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  • Public defence: 2017-04-27 09:15 C8:301, Uppsala
    Zhang, Lu
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.
    IgG3 Complements IgM in the Complement-Mediated Regulation of Immune Responses2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    An intact complement system is essential for the initiation of a normal antibody response. Antibodies can regulate their own production against the antigens that they are specific for. Both IgG3 and IgM are able to enhance the antibody response via complement. Here, we have compared the fate of OVA-TNP (ovalbumin-2,4,6-trinitrophenyl) administered intravenously to mice either alone or in complex with monoclonal IgG3 anti-TNP. IgG3-antigen complexes bind to marginal zone (MZ) B cells via complement receptors 1 and 2 (CR1/2) and are transported into splenic follicles. The majority (50% - 90%) of the antigens is deposited on follicular dendritic cells (FDC) and the antigen distribution pattern is strikingly similar to peripheral dendrites/processes of FDC already 2 h after immunization. The development of germinal centers (GC) induced by IgG3-antigen complexes is impaired in mice lacking CR1/2. Experiments on bone marrow chimeric mice show that CR1/2 expression on both MZ B cells and FDC is required for optimal IgG3-mediated enhancement of antibody responses. Complement factors C3 and C1q are essential for OVA-TNP delivery and deposition on splenic FDC. The production of IgG anti-OVA is abrogated in mice lacking CR1/2, C1q, and C3. Further, IgG3-antigen complexes dramatically upregulate the memory response against OVA-TNP by inducing OVA-specific memory cells. Besides small protein OVA, IgG3 can also upregulate humoral responses against large soluble keyhole limpet hemocyanin.

    To further study the role of MZ B-cells and CR1/2 in enhancement of antibody responses, a knock-in mouse strain, Cμ13, was used. IgM in this mouse strain is unable to activate complement due to a point mutation in the constant µ-heavy chain. Cμ13 mice have a higher proportion of MZ B cells, with higher CR1/2 expression, than wild-type mice. More IgG3-immune complexes are captured by MZ B cells and deposited on FDC in Cμ13 than in WT mice. In spite of this, IgG3 did not enhance the primary antibody response more efficiently in Cμ13 mice. The existence of endogenous IgM-mediated feedback regulation was suggested by the observation that GC development and antibody responses, after priming and boosting with suboptimal doses of SRBC, was lower in Cμ13 than in WT mice.

    List of papers
    1. Marginal Zone B Cells Transport IgG3-Immune Complexes to Splenic Follicles
    Open this publication in new window or tab >>Marginal Zone B Cells Transport IgG3-Immune Complexes to Splenic Follicles
    2014 (English)In: Journal of Immunology, ISSN 0022-1767, E-ISSN 1550-6606, Vol. 193, no 4, 1681-1689 p.Article in journal (Refereed) Published
    Abstract [en]

    Ag administered together with specific IgG3 induces a higher Ab response than Ag administered alone, an effect requiring the presence of complement receptors 1 and 2 (CR1/2). In this study, we have investigated the fate of Ag, the development of germinal centers (GCs), and the Ab response after i.v. administration of IgG3 anti-trinitrophenyl (TNP) in complex with OVA-TNP. After 2 h, OVA-TNP was detected on marginal zone (MZ) B cells, and a substantial amount of Ag was detected in splenic follicles and colocalized with follicular dendritic cells (FDCs). After 10 d, the percentage of GCs and the IgG responses were markedly higher than in mice immunized with uncomplexed OVA-TNP. The effects of IgG3 were dependent on CR1/2 known to be expressed on B cells and FDCs. Using bone marrow chimeric mice, we demonstrate that an optimal response to IgG3-Ag complexes requires that CR1/2 is expressed on both cell types. These data suggest that CR1/2(+) MZ B cells transport IgG3-Ag-C complexes from the MZ to the follicles, where they are captured by FDCs and induce GCs and IgG production. This pathway for initiating the transport of Ags into splenic follicles complements previously known B-cell dependent pathways where Ag is transported by 1) MZ B cells, binding large Ags-IgM-C complexes via CR1/2; 2) recirculating B cells, binding Ag via BCR; or 3) recirculating B cells, binding IgE-Ag complexes via the low-affinity receptor for IgE, CD23.

    Keyword
    antigen transport, marginal zone B cells, complement receptors 1 and 2
    National Category
    Immunology in the medical area
    Research subject
    Immunology
    Identifiers
    urn:nbn:se:uu:diva-233024 (URN)10.4049/jimmunol.1400331 (DOI)000341139300019 ()
    Available from: 2014-10-06 Created: 2014-09-29 Last updated: 2017-03-08
    2. IgG3-Antigen Complexes Are Deposited on Follicular Dendritic Cells in the Presence of C1q and C3
    Open this publication in new window or tab >>IgG3-Antigen Complexes Are Deposited on Follicular Dendritic Cells in the Presence of C1q and C3
    (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322Article in journal (Other academic) Submitted
    Keyword
    follicular dendritic cells, C1q, C3, memory response
    National Category
    Immunology in the medical area
    Research subject
    Immunology
    Identifiers
    urn:nbn:se:uu:diva-316615 (URN)
    Available from: 2017-03-05 Created: 2017-03-05 Last updated: 2017-03-08
    3. Mice Producing IgM Unable to Activate Complement Have Impaired Endogenous Feedback Regulation but Increased Antigen Trapping in Follicles
    Open this publication in new window or tab >>Mice Producing IgM Unable to Activate Complement Have Impaired Endogenous Feedback Regulation but Increased Antigen Trapping in Follicles
    (English)Manuscript (preprint) (Other academic)
    Keyword
    complement-activating IgM, marginal zone B cells, follicular dendritic cells, antigen trapping
    National Category
    Immunology in the medical area
    Research subject
    Immunology
    Identifiers
    urn:nbn:se:uu:diva-310226 (URN)
    Available from: 2017-03-05 Created: 2017-03-05 Last updated: 2017-03-08
  • Public defence: 2017-04-27 13:00 Vårdskolans Aula, Västerås
    Berling Holm, Katarina
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland.
    The Chorda Tympani Nerve: Role in Taste Impairment in Middle Ear Disease and after Ear Surgery2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The chorda tympani nerve, also known as the taste nerve, runs uncovered through the middle ear cavity, a localization that exposes the nerve to pathological processes and surgical trauma in the middle ear. People operated on for otosclerosis tend to complain more about postoperative taste disturbances than those operated on for chronic otitis media. It has been suggested that this difference may be explained by gradual deterioration of chorda tympani nerve function caused by chronic otitis media infection and that further impairment caused by surgery is less noticeable in these patients.

    This thesis aimed to evaluate the function of the chorda tympani nerve, the effects of middle ear disease on taste and complications resulting from ear surgery for chronic otitis media or otosclerosis. This information will help to improve the ear surgeon’s ability to predict the prognosis of iatrogenic taste disturbances in patients with middle ear disease and after ear surgery.

    Taste was assessed using electrogustometry and the filter paper disc method before and after surgery for chronic otitis media or otosclerosis. Patients also completed questionnaires about symptoms and quality of life. The status of the chorda tympani nerve upon surgical opening of the ear and grading of the trauma to the nerve during the surgery were recorded. The ultrastructure of the chorda tympani nerve from healthy ears and from ears with chronic otitis media was examined. Electrogustometry and the filter paper disc method were evaluated.

    The results of electrogustometry and the filter paper disc method were highly reproducible, although their correlation was moderate. Patients with chronic otitis media, patients with a more traumatized nerve, female patients and younger patients were more likely to report postoperative taste disturbances. Most of the patients recovered their taste after 1 year. The quality of life study showed only minor changes after surgery. Electron microscopic observations of nerves from ears with chronic otitis media showed signs of structural degeneration, although signs of regeneration, such as sprouting were also observed. This results may explain the recovery of taste postoperatively and indicate that the nerve should be carefully handled during surgery.

    List of papers
    1. Evaluation of electrogustometry and the filter paper disc method for taste assessment
    Open this publication in new window or tab >>Evaluation of electrogustometry and the filter paper disc method for taste assessment
    2011 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 131, no 5, 488-493 p.Article in journal (Refereed) Published
    Abstract [en]

    Conclusion:

    The results indicate that electrogustometry and the filter paper disc method are reliable methods to measure taste with a high degree of reproducibility.

    Objectives:

    To thoroughly evaluate the reliability of electrogustometry and the filter paper disc method for taste assessments.

    Methods:

    Thirty-nine healthy test persons without any history of chronic middle ear disease, aged between 27 and 62 years, were recruited. In all, 772 electrogustometry and 30 filter paper disc assessments were made. A nerve decay test was performed, with measures taken before and after eating sweet, sour, bitter, salt, a mild or spicy meal, after smoking, and after taking Swedish tobacco snuff ('snus'), as well as before and after local anesthesia of the tongue. Measurements were performed on 5 consecutive days and repeatedly during 1 day. The correlation between electrogustometry and the filter paper disc method was also studied.

    Results:

    The results indicate that electrogustometry and the filter paper disc method are reliable methods to measure taste with a high degree of reproducibility. The only actions causing significant changes in the electrogustometry readings were eating bitter a substance and having local anesthesia of the tongue. The correlation between the methods was statistically significant except for the bitter flavor, where the correlation was just below the level of significance.

    Keyword
    Chorda tympani, ear disease, ear surgery
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-152942 (URN)10.3109/00016489.2010.535850 (DOI)000289562600005 ()21391775 (PubMedID)
    Available from: 2011-05-03 Created: 2011-05-03 Last updated: 2017-03-07Bibliographically approved
    2. The chorda tympani degenerates during chronic otitis media: an electron microscopy study
    Open this publication in new window or tab >>The chorda tympani degenerates during chronic otitis media: an electron microscopy study
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    2015 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 135, no 6, 542-548 p.Article in journal (Refereed) Published
    Abstract [en]

    Conclusion: Chorda tympani nerve specimens from ears with chronic inflammatory middle ear disease exhibit structural signs of degeneration. These correlate well with taste disturbance. Simultaneously, they exhibit signs of regeneration, which may explain the ability for taste recovery. Objectives: The chorda tympani, the major taste nerve, runs uncovered through the middle ear cavity. This situation exposes it to various forms of middle ear pathology. A difference has been noticed regarding taste symptoms pre- and postoperatively between inflammatory and non-inflammatory diseases. The present study aimed to investigate ultrastructural changes of chorda tympani in different forms of inflammatory middle ear disease, such as chronic suppurative otitis media and cholesteatoma, as compared with normal. Methods: Five chorda tympani specimens were collected from healthy middle ears of patients subjected to surgery for acoustic neuroma, to be used as normal controls, and five from middle ears with chronic otitis media or cholesteatoma, where the nerve could not be saved during the operation. Light and electron microscopy were performed. Results: For all five nerves from diseased ears, microscopy showed a higher percentage of axon and myelin sheath degeneration than in the normal controls. Furthermore, three of the five also exhibited sprouting.

    Keyword
    Taste, otosurgery, degeneration, sprouting
    National Category
    Otorhinolaryngology
    Identifiers
    urn:nbn:se:uu:diva-255041 (URN)10.3109/00016489.2014.999875 (DOI)000354215700004 ()25719908 (PubMedID)
    Funder
    Swedish Research Council, 2010-7209
    Available from: 2015-06-23 Created: 2015-06-12 Last updated: 2017-03-07Bibliographically approved
    3. Taste disturbance after stapes surgery: an evaluation of frequency, severity, duration, and quality-of-life
    Open this publication in new window or tab >>Taste disturbance after stapes surgery: an evaluation of frequency, severity, duration, and quality-of-life
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    2017 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 37, no 1, 39-43 p.Article in journal (Refereed) Published
    Abstract [en]

     

    Conclusion: The incidence of taste disturbance after stapes surgery is high (61.9 %), whereas the majority (94.8 %) recovers within 1 year. More severe surgical nerve trauma caused more disturbance, implying that the nerve should be handled carefully during surgery.

     

    Objectives: Patients operated on for otosclerosis seem more often to complain about post-operative taste disturbance than those operated on for chronic otitis media, although the chorda tympani nerve more seldom becomes maltreated in stapedotomy. These observations seem paradoxical. It is unclear to what extent a post-operative taste disturbance affects the quality-of-life. This study aims to shed light on the occurrence of post-operative taste disturbances, on possible prognostic factors, and to what extent post-operative taste disturbance impairs the quality-of-life.

     

    Methods: One hundred and thirty-four adults undergoing primary stapedotomy were included. Questionnaires on taste disturbance and quality-of-life (SF-36) were answered before and after surgery, until 1 year post-operatively.

     

    Results: Eighty-three (61.9%) study persons reported post-operative taste disturbance. Seven (5.2%) reported persisting disturbance at 1 year. Surgically more traumatized chorda tympani nerves correlated with more severe taste disturbance post-operatively than less traumatized.  Taste disturbance at 1 year post-operatively correlate with a decrease of the physical function domain in the SF-36.

    Place, publisher, year, edition, pages
    Taylor & Francis Group, 2017
    Keyword
    Chorda tympani nerve, otosclerosis, stapedotomy, taste, questionnaire, QoL, SF-36
    National Category
    Otorhinolaryngology
    Research subject
    Oto-Rhino-Laryngology
    Identifiers
    urn:nbn:se:uu:diva-315775 (URN)10.1080/00016489.2016.1217562 (DOI)
    Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-03-07Bibliographically approved
    4. Surgery for chronic otitis media causes greater taste disturbance than surgery for otosclerosis
    Open this publication in new window or tab >>Surgery for chronic otitis media causes greater taste disturbance than surgery for otosclerosis
    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Objectives: Patients with otosclerosis more often complain about postoperative taste disturbance than those with chronic otitis media, which seems paradoxical. During surgery, the chorda tympani nerve (CTN) is thought to be severely traumatized less frequently, in the former than in the latter.

    Study design: Objective and subjective measurements of taste impairment were obtained to document the occurrence of taste disturbance before and after surgery, possible prognostic factors, and to what extent such complications affect quality of life (QoL).

    Methods: Sixty-five adults undergoing primary middle ear surgery were included. Thirty-seven were operated on for chronic suppurative otitis media (CSOM) and 28 for otosclerosis. Taste was assessed using electrogustometry (EGM) and the filter paper disc (FPD) method before and up to 1 year after surgery.  Questionnaires on taste disturbance and on QoL were completed before and up to 1 year after surgery.

    Results: The FPD method indicated preoperative taste disturbance for participants with CSOM, who reported more postoperative taste disturbance than did those with otosclerosis. Severe traumatization of the CTN during surgery or an abnormal CTN before surgery predicted more severe symptoms after surgery. Younger people and females were also at higher risk for postoperative taste disturbance. QoL was slightly impairment after surgery in patients with abnormal CTN status at start of surgery.

    Conclusion: People operated for CSOM had greater postoperative taste disturbances than did those operated on for otosclerosis. Females and younger people seemed to be more prone to postoperative taste disturbance. Traumatization of the CTN significantly reduced taste ability. 

    Keyword
    Chorda tympani nerve, ear surgery, taste, electrogustometry, chronic otitis media, otosclerosis
    National Category
    Medical and Health Sciences
    Research subject
    Oto-Rhino-Laryngology
    Identifiers
    urn:nbn:se:uu:diva-315778 (URN)
    Available from: 2017-02-21 Created: 2017-02-21 Last updated: 2017-03-07
  • Public defence: 2017-04-28 09:00 Häggsalen, Uppsala
    Blidberg, Andreas
    Uppsala University, Disciplinary Domain of Science and Technology, Chemistry, Department of Chemistry - Ångström, Structural Chemistry.
    Iron Based Materials for Positive Electrodes in Li-ion Batteries: Electrode Dynamics, Electronic Changes, Structural Transformations2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Li-ion battery technology is currently the most efficient form of electrochemical energy storage. The commercialization of Li-ion batteries in the early 1990’s revolutionized the portable electronics market, but further improvements are necessary for applications in electric vehicles and load levelling of the electric grid. In this thesis, three new iron based electrode materials for positive electrodes in Li-ion batteries were investigated. Utilizing the redox activity of iron is beneficial over other transition metals due to its abundance in the Earth’s crust. The condensed phosphate Li2FeP2O7 together with two different LiFeSO4F crystal structures that were studied herein each have their own advantageous, challenges, and scientific questions, and the combined insights gained from the different materials expand the current understanding of Li-ion battery electrodes.

    The surface reaction kinetics of all three compounds was evaluated by coating them with a conductive polymer layer consisting of poly(3,4-ethylenedioxythiophene), PEDOT. Both LiFeSO4F polymorphs showed reduced polarization and increased charge storage capacity upon PEDOT coating, showing the importance of controlling the surface kinetics for this class of compounds. In contrast, the electrochemical performance of PEDOT coated Li2FeP2O7 was at best unchanged. The differences highlight that different rate limiting steps prevail for different Li-ion insertion materials.

    In addition to the electrochemical properties of the new iron based energy storage materials, also their underlying material properties were investigated. For tavorite LiFeSO4F, different reaction pathways were identified by in operando XRD evaluation during charge and discharge. Furthermore, ligand involvement in the redox process was evaluated, and although most of the charge compensation was centered on the iron sites, the sulfate group also played a role in the oxidation of tavorite LiFeSO4F. In triplite LiFeSO4F and Li2FeP2O7, a redistribution of lithium and iron atoms was observed in the crystal structure during electrochemical cycling. For Li2FeP2O7, and increased randomization of metal ions occurred, which is similar to what has been reported for other iron phosphates and silicates. In contrast, triplite LiFeSO4F showed an increased ordering of lithium and iron atoms. An electrochemically induced ordering has previously not been reported upon electrochemical cycling for iron based Li-ion insertion materials, and was beneficial for the charge storage capacity of the material.

    List of papers
    1. Identifying the electrochemical processes in LiFeSO4F cathodes for Li-ion batteries
    Open this publication in new window or tab >>Identifying the electrochemical processes in LiFeSO4F cathodes for Li-ion batteries
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    (English)Article in journal (Other academic) Accepted
    National Category
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-317003 (URN)10.1002/celc.201700192 (DOI)
    Funder
    Swedish Foundation for Strategic Research , EM11-0028
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-20
    2. Direct Observations of Phase Distributions in Operating Lithium Ion Batteries
    Open this publication in new window or tab >>Direct Observations of Phase Distributions in Operating Lithium Ion Batteries
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    (English)Article in journal (Other academic) Submitted
    National Category
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-317005 (URN)
    Funder
    Swedish Foundation for Strategic Research , EM11-0028
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-20
    3. Electronic Changes in LiFeSO4F-PEDOT Battery Cathodes upon Oxidation
    Open this publication in new window or tab >>Electronic Changes in LiFeSO4F-PEDOT Battery Cathodes upon Oxidation
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-317007 (URN)
    Funder
    Swedish Foundation for Strategic Research , EM11-0028
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-20
    4. Structural and Electronic Changes in Li2FeP2O7 during Electrochemical Cycling
    Open this publication in new window or tab >>Structural and Electronic Changes in Li2FeP2O7 during Electrochemical Cycling
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    2015 (English)In: Chemistry of Materials, ISSN 0897-4756, E-ISSN 1520-5002, Vol. 27, no 11, 3801-3804 p.Article in journal (Refereed) Published
    National Category
    Chemical Sciences Physical Sciences
    Identifiers
    urn:nbn:se:uu:diva-258346 (URN)10.1021/acs.chemmater.5b00440 (DOI)000356202800004 ()
    Available from: 2015-07-13 Created: 2015-07-13 Last updated: 2017-03-08Bibliographically approved
    5. Surface Coating and Structural Changes in Triplite LiFeSO4F Cathodes
    Open this publication in new window or tab >>Surface Coating and Structural Changes in Triplite LiFeSO4F Cathodes
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Inorganic Chemistry
    Identifiers
    urn:nbn:se:uu:diva-317008 (URN)
    Funder
    Swedish Foundation for Strategic Research , EM11-0028
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-08
  • Public defence: 2017-04-28 09:00 Auditorium Minus, Uppsala
    Wrammert, Johan
    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).
    Surviving birth: Studies of a simplified neonatal resuscitation protocol in a low-income context using a mixed-methods approach2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    United Nations has lately stated ambitious health targets for 2030 in the Sustainable Development Goal agenda, following the already achieved progress between 1990 and 2015 when the number of children dying before the age of five was reduced by more than half. However, the mortality reduction in the first month of life after birth has not kept the same pace. Furthermore, a large number of stillbirths have previously not been accounted for. The aim of this thesis was to evaluate the impact of clinical training in neonatal resuscitation, and to identify strategies for an effective implementation at a maternal health facility in Nepal.

    Focus group discussions were used to explore the perceptions of teamwork among staff working closest to the infant at the facility. A prospective cohort study with nested referents was applied to determine effect on birth outcomes after an intervention with Helping Babies Breathe, a simplified protocol for neonatal resuscitation. Sustainability of the acquired skills after training was addressed by employing a quality improvement cycle. Video recordings of health workers performance were collected to analyse adherence to protocol.

    Midwives described the need for universal protocols in neonatal resuscitation and management involvement in clinical audit and feedback. There was a reduction of intrapartum stillbirth (aOR 0.46, 95% CI 0.32–0.66) and neonatal mortality within 24 hours of life (aOR 0.51, 95% CI 0.31–0.83) after the intervention. Ventilation of infants increased (OR 2.56, 95% CI 1.67–3.93) and potentially harmful suctioning was reduced (OR 0.13, 95% CI 0.09–0.17). Neonatal death from intrapartum-related complications was reduced and preterm infants survived additional days in the neonatal period after the intervention. Low birth weight was not found to be a predictor of deferred resuscitation in the studied context.

    This study confirmed the robustness of Helping Babies Breathe as an educational tool for training in neonatal resuscitation. Accompanied with a quality improvement cycle it reduced intrapartum stillbirth and mortality on the day of delivery in a low-income facility setting. Improved postnatal care is needed to maintain the gains in survival through the neonatal period. Increased management involvement in audit and quality of care could improve clinical performance among health workers.

    List of papers
    1. Teamwork among midwives during neonatal resuscitation at a maternity hospital in Nepal.
    Open this publication in new window or tab >>Teamwork among midwives during neonatal resuscitation at a maternity hospital in Nepal.
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    2017 (English)In: Women and Birth, ISSN 1871-5192, E-ISSN 1878-1799, S1871-5192(16)30120-2Article in journal (Refereed) Epub ahead of print
    Abstract [en]

    PROBLEM: The ability of health care providers to work together is essential for favourable outcomes in neonatal resuscitation, but perceptions of such teamwork have rarely been studied in low-income settings.

    BACKGROUND: Neonatal resuscitation is a proven intervention for reducing neonatal mortality globally, but the long-term effects of clinical training for this skill need further attention. Having an understanding of barriers to teamwork among nurse midwives can contribute to the sustainability of improved clinical practice.

    AIM: To explore nurse midwives' perceptions of teamwork when caring for newborns in need of resuscitation.

    METHODS: Nurse midwives from a tertiary-level government hospital in Nepal participated in five focus groups of between 4 and 11 participants each. Qualitative Content Analysis was used for analysis.

    FINDINGS: One overarching theme emerged: looking for comprehensive guidelines and shared responsibilities in neonatal resuscitation to avoid personal blame and learn from mistakes. Participants discussed the need for protocols relating to neonatal resuscitation and the importance of shared medical responsibility, and the importance of the presence of a strong and transparent leadership.

    DISCUSSION: The call for clear and comprehensive protocols relating to neonatal resuscitation corresponded with previous research from different contexts.

    CONCLUSION: Nurse midwives working at a maternity health care facility in Nepal discussed the benefits and challenges of teamwork in neonatal resuscitation. The findings suggest potential benefits can be made from clarifying guidelines and responsibilities in neonatal resuscitation. Furthermore, a structured process to deal with clinical incidents must be considered. Management must be involved in all processes.

    Keyword
    Low-income population, Neonatal resuscitation, Nurse midwives, Practice guidelines, Teamwork
    National Category
    Nursing
    Identifiers
    urn:nbn:se:uu:diva-316658 (URN)10.1016/j.wombi.2017.02.002 (DOI)28254364 (PubMedID)
    Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-03-07
    2. Reducing perinatal mortality in Nepal using Helping Babies Breathe
    Open this publication in new window or tab >>Reducing perinatal mortality in Nepal using Helping Babies Breathe
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    2016 (English)In: Pediatrics, ISSN 0031-4005, E-ISSN 1098-4275, Vol. 137, no 6, e20150117Article in journal (Refereed) Published
    Abstract [en]

    Objective: Newborns are at the highest risk of dying around the time of birth, due to intrapartum-related complications. Our study’s objective was to improve adherence to the Helping Babies Breathe (HBB) neonatal resuscitation protocol and reduce perinatal mortality using a quality improvement cycle (QIC) in a tertiary hospital in Nepal.

     

    Methods: The HBB QIC was implemented through a multi-faceted approach, including: the formation of quality improvement teams; development of quality improvement goals, objectives and standards; HBB protocol training; weekly review meetings; daily skill checks; use of self-evaluation checklists; and refresher trainings. A cohort design including a nested case-control study was used to measure changes in clinical outcomes and adherence to the resuscitation protocol through video recording, before and after implementation of the QIC.

     

    Results: The intrapartum stillbirth rate decreased from 9 to 3.2 per thousand deliveries, and first-day mortality from 5.2 to 1.9 per thousand live births after intervention, demonstrating a reduction of about half in the odds of intrapartum stillbirth (aOR=0.46, 95% CI 0.32-0.66) and first-day mortality (aOR=0.51, 95% CI 0.31-0.83). After intervention, the odds of inappropriate use of suction and stimulation decreased by 87% (OR=0.13, 95% CI 0.09-0.17) and 62% (OR=0.38, 95% CI 0.29-0.49), respectively. Prior to intervention, none of the babies received bag-and-mask ventilation within 1 minute of birth, compared to 83.9% of babies after.

     

    Conclusion: The HBB QIC reduced intrapartum stillbirth and first-day neonatal mortality and led to use of suctioning and stimulation more frequently. The HBB QIC requires further testing in primary settings across Nepal.

    Keyword
    intrapartum stillbirth, intrapartum-related neonatal death, Helping Babies Breathe, quality improvement cycle, Nepal
    National Category
    Pediatrics Public Health, Global Health, Social Medicine and Epidemiology
    Research subject
    International Health; Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-267919 (URN)10.1542/peds.2015-0117 (DOI)000378520100001 ()
    Funder
    Swedish Society of Medicine
    Available from: 2015-11-29 Created: 2015-11-29 Last updated: 2017-03-07Bibliographically approved
    3. Improved postnatal care is needed to maintain gains in neonatal survival after the implementation of the Helping Babies Breathe initiative
    Open this publication in new window or tab >>Improved postnatal care is needed to maintain gains in neonatal survival after the implementation of the Helping Babies Breathe initiative
    (English)Article in journal (Refereed) Accepted
    Abstract [en]

    Aim

    Helping Babies Breathe (HBB) is a neonatal resuscitation protocol proven to reduce intrapartum-related mortality in low-income settings. The aim of this study was to describe the timing and causes of neonatal in-hospital deaths before and after HBB training at a maternity health facility in Nepal.

    Methods

    A prospective cohort study was conducted at the facility between July 2012 and September 2013. All 137 staff, including medical doctors and midwives, were trained in January 2013. The causes of 299 neonatal deaths and the day of death, up to 27 days, were collected before and after the training course.

    Results

    Deaths caused by intrapartum-related complications were reduced from 51% to 33%.  Preterm infants survived for more days (p<0.01) during the neonatal period, but overall in-hospital neonatal mortality was unchanged (p=0.46) after training. The survival rates linked to complications of infection, congenital anomalies and other causes were unaffected by the intervention.

    Conclusion

    The continuum of postnatal care for newborn infants needs to be strengthened after Helping Babies Breathe training, in order to maintain the gains in neonatal survival on the day of delivery. Additional interventions in the postnatal period are therefore required to increase neonatal survival at facilities in low-income settings.

    Keyword
    cause of death, low-income settings, neonatal resuscitation, perinatal mortality, postnatal
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-316710 (URN)
    Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-03-14
    4. Resuscitation practices of low and normal birth weight infants in Nepal: an observational study using video camera recordings
    Open this publication in new window or tab >>Resuscitation practices of low and normal birth weight infants in Nepal: an observational study using video camera recordings
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    (English)Article in journal (Other academic) Submitted
    Abstract [en]

    Background: The global burden of stillbirth and neonatal deaths remains achallenge in low-income countries. Training in neonatal resuscitation canreduce intrapartum stillbirth and early neonatal mortality. Previous resultsdemonstrate that infants who previously would have been registered asstillbirths are successfully resuscitated after such training, suggesting thatthere is a process of selection for resuscitation that needs to be explored.

    Objective: To compare neonatal resuscitation of low birth weight andnormal birth weight infants born at a facility in a low-income setting.

    Methods: Motion-triggered video cameras were installed above theresuscitation tables at a maternity health facility during an interventionstudy (ISRCTN97846009) employing the Helping Babies Breatheresuscitation protocol in Kathmandu, Nepal. Recordings were analysed,noting crying, stimulation, ventilation, suctioning and oxygenadministration during resuscitation. Birth weight, Apgar scores and sex ofthe infant were retrieved from matched hospital registers. The results wereanalysed by chi-square and logistic regression.

    Results: A total of 2253 resuscitation cases were recorded. Low birthweight infants in need of resuscitation had higher odds of receivingventilation (aOR 1.73), and lower odds of receiving suctioning (aOR 0.53)after adjustment for the Helping Babies Breathe intervention, sex of theinfant and place of resuscitation within the facility. The rate of stimulationand administration of oxygen was the same in both groups.

    Conclusions: Low birth weight was associated with more ventilation andless suctioning during neonatal resuscitation in a low-income setting. Asventilation is the most important intervention when the infant does notinitiate breathing after birth, low birth weight was not a predictor for thedecision to withhold resuscitation. Frequent routine use of suctioning of thelower airways continues to be a problem in the studied context, even afterthe introduction of the Helping Babies Breathe protocol.

    Keyword
    neonatal resuscitation, low birth weight, guideline adherence, video recording, low-income population
    National Category
    Pediatrics
    Identifiers
    urn:nbn:se:uu:diva-316720 (URN)
    Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-03-07
  • Public defence: 2017-04-28 09:00 Polhemssalen/10134, Uppsala
    Hinnemo, Malkolm
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Solid State Electronics.
    On the Road to Graphene Biosensors2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Biosensors are devices that detect biological elements and then transmit a readable signal. Biosensors can automatize diagnostics that would otherwise have to be performed by a physician or perhaps not be possible to perform at all. Current biosensors are however either limited to particular diseases or prohibitively expensive. In order to further the field, sensors capable of many parallel measurements at a lower cost need to be developed. Field effect transistor (FET) based sensors are possible candidates for delivering this, mainly by allowing miniaturization. Smaller sensors could be cheaper, and enable parallel measurements.

    Graphene is an interesting material to use as the channel of FET-sensors. The low electrochemical reactivity of its plane makes it possible to have graphene in direct contact with the sample liquid, which enhances the signal from impedance changes. Graphene-FET based impedance sensors should be able to sense almost all possible analytes and allow for scaling without losing sensitivity.

    In this work the steps needed to make graphene based biosensors are presented. An improved graphene transfer is described which by using low pressure to dry the graphene removes most contamination. A method to measure the contamination of graphene by surface enhanced Raman scattering is presented. Methods to produce double gated and electrolyte gated graphene transistors on a large scale in an entirely photolithographic process are detailed. The deposition of 1-pyrenebutyric acid (PBA) on graphene is studied. It is shown that at high surface concentrations the PBA stands up on graphene and forms a dense self-assembled monolayer. A new process of using Raman spectroscopy data to quantify adsorbents was developed in order to quantify the molecule adsorption. Biosensing has been performed in two different ways. Graphene FETs have been used to read the signal generated by a streaming potential setup. Using FETs in this context enables a more sensitive readout than what would be possible without them. Graphene FETs have been used to directly sense antibodies in high ionic strength. This sensing was done by measuring the impedance of the interface between the FET and the electrolyte.

    List of papers
    1. Scalable residue-free graphene for surface-enhanced Raman scattering
    Open this publication in new window or tab >>Scalable residue-free graphene for surface-enhanced Raman scattering
    Show others...
    2016 (English)In: Carbon, ISSN 0008-6223, E-ISSN 1873-3891, Vol. 98, 567-571 p.Article in journal (Refereed) Published
    Abstract [en]

    A room-temperature polymer-assisted transfer process is developed for large-area, single-layer graphene grown by means of chemical vapor deposition (CVD). This process leads to transferred graphene layers free of polymer contamination. The absence of polymer residues boosts the surface-enhanced Raman scattering (SERS) of the CVD graphene with gold nanoparticles (Au NPs) deposited atop by evaporation. The SERS enhancement of the CVD graphene reaches similar to 120 for the characteristic 2D peak of graphene, the highest enhancement factor achieved to date, when the Au NPs are at the threshold of percolation. Our simulation supported by experiment suggests that the polymer residues persistently present on the graphene transferred by the conventional polymer-assisted method are equivalent to an ultrathin film of less than 1 nm thickness. The presence of polymer residues drastically reduces SERS due to the separation of the Au NPs from the underlying graphene. The scalability of CVD graphene opens up for the possibility of graphene-based SERS sensors.

    National Category
    Physical Sciences Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-269192 (URN)10.1016/j.carbon.2015.11.043 (DOI)000367233000070 ()
    Funder
    Knut and Alice Wallenberg Foundation, 2011.0113Knut and Alice Wallenberg Foundation, 2011.0082Swedish Foundation for Strategic Research , SE13-0061Swedish Research Council, 621-2014-5591
    Available from: 2015-12-14 Created: 2015-12-14 Last updated: 2017-03-10Bibliographically approved
    2. A two-in-one process for reliable graphene transistors processed with photolithography
    Open this publication in new window or tab >>A two-in-one process for reliable graphene transistors processed with photolithography
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    2015 (English)In: Applied Physics Letters, ISSN 0003-6951, E-ISSN 1077-3118, Vol. 107, no 20, 203104Article in journal (Refereed) Published
    Abstract [en]

    Research on graphene field-effect transistors (GFETs) has mainly relied on devices fabricated using electron-beam lithography for pattern generation, a method that has known problems with polymer contaminants. GFETs fabricated via photo-lithography suffer even worse from other chemical contaminations, which may lead to strong unintentional doping of the graphene. In this letter, we report on a scalable fabrication process for reliable GFETs based on ordinary photo-lithography by eliminating the aforementioned issues. The key to making this GFET processing compatible with silicon technology lies in a two-in-one process where a gate dielectric is deposited by means of atomic layer deposition. During this deposition step, contaminants, likely unintentionally introduced during the graphene transfer and patterning, are effectively removed. The resulting GFETs exhibit current-voltage characteristics representative to that of intrinsic non-doped graphene. Fundamental aspects pertaining to the surface engineering employed in this work are investigated in the light of chemical analysis in combination with electrical characterization.

    National Category
    Physical Sciences Engineering and Technology
    Identifiers
    urn:nbn:se:uu:diva-269191 (URN)10.1063/1.4935985 (DOI)000365688700049 ()
    Funder
    Knut and Alice Wallenberg Foundation, 2011.0113, 2011.0082Swedish Foundation for Strategic Research , SE13-0061Swedish Research Council, 621-2014-5591
    Available from: 2015-12-14 Created: 2015-12-14 Last updated: 2017-03-10Bibliographically approved
    3. On Monolayer Formation of Pyrenebutyric Acid on Graphene
    Open this publication in new window or tab >>On Monolayer Formation of Pyrenebutyric Acid on Graphene
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    (English)In: Langmuir, ISSN 0743-7463, E-ISSN 1520-5827Article in journal (Refereed) Submitted
    National Category
    Physical Chemistry
    Identifiers
    urn:nbn:se:uu:diva-317087 (URN)
    Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2017-03-10
    4. Highly sensitive detection of allergic proteins by nano-scale field effect transistor-integrated electrokinetic sensor
    Open this publication in new window or tab >>Highly sensitive detection of allergic proteins by nano-scale field effect transistor-integrated electrokinetic sensor
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-317089 (URN)
    Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2017-04-07
    5. Protein sensing beyond the Debye Length Using Graphene Field-effect Transistors
    Open this publication in new window or tab >>Protein sensing beyond the Debye Length Using Graphene Field-effect Transistors
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Other Electrical Engineering, Electronic Engineering, Information Engineering
    Identifiers
    urn:nbn:se:uu:diva-317088 (URN)
    Available from: 2017-03-10 Created: 2017-03-10 Last updated: 2017-03-10
  • Public defence: 2017-04-28 09:15 B42, Uppsala
    Ghadzi, Siti Maisharah Sheikh
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
    Pharmacometrics Modelling in Type 2 Diabetes Mellitus: Implications on Study Design and Diabetes Disease Progression2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Pharmacometric modelling is widely used in many aspects related to type 2 diabetes mellitus (T2DM), for instance in the anti-diabetes drug development, and in quantifying the disease progression of T2DM.

    The aim of this thesis were to improve the design of early phase anti-diabetes drug development studies with the focus on the power to identify mechanism of drug action (MoA), and to characterize and quantify the progression from prediabetes to overt diabetes, both the natural progression and the progression with diet and exercise interventions, using pharmacometrics modelling.

    The appropriateness of a study design depends on the MoAs of the anti-hyperglycaemic drug. Depending on if the focus is power to identify drug effect or accuracy and precision of drug effect, the best design will be different. Using insulin measurements on top of glucose has increase the power to identify a correct drug effect, distinguish a correct MoA from the incorrect, and to identify a secondary MoA in most cases. The accuracy and precision of drug parameter estimates, however, was not affected by insulin. A natural diabetes disease progression model was successfully added in a previously developed model to describe parameter changes of glucose and insulin regulation among impaired glucose tolerance (IGT) subjects, with the quantification of the lifestyle intervention. In this model, the assessment of multiple short-term provocations was combined to predict the long-term disease progression, and offers apart from the assessment of the onset of T2DM also the framework for how to perform similar analysis. Another previously published model was further developed to characterize the weight change in driving the changes in glucose homeostasis in subjects with IGT. This model includes the complex relationship between dropout from study and weight and glucose changes.

    This thesis has provided a first written guidance in designing a study for pharmacometrics analysis when characterizing drug effects, for early phase anti-diabetes drug development. The characterisation of the progression from prediabetes to overt diabetes using pharmacometrics modelling was successfully performed. Both the natural progression and the progression with diet and exercise interventions were quantified in this thesis.

    List of papers
    1. The impact of insulin measurements in oral glucose tolerance test: a simulation study in type 2 diabetes to assess power to characterize drug effects
    Open this publication in new window or tab >>The impact of insulin measurements in oral glucose tolerance test: a simulation study in type 2 diabetes to assess power to characterize drug effects
    (English)Article in journal (Other academic) Submitted
    Keyword
    study power, insulin measurements, oral glucose tolerance test, drug effects
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Science
    Identifiers
    urn:nbn:se:uu:diva-316810 (URN)
    Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-03-10
    2. Study design selection in early clinical anti-diabetic drug development; A simulation study of glucose tolerance tests
    Open this publication in new window or tab >>Study design selection in early clinical anti-diabetic drug development; A simulation study of glucose tolerance tests
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Phase I clinical trials, study design, power, precision, pharmacometric simulations
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Science
    Identifiers
    urn:nbn:se:uu:diva-316819 (URN)
    Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-03-10
    3. Mathematical diabetes disease progression modeling in the integrated glucose-insulin (IGI) model among impaired glucose tolerance subjects from the Finnish Diabetes Prevention Study
    Open this publication in new window or tab >>Mathematical diabetes disease progression modeling in the integrated glucose-insulin (IGI) model among impaired glucose tolerance subjects from the Finnish Diabetes Prevention Study
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    (English)Manuscript (preprint) (Other academic)
    Keyword
    mathematical model, impaired glucose tolerance, diabetes disease progression model, lifestyle intervention, insulin secretion, insulin sensitivity
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Science
    Identifiers
    urn:nbn:se:uu:diva-316825 (URN)
    Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-03-10
    4. Model-based quantification of the natural diabetes disease progression and lifestyle intervention effects on weight, beta cell function and insulin sensitivity for subjects with impaired glucose tolerance
    Open this publication in new window or tab >>Model-based quantification of the natural diabetes disease progression and lifestyle intervention effects on weight, beta cell function and insulin sensitivity for subjects with impaired glucose tolerance
    Show others...
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Model-based, impaired glucose tolerance, diabetes disease progression model, lifestyle intervention, insulin sensitivity, beta cell function, postprandial glucose, weight, fasting plasma glucose, fasting serum insulin, HbA1c
    National Category
    Pharmaceutical Sciences
    Research subject
    Pharmaceutical Science
    Identifiers
    urn:nbn:se:uu:diva-316834 (URN)
    Available from: 2017-03-09 Created: 2017-03-09 Last updated: 2017-03-10
  • Public defence: 2017-04-28 09:15 Friessalen, Uppsala
    Mostovaya, Alina
    Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Ecology and Genetics, Limnology.
    Dissolved organic matter in lakes: Chemical diversity and continuum of reactivity2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Dissolved organic matter (DOM) is the largest pool of organic carbon in aquatic systems and an important component of the global carbon cycle. Large amounts of DOM are decomposed within lakes, resulting in fluxes of CO2 and CH4 to the atmosphere. Therefore, there is a considerable interest in understanding the controls of DOM decomposition in freshwaters. There is evidence that in lakes intrinsic controls related to DOM composition are of primary importance, yet our knowledge about molecular drivers of DOM degradation is limited. This thesis addresses the link between chemical composition and reactivity of lake DOM by applying an experimental approach, molecular-level DOM characterization, and kinetic modeling of DOM decay.

    The first study shows that photoinduced transformations and partial removal of colored aromatic components of DOM have profound effects on DOM degradation kinetics, mediated by the shifts in the relative share of rapidly and slowly degrading DOM fractions. Two following studies estimate exponential decay coefficients for each individual molecular formula identified within bulk DOM. A continuous distribution of exponential decay coefficients is found within bulk DOM, which directly corroborates the central and previously empirically untested assumption behind the reactivity continuum model of DOM decay. Further, individual decay rates are evaluated in connection to specific molecular properties. On average, highly unsaturated and phenolic compounds appear to be more persistent than compounds with higher aromatic content (plant polyphenols and polycondensed aromatics), and aliphatic compounds demonstrate the highest decay rates. The reactivity of aromatics additionally increases with increasing nominal oxidation state of carbon. Molecular analysis further indicates that increasing reactivity of DOM after UV exposure is caused by disintegration of supramolecular complexes. Study IV shows that changes in relative proportion of terrestrial versus algal DOM control degradability of DOM through seasons. Under ice, when algal-derived DOM is maximally depleted, DOM degradation potential converges to similarly low levels, regardless of lake type (productive or humic), and bacterial respiration primarily relies on terrestrial carbon. This suggests a general pattern of baseline metabolism across boreal lakes. I conclude that DOM is a dynamic reactivity continuum and a tight link exists between DOM behavior and compositional properties.

    List of papers
    1. Effects of compositional changes on reactivity continuum and decomposition kinetics of lake dissolved organic matter
    Open this publication in new window or tab >>Effects of compositional changes on reactivity continuum and decomposition kinetics of lake dissolved organic matter
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    2016 (English)In: Journal of Geophysical Research - Biogeosciences, ISSN 2169-8953, E-ISSN 2169-8961, Vol. 121, no 7, 1733-1746 p.Article in journal (Refereed) Published
    Abstract [en]

    To address the link between the composition and decomposition of freshwater dissolved organic matter (DOM), we manipulated the DOM from three boreal lakes using preincubations with UV light to cleave large aromatic molecules and polyvinylpyrrolidone (PVP) to remove colored phenolic compounds. Subsequently, we monitored the dissolved organic carbon (DOC) loss over 4months of microbial degradation in the dark to assess how compositional changes in DOM affected different aspects of the reactivity continuum, including the distribution of the apparent decay coefficients. We observed profound effects on decomposition kinetics, with pronounced shifts in the relative share of rapidly and more slowly decomposing fractions of the DOM. In the UV-exposed treatment initial apparent decay coefficient k(0) was almost threefold higher than in the control. Significantly higher relative DOC loss in the UV-exposed treatment was sustained for 2months of incubation, after which decay coefficients converged with those in the control. The PVP removed compounds with absorbance and fluorescence characteristics representative of aromatic compounds, which led to slower decomposition, compared to that in the control. Our results demonstrate the reactivity continuum underlying the decomposition of DOM in freshwaters and highlight the importance of intrinsic properties of DOM in determining its decomposition kinetics.

    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-304303 (URN)10.1002/2016JG003359 (DOI)000382581900002 ()
    Funder
    Swedish Research Council, 2011-3475-88773-67Knut and Alice Wallenberg Foundation
    Available from: 2016-10-04 Created: 2016-10-04 Last updated: 2017-03-08Bibliographically approved
    2. The emergence of the reactivity continuum of organic matter from kinetics of a multitude of individual molecular constituents
    Open this publication in new window or tab >>The emergence of the reactivity continuum of organic matter from kinetics of a multitude of individual molecular constituents
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    (English)Manuscript (preprint) (Other academic)
    Keyword
    dissolved organic matter, reactivity continuum model, FT-ICR-MS
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-316887 (URN)
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-08
    3. Molecular determinants of dissolved organic matter reactivity in lake water
    Open this publication in new window or tab >>Molecular determinants of dissolved organic matter reactivity in lake water
    (English)Manuscript (preprint) (Other academic)
    Keyword
    Dissolved organic matter, FT-ICR-MS, molecular composition, DOM degradation
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-316890 (URN)
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-08
    4. Seasonal variability in dissolved organic carbon degradation in boreal lakes: links to composition, sources, and baseline metabolism
    Open this publication in new window or tab >>Seasonal variability in dissolved organic carbon degradation in boreal lakes: links to composition, sources, and baseline metabolism
    (English)Manuscript (preprint) (Other academic)
    Keyword
    DOC, bacterioplankton, boreal lakes, seasonality, carbon source, baseline metabolism
    National Category
    Natural Sciences
    Identifiers
    urn:nbn:se:uu:diva-316892 (URN)
    Available from: 2017-03-08 Created: 2017-03-08 Last updated: 2017-03-08
  • Public defence: 2017-04-28 13:00 Lecture hall 2, Uppsala
    Paçacı, Görkem
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Informatics and Media, Information Systems.
    Representation of Compositional Relational Programs2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    Usability aspects of programming languages are often overlooked, yet have a substantial effect on programmer productivity. These issues are even more acute in the field of Inductive Synthesis, where programs are automatically generated from sample expected input and output data, and the programmer needs to be able to comprehend, and confirm or reject the suggested programs.

    A promising method of Inductive Synthesis, CombInduce, which is particularly suitable for synthesizing recursive programs, is a candidate for improvements in usability as the target language Combilog is not user-friendly. The method requires the target language to be strictly compositional, hence devoid of variables, yet have the expressiveness of definite clause programs. This sets up a challenging problem for establishing a user-friendly but equally expressive target language.

    Alternatives to Combilog, such as Quine's Predicate-functor Logic and Schönfinkel and Curry's Combinatory Logic also do not offer a practical notation: finding a more usable representation is imperative. This thesis presents two distinct approaches towards more convenient representations which still maintain compositionality.

    The first is Visual Combilog (VC), a system for visualizing Combilog programs. In this approach Combilog remains as the target language for synthesis, but programs can be read and modified by interacting with the equivalent diagrams instead. VC is implemented as a split-view editor that maintains the equivalent Combilog and VC representations on-the-fly, automatically transforming them as necessary.

    The second approach is Combilog with Name Projection (CNP), a textual iteration of Combilog that replaces numeric argument positions with argument names. The result is a language where argument names make the notation more readable, yet compositionality is preserved by avoiding variables. Compositionality is demonstrated by implementing CombInduce with CNP as the target language, revealing that programs with the same level of recursive complexity can be synthesized in CNP equally well, and establishing the underlying method of synthesis can also work with CNP.

    Our evaluations of the user-friendliness of both representations are supported by a range of methods from Information Visualization, Cognitive Modelling, and Human-Computer Interaction. The increased usability of both representations are confirmed by empirical user studies: an often neglected aspect of language design.

  • Public defence: 2017-04-28 13:00 Häggsalen, Uppsala
    Möllerström, Erik
    Uppsala University, Disciplinary Domain of Science and Technology, Technology, Department of Engineering Sciences, Electricity.
    Noise, eigenfrequencies and turbulence behavior of a 200 kW H-rotor vertical axis wind turbine2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Vertical-axis wind turbines (VAWTs) have with time been outrivaled by the today more common and economically feasible horizontal-axis wind turbines (HAWTs). However, VAWTs have several advantages which still make them interesting, for example, the VAWTs can have the drive train at ground level and it has been argued that they have lower noise emission. Other proposed advantages are suitability for both up-scaling and floating offshore platforms.

    The work within this thesis is made in collaboration between Halmstad University and Uppsala University. A 200-kW semi-guy-wired VAWT H-rotor, owned by Uppsala University but situated in Falkenberg close to Halmstad, has been the main subject of the research although most results can be generalized to suit a typical H-rotor.

    This thesis has three main topics regarding VAWTs: (1) how the wind energy extraction is influenced by turbulence, (2) aerodynamical noise generation and (3) eigenfrequencies of the semi-guy-wired tower.

    The influence from turbulence on the wind energy extraction is studied by evaluating logged operational data and examining how the power curve and the tip-speed ratio for maximum Cp is impacted by turbulence. The work has showed that the T1-turbine has a good ability to extract wind energy at turbulent conditions, indicating an advantage in energy extraction at turbulent sites for VAWTs compared to HAWTs.The noise characteristics are studied experimentally, and models of the two most likely aerodynamic noise mechanisms are applied. Here, inflow-turbulence noise is deemed as the prevailing noise source rather than turbulent-boundary-layer trailing-edge noise (TBL-TE) which is the most important noise mechanism for HAWTs. The overall noise emission has also been measured and proven low compared to similar sized HAWTs.

    The eigenfrequencies of a semi-guy-wired tower are also studied. Analytical expressions describing the first-mode eigenfrequency of both tower and guy wire has been derived and verified by experiments and simulations.

    List of papers
    1. Turbulence influence on wind energy extraction for a medium size vertical axis wind turbine
    Open this publication in new window or tab >>Turbulence influence on wind energy extraction for a medium size vertical axis wind turbine
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    2016 (English)In: Wind Energy, ISSN 1095-4244, E-ISSN 1099-1824, Vol. 19, no 11, 1963-1973 p.Article in journal (Refereed) Published
    Abstract [en]

    The relation between power performance and turbulence intensity for a VAWT H-rotor is studied using logged data from a 14 month (discontinuous) period with the H-rotor operating in wind speeds up to 9 m/s. The turbine, designed originally fora nominal power of 200 kW, operated during this period mostly in a restricted mode due to mechanical concerns, reachingpower levels up to about 80 kW. Two different approaches are used for presenting results, one that can be compared topower curves consistent with the International Electrotechnical Commission (IEC) standard and one that allows isolatingthe effect of turbulence from the cubic variation of power with wind speed. Accounting for this effect, the turbine stillshows slightly higher efficiency at higher turbulence, proposing that the H-rotor is well suited for wind sites with turbulentwinds. The operational data are also used to create a Cp(λ) curve, showing slightly lower Cp compared with a curvesimulated by a double multiple streamtube model.

    Keyword
    VAWT; H-rotor; turbulence intensity; power coefficient curve
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-277352 (URN)10.1002/we.1962 (DOI)000386149700001 ()
    Funder
    StandUp
    Available from: 2016-02-19 Created: 2016-02-19 Last updated: 2017-03-01Bibliographically approved
    2. Turbulence influence on optimum tip speed ratio for a 200 kW vertical axis wind turbine
    Open this publication in new window or tab >>Turbulence influence on optimum tip speed ratio for a 200 kW vertical axis wind turbine
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    2016 (English)Conference paper (Refereed)
    Abstract [en]

    The influence of turbulence intensity (TI) on the tip speed ratio for maximum power coefficient, here called λCp-max, is studied for a 200 kW VAWT H-rotor using logged data from a 14 month period with the H-rotor operating in wind speeds up to 9 m/s. The TI - λCp-max relation is examined by dividing 10 min mean values in different turbulence intensity ranges and producing multiple CP(λ) curves. A clear positive relation between TI and λCp-max is shown and is further strengthened as possible secondary effects are examined and deemed non-essential. The established relation makes it possible to tune the control strategy to enhance the total efficiency of the turbine.

    Series
    Journal of Physics Conference Series, ISSN 1742-6588 ; 753
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-304789 (URN)10.1088/1742-6596/753/3/032048 (DOI)
    Conference
    6th Science of Making Torque from Wind Conference, Technical University of Munich, Munich, Germany, Oct. 5-7, 2016
    Funder
    StandUp
    Available from: 2016-10-10 Created: 2016-10-10 Last updated: 2017-03-01
    3. Noise Emission of a 200 kW Vertical Axis Wind Turbine
    Open this publication in new window or tab >>Noise Emission of a 200 kW Vertical Axis Wind Turbine
    2016 (English)In: Energies, ISSN 1996-1073, E-ISSN 1996-1073, Vol. 9, no 1, 19Article in journal (Refereed) Published
    Abstract [en]

    The noise emission from a vertical axis wind turbine (VAWT) has been investigated. A noise measurement campaign on a 200 kW straight-bladed VAWT has been conducted, and the result has been compared to a semi-empirical model for turbulent-boundary-layer trailing edge (TBL-TE) noise. The noise emission from the wind turbine was measured, at wind speed 8 m/s, 10 m above ground, to 96.2 dBA. At this wind speed, the turbine was stalling as it was run at a tip speed lower than optimal due to constructional constraints. The noise emission at a wind speed of 6 m/s, 10 m above ground was measured while operating at optimum tip speed and was found to be 94.1 dBA. A comparison with similar size horizontal axis wind turbines (HAWTs) indicates a noise emission at the absolute bottom of the range. Furthermore, it is clear from the analysis that the turbulent-boundary-layer trailing-edge noise, as modeled here, is much lower than the measured levels, which suggests that other mechanisms are likely to be important, such as inflow turbulence.

    Keyword
    vertical axis wind turbine (VAWT); H-rotor; noise; noise emission; sound power level
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-242263 (URN)10.3390/en9010019 (DOI)000369501500013 ()
    Funder
    StandUp
    Available from: 2015-01-19 Created: 2015-01-22 Last updated: 2017-03-01Bibliographically approved
    4. Location of aerodynamic noise sources from a 200-kW vertical-axis wind turbine
    Open this publication in new window or tab >>Location of aerodynamic noise sources from a 200-kW vertical-axis wind turbine
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-316384 (URN)
    Available from: 2017-02-28 Created: 2017-02-28 Last updated: 2017-03-01
    5. Eigen Frequencies of A Vertical Axis Wind Turbine Tower Made of Laminated Wood and the Effect Upon Attaching Guy Wires
    Open this publication in new window or tab >>Eigen Frequencies of A Vertical Axis Wind Turbine Tower Made of Laminated Wood and the Effect Upon Attaching Guy Wires
    2014 (English)In: Wind Engineering: The International Journal of Wind Power, ISSN 0309-524X, E-ISSN 2048-402X, Vol. 38, no 3, 277-290 p.Article in journal (Refereed) Published
    Abstract [en]

    Eigen frequencies of a vertical axis wind turbine tower made out of laminated wood which are both bolted to the ground and supported by guy wires are studied and compared. Using beam theory, an analytical model taking the guy wires into account for calculating the first mode eigen frequency of the tower has been derived. The analytical model is then evaluated by comparing with FEM-simulations and measurements performed on the actual tower. The model is found to be reasonably accurate keeping in mind that the estimated masses and second moments of area are somewhat rough. Furthermore the model can be used to give an indication of the magnitude of change in eigen frequency when modifying a tower or guy wire property.

    Place, publisher, year, edition, pages
    Brentwood, United Kingdom: Multi-Science Publishing, 2014
    Keyword
    VAWT, Vertical Axis Wind Turbine, Semi-guy-wired, Natural frequency, Eigen frequency, Resonance
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-242265 (URN)10.1260/0309-524X.38.3.277 (DOI)2-s2.0-84901792518 (ScopusID)
    Available from: 2014-06-02 Created: 2015-01-22 Last updated: 2017-03-01
    6. Avoidance of resonances in a semi-guy-wired vertical axis wind turbine
    Open this publication in new window or tab >>Avoidance of resonances in a semi-guy-wired vertical axis wind turbine
    2014 (English)In: Proceedings of EWEA 2014 - Annual Event (Conference), Barcelona, 10-13 March 2014, 2014Conference paper (Refereed)
    Abstract [en]

    Resonance analysis for a vertical axis wind turbine is performed. The turbine may be described as semi-guy wired, being bolted stiffly to the ground as well as supported by guy wires. The influence of the first mode eigen frequency of the guy wires and how it is affected by wind load is examined. Using beam theory, an analytical model for calculating the first mode eigen frequency of the guy wire for different wind loads is derived. The analytical model is verified with FEM-simulations and then used to assemble a diagram showing how to combine the wire size, inclination angle and pre-tension for an eigen frequency range over the 3P load for nominal rotational speed and for a certain effective spring force acting on the tower. This diagram, here called an EA-T diagram, may be used as a quick tool for comparing wire setups and a similar diagram can be used for other guy wired structures.

    Keyword
    VAWT, guy wire, semi-guy-wired, resonance, eigen frequency, natural frequency
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-242266 (URN)
    Conference
    EWEA 2014 - Annual Event (Conference), Barcelona, Spain, 10-13 March 2014
    Available from: 2014-03-19 Created: 2015-01-22 Last updated: 2017-03-01
    7. Noise Propagation from a Vertical Axis Wind Turbine
    Open this publication in new window or tab >>Noise Propagation from a Vertical Axis Wind Turbine
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    2014 (English)In: Proceedings of 43rd International Congress on Noise Control Engineering: Internoise 2014 / [ed] John Davy, Charles Don, Terry McMinn, Liz Dowsett, Norm Broner & Marion Burgess, Brisbane, QLD: Australian Acoustical Society , 2014Conference paper (Refereed)
    Abstract [en]

    Initial noise measurements were performed on a 200kW vertical axis wind turbine (VAWT) and results were compared to that of a Vestas V27, a similar size horizontal axis wind turbine (HAWT). Multiple recording units were placed in line downwind of the turbine to investigate noise propagation. The frequency distribution of the noise were analyzed indicating that the VAWT has lower relative levels for frequencies under 3000 Hz, especially within 600-1200 Hz. Furthermore, VAWT noise seems to occur more around the same frequencies as the natural background noise, increasing masking probability. Results from propagation measurements seemed to indicate that noise declines more rapidly with distance for the VAWT then for the reference HAWT, possibly explained by the lower levels at low frequencies. Further investigation is needed to establish these differences and the 200 kW VAWT creates an opportunity doing so utilizing arguably the largest operational VAWT existing today.

    Place, publisher, year, edition, pages
    Brisbane, QLD: Australian Acoustical Society, 2014
    Keyword
    VAWT, Wind Turbine, Propagation
    National Category
    Energy Engineering
    Identifiers
    urn:nbn:se:uu:diva-242264 (URN)978-0-909882-02-0 (ISBN)978-0-909882-03-7 (ISBN)978-0-909882-04-4 (ISBN)
    Conference
    inter.noise 2014, 43rd International Congress on Noise Control Engineering, Melbourne, Australia, November 16-19, 2014
    Available from: 2014-11-25 Created: 2015-01-22 Last updated: 2017-03-01
  • Public defence: 2017-04-28 13:00 Hedstrandsalen, Uppsala
    Edsfeldt, Sara
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Hand Surgery.
    Intrasynovial flexor tendon injuries and repair2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Complications after surgical repair of intrasynovial flexor tendon injuries in the hand occur despite advanced suture techniques and structured postoperative rehabilitation regimens. Early controlled tendon mobilization prevents adhesion formations and improves tendon healing as well as digit range of motion. To allow early postoperative rehabilitation, the strength of the repair must withstand forces created during the rehabilitation maneuvers. Improvements in suture biomechanics have increased repair strength, but up to 18 percent of repaired tendons still rupture. The overarching aim of this thesis was to investigate how to best treat intrasynovial flexor tendon injuries with limited risk of repair rupture, decreased adhesion formations, and to estimate the effect of individual patient and injury characteristics on functional outcome.

    In two observational studies, we identified risk factors for rupture of repaired intrasynovial flexor digitorum profundus (FDP) tendons, and studied effects of these risk factors on the long-term outcome. Age was associated with increased risk of repair rupture and impaired digital mobility the first year after surgical repair. Concomitant flexor digitorum superficialis (FDS) transection was associated with increased risk of repair rupture without affecting digital mobility. Concomitant nerve transection lowered the rupture risk without affecting digital mobility.

    To better understand forces generated in the flexor tendons during rehabilitation maneuvers, we measured in vivo forces in the index finger FDP and FDS tendons during rehabilitation exercises. Highest forces were measured during isolated FDP and FDS flexion for the FDP and FDS respectively. For the FDS tendon, higher forces were observed with the wrist at 30° flexion compared to neutral position, and for the FDP tendon, forces were higher during active finger flexion compared to place and hold.

    PXL01 is a lactoferrin peptide with anti-adhesive effects previously demonstrated in animal studies and a clinical trial to improve digital mobility when administrated around repaired tendons. We studied the mechanism of action of its corresponding rabbit peptide, rabPXL01 in sodium hyaluronate (HA) in a rabbit model of flexor tendon transection and repair and used RT-qPCR to assess mRNA levels for different genes. Increased levels of PRG4 (encoding lubricin) were observed in rabPXL01 in HA treated tendons. The expression of Interleukin 1β, 6, and 8 was repressed in tendon sheaths. RabPXL01 in HA might stimulate the release of lubricin and diminish inflammation, which correspondingly reduces tendon-gliding resistance and adhesion formations during postoperative rehabilitation exercises.

    The results of this thesis suggest individually adapted treatment plans, depending on repair strength, patient and injury characteristics, as a possible way to improve outcome after flexor tendon repair.

    List of papers
    1. Risk factors for rupture of repaired flexor tendons in zone I and II
    Open this publication in new window or tab >>Risk factors for rupture of repaired flexor tendons in zone I and II
    (English)Article in journal (Other academic) Submitted
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-316557 (URN)
    Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-03-15
    2. Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair - Long-term follow-up on 311 patients treated with active extension-passive flexion with rubber bands
    Open this publication in new window or tab >>Prognostic factors for digital range of motion after intrasynovial flexor tendon injury and repair - Long-term follow-up on 311 patients treated with active extension-passive flexion with rubber bands
    (English)Article in journal (Other academic) Submitted
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-316558 (URN)
    Available from: 2017-03-02 Created: 2017-03-02 Last updated: 2017-03-15
    3. In vivo flexor tendon forces generated during different rehabilitation exercises
    Open this publication in new window or tab >>In vivo flexor tendon forces generated during different rehabilitation exercises
    Show others...
    2015 (English)In: Journal of Hand Surgery, European Volume, ISSN 1753-1934, E-ISSN 2043-6289, Vol. 40, no 7, 705-710 p.Article in journal (Refereed) Published
    Abstract [en]

    UNLABELLED: We measured in vivo forces in the flexor digitorum profundus and the flexor digitorum superficialis tendons during commonly used rehabilitation manoeuvres after flexor tendon repair by placing a buckle force transducer on the tendons of the index finger in the carpal canal during open carpal tunnel release of 12 patients. We compared peak forces for each manoeuvre with the reported strength of a flexor tendon repair. Median flexor digitorum profundus force (24 N) during isolated flexor digitorum profundus flexion and median flexor digitorum superficialis force (13 N) during isolated flexor digitorum superficialis flexion were significantly higher than during the other manoeuvres. Significantly higher median forces were observed in the flexor digitorum superficialis with the wrist at 30° flexion (6 N) compared with the neutral wrist position (5 N). Median flexor digitorum profundus forces were significantly higher during active finger flexion (6 N) compared with place and hold (3 N). Place and hold and active finger flexion with the wrist in the neutral position or tenodesis generated the lowest forces; isolated flexion of these tendons generated higher forces along the flexor tendons.

    LEVEL OF EVIDENCE: III (controlled trial without randomization).

    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-284410 (URN)10.1177/1753193415591491 (DOI)26115682 (PubMedID)
    Available from: 2016-04-18 Created: 2016-04-18 Last updated: 2017-03-02
    4. PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion
    Open this publication in new window or tab >>PXL01 in sodium hyaluronate results in increased PRG4 expression: a potential mechanism for anti-adhesion
    Show others...
    2017 (English)In: Upsala Journal of Medical Sciences, ISSN 0300-9734, E-ISSN 2000-1967, Vol. 122, no 1, 28-34 p.Article in journal (Refereed) Published
    Abstract [en]

    PURPOSE: To investigate the anti-adhesive mechanisms of PXL01 in sodium hyaluronate (HA) by using the rabbit lactoferrin peptide, rabPXL01 in HA, in a rabbit model of healing tendons and tendon sheaths. The mechanism of action for PXL01 in HA is interesting since a recent clinical study of the human lactoferrin peptide PXL01 in HA administered around repaired tendons in the hand showed improved digit mobility.

    MATERIALS AND METHODS: On days 1, 3, and 6 after tendon injury and surgical repair, reverse transcriptase-quantitative polymerase chain reaction (RT-qPCR) was used to assess mRNA expression levels for genes encoding the mucinous glycoprotein PRG4 (also called lubricin) and a subset of matrix proteins, cytokines, and growth factors involved in flexor tendon repair. RabPXL01 in HA was administered locally around the repaired tendons, and mRNA expression was compared with untreated repaired tendons and tendon sheaths.

    RESULTS: We observed, at all time points, increased expression of PRG4 mRNA in tendons treated with rabPXL01 in HA, but not in tendon sheaths. In addition, treatment with rabPXL01 in HA led to repression of the mRNA levels for the pro-inflammatory mediators interleukin (IL)-1β, IL-6, and IL-8 in tendon sheaths.

    CONCLUSIONS: RabPXL01 in HA increased lubricin mRNA production while diminishing mRNA levels of inflammatory mediators, which in turn reduced the gliding resistance and inhibited the adhesion formation after flexor tendon repair.

    Keyword
    Carcinoid heart disease, Cardiac imaging, Heart metastases, Neuroendocrine tumors
    National Category
    Surgery
    Identifiers
    urn:nbn:se:uu:diva-309615 (URN)10.1080/03009734.2016.1230157 (DOI)000396476600004 ()27658527 (PubMedID)
    Funder
    Swedish Foundation for Strategic Research
    Available from: 2016-12-06 Created: 2016-12-06 Last updated: 2017-04-12Bibliographically approved
  • Public defence: 2017-04-28 13:15 A1:111a, Uppsala
    Sandvik, Pernilla
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Social Sciences, Department of Food, Nutrition and Dietetics.
    Rye bread in Sweden: Health-related and sensory qualities, consumer perceptions and consumption patterns2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Rye bread has shown potential as a health-beneficial component in the diet, especially in relation to non-communicable diseases. To have a beneficial effect in reality, however, it also needs to be available, chosen and eaten. Less research has focused on rye bread from a consumer perspective. The main aim was to investigate consumption patterns, health-related and sensory qualities and consumer perceptions of bread, more specifically commercial rye bread. In Study I, secondary analysis was performed on bread consumption data from a national dietary survey (n=1,435, 18-80 years). In Study II, commercial rye breads (n=24) were characterized by sensory descriptive analysis; the in vitro measurement fluidity index (FI) was used to predict glycemic properties, and chemical acidity was measured. Study III was a consumer test (n=398, 18-80 years), where acceptance and perceptions of nine rye breads were investigated. Study IV was a web-based and postal sequential mixed-mode survey (n=1,134, 18-80 years) with open-ended items covering health-related perceptions of bread. Consumers with the lowest intake of whole grain and rye bread were from younger age groups, families with children and groups with lower educational levels. Health-related and sensory properties of commercial rye bread varied widely. The FI indicated more beneficial glycemic properties in half of the samples and this was associated with a chewy, dry texture and sour flavor. The younger consumer group (18-44 years) differed in their liking compared to the older group (45-80 years) and displayed a preference toward bread with less whole grain and rye, although different clusters were identified. Rye bread liking was associated with bread type consumed in childhood, food choice motives and educational level. Most (75%) knew of bread they considered healthy. Coarse, whole grain, fiber, sourdough and rye were perceived to be good for the stomach, bowel and, to have good satiation and glycemic properties. Few health claims have been authorized, making it challenging for consumers to identify bread with these properties. Front-of-package label indicating rye bread was sometimes found on breads with very little rye flour. Sensory attributes, foremost textural and flavor, e.g., sourness, correlated with beneficial FI values and could thereby help guide consumers.

    List of papers
    1. Bread consumption patterns in a Swedish national dietary survey focusing particularly on whole-grain and rye bread
    Open this publication in new window or tab >>Bread consumption patterns in a Swedish national dietary survey focusing particularly on whole-grain and rye bread
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    2014 (English)In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 58, 24024- p.Article in journal (Refereed) Published
    Abstract [en]

    Background: Bread types with high contents of whole grains and rye are associated with beneficial health effects. Consumer characteristics of different bread consumption patterns are however not well known.

    Objective: To compare bread consumption patterns among Swedish adults in relation to selected socio-demographic, geographic, and lifestyle-related factors. For selected consumer groups, the further aim is to investigate the intake of whole grains and the context of bread consumption, that is, where and when it is consumed.

    Design: Secondary analysis was performed on bread consumption data from a national dietary survey (n=1,435). Respondents were segmented into consumer groups according to the type and amount of bread consumed. Multiple logistic regressions were performed to study how selected socio-demographic, geographic, and lifestyle-related factors were associated with the consumer groups. Selected consumption groups were compared in terms of whole-grain intake and consumption context. Consumption in different age groups was analysed more in detail.

    Results: One-third of the respondents consumed mainly white bread. Socio-demographic, geographic, and healthy-lifestyle-related factors were associated with the bread type consumed. White bread consumption was associated with younger age groups, less education, children in the family, eating less fruit and vegetables, and more candy and snacks; the opposite was seen for mainly whole-grain bread consumers. Older age groups more often reported eating dry crisp bread, whole-grain bread, and whole-grain rye bread with sourdough whereas younger respondents reported eating bread outside the home, something that also mainly white bread eaters did. Low consumers of bread also consumed less whole grain in total.

    Conclusions: Traditional bread consumption structures were observed, as was a transition among young consumers who more often consumed fast food bread and bread outside the home, as well as less rye and whole-grain bread. Target groups for communication strategies and product development of more sensorily attractive rye or whole-grain-rich bread should be younger age groups (18–30 years), families with children, and groups with lower educational levels.

    Keyword
    public health, whole-grain bread, consumption context
    National Category
    Other Social Sciences not elsewhere specified
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-231967 (URN)10.3402/fnr.v58.24024 (DOI)000342086600001 ()25278822 (PubMedID)
    Available from: 2014-09-12 Created: 2014-09-12 Last updated: 2017-03-09Bibliographically approved
    2. Characterization of Commercial Rye Bread Based on Sensory Properties, Fluidity Index and Chemical Acidity
    Open this publication in new window or tab >>Characterization of Commercial Rye Bread Based on Sensory Properties, Fluidity Index and Chemical Acidity
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    2016 (English)In: Journal of sensory studies, ISSN 0887-8250, E-ISSN 1745-459X, Vol. 31, no 4, 283-295 p.Article in journal (Refereed) Published
    Abstract [en]

    Rye bread is often considered healthy, especially regarding its potential beneficial effect on blood glucose and insulin regulation, but the characteristics of Swedish rye bread have not previously been described. The aim was to characterize commercial rye bread (n = 24) using sensory descriptive analysis (11 panelists, 15 attributes, 2 replicates), fluidity index (FI; an in vitromeasurement to predict glycemic properties), chemical acidity and selected package information. The associations between sensory and chemical measurements were explored to identify the opportunities and challenges of increased consumption of rye bread with potential health benefits.

    Six categories of rye bread were identified on the basis of their sensory profiles. The FI indicated that bread from three of the categories possessed beneficial glycemic properties (FI 50–75). These categories contained 31–100% rye, displaying pH 4.3–4.8. Sensory attributes, foremost textural (e.g., chewiness), but also flavor (e.g., sourness), were highly correlated with FI values, thereby revealing their potential to aid consumers, in that they can serve as quality indicators of the glycemic properties of commercial rye bread. However, this also highlights potential sensory barriers to consumption. Front-of-package rye and sourdough labels on some samples could potentially mislead consumers given the low content of rye/sourdough, despite the labels.

    National Category
    Other Social Sciences not elsewhere specified
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-305430 (URN)10.1111/joss.12211 (DOI)000385559600002 ()
    Funder
    VINNOVASwedish Research Council Formas
    Available from: 2016-10-18 Created: 2016-10-18 Last updated: 2017-03-09Bibliographically approved
    3. Different liking but similar healthiness perceptions of rye bread among younger and older consumers
    Open this publication in new window or tab >>Different liking but similar healthiness perceptions of rye bread among younger and older consumers
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    (English)In: Food Quality and Preference, ISSN 0950-3293, E-ISSN 1873-6343Article in journal (Refereed) Submitted
    Abstract [en]

    Rye breads, especially those with a chewy texture and sour flavor, have shown several health benefits but their consumption is lower among younger consumers than older. This study explored liking of commercial rye bread in younger and older consumers in relation to socio-demographics, childhood bread-eating habits and food choice motives. Further, sensory attributes are explored in relation to the consumers’ concepts of a rye bread and healthiness in bread.

         Nine commercial rye breads previously profiled by descriptive analysis were tasted by 225 younger (18-44 years) and 173 older (45-80 years) consumers. Internal preference mappings by principal component regression for each age group showed low liking for rye bread with a chewy texture and sour flavor in the younger group. Based on the preference mappings, the age groups were separately clustered. Associations between clusters and background variables were studied using discriminant partial least squares regression. Liking of rye bread with a chewy texture and sour flavor in the younger consumer group was associated with higher education, females and the food choice motives health, ethical concern and natural content. In the older consumer group, it was especially related to higher education and background in another Nordic country. Partial least regression-1 showed that the combination of sensory attributes such as a light color and soft texture led to the perception of bread being less healthy and not a rye bread, and a dark brown color, tough texture, sour and bitter flavor to the perception of a healthier bread and rye bread.

    Keyword
    Food choice questionnaire, childhood bread consumption, preference mapping, healthiness mapping, consumer test
    National Category
    Other Social Sciences not elsewhere specified
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-316596 (URN)
    Funder
    Swedish Research Council Formas, 2011-242VINNOVA, 2011-242
    Available from: 2017-03-04 Created: 2017-03-04 Last updated: 2017-03-09
    4. Consumers' health-related perceptions of bread - Implications for labeling and dietary counceling
    Open this publication in new window or tab >>Consumers' health-related perceptions of bread - Implications for labeling and dietary counceling
    (English)In: Appetite, ISSN 0195-6663, E-ISSN 1095-8304Article in journal (Refereed) Submitted
    Abstract [en]

    Purpose: From a health perspective, there is a wide variety of commercial bread types. The aim is to describe consumers’ health-related perceptions of bread by exploring which health-related quality attributes consumers associate with bread and whether there are differences with regard to age and education level.

    Methodology: A postal and web-based sequential mixed-mode survey (n=1134, 63% responded online and 37% by paper). Open-ended questions and an elicitation task with pictures of commercial breads were used. Responses were analyzed for their content and inductively categorized.

    Findings: Three fourths (n=844) knew of breads they considered healthy; these were most commonly described using terms such as “coarse,” “whole-grain,” “fiber rich,” “sourdough,” “crisp,” “less sugar,” “dark,” “rye,” “seeds,” “a commercial brand,” “homemade” and “kernels.” The attributes were perceived as healthy mainly because they “contain fiber” and are “good for the stomach,” or have good “satiation” and beneficial “glycemic properties.” The frequency of several elicited attributes and health effects differed as a function of age group (18-44 vs. 45-80 years) and education level group (up to secondary education vs. university). Difficulties identifying healthy bread were perceived as a barrier for consumption especially among consumers with a lower education level (38%) compared to a higher (28%) (p=.004).

    Originality/value: The present study identifies potential pitfalls in consumer evaluations of bread from a health perspective, particularly in relation to labels and packing. The findings are relevant to health professionals working in dietary counseling as well as to industry when designing packaging and to authorities when drawing up regulations.

    Keyword
    quality perception, cues, labeling, whole grain, age groups, educational level
    National Category
    Other Social Sciences not elsewhere specified
    Research subject
    Food, Nutrition and Dietetics
    Identifiers
    urn:nbn:se:uu:diva-316597 (URN)
    Funder
    Swedish Research Council Formas, 2011-242VINNOVA, 2011-242
    Available from: 2017-03-04 Created: 2017-03-04 Last updated: 2017-03-16
  • Public defence: 2017-04-29 13:00 Linnésalen, Uppsala
    Garland, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Orthopaedics.
    Early Mortality After Total Hip Arthroplasty In Sweden2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Every year 16 000 individuals receive a total hip arthroplasty (THA) in Sweden. Even though THA is a common procedure, adverse events do occur. The most dramatic complication is death in the postoperative phase. The overall aim of this thesis was to describe and investigate early mortality after THA in Sweden.

    Sweden has an ideal platform for national observational registry studies, thanks to the use of personal identity numbers. Operation-specific information was collected from the Swedish Hip Arthroplasty Register, medical information from the National Board of Health and Welfare, and socioeconomic information was collected from Statistics Sweden. Main outcome was 90-day mortality.

    Study I was a prospective observational register study investigating the risk of mortality after a simultaneous bilateral THA compared with staged bilateral THA. There was no clinically relevant difference in early postoperative mortality between the two groups.

    Studies II and III were nation-wide matched cohort studies, with adjustment for comorbidity and socioeconomic background. Adjusted early mortality in femoral neck fracture patients receiving a THA is about double compared with a matched control population. Young (60-69 years) femoral neck fracture patients receiving a THA have a low absolute mortality risk, while those who are older than 80 years with a higher degree of medical comorbidity run a high risk of early death (II). In study III healthier, younger patients with higher socioeconomic status tended to be selected for cementless THA, resulting in selection bias. Even after accounting for this bias, however, there remains a small absolute and adjusted increase in the risk of death within 14 days after elective THA surgery using fully cemented implants.

    Study IV was a nationwide prospective cohort study comparing different comorbidity measures in terms of predicting early postoperative mortality after THA. A less data-demanding comorbidity measure is better at predicting 90-day mortality than more commonly used coding algorithms.

    In conclusion, socioeconomic background and the presence of comorbidities have an important influence on early mortality after THA, while the type of fixation is of less importance. Future mortality studies could benefit from the use of data that are routinely collected, and thus avoid the logistically complicated procedure now necessary to merge national databases.

    List of papers
    1. Early postoperative mortality after simultaneous or staged bilateral primary total hip arthroplasty: an observational register study from the swedish Hip arthroplasty register
    Open this publication in new window or tab >>Early postoperative mortality after simultaneous or staged bilateral primary total hip arthroplasty: an observational register study from the swedish Hip arthroplasty register
    Show others...
    2015 (English)In: BMC Musculoskeletal Disorders, ISSN 1471-2474, E-ISSN 1471-2474, Vol. 16, 77Article in journal (Refereed) Published
    Abstract [en]

    Background: Approximately a fifth of all total hip arthroplasty (THA) patients suffers from bilateral osteoarthritis of the hip. It is unclear whether mortality risks differ between simultaneous bilateral THA and staged bilateral THA. We investigated mortality after simultaneous THA compared with staged bilateral THA in the largest cohort hitherto reported. Methods: The 42,238 patients reported to have received bilateral primary THA from 1992 to 2012 in the Swedish Hip Arthroplasty Register were included. Tumours and fractures as underlying diagnoses were excluded. The time interval between the first and second THA was divided into four categories or treated as a continuous variable. Unadjusted survival was calculated according to Kaplan-Meier and adjusted Cox regression models were fitted in order to calculate crude and adjusted hazard ratios (HR) for the risk of death within different time frames. Results: Patients selected for simultaneous bilateral surgery were younger, more often male, and had lower ASA (American Society of Anesthesiologists) class than patients receiving staged procedures. The adjusted 90-day mortality after the second procedure did not differ between the four investigated groups (simultaneous bilateral [HR 1.3, CI 0.5-3.3], surgeries within 6 months [HR 1.1, CI 0.6-2.0], surgeries between 7 and 12 months [HR 0.7, CI 0.4-1.2], with second surgery after > 12 months as the reference group). For patients older than 75 years, men, patients with ASA class 3 or above, and for patients with rheumatoid arthritis (RA) the 90-day mortality was increased. The unadjusted risk of implant revision of any hip was slightly higher for patients with simultaneous bilateral THA compared to those with staged procedure within one year, but after adjustment for age, gender, diagnosis and implant fixation these differences were no longer statistically significant. Conclusion: There were no clinically relevant differences in early postoperative mortality between simultaneous and staged bilateral surgery in healthy patients. Advanced age, RA, a high ASA class and male sex increased the risk of death within 90 days. There may be an issue with enhanced risk of implant revision in patients with simultaneous bilateral THA that needs to be explored further.

    Keyword
    Postoperative mortality, Perioperative mortality, Simultaneous bilateral total hip arthroplasty, Register, Registry, Total hip replacement, One-stage bilateral THR/THA, Two-stage bilateral THR/THA
    National Category
    Orthopedics
    Identifiers
    urn:nbn:se:uu:diva-252170 (URN)10.1186/s12891-015-0535-0 (DOI)000352609400001 ()25887667 (PubMedID)
    Note

    Erratum in BMC Musculoskeletal Disorders 2015:16, 263, doi:10.1186/s12891-015-0717-9.

    Available from: 2015-05-06 Created: 2015-05-04 Last updated: 2017-03-08Bibliographically approved
    2. Early mortality and morbidity after total hip arthroplasty in patients with femoral neck fracture
    Open this publication in new window or tab >>Early mortality and morbidity after total hip arthroplasty in patients with femoral neck fracture
    Show others...
    2016 (English)In: Acta Orthopaedica, ISSN 1745-3674, E-ISSN 1745-3682, Vol. 87, no 6, 560-566 p.Article in journal (Refereed) Published
    Abstract [en]

    Background and purpose - Early postoperative mortality is relatively high after total hip arthroplasty (THA) that has been performed due to femoral neck fracture. However, this has rarely been investigated after adjustment for medical comorbidity and comparison with the mortality in an age-matched population. We therefore assessed early mortality in hip fracture patients treated with a THA, in the setting of a nationwide matched cohort study.

    Patients and methods - 24,699 patients who underwent THA due to a femoral neck fracture between 1992 and 2012 were matched with 118,518 controls. Kaplan-Meier survival analysis was used to calculate cumulative unadjusted survival, and Cox regression models were fitted to compute hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustment for age, sex, comorbidity, and socioeconomic background.

    Results - 90-day survival was 96.3% (95% CI: 96.0-96.5) for THA cases and 98.7% (95% CI: 98.6-98.8) for control individuals, giving an adjusted HR of 2.2 (95% CI: 2.0-2.4) for THA cases compared to control individuals. Comorbidity burden increased in THA cases over time, but the adjusted risk of death within 90 days did not differ statistically significantly between the time periods investigated (1992-1998, 1999-2005, and 2006-2012). A Charlson comorbidity index of 3 or more, an American Society of Anesthesiologists (ASA) grade of 3 and above, male sex, an age of 80 years and above, an income below the first quartile, and a lower level of education were all associated with an increased risk of 90-day mortality.

    Interpretation - The adjusted early mortality in femoral neck fracture patients who underwent THA was about double that in a matched control population. Patients with femoral neck fracture but with no substantial comorbidity and an age of less than 80 years appear to have a low risk of early death. Patients older than 80 years and those with a Charlson comorbidity index of more than 2 have a high risk of early death, and such patients would perhaps benefit from treatment strategies other than THA, but this should be investigated further.

    National Category
    Orthopedics
    Identifiers
    urn:nbn:se:uu:diva-309086 (URN)10.1080/17453674.2016.1234869 (DOI)000388757800005 ()27649030 (PubMedID)
    Available from: 2016-12-02 Created: 2016-12-02 Last updated: 2017-03-08Bibliographically approved
    3. Risk of early mortality after cemented compared with cementless total hip arthroplasty: a nationwide matched cohort study
    Open this publication in new window or tab >>Risk of early mortality after cemented compared with cementless total hip arthroplasty: a nationwide matched cohort study
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    2017 (English)In: The Bone & Joint Journal, ISSN 2049-4394, E-ISSN 2049-4408, Vol. 99-B, no 1, 37-43 p.Article in journal (Refereed) Published
    Abstract [en]

    Aims It has been suggested that cemented fixation of total hip arthroplasty (THA) is associated with an increased peri-operative mortality compared with cementless THA. Our aim was to investigate this through a nationwide matched cohort study adjusting for age, comorbidity, and socioeconomic background. Patients and Methods A total of 178 784 patients with osteoarthritis who underwent either cemented or cementless THA from the Swedish Hip Arthroplasty Register were matched with 862 294 controls from the general population. Information about the causes of death, comorbidities, and socioeconomic background was obtained. Mortality within the first 90 days after the operation was the primary outcome measure. Results Patients who underwent cemented THA had an increased risk of death during the first 14 days compared with the controls (hazard ratio (HR) 1.3, confidence interval (CI) 1.11 to 1.44), corresponding to an absolute increase in risk of five deaths per 10 000 observations. No such early increase of risk was seen in those who underwent cementless THA. Between days 15 and 29 the risk of mortality was decreased for those with cemented THA (HR 0.7, CI 0.62 to 0.87). Between days 30 and 90 all patients undergoing THA, irrespective of the mode of fixation, had a lower risk of death than controls. Patients selected for cementless fixation were younger, healthier and had a higher level of education and income than those selected for cemented THA. A supplementary analysis of 16 556 hybrid THAs indicated that cementation of the femoral component was associated with a slight increase in mortality up to 15 days, whereas no such increase in mortality was seen in those with a cemented acetabular component combined with a cementless femoral component. Conclusion This nationwide matched cohort study indicates that patients receiving cemented THA have a minimally increased relative risk of early mortality that is reversed from day 15 and thereafter. The absolute increase in risk is very small. Our findings lend support to the idea that cementation of the femoral component is more dangerous than cementation of the acetabular component.

    National Category
    Orthopedics
    Research subject
    Orthopaedics
    Identifiers
    urn:nbn:se:uu:diva-314962 (URN)10.1302/0301-620X.99B1 (DOI)000393669400008 ()28053255 (PubMedID)
    Available from: 2017-02-07 Created: 2017-02-07 Last updated: 2017-03-31Bibliographically approved
    4. Prediction of 90-day mortality after major surgery made simpler: An analysis of different comorbidity measures based on 38,735 patients from the Swedish Hip Arthroplasty Register
    Open this publication in new window or tab >>Prediction of 90-day mortality after major surgery made simpler: An analysis of different comorbidity measures based on 38,735 patients from the Swedish Hip Arthroplasty Register
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Orthopedics
    Identifiers
    urn:nbn:se:uu:diva-314963 (URN)
    Available from: 2017-02-07 Created: 2017-02-07 Last updated: 2017-03-08
  • Public defence: 2017-05-03 10:15 room 80101, Uppsala
    Dyrssen, Hannah
    Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Applied Mathematics and Statistics. Uppsala University, Disciplinary Domain of Science and Technology, Mathematics and Computer Science, Department of Mathematics, Analysis and Probability Theory.
    Valuation and Optimal Strategies in Markets Experiencing Shocks2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis treats a range of stochastic methods with various applications, most notably in finance. It is comprised of five articles, and a summary of the key concepts and results these are built on.

    The first two papers consider a jump-to-default model, which is a model where some quantity, e.g. the price of a financial asset, is represented by a stochastic process which has continuous sample paths except for the possibility of a sudden drop to zero. In Paper I prices of European-type options in this model are studied together with the partial integro-differential equation that characterizes the price. In Paper II the price of a perpetual American put option in the same model is found in terms of explicit formulas. Both papers also study the parameter monotonicity and convexity properties of the option prices.

    The third and fourth articles both deal with valuation problems in a jump-diffusion model. Paper III concerns the optimal level at which to exercise an American put option with finite time horizon. More specifically, the integral equation that characterizes the optimal boundary is studied. In Paper IV we consider a stochastic game between two players and determine the optimal value and exercise strategy using an iterative technique.

    Paper V employs a similar iterative method to solve the statistical problem of determining the unknown drift of a stochastic process, where not only running time but also each observation of the process is costly.

    List of papers
    1. Pricing equations in jump-to-default models
    Open this publication in new window or tab >>Pricing equations in jump-to-default models
    2014 (English)In: Int. J. Theor. Appl. Finance, ISSN 0219-0249, Vol. 17, no 3Article in journal (Refereed) Published
    National Category
    Probability Theory and Statistics
    Identifiers
    urn:nbn:se:uu:diva-313325 (URN)10.1142/S0219024914500198 (DOI)
    Available from: 2017-01-19 Created: 2017-01-19 Last updated: 2017-03-14
    2. The perpetual American put option in jump-to-default models
    Open this publication in new window or tab >>The perpetual American put option in jump-to-default models
    2017 (English)In: Stochastics: An International Journal of Probablitiy and Stochastic Processes, ISSN 1744-2508, E-ISSN 1744-2516, Vol. 89, no 2, 510-520 p.Article in journal (Refereed) Published
    Abstract [en]

    We study the perpetual American put option in a general jump-to-default model, deriving an explicit expression for the price of the option.

    We find that in some cases the optimal stopping boundary vanishes and thus it is not optimal to exercise the option before default occurs. Precise conditions for when this situation arises are given.

    Furthermore we present a necessary and sufficient condition for convexity of the option price, and also show that a nonincreasing intensity is sufficient, but not necessary, to have convexity.

    From this we also get conditions for when option prices are monotone in the model parameters.

    National Category
    Probability Theory and Statistics
    Research subject
    Mathematics with specialization in Applied Mathematics
    Identifiers
    urn:nbn:se:uu:diva-313326 (URN)10.1080/17442508.2016.1267177 (DOI)000392492800004 ()
    Available from: 2017-01-19 Created: 2017-01-19 Last updated: 2017-03-14Bibliographically approved
    3. The integral equation for the American put boundary in models with jumps
    Open this publication in new window or tab >>The integral equation for the American put boundary in models with jumps
    (English)Article in journal (Other academic) Submitted
    Abstract [en]

    The price of the American put option is frequently studied as the solution to an associated free-boundary problem. This free boundary, the optimal exercise boundary, determines the value of the option. In spectrally negative models the early exercise premium representation for the value of the option gives rise to an integral equation for the boundary. We study this integral equation and prove that the optimal exercise boundary is the unique solution and thus that the equation characterizes the free boundary. In a spectrally positive model, this approach does not give an equation for the boundary. We instead find lower and upper bounds for the true boundary which can be found by solving related equations.

    National Category
    Probability Theory and Statistics
    Research subject
    Mathematics with specialization in Applied Mathematics
    Identifiers
    urn:nbn:se:uu:diva-316576 (URN)
    Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-03-14
    4. Optimal stopping games for a process with jumps
    Open this publication in new window or tab >>Optimal stopping games for a process with jumps
    (English)Article in journal (Other academic) Submitted
    Abstract [en]

    This paper presents a study of a general two-player optimal stopping game in a jump-diffusion model. An iterative scheme to find the value of this game is derived, specifically the value is shown to be the limit of a sequence of stopping games for a related diffusion but with a running reward. Furthermore the convergence is uniform and exponential. The special case of a cancellable put option is studied.

    National Category
    Probability Theory and Statistics
    Identifiers
    urn:nbn:se:uu:diva-316577 (URN)
    Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-03-14
    5. Sequential testing of a Wiener process with costly observations
    Open this publication in new window or tab >>Sequential testing of a Wiener process with costly observations
    (English)Article in journal (Other academic) Submitted
    Abstract [en]

    We consider the sequential testing of two simple hypotheses for the drift of a Brownian motion when each observation of the underlying process is associated with a positive cost. In this setting where continuous monitoring of the underlying process is not feasible, the question is not only whether to stop or to continue at a given observation time, but also, if continuing,how to distribute the next observation time. Adopting a Bayesian methodology, we show that the value function can be characterized as the unique fixed point of an associated operator, and that it can be constructed using an iterative scheme. Moreover, the optimal sequential distribution of observation times can be described in terms of the fixed point.

    National Category
    Probability Theory and Statistics
    Research subject
    Mathematics with specialization in Applied Mathematics
    Identifiers
    urn:nbn:se:uu:diva-316571 (URN)
    Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-03-22
  • Public defence: 2017-05-04 10:00 Geijersalen, Uppsala
    Jedenheim Edling, Magnus
    Uppsala University, Disciplinary Domain of Humanities and Social Sciences, Faculty of Arts, Department of Philosophy, Ethics and Social Philosophy.
    Over-Determination and Act-Consequentialism2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This dissertation is a discussion of the challenge that cases of over-determination pose to Act-Consequentialism. Although there are many realistic examples of such cases – for example, pollution, overfishing, or the election of an inappropriate politician – I consider structurally purer examples, one of which I call “Case One.” Suppose that you and I independently shoot and kill a third person called “Victim.” Our bullets arrive at the same time and each shot would have killed Victim by itself. Finally, Victim would not have been killed, if neither of us had pulled the trigger. According to the Standard Version of Act-Consequentialism, an action is wrong if and only if it has an alternative whose consequences would be intrinsically better. Case One challenges the Standard Version because there does not seem to be such an alternative to my action: Victim would have died by your shot if I had not shot him, and similar remarks apply to your action.

    The dissertation is structured as follows. After Chapter One, which briefly introduces the main issues of the dissertation, I turn to Chapter Two – “Preliminaries” – where I outline the Standard Version and highlight the main characteristics of over-determination cases. These cases are divided into cases of redundant difference making and cases of redundant causation. Cases of redundant causation are subdivided further into cases of causal over-determination and pre-emption. I make an important stipulation in this chapter. I say that our actions in Case One and similar cases are “redundant negative difference makers.”

    In Chapter Three – “Replies” – I consider whether the proponent of Act-Consequentialism might question the intuition that you and I, respectively, act wrongly in Case One. The proponent might accept that we have this intuition but explain it away, or she might deny that we have the intuition and instead point to something else that is wrong in this kind of case. For example, she could suggest that although neither you nor I act wrongly individually, we act wrongly together. I argue that these replies are problematic.  For instance, explaining away this intuition might also force us to explain away intuitions that support the Standard Version.

    In Chapter Four – “Causal Consequences” – I discuss an alternative version of Act-Consequentialism that might seem to fare better. The Standard Version interprets the term “outcome of an action” as referring to the entire possible world that would obtain, if the action were performed. The version I have in mind, the “Causal Consequences Version of Act-Consequentialism,” understands “outcome of an action” as instead referring to the causal consequences of the action. It seems clear that you and I, respectively, cause the state of affairs that Victim dies in Case One. However, I show that the Causal Consequences Version has a number of unattractive implications.

    In Chapter Five – “the Non-Standard Version” – I suggest another alternative version of Act-Consequentialism. This version – the Non-Standard Version – implies that you and I act wrongly in Case One. Roughly, the Non-Standard Version says that an action is wrong if and only if it has an alternative whose consequences would be intrinsically better, or is a redundant negative difference maker. The Non-Standard Version is similar to a principle suggested by Derek Parfit. However, I shall argue that the Non-Standard Version is preferable to Parfit’s principle.

    In Chapter Six – “Further Cases” – I discuss a number of cases that challenge the Non-Standard Version. For example, what would the Non-Standard Version imply in a case very similar to Case One but where I would have killed another person, if I had not shot Victim? I argue that the Non-Standard Version handles this and other problematic cases, and that it is therefore a plausible alternative to the Standard Version. 

  • Public defence: 2017-05-04 13:00 A1:111a, Uppsala
    Björk, Anne
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Public Health and Caring Sciences, Family Medicine and Preventive Medicine.
    Aspects of Vitamin D: Prevalence of deficiency and impact on musculoskeletal parameters2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Vitamin D is central in calcium turnover, and adequate levels are important for skeletal health. It is not clear how large contributions from food and sunlight are in Swedish primary care patients, considering the low radiation of UVB in Sweden and fortification of some foods, and whether differences exist between patients of immigrant and Swedish origin. Increasing incidence of osteoporosis-related fractures is a major global health problem. Genetic variations in metabolising enzymes and in the Vitamin D receptor (VDR) have also been shown to be of importance to the overall effect of vitamin D. Polymorphic variation in the gene CYP2R1 encoding the 25-hydroxylase has previously been reported to correlate with circulating levels of 25(OH)D3. Results of association studies between genetic variants of the VDR and muscle strength, as well as falls have been contradictory.

    The purposes of this thesis were to examine possible differences in plasma-25(OH)D3 levels and intake of vitamin D between Swedish and immigrant female primary care patients, to estimate what foods contribute the most, and to identify contributors to vitamin D status (Paper I-II). Furthermore, the relationship between polymorphisms in the CYP2R1 gene and levels of 25(OH)D3 as well as other biochemical parameters (parathyroid hormone, calcium, phosphate and fibroblast growth factor 23) of skeletal homeostasis, bone mineral density and incidence of fractures was investigated (Paper III). Also, the association between genetic variations in the gene for the vitamin D receptor and measures of muscle strength, physical performance and falls (Paper IV), was investigated by using data from a Swedish multicenter study of elderly men (MrOS).

    Most important results: Vitamin D deficiency was common, with significant difference between Swedish born and immigrant patients (Paper I). Food intake of vitamin D is associated with circulating vitamin D, but the factors most strongly affecting vitamin D levels were reported sun holiday and origin (Paper II). CYP2R1 polymorphisms are associated with circulating levels of 25(OH)D3 and bone mineral density (Paper III). VDR genetic variants do not appear to have a direct effect on muscle strength or physical performance and incidence of falls in elderly Swedish men (Paper IV).

    List of papers
    1. Vitamin D intake and status in immigrant and native Swedish women: a study at a primary health care centre located at 60 degrees N in Sweden
    Open this publication in new window or tab >>Vitamin D intake and status in immigrant and native Swedish women: a study at a primary health care centre located at 60 degrees N in Sweden
    2013 (English)In: Food & Nutrition Research, ISSN 1654-6628, E-ISSN 1654-661X, Vol. 57, UNSP 20089- p.Article in journal (Refereed) Published
    Abstract [en]

    Background: Immigration to Sweden from lower latitude countries has increased in recent years. Studies in the general population in other Nordic countries have demonstrated that these groups are at risk of developing vitamin D deficiency, but studies in primary health care patients are rare. Objectives: The aim of this study is to examine possible differences in plasma-25(OH)-vitamin D levels and intake of vitamin D between Swedish and immigrant female patients in a primary health care centre located at 60 degrees N, where half of the inhabitants have an immigrant background. Another objective was to estimate what foods contribute with most vitamin D. Design: Thirty-one female patients from the Middle East and Africa and 30 from Sweden were recruited. P-25(OH)D was measured and intake of vitamin D was estimated with a modified food frequency questionnaire (FFQ). Results: Vitamin D deficiency (plasma-25(OH)D<25 nmol/L) was common among immigrant women (61%). One immigrant woman and half of the Swedish women had optimal levels (plasma-25(OH)D>50 nmol/L). There was a positive correlation between the intake of vitamin D from food and plasma-25(OH) D. Only three women, all Swedish, reached the recommended intake of vitamin D from food. The immigrant women had lower intake compared to Swedish women (median: 3.1 vs. 5.1 mu g/day). The foods that contributed with most vitamin D were fatty fish, fortified milk and margarine. Immigrant women consumed less fortified milk and margarine but more meat. Irrespective of origin, patients with plasma-25(OH)D<25 nmol/L consumed less margarine but more meat. Conclusion: Vitamin D deficiency was common in the immigrant patients and their intake of vitamin D was lower. This highlights the need to target information about vitamin D to immigrant women in order to decrease the risk for vitamin D deficiency. The FFQ was well adapted to its purpose to estimate intake of vitamin D.

    Keyword
    immigrants, vitamin D deficiency, primary health care, food, nutrition requirements
    National Category
    Medical and Health Sciences
    Identifiers
    urn:nbn:se:uu:diva-203368 (URN)10.3402/fnr.v57i0.20089 (DOI)000319261600001 ()
    Available from: 2013-07-09 Created: 2013-07-09 Last updated: 2017-03-30Bibliographically approved
    2. Evaluation of sun holiday, diet habits, origin and other factors as determinants of vitamin D status in Swedish primary health care patients: a cross-sectional study with regression analysis of ethnic Swedish and immigrant women
    Open this publication in new window or tab >>Evaluation of sun holiday, diet habits, origin and other factors as determinants of vitamin D status in Swedish primary health care patients: a cross-sectional study with regression analysis of ethnic Swedish and immigrant women
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    2013 (English)In: BMC Family Practice, ISSN 1471-2296, Vol. 14, 129- p.Article in journal (Refereed) Published
    Abstract [en]

    Background

    Determinants of vitamin D status measured as 25-OH-vitamin D in blood are exposure to sunlight and intake of vitamin D through food and supplements. It is unclear how large the contributions are from these determinants in Swedish primary care patients, considering the low radiation of UVB in Sweden and the fortification of some foods. Asian and African immigrants in Norway and Denmark have been found to have very low levels, but it is not clear whether the same applies to Swedish patients. The purpose of our study was to identify contributors to vitamin D status in Swedish women attending a primary health care centre at latitude 60°N in Sweden.

    Methods

    In this cross-sectional, observational study, 61 female patients were consecutively recruited between January and March 2009, irrespective of reason for attending the clinic. The women were interviewed about their sun habits, smoking, education and food intake at a personal appointment and blood samples were drawn for measurements of vitamin D and calcium concentrations.

    Results

    Plasma concentration of 25-OH-vitamin D below 25 nmol/L was found in 61% (19/31) of immigrant and 7% (2/30) of native women. Multivariate analysis showed that reported sun holiday of one week during the last year at latitude below 40°N with the purpose of sun-bathing and native origin, were significantly, independently and positively associated with 25-OH-vitamin D concentrations in plasma with the strongest association for sun holiday during the past year.

    Conclusions

    Vitamin D deficiency was common among the women in the present study, with sun holiday and origin as main determinants of 25-OH-vitamin D concentrations in plasma. Given a negative effect on health this would imply needs for vitamin D treatment particularly in women with immigrant background who have moved from lower to higher latitudes.

    Keywords: Vitamin D; Sun habits; Immigrant; Women; Primary health care

    National Category
    Family Medicine
    Identifiers
    urn:nbn:se:uu:diva-208596 (URN)10.1186/1471-2296-14-129 (DOI)000324297400001 ()
    Available from: 2013-10-04 Created: 2013-10-04 Last updated: 2017-03-30Bibliographically approved
    3. Polymorphisms in the CYP2R1 gene are associated with 25OHD3 and bone mineral density, but not with calcium and phosphate concentrations (MrOS Sweden).
    Open this publication in new window or tab >>Polymorphisms in the CYP2R1 gene are associated with 25OHD3 and bone mineral density, but not with calcium and phosphate concentrations (MrOS Sweden).
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Clinical Medicine
    Research subject
    Endocrinology and Diabetology
    Identifiers
    urn:nbn:se:uu:diva-317312 (URN)
    Available from: 2017-03-13 Created: 2017-03-13 Last updated: 2017-03-13
    4. Genetic variation in the vitamin D receptor gene is not associated with measures of muscle strength, physical performance, or falls in elderly men. Data from MrOS Sweden.
    Open this publication in new window or tab >>Genetic variation in the vitamin D receptor gene is not associated with measures of muscle strength, physical performance, or falls in elderly men. Data from MrOS Sweden.
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    (English)Manuscript (preprint) (Other academic)
    National Category
    Endocrinology and Diabetes
    Identifiers
    urn:nbn:se:uu:diva-315701 (URN)
    Available from: 2017-02-19 Created: 2017-02-19 Last updated: 2017-03-30
  • Public defence: 2017-05-05 09:00 Hedstrandsalen, Uppsala
    Flygt, Johanna
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Neuroscience.
    Oligodendrocyte pathology following Traumatic Brain Injury: Experimental and clinical studies2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Traumatic brain injury (TBI) caused by traffic and fall accidents, sports-related injuries and violence commonly results in life-changing disabilities. Cognitive impairments following TBI may be due to disruption of axons, stretched by the acceleration/deceleration forces of the initial impact, and their surrounding myelin in neuronal networks. The primary injury, which also results in death to neuronal and glial cells, is followed by a cascade of secondary injury mechanisms including a complex inflammatory response that will exacerbate the white matter injury.

    Axons are supported and protected by the ensheathing myelin, ensuring fast conduction velocity. Myelin is produced by oligodendrocytes (OLs), a cell type vulnerable to many of the molecular processes, including several inflammatory mediators, elicited by TBI. Since one OL extends processes to several axons, the protection of OLs is an important therapeutic target post-TBI.  During development, OLs mature from oligodendrocyte progenitor cells (OPCs), also present in the adult brain.

    The aim of this thesis was to investigate white matter pathology, with a specific focus on the OL population, in experimental and clinical TBI. Since the inflammatory response may contribute to OL cell death and OPC proliferation, neutralization of interleukin-1β (IL-1β) was investigated.

    The lateral and central fluid percussion injury models were used in mice and rats where memory, learning and complex behaviors were investigated by two functional tests. Brain tissue, surgically resected due to life-threatening brain swelling or hemorrhage, from TBI patients was also investigated. Axonal injury, myelin damage, microglia alterations and OPCs and OL cell death were investigated by immunohistochemical techniques. In focal and diffuse experimental TBI, OL cell death was observed in important white matter tracts. OL cell death was accompanied by myelin damage, axonal injury and presence of microglia as well as an increased number of OPCs in both the experimental and human setting. OPCs were found to proliferate in diffuse TBI in mice where both complex behavioral changes and impaired memory were observed. Neutralization of IL-1β normalized and improved these behavioral alterations and also lead to a preserved number of mature OLs although without influencing OPC proliferation.

    The results provided in this thesis indicate that white matter pathology is a key component of the pathophysiology of TBI. The OPC proliferation may influence regeneration post-injury and might be an important future therapeutic targets for TBI. The present studies also suggest that treatment strategies targeting neuroinflammation may positively influence behavioral outcome and OL cell death in TBI.

    List of papers
    1. Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat
    Open this publication in new window or tab >>Myelin loss and oligodendrocyte pathology in white matter tracts following traumatic brain injury in the rat
    2013 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 38, no 1, 2153-2165 p.Article, review/survey (Refereed) Published
    Abstract [en]

    Axonal injury is an important contributor to the behavioral deficits observed following traumatic brain injury (TBI). Additionally, loss of myelin and/or oligodendrocytes can negatively influence signal transduction and axon integrity. Apoptotic oligodendrocytes, changes in the oligodendrocyte progenitor cell (OPC) population and loss of myelin were evaluated at 2, 7 and 21 days following TBI. We used the central fluid percussion injury model (n = 18 and three controls) and the lateral fluid percussion injury model (n = 15 and three controls). The external capsule, fimbriae and corpus callosum were analysed. With Luxol Fast Blue and RIP staining, myelin loss was observed in both models, in all evaluated regions and at all post-injury time points, as compared with sham-injured controls (P ≤ 0.05). Accumulation of β-amyloid precursor protein was observed in white matter tracts in both models in areas with preserved and reduced myelin staining. White matter microglial/macrophage activation, evaluated by isolectin B4 immunostaining, was marked at the early time points. In contrast, the glial scar, evaluated by glial fibrillary acidic protein staining, showed its highest intensity 21 days post-injury in both models. The number of apoptotic oligodendrocytes, detected by CC1/caspase-3 co-labeling, was increased in both models in all evaluated regions. Finally, the numbers of OPCs, evaluated with the markers Tcf4 and Olig2, were increased from day 2 (Olig2) or day 7 (Tcf4) post-injury (P ≤ 0.05). Our results indicate that TBI induces oligodendrocyte apoptosis and widespread myelin loss, followed by a concomitant increase in the number of OPCs. Prevention of myelin loss and oligodendrocyte death may represent novel therapeutic targets for TBI.

    Keyword
    apoptosis; central fluid percussion; lateral fluid percussion; myelin damage; Olig2; Tcf4
    National Category
    Clinical Medicine
    Identifiers
    urn:nbn:se:uu:diva-198321 (URN)10.1111/ejn.12179 (DOI)000321205000012 ()
    Available from: 2013-04-11 Created: 2013-04-11 Last updated: 2017-03-07Bibliographically approved
    2. Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β
    Open this publication in new window or tab >>Diffuse traumatic axonal injury in mice induces complex behavioural alterations that are normalized by neutralization of interleukin-1β
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    2016 (English)In: European Journal of Neuroscience, ISSN 0953-816X, E-ISSN 1460-9568, Vol. 43, no 8, 1016-1033 p.Article in journal (Refereed) Published
    Abstract [en]

    Widespread traumatic axonal injury (TAI) results in brain network dysfunction, which commonly leads to persisting cognitive and behavioural impairments following traumatic brain injury (TBI). TBI induces a complex neuroinflammatory response, frequently located at sites of axonal pathology. The role of the pro-inflammatory cytokine interleukin (IL)-1 has not been established in TAI. An IL-1-neutralizing or a control antibody was administered intraperitoneally at 30min following central fluid percussion injury (cFPI), a mouse model of widespread TAI. Mice subjected to moderate cFPI (n=41) were compared with sham-injured controls (n=20) and untreated, naive mice (n=9). The anti-IL-1 antibody reached the target brain regions in adequate therapeutic concentrations (up to similar to 30g/brain tissue) at 24h post-injury in both cFPI (n=5) and sham-injured (n=3) mice, with lower concentrations at 72h post-injury (up to similar to 18g/g brain tissue in three cFPI mice). Functional outcome was analysed with the multivariate concentric square field (MCSF) test at 2 and 9days post-injury, and the Morris water maze (MWM) at 14-21days post-injury. Following TAI, the IL-1-neutralizing antibody resulted in an improved behavioural outcome, including normalized behavioural profiles in the MCSF test. The performance in the MWM probe (memory) trial was improved, although not in the learning trials. The IL-1-neutralizing treatment did not influence cerebral ventricle size or the number of microglia/macrophages. These findings support the hypothesis that IL-1 is an important contributor to the processes causing complex cognitive and behavioural disturbances following TAI.

    Keyword
    axonal injury, behavioural outcome, central fluid percussion injury, interleukin-1, traumatic brain injury
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-297130 (URN)10.1111/ejn.13190 (DOI)000374645700004 ()27091435 (PubMedID)
    Funder
    Swedish Research Council
    Available from: 2016-06-22 Created: 2016-06-21 Last updated: 2017-03-07Bibliographically approved
    3. Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells
    Open this publication in new window or tab >>Human Traumatic Brain Injury Results in Oligodendrocyte Death and Increases the Number of Oligodendrocyte Progenitor Cells
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    2016 (English)In: Journal of Neuropathology and Experimental Neurology, ISSN 0022-3069, E-ISSN 1554-6578, Vol. 75, no 6, 503-515 p.Article in journal (Refereed) Published
    Abstract [en]

    Oligodendrocyte (OL) death may contribute to white matter pathology, a common cause of network dysfunction and persistent cognitive problems in patients with traumatic brain injury (TBI). Oligodendrocyte progenitor cells (OPCs) persist throughout the adult CNS and may replace dead OLs. OL death and OPCs were analyzed by immunohistochemistry of human brain tissue samples, surgically removed due to life-threatening contusions and/or focal brain swelling at 60.6 +/- 75 hours (range 4-192 hours) postinjury in 10 severe TBI patients (age 51.7 +/- 18.5 years). Control brain tissue was obtained postmortem from 5 age-matched patients without CNS disorders. TUNEL and CC1 co-labeling was used to analyze apoptotic OLs, which were increased in injured brain tissue (p < 0.05), without correlation with time from injury until surgery. The OPC markers Olig2, A2B5, NG2, and PDGFR-alpha were used. In contrast to the number of single-labeled Olig2, A2B5, NG2, and PDGFR-alpha-positive cells, numbers of Olig2 and A2B5 co-labeled cells were increased in TBI samples (p < 0.05); this was inversely correlated with time from injury to surgery (r = -0.8, p < 0.05). These results indicate that severe focal human TBI results in OL death and increases in OPCs postinjury, which may influence white matter function following TBI.

    Keyword
    Apoptosis, Human, Immunohistochemistry, Oligodendrocyte, Oligodendrocyte progenitor cells, Traumatic brain injury
    National Category
    Neurology
    Identifiers
    urn:nbn:se:uu:diva-299587 (URN)10.1093/jnen/nlw025 (DOI)000377665000003 ()27105664 (PubMedID)
    Available from: 2016-07-22 Created: 2016-07-22 Last updated: 2017-03-07Bibliographically approved
    4. Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts
    Open this publication in new window or tab >>Diffuse traumatic brain injury in the mouse induces a transient proliferation of oligodendrocyte progenitor cells in injured white matter tracts
    2016 (English)In: Restorative Neurology and Neuroscience, ISSN 0922-6028, E-ISSN 1878-3627Article in journal (Refereed) Published
    Abstract [en]

    Background: Injury to the white matter may lead to impaired neuronal signaling and is commonly observed following traumatic brain injury (TBI). Although endogenous repair of TBI-induced white matter pathology is limited, oligodendrocyte progenitor cells (OPCs) may be stimulated to proliferate and regenerate functionally myelinating oligodendrocytes. Even though OPCs are present throughout the adult brain, little is known about their proliferative activity following axonal injury caused by TBI.

    Objective: We hypothesized that central fluid percussion injury (cFPI) in mice, a TBI model causing wide-spread axonal injury, results in OPC proliferation.

    Methods: Proliferation of OPCs was evaluated in 27 cFPI mice using 5-ethynyl-2-deoxyuridine (EdU) labeling and a cell proliferation assay at 2 (n=9), 7 (n = 8) and 21 (n = 10) days post injury (dpi). Sham-injured mice (n = 14) were used as controls. OPC proliferation was quantified by immunohistochemistry using the OPC markers NG2 and Olig2 in several white matter loci including the corpus callosum, external capsule, fimbriae, the internal capsule and cerebral peduncle.

    Results: The number of EdU/DAPI/Olig2-positive cells were increased in the cFPI group compared to sham-injured animals at 7 days post-injury (dpi; p≤0.05) in the majority of white matter regions. The OPC proliferation had subsided by 21 dpi. The number of EdU/DAPI/NG2 cells was also increase at 7 dpi in the external capsule and fimbriae.

    Conclusion: These results suggest that traumatic axonal injury in the mouse induces a transient proliferative response of residing OPCs. These proliferating OPCs may replace dead oligodendrocytes and contribute to remyelination, which needs evaluation in future studies.

    Keyword
    traumatic brain injury, proliferation, axonal injury, EdU, oligodendrocyte progenitor cell, white matter, myelin, central fluid percussion injury
    National Category
    Neurology
    Research subject
    Neuroscience
    Identifiers
    urn:nbn:se:uu:diva-316586 (URN)10.3233/RNN-160675 (DOI)
    Available from: 2017-03-03 Created: 2017-03-03 Last updated: 2017-03-08Bibliographically approved
    5. Reduced loss of mature Oligodendrocytes following Diffuse Traumatic Brain Injury in the mouse by Neutralization of Interleukin-1β
    Open this publication in new window or tab >>Reduced loss of mature Oligodendrocytes following Diffuse Traumatic Brain Injury in the mouse by Neutralization of Interleukin-1β
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    (English)Manuscript (preprint) (Other academic)
    Abstract [en]

    Abstract

    Background: Traumatic brain injury (TBI) leads to several secondary consequences impairing patient outcome. Injury to the components of the white matter, the oligodendrocyte population, myelin and axons, associate with post-injury cognitive deficits. Oligodendrocytes (OLs), the myelin-producing cell, are highly vulnerable post-TBI. Lost OLs may be replaced by proliferating oligodendrocyte progenitor cells (OPCs). A complex inflammatory response is also initiated following TBI, which is an important therapeutic target in TBI. The cytokine, interleukin-1β (IL-1β), is a key mediator of the inflammatory response. When neutralized following experimental TBI, behavioral and histological outcome is improved by unknown mechanisms.

    Methods: The central fluid percussion injury (cFPI) and sham injury was used in mice at three survival end-points; 2, 7 and 14 days post-injury. Mice were, at 30 min post-injury, randomly administered a neutralizing IL-1β antibody or a control antibody.  OPC proliferation (5-ethynyl 2´- deoxyuridine (EdU)/Olig 2 co-labeling) and mature OL cell death was evaluated in injured white matter tracts. In situ hybridization for Olig2 transcripts in EdU positive cells and microglia ramification was also evaluated.

    Results: Attenuated cell death, indicated by cleaved caspase-3 expression, and OL cell loss was observed in brain-injured animals treated with the IL-1β neutralizing antibody without influencing proliferation of OPCs, the number of Olig2 transcript or the ramification of microglia. 

     

    Conclusion: Although OPC proliferation was not influenced, IL-1β neutralization reduced oligodendrocyte cell death in diffuse TBI which may partly explain the beneficial outcome observed using this anti-inflammatory treatment.   

     

    Keyword
    Oligodendrocyte progenitor cell, central fluid percussion injury, microglia, Olig2, IL-1β
    National Category
    Neurology
    Research subject
    Neuroscience; Neurosurgery
    Identifiers
    urn:nbn:se:uu:diva-316727 (URN)
    Available from: 2017-03-06 Created: 2017-03-06 Last updated: 2017-03-07
  • Public defence: 2017-05-05 09:00 Rosénsalen, Uppsala
    Englund, Annika
    Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Women's and Children's Health.
    Hodgkin Lymphoma in children, adolescents and young adults2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Hodgkin lymphoma (HL) is a heterogeneous condition varying from engaging one single lymph node site to a widespread condition. The prognosis with contemporary treatment is excellent for the vast majority. However, the treatment might cause severe late adverse effects in a proportion of the affected individuals.

    We evaluated all children and adolescents diagnosed in Sweden and registered in the Swedish Childhood Cancer Register over a period of 25 years. The incidence has been stable and the overall survival (OS) is very good, comparable to the best results in the world. Approximately ten percent encountered a relapse, but even after relapse the chances of survival were good. During the study period there were no detectable changes in survival estimates. The use of radiotherapy has decreased.

    Epstein Barr virus (EBV) and numbers of eosinophils, mast cells and macrophages in the tumors were investigated in 98 cases. Young children were more likely to express EBV. In patients with advanced disease the mast cell and macrophage counts were higher and they also had more affected laboratory parameters. Patients with Nodular Lymphocyte Predominant Hodgkin Lymphoma did not express EBV in the tumor, had significantly lower numbers of eosinophils, mast cells and macrophages and less affected laboratory parameters compared to classical HL.

    Outcome and clinical presentation were investigated in a cohort of children, adolescents and young adults in Sweden and Denmark and treatment in pediatric and adult departments was compared. OS and event-free survival (EFS) did not differ between the three age groups nor between pediatric and adult treatment. However, the Danish pediatric patients had lower EFS, which corresponded to less use of radiotherapy. Adolescents and young adults shared similar characteristics, while children presented differently with less advanced disease and male preponderance.

    Hospitalization rates and outpatient visits after end of treatment were evaluated to see whether the excess need of resources described in the literature is evenly distributed among the survivors or whether it is limited to a smaller group. Most of the patients had a low burden of health care use and the relapsing patients were the main drivers of the excess need.

    List of papers
    1. Hodgkin lymphoma - a survey of children and adolescents treated in Sweden 1985-2009.
    Open this publication in new window or tab >>Hodgkin lymphoma - a survey of children and adolescents treated in Sweden 1985-2009.
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    2015 (English)In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 54, no 1, 41-8 p.Article in journal (Refereed) Published
    Abstract [en]

    Abstract Background. Hodgkin lymphoma (HL) in children constitutes approximately 30% of all pediatric lymphomas in Sweden. The chance of cure is high, but the frequency of late effects has been considerable. Over recent years, efforts have been made to reduce treatment with maintained survival. Material and methods. All patients 0-17 years, identified in the Swedish Childhood Cancer Register as diagnosed between 1985 and 2009, were included. The material was analyzed using descriptive statistics and for survival estimates the Kaplan-Meier method was used. Results. Three hundred and thirty-four patients were identified during this time period. The median age was 14 years. Male sex was over-represented, especially in lower age groups and in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL). In nodular sclerosis and in age group 15-17 years, female sex dominated. Most of the cases presented in stages I or II. B-symptoms were present in 38% of cHL, but only in 7% of NLPHL. The number of patients receiving radiotherapy has been significantly reduced during the period studied. The relapse rate in cHL was 10 ± 2% and in NLPHL 16 ± 7%. The relapse rate was significantly higher in cHL stage IIB compared to other stages in the same therapy group. In cHL 6% died, and in NLPHL 0%. The 5-, 10- and 20-year overall survival estimates in cHL were 96 ± 1%, 95 ± 1% and 90 ± 3%, respectively, with no significant difference when comparing different treatment regimens and time periods. The 5- and 10-year overall survival after relapse in cHL was 81 ± 8% and 75 ± 10%, respectively. Conclusion. During the period studied there is no indication of a decline in survival despite changes in treatment. Survival rates in Sweden are high, and even after relapse chances of cure are high. We were not able to identify any characteristics specific for the group of patients that did not survive.

    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-240256 (URN)10.3109/0284186X.2014.948058 (DOI)000346571700006 ()25203597 (PubMedID)
    Available from: 2015-01-06 Created: 2015-01-06 Last updated: 2017-03-12Bibliographically approved
    2. The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
    Open this publication in new window or tab >>The role of tumour-infiltrating eosinophils, mast cells and macrophages in Classical and Nodular Lymphocyte Predominant Hodgkin Lymphoma in children
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    2016 (English)In: European Journal of Haematology, ISSN 0902-4441, E-ISSN 1600-0609, Vol. 97, no 5, 430-438 p.Article in journal (Refereed) Published
    Abstract [en]

    OBJECTIVES: To study Hodgkin lymphoma (HL) microenvironment in a Swedish paediatric population and its relation to clinical parameters.

    METHODS: Tumour tissue from classical HL (cHL) (n=87) and nodular lymphocyte predominant HL (NLPHL) (n=11) was investigated for Epstein-Barr Virus (EBV) and analysed for eosinophils, mast cells and macrophages.

    RESULTS: In cHL, EBV positivity was more common in low age (p<0.001) and in mixed cellularity (MC) (p<0.001). Higher mast cell infiltration was seen in stage III-IV (p<0.001), and with presence of B-symptoms (p=0.01). Cases with high mast cell counts displayed higher erythrocyte sedimentation rate (ESR), lower haemoglobin and albumin levels. Higher macrophage infiltration was seen in stage III-IV (p=0.02) and there was elevated ESR and neutrophil count. All NLPHL cases were EBV negative, had lower rates of inflammatory cells and lower degree of inflammatory reaction in laboratory parameters. There was no difference in survival estimates with regard to infiltration of inflammatory cells.

    CONCLUSIONS: Higher levels of mast cells and macrophages in cHL tumours reflected the clinical presentation in laboratory parameters, B-symptoms and more advanced stages. NLPHL differs from cHL in numbers of inflammatory cells in the tumour, and in laboratory parameters. This article is protected by copyright. All rights reserved.

    Keyword
    paediatric, Hodgkin, Microenvironment, mast cells, eosinophils, macrophages
    National Category
    Clinical Laboratory Medicine Basic Medicine
    Research subject
    Pathology
    Identifiers
    urn:nbn:se:uu:diva-278917 (URN)10.1111/ejh.12747 (DOI)000388630800003 ()26872637 (PubMedID)
    Funder
    Swedish Childhood Cancer Foundation
    Note

    Both last authors contributed equally.

    Available from: 2016-02-26 Created: 2016-02-26 Last updated: 2017-03-12Bibliographically approved
    3. Hodgkin Lymphoma in children adolescents and young adults-a comparative study of clinical presentation and treatment outcome
    Open this publication in new window or tab >>Hodgkin Lymphoma in children adolescents and young adults-a comparative study of clinical presentation and treatment outcome
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    (English)Article in journal (Other academic) Submitted
    Keyword
    Hodgkin, pediatric, adolescent, radiotherapy, treatment
    National Category
    Cancer and Oncology
    Research subject
    Medical Science
    Identifiers
    urn:nbn:se:uu:diva-316792 (URN)
    Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-03-12
    4. Late adverse effects in children, adolescents and young adults in relapsing and non-relapsing patients with Hodgkin lymphoma
    Open this publication in new window or tab >>Late adverse effects in children, adolescents and young adults in relapsing and non-relapsing patients with Hodgkin lymphoma
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    (English)Manuscript (preprint) (Other academic)
    Keyword
    Late effects, children, adolescents, young adults, hospitalisation, Hodgkin
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:uu:diva-316794 (URN)
    Available from: 2017-03-07 Created: 2017-03-07 Last updated: 2017-03-13
  • Public defence: 2017-05-05 09:15 B42, Uppsala
    Brolin, Erika