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  • 251.
    Acosta, Naydú
    et al.
    Universidad Industrial de Santander .
    Pollard, Jennifer
    National University of Colombia.
    Mosquera, Paola
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Reveiz, Ludovic
    National University of Colombia.
    Equidad en el desarrollo de guias de practica clinica: [The concept of equity when developing clinical practice guidelines]2011In: Revista de Salud Pública, ISSN 0124-0064, Vol. 13, no 2, p. 327-38Article in journal (Refereed)
    Abstract [en]

    This systematic literature review sought to identify methodologies and technical strategies emphasising healthcare services and outcomes when incorporating the concept of equity into Clinical Practice Guidelines (CPG). 940 references were identified, of which 20 fulfilling the inclusion criteria were selected. While no reports were found describing or evaluating an explicit methodology for incorporating considerations of equity into CPG, some studies revealed related strategies or processes, summarised as follows: 1. Target population involvement during all phases of designing, implementing and evaluating CPG; 2. "Cultural capacity" seen as being necessary in CPGs' "cultural translation" for interventions to have less disparity regarding their application and results; 3. Considering psycho-social factors which could affect implementing CPG, and; 4. Considering system inequities so that any health intervention would also confront risks and obstacles to health care due to socioeconomic status. It was concluded that CPGs could be a potential route for promoting more equitable healthcare effects by standardising health interventions if, by incorporating some of the processes described above, they actively seek to avoid unjust differences in access to and/or the quality of the interventions that they prescribe.

  • 252.
    Acosta Romero, Carolin
    Umeå University, Faculty of Medicine, Department of Community Medicine and Rehabilitation, Occupational Therapy.
    Arbetsterapeutiska interventioner vid depression – en systematisk litteraturöversikt: Occupational therapy interventions for depression - a systematic literature review2017Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
    Abstract [sv]

    Depression kan drabba personer i alla åldrar och är en av de vanligaste psykiska sjukdomarna i Sverige och i världen. I Sverige drabbas ca 4-10% av befolkningen av depression och symtom kan återkomma flera gånger under en livstid, vilket beskrivs som depressiva episoder. Sjukdomstillståndet kan leda till nedsatt livskvalitet som orsakas av depressiva symtom som nedstämdhet, minskat intresse, aptitförändring, sömnsvårigheter, energilöshet, pessimistiska tankar, koncentrationssvårigheter och självmordstankar. Studiens syfte var att identifiera och beskriva effekten av arbetsterapeutiska interventioner vid diagnostiserad depression samt att belysa upplevelsen av dessa interventioner.  Nio vetenskapliga artiklar granskades och analyserades i en litteraturöversikt. Endast vuxna deltagare med egentlig depression som primär diagnos inkluderades i sökning i databaserna PsycINFO, Academic Search Elite, PubMed, - OT-Seeker och CINAHL. Resultatet presenterar aktivitetsbaserade interventioner för att hantera vardagen så som arbetsinriktade interventioner, skapande aktiviteter och programbaserade interventioner. Effekter av dessa arbetsterapeutiska interventioner beskrivs förbättra klientens livskvalitet, minska depressions symtom, öka känsla av delaktighet och tillfredställelse i vardagliga aktiviteter, samt främja klientens återgång till arbete utan att uppleva ökad stress. Författaren i den här studien anser att det kan vara av stor betydelse för yrkesverksamma arbetsterapeuter att använda sig av aktivitetsbaserade interventioner som känns meningsfulla och tillfredställande för klienten. Ytterligare forskning behövs dock, då det finns för få studier som undersöker effekten av arbetsterapeutiska interventioner för personer med depression och upplevelse av att leva med depression. 

  • 253. Acosta, Stefan
    et al.
    Block, Tomas
    Björnsson, Steinarr
    Resch, Timothy
    Björck, Martin
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Diagnostic pitfalls at admission in patients with acute superior mesenteric artery occlusion2012In: Journal of Emergency Medicine, ISSN 0736-4679, E-ISSN 1090-1280, Vol. 42, no 6, p. 635-641Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Acute superior mesenteric artery (SMA) occlusion leads to acute intestinal ischemia and is associated with high mortality. Early diagnosis is often missed, and confounding factors leading to diagnostic delays need to be highlighted. OBJECTIVES: To identify potential diagnostic laboratory pitfalls at admission in patients with acute SMA occlusion. METHODS: Fifty-five patients with acute SMA occlusion were identified from the in-hospital register during a 4-year period, 2005-2009. RESULTS: The median age was 76 years; 78% were women. The occlusion was embolic in 53% and thrombotic in 47% of patients. At admission, troponin I was above the clinical decision level (> 0.06 μg/L) for acute ischemic myocardial injury in 9/19 (47%) patients with embolic occlusion. Elevated pancreas amylase and normal plasma lactate were found in 12/45 and 13/27, respectively. A troponin I (TnI) above the clinical decision level was associated with a high frequency of referrals from the general surgeon to a specialist in internal medicine (p = 0.011) or a cardiologist (p = 0.024). The diagnosis was established after computed tomography angiography in 98% of the patients. The overall in-hospital mortality rate was 33%. Attempting intestinal revascularization (n = 43; p < 0.001), with a 95% frequency rate of completion control of the vascular procedure, was associated with a higher survival rate, whereas referral to the cardiologist was associated with a higher mortality rate (p = 0.018). CONCLUSION: Elevated TnI was common in acute SMA occlusion, and referral to the cardiologist was found to be associated with adverse outcome. Elevated pancreas amylase and normal plasma lactate values are also potential pitfalls at admission in patients with acute SMA occlusion.

  • 254. Acosta, Stefan
    et al.
    Nilsson, Torbjörn K
    Department of Clinical Chemistry, Örebro University Hospital.
    Current status on plasma biomarkers for acute mesenteric ischemia2012In: Journal of Thrombosis and Thrombolysis, ISSN 0929-5305, E-ISSN 1573-742X, Vol. 33, no 4, p. 355-361Article in journal (Refereed)
    Abstract [en]

    Clinical diagnosis of acute mesenteric ischemia is difficult. The aim of this review is to provide current status on the search for an accurate plasma biomarker for acute mesenteric ischemia. A search using the medical subject heading terms marker and mesenteric ischemia or intestinal ischemia or superior mesenteric artery occlusion or mesenteric venous thrombosis in the Medline and Embase databases from 1980 to 2011. Studies without a control group or a control group consisted of healthy individuals (human studies), or studies on intestinal reperfusion were excluded. Twenty animal and twelve human studies were identified. In human studies, the studied series of patients had a control group that had a need of laparotomy (n = 2), suspected acute mesenteric ischemia (n = 7), acute abdomen (n = 2) or systemic inflammatory response syndrome (n = 1). D: -dimer has been found to be the most consistent highly sensitive early marker, but specificity was low. The follow-up study on α-glutathione S-transferase yielded inferior sensitivity and accuracy than the preliminary study, clearly questioning the value of this marker. Intestinal fatty acid binding globulin (I-FABP) and D: -lactate are both interesting markers, but the results were conflicting. Different cut-off levels have been used in the studies on I-FABP. The encouraging preliminary result of cobalt-albumin and urinary FABP as an accurate marker needs to be addressed in other study populations. The early clinical and laboratory diagnosis of intestinal ischemia remains a challenge. None of the proposed plasma-derived tests for acute mesenteric ischemia has as yet entered routine clinical practice. The proposed biomarkers need to be evaluated in a prospective clinical research project in patients with acute abdomen.

  • 255. Acuña Mora, Mariela
    et al.
    Sparud-Lundin, Carina
    Burström, Åsa
    Hanseus, Katarina
    Rydberg, Annika
    Umeå University, Faculty of Medicine, Department of Clinical Sciences, Paediatrics.
    Moons, Philip
    Bratt, Ewa-Lena
    Patient empowerment and its correlates in young persons with congenital heart disease2019In: European Journal of Cardiovascular Nursing, ISSN 1474-5151, E-ISSN 1873-1953, Vol. 18, no 5, p. 389-398, article id 1474515119835434Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:: The objective of this study was to measure the level of empowerment and identify its correlates in young persons with congenital heart disease.

    STUDY DESIGN:: Patients aged 14-18 years with congenital heart disease, and under active follow-up in one of four paediatric cardiology centres in Sweden were invited to participate in a cross-sectional study. A total of 202 young persons returned the questionnaires. Patient empowerment was measured with the Gothenburg Young Persons Empowerment Scale that allows the calculation of total and subscale scores. Univariate and multivariate linear regression analyses were undertaken to analyse possible correlates, including: sex, age, health behaviours, knowledge of congenital heart disease, quality of life, patient-reported health, congenital heart disease complexity, transition readiness and illness perception.

    RESULTS:: The mean empowerment score was 54.6±10.6 (scale of 15-75). Univariate analyses showed that empowerment was associated with age, quality of life, transition readiness, illness perception, health behaviours and patient-reported health (perceived physical appearance, treatment anxiety, cognitive problems and communication issues). However, multivariable linear regression analyses identified that only transition readiness (β=0.28, P<0.001) and communication (β=0.36, P<0.001) had a positive association with patient empowerment. These variables were also significantly associated with the subscale scores of the empowerment scale of knowledge and understanding ( P<0.001), shared decision-making ( P<0.001) and enabling others ( P<0.01). The overall models' explained variance ranged from 8% to 37%.

    CONCLUSION:: Patient empowerment was associated with transition readiness and fewer problems communicating. While it is not possible to establish the directionality of the associations, interventions looking to increase empowerment could benefit from using these variables (or measurements) for evaluation purposes.

  • 256. Adam, Martin
    et al.
    Schikowski, Tamara
    Carsin, Anne Elie
    Cai, Yutong
    Jacquemin, Benedicte
    Sanchez, Margaux
    Vierkötter, Andrea
    Marcon, Alessandro
    Keidel, Dirk
    Sugiri, Dorothee
    Al Kanani, Zaina
    Nadif, Rachel
    Siroux, Valérie
    Hardy, Rebecca
    Kuh, Diana
    Rochat, Thierry
    Bridevaux, Pierre-Olivier
    Eeftens, Marloes
    Tsai, Ming-Yi
    Villani, Simona
    Phuleria, Harish Chandra
    Birk, Matthias
    Cyrys, Josef
    Cirach, Marta
    de Nazelle, Audrey
    Nieuwenhuijsen, Mark J
    Forsberg, Bertil
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Occupational and Environmental Medicine.
    de Hoogh, Kees
    Declerq, Christophe
    Bono, Roberto
    Piccioni, Pavilio
    Quass, Ulrich
    Heinrich, Joachim
    Jarvis, Deborah
    Pin, Isabelle
    Beelen, Rob
    Hoek, Gerard
    Brunekreef, Bert
    Schindler, Christian
    Sunyer, Jordi
    Krämer, Ursula
    Kauffmann, Francine
    Hansell, Anna L
    Künzli, Nino
    Probst-Hensch, Nicole
    Adult lung function and long-term air pollution exposure. ESCAPE: a multicentre cohort study and meta-analysis2015In: European Respiratory Journal, ISSN 0903-1936, E-ISSN 1399-3003, Vol. 41, no 5, p. 38-50Article in journal (Refereed)
    Abstract [en]

    The chronic impact of ambient air pollutants on lung function in adults is not fully understood. The objective of this study was to investigate the association of long-term exposure to ambient air pollution with lung function in adult participants from five cohorts in the European Study of Cohorts for Air Pollution Effects (ESCAPE). Residential exposure to nitrogen oxides (NO2, NOx) and particulate matter (PM) was modelled and traffic indicators were assessed in a standardised manner. The spirometric parameters forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) from 7613 subjects were considered as outcomes. Cohort-specific results were combined using meta-analysis. We did not observe an association of air pollution with longitudinal change in lung function, but we observed that a 10 μg·m(-3) increase in NO2 exposure was associated with lower levels of FEV1 (-14.0 mL, 95%CI -25.8- -2.1) and FVC (-14.9 mL, 95% CI -28.7- -1.1). An increase of 10 μg·m(-3) in PM10, but not other PM metrics (PM2.5, coarse fraction of PM, PM absorbance), was associated with a lower level of FEV1 (-44.6 mL, 95% CI -85.4- -3.8) and FVC (-59.0 mL, 95% CI -112.3- -5.6). The associations were particularly strong in obese persons. This study adds to the evidence for an adverse association of ambient air pollution with lung function in adults at very low levels in Europe.

  • 257. Adam, Zach
    et al.
    Adamska, Iwona
    Nakabayashi, Kazumi
    Ostersetzer, Oren
    Haussuhl, Kirsten
    Manuell, Andrea
    Zheng, Bo
    Umeå University, Faculty of Science and Technology, Department of Plant Physiology. Umeå University, Faculty of Science and Technology, Umeå Plant Science Centre (UPSC).
    Vallon, Olivier
    Rodermel, Steven
    Shinozaki, Kazuo
    Chloroplast and mitochondrial proteases in Arabidopsis: a proposed nomenclature2001In: Plant Physiology, ISSN 0032-0889, E-ISSN 1532-2548, Vol. 125, no 4, p. 1912-1918Article in journal (Refereed)
    Abstract [en]

    The identity and scope of chloroplast and mitochondrial proteases in higher plants has only started to become apparent in recent years. Biochemical and molecular studies suggested the existence of Clp, FtsH, and DegP proteases in chloroplasts, and a Lon protease in mitochondria, although currently the full extent of their role in organellar biogenesis and function remains poorly understood. Rapidly accumulating DNA sequence data, especially from Arabidopsis, has revealed that these proteolytic enzymes are found in plant cells in multiple isomeric forms. As a consequence, a systematic approach was taken to catalog all these isomers, to predict their intracellular location and putative processing sites, and to propose a standard nomenclature to avoid confusion and facilitate scientific communication. For the Clp protease most of the ClpP isomers are found in chloroplasts, whereas one is mitochondrial. Of the ATPase subunits, the one ClpD and two ClpC isomers are located in chloroplasts, whereas both ClpX isomers are present in mitochondria. Isomers of the Lon protease are predicted in both compartments, as are the different forms of FtsH protease. DegP, the least characterized protease in plant cells, has the most number of isomers and they are predicted to localize in several cell compartments. These predictions, along with the proposed nomenclature, will serve as a framework for future studies of all four families of proteases and their individual isomers.

  • 258.
    Adama, Blekou
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History, Economic and social geography.
    Assessing the walking access to bus stops in Umeå urban area and the relationship with the socio-economic characteristics2018Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    To reduce greenhouse gas emissions in the atmosphere and protect the environment, Swedish cities are heavily invested in sustainable development by developing pedestrian roads and intensifying public transport. Their goal is to make the population less dependent on cars by facilitating accessibility to transit transport. The urban area of ​​Umeå (Sweden), which is experiencing an annual increasing of it population due to urban development, includes 244 km of pedestrian or bike routes and an intensified bus network. The purpose of this paper is to evaluate the walking accessibility of the population at bus stops and to analyze the socio-economic relationship. The use of GIS tools allowed to calculate the proportion of the population and the houses around the bus stop, the average distance accessibility. The use of 3D allowed the observation of access constraints related to the topography and to calculate the slope. The use of the multiple regression model has analyzed the relationship between the shortest accessibility distance and the socio-economic factors that are the income, gender and age. The results show that the average distance of access to the bus stop is 186m. 99.2% of the population lives within 800m from the bus stops. The results of the regression showed that income is the main factor that pushes people to take the bus and live in certain types of housing. The observation of the 3d map and the calculation of the slope made it possible to know the neighborhoods established in the hill and whose residents are susceptible to spend more energy than the other inhabitant living on flat ground. The results mean that most people living in the urban area of ​​Umeå have good access to the bus stop whatever the social group, the level of income and the type of housing.

  • 259.
    Adamiak, Czeslaw
    et al.
    Umeå University, Faculty of Social Sciences, Department of Geography. Department of Spatial Planning and Tourism, Faculty of Earth Sciences, Nicolaus Copernicus University, 87-100 Toruń, Poland.
    Szyda, Barbara
    Dubownik, Anna
    Garcia-Alvarez, David
    Airbnb Offer in Spain-Spatial Analysis of the Pattern and Determinants of Its Distribution2019In: ISPRS International Journal of Geo-Information, ISSN 2220-9964, Vol. 8, no 3, article id 155Article in journal (Refereed)
    Abstract [en]

    The rising number of homes and apartments rented out through Airbnb and similar peer-to-peer accommodation platforms cause concerns about the impact of such activity on the tourism sector and property market. To date, spatial analysis on peer-to-peer rental activity has been usually limited in scope to individual large cities. In this study, we take into account the whole territory of Spain, with special attention given to cities and regions with high tourist activity. We use a dataset of about 250 thousand Airbnb listings in Spain obtained from the Airbnb webpage, aggregate the numbers of these offers in 8124 municipalities and 79 tourist areas/sites, measure their concentration, spatial autocorrelation, and develop regression models to find the determinants of Airbnb rentals' distribution. We conclude that apart from largest cities, Airbnb is active in holiday destinations of Spain, where it often serves as an intermediary for the rental of second or investment homes and apartments. The location of Airbnb listings is mostly determined by the supply of empty or secondary dwellings, distribution of traditional tourism accommodation, coastal location, and the level of internationalization of tourism demand.

  • 260.
    Adamo, Hanibal
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Dahl Scherdin, Tove
    Egevad, Lars
    Granfors, Torvald
    Stattin, Pär
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Urology and Andrology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Prostate cancer induces C/EBPβ expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcomeManuscript (preprint) (Other academic)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of a tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein-β (C/EBPβ). To explore this further, we examined C/EBPβ expression by quantitative RT-PCR, immunohistochemistry, and western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors―and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    In rats, C/EBPβ mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBPβ was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBPβ expression in the tumor-bearing prostates was associated with tumor size, with distance to the tumor, and with tumor cell metastatic capacity.

    In prostate cancer patients, high expression of C/EBPβ in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and a favorable outcome. High expression of C/EBPβ in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, the presence of metastases at diagnosis, and poor outcome. 

  • 261.
    Adamo, Hanibal Hani
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    TINT Tumor Indicating Normal Tissue: new field of diagnostic biomarkers for prostate cancer2016Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background: Prostate cancer is the most common cancer in Sweden. Due its highly variable behavior, multifocal nature, and insufficient diagnostic methods, prostate cancer is difficult to diagnose and prognosticate. Some patients have an aggressive lethal disease, but the majority of prostate cancer patients have slow-growing, non-lethal disease with long expected survival without treatment. Current diagnostic methods―serum levels of prostate-specific antigen (PSA) and histological grading of biopsied prostate tissue―often do not give the information required to be able to safely differentiate indolent tumors from potentially lethal ones. Many prostate cancers are difficult to detect by imaging, so tissue biopsy cannot be safely guided towards the tumor, and particularly not towards the most aggressive forms. To overcome this problem, multiple needle biopsies are taken from the organ, but biopsies are small and they sample less than 1% of the whole prostate. In this thesis, we explore the non-malignant prostate tissue adjacent to tumors, which is always sampled in biopsies, and we study adaptive changes in this tissue, which may provide new diagnostic and prognostic markers for prostate cancer. We have therefore proposed that this type of tissue should be termed TINT (Tumor Instructed/indicating Normal Tissue).

     Methods: In our studies, we used orthotopic rat prostate cancer models with tumors of different aggressiveness. We also used clinical materials from patients diagnosed with prostate cancer at transurethral resection (1975‒1990); the majority of these men were followed with watchful waiting. Analyses were performed with whole-genome expression array, quantitative real-time PCR, immunohistochemistry, and western blotting.

     Results: Using the animal model, we found that the presence of a tumor induces changes in gene expression in the surrounding tumor-bearing organ (TINT). The gene signature of TINT was linked to processes such as extracellular matrix organization, immune responses, and inflammation. We also showed that some of these adaptive TINT changes appear to be related to the aggressiveness and metastatic potential of the growing tumor, such as increases in macrophages, in mast cells, in vascular densities, and in vascular cell-proliferation. Some of these findings were confirmed by our observations in patient samples. We found that high staining of the extracellular matrix component hyaluronan in the stroma of the non-malignant prostate tissue was prognostic for short cancer-specific survival. We also found that an elevated proportion of C/EBP-beta positive epithelial cells in non-malignant (TINT) prostate tissue was associated with a good prognosis.

     Conclusions: Using animal experiments and patient samples, we showed that the presence of prostate cancer induces changes in the tumor-bearing organ, alterations associated with tumor aggressiveness, and that grading of these changes in TINT can be used to predict outcome in prostate cancer patients. 

  • 262.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergström, Sofia Halin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Characterization of a Gene Expression Signature in Normal Rat Prostate Tissue Induced by the Presence of a Tumor Elsewhere in the Organ2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 6, article id e0130076Article in journal (Refereed)
    Abstract [en]

    Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating changes in the tumor-bearing organ, for example growth of the vasculature, an altered extracellular matrix, and influx of inflammatory cells. To investigate this response further, we compared prostate morphology and the gene expression profile of tumor-bearing normal rat prostate tissue (termed tumor-instructed/indicating normal tissue (TINT)) with that of prostate tissue from controls. Dunning rat AT-1 prostate cancer cells were injected into rat prostate and tumors were established after 10 days. As controls we used intact animals, animals injected with heat-killed AT-1 cells or cell culture medium. None of the controls showed morphological TINT-changes. A rat Illumina whole-genome expression array was used to analyze gene expression in AT-1 tumors, TINT, and in medium injected prostate tissue. We identified 423 upregulated genes and 38 downregulated genes (p<0.05, >= 2-fold change) in TINT relative to controls. Quantitative RT-PCR analysis verified key TINT-changes, and they were not detected in controls. Expression of some genes was changed in a manner similar to that in the tumor, whereas other changes were exclusive to TINT. Ontological analysis using GeneGo software showed that the TINT gene expression profile was coupled to processes such as inflammation, immune response, and wounding. Many of the genes whose expression is altered in TINT have well-established roles in tumor biology, and the present findings indicate that they may also function by adapting the surrounding tumor-bearing organ to the needs of the tumor. Even though a minor tumor cell contamination in TINT samples cannot be ruled out, our data suggest that there are tumor-induced changes in gene expression in the normal tumor-bearing organ which can probably not be explained by tumor cell contamination. It is important to validate these changes further, as they could hypothetically serve as novel diagnostic and prognostic markers of prostate cancer.

  • 263.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hammarsten, Peter
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Hägglöf, Christina
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Scherdin, Tove Dahl
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Egevad, Lars
    Stattin, Paer
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences.
    Prostate cancer induces C/EBP expression in surrounding epithelial cells which relates to tumor aggressiveness and patient outcome2019In: The Prostate, ISSN 0270-4137, E-ISSN 1097-0045, Vol. 79, no 5Article in journal (Refereed)
    Abstract [en]

    Background: Implantation of rat prostate cancer cells into the normal rat prostate results in tumor-stimulating adaptations in the tumor-bearing organ. Similar changes are seen in prostate cancer patients and they are related to outcome. One gene previously found to be upregulated in the non-malignant part of tumor-bearing prostate lobe in rats was the transcription factor CCAAT/enhancer-binding protein- (C/EBP).

    Methods: To explore this further, we examined C/EBP expression by quantitative RT-PCR, immunohistochemistry, and Western blot in normal rat prostate tissue surrounding slow-growing non-metastatic Dunning G, rapidly growing poorly metastatic (AT-1), and rapidly growing highly metastatic (MatLyLu) rat prostate tumors?and also by immunohistochemistry in a tissue microarray (TMA) from prostate cancer patients managed by watchful waiting.

    Results: In rats, C/EBP mRNA expression was upregulated in the surrounding tumor-bearing prostate lobe. In tumors and in the surrounding non-malignant prostate tissue, C/EBP was detected by immunohistochemistry in some epithelial cells and in infiltrating macrophages. The magnitude of glandular epithelial C/EBP expression in the tumor-bearing prostates was associated with tumor size, distance to the tumor, and metastatic capacity. In prostate cancer patients, high expression of C/EBP in glandular epithelial cells in the surrounding tumor-bearing tissue was associated with accumulation of M1 macrophages (iNOS+) and favorable outcome. High expression of C/EBP in tumor epithelial cells was associated with high Gleason score, high tumor cell proliferation, metastases, and poor outcome.

    Conclusions: This study suggest that the expression of C/EBP-beta, a transcription factor mediating multiple biological effects, is differentially expressed both in the benign parts of the tumor-bearing prostate and in prostate tumors, and that alterations in this may be related to patient outcome.

  • 264.
    Adamo, Hanibal Hani
    et al.
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Strömvall, Kerstin
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Nilsson, Maria
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Halin Bergström, Sofia
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Bergh, Anders
    Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
    Adaptive (TINT) Changes in the Tumor Bearing Organ Are Related to Prostate Tumor Size and Aggressiveness2015In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 11, article id e0141601Article in journal (Refereed)
    Abstract [en]

    In order to grow, tumors need to induce supportive alterations in the tumor-bearing organ, by us named tumor instructed normal tissue (TINT) changes. We now examined if the nature and magnitude of these responses were related to tumor size and aggressiveness. Three different Dunning rat prostate tumor cells were implanted into the prostate of immune-competent rats; 1) fast growing and metastatic MatLyLu tumor cells 2) fast growing and poorly metastatic AT-1 tumor cells, and 3) slow growing and non-metastatic G tumor cells. All tumor types induced increases in macrophage, mast cell and vascular densities and in vascular cell-proliferation in the tumor-bearing prostate lobe compared to controls. These increases occurred in parallel with tumor growth. The most pronounced and rapid responses were seen in the prostate tissue surrounding MatLyLu tumors. They were, also when small, particularly effective in attracting macrophages and stimulating growth of not only micro-vessels but also small arteries and veins compared to the less aggressive AT-1 and G tumors. The nature and magnitude of tumor-induced changes in the tumor-bearing organ are related to tumor size but also to tumor aggressiveness. These findings, supported by previous observation in patient samples, suggest that one additional way to evaluate prostate tumor aggressiveness could be to monitor its effect on adjacent tissues.

  • 265.
    Adamo, Karin
    et al.
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Sandblom, Gabriel
    Brännström, Fredrik
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Strigård, Karin
    Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Surgery.
    Prevalence and recurrence rate of perianal abscess -a population-based study, Sweden 1997-20092016In: International Journal of Colorectal Disease, ISSN 0179-1958, E-ISSN 1432-1262, Vol. 31, no 3, p. 669-673Article in journal (Refereed)
    Abstract [en]

    INTRODUCTION: The aim of this study was to assess the impact of diabetes mellitus, Crohn's disease, HIV/aids, and obesity on the prevalence and readmission rate of perianal abscess.

    METHODS: The study cohort was based on the Swedish National Patient Register and included all patients treated for perianal abscess in Sweden 1997-2009. The prevalence and risk for readmission were assessed in association with four comorbidity diagnoses: diabetes mellitus, Crohn's disease, HIV, and/or AIDS and obesity.

    RESULTS: A total of 18,877 patients were admitted during the study period including 11,138 men and 4557 women (2.4:1). Crohn's disease, diabetes, and obesity were associated with a significantly higher prevalence of perianal abscess than an age- and gender-matched background population (p < 0.05). In univariate analysis, neither age nor gender had any significant impact on the risk for readmission. In a multivariate Cox proportional hazard analysis, Crohns disease was the only significant risk factor for readmission of perianal abscess.

    CONCLUSION: Crohn's disease, diabetes, and obesity increase the risk for perianal abscess. Of these, Crohn's and HIV has an impact on readmission. The pathogenesis and the influence of diabetes and obesity need further research if we are to understand why these diseases increase the risk for perianal abscess but not its recurrence.

  • 266.
    Adamowicz, Tomasz
    et al.
    Institute of Mathematics of the Polish Academy of Sciences, Warsaw, Poland.
    Lundström, Niklas L.P.
    Umeå University, Faculty of Science and Technology, Department of Mathematics and Mathematical Statistics.
    The boundary Harnack inequality for variable exponent p-Laplacian, Carleson estimates, barrier functions and p(⋅)-harmonic measures2016In: Annali di Matematica Pura ed Applicata, ISSN 0373-3114, E-ISSN 1618-1891, Vol. 195, no 2, p. 623-658Article in journal (Refereed)
    Abstract [en]

    We investigate various boundary decay estimates for p(⋅)-harmonic functions. For domains in Rn,n≥2satisfying the ball condition (C1,1-domains), we show the boundary Harnack inequality for p(⋅)-harmonic functions under the assumption that the variable exponent p is a bounded Lipschitz function. The proof involves barrier functions and chaining arguments. Moreover, we prove a Carleson-type estimate for p(⋅)-harmonic functions in NTA domains in Rn and provide lower and upper growth estimates and a doubling property for a p(⋅)-harmonic measure.

  • 267. Adam-Poupart, Ariane
    et al.
    Labreche, France
    Smargiassi, Audrey
    Duguay, Patrice
    Busque, Marc-Antoine
    Gagne, Charles
    Rintamaki, Hannu
    Kjellström, Tord
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Zayed, Joseph
    Climate Change and Occupational Health and Safety in a Temperate Climate: Potential Impacts and Research Priorities in Quebec, Canada2013In: Industrial Health, ISSN 0019-8366, E-ISSN 1880-8026, Vol. 51, no 1, p. 68-78Article in journal (Refereed)
    Abstract [en]

    The potential impacts of climate change (CC) on Occupational Health and Safety (OHS) have been studied a little in tropical countries, while they received no attention in northern industrialized countries with a temperate climate. This work aimed to establish an overview of the potential links between CC and OHS in those countries and to determine research priorities for Quebec, Canada. A narrative review of the scientific literature (2005-2010) was presented to a working group of international and national experts and stakeholders during a workshop held in 2010. The working group was invited to identify knowledge gaps, and a modified Delphi method helped prioritize research avenues. This process highlighted five categories of hazards that are likely to impact OHS in northern industrialized countries: heat waves/increased temperatures, air pollutants, UV radiation, extreme weather events, vector-borne/zoonotic diseases. These hazards will affect working activities related to natural resources (i.e. agriculture, fishing and forestry) and may influence the socioeconomic context (built environment and green industries), thus indirectly modifying OHS. From this consensus approach, three categories of research were identified: 1) Knowledge acquisition on hazards, target populations and methods of adaptation; 2) Surveillance of diseases/accidents/occupational hazards; and 3) Development of new occupational adaptation strategies.

  • 268.
    Adams, Brent Michael
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Tran, Thi Bich Van
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Project Manager Competencies in managing International Development Projects: The Project Managers' Perspective2017Independent thesis Advanced level (degree of Master (One Year)), 10 credits / 15 HE creditsStudent thesis
    Abstract [en]

    This research studies the competencies of International Development (ID) project managers from their perspectives, taking into consideration the contextual factors and the challenges that they face when managing ID projects.

    The study adopts a constructionist ontological viewpoint and an interpretivist epistemological philosophical assumption. The nature of the research is exploratory with an inductive approach, using qualitative research method. The data was collected through semi-structured interviews with experienced project managers in International Development projects. Template analysis strategy was used to analyse the data.

    The findings show that contextual factors have a significant influence on the challenges that ID project managers face when managing projects. Contextual factors are operating environment, large network of stakeholders and intangible goals of ID projects. Five challenges were identified as the results of the context, namely stakeholder management challenge, beneficiary needs analysis challenge, the challenge of balancing strategic and operational views, capacity building and training challenge and sustainable funding challenge. To overcome these challenges, seven ID project manager competencies were identified management skills, personal qualities, interpersonal skills, stakeholder engagement skills, capacity building skills, and change management skills. These competencies are found to be interrelated and complementary. While the role and responsibilities of ID project managers were also uncovered during the research, the findings on contextual factors, challenges and competencies help to better understand the ID project manager role and responsibilities.

    This study makes the contributions from both theoretical and practical point of view. With regards to theoretical contribution, our findings expanded on ID project manager competencies as well as relating them to the context and challenges in ID projects. The role and responsibilities of ID project manager is another theoretical contribution in this study. From a practical point of view, this thesis’s findings would be useful for various organizations who deliver ID projects, particularly human resources management. In addition, it can act as knowledge sharing with ID project managers and help in designing and enhancing educational programmes in ID project management. Overall, this could result in better delivery and overcoming the challenges of International Development projects.

  • 269. Adams, D.
    et al.
    Coelho, T.
    Conceicao, E.
    Waddington-Cruz, M.
    Schmidt, H.
    Buades, J.
    Campistol, J. M.
    Pouget, J.
    Berk, J. L.
    Polydefkis, M.
    Ziyadeh, N.
    Partisano, A. M.
    Chen, J.
    Gollob, J.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    PHASE 2 OPEN-LABEL EXTENSION (OLE) STUDY OF PATISIRAN, AN INVESTIGATIONAL RNA INTERFERENCE (RNAI) THERAPEUTIC FOR THE TREATMENT OF HEREDITARY ATTR AMYLOIDOSIS WITH POLYNEUROPATHY2017In: Value in Health, ISSN 1098-3015, E-ISSN 1524-4733, Vol. 20, no 5, p. A211-A212Article in journal (Other academic)
  • 270. Adams, D.
    et al.
    Coelho, T.
    Conceicao, I.
    Cruz, M. Waddington
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J. L.
    Ziyadeh, N.
    Partisano, A. M.
    Sweetser, M.
    Chen, J.
    Gollob, J.
    Suhr, Ole
    Umeå University.
    Phase 2 open-label extension (OLE) study of patisiran for the treatment of hereditary ATTR (hATTR) amyloidosis: 24-month safety and efficacy in subgroup of patients with cardiac involvement2017In: European Journal of Heart Failure, ISSN 1388-9842, E-ISSN 1879-0844, Vol. 19, no Suppl: 1, p. 19-19Article in journal (Refereed)
  • 271. Adams, D.
    et al.
    Coelho, T.
    Conceicao, I.
    Cruz, M. Waddington
    Schmidt, H.
    Buades, J.
    Campistol, J.
    Pouget, J.
    Berk, J.
    Ziyadeh, N.
    Partisano, A.
    Chen, J.
    Sweetser, M.
    Gollob, J.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Phase 2 open-label extension (OLE) study of patisiran with or without a TTR stabilizer for the treatment of hereditary ATTR (hATTR) amyloidosis with polyneuropathy2017In: European Journal of Neurology, ISSN 1351-5101, E-ISSN 1468-1331, Vol. 24, p. 31-32Article in journal (Other academic)
  • 272. Adams, D.
    et al.
    Coelho, T.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, I.
    Waddington-Cruz, M.
    Schmidt, H.
    Campistol, J.
    Pouget, J.
    Buades, J.
    Falzone, R.
    Harrop, J.
    De Frutos, R.
    Butler, J.
    Cehelsky, J.
    Nochur, S.
    Vaishnaw, A.
    Gollob, J.
    Interim results from phase ii trial of aln-ttr02, a novel RNAi therapeutic for the treatment of familial amyloidotic polyneuropathy2013In: Journal of the peripheral nervous system, ISSN 1085-9489, E-ISSN 1529-8027, Vol. 18, no Supplement 2, p. 1-2Article in journal (Other academic)
  • 273. Adams, D.
    et al.
    Gonzalez-Duarte, A.
    O'Riordan, W. D.
    Yang, C. -C
    Ueda, M.
    Kristen, A. V.
    Tournev, I.
    Schmidt, H. H.
    Coelho, T.
    Berk, J. L.
    Lin, K. -P
    Vita, G.
    Attarian, S.
    Plante-Bordeneuve, V.
    Mezei, M. M.
    Campistol, J. M.
    Buades, J.
    Brannagan, T. H. , I I I
    Kim, B. J.
    Oh, J.
    Parman, Y.
    Sekijima, Y.
    Hawkins, P. N.
    Solomon, S. D.
    Polydefkis, M.
    Dyck, P. J.
    Gandhi, P. J.
    Goyal, S.
    Chen, J.
    Strahs, A. L.
    Nochur, S. V.
    Sweetser, M. T.
    Garg, P. P.
    Vaishnaw, A. K.
    Gollob, J. A.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis2018In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 379, no 1, p. 11-21Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Patisiran, an investigational RNA interference therapeutic agent, specifically inhibits hepatic synthesis of transthyretin.

    METHODS: In this phase 3 trial, we randomly assigned patients with hereditary transthyretin amyloidosis with polyneuropathy, in a 2:1 ratio, to receive intravenous patisiran (0.3 mg per kilogram of body weight) or placebo once every 3 weeks. The primary end point was the change from baseline in the modified Neuropathy Impairment Score+7 (mNIS+7; range, 0 to 304, with higher scores indicating more impairment) at 18 months. Other assessments included the Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) questionnaire (range, -4 to 136, with higher scores indicating worse quality of life), 10-m walk test (with gait speed measured in meters per second), and modified body-mass index (modified BMI, defined as [weight in kilograms divided by square of height in meters] x albumin level in grams per liter; lower values indicated worse nutritional status).

    RESULTS: A total of 225 patients underwent randomization (148 to the patisiran group and 77 to the placebo group). The mean (+/- SD) mNIS+7 at baseline was 80.9 +/- 41.5 in the patisiran group and 74.6 +/- 37.0 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.0 +/- 1.7 versus 28.0 +/- 2.6 (difference, -34.0 points; P<0.001) at 18 months. The mean (+/- SD) baseline Norfolk QOL-DN score was 59.6 +/- 28.2 in the patisiran group and 55.5 +/- 24.3 in the placebo group; the least-squares mean (+/- SE) change from baseline was -6.7 +/- 1.8 versus 14.4 +/- 2.7 (difference, -21.1 points; P<0.001) at 18 months. Patisiran also showed an effect on gait speed and modified BMI. At 18 months, the least-squares mean change from baseline in gait speed was 0.08 +/- 0.02 m per second with patisiran versus -0.24 +/- 0.04 m per second with placebo (difference, 0.31 m per second; P<0.001), and the least-squares mean change from baseline in the modified BMI was -3.7 +/- 9.6 versus -119.4 +/- 14.5 (difference, 115.7; P<0.001). Approximately 20% of the patients who received patisiran and 10% of those who received placebo had mild or moderate infusion-related reactions; the overall incidence and types of adverse events were similar in the two groups.

    CONCLUSIONS: In this trial, patisiran improved multiple clinical manifestations of hereditary transthyretin amyloidosis.

  • 274. Adams, David
    et al.
    Suhr, Ole B.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Hund, Ernst
    Obici, Laura
    Tournev, Ivailo
    Campistol, Josep M.
    Slama, Michel S.
    Hazenberg, Bouke P.
    Coelho, Teresa
    First European consensus for diagnosis, management, and treatment of transthyretin familial amyloid polyneuropathy2016In: Current Opinion in Neurology, ISSN 1350-7540, E-ISSN 1473-6551, Vol. 29, p. S14-S26Article in journal (Refereed)
    Abstract [en]

    Purpose of review Early and accurate diagnosis of transthyretin familial amyloid polyneuropathy (TTR-FAP) represents one of the major challenges faced by physicians when caring for patients with idiopathic progressive neuropathy. There is little consensus in diagnostic and management approaches across Europe. Recent findings The low prevalence of TTR-FAP across Europe and the high variation in both genotype and phenotypic expression of the disease means that recognizing symptoms can be difficult outside of a specialized diagnostic environment. The resulting delay in diagnosis and the possibility of misdiagnosis can misguide clinical decision-making and negatively impact subsequent treatment approaches and outcomes. Summary This review summarizes the findings from two meetings of the European Network for TTR-FAP (ATTReuNET). This is an emerging group comprising representatives from 10 European countries with expertise in the diagnosis and management of TTR-FAP, including nine National Reference Centres. The current review presents management strategies and a consensus on the gold standard for diagnosis of TTR-FAP as well as a structured approach to ongoing multidisciplinary care for the patient. Greater communication, not just between members of an individual patient's treatment team, but also between regional and national centres of expertise, is the key to the effective management of TTR-FAP.

  • 275. Adams, David
    et al.
    Suhr, Ole
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
    Conceicao, Isabel
    Waddington-Cruz, Marcia
    Schmidt, Hartmut
    Buades, Juan
    Campistol, Josep
    Pouget, Jean
    Berk, John
    Coelho, Teresa
    Phase 2 open-label extension study of patisiran, an investigational RNAi therapeutic for the treatment of familial amyloid polyneuropathy2015In: Journal of Neurology, Neurosurgery and Psychiatry, ISSN 0022-3050, E-ISSN 1468-330X, Vol. 86, no 11Article in journal (Other academic)
  • 276. Adams, Hieab H. H.
    et al.
    Hibar, Derrek P.
    Chouraki, Vincent
    Stein, Jason L.
    Nyquist, Paul A.
    Renteria, Miguel E.
    Trompet, Stella
    Arias-Vasquez, Alejandro
    Seshadri, Sudha
    Desrivieres, Sylvane
    Beecham, Ashley H.
    Jahanshad, Neda
    Wittfeld, Katharine
    Van der Lee, Sven J.
    Abramovic, Lucija
    Alhusaini, Saud
    Amin, Najaf
    Andersson, Micael
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Arfanakis, Konstantinos
    Aribisala, Benjamin S.
    Armstrong, Nicola J.
    Athanasiu, Lavinia
    Axelsson, Tomas
    Beiser, Alexa
    Bernard, Manon
    Bis, Joshua C.
    Blanken, Laura M. E.
    Blanton, Susan H.
    Bohlken, Marc M.
    Boks, Marco P.
    Bralten, Janita
    Brickman, Adam M.
    Carmichael, Owen
    Chakravarty, M. Mallar
    Chauhan, Ganesh
    Chen, Qiang
    Ching, Christopher R. K.
    Cuellar-Partida, Gabriel
    Den Braber, Anouk
    Doan, Nhat Trung
    Ehrlich, Stefan
    Filippi, Irina
    Ge, Tian
    Giddaluru, Sudheer
    Goldman, Aaron L.
    Gottesman, Rebecca F.
    Greven, Corina U.
    Grimm, Oliver
    Griswold, Michael E.
    Guadalupe, Tulio
    Hass, Johanna
    Haukvik, Unn K.
    Hilal, Saima
    Hofer, Edith
    Hoehn, David
    Holmes, Avram J.
    Hoogman, Martine
    Janowitz, Deborah
    Jia, Tianye
    Kasperaviciute, Dalia
    Kim, Sungeun
    Klein, Marieke
    Kraemer, Bernd
    Lee, Phil H.
    Liao, Jiemin
    Liewald, David C. M.
    Lopez, Lorna M.
    Luciano, Michelle
    Macare, Christine
    Marquand, Andre
    Matarin, Mar
    Mather, Karen A.
    Mattheisen, Manuel
    Mazoyer, Bernard
    Mckay, David R.
    McWhirter, Rebekah
    Milaneschi, Yuri
    Mirza-Schreiber, Nazanin
    Muetzel, Ryan L.
    Maniega, Susana Munoz
    Nho, Kwangsik
    Nugent, Allison C.
    Loohuis, Loes M. Olde
    Oosterlaan, Jaap
    Papmeyer, Martina
    Pappa, Irene
    Pirpamer, Lukas
    Pudas, Sara
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Puetz, Benno
    Rajan, Kumar B.
    Ramasamy, Adaikalavan
    Richards, Jennifer S.
    Risacher, Shannon L.
    Roiz-Santianez, Roberto
    Rommelse, Nanda
    Rose, Emma J.
    Royle, Natalie A.
    Rundek, Tatjana
    Saemann, Philipp G.
    Satizabal, Claudia L.
    Schmaal, Lianne
    Schork, Andrew J.
    Shen, Li
    Shin, Jean
    Shumskaya, Elena
    Smith, Albert V.
    Sprooten, Emma
    Strike, Lachlan T.
    Teumer, Alexander
    Thomson, Russell
    Tordesillas-Gutierrez, Diana
    Toro, Roberto
    Trabzuni, Daniah
    Vaidya, Dhananjay
    Van der Grond, Jeroen
    Van der Meer, Dennis
    Van Donkelaar, Marjolein M. J.
    Van Eijk, Kristel R.
    Van Erp, Theo G. M.
    Van Rooij, Daan
    Walton, Esther
    Westlye, Lars T.
    Whelan, Christopher D.
    Windham, Beverly G.
    Winkler, Anderson M.
    Woldehawariat, Girma
    Wolf, Christiane
    Wolfers, Thomas
    Xu, Bing
    Yanek, Lisa R.
    Yang, Jingyun
    Zijdenbos, Alex
    Zwiers, Marcel P.
    Agartz, Ingrid
    Aggarwal, Neelum T.
    Almasy, Laura
    Ames, David
    Amouyel, Philippe
    Andreassen, Ole A.
    Arepalli, Sampath
    Assareh, Amelia A.
    Barral, Sandra
    Bastin, Mark E.
    Becker, Diane M.
    Becker, James T.
    Bennett, David A.
    Blangero, John
    van Bokhoven, Hans
    Boomsma, Dorret I.
    Brodaty, Henry
    Brouwer, Rachel M.
    Brunner, Han G.
    Buckner, Randy L.
    Buitelaar, Jan K.
    Bulayeva, Kazima B.
    Cahn, Wiepke
    Calhoun, Vince D.
    Cannon, Dara M.
    Cavalleri, Gianpiero L.
    Chen, Christopher
    Cheng, Ching -Yu
    Cichon, Sven
    Cookson, Mark R.
    Corvin, Aiden
    Crespo-Facorro, Benedicto
    Curran, Joanne E.
    Czisch, Michael
    Dale, Anders M.
    Davies, Gareth E.
    De Geus, Eco J. C.
    De Jager, Philip L.
    de Zubicaray, Greig I.
    Delanty, Norman
    Depondt, Chantal
    DeStefano, Anita L.
    Dillman, Allissa
    Djurovic, Srdjan
    Donohoe, Gary
    Drevets, Wayne C.
    Duggirala, Ravi
    Dyer, Thomas D.
    Erk, Susanne
    Espeseth, Thomas
    Evans, Denis A.
    Fedko, Iryna
    Fernandez, Guillen
    Ferrucci, Luigi
    Fisher, Simon E.
    Fleischman, Debra A.
    Ford, Ian
    Foroud, Tatiana M.
    Fox, Peter T.
    Francks, Clyde
    Fukunaga, Masaki
    Gibbs, J. Raphael
    Glahn, David C.
    Gollub, Randy L.
    Goring, Harald H. H.
    Grabe, Hans J.
    Green, Robert C.
    Gruber, Oliver
    Gudnason, Vilmundur
    Guelfi, Sebastian
    Hansell, Narelle K.
    Hardy, John
    Hartman, Catharina A.
    Hashimoto, Ryota
    Hegenscheid, Katrin
    Heinz, Andreas
    Le Hellard, Stephanie
    Hernandez, Dena G.
    Heslenfeld, Dirk J.
    Ho, Beng-Choon
    Hoekstra, Pieter J.
    Hoffmann, Wolfgang
    Hofman, Albert
    Holsboer, Florian
    Homuth, Georg
    Hosten, Norbert
    Hottenga, Jouke-Jan
    Pol, Hilleke E. Hulshoff
    Ikeda, Masashi
    Ikram, M. Kamran
    Jack, Clifford R., Jr.
    Jenldnson, Mark
    Johnson, Robert
    Jonsson, Erik G.
    Jukema, J. Wouter
    Kahn, Rene S.
    Kanai, Ryota
    Kloszewska, Iwona
    Knopman, David S.
    Kochunov, Peter
    Kwok, John B.
    Lawrie, Stephen M.
    Lemaitre, Herve
    Liu, Xinmin
    Longo, Dan L.
    Longstreth, W. T., Jr.
    Lopez, Oscar L.
    Lovestone, Simon
    Martinez, Oliver
    Martinot, Jean-Luc
    Mattay, Venkata S.
    McDonald, Colm
    McIntosh, Andrew M.
    McMahon, Katie L.
    McMahon, Francis J.
    Mecocci, Patrizia
    Melle, Ingrid
    Meyer-Lindenberg, Andreas
    Mohnke, Sebastian
    Montgomery, Grant W.
    Morris, Derek W.
    Mosley, Thomas H.
    Muhleisen, Thomas W.
    Mueller-Myhsok, Bertram
    Nalls, Michael A.
    Nauck, Matthias
    Nichols, Thomas E.
    Niessen, Wiro J.
    Noethen, Markus M.
    Nyberg, Lars
    Umeå University, Faculty of Medicine, Department of Integrative Medical Biology (IMB). Umeå University, Faculty of Medicine, Umeå Centre for Functional Brain Imaging (UFBI).
    Ohi, Kazutaka
    Olvera, Rene L.
    Ophoff, Roel A.
    Pandolfo, Massimo
    Paus, Tomas
    Pausova, Zdenka
    Penninx, Brenda W. J. H.
    Pike, G. Bruce
    Potkin, Steven G.
    Psaty, Bruce M.
    Reppermund, Simone
    Rietschel, Marcella
    Roffman, Joshua L.
    Romanczuk-Seiferth, Nina
    Rotter, Jerome I.
    Ryten, Mina
    Sacco, Ralph L.
    Sachdev, Perminder S.
    Saykin, Andrew J.
    Schmidt, Reinhold
    Schofield, Peter R.
    Sigurdsson, Sigurdur
    Simmons, Andy
    Singleton, Andrew
    Sisodiya, Sanjay M.
    Smith, Colin
    Smoller, Jordan W.
    Soininen, Hindu.
    Srikanth, Velandai
    Steen, Vidar M.
    Stott, David J.
    Sussmann, Jessika E.
    Thalamuthu, Anbupalam
    Tiemeier, Henning
    Toga, Arthur W.
    Traynor, Bryan J.
    Troncoso, Juan
    Turner, Jessica A.
    Tzourio, Christophe
    Uitterlinden, Andre G.
    Hernandez, Maria C. Valdes
    Van der Brug, Marcel
    Van der Lugt, Aad
    Van der Wee, Nic J. A.
    Van Duijn, Cornelia M.
    Van Haren, Neeltje E. M.
    Van't Ent, Dennis
    Van Tol, Marie Jose
    Vardarajan, Badri N.
    Veltman, Dick J.
    Vernooij, Meike W.
    Voelzke, Henry
    Walter, Henrik
    Wardlaw, Joanna M.
    Wassink, Thomas H.
    Weale, Michael E.
    Weinberger, Daniel R.
    Weiner, Michael W.
    Wen, Wei
    Westman, Eric
    White, Tonya
    Wong, Tien Y.
    Wright, Clinton B.
    Zielke, H. Ronald
    Zonderman, Alan B.
    Deary, Ian J.
    DeCarli, Charles
    Schmidt, Helena
    Martin, Nicholas G.
    De Craen, Anton J. M.
    Wright, Margaret J.
    Launer, Lenore J.
    Schumann, Gunter
    Fornage, Myriam
    Franke, Barbara
    Debette, Stephanie
    Medland, Sarah E.
    Ikram, M. Arfan
    Thompson, Paul M.
    Novel genetic loci underlying human intracranial volume identified through genome-wide association2016In: Nature Neuroscience, ISSN 1097-6256, E-ISSN 1546-1726, Vol. 19, no 12, p. 1569-1582Article in journal (Refereed)
    Abstract [en]

    Intracranial volume reflects the maximally attained brain size during development, and remains stable with loss of tissue in late life. It is highly heritable, but the underlying genes remain largely undetermined. In a genome-wide association study of 32,438 adults, we discovered five previously unknown loci for intracranial volume and confirmed two known signals. Four of the loci were also associated with adult human stature, but these remained associated with intracranial volume after adjusting for height. We found a high genetic correlation with child head circumference (rho(genetic) = 0.748), which indicates a similar genetic background and allowed us to identify four additional loci through meta-analysis (N-combined = 37,345). Variants for intracranial volume were also related to childhood and adult cognitive function, and Parkinson's disease, and were enriched near genes involved in growth pathways, including PI3K-AKT signaling. These findings identify the biological underpinnings of intracranial volume and their link to physiological and pathological traits.

  • 277. Adams, M.
    et al.
    Andersson, Lars-Fredrik
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Lindmark, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Veprauskaite, E.
    Competing models of organizational form: Risk management strategies and underwriting profitability in the Swedish fire insurance market between 1903 and 19392012In: Journal of Economic History, ISSN 0022-0507, E-ISSN 1471-6372, Vol. 72, no 4, p. 990-1014Article in journal (Refereed)
    Abstract [en]

    Mutual and stock insurers have coexisted and competed against each other in insurance markets for centuries. In this article, we examine the risk management strategies and underwriting profitability of the different organizational forms in Sweden's property fire insurance market between 1903 and 1939. We demonstrate that stock insurers acted as intermediaries between policyholders and reinsurers to operate effectively in the potentially high-risk segments of the fire insurance market. In contrast, nationwide mutual insurers kept larger reserves to balance fluctuations in claims experiences, while local insurance pools relied on social obligation and trust to mobilize capital after adverse fire events.

  • 278.
    Adams, Mike
    et al.
    Swansea University, UK.
    Andersson, Jonas
    Norwegian School of Economics and Business Administration, Norway.
    Andersson, Lars Fredrik
    Umeå University, Faculty of Social Sciences, Department of Economic History.
    Lindmark, Magnus
    Umeå University, Faculty of Social Sciences, Department of Economic History.
    Commercial banking, insurance and economic growth in Sweden between 1830 and 19982009In: Accounting Business and Financial History, ISSN 0958-5206, E-ISSN 1466-4275, Vol. 19, no 1, p. 21-39Article in journal (Refereed)
    Abstract [en]

    We examine empirically the dynamic historical relation between commercial bank lending, insurance and economic (income) growth in Sweden using time-series data from 1830 to 1998 and performing tests for Granger causality. Because of the non-stationary nature of the time series examined the procedure of Toda andYamamoto (1995) is used. Our results, which have accounted for possible regime changes due to different exchange rate mechanisms over time, indicate that insurance has Granger-caused economic growth and bank lending. Therefore, we conclude that insurance is an important prerequisite for stimulating economic growth and that this could have important implications for contemporary developing economies.

  • 279. Adams, Mike
    et al.
    Andersson, Lars Fredrik
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Lindmark, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Eriksson, Liselotte
    Umeå University, Faculty of Social Sciences, Umeå Centre for Gender Studies (UCGS).
    Veprauskaite, Elena
    Managing policy lapse risk in Sweden’s life insurance market between 1915 and 19472018In: Business History, ISSN 0007-6791, E-ISSN 1743-7938Article in journal (Refereed)
    Abstract [en]

    We examine the challenges that Swedish life insurers faced in managing the lapse risk of policies written on the lives of the industrial urban working class between 1915 and 1947. We observe that with the threat of State socialisation of insurance in the 1930s, industrial life insurers modified their business practices to better control policy lapses. Using firm-level data, we also analyse the effect of socio-economic changes, such as rising real wages, interest rate fluctuations and unemployment on life insurance policy lapses. Our results support contemporary tests of the emergency fund and interest rate explanations for the voluntary premature termination of life insurance policies.

  • 280. Adams, Mike
    et al.
    Andersson, Lars Fredrik
    Umeå University, Faculty of Social Sciences, Department of Economic History.
    Yihui Jia, Joy
    Lindmark, Magnus
    Umeå University, Faculty of Social Sciences, Department of Economic History.
    Mutuality as a control for information asymmetry: a historical analysis of the claims experience of mutual and stock fire insur ance companies in Sweden, 1889 to 19392011In: Business History, ISSN 0007-6791, E-ISSN 1743-7938, Vol. 53, no 7, p. 1074-1091Article in journal (Refereed)
    Abstract [en]

    We test two competing arguments regarding the influence of organisational form onunderwritingperformance usingdatafromtheSwedish fireinsuranceindustry for the years 1889 to 1939 – a period of both economic growth and stagnation. Since mutuality is a response to information asymmetry problems, mutual insurers are expected to report lower annual claims relative to premiums than stock insurance companies. However, an alternative view is that stock insurers seek to reduce information asymmetry problems by issuing non-participatory rights insurance contracts with high deductibles that induce risk-sharing between the insurer’s shareholders and policyholders. This implies that stock insurers are likely to report lower annual claims than mutual insurers. Our results show that organisational form is an important determinant of the claims experience of Swedish fire insurers, suggesting that mutuality acts as an effective control for information asymmetries in the market.

  • 281. Adams, Mike
    et al.
    Andersson, Lars-Fredrik
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Hardwick, Philip
    Lindmark, Magnus
    Umeå University, Faculty of Social Sciences, Department of Geography and Economic History.
    Firm size and growth in Sweden's life insurance market between 1855 and 1947: A test of Gibrat's law2014In: Business History, ISSN 0007-6791, E-ISSN 1743-7938, Vol. 56, no 6, p. 956-974Article in journal (Refereed)
    Abstract [en]

    Using data for the period from 1855 to 1947 and the two sub-periods, 1855-1902 and 1903-47, the article examines whether the organic growth rates of 38 Swedish life insurance firms are independent of size, as predicted by Gibrat's (1931) Law of Proportionate Effects. Using panel unit root tests and panel Generalised Method of Moments (GMM) regression, the article finds a significant difference between the growth rates of small and large Swedish life insurance firms (with smaller firms tending to grow faster than larger firms), a result that clearly contradicts Gibrat's Law as a long-run tendency in the Swedish life insurance sector. significant influences were also found on firm growth from profitability, organisational form, reinsurance, the real rate of interest and the Swedish regulatory environment.

  • 282. Adams, R.
    et al.
    Fincher, S.
    Pears, A.
    Börstler, Jürgen
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Bousted, J.
    Dalenius, P.
    Eken, G.
    Heyer, T.
    Jacobsson, A.
    Lindberg, V.
    Molin, B.
    Moström, J.-E.
    Umeå University, Faculty of Science and Technology, Department of Computing Science.
    Wiggberg, M.
    What is the Word for Engineering in Swedish: Swedish Students' Conceptions of their Discipline2007Report (Other academic)
  • 283.
    Adamson, Frank
    et al.
    Stanford University.
    Åstrand, Björn
    Karlstads universitet.
    Privatization or public investment? A global question2016In: Global education reform: How privatization and public investment influence education outcomes / [ed] Adamson, F, Åstrand, B & Darling-Hammond, L, Routledge , 2016, 1, p. 1-15Chapter in book (Other academic)
  • 284.
    Adamson, Frank
    et al.
    Stanford University.
    Åstrand, BjörnKarlstads universitet.Darling-Hammond, LindaStanford University.
    Global education reform: How privatization and public investment influence education outcomes2016Collection (editor) (Other academic)
  • 285.
    Adamsson, Erik
    et al.
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    Johansson, Peder
    Umeå University, Faculty of Social Sciences, Department of Informatics.
    Kön, IT och domesticeringsprocessen. 2003Independent thesis Basic level (degree of Bachelor), 10 credits / 15 HE creditsStudent thesis
  • 286.
    Adamsson, Malin
    et al.
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Johansson, Jennifer
    Umeå University, Faculty of Social Sciences, Umeå School of Business and Economics (USBE), Business Administration.
    Effekterna av Särskilt Betydelsefulla Områden: En kvantitativ studie om den utökade revisionsberättelsen2019Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [sv]

    Revisionsberättelsen och dess roll att förmedla trovärdig och väsentlig information har länge varit uppe för diskussion. Kritiker menar att revisionsberättelsen har utvecklats till en alltför standardiserad rapport där det råder brist på transparens i revisionen samt att kommunikationen med intressenter är bristfällig. Detta resulterade i att IAASB, parallellt med EU, utvecklade den nya utökade revisionsberättelsen i syfte att höja dess kommunikativa värde, relevans och kvalitet. De nya direktiven trädde i kraft den 15:e december 2016 i form av sex reviderade och en helt ny standard. Den mest signifikanta förändringen är den nya standarden ISA 701 som handlar om Särskilt Betydelsefull Områden (SBO). SBO omfattar de områden som i revisorns professionella bedömning är av särskilt betydande karaktär för det reviderade företaget. Dessa områden ska vidare vara specifika för varje enskilt företag och även behandla vad som har varit mest problematiskt i revisionen. Den ytterligare informationen ska ge användarna mer insyn i revisionsprocessen och öka förståelsen för de områden som krävt betydande bedömningar. 

    Denna studie syftar därmed att ge en bild av hur den nya standarden gällande SBO fungerar i praktiken, vilken utformning de SBO som rapporterats har och om införandet av SBO har förändrat revisionsberättelsen sett till räkenskapsåren 2015 och 2017. För att få en bredare bild kompletteras detta med att undersöka och jämföra om revisionskvaliteten förändrats i och med den utökade revisionsberättelsen. 

    Med utgångspunkt i teorierna om informationsgapet och förväntningsgapet samt agentteorin undersöktes studiens syfte genom en kvantitativ innehållsanalys, där revisionsberättelser från svenska börsnoterade bolag kodats och analyserats efter framtagna kategorier. Denna information har sammanställts som deskriptiv statistik för att konkret se förändringarna mellan åren sett till bland annat längd, antal SBO och utvalda nyckelord. För att mäta revisionskvaliteten prövades istället en huvud- och tre delhypoteser genom en multipel regressionsanalys. Den data som användes som grund för både innehållsanalysen och hypotesprövningen kommer från databasen Orbis Europe och är ett register på 394 svenska börsnoterade företag. 

    Resultatet visar att det skett märkbara förändringar från ett år innan till ett år efter implementeringen av den utökade revisionsberättelsen. Detta i form av en längre rapport, där olika typer av SBO rapporteras i majoriteten av företagen, och där rapporten frångått sin standardiserade mall genom en större spridning på valda nyckelord. Resultatet finner däremot inte stöd för att det finns en negativ, signifikant effekt mellan den utökade revisionsberättelsen och revisionskvalitet som följd av lägre oväntade periodiseringar. Det finns dock ett stöd för att rapporteringen av SBO har en negativ, signifikant effekt på oväntade periodiseringar vilket således betyder en högre revisionskvalitet.

  • 287. Adamsson, Viola
    et al.
    Ellegård, Lasse
    Rossander Hulthén, Lena
    Hambraeus, Leif
    Larsson, Christel
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Validity of reported energy intake and energy expenditure of Swedish elite cross-country skiers2004In: Public Health Nutrition 8th Nordic Nutrition Conference, Tønsberg, Norway, 2004Conference paper (Other (popular science, discussion, etc.))
  • 288. Adamsson, Viola
    et al.
    Larsson, Christel
    Umeå University, Faculty of Social Sciences, Department of Food and Nutrition.
    Viktigt att granska kostundersökningar2005In: Svensk Idrottsmedicin, ISSN 1103-7652, no 2, p. 14-17Article in journal (Other academic)
  • 289.
    Adane, Daniel
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Global Health.
    Effectiveness of PMTCT programs in Sub-Saharan Africa, a meta-analysis2012Independent thesis Advanced level (degree of Master (Two Years)), 20 credits / 30 HE creditsStudent thesis
  • 290.
    Adawi, Nadia
    et al.
    Umeå University, Faculty of Medicine, Department of Odontology.
    Jewaratnam, Sukanya
    Umeå University, Faculty of Medicine, Department of Odontology.
    Tooth Extraction and Implant Placement Causes Changes in Both Muscle Fiber Composition and Motor Cortex in Rats. Experimental study2016Independent thesis Advanced level (professional degree), 20 credits / 30 HE creditsStudent thesis
    Abstract [en]

    Tooth loss has been shown to induce neuroplastic changes in the sensorimotor cortical area of the brain that represents jaw muscles. Dental implants placed into extraction sites reversed these changes. Since muscles are highly plastic, we hypothesize that the cortical changes after dental extraction also are reflected in jaw-opening muscles and that these changes are prevented/reversed following dental implant placement.

     

    Fifteen rats were randomly allocated in four groups; extraction 1 (Ext-1, n=4), extraction 2 (Ext-2, n=4), implant group (n=4) and control group (n=3). The anterior digastric (AD) muscle was obtained from the extraction groups after 1 and 2 months, respectively, and from the implant group after 3 weeks. The samples were analyzed with immunohistochemical and morphological techniques. Our results showed; 1) intermediate and low oxidative fast MyHCII fibers predominated AD muscle, 2) oxidative capacity of fibers was higher in the central region, 3) extraction caused a shift towards fibers with lower oxidative capacity in the central region, 4) placement of dental implants increased the oxidative capacity of fibers in both central and peripheral region.

     

    We conclude that in the AD muscle, loss of teeth cause a tendency to shift against fibers with faster contraction properties and lower oxidative capacity, while treatment with implants tends to reverse it. Interestingly, these alterations followed the change pattern of the cortical motor area for the AD muscle i.e. larger proportion of fibers with higher oxidative capacity and fine motor control were associated with increased motor representation sites (MRS) for the AD muscle.

     

  • 291.
    Adcock, Joanna
    et al.
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences. Overseas Development Institute, London, UK.
    Fottrell, Edward
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Epidemiology and Public Health Sciences.
    The North-South information highway: case studies of publication access among health researchers in resource-poor countries2008In: Global Health Action, ISSN 1654-9716, E-ISSN 1654-9880, Vol. 1Article in journal (Refereed)
    Abstract [en]

    Background: Less than 2% of scientific publications originate in low-income countries. Transfer of information from South to North and from South to South is grossly limited and hinders understanding of global health, while Northern-generated information fails to adequately address the needs of a Southern readership.

    Methods: A survey of a new generation of health researchers from nine low-income countries was conducted using a combination of email questionnaires and face-to-face interviews. Data were gathered on personal experiences, use and aspirations regarding access and contribution to published research.

    Results: A total of 23 individuals from 9 countries responded. Preference for journal use over textbooks was apparent, however a preference for print over online formats was described among African respondents compared to respondents from other areas. Almost all respondents (96%) described ambition to publish in international journals, but cited English language as a significant barrier.

    Conclusion: The desire to contribute to and utilise contemporary scientific debate appears to be strong among study respondents. However, longstanding barriers

  • 292. Adcock, Tina
    et al.
    Roberts, Peder
    Nations, Natures, and Networks: The New Environments of Northern Studies2015In: Journal of Northern Studies, ISSN 1654-5915, Vol. 9, no 1, p. 7-11Article in journal (Refereed)
  • 293.
    Addario, Barbara
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Alpha-actinin - an amazing journey through time and species2011Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    In eukaryotes, the actin cytoskeleton plays an important role in a large variety of cellular events. Its reorganization is regulated by a plethora of actin-modulating proteins, such as α-actinin.

    α-actinin is a ubiquitous actin-binding protein that belongs to the spectrin superfamily. This family, besides α-actinin, includes spectrin, dystrophin and utrophin. Phylogenetic analyses have indicated that the family members arose after several intragene duplications and rearrangements of a common ancestral α-actinin isoform. Up to the invertebrate-vertebrate bifurcation, organisms seemed to have a single, calcium-dependent α‑actinin. After the split, invertebrates have kept this single isoform, in contrast to vertebrates that acquired four distinct isoforms. Of the four vertebrate α-actinin isoforms, the two present in non-muscle cells are typically calcium sensitive while the two muscle isoforms are calcium insensitive.

    α-actinin in higher organisms is characterized by the presence of three distinct structural domains: a highly conserved N-terminal actin-binding domain, a central rod domain with four spectrin repeats and a calcium-binding C terminus with EF-hand motifs. In some primitive organisms, such as protozoa and fungi, the rod domain of α-actinin contains only one or two spectrin repeats. With the completion of an ever increasing number of genomes, new and atypical α‑actinin sequences had been available that have not been characterized yet. To obtain a firmer understanding of the evolutionary history of α-actinin, the main objective of this study was to identify, purify and biochemically characterize atypical α‑actinin or α‑actinin-like proteins of the parasite Entamoeba histolytica and of the fungus Schizosaccharomyces pombe. Our results show that both isoforms, despite the much shorter rod domain, are able to bind and cross-link actin filaments and therefore can be considered genuine α-actinins. 

  • 294.
    Addario, Barbara
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Backman, Lars
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Alpha-actinin of Schizosaccharomyces pombeManuscript (preprint) (Other academic)
  • 295.
    Addario, Barbara
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Backman, Lars
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    The domain structure of Entamoeba α-actinin22010In: Cellular & Molecular Biology Letters (Druk), ISSN 1425-8153, E-ISSN 1689-1392, Vol. 15, no 4, p. 665-78Article in journal (Refereed)
    Abstract [en]

    Entamoeba histolytica, a major agent of human amoebiasis, expresses two distinct forms of α-actinin, a ubiquitous actin-binding protein that is present in most eukaryotic organisms. In contrast to all metazoan α-actinins, in both isoforms the intervening rod domain that connects the N-terminal actin-binding domain with the C-terminal EF-hands is much shorter. It is suggested that these α-actinins may be involved in amoeboid motility and phagocytosis, so we cloned and characterised each domain of one of these α-actinins to better understand their functional role. The results clearly showed that the domains have properties very similar to those of conventional α-actinins.

  • 296.
    Addario, Barbara
    et al.
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Huang, Shenghua
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Sauer, Uwe
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Backman, Lars
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Crystallization and preliminary X-ray analysis of the Entamoeba histolytica α-actinin-2 rod domain2011In: Acta Crystallographica. Section F: Structural Biology and Crystallization Communications, ISSN 1744-3091, E-ISSN 1744-3091, Vol. 67, no 10, p. 1214-1217Article in journal (Refereed)
    Abstract [en]

    -Actinins form antiparallel homodimers that are able to cross-link actin filaments. The protein contains three domains: an N-terminal actin-binding domain followed by a central rod domain and a calmodulin-like EF-hand domain at the C-terminus. Here, crystallization of the rod domain of Entamoeba histolytica -actinin-2 is reported; it crystallized in space group P212121, with unit-cell parameters a = 47.8, b = 79.1, c = 141.8 Å. A Matthews coefficient VM of 2.6 Å3 Da-1 suggests that there are two molecules and 52.5% solvent content in the asymmetric unit. A complete native data set extending to a d-spacing of 2.8 Å was collected on beamline I911-2 at MAX-lab, Sweden.

     

  • 297. Addario, Barbara
    et al.
    Sandblad, Linda
    Umeå University, Faculty of Medicine, Department of Molecular Biology (Faculty of Medicine).
    Persson, Karina
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Backman, Lars
    Umeå University, Faculty of Science and Technology, Department of Chemistry.
    Characterisation of Schizosaccharomyces pombe alpha-actinin2016In: PeerJ, ISSN 2167-8359, E-ISSN 2167-8359, Vol. 4, article id e1858Article in journal (Refereed)
    Abstract [en]

    The actin cytoskeleton plays a fundamental role in eukaryotic cells. Its reorganization is regulated by a plethora of actin-modulating proteins, such as a-actinin. In higher organisms, alpha-actinin is characterized by the presence of three distinct structural domains: an N-terminal actin-binding domain and a C-terminal region with EF-hand motif separated by a central rod domain with four spectrin repeats. Sequence analysis has revealed that the central rod domain of alpha-actinin from the fission yeast Schizosaccharomyces pombe consists of only two spectrin repeats. To obtain a firmer understanding of the structure and function of this unconventional alpha-actinin, we have cloned and characterized each structural domain. Our results show that this alpha-actinin isoform is capable of forming dimers and that the rod domain is required for this. However, its actin-binding and cross-linking activity appears less efficient compared to conventional alpha-actinins. The solved crystal structure of the actin-binding domain indicates that the closed state is stabilised by hydrogen bonds and a salt bridge not present in other a-actinins, which may reduce the affinity for actin.

  • 298.
    Addi, Simon
    et al.
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Hedayati-Khams, Arjang
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Poya, Amin
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Sjögren, Göran
    Umeå University, Faculty of Medicine, Odontology, Dental Materials Science.
    Interface gap size of manually and CAD/CAM-manufactured ceramic inlays/onlays in vitro.2002In: Journal of Dentistry, ISSN 0300-5712, E-ISSN 1879-176X, Vol. 30, no 1, p. 53-58Article in journal (Refereed)
    Abstract [en]

    Objectives : To determine the fit of ceramic inlays manufactured using a recently introduced CAD/CAM-system (Decim) and of two types of laboratory-made heat-pressed ceramics (IPS Empress and Opc).

    Materials and methods : Extracted human premolars were prepared to receive mesio-occlusodistal (MOD) ceramic inlays, for which 10 Denzir, 10 IPS Empress, and 10 Opc were fabricated. The Denzir restorations were produced by the manufacturer of the CAD/CAM-system, and the IPS Empress and Opc by student dental technicians. Before luting the internal fit on the diestone models and on the premolars was determined using replicas. After luting on the premolars with a resin composite the marginal and internal fit were measured. The values were analyzed statistically using ANOVA and Scheffe's test at a significance level of p<0.05.

    Results : Before luting there were no significant differences ( p>0.05) in the internal gap width between the three systems studied when placed on their matching diestone models. When placed on the premolars a significant difference ( p<0.01) in the internal fit was seen between Empress and Opc before luting, whereas there were no significant differences ( p>0.05) between Empress and Denzir and between Opc and Denzir. Between the diestone models and the premolars there were significant differences ( p<0.01) in the internal fit, except for IPS Empress. After luting there were no significant differences ( p>0.05) between IPS Empress and Denzir, whereas the marginal gap width was significantly wider ( p<0.001) for Opc than for IPS Empress and Denzir. The internal fit was significantly ( p<0.001) wider for Opc than for IPS Empress, whereas there were no significant differences ( p>0.05) between IPS Empress and Denzir or between Opc and Denzir.

    Conclusion : After luting there were only slight differences in the fit between the restorations fabricated using the three different manufacturing techniques and ceramics. Therefore, long-term follow-up studies are needed to assess the clinical significance of the slight differences between the three systems.

  • 299. Adebahr, J
    et al.
    Forsyth, M
    Gavelin, P
    Jacobsson, P
    Orädd, Greger
    Umeå University, Faculty of Science and Technology, Chemistry.
    Ion and Solvent Dynamics in Gel Electrolytes Based on Ethylene Oxide Grafted Acrylate Polymers2002In: The Journal of Physical Chemistry B, Vol. 106, no 47, p. 12119-12123Article in journal (Refereed)
    Abstract [en]

    Multinuclear pulsed field gradient NMR measurements and rheological viscosity measurements were performed on three series of polymer gel electrolytes. The gels were based on a lithium salt electrolyte swollen into a copolymer matrix comprising an acrylate backbone and ethylene oxide side chains. In each series the side chains differed in length and number, but the acrylate-to-ethylene oxide ratio was kept constant. It was found that the self-diffusion coefficient of the cations was much lower than that of the anions, and that it decreased rapidly when the side chains got longer. In contrast, the self-diffusion coefficient of the anions was found to be independent of chain length. In the gel electrolytes, the diffusion coefficients of the solvent molecules are relatively constant despite an increased viscosity with increasing length of the side chains. However, in salt-free gels made for comparison, the diffusion coefficients of the solvent molecules decreased with increasing length of the side chains, which is consistent with an increased viscosity.

  • 300.
    Adebiyi, Abdulafeez
    et al.
    Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, West Virginia 26506, USA.
    Alkandari, Rawan
    Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, West Virginia 26506, USA.
    Valiev, Damir
    Umeå University, Faculty of Science and Technology, Department of Applied Physics and Electronics. Center for Combustion Energy, Key Laboratory for Thermal Science and Power Engineering of the Ministry of Education of China, Department of Energy and Power Engineering, Tsinghua University, Beijing, China.
    Akkerman, V’yacheslav
    Department of Mechanical and Aerospace Engineering, West Virginia University, Morgantown, West Virginia, USA.
    Effect of surface friction on ultrafast flame acceleration in obstructed cylindrical pipes2019In: AIP Advances, ISSN 2158-3226, E-ISSN 2158-3226, Vol. 9, no 3, article id 035249Article in journal (Refereed)
    Abstract [en]

    The Bychkov model of ultrafast flame acceleration in obstructed tubes [Valiev et al., “Flame Acceleration in Channels with Obstacles in the Deflagration-to-Detonation Transition,” Combust. Flame 157, 1012 (2010)] employed a number of simplifying assumptions, including those of free-slip and adiabatic surfaces of the obstacles and of the tube wall. In the present work, the influence of free-slip/non-slip surface conditions on the flame dynamics in a cylindrical tube of radius R, involving an array of parallel, tightly-spaced obstacles of size αR, is scrutinized by means of the computational simulations of the axisymmetric fully-compressible gasdynamics and combustion equations with an Arrhenius chemical kinetics. Specifically, non-slip and free-slip surfaces are compared for the blockage ratio, α, and the spacing between the obstacles, ΔZ, in the ranges 1/3 ≤ α ≤ 2/3 and 0.25 ≤ ΔZ/R ≤ 2.0, respectively. 

    For these parameters, an impact of surface friction on flameacceleration is shown to be minor, only 1-4%, slightly facilitating acceleration in a tube with ΔZ/R = 0.5 and moderating acceleration in thecase of ΔZ/R = 0.25. Given the fact that the physical boundary conditions are non-slip as far as the continuum assumption is valid, the presentwork thereby justifies the Bychkov model, employing the free-slip conditions, and makes its wider applicable to the practical reality. Whilethis result can be anticipated and explained by a fact that flame propagation is mainly driven by its spreading in the unobstructed portion ofan obstructed tube (i.e. far from the tube wall), the situation is, however, qualitatively different from that in the unobstructed tubes, wheresurface friction modifies the flame dynamics conceptually.

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