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  • Public defence: 2017-03-31 09:00 Sal E04, Trapphus R, en trappa ned, Umeå
    Skagerlind, Malin
    Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine. Umeå University, Faculty of Medicine, Department of Nursing.
    How to reduce the exposure to anticoagulants when performing haemodialysis in patients with a bleeding risk: a study of methods used in clinical practise2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    When a patient suffers from kidney failure and also has an enhanced risk of bleeding, the standard haemodialysis (HD) treatment becomes a problem. When human blood comes in contact with artificial material, as in the tubing system and in the dialyser (the extra corporeal circuit, ECC), the coagulation system is activated. If there is no increased risk of bleeding a bolus dose of anticoagulation is given intravenous to the patient before HD to avoid clotting. The most common anticoagulants used during HD are unfractionated heparin (UFH) and low molecule weight heparins (LMWH). Without anticoagulants there will be a total coagulation (clotting) of the blood in the ECC, an interrupted treatment and a blood loss of up to 300 ml for the patient. With an ongoing bleeding or an increased risk of bleeding in a patient that also needs HD, there are various alternatives that can be used to avoid or lower the need of anticoagulation. However, there is no golden standard, neither in Sweden or worldwide.

    The overall aim of this Thesis was to evaluate the safety and the efficacy of various models of anticoagulation that may be used in patients with a bleeding risk.

    The first study examined a low-dose anticoagulation model that was locally developed in Umeå, Sweden in the 1980s. The primary aim was to clarify to what extent this priming model was safe and efficient during intermittent HD for patients with a bleeding risk. Consecutive acute HD treatment protocols (248 procedures in 68 patients) were included. There were 178 patients with an increased bleeding risk who had their ECC (tubes, chambers and dialyser) flushed through (priming) with Heparin-Albumin-priming (HA-priming). There were 70 patients with no increased bleeding risk who received standard intermittent HD (priming with saline); these patients also received a bolus dose of anticoagulation intravenous before dialysis.

    The low-dose method entailed priming of the ECC with HA-priming with the intention to coat the surfaces with the solution and protect from blood to attach to it. Comparisons were made to dialysis in patients with no increased bleeding risk, who had received standard anticoagulation (SHD) with UFH or LMWH. The priming solutions were always discarded before HD was initiated. None or limited doses of UFH were added during the HD. There was no difference in extent of prematurely interrupted HA-primed dialysis compared to SHD (2.2 vs. 4.3%, p = 0.62). No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 2 was performed to further clarify data in an extended group of acute intermittent HD using either HA-priming (885 treatments in 221 patients at risk of bleeding) or SHD (523 treatments in 100 patients with no bleeding risk who had received standard anticoagulation). In this extended study there was no difference in the extent of prematurely interrupted HA-dialysis (0.8%) compared to SHD (1%, p = 0.8). The results also showed less clotting for dialysers with a membrane area ≤ 1.7 m2. No secondary bleeding due to anticoagulation was reported in the protocols.

    Study 3 was an experimental in vitro study. The aim was to compare the anticoagulation effect of priming the ECC with different concentrations of albumin and/or heparin in saline. Priming with saline only was also evaluated. The priming fluids were always discarded after priming. Fresh whole blood from healthy human donors was used to perform in vitro dialyses in a recirculation system. The donated blood was equally divided into two bags, whereas one bag represented the control group and the other the intervention group. Priming with saline only and priming with albumin in saline resulted in rapid clotting of the blood in the ECC. These experiments indicated that HA-priming or priming with heparin in saline enabled fulfilment of all the in vitro dialyses.

    Study 4 was a clinical randomized cross-over study. The aim was to minimize the use of anticoagulant during HD in patients with a bleeding risk. Four different low-dose anticoagulation models were compared to SHD. Stable chronic HD patients participated in the study. The patients were their own controls. Aside from SHD, the four models of low-dose anticoagulation used were Heparin priming (H), HA-priming (HA), HA-priming in combination with a citrate containing dialysate (HAC), and a dialyser manufactured with a heparin-grafted membrane (Evodial®). The H-model was least suitable with 33 % interrupted treatments and the most extra doses of UFH needed. The HAC and Evodial® models were most preferable, both with an activated partial thromboplastin time (APTT) within references and with the least amounts of UFH needed. Evodial® had a lower urea reduction rate compared to the other models. HAC was the only model with no interrupted treatment. One patient suffered from a severe hypersensitivity reaction using Evodial®. No other side-effects were reported during the study.

    In conclusion an acute kidney injury is a life-threating situation that also includes patients with an increased bleeding risk and in need of HD for survival. If intermittent HD is the selected option, a priming of the ECC with a HA-solution in combination with a citrate containing dialysis fluid (HAC) is a safe and sufficient option for anticoagulation. Another option could be the heparin-grafted dialyser (Evodial®), although with a lower clearance coefficient and with a caution for a risk for hypersensitivity reaction or anaphylaxis.

    The full text will be freely available from 2018-03-31 00:00
  • Public defence: 2017-03-31 10:30 Horsal G, Umeå
    Gheitasi, Parvin
    Umeå University, Faculty of Arts, Department of language studies.
    "Say It Fast, Fluent and Flawless": formulaicity in the oral language production of young foreign language learners2017Doctoral thesis, monograph (Other academic)
    Abstract [en]

    This thesis reports on a study, which investigated the process of early foreign language learning in a classroom context and the functions of multi-word units of language known as formulaic sequences in the oral language production of young foreign language learners. A classroom with 11 students in the age range 9 to 11 years was observed and video recorded for 16 sessions (90 minutes per session). The observations were accompanied by two elicitation tasks. 10 sessions out of the 16 sessions of the collected speech samples were transcribed chronologically. In the next step, formulaic sequences were identified based on pre-established criteria, which were further developed during the analysis. The data was analyzed in order to identify the functions of formulaic sequences in learners’ oral language production in addition to the inter-learner variations in the application of formulaic sequences for different functions.

    The results revealed evidence of incidental learning of formulaic sequences from input; the language input provided instances for the learners to learn multi-word units. In addition, formulaic sequences played different roles in the language production of the learners. These sequences helped young language learners to overcome their lack of knowledge, to improve their fluency, and to enjoy some language play. Formulaic sequences were used as a strategy to economize effort on processing and also to buy time for processing. The findings of the study suggested that language users might introduce dis-fluency in the production of their sequences in order to buy time for further processing. Moreover, the data provided examples illustrating communicative functions of formulaic sequences where the use of formulaic sequences was affected by the relationship between the speaker and listener. The analysis revealed that although all the learners applied formulaic sequences in their language production, there was a great variation among individual learners in their intention and the extent of the application of formulaic sequences. Some learners used these sequences to be able to extend their utterances and produce more of the language, whereas other learners used them to avoid further language production. In sum, it seemed that individual learners' different personalities, needs or limitations served as explanation for the application of formulaic sequences in different contexts.

  • Public defence: 2017-04-07 09:00 Hörsal D, byggnad 1D, Umeå
    Forsell, Joakim
    Umeå University, Faculty of Medicine, Department of Clinical Microbiology.
    Genetic subtypes in unicellular intestinal parasites with special focus on Blastocystis2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    The development of molecular tools for detection and typing of unicellular intestinal parasites has revealed genetic diversities in species that were previously considered as distinct entities. Of great importance is the genetic distinction found between the pathogenic Entamoeba histolytica and the non-pathogenic Entamoeba dispar, two morphologically indistinguishable species. Blastocystis sp. is a ubiquitous intestinal parasite with unsettled pathogenicity. Molecular studies of Blastocystis sp. have identified 17 genetic subtypes, named ST1-17. Genetically, these subtypes could be considered as different species, but it is largely unknown what phenotypic or pathogenic differences exist between them. This thesis explores molecular methods for detection and genetic subtyping of unicellular intestinal parasites, with special focus on Blastocystis.

    We found that PCR-based methods were highly sensitive for detection of unicellular intestinal parasites, but could be partially or completely inhibited by substances present in faeces. A sample transport medium containing guanidinium thiocyanate was shown to limit the occurrence of PCR inhibition.

    The prevalence of Blastocystis in Swedish university students was over 40%, which is markedly higher than what was previously estimated. Blastocystis ST3 and ST4 were the two most commonly found Blastocystis subtypes in Sweden, which is similar to results from other European countries.

    Blastocystis sp. and Giardia intestinalis were both commonly detected in Zanzibar, Tanzania, each with a prevalence exceeding 50%. Blastocystis ST1, ST2, and ST3 were common, but ST4 was absent. While G. intestinalis was most common in the ages 2-5 years, the prevalence of Blastocystis increased with increasing age, at least up to young adulthood. We found no statistical association between diarrhoea and Blastocystis sp., specific Blastocystis subtype or G. intestinalis.

    Metagenomic sequencing of faecal samples from Swedes revealed that Blastocystis was associated with high intestinal bacterial genus richness, possibly signifying gastrointestinal health. Blastocystis was also positively associated with the bacterial genera Sporolactobacillus and Candidatus Carsonella, and negatively associated with the genus Bacteroides.

    Blastocystis ST4 was shown to have limited intra-subtype genetic diversity and limited geographic spread. ST4 was also found to be the major driver behind the positive association between Blastocystis and bacterial genus richness and the negative association with Bacteroides.

  • Public defence: 2017-04-07 10:00 Hörsal E, Umeå
    Fjellström, Magnus
    Umeå University, Faculty of Social Sciences, Department of Education.
    Becoming a construction worker: a study of vocational learning in school and work life2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    This thesis describes and analyses vocational learning in school and workplaces, particularly the vocational learning involved in becoming a construction worker in Sweden. This includes learning the trade in upper secondary school education and a subsequent apprenticeship. An underlying argument is that activities in these contexts enable a diverse vocational learning outcome. However, there are potential tensions and contradictions, especially between production- and education-oriented aspects of the learning activities in these settings. To address these and associated issues, two research questions were posed. First, how do work-based activities enable vocational learning? Second, what forms of learning are enabled in school and work life settings and how are these forms of learning constituted? These questions were addressed using information drawn from observations, interviews and a survey. Analyses of the data, using a theoretical framework based on activity and forms of learning theory, show that the school and workplace settings enable different types of learning that form a joint constructed object. Further, the contexts provide diverse tasks that, with guidance from more experienced persons, can enhance the learning outcomes. So, vocational learning is enabled through tensions in the activity systems that form a learning outcome. In project-based vocational education and training (PBVET) provided in upper secondary school, vocational learning is enabled through basic training and opportunities to learn key techniques. In subsequent apprenticeships, the transformation of basic knowledge into specialized knowledge is enabled through close guidance and by the apprentices performing complex tasks. There are also clear differences in the freedom allowed in the performance of tasks between the PBVET and apprenticeships. The PBVET does not allow students to develop and apply their own solutions, while apprentices are encouraged to discover and implement solutions that enhance the performance of tasks. So, different forms of learning are enabled in the two contexts; the PBVET largely promotes reproductive learning and the apprenticeships largely promote productive learning. Scope for improvement was detected, as the PBVET does not appear to provide knowledge that fully meets criteria in the syllabuses, and the apprenticeship does not fully meet the learners’ educational needs. However, the settings provide complementary vocational learning opportunities. Thus, tensions and contradictions can be identified in the activity systems in the school and workplace settings that collectively form the boundaries of a learning outcome that largely corresponds to what the learners need to know and (hence) become construction workers.

  • Public defence: 2017-04-07 13:00 Triple Heli, Umeå
    Strinnholm, Åsa
    Umeå University, Faculty of Medicine, Department of Nursing.
    Food hypersensitivity among schoolchildren: -prevalence, Health Related Quality of Life and experiences of double-blind placebo-controlled food challenges. The Obstructive Lung Disease in Northern Sweden (OLIN) Studies, Thesis XVIII.2017Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Background

    The prevalence of reported food hypersensitivity among children has increased in Western countries. However, the prevalence varies largely due to differences in methods used in different studies. Double-blind placebo-controlled food challenge (DBPCFC) is the most reliable method to verify or exclude food hypersensitivity. The use of double-blind food challenges is increasing in clinical praxis, but since the method is time- and resource consuming it is rarely used in population-based cohort studies. There is a lack of knowledge on how adolescents and mothers experience participation in double-blind placebocontrolled food challenges and to what extent the food is reintroduced after a negative challenge. While several studies have described the impact of IgEmediated food allergy on Health-Related Quality of Life (HRQL), few studies have described HRQL among children with other food hypersensitivity phenotypes.

    Aim

    The aim of this thesis was to estimate the prevalence of reported food hypersensitivity, associated risk factors, and symptom expressions among schoolchildren. We also examined HRQL among children with total elimination of cow’s milk, hen’s egg, fish or wheat due to food hypersensitivity as a group compared with children with unrestricted diet, and after we categorised the children with eliminated foods into different phenotypes of FHS. Finally, adolescents’ and mothers’ experience of DBPCFC was examined as well if the food had been reintroduced.

    Methods

    Three studies were based on the Obstructive Lung Disease in Northern Sweden (OLIN) paediatric cohort II. The cohort was recruited in 2006 when all children in first and second grade (7-8 years) in three municipalities in Norrbotten were invited to a parental questionnaire study and 2,585 (96% of invited) participated. The questionnaire included questions about food hypersensitivity, asthma, rhinitis, eczema and possible risk factors. The children in two municipalities were also invited to skin prick testing with 10 airborne allergens, and 1,700 (90%) participated. Paper I is based on this initial survey of the cohort. Four years later, at age 11-12 years, the cohort was followed up using the same methods and with the same high participation rate. At the follow-up, 125 children (5% of the cohort) reported total elimination of cow’s milk, hen’s egg, fish or wheat due to food hypersensitivity. These children were invited to a clinical examination and to complete a generic (KIDSCREEN-52) and a diseasespecific HRQL questionnaire (FAQLQ-TF) (n=75). Based on the clinical examination the children were categorised into different phenotypes of food hypersensitivity: current food allergy, outgrown food allergy and lactose intolerance. In addition, a random sample of children with unrestricted diet from the same cohort, answered the generic questionnaire (n=209). Paper II is based on this HRQL study. Children categorised as having current food allergy were invited to a further evaluation including DBPCFC. Eighteen months after the challenges, these children were interviewed about their experiences during and after the challenge (n=17). Paper III is based on these interviews. Paper IV was based on interviews with mothers to children referred to a paediatric allergy specialist for evaluation of food allergy using DBPCFC (n=8). In the two interview studies results were analysed using qualitative content analysis.

    Results

    At age 7-8 years, the prevalence of reported food hypersensitivity was 21%. Food hypersensitivity to milk, egg, fish, wheat or soy was reported by 10.9% and hypersensitivity to fruits or nuts by 14.6%. The most common essential food to trigger symptoms was milk, reported by 9%. The most frequently reported food induced symptoms, were oral symptoms mainly caused by fruits, followed by gastrointestinal symptoms mainly caused by milk. The risk factor pattern was different for food hypersensitivity to milk compared to hypersensitivity to other foods. No significant difference in distribution in generic or disease-specific HRQL was found among children with reported total elimination of milk, egg, fish and/or wheat due to FHS compared to children with unrestricted diet. However, a trend indicated that the disease-specific HRQL was most impaired among children with current food allergy compared to children with outgrown food allergy and lactose intolerance. The proportion of poor HRQL defined as ≥75 percentile was significantly higher among children with current food allergy than the other phenotypes. A DBPCFC was an opportunity for the adolescents and the mothers to overcome the fear of reactions to food that had been eliminated for a long time. After the challenge, when the food was partially or fully reintroduced, socializing became easier and both adolescents and mothers experienced more freedom regarding food intake. A negative challenge was not consistently associated with reintroduction of the food. Reasons for reintroduction failure were fear of allergic reactions, that the adolescent did not like the taste of the food, or that living with an elimination diet was considered as normal. Conclusion In this population-based study, one in five of children at age 7-8 years reported food hypersensitivity to any food. The generic HRQL was similar among children with and without food hypersensitivity. However, poor disease-specific HRQL was more common among children with current food allergy compared to children with other FHS phenotypes. If the tested food was reintroduced after a DBPCFC, both adolescents and mothers described a changed life with less fear, and that life had become easier regarding meal preparations and social events. As reintroduction failure was present despite a negative food challenge, follow-ups and evaluations of food reintroduction should be performed independent of the outcome of a food challenge.