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  • Brussee, Janneke M.
    et al.
    Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
    Yu, Huixin
    Novartis, Basel, Switzerland;Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
    Krekels, Elke H. J.
    Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
    Palic, Semra
    Netherlands Canc Inst NKI, Amsterdam, Netherlands;Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
    Brill, Margreke J.E.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Barrett, Jeffrey S.
    Sanofi, Translat Informat, Bridgewater, NJ USA;Childrens Hosp Philadelphia, Dept Pediat, Div Clin Pharmacol & Therapeut, Philadelphia, PA 19104 USA.
    Rostami-Hodjegan, Amin
    Univ Manchester, Ctr Appl Pharmacokinet Res, Manchester, Lancs, England;Simcyp Ltd, Sheffield, S Yorkshire, England.
    de Wildt, Saskia N.
    Erasmus MC Sophia Childrens Hosp, Dept Pediat Surg, Rotterdam, Netherlands;Radboud Univ Nijmegen, Dept Pharmacol & Toxicol, Med Ctr, Nijmegen, Netherlands;Erasmus MC Sophia Childrens Hosp, Intens Care, Rotterdam, Netherlands.
    Knibbe, Catherijne A. J.
    St Antonius Hosp, Dept Clin Pharm, Nieuwegein, Netherlands;Leiden Univ, LACDR, Div Syst Biomed & Pharmacol, Leiden, Netherlands.
    Characterization of Intestinal and Hepatic CYP3A-Mediated Metabolism of Midazolam in Children Using a Physiological Population Pharmacokinetic Modelling Approach2018In: Pharmaceutical research, ISSN 0724-8741, E-ISSN 1573-904X, Vol. 35, no 9, article id 182Article in journal (Refereed)
    Abstract [en]

    Purpose Changes in drug absorption and first-pass metabolism have been reported throughout the pediatric age range. Our aim is to characterize both intestinal and hepatic CYP3A-mediated metabolism of midazolam in children in order to predict first-pass and systemic metabolism of CYP3A substrates. Methods Pharmacokinetic (PK) data of midazolam and 1-OH-midazolam from 264 post-operative children 1-18 years of age after oral administration were analyzed using a physiological population PK. modelling approach. In the model, consisting of physiological compartments representing the gastro-intestinal tract and liver,intrinsic intestinal and hepatic clearances were estimated to derive values for bioavailability and plasma clearance. Results The whole-organ intrinsic clearance in the gut wall and liver were found to increase with body weight, with a 105 (95% confidence interval (CI): 5-405) times lower intrinsic gut wall clearance than the intrinsic hepatic dearance (i.e. 5.08 L/h (relative standard error (RSE) 10%) versus 527 L/h (RSE 7%) for a 16 kg individual, respectively). When expressed per gram of organ, intrinsic clearance increases with increasing body weight in the gut wall, but decreases in the liver, indicating that CYP3A-mediated intrinsic clearance and local bioavailability in the gut wall and liver do not change with age in parallel. The resulting total bioavailability was found to be age-independent with a median of 20.8% in children (95%CI: 3.8-50.0%). Conclusion In conclusion, the intrinsic CYP3A-mediated gut wall clearance is substantially lower than the intrinsic hepatic CYP3A-mediated clearance in children from 1 to 18 years of age, and contributes less to the overall first-pass metabolism compared to adults.

  • Olsson, Sofia
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology, Department of Theology.
    Ett progressivt flyktingmottagande?: En kritisk studie av rättighetsskyddet för flyktingar och medborgare i norra Uganda2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Uganda is known for its progressive refugee rights and policy framework towards South Sudanese refugees. The refugees are hosted in long term refugee settlements within host communities in northern Uganda. By using a rights and critical development perspective, this thesis aims to compare and critically review the legal protection of refugees and host communities’ the targeted area. The study identifies several challenges in realizing the aims of the strategic framework and discusses the legal protection of refugees and citizens. The discussion is based on theories from Hannah Arendt, Seyla Benhabib and Balakrishnan Rajagopal. The theories provide rights perspectives on citizenship and global human rights norms, as well as critical perspectives on development and how the human rights discourse can be exploited to the interests of the hegemonic world order.

    The study is based on a critical review of legislation, the policy framework, reports, and literature. The review has been supplemented with a limited field study in a refugee settlement in northern Uganda. Along with the field study, interviews were conducted with representatives from an aid organization that operates in the area.

    The results of this study show that refugees’ rights are generous and in line with global human rights norms. However, the review of the legal protection shows that all rights are not respected and the thesis highlight areas where duty bearers fail to maintain the protection. Interviews and field studies also show that integration between refugees and citizens is essential for the local legal protection. The thesis concludes that lack of local perspectives from rights holders in the refugee policy may prevent integration processes in northern Uganda.

  • Public defence: 2018-11-09 13:00 Rudbecksalen, Uppsala
    Rosestedt, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Theranostics.
    Affibody Molecules for HER3-targeted Theranostics of Malignant Tumours2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The HER3 receptor plays a strong role in disease progression and resistance to therapies in several cancer types. Due to its endogenous expression and low overexpression in malignant tumours, it is a particularly challenging target. The primary aim of this thesis project was to develop, evaluate and characterize affibody molecules for theranostic applications in HER3-expressing malignant tumours.

    Paper I investigated the in vivo targeting properties and therapeutic efficacy of a bivalent affibody construct fused with an albumin binding domain, ZHER3-ABD-ZHER3. This construct could slow down the growth of HER3-expressing tumour xenografts without causing health problems or side effects in mice.

    Paper II compared the in vitro and in vivo properties of two HER3-targeting affibody molecules (Z08698 and Z08699) to select an imaging probe for HER3 diagnostics. While the two constructs had similar properties, Z08698 demonstrated better blood clearance and better radioactivity retention in tumours.

    Paper III and IV present the development of a HER3 imaging probe for PET using gallium and cobalt isotopes. We demonstrated that imaging of HER3 expression could be obtained as soon as 3 h pi using gallium-68. Additionally, we demonstrated that affibody molecules labelled with a neutral cobalt-NOTA complex had a lower radioactivity uptake in the liver than molecules radiolabelled with a positive gallium-NOTA complex. Imaging contrast increased over time. As the dose of the injected protein increased, the activity uptake in normal organs decreased, whereas the tumour uptake remained the same, which improved the imaging contrast and allowed discrimination between xenografts with high and low HER3 expression. This modification did not influence tumour activity uptake.

    Paper V presents the HER3-targeting affibody molecule trimer as a tool to block hepatic uptake in order to increase the imaging contrast in the liver. The trimer demonstrated its ability to bind to endogenous receptors in the liver, which decreased the hepatic uptake of the radiolabelled monomer. This phenomenon enabled the monomer to pass the liver barrier, which increased tumour radioactivity uptake and improved imaging contrast.

    List of papers
    1. In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct
    Open this publication in new window or tab >>In vivo evaluation of a novel format of a bivalent HER3-targeting and albumin- binding therapeutic affibody construct
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    2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 43118Article in journal (Refereed) Published
    Abstract [en]

    Overexpression of human epidermal growth factor receptor 3 (HER3) is involved in resistance to several therapies for malignant tumours. Currently, several anti-HER3 monoclonal antibodies are under clinical development. We introduce an alternative approach to HER3-targeted therapy based on engineered scaffold proteins, i.e. affibody molecules. We designed a small construct (22.5 kDa, denoted 3A3), consisting of two high-affinity anti-HER3 affibody molecules flanking an albumin-binding domain ABD, which was introduced for prolonged residence in circulation. In vitro, 3A3 efficiently inhibited growth of HER3-expressing BxPC-3 cells. Biodistribution in mice was measured using 3A3 that was site-specifically labelled with In-111 via a DOTA chelator. The residence time of In-111-DOTA-3A3 in blood was extended when compared with the monomeric affibody molecule. In-111-DOTA-3A3 accumulated specifically in HER3-expressing BxPC-3 xenografts in mice. However, In-111-DOTA-3A3 cleared more rapidly from blood than a size-matched control construct In-111-DOTA-TAT, most likely due to sequestering of 3A3 by mErbB3, the murine counterpart of HER3. Repeated dosing and increase of injected protein dose decreased uptake of In-111-DOTA-3A3 in mErbB3-expressing tissues. Encouragingly, growth of BxPC-3 xenografts in mice was delayed in an experimental (pilot-scale) therapy study using 3A3. We conclude that the 3A3 affibody format seems promising for treatment of HER3-overexpressing tumours.

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-318958 (URN)10.1038/srep43118 (DOI)000394748000001 ()28230065 (PubMedID)
    Funder
    Swedish Cancer Society, CAN2013-586, CAN 2016/463, CAN2014-474, CAN2015/350Swedish Research Council, Swedish Research Council 621-2012-5236, 2015-02509, 2015-02353VINNOVA, 2016-04060
    Available from: 2017-03-30 Created: 2017-03-30 Last updated: 2018-09-20Bibliographically approved
    2. Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
    Open this publication in new window or tab >>Comparative evaluation of 111In-labeled NOTA‑conjugated affibody molecules for visualization of HER3 expression in malignant tumors
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    2015 (English)In: Oncology Reports, ISSN 1021-335X, E-ISSN 1791-2431, Vol. 34, no 2, p. 1042-1048Article in journal (Refereed) Published
    Abstract [en]

    Expression of human epidermal growth factor receptor type 3 (HER3) in malignant tumors has been associated with resistance to a variety of anticancer therapies. Several anti-HER3 monoclonal antibodies are currently under pre-clinical and clinical development aiming to overcome HER3-mediated resistance. Radionuclide molecular imaging of HER3 expression may improve treatment by allowing the selection of suitable patients for HER3-targeted therapy. Affibody molecules are a class of small (7 kDa) high-affinity targeting proteins with appreciable potential as molecular imaging probes. In a recent study, we selected affibody molecules with affinity to HER3 at a low picomolar range. The aim of the present study was to develop an anti-HER3 affibody molecule suitable for labeling with radiometals. The HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA HER3-specific affibody molecules were labeled with indium-111 (In-111) and assessed in vitro and in vivo for imaging properties using single photon emission computed tomography (SPECT). Labeling of HEHEHE-Z08698-NOTA and HEHEHE-Z08699-NOTA with In-111 provided stable conjugates. In vitro cell tests demonstrated specific binding of the two conjugates to HER3-expressing BT-474 breast carcinoma cells. In mice bearing BT-474 xenografts, the tumor uptake of the two conjugates was receptor-specific. Direct in vivo comparison of In-111-HEHEHE-Z08698-NOTA and In-111-HEHEHE-Z08699-NOTA demonstrated that the two conjugates provided equal radioactivity uptake in tumors, although the tumor-to-blood ratio was improved for In-111-HEHEHE-Z08698-NOTA [12 +/- 3 vs. 8 +/- 1,4 h post injection (p.i)] due to more efficient blood clearance. In-111-HEHEHE-Z08698-NOTA is a promising candidate for imaging of HER3-expression in malignant tumors using SPECT. Results of the present study indicate that this conjugate could be used for patient stratification for anti-HER3 therapy.

    Keywords
    NOTA, indium-111, affibody molecules, HER3, molecular imaging
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-260279 (URN)10.3892/or.2015.4046 (DOI)000357965600060 ()26059265 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Research Council
    Available from: 2015-08-21 Created: 2015-08-18 Last updated: 2018-09-20Bibliographically approved
    3. Affibody-mediated PET imaging of HER3 expression in malignant tumours
    Open this publication in new window or tab >>Affibody-mediated PET imaging of HER3 expression in malignant tumours
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    2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 15226Article in journal (Refereed) Published
    Abstract [en]

    Human epidermal growth factor receptor 3 (HER3) is involved in the progression of various cancers and in resistance to therapies targeting the HER family. In vivo imaging of HER3 expression would enable patient stratification for anti-HER3 immunotherapy. Key challenges with HER3-targeting are the relatively low expression in HER3-positive tumours and HER3 expression in normal tissues. The use of positron-emission tomography (PET) provides advantages of high resolution, sensitivity and quantification accuracy compared to SPECT. Affibody molecules, imaging probes based on a non-immunoglobulin scaffold, provide high imaging contrast shortly after injection. The aim of this study was to evaluate feasibility of PET imaging of HER3 expression using Ga-68-labeled affibody molecules. The anti-HER3 affibody molecule HEHEHE-Z08698-NOTA was successfully labelled with Ga-68 with high yield, purity and stability. The agent bound specifically to HER3-expressing cancer cells in vitro and in vivo. At 3 h pi, uptake of Ga-68-HEHEHE-Z08698-NOTA was significantly higher in xenografts with high HER3 expression (BT474, BxPC-3) than in xenografts with low HER3 expression (A431). In xenografts with high expression, tumour-to-blood ratios were >20, tumour-to-muscle >15, and tumour-to-bone >7. HER3-positive xenografts were visualised using microPET 3 h pi. In conclusion, PET imaging of HER3 expression is feasible using Ga-68-HEHEHE-Z08698-NOTA shortly after administration.

    National Category
    Medical Image Processing Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-266695 (URN)10.1038/srep15226 (DOI)000362985400001 ()26477646 (PubMedID)
    Funder
    Swedish Cancer SocietySwedish Research Council
    Available from: 2015-11-12 Created: 2015-11-10 Last updated: 2018-09-20Bibliographically approved
    4. Evaluation of radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression
    Open this publication in new window or tab >>Evaluation of radiocobalt-labelled affibody molecule for imaging of human epidermal growth factor receptor 3 expression
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    2017 (English)In: International Journal of Oncology, ISSN 1019-6439, Vol. 51, no 6, p. 1765-1774Article in journal (Refereed) Published
    Abstract [en]

    The human epidermal growth factor receptor 3 (HER3) is involved in the development of cancer resistance towards tyrosine kinase-targeted therapies. Several HER3‑targeting therapeutics are currently under clinical evaluation. Non-invasive imaging of HER3 expression could improve patient management. Affibody molecules are small engineered scaffold proteins demonstrating superior properties as targeting probes for molecular imaging compared with monoclonal antibodies. Feasibility of in vivo HER3 imaging using affibody molecules has been previously demonstrated. Preclinical studies have shown that the contrast when imaging using anti-HER3 affibody molecules can be improved over time. We aim to develop an agent for PET imaging of HER3 expression using the long-lived positron-emitting radionuclide cobalt-55 (55Co) (T1/2=17.5 h). A long-lived cobalt isotope 57Co was used as a surrogate for 55Co in this study. The anti-HER3 affibody molecule HEHEHE-ZHER3-NOTA was labelled with radiocobalt with high yield, purity and stability. Biodistribution of 57Co-HEHEHE-ZHER3-NOTA was measured in mice bearing DU145 (prostate carcinoma) and LS174T (colorectal carcinoma) xenografts at 3 and 24 h post injection (p.i.). Tumour-to-blood ratios significantly increased between 3 and 24 h p.i. (p<0.05). At 24 h p.i., tumour-to-blood ratios were 6 for DU145 and 8 for LS174T xenografts, respectively. HER3‑expressing xenografts were clearly visualized in a preclinical imaging setting already 3 h p.i., and contrast further improved at 24 h p.i. In conclusion, the radiocobalt-labelled anti-HER3 affibody molecule, HEHEHE-ZHER3-NOTA, is a promising tracer for imaging of HER3 expression in tumours.

    Keywords
    HER3, affibody, PET imaging, Cobalt-55/57, NOTA-chelator
    National Category
    Radiology, Nuclear Medicine and Medical Imaging
    Identifiers
    urn:nbn:se:uu:diva-343404 (URN)10.3892/ijo.2017.4152 (DOI)000416685600014 ()
    Funder
    Knut and Alice Wallenberg FoundationSwedish Cancer Society, CAN2014/474Swedish Research Council, 2015-02509Swedish Research Council, 2015-02353Swedish Research Council, 2012-05236Swedish Cancer Society, CAN2015/350Swedish Cancer Society, CAN2016/463VINNOVA, 2016-04060
    Available from: 2018-02-27 Created: 2018-02-27 Last updated: 2018-09-20Bibliographically approved
    5. Improved contrast of affibody-mediated imaging of HER3 expression through co-injection of affibody trimer for in vivo blocking of hepatic uptake
    Open this publication in new window or tab >>Improved contrast of affibody-mediated imaging of HER3 expression through co-injection of affibody trimer for in vivo blocking of hepatic uptake
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    (English)Manuscript (preprint) (Other academic)
    Keywords
    HER3, affibody molecule, molecular imaging, imaging contrast
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-360288 (URN)
    Available from: 2018-09-12 Created: 2018-09-12 Last updated: 2018-09-20
  • Zhou, Yitian
    et al.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Pharmacogenet, Stockholm, Sweden.
    Mägi, Reedik
    Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Milani, Lili
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Molecular Medicine. Uppsala University, Science for Life Laboratory, SciLifeLab. Univ Tartu, Estonian Genome Ctr, Tartu, Estonia.
    Lauschke, Volker M.
    Karolinska Inst, Dept Physiol & Pharmacol, Sect Pharmacogenet, Stockholm, Sweden.
    Global genetic diversity of human apolipoproteins and effects on cardiovascular disease risk2018In: Journal of Lipid Research, ISSN 0022-2275, E-ISSN 1539-7262, Vol. 59, no 10, p. 1987-2000Article in journal (Refereed)
    Abstract [en]

    Abnormal plasma apolipoprotein levels are consistently implicated in CVD risk. Although 30% to 60% of their interindividual variability is genetic, common genetic variants explain only 10% to 20% of these differences. Rare genetic variants may be major sources of the missing heritability, yet quantitative evaluations of their contribution to phenotypic variability are lacking. Here, we analyzed whole-genome and whole-exome sequencing data from 138,632 individuals across seven major human populations to present a systematic overview of genetic apolipoprotein variability. We provide population-specific frequencies of 38 clinically important apolipoprotein alleles and identify further 6,875 genetic variants, 33% of which are novel and 98.7% of which are rare with minor allele frequencies <1%. We predicted the functional impact of rare variants and found that their relative importance differed drastically between genes and among ethnicities. Importantly, we validated the clinical relevance of multiple variants with predicted effects by leveraging association data from the CARDIoGRAM (Coronary Artery Disease Genomewide Replication and Meta-analysis) and Global Lipids Genetics consortia. Overall, we provide a consolidated overview of population-specific apolipoprotein genetics as a valuable data resource for scientists and clinicians, estimate the importance of rare genetic variants for the missing heritability of apolipoprotein-associated disease traits, and pinpoint multiple novel apolipoprotein variants with putative population-specific impacts on serum lipid levels.

  • Public defence: 2018-11-09 09:00 Ekmansalen, Uppsala
    Bogusz, Marcin
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Evolutionary Biology.
    Evolutionary Approaches to Sequence Alignment2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Molecular evolutionary biology allows us to look into the past by analyzing sequences of amino acids or nucleotides. These analyses can be very complex, often involving advanced statistical models of sequence evolution to construct phylogenetic trees, study the patterns of natural selection and perform a number of other evolutionary studies. In many cases, these evolutionary studies require a prerequisite of multiple sequence alignment (MSA) - a technique, which aims at grouping the characters that share a common ancestor, or homology, into columns. This information regarding shared homology is needed by statistical models to describe the process of substitutions in order to perform evolutionary inference. Sequence alignment, however, is difficult and MSAs often contain whole regions of wrongly aligned characters, which impact downstream analyses.

    In this thesis I use two broad groups of approaches to avoid errors in the alignment. The first group addresses the analysis methods without sequence alignment by explicitly modelling the processes of substitutions, and insertions and deletions (indels) between pairs of sequences using pair hidden Markov models. I describe an accurate tree inference method that uses a neighbor joining clustering approach to construct a tree from a matrix of model-based evolutionary distances.

    Next, I develop a pairwise method of modelling how natural selection acts on substitutions and indels. I further show the relationship between the constraints acting on these two evolutionary forces to show that natural selection affects them in a similar way.

    The second group of approaches deals with errors in existing alignments. I use a statistical model-based approach to evaluate the quality of multiple sequence alignments.

    First, I provide a graph-based tool for removing wrongly aligned pairs of residues by splitting them apart. This approach tends to produce better results when compared to standard column-based filtering.

    Second, I provide a way to compare MSAs using a probabilistic framework. I propose new ways of scoring of sequence alignments and show that popular methods produce similar results.

    The overall purpose of this work is to facilitate more accurate evolutionary analyses by addressing the problem of sequence alignment in a statistically rigorous manner.

    List of papers
    1. Phylogenetic Tree Estimation With and Without Alignment: New Distance Methods and Benchmarking
    Open this publication in new window or tab >>Phylogenetic Tree Estimation With and Without Alignment: New Distance Methods and Benchmarking
    2017 (English)In: Systematic Biology, ISSN 1063-5157, E-ISSN 1076-836X, Vol. 66, no 2, p. 218-231Article in journal (Refereed) Published
    Abstract [en]

    Phylogenetic tree inference is a critical component of many systematic and evolutionary studies. The majority of these studies are based on the two-step process of multiple sequence alignment followed by tree inference, despite persistent evidence that the alignment step can lead to biased results. Here we present a two-part study that first presents PaHMM-Tree, a novel neighbor joining-based method that estimates pairwise distances without assuming a single alignment. We then use simulations to benchmark its performance against a wide-range of other phylogenetic tree inference methods, including the first comparison of alignment-free distance-based methods against more conventional tree estimation methods. Our new method for calculating pairwise distances based on statistical alignment provides distance estimates that are as accurate as those obtained using standard methods based on the true alignment. Pairwise distance estimates based on the two-step process tend to be substantially less accurate. This improved performance carries through to tree inference, where PaHMM-Tree provides more accurate tree estimates than all of the pairwise distance methods assessed. For close to moderately divergent sequence data we find that the two-step methods using statistical inference, where information from all sequences is included in the estimation procedure, tend to perform better than PaHMM-Tree, particularly full statistical alignment, which simultaneously estimates both the tree and the alignment. For deep divergences we find the alignment step becomes so prone to error that our distance-based PaHMM-Tree outperforms all other methods of tree inference. Finally, we find that the accuracy of alignment-free methods tends to decline faster than standard two-step methods in the presence of alignment uncertainty, and identify no conditions where alignment-free methods are equal to or more accurate than standard phylogenetic methods even in the presence of substantial alignment error.

    Keywords
    Alignment-free, distance-based phylogenetics, pair Hidden Markov Models, phylogenetic inference, statistical alignment
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-316533 (URN)10.1093/sysbio/syw074 (DOI)000397703800009 ()27633353 (PubMedID)
    Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2018-09-19Bibliographically approved
    2. Selection acting on indels and substitutions in protein coding sequences
    Open this publication in new window or tab >>Selection acting on indels and substitutions in protein coding sequences
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Patterns of selection acting on an expressed protein act to maintain or adapt its structure and function over time. The most widely used method for studying these selective forces is the ratio of synonymous to non-synonymous substitutions (dN/dS), which helps distinguish between neutral, purifying (negative), and adaptive (positive) selection. This ratio, however, examines only amino acid substitutions and ignores other evolutionary forces like small-scale insertions and deletions (indels) that may affect protein evolution. There are currently no statistically robust methods for studying the forces acting on protein sequence indels, with the few ad hoc solutions highly dependent on the gap patterns produced by alignment and filtering steps. This study broadens our understanding of how selection acts on indels in proteins by explicitly examining the relationship between selective constraint acting on substitutions and indels. We present a probabilistic model that jointly estimates dN/dS and the indel rate through statistical alignment, which removes biases in both parameter estimates caused by alignment error. We apply our method to thousands of genes from human-mouse and human-chicken pairwise analyses, revealing that the indel rate and selection (dN/dS) tends to be related, demonstrating that purifying selection acting in proteins tends to affect non-synonymous mutations and indels in a quantifiably similar way. We also investigate how the selective forces acting on substitutions and indels vary along genes. Our findings and methods offer the opportunity to begin studying the interaction between substitutions and indels, and the first widely applicable tools for understanding how they impact protein evolution.

    Keywords
    Natural Selection, Protein Evolution, Pair hidden Markov models
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-360838 (URN)
    Available from: 2018-09-18 Created: 2018-09-18 Last updated: 2018-09-19
    3. A graph-based approach for improving the homologyinference in multiple sequence alignments
    Open this publication in new window or tab >>A graph-based approach for improving the homologyinference in multiple sequence alignments
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Multiple sequence alignment (MSA) is ubiquitous in evolutionary studies and other areas ofbioinformatics. In nearly all cases MSAs are taken to be a known and xed quantity on which toperform downstream analysis despite extensive evidence that MSA accuracy and uncertainty aectsresults. Mistakes in the MSA are known to cause a wide range of problems for downstream evolutionaryinference, ranging from false inference of positive selection to long branch attraction artifacts. The mostpopular approach to dealing with this problem is to remove (lter) specic columns in the MSA thatare thought to be prone to error, either through proximity to gaps or through some scoring function.Although popular, this approach has had mixed success and several studies have even suggested thatltering might be detrimental to phylogenetic studies. Here we present a dierent approach to dealingwith MSA accuracy and uncertainty through a graph-based approach implemented in the freely availablesoftware Divvier. The aim of Divvier is to identify clusters of characters that have strong statisticalevidence of shared homology, based on the output of a pair hidden Markov model. These clusters canthen be used to either lter characters out the MSA, through a process we call partial ltering, or torepresent each of the clusters in a new column, through a process we call divvying up. We validateour approach through its performance on real and simulated benchmarks, nding Divvier substantiallyoutperforms all other ltering software for treating MSAs by retaining more true positive homology callsand removing more false positive homology calls. We also nd that Divvier, in contrast to other lteringtools, can alleviate long branch attraction artifacts induced by MSA and reduces the variation in treeestimates caused by MSA uncertainty.

    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-360839 (URN)
    Available from: 2018-09-18 Created: 2018-09-18 Last updated: 2018-09-21
    4. Examining sequence alignments using a model-based approach
    Open this publication in new window or tab >>Examining sequence alignments using a model-based approach
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Multiple sequence alignment (MSA) is a commonly performed procedure required for a number of evolutionary and comparative analyses. The common two-step process of sequence alignment followed by statistical phylogenetic inference depends on MSA quality. MSA is computationally difficult and as a result in many cases sequence alignments contain regions of spurious homologies. These errors in the alignment affect downstream results, so choosing an accurate MSA is critical.  Researchers often face the problem of choosing an aligner out of many multiple sequence alignment methods (MSAMs). This choice is often based on the results of benchmarks with various popular methods claiming high accuracy scores. These methods compete to obtain the highest scores in the commonly used sum-of-pairs benchmark—which accounts for a fraction of the true homologies recovered—ignoring the fraction of introduced false positive homologies. Furthermore, these benchmarks do not account for the fact that some homologies are more difficult to recover than the others. We take a probabilistic model-based approach to examine the quality of pairwise homologies returned by four popular MSAMs. We use pair-hidden Markov models to break down alignment columns into pairs and obtain distributions of pairwise posterior scores for these aligners. Basing our results on a structural benchmark and a simulation study, we find that MSAMs appear to return a sample from a confidence set defined by high posterior probabilities. Furthermore, we find that the reference alignment contains low pairwise posterior portions of pairwise homologies which cannot be expected to be recovered by any MSAM. Finally, we look at several possible test statistics, with and without the need for reference alignments, and ultimately suggest using positive predictive value (PPV) and mean posterior probability for MSA evaluation.

    Keywords
    Sequence alignment, alignment accuracy, alignment uncertainty, pair hidden Markov models
    National Category
    Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-360840 (URN)
    Available from: 2018-09-19 Created: 2018-09-19 Last updated: 2018-09-21
  • Public defence: 2018-11-09 13:00 Brömssalen, Gävle
    Palm, Andreas
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Research and Development, Gävleborg.
    Obesity, Sleep and Sleep-disordered Breathing2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Sleep problems are associated with impaired quality of life and daytime sleepiness. Obstructive sleep apnoea (OSA) and obesity hypoventilation syndrome (OHS), are associated with metabolic changes and an increased cardiovascular morbidity and mortality. The most preferred treatment of OSA and OHS is positive airway pressure (PAP) therapy. Diagnostic delay and non-adherence to PAP therapy are major clinical problems.

    Aims and methods: Paper I: A longitudinal population-based cohort study aimed to investigate the role of obesity and weight gain in the development of sleep problems in 1,896 men and 5,116 women who responded to questionnaires at baseline and followed up after 10–13 years.

    Paper II: A national registry-based cohort study aimed to analyse gender differences in patients with OHS starting long term mechanical ventilation (LTMV) and to study how the prescription of LTMV due to OHS has changed over time with data on 1,527 patients derived from the Swedish quality registry Swedevox between 1996 and 2014.

    Paper III: A longitudinal observational cohort study aimed to investigate the impact of adherence to continuous positive airway pressure (CPAP) treatment on IGF-1 concentration in 69 patients with OSA followed up after 4.8 ± 2.5 months.

    Paper IV: A national registry-based cohort study aimed to identify protective and risk factors against the discontinuation of CPAP treatment in patients with OSA and to estimate the mortality risk in those who were non-adherent to CPAP therapy on 16,425 patients derived from the Swedish quality registry Swedevox between July 2010 and March 2017.

    Results and conclusions: Weight gain is a risk factor for developing several sleep problems and daytime sleepiness. Women with OHS are older with a more advanced clinical picture at initiation of LTMV and start LTMV more frequently in a non-elective situation than men. CPAP usage ≥ 4 h/night is associated with increased IGF-1 concentration in patients with OSA. Use of humidifier, increasing age, more severe OSA and BMI up to 35 are associated with greater adherence to CPAP treatment. Female gender and coexisting hypertension are risk factors for the discontinuation of CPAP. Failure to adhere to CPAP is associated with increased mortality.

    List of papers
    1. The impact of obesity and weight gain on development of sleep problems in a population-based sample
    Open this publication in new window or tab >>The impact of obesity and weight gain on development of sleep problems in a population-based sample
    2015 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 16, no 5, p. 593-597Article in journal (Refereed) Published
    Abstract [en]

    Objectives: The objective of this study was to investigate the role of obesity and weight gain in the development of sleep problems in a population-based cohort. Material and methods: A population-based sample of men (n = 1896, aged 40-79 years) and women (n = 5116, age = 20 years) responded to questionnaires at baseline and follow-up after 10-13 years. Sleep problems were assessed through questions about difficulties initiating sleep (DIS), difficulties maintaining sleep (DMS), excessive daytime sleepiness (EDS), and insomnia. Body mass index (BMI) was calculated from self-reported weight and height at both baseline and follow-up, while confounding factors (physical activity, tobacco and alcohol use, somatic disease, and snoring) were based on responses at baseline. Results: Although overweight and obese subjects reported more sleep problems at baseline, there was no independent association between BMI level at baseline and development of new sleep problems. Subjects in the quartile with the highest rise in BMI with a weight gain exceeding 2.06 kg/m(2) had a higher risk of developing DMS [adjusted odds ratio (OR) 1.58; 95% confidence interval (CI) 1.25-2.01), EDS (2.25; 1.65-3.06], and insomnia (2.78; 1.60-4.82). Weight gain was not associated with the development of DIS. Conclusions: Weight gain is an independent risk factor for developing several sleep problems and daytime sleepiness. The presence of overweight and weight gain should be considered when treating patients with sleep problems. (C) 2015 Elsevier B.V. All rights reserved.

    Keywords
    Weight gain, Overweight, Obesity, Sleep problems, Insomnia, Sleepiness
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-255278 (URN)10.1016/j.sleep.2015.01.016 (DOI)000353892800010 ()25819416 (PubMedID)
    Funder
    Swedish Heart Lung Foundation, 20080526
    Available from: 2015-06-22 Created: 2015-06-15 Last updated: 2018-09-25Bibliographically approved
    2. Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome
    Open this publication in new window or tab >>Gender differences in patients starting long-term home mechanical ventilation due to obesity hypoventilation syndrome
    2016 (English)In: Respiratory Medicine, ISSN 0954-6111, E-ISSN 1532-3064, Vol. 110, p. 73-78Article in journal (Refereed) Published
    Abstract [en]

    Background and objectives: Obesity hypoventilation syndrome (OHS) is often diagnosed late. The aim of this study was to analyse gender differences at initiation of long-term mechanical ventilation (LTMV) in patients with (OHS), to analyse gender differences in treatment effect and to study how the prescription of LTMV due to OHS has changed over time. Methods: Data on patients on LTMV due to OHS between 1996 and 2014 were obtained from Swedevox, a nationwide health quality registry of patients on LTMV in Sweden. Results: When starting LTMV, women were generally older (age 64.4 +/- 11.2 vs. 60.1 +/- 12.1 years, p < 0.001), more obese (BMI 43.0 +/- 8.2 vs. 41.5 +/- 7.9 kg/m(2), p < 0.001), more hypoxic (PaO2 7.6 +/- 1.5 vs. 7.9 +/- 1.6 kPa, p +/- 0.001), had more hypercapnia (PaCO2 7.2 +/- 1.3 vs. 6.9 +/- 1.3 kPa, p = 0.001), had higher base excess (6.9 +/- 4.1 vs. 5.8 +/- 4.7 kPa, p < 0.001) and more frequently started LTMV in a non-elective situation (43.2% vs. 37.5%, p = 0.026) than men. Improvement of arterial blood gas values or in age-adjusted mortality at one-year follow-up did not differ. During the study period, the age of patients at the initiation of LTMV rose by 3.4 years/decade (P = 0.001) in women and with 1.9 years/decade (P = 0.048) in men but there were no significant changes in BMI (P = 0.425). Conclusions: Diagnosis of OHS is more delayed in women and as a consequence the disease is more advanced when diagnosed. In spite of this, there is no gender difference in survival rate in patients with OHS treated with LTMV. More and older patients with OHS nowadays gain access to LTMV.

    Keywords
    Body mass index, Gender differences, Long-term mechanical ventilation, Obesity hypoventilation syndrome
    National Category
    Respiratory Medicine and Allergy Cardiac and Cardiovascular Systems
    Identifiers
    urn:nbn:se:uu:diva-274924 (URN)10.1016/j.rmed.2015.11.010 (DOI)000367380700010 ()26680503 (PubMedID)
    Funder
    Swedish Association of Local Authorities and Regions
    Available from: 2016-01-27 Created: 2016-01-26 Last updated: 2018-09-25Bibliographically approved
    3. The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea
    Open this publication in new window or tab >>The Impact of Continuous Positive Airway Pressure on Circulating IGF-1 in Patients With Obstructive Sleep Apnea
    Show others...
    2018 (English)In: Journal of Clinical Sleep Medicine (JCSM), ISSN 1550-9389, E-ISSN 1550-9397, p. 385-391Article in journal (Refereed) Published
    Abstract [en]

    Study Objectives: Obstructive sleep apnea (OSA) is a disease with metabolic and cardiovascular consequences and is associated with decreased serum concentrations of insulin-like growth factor-1 (IGF-1). The aim of this study was to investigate whether continuous positive airway pressure (CPAP) will increase serum IGF-1 concentration in patients with OSA. Methods: Patients with moderate to severe OSA were recruited from a sleep clinic and serum IGF-1 was measured before initiation of CPAP and at follow-up after 4.8 +/- 2.5 months. Patients adherent to CPAP treatment (usage >= 4 h/night) were compared with those considered to be nonadherent (usage < 4 h/night). Results: Complete data were obtained from 69 patients (86% male, age 56 +/- 12 years, respiratory event index 43 +/- 21 events/h, Epworth Sleepiness Scale score 12 +/- 5). In those adherent to CPAP (n = 42), there was an increase in serum IGF-1 concentration with 21.1 (95% confidence interval [CI]: 13.1 to 29.2) mu g/L compared to 4.7 (95% CI: -4.1 to 13.5) mu g/L in the nonadherent group (n = 27) (P =.0083). In a linear multivariate model adjusting for sex, age, body mass index, respiratory event index, and mean oxygen saturation during the night recording, the change in serum IGF-1 concentration was significantly associated with adherence to CPAP treatment (adjusted beta coefficient: 21.8, 95% CI: 10.2 to 33.4) and inversely associated with change in body mass index (adjusted beta coefficient: -7.1, 95% CI: -11.3 to -3.0) and change in hemoglobin A1c (adjusted beta coefficient: -1.8, 95% CI: - 33 to -0.3). Conclusions: CPAP usage >= 4 h/night is associated with increased serum IGF-1 concentration in male patients with OSA.

    Keywords
    adherence, continuous positive airway pressure, IGF-1, obstructive sleep apnea
    National Category
    Respiratory Medicine and Allergy
    Identifiers
    urn:nbn:se:uu:diva-343619 (URN)10.5664/jcsm.6982 (DOI)000427477700011 ()29458693 (PubMedID)
    Funder
    Swedish Research Council
    Available from: 2018-02-28 Created: 2018-02-28 Last updated: 2018-09-25
    4. Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study.
    Open this publication in new window or tab >>Factors influencing adherence to continuous positive airway pressure treatment in obstructive sleep apnea and mortality associated with treatment failure - a national registry-based cohort study.
    Show others...
    2018 (English)In: Sleep Medicine, ISSN 1389-9457, E-ISSN 1878-5506, Vol. 51, p. 85-91, article id S1389-9457(18)30401-5Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    OBJECTIVES: Adherence to continuous positive airway pressure (CPAP) in patients with obstructive sleep apnea (OSA) is crucial. Our aim was to identify protective and risk factors against the discontinuation of CPAP treatment in patients with OSA and to estimate the mortality risk in those who were non-adherent to CPAP therapy.

    METHODS: This was a registry-based cohort study from 37 centers across Sweden with OSA patients on CPAP in the Swedevox Swedish national registry between July 2010 and March 2017.

    RESULTS: In 16,425 patients (70.8% men) with complete follow-up data after 1.2 ± 0.8 years the adjusted relative risk ratio (aRRR) for the discontinuation of CPAP was 0.57 (95% confidence interval (CI) 0.50-0.65) for use of humidifier, 0.87 (95% CI 0.82-0.92) for increasing age per 10 years, 0.80 (95% CI 0.77-0.83) for increasing apnea hypopnea index (AHI) per 5 units/hour, and 0.96 (95% CI 0.95-0.97) per increased unit on the Epworth Sleepiness Scale (ESS). Increasing BMI was associated with increased adherence up to BMI 35. Women and patients with hypertension ran an increased risk of discontinuing CPAP treatment, aRRR 1.28 (95% CI 1.12-1.46) and 1.24 (95% CI 1.12-1.42) respectively. The adjusted hazard ratio (HR) for mortality was 1.74 (95% CI 1.32-2.28) among those who did not adhere to CPAP (median follow-up period 2.4 years after the one year adherence evaluation).

    CONCLUSION: Use of humidifier is associated with greater adherence to CPAP treatment. Other factors predicting adherence are increasing age, more severe OSA and overweight up to BMI 35, whereas female gender and coexisting hypertension are risk factors for discontinuation of CPAP. Failure to adhere to CPAP is associated with increased mortality.

    Keywords
    Adherence, BMI, Continuous positive airway pressure (CPAP), Gender, Humidifier, Obstructive sleep apnea (OSA)
    National Category
    Respiratory Medicine and Allergy
    Identifiers
    urn:nbn:se:uu:diva-361337 (URN)10.1016/j.sleep.2018.07.007 (DOI)30103074 (PubMedID)
    Available from: 2018-09-23 Created: 2018-09-23 Last updated: 2018-09-25
  • Andersson, Roger
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Institute for Housing and Urban Research. Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Social and Economic Geography.
    Musterd, Sako
    University of Amsterdam.
    Galster, George
    Wayne State University.
    Port-of-Entry Neighbourhood and its Effects on the Economic Success of Refugees in Sweden2018In: International Migration ReviewArticle in journal (Refereed)
    Abstract [en]

    We investigate the degree to which the ethnic group composition of "port-of-entry neighborhood" (PoE), the first permanent settlement after immigration, affects the employment prospects of refugees in Sweden during the subsequent 10 years. We use panel data on working-age adults from Iran, Iraq, and Somalia immigrating into Sweden from 1995 to 2004. We control for initial individual and labor market characteristics, use instrumental variable regression to avoid bias from geographic selection, and stratify models by gender and co-ethnic employment and education rates within the neighborhood. We find that the impact of co-ethnic neighbors in the PoE varies dramatically by gender.

  • Hajdarevic, Demir
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    The Role of Product Owners: An Empirical Investigation of the Role of Product Owners and Challenges in Agile Scrum Projects2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Within Scrum framework the role of the product owner is critical for the success of a Scrum project. Today, there exist little empirical evidence of how the role of product owner is practiced and the challenges they are faced with. This research seeks through a multiple-case study approach to explore the role of product owners. The aim of the research was to investigate the existence of a gap between theory and practice in terms of the product owner role. Qualitative data collection consisted of eight semi-structured interviews with product owners and agile coaches which then was analyzed according to what theory of the role suggests. Results showed partly multiple factors confirming a gap, for example regarding vision, prioritizing and communication, and challenges that arise from the gap, for example concerning decision-making.

  • Mondal, Sourabh
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    A self-assessment screening tool to prioritize patients with mental disorders2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Due to the continuous growth of patients with mental disorders, it has been a strenuous job to look after each patient and tailor the appropriate treatments for them on time. The thesis proposes a design science framework in the form of an IT artefact to prioritize the patients with mental disorders, considering the severity of the situation. The IT arte-fact will be using expert’s knowledge to design a self-assessment screen-ing tool that will evaluate the criticality of a patient’s mental health. This tool will also incorporate the psychometric scale DSM-5 Self-Rated Level 1 Cross-Cutting Symptom Measure, Adult electronically to de-termine what will be the next stage in the process of patients’ treat-ments. The process of prioritizing patients is prolonged and remains to be tedious at the hospital and also there is always a possibility of miss-ing some information while carrying out the job manually. The self-assessment system will serve two goals. It will shorten the initial screen-ing process and also the likelihood of any human error. The system is not meant to replace healthcare professionals but to build a bridge be-tween the patients and the doctors to make everyone’s life more orga-nized. The results indicate that it is possible to create a framework and the relevant prototype with the help of expert’s knowledge that can prioritize patients with mental disorders. It also demonstrates that the system can digitalize DSM-5 Self-Rated Level 1 Cross-Cutting Symp-tom Measure, Adult scale to determine possible problem domains for further diagnosis.

  • Enell, Jacob
    et al.
    Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden.
    Bayadsi, Haytham
    Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden.
    Lundgren, Ewa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Endocrine Surgery.
    Hennings, Joakim
    Umea Univ, Dept Surg & Perioperat Sci, S-90185 Umea, Sweden.
    Primary Hyperparathyroidism is Underdiagnosed and Suboptimally Treated in the Clinical Setting2018In: World Journal of Surgery, ISSN 0364-2313, E-ISSN 1432-2323, Vol. 42, no 9, p. 2825-2834Article in journal (Refereed)
    Abstract [en]

    To evaluate whether patients presenting with laboratory results consistent with primary hyperparathyroidism (pHPT) are managed in accordance with guidelines. The laboratory database at a hospital in Sweden, serving 127,000 inhabitants, was searched for patients with biochemically determined pHPT. During 2014, a total of 365 patients with biochemical laboratory tests consistent with pHPT were identified. Patients with possible differential diagnoses or other reasons for not being investigated according to international guidelines were excluded after scrutinizing records, after new blood tests, and clinical assessments by endocrine surgeons. Altogether, 92 patients had been referred to specialists and 82 had not. The latter group had lower serum calcium (median 2.54 mmol/L) and PTH (5.7 pmol/L). Out of these 82 cases, 9 patients were diagnosed with pHPT or had some sort of long-term follow-up planned as outpatients. Primary hyperparathyroidism is overlooked and underdiagnosed in a number of patients in the clinical setting. It is important to provide local guidelines for the management of patients presenting with mild pHPT to ensure that these patients receive proper evaluation and follow-up according to current research.

  • Public defence: 2018-11-08 10:15 Lindahlsalen, 05:01058, EBC, Uppsala
    Naidoo, Thijessen
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Human Evolution.
    Population Genetics of Human Genomic Elements2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The genomes of living organisms are composed of a multitude of functional units, which interact with each other and their environment in a highly regulated fashion, to facilitate the expression of an enduring (and evolving) phenotype. Several approaches have emerged in the effort to identify these functional units and explore their activities. In this thesis, I have taken a population genetics approach; evaluating how the distribution of genetic variation in the human genome has been shaped through the actions of natural selection on functional genomic elements. In the first paper, I interrogate a catalogue of elements derived from biochemical signatures for signals of selection; finding significant signals of purifying selection on regulatory elements, independent of linked-purifying selection. In the second paper, I explore the pseudogene class of genomic elements, and find that a large proportion of a particular subclass, transcribed duplicated pseudogenes, has experienced significant amounts of positive selection. In the third paper, I focus on protein coding genes and variants that disrupt their open reading frames. Specifically, I examine the distribution of loss-of-function variants in the Khoe-San population; gauging their functional significance and exploring the biological roles of affected genes. In the final paper, instead of using population genetics to uncover and explore genomic elements, I use a major genomic element – the Y chromosome – as an effective tool to study the evolutionary history of a human population.

    List of papers
    1. Patterns of variation in cis-regulatory regions: examining evidence of purifying selection
    Open this publication in new window or tab >>Patterns of variation in cis-regulatory regions: examining evidence of purifying selection
    2018 (English)In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 19, article id 95Article in journal (Refereed) Published
    Abstract [en]

    Background: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.

    Results: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.

    Conclusions: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements.

    Place, publisher, year, edition, pages
    BIOMED CENTRAL LTD, 2018
    Keywords
    Regulatory regions, Purifying selection, Selection efficacy, Non-coding DNA, Functional elements, Population genetics
    National Category
    Genetics Developmental Biology
    Identifiers
    urn:nbn:se:uu:diva-343792 (URN)10.1186/s12864-017-4422-y (DOI)000423443900002 ()29373957 (PubMedID)
    Funder
    Göran Gustafsson Foundation for Research in Natural Sciences and MedicineKnut and Alice Wallenberg FoundationSwedish Research Council
    Available from: 2018-03-05 Created: 2018-03-05 Last updated: 2018-09-28Bibliographically approved
    2. Selective sweeps among transcribed pseudogenes underline their utility in the human genome
    Open this publication in new window or tab >>Selective sweeps among transcribed pseudogenes underline their utility in the human genome
    (English)Manuscript (preprint) (Other academic)
    National Category
    Genetics Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-361122 (URN)
    Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2018-09-20
    3. Loss-of-function variants among Khoe and San individuals
    Open this publication in new window or tab >>Loss-of-function variants among Khoe and San individuals
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Genetics Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-361123 (URN)
    Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2018-09-20
    4. Full genomic Y chromosomal variation in southern African Khoe-San populations
    Open this publication in new window or tab >>Full genomic Y chromosomal variation in southern African Khoe-San populations
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Genetics Evolutionary Biology
    Identifiers
    urn:nbn:se:uu:diva-361124 (URN)
    Available from: 2018-09-20 Created: 2018-09-20 Last updated: 2018-09-20
  • Cárdenas, Paco
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Medicinal Chemistry, Farmakognosi. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Systematic Biology.
    Moore, Jon A.
    Wilkes Honors College, Florida Atlantic University.
    First records of Geodia demosponges from the New England seamounts, an opportunity to test the use of DNA mini-barcodes on museum specimens2017In: Marine Biodiversity, ISSN 1867-1616, E-ISSN 1867-1624Article in journal (Refereed)
    Abstract [en]

    We report the first records of the sponge genus Geodia (Demospongiae, Tetractinellida, Geodiidae) from the New England Seamounts and Muir Seamount, at lower bathyal depths. Nine specimens collected between 2000 and 2005 belong to two boreal species (Geodia macandrewii and Geodia barretti) and a temperate species (Geodia megastrella). These records extend the distributions of these deep-sea amphi-Atlantic species to the west. Most of these specimens were originally fixed in formalin, which substantially degraded the DNA. We nonetheless managed to sequence two cytochrome c oxidase subunit I (COI) mini-barcodes: the universal mini-barcode at the 5′ end of the Folmer barcode (130 bp) and a newly proposed mini-barcode at the 3′ end of the Folmer barcode (296 bp). These mini-barcodes unambiguously confirmed our identifications. As an additional test, we also successfully sequenced these two mini-barcodes from the holotype of G. barretti, collected in 1855. We conclude by advocating the use of mini-barcodes on formalin-fixed or old specimens with degraded DNA.

  • Public defence: 2018-11-09 13:15 B42, BMC, Uppsala
    Garoff, Linnéa
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Exploring the Ciprofloxacin Resistome2018Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis presents an exploration of the resistance evolution in Escherichia coli towards the antibiotic ciprofloxacin. High level ciprofloxacin resistance is typically acquired by an accumulation of mutations and plasmid borne genes reducing drug target binding, increasing drug efflux, and modifying the drug.

    Paper I describes the finding that novel mutations in tRNA synthetase gene leuS conferred resistance to ciprofloxacin. We also provided evidence for a mechanism, where the leuS mutations induced global changes in transcription that generated a net effect of increased drug efflux.

    In Paper II we observed that the evolutionary trajectory towards high level ciprofloxacin resistance in E. coli is repeatable and predictable in in vitro evolution experiments. However, the types and order of appearance of selected mutations was highly dependent on the bottleneck size used. In addition to the findings in Paper I, we found that mutations involved in transcription and translation were repeatedly selected upon subjection to high concentrations of ciprofloxacin.

    Paper III explored the resistance capacity of the plasmid-borne gene qnr, which reduces ciprofloxacin susceptibility by a target protection mechanism. We found that upon increased expression, the gene qnrS was able to bring E. coli to clinically resistant levels of ciprofloxacin without the addition of other resistance elements.  

    In Paper IV we aimed for a similar study as described above but with another plasmid-borne gene, the inner-membrane efflux pump qepA. However, we ran into the interesting finding of a potentially undescribed regulatory mechanism of qepA expression, which we are currently investigating.

    The work in this thesis presents a new addition of mutations causing ciprofloxacin resistance, and evidence that the dogma of accumulative mutations being a requirement to develop clinical resistance to ciprofloxacin in E. coli can be circumvented. This shows that there is still much to explore, even with a drug used for several decades with an already well documented resistome. We need to learn more about the evolutionary trajectories leading to antibiotic resistance, in order to slow down its development towards existing and future antibiotics to the furthest extent possible.

    List of papers
    1. Effect of aminoacyl-tRNA synthetase mutations on susceptibility to ciprofloxacin in Escherichia coli
    Open this publication in new window or tab >>Effect of aminoacyl-tRNA synthetase mutations on susceptibility to ciprofloxacin in Escherichia coli
    2018 (English)In: J Antimicrob ChemotherArticle in journal (Refereed) Published
    Abstract [en]

    Background: Chromosomal mutations that reduce ciprofloxacin susceptibility in Escherichia coli characteristically map to drug target genes (gyrAB and parCE), and genes encoding regulators of the AcrAB-TolC efflux pump. Mutations in RNA polymerase can also reduce susceptibility, by up-regulating the MdtK efflux pump. Objectives: We asked whether mutations in additional chromosomal gene classes could reduce susceptibility to ciprofloxacin. Methods: Experimental evolution, complemented by WGS analysis, was used to select and identify mutations that reduce susceptibility to ciprofloxacin. Transcriptome analysis, genetic reconstructions, susceptibility measurements and competition assays were used to identify significant genes and explore the mechanism of resistance. Results: Mutations in three different aminoacyl-tRNA synthetase genes (leuS, aspS and thrS) were shown to re- duce susceptibility to ciprofloxacin. For two of the genes (leuS and aspS) the mechanism was partially dependent on RelA activity. Two independently selected mutations in leuS (Asp162Asn and Ser496Pro) were studied in most detail, revealing that they induce transcriptome changes similar to a stringent response, including up-regulation of three efflux-associated loci (mdtK, acrZ and ydhJK). Genetic analysis showed that reduced susceptibility depended on the activity of these loci. Broader antimicrobial susceptibility testing showed that the leuS mutations also reduce susceptibility to additional classes of antibiotics chloramphenicol, rifampicin, mecillinam, ampicillin and trimethoprim). Conclusions: The identification of mutations in multiple tRNA synthetase genes that reduce susceptibility to ciprofloxacin and other antibiotics reveals the existence of a large mutational target that could contribute to re- sistance development by up-regulation of an array of efflux pumps.

    National Category
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-361197 (URN)
    Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21
    2. Evolutionary Trajectories Dependent on Bottleneck Size and a New Class of Genes Selected During the Development of Ciprofloxacin Resistance in Escherichia coli
    Open this publication in new window or tab >>Evolutionary Trajectories Dependent on Bottleneck Size and a New Class of Genes Selected During the Development of Ciprofloxacin Resistance in Escherichia coli
    Show others...
    2018 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The evolution of resistance to ciprofloxacin (CIP) in Escherichia coli is strongly associated with the accumulation of multiple chromosomal mutations. Mutations are selected in genes encoding subunits of the target enzymes, and genes encoding direct or indirect regulators of drug efflux. We asked whether and how transmission bottleneck size would affect the evolutionary trajectory of chromosomal mutation accumulation. Independent lineages of E. coli were selected for growth at increasing concentrations of ciprofloxacin up to and above the clinical resistance breakpoint. Evolution experiments were made with three different transmission bottlenecks: single cell, ≈ 3x108, and ≈ 3x1010 cfu. Whole genome sequencing was used to analyse selected clones and populations at different stages during evolution. Under all conditions mutations in gyrA were the first to be selected and to approach or reach fixation. Evolution with the largest population bottleneck selected combinations of mutations similar to those found in resistant clinical isolates (gyrA S83, D87, with parC S80). As predicted by population genetics theory, evolution with a single cell bottleneck resulted in a greater diversity of mutations. Mutations were selected in genes directly regulating drug efflux, and in novel genes involved in transcription and translation, at least some of which are known to indirectly affect drug efflux. Evolution with the intermediate bottleneck, ≈ 3x108, also selected for mutations in a wide variety of genes, similar to the profile associated with the single cell bottleneck. The data suggest that the order of chromosomal mutations accumulated under selection for resistance to ciprofloxacin is highly predictable but the precise evolutionary trajectories differ significantly as a function of transmission bottleneck size.

    National Category
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-361198 (URN)
    Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21
    3. Increased expression of Qnr is sufficient to confer clinical resistance to ciprofloxacin in Escherichia coli
    Open this publication in new window or tab >>Increased expression of Qnr is sufficient to confer clinical resistance to ciprofloxacin in Escherichia coli
    2018 (English)In: J Antimicrob Chemother, Vol. 73, no 2, p. 348-352Article in journal (Refereed) Published
    Abstract [en]

    Background: Ciprofloxacin, a fluoroquinolone, targets two essential bacterial enzymes, DNA gyrase and topoisomerase IV. Plasmid-borne qnr genes, encoding proteins that protect DNA gyrase and topoisomerase IV from inhibition by fluoroquinolones, contribute to resistance development. However, the presence of a plasmid-borne qnr gene alone is insufficient to confer clinical resistance. Objectives: We asked whether the level of expression of qnr was a limiting factor in its ability to confer clinical resistance and whether expression could be increased without reducing fitness or viability. Methods: qnrB and qnrS were recombineered onto the chromosome of Escherichia coli under the control of constitutive promoters of various strengths. Expression was measured by qPCR, MIC and relative fitness as a function of expression level were determined. Results: For both qnr genes there was a positive relationship between the level of qnr mRNA and the MIC of ciprofloxacin. The highest MICs achieved with qnrB or qnrS as the sole resistance determinant were 0.375 and 1 mg/L, respectively, and were reached at expression levels that did not affect growth rate or viability. The qnrS-mediated MIC is above the EUCAST clinical breakpoint for resistance to ciprofloxacin. In the absence of Lon protease activity, overexpression of qnr genes was associated with high fitness cost, possibly explaining observations of toxicity in other genetic backgrounds. Conclusions: The ability to generate a high MIC without incurring a fitness cost shows that, in an appropriate genetic context, qnrS has the potential to generate clinical resistance to ciprofloxacin in one step.

    National Category
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-361199 (URN)1460-2091 (Electronic) 0305-7453 (Linking) (ISBN)
    Note

    Garoff, Linnea Yadav, Kavita Hughes, Diarmaid eng England J Antimicrob Chemother. 2018 Feb 1;73(2):348-352. doi: 10.1093/jac/dkx375.

    Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21
    4. The qepA Gene is Dependent on Upstream Sequences to Reduce Susceptibility to Ciprofloxacin
    Open this publication in new window or tab >>The qepA Gene is Dependent on Upstream Sequences to Reduce Susceptibility to Ciprofloxacin
    2018 (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    The plasmid-borne qepA gene encodes a quinolone efflux pump that confers resistance to ciprofloxacin in clinical isolates of Escherichia coli. According to published data qepA is transcribed from a promoter 31 bp upstream of the coding sequence. We asked whether ciprofloxacin MIC associated with qepA in E. coli would vary as a function of mRNA expression level. To our surprise we found that the annotated qepA coding sequence was not sufficient to increase MIC. We decided to investigate the role played by surrounding sequences in determining resistance to ciprofloxacin. The qepA region was engineered onto the E. coli chromosome and mutations were generated to test the significance of surrounding sequences for expression of resistance. MIC was measured by broth microdilution. A 3.2 kb fragment from a resistance plasmid, including the annotated qepA coding sequence (1.5 kb), generated an 8-fold ciprofloxacin MIC increase when recombined into the E. coli chromosome. Deletion analysis revealed that the MIC increase was dependent on sequences upstream of qepA, annotated as ∆int1/groEL and ∆dfr2. Combining sequence analysis and mutagenesis, we identified a promoter within the ∆int1/groEL sequence, required for expression of resistance. The predicted transcript included two open reading frames (orf1 261 bp, orf2 189 bp) upstream of qepA. Deletion analysis revealed the essentiality of orf2 for the MIC increase. In conclusion, we have identified a new promoter for qepA, provided evidence that expression of the qepA coding sequence is not sufficient for resistance, and that resistance is influenced by sequences upstream of the qepA coding sequence. Details of the resistance mechanism remain to be elucidated.

    National Category
    Microbiology
    Identifiers
    urn:nbn:se:uu:diva-361200 (URN)
    Available from: 2018-09-21 Created: 2018-09-21 Last updated: 2018-09-21
  • Sjöstrand, Axel
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Social and Economic Geography.
    Arkitektens roll och ansvar: Arkitekten och samhället - en splittrad skildring2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    En viktig faktor i våra liv är omgivningen vi lever och rör oss i. Vi är en del av arkitekturen som är med oss i vardagen. För vissa är arkitektur och de byggnader vi rör oss bland, inte lika viktigt som för andra. Vissa går så långt som att bilda grupper för att göra sina kritiska röster hörda. Dessa kritiska röster menar i de flesta fall att den rådande arkitekturen är direkt oduglig - att majoriteten av det som byggs har för stela former och saknar detaljer som en gång varit mer närvarande än vad den är idag. Enligt kritiska röster ritar och skapar arkitekter byggnader som de själva och resten av arkitektkårens sympatisörer anser vara vackra. Två arkitekter i Uppsala menar att de är medvetna om den kritik som finns, men att debatten och den allmänna diskussionen är för onyanserad och att den saknar djup. Med detta sagt är syftet med denna uppsats att undersöka vad arkitekter själva har att framföra för åsikter och tankar angående den rådande arkitekturens situation idag, samt att höra deras åsikter om vad deras roll och ansvar i samhället är. Studiens teori bygger på att det finns en polarisering mellan arkitekter och allmänheten, och empirin baseras på två intervjuer som gjorts med två arkitekter i Uppsala. Sammanfattningsvis går det att i stora drag, dra vissa slutsatser om att arkitekterna som intervjuats är väl medvetna om kritiken som finns, men att vanliga lekmän inte kan uttala sig om arkitektur på samma sätt som en arkitekt kan. Den konstnärliga och estetiska aspekten av arkitektyrket, menar arkitekterna, är en viktig del av yrket och de ser sig som konstnärer och bärare av en fackkunskap som ska bidra till ett bättre samhälle.

  • Mogensen, Ronnie
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Maibach, Julia
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Naylor, Andrew J.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Younesi, Reza
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Capacity fading mechanism of tin phosphide anodes in sodium-ion batteries2018In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 47, no 31, p. 10752-10758Article in journal (Refereed)
    Abstract [en]

    Tin phosphide (Sn4P3) is here investigated as an anode material in half-cell, symmetrical, and full-cell sodium-ion batteries. Results from the half-cells using two different electrolyte salts of sodium bis(fluorosulfonyl)imide (NaFSI) or sodium hexafluorophosphate (NaPF6) show that NaFSI provides improved capacity retention but results from symmetrical cells disclose no advantage for either salt. The impact of high and low desodiation cut-off potentials is studied and the results show a drastic increase in capacity retention when using the desodiation cut-off potential of 1.2 V as compared to 2.5 V. This effect is clear for both NaFSI and NaPF6 salts in a 1:1 binary mixture of ethylene carbonate and diethylene carbonate with 10 vol% fluoroethylene carbonate. Hard X-ray photoelectron spectroscopy (HAXPES) results revealed that the thickness of the solid electrolyte interphase (SEI) changed during cycling and that SEI was stripped from tin particles when tin phosphide was charged to 2.5 V with NaPF6 based electrolyte.

  • Weiberg, Erika
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History, Classical archaeology and ancient history.
    Finné, Martin
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History, Classical archaeology and ancient history.
    Resilience and persistence of ancient societies in the face of climate change: a case study from Late Bronze Age Peloponnese2018In: World archaeology, ISSN 0043-8243, E-ISSN 1470-1375Article in journal (Refereed)
    Abstract [en]

    Instances of resilience and persistence in ancient societies during periods of climate stress are necessary as counter weights to simplified collapse archaeology. The authors offer an evaluation of societal trajectories during the Late Bronze Age (LBA) in the Peloponnese against the backdrop of recently available local climate data. By considering climate volatility as well as climate change, the long-term perspective suggests that the end of the LBA should be viewed in light of the socio-environmental mismatches that developed during its earlier phases. Varying socio-political complexity and population densities are preconditioning components for inherent resilience under climate stress and climate impacts cannot be determined by climate conditions alone. While arid climate does not equal negative societal change, beneficial climate conditions may be favourable in the relative short term while at the same time supporting an ultimately unsustainable economy that proved detrimental in the long term.

  • Jahankhah, Pegah
    et al.
    Svanholm, Ann
    Förbättring av produktions- och packningsprocessen hos Eazpac AB2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Företaget som har valts för detta examensarbete är Eazpac AB. Företaget producerar plasthättor, Eazycover ™ att täcka och skydda mat med, för att förlänga hållbarheten på mat och råvaror.

    Företaget Eazpac AB har haft problem med svinn av hättor i produktions- och packningsprocessen. Syftet med examensarbetet är att kartlägga var svinnet uppstår, orsakerna till detta samt ge förslag på förbättringsåtgärder för produktions- och packningsprocessen för Eazpac.

    Mängden av svinnet är oklart på grund av att företaget inte har mätt det över tid. Under examensarbetet används relevanta teorier från både artiklar och kurslitteratur. Teorier har valts baserat på företagets problem och mest inom kvalitetsstyrning och hur företaget ska förebygga slöseri.

    DMAIC-modellen har utgjort grunden för studiens arbetsgång. Verktyg som användes i define fasen är intervju, observation och litteraturstudie. Nästa fas är measure, i denna fas samlades tillgängliga data in om hur mycket svinn uppstår under produktions och- packningsprocessen. Med hjälp av primär- och sekundärdata som är både kvalitativa och kvantitativa började författarna analyse fasen. Baserat på analysen kunde möjliga förbättringsförslag föreslås.

    Svinnet inträffar dels vid produktionslinorna när trasiga hättor produceras och dessa upptäcks. Här är det främst hättorna av storlek large som måste kasseras och till en mindre del medium. Produktionsprocessen för storlek small har en mycket låg kassation. Nästa ställe i processen där svinnet inträffar är vid packningen. När hättorna packas upptäcks de trasiga hättor som inte har hittats vid produktionslinorna.

    Data som varit tillgängliga visar en ögonblicksbild, i procent, av hur många hättor som försvinner. Processen för att tillverka small är stabil. Svinnet varierar mellan 0,4 och 1,5 %. För medium är processen också stabil, även om svinnet ligger lite högre då det varierar mellan 2 och 3 %. För large är skillnaden större och svinnet varierar mellan 2,3 och 7,8 %. Förutom svinn av hättor, så har företaget också ett spill av råvaran plast.

    Examensarbetet visar att svinnet finns på två ställen. Dels vi produktion och del vid packningen. En del av svinnet är på grund av uttag för marknadsföring, övrigt svinn beror förmodligen på trasiga hättor. Företaget bör få till rutiner och standarder för att styra och följa upp produktions- och packningsprocessen.

  • Kakko, Johan
    et al.
    Umeå Univ, Norrlands Univ Sjukhus, Psykiatriska Klin Umeå, Dept Clin Sci,Psychiat, Umeå, Sweden.
    Gedeon, Charlotte
    Solstenen i Skane, Addict Ctr, Lund, Sweden.
    Sandell, Mikael
    Capio Maria, Stockholm, Sweden; Capio Maria, Skåne, Sweden.
    Grelz, Henrik
    Lund Univ, Dept Clin Sci, Malmo, Sweden; Skåne Univ Hosp, Pain Rehabil Dept, Skåne, Sweden.
    Birkemose, Inge
    Misbrugsbehandling, Odense Kommune, Overlaege, Odense, Denmark.
    Clausen, Thomas
    Univ Oslo, Norwegian Ctr Addict Res, Oslo, Norway.
    Runarsdottir, Valgerour
    Vogur Hosp, SAA Natl Ctr Addict Med, Reykjavik, Iceland.
    Simojoki, Kaarlo
    Univ Helsinki, A Clin Fdn A Clin Oy, Helsinki, Finland; Helsinki Univ Hosp, Helsinki, Finland.
    Littlewood, Richard
    Applied Strateg, London, England.
    Alho, Hannu
    Univ Hosp, Abdominal Ctr, Helsinki, Finland; Univ Helsinki, Helsinki, Finland.
    Nyberg, Fred
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Principles for managing OUD related to chronic pain in the Nordic countries based on a structured assessment of current practice2018In: Substance Abuse Treatment, Prevention, and Policy, ISSN 1747-597X, E-ISSN 1747-597X, Vol. 13, article id 22Article, review/survey (Refereed)
    Abstract [en]

    Background: Long-term use of opioid analgesics (OA) for chronic pain may result in opioid use disorder (OUD). This is associated with adverse outcomes for individuals, families and society. Treatment needs of people with OUD related to chronic pain are different compared to dependence related to use, and also injection, of illicit opioids. In Nordic countries, day-to-day practical advice to assist clinical decision-making is insufficient.

    Aim: To develop principles based on expert clinical insights for treatment of OUD related to the long-term use of OA in the context of chronic pain.

    Methods: Current status including an assessment of barriers to effective treatment in Finland, Denmark, Iceland, Norway, Sweden was defined using a patient pathway model. Evidence to describe best practice was identified from published literature, clinical guidelines and expert recommendations from practice experience.

    Results: Availability of national treatment guidelines for OUD related to chronic pain is limited across the Nordics. Important barriers to effective care identified: patients unlikely to present for help, healthcare system set up limits success, diagnosis tools not used, referral pathways unclear and treatment choices not elucidated. Principles include the development of a specific treatment pathway, awareness/ education programs for teams in primary care, guidance on use of diagnostic tools and a flexible treatment plan to encourage best practice in referral, treatment assessment, choice and ongoing management via an integrated care pathway. Healthcare systems and registries in Nordic countries offer an opportunity to further research and identify population risks and solutions.

    Conclusions: There is an opportunity to improve outcomes for patients with OUD related to chronic pain by developing and introducing care pathways tailored to specific needs of the population.

  • Lindh, E. Mattias
    et al.
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lundberg, Petter
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Lanz, Thomas
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Mindemark, Jonas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry. Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Edman, Ludvig
    Umeå Univ, Dept Phys, Organ Photon & Elect Grp, Umeå, Sweden.
    Publisher Correction: The Weak Microcavity as an Enabler for Bright and Fault-tolerant Light-emitting Electrochemical Cells2018In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 8, article id 8697Article in journal (Other academic)
  • Hermansson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences.
    Communicating Biodiversity Offsetting in Sweden2018Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    At a time when biodiversity is declining, there needs to be a shift in how development projects take responsibility for lost natural values. Such a change is provided by biodiversity offsetting which give project owners an opportunity to compensate for declines in natural quality. However, offsetting for biodiversity costs money and therefore a clear business case is needed. Like all types of Corporate Sustainable Responsibility (CSR) work the expected competitive advantages are dependent on the stakeholders’ knowledge of the CSR measures. The aim of this study was therefore to explain how ecological compensation is communicated to stakeholders and why communication is carried out from the perspective of the project owner in a Swedish context. Through interviews and building on theories of CSR, stakeholders, and communication, the results from the five cases herein shows that communication is regarded as very important to most biodiversity offsetting projects. How, when and to whom the communication was directed seemed to depend on the goal which was most important to the project owner. Four goals highlighted in the results were: To gain a social licence to operate; gain new knowledge and to further the indirect increase in natural values inherent in all biodiversity offsetting projects. Also, claiming legal permits for development was a goal for most of the responding organizations. The goals influenced which stakeholders became the most important to communicate with, and different communication strategies were used for the different stakeholders. Some stakeholders could clearly be grouped into general categories, e.g. legal authorities and non-governmental organizations, but this study concluded that the heterogenous character of many of the stakeholders mentioned by the participating organizations made it difficult to categorize these into specific groups.

  • Hyvärinen, Elisabet
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Infante Damnjanovic, Francisca
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Den expansiva Utvecklingszonen: En kvalitativ studie om mångfaldsarbete.2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This essay analyses eight different individuals perspectives on diversity in order to find knowledge about how a positive diversity work can be done. To achieve this purpose, the following question will be answered: What promotes diversity work according to informants with special expertise in the field? What tools are there that can promote and make use of diversity in different areas? The study is a qualitative study based on interviews where a deductive analysis approach, inspired from the Thematic analysis model created by Braun and Clarke was adopted. A theoretical analysis tool was created based on the third generation of Activity theory - which is based on the theories of Vygotsky, Leontyev and Engeström, as well as the Zone of proximal development and the theory of Expansive Learning. The result of the analysis of the interviewees interviews stories where placed in Engeströms third generation Activity theory. In the analysis of the result we found that there were a variety of factors that could be used to promote diversity work and that there were many tools used to promote diversity. In the interviews we found factors and tools in the form of: anonymization, competence-based recruitment, norm criticism, diversity analysis, intersectionality, separatism, representation, inclusion analysis and transparency. In addition to the above, a parallel learning process emerged: the embryo of a fourth generation Activity theory - the zone of expansive development. 

  • Hanhart, C.
    et al.
    Forschungszentrum Julich, Inst Adv Simulat, Inst Kernphys, Julich, Germany; Forschungszentrum Julich, Julich Ctr Hadron Phys, Julich, Germany.
    Holz, S.
    Univ Bonn, Helmholtz Inst Strahlen & Kernphys, Bonn, Germany.
    Kubis, B.
    Univ Bonn, Helmholtz Inst Strahlen & Kernphys, Bonn, Germany; Univ Bonn, Bethe Ctr Theoret Phys, Bonn, Germany.
    Kupść, Andrzej
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Nuclear Physics. Natl Ctr Nucl Res, High Energy Phys Dept, Warsaw, Poland.
    Wirzba, A.
    Forschungszentrum Julich, Inst Adv Simulat, Inst Kernphys, Julich, Germany; Forschungszentrum Julich, Julich Ctr Hadron Phys, Julich, Germany; Univ Calif Santa Barbara, Kavli Inst Theoret Phys, Kohn Hall, Santa Barbara, CA USA.
    Xiao, C. W.
    Forschungszentrum Julich, Inst Adv Simulat, Inst Kernphys, Julich, Germany; Forschungszentrum Julich, Julich Ctr Hadron Phys, Julich, Germany.
    Erratum to: The branching ratio omega ->pi(+) pi(-) revisited2018In: European Physical Journal C, ISSN 1434-6044, E-ISSN 1434-6052, Vol. 78, no 6, article id 450Article in journal (Other academic)
  • Hartana, C. A.
    et al.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Bergman, E. Ahlen
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Broome, A.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Berglund, S.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Johansson, M.
    Sundsvall Hosp, Dept Urol, Sundsvall, Sweden.
    Alamdari, F.
    Vastmanland Hosp, Dept Urol, Vasteras, Sweden.
    Jakubczyk, T.
    Lanssjukhuset Ryhov, Dept Urol, Jonkoping, Sweden.
    Huge, Y.
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Aljabery, F.
    Linkoping Univ, Div Urol, Dept Clin & Expt Med, Linkoping, Sweden.
    Palmqvist, K.
    Ostersund Cty Hosp, Dept Surg, Urol Sect, Ostersund, Sweden.
    Holmström, Benny
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Urology.
    Glise, H.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Riklund, K.
    Umea Univ, Dept Radiat Sci, Diagnost Radiol, Umea, Sweden.
    Sherif, A.
    Umea Univ, Dept Surg & Perioperat Sci Urol & Androl, Umea, Sweden.
    Winqvist, O.
    Karolinska Inst, Dept Med Solna, Unit Immunol & Allergy, Stockholm, Sweden.
    Tissue-resident memory T cells are epigenetically cytotoxic with signs of exhaustion in human urinary bladder cancer2018In: Clinical and Experimental Immunology, ISSN 0009-9104, E-ISSN 1365-2249, Vol. 194, no 1, p. 39-53Article in journal (Refereed)
    Abstract [en]

    Tissue-resident memory T (T-RM) cells are CD8(+) T lymphocytes that reside in the tissues, including tumours. This T cell subset possesses a magnitude of cytotoxicity, but its epigenetic regulation has not been studied. Here, we investigate the impact of perforin DNA methylation in T-RM cells and correlate it with their functional potential. Fifty-three urothelial urinary bladder cancer (UBC) patients were recruited prospectively. The DNA methylation status of the perforin gene (PRF1) locus in T-RM cells was investigated by pyrosequencing. Flow cytometry with ViSNE analysis and in-vitro stimulation were used to evaluate T-RM cell phenotypes. We discovered that tumour T-RM cells have low DNA methylation in the PRF1 locus (32<bold></bold>9% methylation), which corresponds to increased numbers of perforin-expressing T-RM cells. Surprisingly, programmed cell death 1 (PD-1) expression is high in tumour T-RM cells, suggesting exhaustion. Following interleukin-15 and T cell receptor stimulation, perforin and T-bet expressions are enhanced, indicating that T-RM cells from tumours are not terminally exhausted. Moreover, a high number of T-RM cells infiltrating the tumours corresponds to lower tumour stage in patients. In conclusion, T-RM cells from UBC tumours are epigenetically cytotoxic with signs of exhaustion. This finding identifies T-RM cells as potential new targets for cancer immunotherapy.

  • Carlzon, Eric
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Archaeology and Ancient History.
    Spår av sjukliga förändringar i gotländskt, mänskligt benmaterial, från stenålder till medeltid – en sammanställning av forskningsläget på Gotland2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This bachelor thesis is a compilation of previous master and bachelor theses written by osteology students at Högskolan på Gotland and Uppsala University Campus Gotland, with a focus on palaeopathology in individuals from the island of Gotland, from the Stone Age through the Middle Ages. The purpose of this thesis is to shed light on the history of disease on the island of Gotland on a bigger scale than previous theses have done. Most master and bachelor theses have typically focused on one site or settlement, set in a particular time period in their study, whereas I chose to combine all of the studies into one cohesive examination of all disease surveyable in the skeleton of these individuals. This, in order to see if there are differences to be found in the various time periods, or even differences among the population within a specific time period. And there are some differences to be seen, indeed; most notably perhaps between the Iron Age and the Middle Ages, where a difference in the dental health can clearly be seen. When comparing the other time periods however, caution must be advised; the skeletal material is lacking in most eras other than the Iron Age and the Middle Ages.

  • Abdallah, Sam
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Educational Sciences, Department of Education.
    Grupputvecklingssamtal - lärande för individen?: En kvalitativ studie om grupputvecklingssamtal och lärande hos medarbetare2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med denna studie är att undersöka grupputvecklingssamtal mellan chef och medarbetare på en avdelning på Akademiska sjukhuset som grund för medarbetarens lärande. Lärandet som undersöks är hur individer kan tillgodogöra sig arbetskunskap utifrån de lärandeprocesser som eventuellt uppstår i samband med gruppsamtal. Frågeställningarna som följer i denna uppsats är ”vad innefattar ett grupputvecklingssamtal på avdelningen på Akademiska sjukhuset?”, ”hur upplever medarbetarna grupputvecklingssamtalet som grund för deras professionella lärande?” och ”vilket slags lärande har premierats?”. Undersökningsmetoderna för denna studie är observation och intervju. Observation har genomförts för att ge svar på vad ett grupputvecklingssamtal på avdelningen på Akademiska sjukhuset innefattar och intervjuer har genomförts för att ge en bild av hur medarbetarna upplever grupputvecklingssamtalen som grund för deras professionella lärande. De analysverktyg som använts för att framställa studiens resultat är det empiriska materialet som framkommit från observationen samt intervjuerna och de teoretiska infallsvinklarna, ”kollektivt lärande” och ”dialog”. Resultaten har visat att ett grupputvecklingssamtal innefattar ett möte där medarbetarna får information om olika saker gällande arbetet och vad som händer på arbetsplatsen. Vidare har resultaten indikerat på att medarbetarna upplever grupputvecklingssamtalen som grund för deras professionella lärande och att det är kollektivt lärande som premierats. Denna studie har främst bidragit till att ge avdelningschefen och gruppcheferna som genomför dessa samtal en uppfattning om att samtalen gynnar medarbetarna i den mån att det ger dem ett kollektivt lärande. Det gör också medarbetarna uppmärksamma på att samtalen kan främja interaktionen mellan dem liksom utförandet av deras arbetsuppgifter.

  • Svensson, Josefin
    Uppsala University, University Administration, Communications Division.
    Universen 3:2018: En tidning för Uppsala universitets medarbetare2018Collection (editor) (Other (popular science, discussion, etc.))
    Abstract [sv]

    Innehåll i Universen nr 3:2018

    Sid 2: Ledare

    Sid 3: Kritiska samtal i Humanistiska teatern

    Sid 4: Nytt karriärcentrum för personal i akademin

    Sid 5: EU-godkännande ska driva på HR-arbetet

    Sid 6: Samlat grepp kring it-verksamheten

    Sid 7: 3D-skrivare ger nya möjligheter

    Sid 8: Svårt att få tiden att räcka till

    Sid 9: "Förutsättningarna för mänskligheten påverkas"

    Sid 10: På jobbet - Förändring som tar tid

    Sid 12: Behandling av Alzheimer visar unika resultat

    Sid 13: Tänker nytt kring vattenfrågor

    Sid 14: Grogrund för smarta idéer

    Sid 17: Forskning i samarbete med Cirkus Cirkör

    Sid 19: Krönika: Campus Gotland fyller fem år

    Sid 20: Profilen - Sanna Wolk

  • Apler, Anna
    et al.
    Geological Survey of Sweden.
    Snowball, Ian
    Uppsala University, Disciplinary Domain of Science and Technology, Earth Sciences, Department of Earth Sciences, Natural Resources and Sustainable Development.
    Frogner-Kockum, Paul
    Swedish Geotechnical Institute.
    Josefsson, Sarah
    Geological Survey of Sweden.
    Distribution and dispersal of metals in contaminated fibrous sediments of industrial origin2019In: Chemosphere, ISSN 0045-6535, E-ISSN 1879-1298, Vol. 215, p. 470-481Article in journal (Refereed)
    Abstract [en]

    Industrial emissions can impact aquatic environments and unregulated discharges from pulp and paper factories have resulted in deposits of cellulose fiber along the Swedish coast. These deposits are contaminated by metals, but due to their unique fibrous character the extent of sorption and dispersal of the metals is unclear. Fibrous sediments were sampled at two sites in the Ångermanälven river estuary, Sweden. The partitioning of metals between the sediment, pore water and bottom water was investigated and the degree of bioavailability was evaluated. The levels of metals in the sediment were high in fibrous or offshore samples, depending on the metal, whereas the levels of dissolved metals in pore water were low or below the limit of quantification. Partition coefficients (KD) showed that sorption to the sediment was stronger at one of the fibrous sites, possibly related to the type and size of organic matter. Undisturbed bottom water samples contained low levels of both dissolved and particle bound metals, but when comparing measured metal concentrations to threshold values of ecological status and ecotoxicological assessment criteria, both sediments and bottom water may be detrimental to living organisms. In-situ re-suspension experiments showed that the concentrations of particle bound metals increased whereas the dissolved concentrations decreased. The analyzed metals are probably retained by the solid phases of the fibrous sediment or adsorbed to particles in the water, reducing their bioavailability.

  • Kovacs, Daniel
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Phipps, Dulcie
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Orthaber, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Borbas, K. Eszter
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Molecular Biomimetics.
    Highly luminescent lanthanide complexes sensitised by tertiary amide-linked carbostyril antennae2018In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 47, no 31, p. 10702-10714Article in journal (Refereed)
    Abstract [en]

    Carbostyrils are among the most widely used sensitising antennae for luminescent lanthanides; they afford bright complexes with Eu and Tb, and can also sensitise the emissions of the less commonly used Sm, Dy, Yb and Nd. Systematic studies on the effect of structural variations on the photophysical properties and lanthanide sensitising abilities of carbostyrils can therefore have a large impact. We replaced the secondary amide linker that connects the metal binding site to the antenna with a carboxymethyl-substituted tertiary amide. Eight Tb and Eu complexes were prepared. All had higher lanthanide luminescence quantum yields (phi(Ln)) than their secondary amide analogues; three Tb emitters had phi(Tb) > 40%. Eu complexes had phi(Eu) up to 11.6%. The antenna singlet and triplet excited states are slightly shifted, while the metal coordination sphere is unchanged by the introduction of the carboxymethyl group.

  • Hattori, Yocefu
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Abdellah, Mohamed
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. South Valley Univ, Qena Fac Sci, Dept Chem, Qena 83523, Egypt.
    Rocha, Igor
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Nanotechnology and Functional Materials.
    Pavliuk, Mariia V.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Fernandes, Daniel L. A.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Sá, Jacinto
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry. Polish Acad Sci, Inst Phys Chem, PL-01224 Warsaw, Poland.
    Light-induced ultrafast proton-coupled electron transfer responsible for H-2 evolution on silver plasmonics2018In: Materials Today, ISSN 1369-7021, E-ISSN 1873-4103, Vol. 21, no 6, p. 590-593Article in journal (Refereed)
    Abstract [en]

    Light-driven proton-coupled electron transfer (PCET) reactions on nanoplasmonics would bring temporal control of their reactive pathways, in particular, prolong their charge separation state. Using a silver nano-hybrid plasmonic structure, we observed that optical excitation of Ag-localized surface plasmon instigated electron injection into TiO2 conduction band and oxidation of isopropanol alcoholic functionality. Femtosecond transient infrared absorption studies show that electron transfer from Ag to TiO2 occurs in ca. 650 fs, while IPA molecules near the Ag surface undergo an ultrafast bidirectional PCET step within 400 fs. Our work demonstrates that ultrafast PCET reaction plays a determinant role in prolonging charge separation state, providing an innovative strategy for visible-light photocatalysis with plasmonic nanostructures.

  • Jonasson, Fredrik
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Sparresäter, Björn
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Monte Carlo-simuleringar av germaniumdetektor för gammaspektroskopi2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Syftet med projektet är att undersöka en HPGe-detektors egenskaper med hjälp av Monte Carlo-simuleringar i simuleringskoden FLUKA. Resultaten från detta projekt ska sedan användas som underlag för en kartläggning där halten av den radioaktiva isotopen cesium-137 ska mätas på svampprover insamlade från hela landet. En rad simuleringar har gjorts med olika typer av strålningskällor och med variationer på detektorns geometri. Den detektor som ska användas för dessa mätningar är över 30 år gammal vilket kan medföra att vissa egenskaper kan ha förändrats med tiden. Resultaten från simuleringarna visar dock att eventuella förändringar är försumbara. En annan del av detektorns geometri, ett kylningshål i botten av germaniumkristallen, specificeras inte tydligt i produktspecifikationerna från tillverkaren. Även här visar dock simuleringarna att hålets storlek inte har någon större betydelse. Däremot visar simuleringarna, som förväntat, att detektorns effektivitet varierar beroende på strålningens energi och avståndet från strålningskällan.

  • Huang, Jing
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Gilbert Gatty, Mélina
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Xu, Bo
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Pati, Palas Baran
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Etman, Ahmed S.
    Stockholm Univ, Dept Mat & Environm Chem MMK, SE-10691 Stockholm, Sweden.
    Tian, Lei
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Sun, Junliang
    Stockholm Univ, Dept Mat & Environm Chem MMK, SE-10691 Stockholm, Sweden.
    Hammarström, Leif
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Tian, Haining
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Physical Chemistry.
    Covalently linking CuInS2 quantum dots with a Re catalyst by click reaction for photocatalytic CO2 reduction2018In: Dalton Transactions, ISSN 1477-9226, E-ISSN 1477-9234, Vol. 47, no 31, p. 10775-10783Article in journal (Refereed)
    Abstract [en]

    Covalently linking photosensitizers and catalysts in an inorganic-organic hybrid photocatalytic system is beneficial for efficient electron transfer between these components. However, general and straightforward methods to covalently attach molecular catalysts on the surface of inorganic semiconductors are rare. In this work, a classic rhenium bipyridine complex (Re catalyst) has been successfully covalently linked to the low toxicity CuInS2 quantum dots (QDs) by click reaction for photocatalytic CO2 reduction. Covalent bonding between the CuInS2 QDs and the Re catalyst in the QD-Re hybrid system is confirmed by UV-visible absorption spectroscopy, Fourier-transform infrared spectroscopy and energy-dispersive X-ray measurements. Time-correlated single photon counting and ultrafast time-resolved infrared spectroscopy provide evidence for rapid photo-induced electron transfer from the QDs to the Re catalyst. Upon photo-excitation of the QDs, the singly reduced Re catalyst is formed within 300 fs. Notably, the amount of reduced Re in the linked hybrid system is more than that in a sample where the QDs and the Re catalyst are simply mixed, suggesting that the covalent linkage between the CuInS2 QDs and the Re catalyst indeed facilitates electron transfer from the QDs to the Re catalyst. Such an ultrafast electron transfer in the covalently linked CuInS2 QD-Re hybrid system leads to enhanced photocatalytic activity for CO2 reduction, as compared to the conventional mixture of the QDs and the Re catalyst.

  • Göras, Axel
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Government.
    Miljonprogrammet: spelade historien roll?: En kvalitativ textanalys om miljonprogrammets stigberoende och dess konsekvenser2018Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    The aim of this study is to see whether or not the so called Million Homes Programme, that was established in 1965 with the aim to build one million residencies within a ten year span, could have had alternative paths of development and outcomes and whether or not those outcomes would have affected segregation in Sweden to the same degree that many consider the programme to have done today.

    To study this, the theoretical framework of historical institutionalism will be used, more specifically with the help of an analytical tool within that framework that is called “path dependence” where the purpose is to identify critical junctures, at which actors, through influence from institutions, significantly limit the choice of actions by actors at a future point in the process. Furthermore, the study will be performed by means of analysing texts, specifically state public reports from 1965, 1975 and 1990.

    The results of the study show that there is a degree of path dependence in the Million Homes Programme, although the degree is not as great as expected. The urbanization and struggle of balance between state and municipalities in city planning are the main factors that enable a certain path dependence. However, more material must be analysed in order to establish a stronger degree of path dependence. The study is able to confirm that the Million Homes Programme could have developed alternatively and had different outcomes, but it is not possible to confirm whether or not those outcomes would have affected or significantly changed the segregation that is seen in Sweden today.

  • Sylvester, Boniphace
    et al.
    Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth & Social Sci, Dept Parasitol & Med Entomol, POB 65001, Dar Es Salaam, Tanzania.
    Gasarasi, Dinah B.
    Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth & Social Sci, Dept Parasitol & Med Entomol, POB 65001, Dar Es Salaam, Tanzania.
    Aboud, Said
    Muhimbili Univ Hlth & Allied Sci, Sch Med, Dept Microbiol & Immunol, POB 65001, Dar Es Salaam, Tanzania.
    Tarimo, Donath
    Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth & Social Sci, Dept Parasitol & Med Entomol, POB 65001, Dar Es Salaam, Tanzania.
    Masawe, Siriel
    Muhimbili Univ Hlth & Allied Sci, Sch Med, Dept Obstet & Gynaecol, POB 65001, Dar Es Salaam, Tanzania.
    Mpembeni, Rose
    Muhimbili Univ Hlth & Allied Sci, Sch Publ Hlth & Social Sci, Dept Epidemiol & Biostat, Dar Es Salaam, Tanzania.
    Swedberg, Göte
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    Interferon-gamma and Interleukin-10 Responses during Clinical Malaria Episodes in Infants Aged 0-2 Years Prenatally Exposed to Plasmodium falciparum: Tanzanian Birth Cohort2018In: Journal of Tropical Medicine, ISSN 1687-9686, E-ISSN 1687-9694, article id 6847498Article in journal (Refereed)
    Abstract [en]

    Background: Infants born to mothers with placental malaria are prenatally exposed to Plasmodium falciparum antigens. However, the effect of that exposure to subsequent immune responses has not been fully elucidated. This study aimed at determining the effect of prenatal exposure to P. falciparum on Interleukin-10 and Interferon-gamma responses during clinical malaria episodes in the first 24 months of life.

    Methods: This prospective cohort study involved 215 infants aged 0-2 years born to mothers with or without placental malaria. Enzyme-linked immunosorbent assay (ELISA) was used to determine levels of IL-10 and IFN-gamma in infants and detect IgM in cord blood. Data were analyzed using SPSS version 20.

    Findings: Geometric mean for IFN-gamma in exposed infants was 557.9 pg/ml (95% CI: 511.6-604.1) and in unexposed infants it was 634.4 pg/ml (95% CI: 618.2-668.5) (P=0.02). Mean IL-10 was 22.4 pg/ml (95% CI: 19.4-28.4) and 15.1 pg/ml (95% CI: 12.4-17.6), respectively (P=0.01).

    Conclusions: Prenatal exposure to P. falciparum antigens significantly affects IL-10 and IFN-gamma responses during clinical malaria episodes in the first two years of life.

  • Escaned, Javier
    et al.
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Ryan, Nicola
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Mejia-Renteria, Hernan
    Hosp Clin San Carlos, IDISSC, Madrid, Spain;Univ Complutense Madrid, Madrid, Spain.
    Cook, Christopher M.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Dehbi, Hakim-Moulay
    UCL, CRUK & UCL Canc Trials Ctr, London, England.
    Alegria-Barrero, Eduardo
    Hosp Univ Torrejon, Madrid, Spain;Univ Francisco de Vitoria, Madrid, Spain.
    Alghamdi, Ali
    King Abdulaziz Med City Cardiac Ctr, Riyadh, Saudi Arabia.
    Al-Lamee, Rasha
    Imperial Coll London, Hammersmith Hosp, London, England.
    Altman, John
    Colorado Heart & Vasc, Lakewood, CO USA.
    Ambrosia, Alphonse
    Baptista, Sergio B.
    Hosp Prof Doutor Fernando Fonseca, Amadora, Portugal.
    Bertilsson, Maria
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, UCR-Uppsala Clinical Research Center.
    Bhindi, Ravinay
    Royal North Shore Hosp, Sydney, NSW, Australia.
    Birgander, Mats
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Bojara, Waldemar
    Kemperhof Koblenz, Gemeinschaftsklinikum Mittelrhein, Koblenz, Germany.
    Brugaletta, Salvatore
    Inst Invest Biomed August Pi & Sunyer, Hosp Clin, Cardiovasc Inst, Barcelona, Spain.
    Buller, Christopher
    St Michaels Hosp, Toronto, ON, Canada.
    Calais, Fredrik
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Silva, Pedro Canas
    Hosp Santa Maria, Lisbon, Portugal.
    Carlsson, Jorg
    Linnaeus Univ, Fac Hlth & Life Sci, Kalmar, Sweden;Kalmar Cty Hosp, Kalmar, Sweden.
    Christiansen, Evald H.
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Danielewicz, Mikael
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Di Mario, Carlo
    Univ Florence, Florence, Italy;Imperial Coll London, Royal Brompton Hosp, London, England.
    Doh, Joon-Hyung
    Inje Univ, Ilsan Paik Hosp, Daehwa Dong, South Korea.
    Erglis, Andrejs
    Pauls Stradins Clin Univ Hosp, Riga, Latvia.
    Erlinge, David
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Gerber, Robert T.
    Conquest Hosp, St Leonards On Sea, England.
    Going, Olaf
    Sana Klinikum Lichtenberg, Lichtenberg, Germany.
    Gudmundsdottir, Ingibjorg
    Reykjavik Univ Hosp, Dept Cardiol, Reykjavik, Iceland.
    Haerle, Tobias
    Carl von Ossietzky Univ Oldenburg, European Med Sch, Klinikum Oldenburg, Oldenburg, Germany.
    Hauer, Dario
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Hellig, Farrel
    Sunninghill Hosp, Johannesburg, South Africa.
    Indolfi, Ciro
    Magna Graecia Univ Catanzaro, Catanzaro, Italy.
    Jakobsen, Lars
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Janssens, Luc
    Imelda Hosp, Bonheiden, Belgium.
    Jensen, Jens
    Sundsvall Hosp, Dept Med, Sundsvall, Sweden;Capio St Gorans Sjukhus, Unit Cardiol, Stockholm, Sweden;Karolinska Inst, Sodersjukhuset, Dept Clin Sci & Educ, Stockholm, Sweden.
    Jeremias, Allen
    SUNY Stony Brook, Med Ctr, Stony Brook, NY 11794 USA.
    Karegren, Amra
    Vastmanland Hosp Vasteras, Dept Internal Med, Vasteras, Sweden.
    Karlsson, Ann-Charlotte
    Halmstad Cty Hosp, Dept Cardiol, Halmstad, Sweden.
    Kharbanda, Rajesh K.
    Oxford Univ Hosp Fdn Trust, John Radcliffe Hosp, Oxford, England.
    Khashaba, Ahmed
    Ain Shams Univ, Cairo, Egypt.
    Kikuta, Yuetsu
    Fukuyama Cardiovasc Hosp, Fukuyama, Hiroshima, Japan.
    Krackhardt, Florian
    Univ Med, Charite Campus Virchow Klinikum, Berlin, Germany.
    Koo, Bon-Kwon
    Seoul Natl Univ Hosp, Seoul, South Korea.
    Koul, Sasha
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Laine, Mika
    Helsinki Univ Hosp, Helsinki, Finland.
    Lehman, Sam J.
    Flinders Univ S Australia, Adelaide, SA, Australia.
    Lindroos, Pontus
    St Goran Hosp, Dept Cardiol, Stockholm, Sweden.
    Malik, Iqbal S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Maeng, Michael
    Aarhus Univ Hosp, Dept Cardiol, Aarhus, Denmark.
    Matsuo, Hitoshi
    Gifu Heart Ctr, Gifu, Japan.
    Meuwissen, Martijn
    Amphia Hosp, Breda, Netherlands.
    Nam, Chang-Wook
    Keimyung Univ, Dongsan Med Ctr, Daegu, South Korea.
    Niccoli, Giampaolo
    Univ Cattolica Sacro Cuore, Rome, Italy.
    Nijjer, Sukhjinder S.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Olsson, Hans
    Karlstad Hosp, Dept Cardiol, Karlstad, Sweden.
    Olsson, Sven-Erik
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Omerovic, Elmir
    Sahlgrenska Univ Gothenburg, Dept Cardiol, Gothenburg, Sweden.
    Panayi, Georgios
    Linkoping Univ, Dept Med & Hlth Sci, Linkoping, Sweden;Linkoping Univ, Dept Cardiol, Linkoping, Sweden.
    Petraco, Ricardo
    Imperial Coll London, Hammersmith Hosp, London, England.
    Piek, Jan J.
    Acad Med Ctr, AMC Heart Ctr, Amsterdam, Netherlands.
    Ribichini, Flavo
    Univ Hosp Verona, Verona, Italy.
    Samady, Habib
    Emory Univ, Atlanta, GA 30322 USA.
    Samuels, Bruce
    Cedars Sinai Heart Inst, Los Angeles, CA USA.
    Sandhall, Lennart
    Helsingborg Hosp, Dept Cardiol, Helsingborg, Sweden;Helsingborg Hosp, Dept Radiol, Helsingborg, Sweden.
    Sapontis, James
    MonashHeart, Melbourne, Vic, Australia;Monash Univ, Melbourne, Vic, Australia.
    Sen, Sayan
    Imperial Coll London, Hammersmith Hosp, London, England.
    Seto, Arnold H.
    Vet Affairs Long Beach Healthcare Syst, Long Beach, CA USA.
    Sezer, Murat
    Istanbul Univ, Istanbul Fac Med, Istanbul, Turkey.
    Sharp, Andrew S. P.
    Univ Exeter, Exeter, Devon, England;Royal Devon & Exeter Hosp, Exeter, Devon, England.
    Shin, Eun-Seok
    Univ Ulsan, Coll Med, Ulsan Univ Hosp, Ulsan, South Korea.
    Singh, Jasvindar
    Washington Univ, Sch Med, St Louis, MO USA.
    Takashima, Hiroaki
    Aichi Med Univ Hosp, Nagakute, Aichi, Japan.
    Talwar, Suneel
    Royal Bournemouth Gen Hosp, Bournemouth, Dorset, England.
    Tanaka, Nobuhiro
    Tokyo Med Univ, Tokyo, Japan.
    Tang, Kare
    Anglia Ruskin Univ, Chelmsford, England;Essex Cardiothorac Ctr, Basildon, England.
    Van Belle, Eric
    Lille Univ Hosp, Inst Coeur Poumon, Lille, France;INSERM, Unite 1011, Lille, France.
    van Royen, Niels
    Vrije Univ Amsterdam Med Ctr, Amsterdam, Netherlands.
    Varenhorst, Christoph
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cardiology.
    Vinhas, Hugo
    Hosp Garcia de Horta, Lisbon, Portugal.
    Vrints, Christiaan J.
    Antwerp Univ Hosp, Antwerp, Belgium.
    Walters, Darren
    Prince Charles Hosp, Brisbane, Qld, Australia.
    Yokoi, Hiroyoshi
    Fukuoka Sannou Hosp, Fukuoka, Japan.
    Frobert, Ole
    Orebro Univ, Fac Hlth, Dept Cardiol, Orebro, Sweden.
    Patel, Manesh R.
    Duke Univ, Durham, NC USA.
    Serruys, Patrick
    Imperial Coll London, Dept Cardiol, London, England.
    Davies, Justin E.
    Imperial Coll London, Hammersmith Hosp, London, England.
    Gotberg, Matthias
    Lund Univ, Dept Cardiol, Clin Sci, Skane Univ Hosp, Lund, Sweden.
    Safety of the Deferral of Coronary Revascularization on the Basis of Instantaneous Wave-Free Ratio and Fractional Flow Reserve Measurements in Stable Coronary Artery Disease and Acute Coronary Syndromes2018In: JACC: Cardiovascular Interventions, ISSN 1936-8798, E-ISSN 1876-7605, Vol. 11, no 15, p. 1437-1449Article in journal (Refereed)
    Abstract [en]

    OBJECTIVES The aim of this study was to investigate the clinical outcomes of patients deferred from coronary revascularization on the basis of instantaneous wave-free ratio (iFR) or fractional flow reserve (FFR) measurements in stable angina pectoris (SAP) and acute coronary syndromes (ACS). BACKGROUND Assessment of coronary stenosis severity with pressure guidewires is recommended to determine the need for myocardial revascularization. METHODS The safety of deferral of coronary revascularization in the pooled per-protocol population (n = 4,486) of the DEFINE-FLAIR (Functional Lesion Assessment of Intermediate Stenosis to Guide Revascularisation) and iFR-SWEDEHEART (Instantaneous Wave-Free Ratio Versus Fractional Flow Reserve in Patients With Stable Angina Pectoris or Acute Coronary Syndrome) randomized clinical trials was investigated. Patients were stratified according to revascularization decision making on the basis of iFR or FFR and to clinical presentation (SAP or ACS). The primary endpoint was major adverse cardiac events (MACE), defined as the composite of all-cause death, nonfatal myocardial infarction, or unplanned revascularization at 1 year. RESULTS Coronary revascularization was deferred in 2,130 patients. Deferral was performed in 1,117 patients (50%) in the iFR group and 1,013 patients (45%) in the FFR group (p < 0.01). At 1 year, the MACE rate in the deferred population was similar between the iFR and FFR groups (4.12% vs. 4.05%; fully adjusted hazard ratio: 1.13; 95% confidence interval: 0.72 to 1.79; p = 0.60). A clinical presentation with ACS was associated with a higher MACE rate compared with SAP in deferred patients (5.91% vs. 3.64% in ACS and SAP, respectively; fully adjusted hazard ratio: 0.61 in favor of SAP; 95% confidence interval: 0.38 to 0.99; p = 0.04). CONCLUSIONS Overall, deferral of revascularization is equally safe with both iFR and FFR, with a low MACE rate of about 4%. Lesions were more frequently deferred when iFR was used to assess physiological significance. In deferred patients presenting with ACS, the event rate was significantly increased compared with SAP at 1 year.

  • Gestrin, Samuel
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de libris in typographia Wisingsburgensi impressis, quam consent. ampliss. ord. philos. Ups. publico examini offerunt ... Samuel Gestrin, ... atque Daniel Axner, Gestricii. In audit. Gust. maj. die XI Dec. MDCCXCIII.1793Dissertation (older thesis) (Other academic)
  • Gestrich, Jonas Samuel
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Theology.
    Comparatio inter apostolos Jesu et præsentis ævi sacerdotes quam loco examinis pastoralis speciali gratia s:æ r:æ majestatis et venia max. venerand. facult. theol Ups. exhibent Jon. Sam. Gestrich ... et Petr. Calvagen Medelpadus in aud. Eccl. d. XIII Decemb. MDCCCIX.1809Dissertation (older thesis) (Other academic)
  • Geringius, Israel
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertationem, qva ordo oeconomiæ publicæ sistitur, consentiente ampliss. senatu phil. publico examini modeste subjiciunt Israël Geringius ... et Johannes Henr. Brantenberg, nericius. In aud. Car. maj. d. X Maj. MDCCLXXVII.1777Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Observationes nonnullas historicas, de aristocratia sub regibus Folkungis, cum cons. ampl. ord. philosoph. in reg. Upsal. acad. præside mag. Carolo Fred. Georgii ... dissertatione academica, ad publicum examen modeste defert stipendiarius regius Jonas Carol. Genberg, Angermannus. In aud. Gustav. maj. d. XXI. Junii. a. MDCCLXXX. H. a. m. s.1780Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio historica de æra Christianæ religionis in Sveo-Gothia receptæ, quam, consent. ampl. phil. ord. in reg. acad. Upsal. præside mag. Carolo Fred. Georgii ... pro obtinendis honoribus philosophicis, publice examinandam modeste sistit Henricus Nylén, Sudermannus. Stipendiarius regius. In audit. Gust. maj. d. [tomrum] Junii 1779. H. a. m. s.1779Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio historica de regione metallica Carlskoga, quam, venia ampl. fac. philos. Ups. praeside mag. Carolo Freder. Georgii, ... Pro gradu philosophico, publice ventilandam exhibet Nicolaus Gustavi Kjellin, Vermelandus. In audit. Gust. maj. d. 5 Maji 1779. H. A. M. C.1779Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Meletemata nonnulla generaliora de usu synchronismorum in antiquiori patria historia, quæ, consent. ampliss. ord. phil. Upsaliensi, praeside mag. Carolo Fred. Georgii, ... dissertatione graduali exhibet Johannes Lange, Gothlandus, in aud. Gust. maj. die XXVII. Mart. a. MDCCLXXIX. Horis ante meridiem solitis.1779Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertationis historicæ, qua disqviritur: quid ad mores et civile imperium gentibus Europæis profuerint expeditiones, quae vocantur cruciatæ, part. I. ... præside mag. Carolo Fred. Georgii ... pro gradu philosophico proponet Jonas Hallenberg, Smolandus. In aud. Car. maj. d. 8. Junii 1776. Horis a. m. solitis.1776Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Observationes qvædam generaliores de peregrinis imperii Sviogothici regibus, ante foedera Calmariensia, quas ven. ampl. fac. phil. Ups. præside mag. Carolo Fred. Georgii, ... Pro gradu publico examini subjicit Jacobus Brander Vestro-Bothniensis. In aud. Carol. maj. d. V Junii a. MDCCLXXVI.1776Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De Emundis, periodi Lodbrochicæ regibus, generaliores quasdam observationes, suffrag. ampliss. in incluto Upsal. athenæo, facultate philosophica, præside, Mag. Carolo Fred. Georgii, ... censuræ publicæ subjicit Petrus Frigelius Calmariensis, in Aud. Carol. Major. Die XXI. Junii MDCCLXXV. Horis, ante meridiem, consvetis.1775Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Disquisitio historica, de vario gentium genio, respectu libertatis, cujus partem secundam, consensu ampliss. facult. philosoph. in reg. acad. Upsal. praeside Mag. Carolo Fred. Georgii, ... in audit. Carol. Majori, Hor. ante Merid. Solitis D. [tomrum] Maji A. MDCCLXXIII. Pro gradu publice ventilandam sistit stipendiarius Nesselianus Simon Nibelius, Vestmannus.1773Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Disquisitio historica, de vario gentium genio, respectu libertatis, cujus partem primam, consensu ampliss. facult. philosoph. in reg. acad. Upsal. praeside Mag. Carolo Fred. Georgii, ... in audit. Gustavian. Hor. ante Merid. Solitis D. XIII. Nov. A. MDCCLXXI, publice ventilandam sistit Auctor Simon Nibelius, Vestmannus, stipendiarius Nesselianus.1771Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Specicum historicum de insula Sela, Sudermanniæ, cujus partem priorem, consensu ampliss. ordin. philos. in regia academia Upsaliensi, præside, mag. Carolo Fred. Georgii, ... Examinandam sistit stipendiarius regius Ericus Humbla Sudermannus, in auditorio Carolino majori, ad diem III Julii. 1771.1771Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    De unione haereditaria Arosiensi, sub Gustavo I. Dissertatio historica, quam, suffrag. ampl. ord. Phil. R. Acad. Upsal. præside M. Carolo Fred. Georgii, ... eruditis placide ventilandam præbet Johannes Ericus Noreen, Reg. Acad. Scient. Stockolm. Adscriptus Stockholmiensis. Die XX. Decembris Anni MDCCLXX. In Audit. Carol. Maj. h. a. m. s.1770Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Disquisitio historica, de variis gentium moribus, cujus partem primam, dissertatione graduali, consensu amplissimi ordinis philosophici, in regia academia Upsaliensi, præside, mag. Carol. Fred. Georgii, ... publice ventilandam sistit stipendiarius Ahllöfvianus, Andreas Norberg, Vestmannus. In auditorio Carol. maj. d. 5. Junii, a. MDDLXX h. a. m. s., P. 11770Dissertation (older thesis) (Other academic)
  • Georgii, Carl Fredrik
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio historica, Dissidia de primatu, inter sedem archiepiscopalem Upsaliensem et Lundensem breviter exponens. Quam ... præside ... Carolo Fred. Georgii ... pro summis in philosophia honoribus publicæ disquisitioni subjicit ... Jonas Tengborg, Vestrogothus. In audit. Carolin. maj. die VII. Junii. Anni MDCCLXVI. H.A.M.S.1766Dissertation (older thesis) (Other academic)