers large protection against migraine and brain aneurysms. Our findings offer new insights with therapeutic potential into the complex biology of migraine and its subtypes.Peer reviewe

Þrívítt jarðfræðilíkan af jarðhitasvæðinu í Kröflu; þróun verklags sem notast var við fyrir Pico Alto jarðhitasvæðið á Azor-eyjum

Compiling and summarising multidisciplinary results from geothermal areas often proves to be a complicated and challenging task. In such tasks, 3D models facilitate data comparison and enable a better understanding of the systems involved, resulting in a better and risk mitigated well targeting processes. This project involves 3D modelling of a geothermal field that has been exploited for years. The Krafla geothermal field is located in NE-Iceland and has a long history of research and exploitation. Here, the Krafla geological static model has been updated using research data that have not been implemented to the model before. These include recently acquired seismic data (location of quakes and tomography), 3D resistivity model, aero-magnetic data and Bouguer and Free-air gravity maps. Borehole data (cuttings analyses and geophysical logs), which have not been available in digital format before, have been included. Furthermore, datasets were compared and cross-correlated through deep structure sub-surface analysis. Lessons learned throughout the construction of the Krafla model resulted in a proposed workflow which was then applied to the less known Pico Alto geothermal area on Terceira Island, Azores. Pico Alto is a promising geothermal field in its early stages of development. Five production wells have been drilled and exploration results presented on maps and cross sections. Here, the existing data were visualised in a 3D model, according to the workflow, in order to gain a better understanding of the Pico Alto geothermal field. The two geological static models presented here provide a useful basis for further research and model workflow applications.Samþáttun og samantekt gagna og rannsókna af jarðhitasvæðum er oft á tíðum flókið ferli. Þrívíð líkangerð er mjög gagnleg við slíka vinnu, auðveldar samanburð og samtúlkun og dregur um leið úr óvissu þegar kemur að staðsetningu jarðhitaholna. Í þessu verkefni er útbúið þrívítt jarðfræðilíkan af jarðhitasvæði sem hefur lengi verið í vinnslu. Jarðhitasvæðið í Kröflu á Norðausturlandi er vel þekkt og á sér langa sögu rannsókna og nýtingar. Þrívítt jarðfræðilíkan af Kröflu var uppfært með eftirfarandi gögnum; nýjum skjálftagögnum (staðsetningu skjálfta og hraðalíkani), þrívíðu viðnámslíkani, flugsegulkorti og þyngdarkortum. Hluti jarðlagamælinga og svarfgreininga úr nokkrum borholum hafði ekki fyrr verið til á tölvutæku formi og var þeim niðustöðum bætt við líkanið. Vinna við líkanið varpar m.a. ljósi á áberandi stefnur sem sjást undir yfirborði og tengjast að öllum líkindum jarðfræðigerð svæðisins. Sú reynsla sem hlaust af uppfærslu líkansins, var notuð til þess að hanna ákveðið verklag sem hægt væri að nota á sambærilegum jarðhitasvæðum. Verklaginu var að lokum beitt við líkangerð á minna þekktu jarðhitasvæði, Pico Alto, sem staðsett er á eyjunni Terceira á Azor eyjum. Pico Alto er lítt þróað jarðhitasvæði sem lofar góðu sem slíkt. Fimm vinnsluholur hafa verið boraðar og niðurstöður settar fram á tvívíðu formi. Niðurstöður voru teknar saman og settar fram í þrívíðu jarðfræðilíkani með það að markmiði að auka skilning á svæðinu. Líkönin tvö leiða að auki í ljós hvers konar rannsóknir gætu gagnast í framtíðinni til þess að auka skilning og betrumbæta nýtingu jarðhitasvæðanna.Verkefnið er styrkt af 7. rammaáætlun Evrópusambandsin

Ignimbrítmyndanir frá Húsafellseldstöðinni. Hegðun flóðs og lega misgengja

Í efstu 1000 metrum í jarðlagastafla Húsafellseldstöðvarinnar hafa fundist þrjár ignimbrítmyndanir. Neðsta myndunin, Hraunfossaignimbrítið er tekið fyrir í þessu verkefni. Tvær opnur voru rannsakaðar, annars vegar við Hvítá á móts við Hraunfossa og hins vegar við Ásgil, litlu vestar. Með því að greina útlit, lögun, magn og uppruna korna eru einstök lög tengd milli opnanna. Minnsta fjarlægð á milli opnanna er um 300 metrar og hæðarmunur 10 metrar. Eitt og sama ignimbrítlagið er til staðar í báðum opnunum en er ill- rekjanlegt vegna eyðu sem liggur á milli þeirra. Gjóskufall sem sést við Ásgilsopnu er ekki sjáanlegt við Hraunfossaopnu. Auk greinilegra veikleika á yfirborði styðja hæðarmunur og takmörkuð útbreiðsla laga hugmyndir um misgengi á svæðinu. Misgengi þessi liggja annars vegar samsíða Ásgili, í norður-suður stefnu, og hins vegar samsíða farvegi Hvítár, í austur-vestur stefnu, þ.e.a.s. bæði þvert á og samsíða jarðlögum. Lóðréttar og láréttar breytingar í lögunum endurspegla hegðun gjóskuflóðsins. Með því að taka tillit til jarðlagahalla má fá nokkuð samfellt snið í gegnum opnuna við Hraunfossa. Neðri lagmót við bólstraberg í Hraunfossaopnu renna stoðum undir þá hugmynd að gjóskufall sem sést í Ásgili hafi sest til ofan þykka ignimbrítsins. Í flestum tilfellum sýna vikurkornin öfuga lóðgreiningu en vikur flýtur gjarnan upp í minni skerspennu á meðan bergbrot sökkva vegna mikils eðlismassa.The uppermost 1000 meters of the lava pile around Húsafell central volcano are comprised of three silicic phases. This paper describes the first silicic phase, the Hraunfossar ignimbrite. Two sections were studied, one by Hvítá river against Hraunfossar and another by Ásgil, slightly further to the west. By analyzing appearance, shape and nature of the deposits, layers are correlated between sections. The least distance between sections is about 300 meters and elevation difference is 10 meters. The same ignimbrite layer is present in the two sections but is physically separated because of a fault that cuts through the topography. Air fall deposit is found in the Ásgil section but not in the Hraunfossar section. Distinct lineaments in the landscape, elevation difference and limited distribution of formations supports ideas of faults in this area. They seem to lie both parallel to Ásgil and the channel of Hvítá river and therefore both perpendicular and parallel to the dip of the lava pile. Vertical and horizontal changes reflect the behavior of the pyroclastic flow. By taking into consideration the dip of the lava pile, a composite cross section is made from the Hraunfossar section. Lower contact with pillow lava supports the idea that the ash cloud, which is seen in the Ásgil section, lies above the thick ignimbrite layer. In most cases the lithic grains show reverse grading but pumice floats up against less shear stress while lithic fragements sink because of greater densit

Ávinningur af innleiðingu straumlínustjórnunar : innleiðing fjarskiptafélagsins Tals

Verkefni er læst almenningi til 1. júní 2017Rannsóknarverkefni þetta er lokaritgerð til B.Sc. prófs í Viðskiptafræði frá Háskólanum á Akureyri. Umfjöllunarefni verkefnisins er innleiðing straumlínustjórnunar hjá fjarskiptafélaginu Tali og markmiðið var að skoða hvernig innleiðing fór fram þar, hvort hún hafi farið fram samkvæmt fræðum um straumlínustjórnun og hvort mælanlegur ávinningur hafi hlotist af innleiðingu. Til að leggja mat á þessi atriði voru fræðilegar kenningar á sviði straumlínustjórnunar skoðaðar, kenningar sem þóttu eiga við viðfangsefnið valdar og þeim gerð skil. Helsta rannsóknarðaðferðin sem var notuð var að taka djúpviðtöl við stjórnendur til að fá upplýsingar um það hvernig innleiðingin fór fram, hvert viðhorf þeirra var til innleiðingar, hvaða væntingar stjórnendur höfðu og hvar þeir töldu möguleika á því að eyða sóun. Töluleg gögn voru fengin til að leggja mat á mælanlegan árangur og sem liður í hagnýtu verkefni var spurningakönnun lögð fyrir alla starfsmenn til að fá innsýn í viðhorf og ánægju starfsmanna við breytingar sem þessar. Helstu niðurstöður sýna að Tal fór heldur óhefðbundnar leiðir við innleiðingu og byggði hana frekar á innsæi heldur en fræðum. Viðhorf stjórnenda gagnvart stefnubreytingum sem þessum virðist hafa áhrif á viðhorf starfsmanna og þrátt fyrir að hafa farið óhefðbundar leiðir við innleiðingu hefur náðst nokkuð góður mælanlegur ávinningur

Stærðfræðiprófið sýndi ekki þann árangur sem ég átti von á : er til snjallræði til að bæta árangur drengja í stærðfræði á Suðurnesjunum og jafnframt allra annarra nemenda á landinu?

B.Ed. í grunnskólakennarafræðiFjallað um slakan árangur drengja í stærðfræði á Suðurnesjum og útbótahugmyndir