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  • Lenhard, Fabian
    et al.
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Healthcare Serv, Stockholm, Sweden..
    Ssegonja, Richard
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Andersson, Erik
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden..
    Feldman, Inna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Ruck, Christian
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Healthcare Serv, Stockholm, Sweden..
    Mataix-Cols, David
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Healthcare Serv, Stockholm, Sweden..
    Serlachius, Eva
    Karolinska Inst, Dept Clin Neurosci, Ctr Psychiat Res, Stockholm, Sweden.;Stockholm Cty Council, Stockholm Healthcare Serv, Stockholm, Sweden..
    Cost-effectiveness of therapist-guided internet-delivered cognitive behaviour therapy for paediatric obsessive-compulsive disorder: results from a randomised controlled trial2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 5, e015246Article in journal (Refereed)
    Abstract [en]

    Objectives To evaluate the cost-effectiveness of a therapist-guided internet-delivered cognitive behaviour therapy (ICBT) intervention for adolescents with obsessive-compulsive disorder (OCD) compared with untreated patients on a waitlist. Design Single-blinded randomised controlled trial. Setting A research clinic within the regular child and adolescent mental health service in Stockholm, Sweden. Participants Sixty-seven adolescents (12-17 years) with a Diagnostic and Statistical Manual of Mental Disorders Fifth Edition diagnosis of OCD. Interventions Either a 12-week, therapist-guided ICBT intervention or a wait list condition of equal duration. Primary outcome measures Cost data were collected at baseline and after treatment, including healthcare use, supportive resources, prescription drugs, prescription-free drugs, school absence and productivity loss, as well as the cost of ICBT. Health outcomes were defined as treatment responder rate and quality-adjusted life years gain. Bootstrapped mixed model analyses were conducted comparing incremental costs and health outcomes between the groups from the societal and healthcare perspectives. Results Compared with waitlist control, ICBT generated substantial societal cost savings averaging US$-144.98 (95% CI -159.79 to -130.16) per patient. The cost reductions were mainly driven by reduced healthcare use in the ICBT group. From the societal perspective, the probability of ICBT being cost saving compared with waitlist control was approximately 60%. From the healthcare perspective, the cost per additional responder to ICBT compared with waitlist control was approximately US$78. Conclusions The results suggest that therapist-guided ICBT is a cost-effective treatment and results in societal cost savings, compared with patients who do not receive evidence-based treatment. Since, at present, most patients with OCD do not have access to evidence-based treatments, the results have important implications for the increasingly strained national and healthcare budgets. Future studies should compare the cost-effectiveness of ICBT with regular face-to-face CBT.

  • Persson, Emilia
    et al.
    Gustafsson, Christian
    Nordström, Fredrik
    Sohlin, Maja
    Gunnlaugsson, Adalsteinn
    Petruson, Karin
    Rintelä, Niina
    Hed, Kristoffer
    Blomqvist, Lennart
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Zackrisson, Björn
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Nyholm, Tufve
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    Olsson, Lars E.
    Siversson, Carl
    Jonsson, Joakim
    Umeå University, Faculty of Medicine, Department of Radiation Sciences.
    MR-OPERA: a multicenter/multivendor validation of magnetic resonance imaging–only prostate treatment planning using synthetic computed tomography images2017In: International Journal of Radiation Oncology, Biology, Physics, ISSN 0360-3016, E-ISSN 1879-355X, Vol. 99, no 3, 692-700 p.Article in journal (Refereed)
    Abstract [en]

    Purpose: To validate the dosimetric accuracy and clinical robustness of a commercially available software for magnetic resonance (MR) to synthetic computed tomography (sCT) conversion, in an MR imaging–only workflow for 170 prostate cancer patients.

    Methods and Materials: The 4 participating centers had MriPlanner (Spectronic Medical), an atlas-based sCT generation software, installed as a cloud-based service. A T2-weighted MR sequence, covering the body contour, was added to the clinical protocol. The MR images were sent from the MR scanner workstation to the MriPlanner platform. The sCT was automatically returned to the treatment planning system. Four MR scanners and 2 magnetic field strengths were included in the study. For each patient, a CT-treatment plan was created and approved according to clinical practice. The sCT was rigidly registered to the CT, and the clinical treatment plan was recalculated on the sCT. The dose distributions from the CT plan and the sCT plan were compared according to a set of dose-volume histogram parameters and gamma evaluation. Treatment techniques included volumetric modulated arc therapy, intensity modulated radiation therapy, and conventional treatment using 2 treatment planning systems and different dose calculation algorithms.

    Results: The overall (multicenter/multivendor) mean dose differences between sCT and CT dose distributions were below 0.3% for all evaluated organs and targets. Gamma evaluation showed a mean pass rate of 99.12% (0.63%, 1 SD) in the complete body volume and 99.97% (0.13%, 1 SD) in the planning target volume using a 2%/2-mm global gamma criteria.

    Conclusions: Results of the study show that the sCT conversion method can be used clinically, with minimal differences between sCT and CT dose distributions for target and relevant organs at risk. The small differences seen are consistent between centers, indicating that an MR imaging–only workflow using MriPlanner is robust for a variety of field strengths, vendors, and treatment techniques.

  • Kindström, Merit
    et al.
    Executive, Universitet, Swedish University of Agricultural Sciences.
    Lundin, Assar
    Executive, Universitet, Swedish University of Agricultural Sciences.
    Nilsson, Björn
    Executive, Universitet, Swedish University of Agricultural Sciences.
    Glimskär, Anders
    Executive, Universitet, Swedish University of Agricultural Sciences.
    Inventering och utveckling för hällmarksnaturtyper, alvar och svämängar 20162016Report (Other academic)
    Abstract [sv]

    Biogeografisk uppföljning ska följa upp areal och utbredning av naturtyper inom art- och habitatdirektivet samt dess viktiga strukturer, funktioner och typiska arter. I rapporten beskrivs resultat från arbete med biogeografisk uppföljning av några naturtyper med sparsam eller aggregerad fördelning i landskapet. Rapporten presenterar resultat för naturtypen 8230 Hällmarkstorräng samt metodiktester och förslag till uppföljning för naturtyperna 6280 Alvar, 6110 Basiska berghällar, 8240 Karsthällmarker och 6450 Svämängar. En mindre förstudie om möjligheten att utveckla metodik för sandmarker (6120, 2320, 2330) och slåtterängar (6510, 6520, 6530) har också genomförts och redovisas i rapporten.

  • Rösblad, Birgit
    Visual and proprioceptive control of arm movements: studies of development and dysfunction1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this dissertation was to examine the role of sensory information for control of goal-directed arm movements in children. The role of visual and proprioceptive information on the target for end point accuracy was examined in normal 4- to 12-year- old children (Study I), and in children with motor impairments (Study II). Accuracy in pointing with the unseen hand was found to improve rapidly during the age period tested, with the most pronounced development taking place in the preschool years. Visual specification of the target was superior to proprioceptive specification for all age groups tested. The performance of children with motor impairments was more variable than that of the non-impaired children, and this effect was most pronounced when visual information about the target was unavailable. The importance of visual information for controlling the transport and handling part of reaching movements were examined in normal 6- to 8-year-old children (Study III), and in children with developmental coordination disorders (Study IV). Object handling required visual information on both target and hand. For the transport phase of the movement visual information on target was sufficient, and sight of hand did not improve performance. The young children were relatively more impaired than the older children when lacking adequate visual information. The children with developmental coordination disorders responded to the withdrawal of visual information in a similar way to that of the normally developed children. A discontinuity at 7 years of age in the development of perceptual control of pointing movements, observed in Study I, was further investigated and confirmed in study V. In this study the ability to control movements visually and prorioceptively was also investigated and found to develop in parallel rather than one being a prerequisite for the other.

  • Niklasson, Urban
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Clinical Physiology.
    Spectral analysis of the heart rate variability: a methodological study1993Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Heart rate and other cardiovascular variables are not steady but fluctuate over time. The evolution of computer technology the last 2 decades has made detailed analysis of the fluctuations possible and has focused the attention to the information content of the variability.

    Autonomic nervous influence on the heart can be assessed by measuring the heart rate variability from R-R intervals in the electrocardiogram. Applications have been developed in many fields where the pathophysiological features of the patients include autonomic dysfunction.

    This thesis is based on clinical studies and model studies compared with results from healthy volunteers. Two patient groups, with familial amyloidosis and with myotonic dystrophy, were evaluated using simple indexes of heart rate variability. Signs of autonomic dysfunction which is a dominant clinical feature in familial amyloidosis with polyneuropathy was confirmed by abnormal heart rate variability indexes. In myotonic dystrophy heart rate variability was normal but recumbent and standing plasma catecholamines were elevated. Reassessment of the heart rate variability with spectral analysis confirmed the results.

    The integral pulse frequency modulation (IPFM) model can be used as a simple analogy of the interface between autonomic activity and the cardiac pacemaker. Computer simulations using the IPFM model revealed marked differences in the estimated modulating variability depending on whether the intervals between simulated beats or the frequency of beats was analyzed. Comparison with data from healthy volunteers indicated that the IPFM model was valid and that heart rate should be preferred instead of R-R intervals for variability measurements.

    Beat-by-beat heart rate can be viewed as an irregular sample of the underlying autonomic activity. Spectral analysis of simulated heart rate variability data using the IPFM model showed attenuation of high frequency variability with decreasing mean heart rate and with increasing variability mean frequency. Application of these results on data from healthy volunteers suggest that the effects can be significant in actual variability measurements.

    Cholinergic blockade resulted in reduced heart rate variability at all spectral frequencies. Adrenergic beta-blockade reduced high-frequency variability in standing position indicating that high-frequency variability might partly be sympathetically mediated.

  • Wikman, Marianne
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Obstetrics and Gynecology. Umeå University, Faculty of Medicine, Department of Clinical Sciences, Psychiatry.
    To desire and to choose: aspects of women's and men's urge to have children1994Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The aim of this study was to increase available knowledge about women's and men’s desire for pregnancy and for a child/children to serve as a basis for further studies of problems and inconsistencies in the reproductive sphere. The motivation to become a parent was hypothesized as being not only of an existential, social, interpersonal and intrapsychic character but also a biologically anchored personality trait.

    The first part of the study deals with the development of a method for collecting valid information concerning this intimate and personal sphere of life and to categorize this information into measurable dimensions. A questionnaire was constructed and factor analysis was used as a statistical tool. There are two versions of the final instrument, one for women and one for men. Interviews were used as a means of testing the validity of the instrument. Experiences from the methodological development process revealed that it was meaningful to deal with the issue though suitable wording was not easily found.

    In the main part of the study, two large populations, one reference group of 416 women and 329 men of fertile ages and one group of expecting parents, 369 women and 345 men, were investigated by means of the questionnaire. Attitudes were dominated by two opposing views of children: 'Children mean existential satisfaction' and 'Children mean restriction of freedom'. This confirmed the findings of earlier studies and clinical experience that ambivalence is a natural phenomenon, that may be associated with feelings of guilt. The view of one's own parents as models in parenthood was a third important dimension. The view of the child's sex was a fourth important and complex dimension.

    The similarities between women and men were striking. There were only subtle differences between reference women and pregnant women. Reference men and child-expecting men had different response patterns, child-expecting men emphasizing more the advantages of having children.

    In the last part of the study 48 women were followed during pregnancy and after childbirth using the questionnaire and determination of levels of the intestinal peptide gastrin. Gastrin may be a marker of energy-storing characteristics, thus influencing reproductive capacity. There were some attitudinal differences between 0-parous women and parous women, the latter agreeing less with the view of 'children as restriction of freedom'. The view of 'children as existential satisfaction' was agreed with more after childbirth than during pregnancy. The view of one’s own parents as models in parenthood correlated with the levels of gastrin during this period.

  • Lorentzon, Ann
    et al.
    RISE - Research Institutes of Sweden, Bioeconomy.
    Lindström, Annika
    RISE - Research Institutes of Sweden, Bioeconomy.
    Wickholm, Kristina
    RISE - Research Institutes of Sweden, Bioeconomy.
    Williams, Helen
    Karlstad university.
    Wikström, Fredrik
    Karlstad university.
    Förpackningssystem för minskat matsvinn: Slutrapportering del 2 : samverkansprojekt2017Report (Other academic)
    Abstract [sv]

    Matsvinn är en stor global samhällsutmaning. Det är ett komplext problem som kräver samverkan och en mängd lösningar för att lösas. Samverkansprojektet har tittat på hur förpackningssystem kan bidra till att minska det globala samhällsproblemet med matsvinn. Resultatet från projektet manifesteras i de nya förpackningslösningar som tagits fram för projektets tre produkter salsa, salladsmix och risgröt. Lösningarna är utvecklade för att minska matsvinn genom hela kedjan, från fyllning till konsument. Inledande konsumenttester indikerar att lösningarna skulle tas väl emot på marknaden. En förenklad klimatanalys visar på att lösningarna medför minskad miljöpåverkan. Utöver förpackningslösningarna, som tagits fram i fysiska prototyper, har projektet lett till att deltagande parter – genom projektets frekventa samverkan i workshopar, uppföljningsmöten samt studiebesök – fått nya kunskaper och fördjupad förståelse kring utmaningar längs produkternas hela värdekedja.

  • Gustafsson, Maria
    et al.
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Mattsson, Sofia
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience.
    Gallego, Gisselle
    Students' satisfaction with a web-based pharmacy program in a re-regulated pharmacy market2017In: Pharmacy, ISSN 2226-4787, E-ISSN 1913-4711, Vol. 5, no 3, E47Article in journal (Refereed)
    Abstract [en]

    In response to the shortage of pharmacists in Northern Sweden, a web-based Bachelor of Science in Pharmacy program was established at Umeå University in 2003. In 2009, the Swedish pharmacy market was re-regulated from a state monopoly to an open market, but it is unknown what impact this has had on education satisfaction. The objectives of this study were to examine the level of satisfaction among graduates from a web-based pharmacy program and to describe what subjects and skills students would have liked more or less of in their education. A secondary objective was to compare the level of satisfaction before and after the Swedish pharmacy market was re-regulated. A cross-sectional survey was conducted in 2015 with all alumni who had graduated from the pharmacy program between 2006 and 2014 (n = 511), and responses to questions about graduates' satisfaction with the program were analyzed (n = 200). Most graduates (88%) agreed or strongly agreed that the knowledge and skills acquired during their education were useful in their current job. The graduates stated that they would have wanted more applied pharmacy practice and self-care counselling, and fewer social pharmacy and histology courses. Further, 82% stated that they would start the same degree program if they were to choose again today, and 92% agreed or strongly agreed that they would recommend the program to a prospective student. Graduates were more likely to recommend the program after the re-regulation (p = 0.007). In conclusion, pharmacy graduates were very satisfied with their education, and no negative effects of the re-regulation could be observed on program satisfaction.

  • Kristensen, Bo Traberg
    Umeå University, Faculty of Medicine, Department of Pharmacology and Clinical Neuroscience, Clinical Neuroscience.
    Stroke in young adults in northern Sweden1998Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Objectives. To study different aspects of cerebral venous and arterial occlusive disease including cerebrospinalfluid hydrodynamics, epidemiology, aetiology, genetics, metabolic and haemostatic disorders, andcognitive function in young adults in Northern Sweden.

    Methods. Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion methodin patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations, upto 15 years after the onset of the disease.

    Epidemiological data on ischaemic stroke in young adults aged 18 to 44 years were collected to calculateincidence and mortality based on the WHO Northern Sweden MONICA register of acute strokeevents. One hundred and seven consecutive patients aged 18-44 years with ischaemic stroke referred toUmeå university hospital were studied prospectively during a five-year period and were extensively evaluatedaccording to a standardized protocol. During follow-up at least three months after onset 102 and 80patients, respectively, were evaluated for disturbances in the fibrinolytic system and in the metabolism ofhomocysteine. A comprehensive neuropsychological battery was performed in a subset of 20 patients withinfratentorial infarcts.

    Results and conclusions. All patients with superior sagittal sinus thrombosis demonstrated a marked increasein intracranial pressure due to raised pressure in the sagittal sinus. A striking feature was the persistentintracranial pressure increase with only a slow decline over time.

    The incidence rate for ischaemic stroke was higher than previously reported from most countries inWestern Europe. The higher incidence was not explained by a higher prevalence of atherosclerotic vasculopathy. In spite of extensive evaluation, including advanced cardiac imaging, the cause of ischaemic strokein young adults still remains uncertain or unknown in most cases.

    Patients had lowered tissue plasminogen activator activity and increased plasminogen activator inhibitortype 1 activity. Increased fibrinogen levels and tissue plasminogen activator mass concentration wereindependently associated with ischaemic stroke. Metabolic perturbations were closely interrelated with tissueplasminogen activator and plasminogen activator inhibitor type 1 activity. Elevated plasma fibrinogenlevels and abnormalities in the fibrinolytic system in conjunction with metabolic perturbations may be importantcontributors to an increased stroke risk among young adults.

    Stroke patients had an exaggerated increase in total homocysteine levels after methionine loading.Abnormal responsivity to methionine loading was associated with higher tissue plasminogen activatormass concentration, plasminogen activator inhibitor 1 levels and lower tissue plasminogen activator activity. Abnormal homocysteine metabolism may provide an additional thrombogenetic risk, partly mediatedby interactions with the fibrinolytic system.

    Circumscribed infratentorial lesions (mainly cerebellar) impaired central aspects of attention andworking memory, and inflicted damage upon visuospatial skills. In contrast, these patients may not sufferfrom global intellectual impairment and difficulties with respect to memory for previous events. The prognosisis favorable in terms of neurological deficits and handicap, but cognitive disability may be the mostsignificant problem in adapting to their former occupations.Key w ords. Cerebral venous thrombosis, cerebrospinal fluid dynamics, ischaemic stroke, young adults, epidemiology,fibrinolysis, homocysteine, cerebellar infarct, neuropsychology.

  • Gärling, Anita
    Umeå University, Faculty of Social Sciences, Department of Psychology.
    Parents' perceptions of children's accident risk1988Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The purpose of the present thesis was, first, to study how parents and other adults percieve or judge children’s accident risk, and, secondly, to relate such judgements to the subjects’ preferences for and satisfaction with different residential conditions.

    A theoretical framework is proposed which assumes that judgements of children’s accident risk are based on beliefs about what causes accidents to children. Such beliefs are furthermore assumed to be acquired more often from indirect sources than from own direct experiences. Nevertheless, because of parents’ higher motivation to protect their children, they are assumed to differ from other adults who are not parents with respect to their causal models and, as a consequence, their risk perceptions.

    To test some implications of the theoretical framework, three empirical studies were carried out in which parents and nonparents were requested to judge the risk children run of having accidents under different circumstances and to judge the strengths of five causes of such accidents, the parent, the child, the environment, other people, and chance. In two of the studies the subjects were also requested to express their preferences for different residential neighborhoods varying in traffic conditions, or satisfaction with their own residential conditions either as it is or if changed in different ways.

    Support for the implications of the theoretical framework was obtained in that causal explanations of accidents were shown to play a decisive role for judgements of accident risk. However, very slight differences were found between parents’ and nonparents’ causal models and risk perceptions. The results furthermore indicated that accident risk was of importance for parents’ satisfaction with their residential conditions if changes with perceived accident consequences were implemented. In this respect parents differed from nonparents. For the latter other things than children’s accident risk tended to be more important.

  • Pettersson, Lars B.
    et al.
    Executive, Universitet, Lunds universitet, LU.
    Sjöström, Caroline
    Executive, Universitet, Lunds universitet, LU.
    Biogeografisk uppföljning 2016 av dag- och nattfjärilar inom habitatdirektivet2016Report (Other academic)
    Abstract [en]

    Pettersson, L. B. & Sjöström C. 2017. Nationwide monitoring of butterflies and moths of theEU Habitats Directive 2016. Department of Biology. Lund University, Sweden. 32 pp.

    This report summarizes the monitoring of butterflies and moths during 2016 within the Biogeographical Monitoring operated by Naturvårdsverket, the Swedish Environmental Protection Agency. This project includes the monitoring of eleven butterfly species and one moth species, all listed in the EU Habitats Directive. Three of the butterfly species can be found in the northernmost part of Sweden and during this year a total of 66 areas were monitored. The Arctic Blue (Agriades aquilo) was found in 20 areas with a total of 80 individuals. The Dusky-winged Fritillary, Boloria improba, was found in 19 areas with a total of 55 individuals. No individuals of Hesperia comma catena could be found this year. During 2016 the species Xestia borealis, the only Swedish noctuid moth listed in the habitat directive, was monitored in 8 areas from Lycksele lappmark to Torne lappmark. The species was found in 6 of these areas with a total of 19 individuals. Large Blue (Phengaris arion) was observed with 155 individuals in 30 areas and combined with the data from the Swedish Butterfly Monitoring Scheme the area of occupancy of this species can be considered to be well covered within its Swedish range. The Scarce Heath (Coenonympha hero) was monitored in 49 areas in Dalarna, Värmland and Västra Götaland counties with a total of 552 individuals noted. Marsh Fritillary (Euphydryas aurinia) and Scarce Fritillary (Euphydryas maturna) are both monitored by counting larval colonies during August-September. 4870 larvae colonies of the Marsh Fritillary were observed in 104 areas, and the Scarce Fritillary was monitored in 4 areas in Uppsala, 13 areas in Örebro and 23 areas in Stockholm counties with a total of 881 colonies in these counties. The Clouded Apollo (Parnassius mnemosyne) was monitored in 32 areas in Blekinge, Stockholm, Uppsala and Västernorrland counties with a total of 585 individuals. The Apollo (Parnassius apollo) was monitored as a pilot experiment in Kalmar and Södermanland counties with 8 butterflies in 18 areas. The Violet Copper (Lycaena helle) was surveyed in 24 areas in Jämtland, Västernorrland and Västerbotten counties where 26 individuals were observed. The monitoring scheme of 2016 also included a survey of the Woodland Brown (Lopinga achine), recording 922 individuals in 4 areas on Gotland and 485 individuals in 6 areas in Östergötland counties.

  • Public defence: 2017-11-10 13:15 B/B7:113a, Uppsala Biomedicinska Centrum BMC, Uppsala
    Khaliq, Zeeshan
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Cell and Molecular Biology, Computational Biology and Bioinformatics.
    Understanding Complex Diseases and Disease Causative Agents: The Machine Learning way2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Diseases can be caused by foreign agents – pathogens – such as viruses, bacteria and other parasites, entering the body or by an internal malfunction of the body itself. The partial understanding of diseases like cancer and the ones caused by viruses, like the influenza A viruses (IAVs) and the human immunodeficiency virus, means we still do not have an efficient cure or defence against them. In this thesis we developed and applied combinations of machine learning strategies to study some of the deadliest human diseases and the agents causing them. The results obtained in this study further our understanding about them, paving the way for the development of more efficient and more reliable counter strategies against them.

    In Paper I we studied the genetic make up of the highly pathogenic (HP) avian influenza viruses and identified a viral genetic background that could potentially transform a low pathogenic (LP) strain into HP. In Paper II we identified combinatorial signatures in the IAVs genome that potentially could affect their adaptation to humans.

    Candidate HIV vaccine studies are usually carried out in nonhuman primate models. In Paper III we analysed the host responses of immunized Rhesus Macaques against the simian immunodeficiency virus infection. We found that protection in Rhesus Macaques is mediated by a gradually built up immune response, in contrast to a strong initial immune response, which we found to be detrimental to protection.

    In Paper IV we analysed 9 different cancer types and identified 38 novel long noncoding RNAs (lncRNAs) that have a disrupted expression in multiple cancer types – pan-cancer differentially expressed (DE) lncRNAs. In addition, we also found 308 novel lncRNAs whose dysregulation was specific to a certain cancer type (cancer-specific DE lncRNAs).

  • Public defence: 2017-11-10 09:15 Siegbahnsalen, Uppsala
    Ulvgård, Liselotte
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Wave Energy Converters: An experimental approach to onshore testing, deployments and offshore monitoring2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The wave energy converter (WEC) concept developed at Uppsala University consists of a point absorbing buoy, directly connected to a permanent magnet linear generator. Since 2006, over a dozen full scale WECs have been deployed at the Lysekil Research Site, on the west coast of Sweden. Beyond the development of the WEC concept itself, the full scale approach enables, and requires, experimental and multidisciplinary research within several peripheral areas, such as instrumentation, offshore operations, and wave power infrastructure.

    This thesis addresses technical challenges of testing, deploying and monitoring full scale WECs. It is divided accordingly into three topics: offshore measurement systems, onshore WEC testing and deployments. Each topic presents new or improved technical solutions to enable offshore wave power research.

    For the offshore measurement systems, a new portable data acquisition unit was developed, together with a new sensor system to be installed inside the WEC. The developed system offers a cheap and flexible option for short term offshore measurement ventures, when or where site infrastructure is not available. The system has been developed and tested during both onshore and offshore experiments, with promising results.

    On the topic of onshore WEC testing, the thesis presents an experimental approach for assessing the power take-off (PTO) damping of the WEC. In previous experimental studies, it has been measured via the generated electrical power, which neglects both mechanical losses and iron losses. Consequently, the full PTO force acting on the WEC has been underestimated. The thesis presents experimentally attained trends for the speed dependence of the PTO damping at different resistive loads, as measured from both generated electric power and from measurements of the buoy line force. A study was also performed on how the generator damping is affected by partial stator overlap, which varies with the translator position. In order to assess how the characterized damping behavior will affect the WEC operation at sea, two simulation case studies were performed.

    Finally, the thesis presents a new WEC deployment method, which has been developed through several deployment trials. By using only a tugboat, a WEC unit is transported and deployed, together with its buoy, in less than half a day. The procedure has proven to be faster, cheaper and safer than the previously used methods.

  • Public defence: 2017-11-10 09:15 Polhemsalen, Ångströmlaboratoriet, Uppsala
    Jansson, Kaj
    Uppsala University, Disciplinary Domain of Science and Technology, Physics, Department of Physics and Astronomy, Applied Nuclear Physics.
    Measurements of Neutron-induced Nuclear Reactions for More Precise Standard Cross Sections and Correlated Fission Properties2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    It is difficult to underestimate the importance of neutron cross section standards in the nuclear data field. Accurate and precise standards are prerequisites for measuring neutron cross sections. Two different projects are presented here with the aim of improving on neutron standards.

    A simulation study was performed for an experiment intended to measure the cross sections of H(n,n), 235U(n,f), and 238U(n,f) relative to each other. It gave the first estimates of the performance of the experimental setup. Its results have aided the development of the experimental setup by setting limits on the target and detector design.

    A second neutron-standard project resulted in three measurements of 6Li(n,α)t relative to 235U(n,f). Each subsequent measurement improved upon the previous one and changed the experimental setup accordingly. Although, preliminary cross sections were agreeing well with evaluated data files in some energy intervals, the main goal to measure the cross section up to 3 MeV was not reached.

    Mass yields and energy spectra are important outcomes of many fission experiments, but in low yield regions the uncertainties are still high even for recurrently studied nuclei. In order to understand the fission dynamics, one also needs correlated fission data. One particular important property is the distribution of excitation energy between the two nascent fission fragments. It is closely connected to the prompt emission of neutrons and γ’s and reveals information about how nucleons and energy are transferred within the fissioning nucleus.

    By measuring both the pre and post neutron-emission fragment masses, the cumbrance of detecting neutrons directly is overcome. This is done using the fission spectrometer VERDI and the 2E-2v method. In this work I describe how both the spectrometer, the analysis method, and the calibration procedures have been further developed. Preliminary experimental data show the great potential of VERDI, but also areas that call for more attention. A previously overlooked consequence of a central assumption was found and a correction method is proposed that can correct previously obtained data as well.

    The last part of this thesis concerns the efficiencies of the fission product extraction at the IGISOL facility. The methodology of the fission yield measurements at IGISOL are reliant on assumptions that have not been systematically investigated. The presented work is a first step of such an investigation that can also be used as a tool for optimising the setup for measurements of exotic nuclei. A simulation framework connecting three different simulation codes was developed to investigate the produced yield of fission products in a buffer gas. Several different variants of the setup were simulated and the findings were generally accordant with previous estimates. A reasonable agreement between experimental data and the simulation results is demonstrated.

  • Hadfield, James
    et al.
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Harris, Simon R
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Seth-Smith, Helena M B
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Applied Microbiology Research, Department of Biomedicine, University of Basel, Basel, Switzerland; Clinical Microbiology, University Hospital Basel, Basel, Switzerland.
    Parmar, Surendra
    Public Health England, Public Health Laboratory Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
    Andersson, Patiyan
    Menzies School of Health Research, Darwin NT, Australia.
    Giffard, Philip M.
    Menzies School of Health Research, Darwin NT, Australia; School of Psychological and Clinical Sciences, Charles Darwin University, Darwin, Australia.
    Schachter, Julius
    Department of Laboratory Medicine, University of California at San Francisco, San Francisco CA, USA.
    Moncada, Jeanne
    Department of Laboratory Medicine, University of California at San Francisco, San Francisco CA, USA.
    Ellison, Louise
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Vaulet, María Lucía Gallo
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Microbiología Clínica, Buenos Aires, Argentina.
    Fermepin, Marcelo Rodríguez
    Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Departamento de Bioquímica Clínica, Microbiología Clínica, Buenos Aires, Argentina.
    Radebe, Frans
    Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa.
    Mendoza, Suyapa
    Jefe Laboratorio de ITS, Laboratorio Nacional de Vigilancia, Jefe Laboratorio de ITS, Laboratorio Nacional de Vigilancia, FM1100, Honduras, Honduras.
    Ouburg, Sander
    Department of Medical Microbiology and Infection Control, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands.
    Morré, Servaas A
    Department of Medical Microbiology and Infection Control, Laboratory of Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands; Department of Genetics and Cell Biology, Institute of Public Health Genomics, School for Oncology & Developmental Biology (GROW), Faculty of Health, Medicine and Life Sciences, University of Maastricht, Maastricht, The Netherlands.
    Sachse, Konrad
    Institute of Molecular Pathogenesis, Friedrich-Loeffler-Institut (Federal Research Institute for Animal Health), Jena, Germany.
    Puolakkainen, Mirja
    Department of Virology, University of Helsinki and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
    Korhonen, Suvi J
    Department of Virology, University of Helsinki and Helsinki University Hospital, University of Helsinki, Helsinki, Finland.
    Sonnex, Chris
    Public Health England, Public Health Laboratory Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
    Wiggins, Rebecca
    Department of Biology, University of York, York, United Kingdom.
    Jalal, Hamid
    Public Health England, Public Health Laboratory Cambridge, Addenbrooke's Hospital, Cambridge, United Kingdom.
    Brunelli, Tamara
    Clinical Chemistry and Microbiology Laboratory, Santo Stefano Hospital, ASL4 Prato, Italy.
    Casprini, Patrizia
    Clinical Chemistry and Microbiology Laboratory, Santo Stefano Hospital, ASL4 Prato, Italy.
    Pitt, Rachel
    Sexually Transmitted Bacteria Reference Unit, Microbiological Services, Public Health England, London, United Kingdom.
    Ison, Cathy
    Sexually Transmitted Bacteria Reference Unit, Microbiological Services, Public Health England, London, United Kingdom.
    Savicheva, Alevtina
    Laboratory of Microbiology, D.O. Ott Research Institute of Obstetrics and Gynecology, St. Petersburg, Russia.
    Shipitsyna, Elena
    Laboratory of Microbiology, D.O. Ott Research Institute of Obstetrics and Gynecology, St. Petersburg, Russia; WHO Collaborating Centre for Gonorrhoea and other STIs, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Hadad, Ronza
    Örebro University, School of Science and Technology. WHO Collaborating Centre for Gonorrhoea and other STIs, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Kari, Laszlo
    Laboratory of Intracellular Parasites, Rocky Mountain Laboratories, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, Montana, USA.
    Burton, Matthew J
    Clinical Research Department, Faculty of Infectious and Tropical Diseases, London School of Hygiene & Tropical Medicine, London, United Kingdom.
    Mabey, David
    Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, Australia.
    Solomon, Anthony W
    Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, Australia.
    Lewis, David
    Centre for HIV and Sexually Transmitted Infections, National Institute for Communicable Diseases, National Health Laboratory Service, Johannesburg, South Africa;Centre for Infectious Diseases and Microbiology and Marie Bashir Institute for Infectious Diseases and Biosecurity, Westmead Clinical School, University of Sydney, Sydney, Australia.
    Marsh, Peter
    Public Health England, Public Health Laboratory Southampton, Southampton General Hospital, Southampton, United Kingdom.
    Unemo, Magnus
    Örebro University, School of Medical Sciences. WHO Collaborating Centre for Gonorrhoea and other STIs, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
    Clarke, Ian N
    Molecular Microbiology Group, University Medical School, Southampton General Hospital, Southampton, United Kingdom.
    Parkhill, Julian
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom.
    Thomson, Nicholas R.
    Pathogen Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, United Kingdom; Department of Pathogen Molecular Biology, The London School of Hygiene and Tropical Medicine, London, United Kingdom.
    Comprehensive global genome dynamics of Chlamydia trachomatis show ancient diversification followed by contemporary mixing and recent lineage expansion2017In: Genome Research, ISSN 1088-9051, E-ISSN 1549-5469, Vol. 27, no 7, 1220-1229 p.Article in journal (Refereed)
    Abstract [en]

    Chlamydia trachomatis is the world's most prevalent bacterial sexually transmitted infection and leading infectious cause of blindness, yet it is one of the least understood human pathogens, in part due to the difficulties of in vitro culturing and the lack of available tools for genetic manipulation. Genome sequencing has reinvigorated this field, shedding light on the contemporary history of this pathogen. Here, we analyze 563 full genomes, 455 of which are novel, to show that the history of the species comprises two phases, and conclude that the currently circulating lineages are the result of evolution in different genomic ecotypes. Temporal analysis indicates these lineages have recently expanded in the space of thousands of years, rather than the millions of years as previously thought, a finding that dramatically changes our understanding of this pathogen's history. Finally, at a time when almost every pathogen is becoming increasingly resistant to antimicrobials, we show that there is no evidence of circulating genomic resistance in C. trachomatis.

  • Hoffman, Victoria
    et al.
    Söderström, Lars
    Samuelsson, Eva
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine.
    Self-management of stress urinary incontinence via a mobile app: two-year follow-up of a randomized controlled trial2017In: Acta Obstetricia et Gynecologica Scandinavica, ISSN 0001-6349, E-ISSN 1600-0412, Vol. 96, no 10, 1180-1187 p.Article in journal (Refereed)
    Abstract [en]

    Introduction. We investigated the long-term effects of using a mobile app to treat stress urinary incontinence with a focus on pelvic floor muscle training. Material and methods. A previous randomized controlled trial of 123 women aged 27-72 years found that three months of self-managing stress urinary incontinence with support from the Tat((R)) app was effective. We followed up the women in the app group (n=62) two years after the initial trial with the same primary outcomes for symptom severity (International Consultation on Incontinence Questionnaire Short Form) and condition-specific quality of life (ICIQ-Lower Urinary Tract Symptom Quality of Life) and compared the scores with those at baseline. Results. Of the 62 women, 61 and 46 (75.4%), respectively, participated in three-month and two-year follow-ups. Baseline data did not differ between responders and non-responders at follow-up. The mean decreases in International Consultation on Incontinence Questionnaire Short Form and ICIQ-Lower Urinary Tract Symptom Quality of Life scores after two years were 3.1 (95% confidence interval 2.0-4.2) and 4.0 (95% confidence interval 2.1-5.9), respectively. Of the 46 women, four (8.7%) rated themselves as very much better, nine (19.6%) as much better, and 16 (34.8%) as a little better. The use of incontinence protection products decreased significantly (p=0.04), and the proportion of women who felt they could contract their pelvic muscles correctly increased from 14/46 (30.4%) at baseline to 31/46 (67.4%) at follow-up (p<0.001). Conclusions. Self-management of stress urinary incontinence with support from the Tat((R)) app had significant and clinically relevant long-term effects and may serve as first-line treatment.

  • Joffre, Thomas
    et al.
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences. Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Isaksson, Per
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Mechanics.
    Procter, Philip
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Persson, Cecilia
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Applied Materials Sciences.
    Trabecular deformations during screw pull-out: a micro-CT study of lapine bone2017In: Biomechanics and Modeling in Mechanobiology, ISSN 1617-7959, E-ISSN 1617-7940, Vol. 16, no 4, 1349-1359 p.Article in journal (Refereed)
    Abstract [en]

    The mechanical fixation of endosseous implants, such as screws, in trabecular bone is challenging because of the complex porous microstructure. Development of new screw designs to improve fracture fixation, especially in high-porosity osteoporotic bone, requires a profound understanding of how the structural system implant/trabeculae interacts when it is subjected to mechanical load. In this study, pull-out tests of screw implants were performed. Screws were first inserted into the trabecular bone of rabbit femurs and then pulled out from the bone inside a computational tomography scanner. The tests were interrupted at certain load steps to acquire 3D images. The images were then analysed with a digital volume correlation technique to estimate deformation and strain fields inside the bone during the tests. The results indicate that the highest shear strains are concentrated between the inner and outer thread diameter, whereas compressive strains are found at larger distances from the screw. Tensile strains were somewhat smaller. Strain concentrations and the location of trabecular failures provide experimental information that could be used in the development of new screw designs and/or to validate numerical simulations.

  • Olsson, Helén
    et al.
    Dalarna University, School of Education, Health and Social Studies, Social Work.
    Porskrog Kristiansen, Lisbeth
    Mittuniversitet; Högskolan i Gävle.
    Violence Risk Assessment in Forensic Nurses’ Clinical Practice: Qualitative Interview Study2017In: Global Journal of Health Science, ISSN 1916-9736, E-ISSN 1916-9744, Vol. 9, no 12, 56-63 p.Article in journal (Refereed)
    Abstract [en]

    Background: The legislation of Swedish forensic psychiatric care states that the risk of further violence must beassessed before a patient is granted release from a forensic psychiatric hospital. The aim of the study was todescribe the experiences of forensic nurses with in-patient risk assessment processes, and their implication fordaily clinical forensic praxis.

    Method: Semi-structured interviews with staff who were involved in the patients risk assessment process. Theinterview texts were analyzed using qualitative latent content analysis.

    Discussion: The forensic nursing staff has to deal with many contradictory realities. The description was aboutbeing able to balance between supporting their work with an EBP approach of risk assessment while trying toestablish interpersonal relationships and to allow for positive meetings with the patient. The study indicated thatstaff used a multiple sources of knowledge in order to make credible and accurate risk assessments.

    Conclusions: If the risk assessment process are to be used in a legally secure manner, the staff must receive regularsupport from team leadership that can provide both guidance and training. Based on a holistic approach, the linkbetween the instinct of staff and their work with structured risk assessment must be founded on routines and solidplatforms.

  • Tjong Kim Sang, Erik
    et al.
    Bollmann, Marcel
    Boschker, Remko
    Casacuberta, Francisco
    Dietz, Feike
    Dipper, Stefanie
    Domingo, Miguel
    van der Goot, Robe
    van Koppen, Marjo
    Ljubešić, Nikola
    Östling, Robert
    Stockholm University, Faculty of Humanities, Department of Linguistics, Computational Linguistics.
    Petran, Florian
    Pettersson, Eva
    Uppsala universitet.
    Scherrer, Yves
    University of Helsinki.
    Schraagen, Marijn
    Sevens, Leen
    Tiedemann, Jörg
    University of Helsinki.
    Vanallemeersch, Tom
    Zervanou, Kalliopi
    The CLIN27 Shared Task: Translating Historical Text to Contemporary Language for Improving Automatic Linguistic Annotation2017In: Computational Linguistics in the Netherlands Journal, ISSN 2211-4009, Vol. 7, 53-64 p.Article in journal (Refereed)
    Abstract [en]

    The CLIN27 shared task evaluates the effect of translating historical text to modern text with the goal of improving the quality of the output of contemporary natural language processing tools applied to the text. We focus on improving part-of-speech tagging analysis of seventeenth-century Dutch. Eight teams took part in the shared task. The best results were obtained by teams employing character-based machine translation. The best system obtained an error reduction of 51% in comparison with the baseline of tagging unmodified text. This is close to the error reduction obtained by human translation (57%).

  • Troiano, Giuseppe
    et al.
    Caponio, Vito Carlo Alberto
    Boldrup, Linda
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Gu, Xiaolian
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Lo Muzio, Lorenzo
    Sgaramella, Nicola
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Wang, Lixiao
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Nylander, Karin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Expression of the long non-coding RNA HOTAIR as a prognostic factor in squamous cell carcinoma of the head and neck: a systematic review and meta-analysis2017In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 8, no 42, 73029-73036 p.Article, review/survey (Refereed)
    Abstract [en]

    Introduction: Long noncoding RNAs (lncRNAs) are often dysregulated in cancer tissue and seem to play an important role in neoplastic processes. Recent studies have shown that the HOX transcript antisense intergenic RNA (HOTAIR) may play a role as a marker of prognosis in squamous cell carcinoma of the head and neck (SCCHN). The aim of this study was to perform a meta-analysis of studies focused on the prognostic role of HOTAIR in SCCHN.

    Results: At the end of the selection process, four studies were considered eligible for inclusion in the meta-analysis, comprising a total of 271 patients. Meta-analysis revealed that high expression of HOTAIR was associated with poor overall survival (HR, 1.90; 95% CI: [1.42, 2.53]; p < 0,0001), advanced tumor stage (OR, 3.44; 95% CI: [1.84, 6.43]; p < 0,001) and lymph-node metastasis (OR, 3.31; 95% CI: [1.24, 8.79]; p = 0,02).

    Materials and Methods: The literature search was performed in the following databases: PUBMED, SCOPUS, EMBASE and Web of Science, in order to find studies that met the inclusion criteria.

    Conclusions: Findings from this systematic review and meta-analysis revealed that HOTAIR represents a potential biomarker of prognosis in patients with squamous cell carcinoma of the head and neck.

  • Public defence: 2017-11-14 13:00 FB42, Stockholm
    Etcheverry Cabrera, Sebastian
    KTH, School of Engineering Sciences (SCI), Applied Physics, Laser Physics.
    Advanced all-fiber optofluidic devices2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Significant technological advances of the last years have been possible by developments in Optofluidics, which is a field that deals with the integration of optics and microfluidics into single devices.

    The work described in this thesis is based on five scientific publications related to the use of fiber optic technology to build integrated optofluidic devices. The first three publications are within the field of life-science and point towards in-vivo and point-of-care applications, whereas the last two publications cover the study and the use of plasmonic nanoparticles for electrical modulation of light.

    Aiming at developing useful tools for in-vivo biological applications, the first publication consists of designing and testing a functional optical fiber for real-time monitoring and selective collection of fluorescent microparticles. This probe relies on a microstructured optical fiber with a hole along its cladding, which is used to selectively aspirate individual particles of interest once their fluorescence signal is detected. On the same line of research, the second publication contemplates the fabrication of a fiber probe that traps single microparticles and allows for remote detection of their optical properties. This probe is also based on a microstructured fiber that enables particle trapping by fluidic forces. The third publication addresses the development of an all-fiber miniaturized flow cytometer for point-of-care applications. This system can analyze, with excellent accuracy and sensitivity, up to 2500 cells per second by measuring their fluorescence and scattering signal. A novel microfluidic technique, called Elasto-inertial microfluidics, is employed for aligning the cells into a single-stream to optimize detection and throughput.

    The fourth publication involves the experimental and theoretical study of the electrical-induced alignment of plasmonic gold nanorods in suspension and its applicability to control light transmission. This study is done by using an all-fiber optofluidic device, based on a liquid-core fiber, which facilitates the interaction of light, electric fields, and liquid suspensions. Results show that nanorods can be aligned in microseconds, providing a much better performance than liquid-crystal devices. Finally, the fifth publication consists of an upgrade of the previous device by integrating four electrodes in the cladding of the liquid-core fiber. This improvement enables nanosecond response time and the possibility of digitally switching nanorods between two orthogonal aligned states, overcoming the limitation of slow thermal relaxation.

    The work presented here shows that optofluidics based on optical fibers is a robust and convenient platform, as well as a promising direction for the developing of novel instruments in fields such as life-science, non-linear optics, plasmonic, and sensing.

  • Sundin, Josefin
    et al.
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience, Physiology.
    Amcoff, Mirjam
    Stockholm Univ, Dept Zool Funct Zoomorphol, Stockholm, Sweden.;Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA..
    Mateos-Gonzalez, Fernando
    Univ Texas Austin, Sect Integrat Biol, Austin, TX 78712 USA.;Univ Konstanz, Max Planck Inst Ornithol, Dept Collect Behav, Constance, Germany..
    Raby, Graham D.
    Australian Inst Marine Sci, Townsville, Qld, Australia.;Univ Windsor, Great Lakes Inst Environm Res, Windsor, ON, Canada..
    Jutfelt, Fredrik
    Norwegian Univ Sci & Technol, Dept Biol, Trondheim, Norway..
    Clark, Timothy D.
    Australian Inst Marine Sci, Townsville, Qld, Australia.;Univ Tasmania, Hobart, Tas, Australia.;CSIRO Agr & Food, Hobart, Tas, Australia..
    Long-term exposure to elevated carbon dioxide does not alter activity levels of a coral reef fish in response to predator chemical cues2017In: Behavioral Ecology and Sociobiology, ISSN 0340-5443, E-ISSN 1432-0762, Vol. 71, no 8, 108Article in journal (Refereed)
    Abstract [en]

    Levels of dissolved carbon dioxide (CO2) projected to occur in the world's oceans in the near future have been reported to increase swimming activity and impair predator recognition in coral reef fishes. These behavioral alterations would be expected to have dramatic effects on survival and community dynamics in marine ecosystems in the future. To investigate the universality and replicability of these observations, we used juvenile spiny chromis damselfish (Acanthochromis polyacanthus) to examine the effects of long-term CO 2 exposure on routine activity and the behavioral response to the chemical cues of a predator (Cephalopholis urodeta). Commencing at similar to 3-20 days post-hatch, juvenile damselfish were exposed to presentday CO2 levels (similar to 420 mu atm) or to levels forecasted for the year 2100 (similar to 1000 mu atm) for 3 months of their development. Thereafter, we assessed routine activity before and after injections of seawater (sham injection, control) or seawater-containing predator chemical cues. There was no effect of CO2 treatment on routine activity levels before or after the injections. All fish decreased their swimming activity following the predator cue injection but not following the sham injection, regardless of CO2 treatment. Our results corroborate findings from a growing number of studies reporting limited or no behavioral responses of fishes to elevated CO2. Significance statement Alarmingly, it has been reported that levels of dissolved carbon dioxide (CO2) forecasted for the year 2100 cause coral reef fishes to be attracted to the chemical cues of predators. However, most studies have exposed the fish to CO2 for very short periods before behavioral testing. Using long-term acclimation to elevated CO2 and automated tracking software, we found that fish exposed to elevated CO2 showed the same behavioral patterns as control fish exposed to present-day CO2 levels. Specifically, activity levels were the same between groups, and fish acclimated to elevated CO2 decreased their swimming activity to the same degree as control fish when presented with cues from a predator. These findings indicate that behavioral impacts of elevated CO2 levels are not universal in coral reef fishes.

  • Tseli, Elena
    et al.
    Grooten, Wilhelmus Johannes Andreas
    Stålnacke, Britt-Marie
    Boersma, Katja
    Enthoven, Paul
    Gerdle, Björn
    Äng, Björn
    Dalarna University, School of Education, Health and Social Studies, Medical Science. Karolinska institutet.
    Predictors of multidisciplinary rehabilitation outcomes in patients with chronic musculoskeletal pain: protocol for a systematic review and meta-analysis2017In: Systematic Reviews, E-ISSN 2046-4053, Vol. 6, no 1, 199Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Chronic musculoskeletal pain is a major public health problem. Early prediction for optimal treatment results has received growing attention, but there is presently a lack of evidence regarding what information such proactive management should be based on. This study protocol, therefore, presents our planned systematic review and meta-analysis on important predictive factors for health and work-related outcomes following multidisciplinary rehabilitation (MDR) in patients with chronic musculoskeletal pain.

    METHODS: We aim to perform a synthesis of the available evidence together with a meta-analysis of published peer-reviewed original research that includes predictive factors preceding MDR. Included are prospective studies of adults with benign, chronic (> 3 months) musculoskeletal pain diagnoses who have taken part in MDR. In the studies, associations between personal and rehabilitation-based factors and the outcomes of interest are reported. Outcome domains are pain, physical functioning including health-related quality of life, and work ability with follow-ups of 6 months or more. We will use a broad, explorative approach to any presented predictive factors (demographic, symptoms-related, physical, psychosocial, work-related, and MDR-related) and these will be analyzed through (a) narrative synthesis for each outcome domain and (b) if sufficient studies are available, a quantitative synthesis in which variance-weighted pooled proportions will be computed using a random effects model for each outcome domain. The strength of the evidence will be evaluated using the Grading of Recommendations, Assessment, Development and Evaluation.

    DISCUSSION: The strength of this systematic review is that it aims for a meta-analysis of prospective cohort or randomized controlled studies by performing an extensive search of multiple databases, using an explorative study approach to predictive factors, rather than building on single predictor impact on the outcome or on predefined hypotheses. In this way, an overview of factors central to MDR outcome can be made and will help strengthen the evidence base and inform a wide readership including health care practitioners and policymakers.


  • Waiswa, P.
    et al.
    Makerere Univ, Sch Publ Hlth, Coll Hlth Sci, Kampala, Uganda.;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Manzi, F.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania..
    Mbaruku, G.
    Ifakara Hlth Inst, Dar Es Salaam, Tanzania..
    Rowe, A. K.
    Ctr Dis Control & Prevent, Malaria Branch, Div Parasit Dis & Malaria, Ctr Global Hlth, Atlanta, GA USA..
    Marx, M.
    Heidelberg Univ, Evaplan GmbH, Heidelberg, Germany..
    Tomson, G.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.;Karolinska Inst, Dept Learning, Informat, Management,Eth, Stockholm, Sweden..
    Marchant, T.
    London Sch Hyg & Trop Med, Dept Dis Control, London, England..
    Willey, B. A.
    London Sch Hyg & Trop Med, Dept Infect Dis Epidemiol, London, England..
    Schellenberg, J.
    London Sch Hyg & Trop Med, Dept Dis Control, London, England..
    Peterson, Stefan
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health, International Maternal and Child Health (IMCH). Makerere Univ, Sch Publ Hlth, Coll Hlth Sci, Kampala, Uganda.;Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden..
    Hanson, C.
    Karolinska Inst, Dept Publ Hlth Sci, Stockholm, Sweden.;London Sch Hyg & Trop Med, Dept Dis Control, London, England..
    Effects of the EQUIP quasi-experimental study testing a collaborative quality improvement approach for maternal and newborn health care in Tanzania and Uganda2017In: Implementation Science, ISSN 1748-5908, E-ISSN 1748-5908, Vol. 12, 89Article in journal (Refereed)
    Abstract [en]

    Background: Quality improvement is a recommended strategy to improve implementation levels for evidence-based essential interventions, but experience of and evidence for its effects in low-resource settings are limited. We hypothesised that a systemic and collaborative quality improvement approach covering district, facility and community levels, supported by report cards generated through continuous household and health facility surveys, could improve the implementation levels and have a measurable population-level impact on coverage and quality of essential services.

    Methods: Collaborative quality improvement teams tested self-identified strategies (change ideas) to support the implementation of essential maternal and newborn interventions recommended by the World Health Organization. In Tanzania and Uganda, we used a plausibility design to compare the changes over time in one intervention district with those in a comparison district in each country. Evaluation included indicators of process, coverage and implementation practice analysed with a difference-of-differences and a time-series approach, using data from independent continuous household and health facility surveys from 2011 to 2014. Primary outcomes for both countries were birth in health facilities, breastfeeding within 1 h after birth, oxytocin administration after birth and knowledge of danger signs for mothers and babies. Interpretation of the results considered contextual factors.

    Results: The intervention was associated with improvements on one of four primary outcomes. We observed a 26percentage- point increase (95% CI 25-28%) in the proportion of live births where mothers received uterotonics within 1 min after birth in the intervention compared to the comparison district in Tanzania and an 8-percentage-point increase (95% CI 6-9%) in Uganda. The other primary indicators showed no evidence of improvement. In Tanzania, we saw positive changes for two other outcomes reflecting locally identified improvement topics. The intervention was associated with an increase in preparation of clean birth kits for home deliveries (31 percentage points, 95% CI 2-60%) and an increase in health facility supervision by district staff (14 percentage points, 95% CI 0-28%).

    Conclusions: The systemic quality improvement approach was associated with improvements of only one of four primary outcomes, as well as two Tanzania-specific secondary outcomes. Reasons for the lack of effects included limited implementation strength as well a relatively short follow-up period in combination with a 1-year recall period for population-based estimates and a limited power of the study to detect changes smaller than 10 percentage points.

  • Public defence: 2017-11-10 14:00 Magnélisalen, Kemiska övningslaboratoriet, Stockholm
    Guala, Dimitri
    Stockholm University, Faculty of Science, Department of Biochemistry and Biophysics. Stockholm, Bioinformatics Center, Science for Life Laboratory.
    Functional association networks for disease gene prediction2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Mapping of the human genome has been instrumental in understanding diseasescaused by changes in single genes. However, disease mechanisms involvingmultiple genes have proven to be much more elusive. Their complexityemerges from interactions of intracellular molecules and makes them immuneto the traditional reductionist approach. Only by modelling this complexinteraction pattern using networks is it possible to understand the emergentproperties that give rise to diseases.The overarching term used to describe both physical and indirect interactionsinvolved in the same functions is functional association. FunCoup is oneof the most comprehensive networks of functional association. It uses a naïveBayesian approach to integrate high-throughput experimental evidence of intracellularinteractions in humans and multiple model organisms. In the firstupdate, both the coverage and the quality of the interactions, were increasedand a feature for comparing interactions across species was added. The latestupdate involved a complete overhaul of all data sources, including a refinementof the training data and addition of new class and sources of interactionsas well as six new species.Disease-specific changes in genes can be identified using high-throughputgenome-wide studies of patients and healthy individuals. To understand theunderlying mechanisms that produce these changes, they can be mapped tocollections of genes with known functions, such as pathways. BinoX wasdeveloped to map altered genes to pathways using the topology of FunCoup.This approach combined with a new random model for comparison enables BinoXto outperform traditional gene-overlap-based methods and other networkbasedtechniques.Results from high-throughput experiments are challenged by noise and biases,resulting in many false positives. Statistical attempts to correct for thesechallenges have led to a reduction in coverage. Both limitations can be remediedusing prioritisation tools such as MaxLink, which ranks genes using guiltby association in the context of a functional association network. MaxLink’salgorithm was generalised to work with any disease phenotype and its statisticalfoundation was strengthened. MaxLink’s predictions were validatedexperimentally using FRET.The availability of prioritisation tools without an appropriate way to comparethem makes it difficult to select the correct tool for a problem domain.A benchmark to assess performance of prioritisation tools in terms of theirability to generalise to new data was developed. FunCoup was used for prioritisationwhile testing was done using cross-validation of terms derived fromGene Ontology. This resulted in a robust and unbiased benchmark for evaluationof current and future prioritisation tools. Surprisingly, previously superiortools based on global network structure were shown to be inferior to a localnetwork-based tool when performance was analysed on the most relevant partof the output, i.e. the top ranked genes.This thesis demonstrates how a network that models the intricate biologyof the cell can contribute with valuable insights for researchers that study diseaseswith complex genetic origins. The developed tools will help the researchcommunity to understand the underlying causes of such diseases and discovernew treatment targets. The robust way to benchmark such tools will help researchersto select the proper tool for their problem domain.

  • Public defence: 2017-11-10 13:00 William-Olssonsalen, Stockholm
    Morlanes, José Igor
    Stockholm University, Faculty of Social Sciences, Department of Statistics.
    Some Extensions of Fractional Ornstein-Uhlenbeck Model: Arbitrage and Other Applications2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This doctoral thesis endeavors to extend probability and statistical models using stochastic differential equations. The described models capture essential features from data that are not explained by classical diffusion models driven by Brownian motion.

    New results obtained by the author are presented in five articles. These are divided into two parts. The first part involves three articles on statistical inference and simulation of a family of processes related to fractional Brownian motion and Ornstein-Uhlenbeck process, the so-called fractional Ornstein-Uhlenbeck process of the second kind (fOU2). In two of the articles, we show how to simulate fOU2 by means of circulant embedding method and memoryless transformations. In the other one, we construct a least squares consistent estimator of the drift parameter and prove the central limit theorem using techniques from Stochastic Calculus for Gaussian processes and Malliavin Calculus.

    The second phase of my research consists of two articles about jump market models and arbitrage portfolio strategies for an insider trader. One of the articles describes two arbitrage free markets according to their risk neutral valuation formula and an arbitrage strategy by switching the markets. The key aspect is the difference in volatility between the markets. Statistical evidence of this situation is shown from a sequential data set. In the other one, we analyze the arbitrage strategies of an strong insider in a pure jump Markov chain financial market by means of a likelihood process. This is constructed in an enlarged filtration using Itô calculus and general theory of stochastic processes.

  • Public defence: 2017-11-10 13:00 Nordenskiöldsalen, Geovetenskapens hus, Stockholm
    Eikje Ramberg, Linn
    Stockholm University, Faculty of Humanities, Department of Archaeology and Classical Studies.
    Mynt er hva mynt gjør: En analyse av norske mynter fra 1100-tallet: produksjon, sirkulasjon og bruk2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    The kings of Norway issued coins on a regular basis starting in the mid-11th century, and probably conducted renovatio monetae whenever a new king came to power. As a privilege of bona regalia, the king could use coin production to serve his own interests. Economic factors are usually the main focus of discussions on coinage, but there were also political, religious and cultural dimensions that must have been important both for the production of coins and in the choice of motives, form and style. From the outset, manipulation of the coinage is visible in the debasement of silver content, followed by a reduction in weight to re-establish the silver level.  In the 12th century, the weights continued to drop and single-faced coins and bracteates became the standard; only a few biface coins are known.

    These small coins and bracteates from the 12th century carry little or no information concerning issuer, date or place of production. This lack of information has resulted in a gap in our knowledge about the role of these coins in medieval society in Norway. This role was dependent both on the intentions of the producer and on how the coins were perceived by the people, and their will to use them in certain ways. What were the reasons behind issuing the smallest coins ever produced in coin history, and what impact did this dramatic reduction in weight have on the understanding and use of the coin?

    To advance the discussion it has been vital to establish new knowledge about chronology, coin-issuing authority and mints. These areas have been addressed through two analyses using numismatic and archaeological methods. The results of the initial analyses are combined with an investigation of the size of the coin production and a study of archaeological contexts, in order to reveal how, where and when the bracteates were used. 

    The theoretical approach to understanding the role of coins is inspired by theories in anthropology and sociology about the many ways in which money can be incorporated in a society, emphasising the complex social component of coins in contrast to the traditional economic emphasis on their neutral qualities as a means of exchange. Central to this are the concepts behind formalism and substantivist and post-substantivist theory. The study concludes with a discussion that explores what can be said about economy and economic systems based on the 12th-century Norwegian coins.

  • Public defence: 2017-11-10 10:00 De Geersalen, Geovetenskapens hus, Stockholm
    Weidenstedt, Linda
    Stockholm University, Faculty of Social Sciences, Department of Sociology.
    A Sociology of Empowerment: The Relevance of Communicative Contexts for Workplace Change2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Empowerment has been a popular concept in management and leadership practice and research for more than forty years. The intentions behind empowerment at the workplace are positive: empowered employees should experience a greater degree of influence, decision-making latitude, and meaningfulness. This is achieved through transfers of power, such as increases in autonomy and responsibility. Although empowerment efforts have often been shown to successfully result in empowered and highly involved employees, there has also been research that shows the opposite: the so-called paradox of empowerment is a well-known problem that refers to failed empowerment efforts through which beneficiaries feel disempowered rather than empowered.

    This thesis comprises three papers intended to contribute to empowerment research and practice within a sociological framework that offers a better understanding of implicit assumptions between employer and employee and the unintended consequences these can have on the outcome of empowerment change efforts. The analyses utilize a communicative approach in line with sociological and social-psychological theories of communication and interaction.

    The first two papers are theoretical analyses, one examining the general concept of empowerment (Paper I), the other focusing more specifically on empowerment in workplace contexts (Paper II). Paper III is an empirical analysis that investigates some of the theoretical assumptions made in Papers I and II.

    The first paper analyzes empowerment from a sociological point of view and identifies possible mechanisms behind the paradox of empowerment. It is argued that such paradoxes may evolve from discrepancies between approaching empowerment from a purely economic and structural perspective versus a communicative and relational one. It concludes with the observation that, although their agency may be increased on a structural level, empowerees may experience a parallel decrease of agential options on a communicative level.

    The second paper deals with empowerment at the workplace as a management or leadership technique. Focusing on relational aspects, a “basic communicative structure” is identified. This is analyzed as comprising a contractual and a communicative context that should be taken into consideration by empowerers in order to avoid misunderstandings in the recipients’ sensemaking processes. Paper II concludes by arguing that the way recipients make sense of their roles and situations as defined by employment and/or psychological contracts might not necessarily be in line with the communicative meanings they ascribe to the change agents’ actions, and vice versa.

    The third paper analyzes employees’ orientations and attitudes toward empowerment and the relevance of their attitudes for the success of empowerment efforts. These issues are explored by means of survey data from 268 employees in the Swedish retail sector. Results indicate that age and work intensity (part-time vs. full-time), as well as cohabitation status may have significant impacts on how empowerment efforts are approached and received by employees.

    The thesis as a whole provides insights into sociological issues of empowerment, both generally and particularly in management and leadership contexts and concludes that the communicative context of empowerment interactions plays a significant role in employees’ empowerment orientations.

  • Makenzius, Marlene
    et al.
    Oguttu, Monica
    Klingberg-Allvin, Marie
    Dalarna University, School of Education, Health and Social Studies, Caring Science/Nursing. Karolinska institutet.
    Gemzell-Danielsson, Kristina
    Odero, Theresa M A
    Faxelid, Elisabeth
    Post-abortion care with misoprostol - equally effective, safe and accepted when administered by midwives compared to physicians: a randomised controlled equivalence trial in a low-resource setting in Kenya2017In: BMJ Open, ISSN 2044-6055, E-ISSN 2044-6055, Vol. 7, no 10, e016157Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To assess the effectiveness of midwives administering misoprostol to women with incomplete abortion seeking post-abortion care (PAC), compared with physicians.

    DESIGN: A multicentre randomised controlled equivalence trial. The study was not masked.

    SETTINGS: Gynaecological departments in two hospitals in a low-resource setting, Kenya.

    POPULATION: Women (n=1094) with incomplete abortion in the first trimester, seeking PAC between 1 June 2013 to 31 May 2016. Participants were randomly assigned to receive treatment from midwives or physicians. 409 and 401 women in the midwife and physician groups, respectively, were included in the per-protocol analysis.

    INTERVENTIONS: 600 µg misoprostol orally, and contraceptive counselling by a physician or midwife.

    MAIN OUTCOME MEASURES: Complete abortion not needing surgical intervention within 7-10 days. The main outcome was analysed on the per-protocol population with a generalised estimating equation model. The predefined equivalence range was -4% to 4%. Secondary outcomes were analysed descriptively.

    RESULTS: The proportion of complete abortion was 94.8% (768/810): 390 (95.4%) in the midwife group and 378 (94.3%) in the physician group. The proportion of incomplete abortion was 5.2% (42/810), similarly distributed between midwives and physicians. The model-based risk difference for midwives versus physicians was 1.0% (-4.1 to 2.2). Most women felt safe (97%; 779/799), and 93% (748/801) perceived the treatment as expected/easier than expected. After contraceptive counselling the uptake of a contraceptive method after 7-10 days occurred in 76% (613/810). No serious adverse events were recorded.

    CONCLUSIONS: Treatment of incomplete abortion with misoprostol provided by midwives is equally effective, safe and accepted by women as when administered by physicians in a low-resource setting. Systematically provided contraceptive counselling in PAC is effective to mitigate unmet need for contraception.


  • Paul, Mandira
    et al.
    Gemzell-Danielsson, Kristina
    Kiggundu, Charles
    Namugenyi, Rebecka
    Klingberg-Allvin, Marie
    Dalarna University, School of Education, Health and Social Studies, Caring Science/Nursing. Karolinska institutet.
    Barriers and facilitators in the provision of post-abortion care at district level in central Uganda – a qualitative study focusing on task sharing between physicians and midwives2014In: BMC Health Services Research, ISSN 1472-6963, E-ISSN 1472-6963, Vol. 14, no 28Article in journal (Refereed)
    Abstract [en]


    Abortion is restricted in Uganda, and poor access to contraceptive methods result in unwanted pregnancies. This leaves women no other choice than unsafe abortion, thus placing a great burden on the Ugandan health system and making unsafe abortion one of the major contributors to maternal mortality and morbidity in Uganda. The existing sexual and reproductive health policy in Uganda supports the sharing of tasks in post-abortion care. This task sharing is taking place as a pragmatic response to the increased workload. This study aims to explore physicians’ and midwives’ perception of post-abortion care with regard to professional competences, methods, contraceptive counselling and task shifting/sharing in post-abortion care.


    In-depth interviews (n = 27) with health care providers of post-abortion care were conducted in seven health facilities in the Central Region of Uganda. The data were organized using thematic analysis with an inductive approach.


    Post-abortion care was perceived as necessary, albeit controversial and sometimes difficult to provide. Together with poor conditions post-abortion care provoked frustration especially among midwives. Task sharing was generally taking place and midwives were identified as the main providers, although they would rarely have the proper training in post-abortion care. Additionally, midwives were sometimes forced to provide services outside their defined task area, due to the absence of doctors. Different uterine evacuation skills were recognized although few providers knew of misoprostol as a method for post-abortion care. An overall need for further training in post-abortion care was identified.


    Task sharing is taking place, but providers lack the relevant skills for the provision of quality care. For post-abortion care to improve, task sharing needs to be scaled up and in-service training for both doctors and midwives needs to be provided. Post-abortion care should further be included in the educational curricula of nurses and midwives. Scaled-up task sharing in post-abortion care, along with misoprostol use for uterine evacuation would provide a systematic approach to improving the quality of care and accessibility of services, with the aim of reducing abortion-related mortality and morbidity in Uganda.

  • Winbo, Annika
    et al.
    Umea Univ, Dept Clin Sci, S-90187 Umea, Sweden.;Univ Auckland, Dept Physiol, Auckland, New Zealand..
    Stattin, Evalena
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Medicinsk genetik och genomik. Uppsala University, Science for Life Laboratory, SciLifeLab.
    Westin, Ida Maria
    Umea Univ, Dept Med Biosci Med & Clin Genet, S-90185 Umea, Sweden..
    Norberg, Anna
    Umea Univ, Dept Med Biosci Med & Clin Genet, S-90185 Umea, Sweden..
    Persson, Johan
    Umea Univ, Dept Clin Sci, S-90187 Umea, Sweden..
    Jensen, Steen M.
    Umea Univ, Heart Ctr, Dept Publ Hlth & Clin Med, S-90185 Umea, Sweden..
    Rydberg, Annika
    Umea Univ, Dept Clin Sci, S-90187 Umea, Sweden..
    Sex is a moderator of the association between NOS1AP sequence variants and QTc in two long QT syndrome founder populations: a pedigree-based measured genotype association analysis2017In: BMC Medical Genetics, ISSN 1471-2350, E-ISSN 1471-2350, Vol. 18, 74Article in journal (Refereed)
    Abstract [en]

    Background: Sequence variants in the NOS1AP gene have repeatedly been reported to influence QTc, albeit with moderate effect sizes. In the long QT syndrome (LQTS), this may contribute to the substantial QTc variance seen among carriers of identical pathogenic sequence variants. Here we assess three non-coding NOS1AP sequence variants, chosen for their previously reported strong association with QTc in normal and LQTS populations, for association with QTc in two Swedish LQT1 founder populations.

    Methods: This study included 312 individuals (58% females) from two LQT1 founder populations, whereof 227 genotype positive segregating either Y111C (n = 148) or R518* (n = 79) pathogenic sequence variants in the KCNQ1 gene, and 85 genotype negatives. All were genotyped for NOS1AP sequence variants rs12143842, rs16847548 and rs4657139, and tested for association with QTc length (effect size presented as mean difference between derived and wildtype, in ms), using a pedigree-based measured genotype association analysis. Mean QTc was obtained by repeated manual measurement (preferably in lead II) by one observer using coded 50 mm/s standard 12-lead ECGs.

    Results: A substantial variance in mean QTc was seen in genotype positives 476 +/- 36 ms (Y111C 483 +/- 34 ms; R518* 462 +/- 34 ms) and genotype negatives 433 +/- 24 ms. Female sex was significantly associated with QTc prolongation in all genotype groups (p < 0.001). In a multivariable analysis including the entire study population and adjusted for KCNQ1 genotype, sex and age, NOS1AP sequence variants rs12143842 and rs16847548 (but not rs4657139) were significantly associated with QT prolongation, + 18 ms (p = 0.0007) and + 17 ms (p = 0.006), respectively. Significant sex-interactions were detected for both sequent variants (interaction term r = 0.892, p < 0. 001 and r = 0.944, p < 0.001, respectively). Notably, across the genotype groups, when stratified by sex neither rs12143842 nor rs16847548 were significantly associated with QTc in females (both p = 0.16) while in males, a prolongation of + 19 ms and + 8 ms (p = 0.002 and p = 0.02) was seen in multivariable analysis, explaining up to 23% of QTc variance in all males.

    Conclusions: Sex was identified as a moderator of the association between NOS1AP sequence variants and QTc in two LQT1 founder populations. This finding may contribute to QTc sex differences and affect the usefulness of NOS1AP as a marker for clinical risk stratification in LQTS.

  • Public defence: 2017-11-10 10:00 Vivi Täckholmsalen (Q-salen), NPQ-huset, Stockholm
    Woronik, Alyssa
    Stockholm University, Faculty of Science, Department of Zoology.
    A functional genomic investigation of an alternative life history strategy: The Alba polymorphism in Colias croceus2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Life history traits affect the timing and pattern of maturation, reproduction, and survival during an organism’s lifecycle and are the major components influencing Darwinian fitness. Co-evolved patterns of these traits are known as life history strategies (LHS) and variation occurs between individuals, populations, and species. The polymorphisms underlying LHS are important targets of natural selection, yet the underlying genes and physiological mechanisms remain largely unknown. Mapping the genetic basis of a LHS and subsequently unraveling the associated physiological mechanisms is a challenging task, as complex phenotypes are often polygenic. However, in several systems discrete LHS are maintained within the population and are inherited as a single locus with pleiotropic effects. These systems provide a promising starting point for investigation into LHS mechanisms and this thesis focuses on one such strategy - the Alba polymorphism in Colias butterflies. Alba is inherited as a single autosomal locus, expressed only in females, and simultaneously affects development rate, reproductive potential, and wing color. Alba females are white, while the alternative morph is yellow/orange. About 28 of 90 species exhibit polymorphic females, though whether the Alba mechanism and associated tradeoffs are conserved across the genus remains to be determined. In this thesis I primarily focus on the species Colias croceus and integrate results from lipidomics, transcriptomics, microscopy, and genomics to gain insights to the proximate mechanisms underlying Alba and Alba’s evolution within the genus. Lipidomics confirm that, consistent with findings in New World species, C. croceus Alba females have larger abdominal lipid stores than orange, an advantage which is temperature dependent and arises primarily due to mobilized lipids. Gene expression data suggests differences in resource allocation, with Alba females investing in reproduction rather than wing color, consistent with previous findings in other Colias species. Additionally, I identify a morphological basis for Alba’s white wing color. Alba females from C. croceus, an Old World species, and Colias eurytheme, a New World species both exhibit a significant reduction in pigment granules, the structures within the wing scale that contain pigment. This is a trait that seems to be unique to Colias as other white Pierid butterflies have an abundance of pigment granules, similar to orange females. I also map the genetic basis of Alba to a single genomic region containing an Alba specific, Jockey-like transposable element insertion. Interestingly this transposable element​ is located downstream of BarH-1, a gene known to affect pigment granule formation in Drosophila. Finally, I construct a phylogeny using a global distribution of 20 Colias species to facilitate investigations of Alba’s evolution within the genus.

  • Public defence: 2017-11-10 10:00 Högbomsalen, Stockholm
    Szabo, Attila
    Stockholm University, Faculty of Science, Department of Mathematics and Science Education.
    Mathematical abilities and mathematical memory during problem solving and some aspects of mathematics education for gifted pupils2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis reports on two different investigations.

    The first is a systematic review of pedagogical and organizational practices associated with gifted pupils’ education in mathematics, and on the empirical basis for those practices. The review shows that certain practices – for example, enrichment programs and differentiated instructions in heterogeneous classrooms or acceleration programs and ability groupings outside those classrooms – may be beneficial for the development of gifted pupils. Also, motivational characteristics of and gender differences between mathematically gifted pupils are discussed. Around 60% of analysed papers report on empirical studies, while remaining articles are based on literature reviews, theoretical discourses and the authors’ personal experiences – acceleration programs and ability groupings are supported by more empirical data than practices aimed for the heterogeneous classroom. Further, the analyses indicate that successful acceleration programs and ability groupings should fulfil some important criteria; pupils’ participation should be voluntary, the teaching should be adapted to the capacity of participants, introduced tasks should be challenging, by offering more depth and less breadth within a certain topic, and teachers engaged in these practices should be prepared for the characteristics of gifted pupils.

    The second investigation reports on the interaction of mathematical abilities and the role of mathematical memory in the context of non-routine problems. In this respect, six Swedish high-achieving students from upper secondary school were observed individually on two occasions approximately one year apart. For these studies, an analytical framework, based on the mathematical ability defined by Krutetskii (1976), was developed. Concerning the interaction of mathematical abilities, it was found that every problem-solving activity started with an orientation phase, which was followed by a phase of processing mathematical information and every activity ended with a checking phase, when the correctness of obtained results was controlled. Further, mathematical memory was observed in close interaction with the ability to obtain and formalize mathematical information, for relatively small amounts of the total time dedicated to problem solving. Participants selected problem-solving methods at the orientation phase and found it difficult to abandon or modify those methods. In addition, when solving problems one year apart, even when not recalling the previously solved problem, participants approached both problems with methods that were identical at the individual level. The analyses show that participants who applied algebraic methods were more successful than participants who applied particular methods. Thus, by demonstrating that the success of participants’ problem-solving activities is dependent on applied methods, it is suggested that mathematical memory, despite its relatively modest presence, has a pivotal role in participants’ problem-solving activities. Finally, it is indicated that participants who applied particular methods were not able to generalize mathematical relations and operations – a mathematical ability considered an important prerequisite for the development of mathematical memory – at appropriate levels.

  • Berggren, ChristianChrbe53
    et al.
    Linköping University, Department of Management and Engineering, Project Innovations and Entrepreneurship. Linköping University, Faculty of Science & Engineering.
    Kågeson, Per
    Royal Institute of Technology, KTH, Stockholm.
    Speeding up electro-mobility: How to electrify half of new car sales by 20302017Report (Other academic)
    Abstract [en]

    Noxious diesel emissions far above official limits and the need to rapidly reduce-greenhouse gases generate widespread calls for banning fossil-fueled cars in Europe. This report shows that it is possible to electrify 50 per cent of all new cars in the EU by 2030.

     This, however, requires massive investment in European battery production capacity, and a long-term commitment to sustainable supply of critical materials. In addition a large-scale expansion of the charging infrastructure is needed, in particular at home and at work places, which account for around 95 per cent of all battery charging. Moreover, local grids will need enforcement in most countries. The additional electricity demand must be satisfied at a time when many coal-fired and nuclear-based power plants will be decommissioned.  Plug-in hybrids, which combine a downsized combustion engine with an electric motor, will probably play an important role, both to relieve long-distance drivers of range anxiety and to reduce the demand for scarce virgin metals, in particular cobalt.

     To make the shift happen, an EU-wide Zero Emission Vehicle (ZEV) mandate needs to be established from 2025, with planned stringency increases every second year or so. Such a regulation is less vulnerable to budget restraints and changing relative prices than financial incentives. At the same time, the regulatory demands on manufacturers to reduce CO2 emissions from combustions engines need to become more stringent and apply to all combustion engines, including those in plug-in hybrids. Such a combination of policies will make it possible to realize the overall target of 50 per cent electrification of new cars in a robust and flexible way.

  • Lindquist, Matthew
    et al.
    Stockholm University, Faculty of Social Sciences, The Swedish Institute for Social Research (SOFI).
    Sol, Joeri
    van Praag, C.Mirjam
    Vladasel, Theodor
    On the Origins of Entrepreneurship: Evidence from Sibling Correlations2017Report (Other academic)
  • Wirén, Mats
    et al.
    Stockholm University, Faculty of Humanities, Department of Linguistics, Computational Linguistics.
    Nilsson Björkenstam, Kristina
    Stockholm University, Faculty of Humanities, Department of Linguistics, Computational Linguistics.
    Östling, Robert
    Stockholm University, Faculty of Humanities, Department of Linguistics, Computational Linguistics.
    Modelling the Informativeness of Non-Verbal Cues in Parent–Child Interaction2017In: Proceedings of the 18th Annual Conference of the International Speech Communication Association (INTERSPEECH 2017), Stockholm: The International Speech Communication Association (ISCA), 2017, 2203-2207 p., 1143Conference paper (Refereed)
    Abstract [en]

    Non-verbal cues from speakers, such as eye gaze and hand positions, play an important role in word learning. This is consistent with the notion that for meaning to be reconstructed, acoustic patterns need to be linked to time-synchronous patterns from at least one other modality. In previous studies of a multimodally annotated corpus of parent–child interaction, we have shown that parents interacting with infants at the early word-learning stage (7–9 months) display a large amount of time-synchronous patterns, but that this behaviour tails off with increasing age of the children. Furthermore, we have attempted to quantify the informativeness of the different nonverbal cues, that is, to what extent they actually help to discriminate between different possible referents, and how critical the timing of the cues is. The purpose of this paper is to generalise our earlier model by quantifying informativeness resulting from non-verbal cues occurring both before and after their associated verbal references.

  • Karaoguz, Hakan
    et al.
    KTH, School of Computer Science and Communication (CSC), Robotics, perception and learning, RPL.
    Bore, Nils
    KTH, School of Computer Science and Communication (CSC), Robotics, perception and learning, RPL. KTH, School of Computer Science and Communication (CSC), Centres, Centre for Autonomous Systems, CAS.
    Folkesson, John
    KTH, School of Computer Science and Communication (CSC), Robotics, perception and learning, RPL. KTH, School of Computer Science and Communication (CSC), Centres, Centre for Autonomous Systems, CAS.
    Jensfelt, Patric
    KTH, School of Computer Science and Communication (CSC), Robotics, perception and learning, RPL. KTH, School of Computer Science and Communication (CSC), Centres, Centre for Autonomous Systems, CAS.
    Human-Centric Partitioning of the Environment2017Conference paper (Refereed)
    Abstract [en]

    In this paper, we present an object based approach for human-centric partitioning of the environment. Our approach for determining the human-centric regionsis to detect the objects that are commonly associated withfrequent human presence. In order to detect these objects, we employ state of the art perception techniques. The detected objects are stored with their spatio-temporal information inthe robot’s memory to be later used for generating the regions.The advantages of our method is that it is autonomous, requires only a small set of perceptual data and does not even require people to be present while generating the regions.The generated regions are validated using a 1-month dataset collected in an indoor office environment. The experimental results show that although a small set of perceptual data isused, the regions are generated at densely occupied locations.

  • Aghanavesi, Somayeh
    et al.
    Dalarna University, School of Technology and Business Studies, Computer Engineering.
    Memedi, Mevludin
    Dalarna University, School of Technology and Business Studies, Computer Engineering.
    Dougherty, Mark
    Dalarna University, School of Technology and Business Studies, Computer Engineering.
    Nyholm, Dag
    Westin, Jerker
    Dalarna University, School of Technology and Business Studies, Computer Engineering.
    Verification of a method for measuring Parkinson's disease related temporal irregularity in spiral drawings2017In: Sensors, ISSN 1424-8220, E-ISSN 1424-8220, Vol. 17, no 10, E2341Article in journal (Refereed)
    Abstract [en]

    Parkinson's disease (PD) is a progressive movement disorder caused by the death of dopamine-producing cells in the midbrain. There is a need for frequent symptom assessment, since the treatment needs to be individualized as the disease progresses. The aim of this paper was to verify and further investigate the clinimetric properties of an entropy-based method for measuring PD-related upper limb temporal irregularities during spiral drawing tasks. More specifically, properties of a temporal irregularity score (TIS) for patients at different stages of PD, and medication time points were investigated. Nineteen PD patients and 22 healthy controls performed repeated spiral drawing tasks on a smartphone. Patients performed the tests before a single levodopa dose and at specific time intervals after the dose was given. Three movement disorder specialists rated videos of the patients based on the unified PD rating scale (UPDRS) and the Dyskinesia scale. Differences in mean TIS between the groups of patients and healthy subjects were assessed. Test-retest reliability of the TIS was measured. The ability of TIS to detect changes from baseline (before medication) to later time points was investigated. Correlations between TIS and clinical rating scores were assessed. The mean TIS was significantly different between healthy subjects and patients in advanced groups (p-value = 0.02). Test-retest reliability of TIS was good with Intra-class Correlation Coefficient of 0.81. When assessing changes in relation to treatment, TIS contained some information to capture changes from Off to On and wearing off effects. However, the correlations between TIS and clinical scores (UPDRS and Dyskinesia) were weak. TIS was able to differentiate spiral drawings drawn by patients in an advanced stage from those drawn by healthy subjects, and TIS had good test-retest reliability. TIS was somewhat responsive to single-dose levodopa treatment. Since TIS is an upper limb high-frequency-based measure, it cannot be detected during clinical assessment.

  • Ström, Annika
    Södertörn University, School of Culture and Education, Rhetoric.
    Gyldenstolpe, Carl (Creator)
    Gyldenstolpe, Gustav (Creator)
    En frånvarandes samtal med en frånvarande: Bröderna Daniel, Carl och Gustav Gyldenstolpes brev till Nils Gyldenstolpe 1660–1679: Utgåva av latinsk text i urval, översättning samt inledning av Annika Ström2017Collection (editor) (Refereed)
    Abstract [sv]

    Denna bok innehåller en utgåva med svensk översättning av 114 brev, skrivna på latin under den andra hälften av 1600-talet. Breven är författade av de tre bröderna Daniel, Carl och Gustav Gyldenstolpe och riktar sig med några få undantag till deras äldre bror Nils som flyttat från hemmet i Åbo till Stockholm för att göra ämbetsmannakarriär.

    I breven erbjuds vi många glimtar av dåtidens samhälle, av det skånska kriget där en av bröderna deltog, om privata händelser och av de vardagliga problem som ofta handlade om att hålla samman familjen under kärva förhållanden. Vi informeras även om de verksamheter som bedrevs av jurister och ämbetsmän i stormaktstidens svenska statsförvaltning med förgreningar kring hela Östersjön.

    Förutom sitt värde som historiska källor ger breven inblickar i dåtidens utbildningsväsen med ett särskilt fokus på inlärningen av latin och retorik. De visar också på den höga latinkompetens som individer besatt under tidigmodern tid i Sverige samt hur detta nylatin var ett kommunikationsmedel som smidigt kunde utnyttjas för alla förekommande sociala behov.

  • Thomson, Suzanne E.
    et al.
    Charalambous, Chloe
    Smith, Carol-Anne
    Tsimbouri, Penelope M.
    Déjardin, Theophile
    Kingham, Paul J.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB).
    Hart, Andrew M.
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). The Centre for Cell Engineering, College of Medical, Veterinary and Life Sciences, University of Glasgow, University Avenue, Hillhead, Glasgow G128QQ, UK; Canniesburn Plastic Surgery Unit, Glasgow Royal Infirmary, 84 Castle Street, Glasgow G4 0SF, UK.
    Riehle, Mathis O.
    Microtopographical cues promote peripheral nerve regeneration via transient mTORC2 activation2017In: Acta Biomaterialia, ISSN 1742-7061, E-ISSN 1878-7568, Vol. 60, 220-231 p.Article in journal (Refereed)
    Abstract [en]

    Despite microsurgical repair, recovery of function following peripheral nerve injury is slow and often incomplete. Outcomes could be improved by an increased understanding of the molecular biology of regeneration and by translation of experimental bioengineering strategies. Topographical cues have been shown to be powerful regulators of the rate and directionality of neurite regeneration, and in this study we investigated the downstream molecular effects of linear micropatterned structures in an organotypic explant model. Linear topographical cues enhanced neurite outgrowth and our results demonstrated that the mTOR pathway is important in regulating these responses. mTOR gene expression peaked between 48 and 72 h, coincident with the onset of rapid neurite outgrowth and glial migration, and correlated with neurite length at 48 h. mTOR protein was located to glia and in a punctate distribution along neurites. mTOR levels peaked at 72 h and were significantly increased by patterned topography (p < 0.05). Furthermore, the topographical cues could override pharmacological inhibition. Downstream phosphorylation assays and inhibition of mTORC1 using rapamycin highlighted mTORC2 as an important mediator, and more specific therapeutic target. Quantitative immunohistochemistry confirmed the presence of the mTORC2 component rictor at the regenerating front where it co-localised with F-actin and vinculin. Collectively, these results provide a deeper understanding of the mechanism of action of topography on neural regeneration, and support the incorporation of topographical patterning in combination with pharmacological mTORC2 potentiation within biomaterial constructs used to repair peripheral nerves.

    Statement of Significance: Peripheral nerve injury is common and functionally devastating. Despite microsurgical repair, healing is slow and incomplete, with lasting functional deficit. There is a clear need to translate bioengineering approaches and increase our knowledge of the molecular processes controlling nerve regeneration to improve the rate and success of healing. Topographical cues are powerful determinants of neurite outgrowth and represent a highly translatable engineering strategy. Here we demonstrate, for the first time, that microtopography potentiates neurite outgrowth via the mTOR pathway, with the mTORC2 subtype being of particular importance. These results give further evidence for the incorporation of microtopographical cues into peripheral nerve regeneration conduits and indicate that mTORC2 may be a suitable therapeutic target to potentiate nerve regeneration.

  • Public defence: 2017-11-09 09:15 Polhemssalen, Uppsala
    Bras, Patrice
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    Sputtering-based processes for thin film chalcogenide solar cells on steel substrates2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Thin film chalcogenide solar cells are promising photovoltaic technologies. Cu(In,Ga)Se2 (CIGS)-based devices are already produced at industrial scale and record laboratory efficiency surpasses 22 %. Cu2ZnSn(S,Se)4 (CZTS) is an alternative material that is based on earth-abundant elements. CZTS device efficiency above 12 % has been obtained, indicating a high potential for improvement.

    In this thesis, in-line vacuum, sputtering-based processes for the fabrication of complete thin film chalcogenide solar cells on stainless steel substrates are studied. CIGS absorbers are deposited in a one-step high-temperature process using compound targets. CZTS precursors are first deposited by room temperature sputtering and absorbers are then formed by high temperature crystallization in a controlled atmosphere. In both cases, strategies for absorber layer improvement are identified and implemented.

    The impact of CZTS annealing temperature is studied and it is observed that the absorber grain size increases with annealing temperature up to 550 °C. While performance also improves from 420 to 510 °C, a drop in all solar cell parameters is observed for higher temperature. This loss is caused by blisters forming in the absorber during annealing. Blister formation is found to originate from gas entrapment during precursor sputtering. Increase in substrate temperature or sputtering pressure leads to drastic reduction of gas entrapment and hence alleviate blister formation resulting in improved solar cell parameters, including efficiency.

    An investigation of bandgap grading in industrial CIGS devices is conducted through one-dimensional simulations and experimental verification. It is found that a single gradient in the conduction band edge extending throughout the absorber combined with a steeper back-grading leads to improved solar cell performance, mainly due to charge carrier collection enhancement.

    The uniformity of both CIGS and CZTS 6-inch solar cells is assessed. For CZTS, the device uniformity is mainly limited by the in-line annealing process. Uneven heat and gas distribution resulting from natural convection phenomenon leads to significant lateral variation in material properties and device performance. CIGS solar cell uniformity is studied through laterally-resolved material and device characterization combined with SPICE network modeling. The absorber material is found to be laterally homogeneous. Moderate variations observed at the device level are discussed in the context of large area sample characterization.

    Power conversion efficiency values above 15 % for 225 cm2 CIGS cells and up to 5.1 % for 1 cm2 CZTS solar cells are obtained.

  • Pulina, Silvia
    et al.
    Univ Cagliari, Dept Life & Environm Sci, I-09126 Cagliari, Italy..
    Brutemark, Andreas
    Calluna AB, S-11321 Stockholm, Sweden..
    Suikkanen, Sanna
    Finnish Environm Inst, Ctr Marine Res, Helsinki 00560, Finland..
    Padedda, Bachisio M.
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Grubisic, Lorena M.
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Satta, Cecilia T.
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Caddeo, Tiziana
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Farina, Pasqualina
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Sechi, Nicola
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Luglie, Antonella
    Univ Sassari, Dept Architecture Design & Urban Planning, I-07100 Sassari, Italy..
    Effects of warming on a Mediterranean phytoplankton community2016In: Web Ecology, ISSN 1399-1183, E-ISSN 1399-1183, Vol. 16, 89-92 p.Article in journal (Refereed)
    Abstract [en]

    Predicting the responses of organisms is a complex challenge especially when water temperature is expected to increase over the coming decades, as a result of global warming. In this work the effects of warming on phytoplankton communities were investigated. An indoor experiment was performed, where water from a Mediterranean lagoon was incubated at different temperatures. Three treatments were applied in triplicate incubation units: the control (11 degrees C), 3 degrees C increase (14 degrees C), and 6 degrees C increase (17 degrees C). Our results showed significant effects by warming on phytoplankton. The abundance of relatively smaller taxa (Chlorella sp. and Planktothrix agardhii-rubescens group) increased at 17 degrees C, whereas the abundance of relatively larger species (Cyclotella sp. and Thalassiosira sp.) decreased, compared with the control. This shift towards smaller taxa resulted in a higher total biomass but lower chlorophyll a concentrations at the highest temperature.

  • Public defence: 2017-11-10 13:00 Clas Ohlson, Borlänge
    Thomas, Ilias
    Dalarna University, School of Technology and Business Studies, Microdata Analysis.
    Optimizing levodopa dosing routines for Parkinson’s disease2017Licentiate thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis in the field of microdata analysis aims to introduce dose optimizing algorithms for the pharmacological management of Parkinson’s disease (PD). PD is a neurodegenerative disease that mostly affects the motor functions of the patients and it is characterized as a movement disorder. The core symptoms of PD are: bradykinesia, postural instability, rigidity, and tremor. There is no cure for PD and the use of levodopa to manage the core symptoms is considered the gold standard. However, long term use of levodopa causes reduced medication efficacy, and side effects, such as dyskinesia, which can also be attributed to overmedication. When that happens precise individualized dosing schedules are required. The goal of this thesis is to examine if algorithmic methods can be used to find dosing schedules that treat PD symptoms and minimize manifestation of side effects. Data from three different sources were used for that purpose: data from a clinical study in Uppsala University hospital in 2015, patient admission chart data from Uppsala University hospital during 2011-2015, and data from a clinical study in Gothenburg University during 2016-2017. The data were used to develop the methods and evaluate the performance of the proposed algorithms.The first algorithm that was developed was a sensor-based method that derives objective measurements (ratings) of PD motor states. The construction of the sensor index was based on subjective ratings of patients’ motor functions made by three movement disorder experts. This sensor-based method was used when deriving algorithmic dosing schedules. Afterwards, a method that uses medication information and ratings of the patients’ motor states to fit individual patient models was developed. This method uses mathematical optimization to individualize specific parameters of dose-effects models for levodopa intake, through minimizing the distance between motor state ratings and dose-effect curves. Finally, two different dose optimization algorithms were developed and evaluated, that had as input the individual patient models. The first algorithm was specific to continuous infusion of levodopa treatment, where the patient’s state was set to a specific target value and the algorithm made dosing adjustments to keep that patients motor functions on that state. The second algorithm concerned oral administration of microtables of levodopa. The ambition with this algorithm was that the suggested doses would find the right balance between treating the core symptoms of PD and, at the same time, minimizing the side effects of long term levodopa use, mainly dyskinesia. Motor state ratings for this study were obtained through the sensor index. Both algorithms followed a principle of deriving a morning dose and a maintenance dose for the patients, with maintenance dose being an infusion rate for the first algorithm, and oral administration doses at specific time points for the second algorithm.The results showed that the sensor-based index had good test-retest reliability, sensitivity to levodopa treatment, and ability to make predictions in unseen parts of the dataset. The dosing algorithm for continuous infusion of levodopa had a good ability to suggest an optimal infusion rating for the patients, but consistently suggested lower morning dose than what the treating personnel prescribed. The dosing algorithm for oral administration of levodopa showed great agreement with the treating personnel’s prescriptions, both in terms of morning and maintenance dose. Moreover, when evaluating the oral medication algorithm, it was clear that the sensor index ratings could be used for building patient specific models.

  • Public defence: 2017-11-13 09:00 Kollegiesalen, Stockholm
    Fridlund, Gustav
    KTH, School of Architecture and the Built Environment (ABE), Urban Planning and Environment, Urban and Regional Studies.
    Utan tvivel är en inte klok: En studie om personliga skavningar som resurs för praktisk klokhet inom svensk kommunal planering2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    How can you as a planner tackle messy realities without losing sight of possible problematic outcomes of what you put in practice? This study explores the value of everyday frictions as a resource for phronetic planning, i.e. the ability to make situated ethical judements of what is ’better’ or ’worse’ in a particular setting. The intent is to offer a situated gaze of frictions from the perspective of a civil servant of the well organised and innovative municipality of Botkyrka in the metropolitan area of Stockholm, Sweden. From this outset, an autoethnographical methodology from a poststructural approach, is used to explore the frictions that the author has experienced as a practicing planner. The study shows that frictions can be used as 'weak signals' to identify possible tricky consequences of the creation and the staging of planning 'simplifications'. Based on this insight a 'seismological' approach to planning is proposed. The argument is that planning practice should on the one hand utilize frictions when they arise and, on the other hand, actively challenge existing 'simplifications'. To achieve this, practical tools are offered to 'evoke', 'narrate' and 'diffract' on frictions and 'trickster-objects' within the constraints of the planner’s role as a municipal civil servant. 

  • Asp, Petrus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio historico-philosophica, de studio sapientum prisci ævi in eruditione comparanda; quam consensu ampliss. facult. philos. in regia academia Upsaliensi, publicæ bonorum disquisitioni sistunt auctor et præses Petrus M. Asp, O-Gothus, nec non respondens alumnus regius Nicolaus Paulin, Jemtius, in audit. Carol. maj. d. XIII. Martii, anni MDCCLVI. h. a. m. s.1756Dissertation (older thesis) (Other academic)
  • Asp, Matthias
    et al.
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Printz, Abraham
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio philosophica, de laude propria; quam, annuente amplissima facultat. philos. in regia acad. Upsal. præside ... Matthia Asp ... pro gradu, publico examini modeste submittit Abraham Printz, fil. Fierdhundrensis. In auditor. Gustav. major. d. XXVII Junii. Anni MDCCXXXVII. Horis ante meridiem solitis.1737Dissertation (older thesis) (Other academic)
  • Asp, Matthias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Exercitium academicum, de Sudercopia; cujus partem priorem, indultu amplissimi senatus philosophici, sub præsidio, ... Matthiæ Asp ... publice examinandam sistit Magnus Samuel Södersten, Sudercopia Oster-Gothus, in audit. Gust. maj. d. X Julii, anni MDCCXXXVI, horis solitis.1736Dissertation (older thesis) (Other academic)
  • Asp, Matthias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio academica de Nycopia metropoli Sudermanniæ; cujus partem priorem cum consensu ampliss. facult. philos. in reg. acad. Upsal., præside ... Matthia Asp ... publice ventilandam sistit alumnus Piperianus Johannes Sundler, Nycopia-Sudermannus. In audit Gust. maj. die 12 Junii an. MDCCXXXV, horis ante meridiem consvetis.1735Dissertation (older thesis) (Other academic)
  • Asp, Matthias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio de Lincopia; cujus partem priorem, cum consensu ampliss. senat. philosoph. in reg. acad. Upsaliensi, præside ... Matthia Asp ... publicæ ventilationi modeste submittit Johannes S. Ryding, Lincopia-Ostergothus, in audit. Gustav. maj. ad d. II. Junii anni MDCCXXXV. Horis ante meridiem solitis.1735Dissertation (older thesis) (Other academic)
  • Asp, Matthias
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Philosophy.
    Dissertatio academica, de societatibus literariis et scientiarum, præcipue hyperboreis, quam consensu ampliss. colleg. philos. ad almam academiam Upsaliensem, præside ... Matthia Asp ... ad publicum examen modeste defert Andreas Westén, And. fil. Ostro-Gothus. In audit. Gust. maj. die 20. Decembris, anni MDCCXXXIV. Horis ante meridiem consvetis.1734Dissertation (older thesis) (Other academic)