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  • Disputas: 2019-10-25 09:00 9D, 9th Floor, Tandläkarhuset, Umeå
    Tinc, Pamela J.
    Umeå universitet, Medicinska fakulteten, Institutionen för epidemiologi och global hälsa.
    Raising the (roll)bar: exploring barriers and facilitators to research translation in US public health2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Background In public health, implementation science work is crucial to protecting the safety and health of populations. Despite this, such efforts have been extremely limited within the specific public health field of occupational safety and health. The overall aim of this thesis is to examine the concept of research translation, the barriers and facilitators that researchers have faced in translating research to the worker environment, and the process of scaling up an evidence-based agricultural safety program. Additionally, this study will provide an opportunity to adapt the clinically based Consolidated Framework for Implementation Research (CFIR), as well as the Proctor Taxonomy (of implementation outcomes), to occupational safety settings.

    The implementation research conducted within this dissertation is focused on a case study in agricultural safety. With an annual fatality rate seven times higher than the all-worker fatality rate, agriculture is one of the most dangerous occupations to work in. Though nearly all aspects of farming can be considered dangerous, tractor overturns claim the greatest number of lives. Rollover protective systems (ROPS) are 99% effective in preventing death and disability in the event of an overturn when used with seatbelts. The ROPS Rebate Program was developed in 2006 to encourage the installation of retrofit ROPS in New York State and has been shown to be effective in this goal and in the long-term goal of reducing overturn fatalities. After expanding to six additional states, the National Tractor Safety Coalition was formed in order to facilitate the scaling up of the ROPS Rebate Programs. The National ROPS Rebate Program (NRRP) was formally announced in June 2017, though implementation of it is currently ongoing. 

    Methods This dissertation is composed of five sub-studies which applied a mixed methods approach. Sub-study I consisted of a scoping literature review. Manuscripts were identified through six databases to explore how research translation is discussed among the research community. In addition, the review aimed at assessing the T0-T4 model of research translation (first developed by the National Institutes of Health) as it applies to agriculture, forestry, and fishing safety and health and used knowledge gained through the review to make modifications to this model.

    To apply the CFIR and Proctor Taxonomy to agricultural safety settings (sub-study II), a survey was developed to assess the relevance of the constructs included in each framework to the NRRP implementation. The final survey was distributed to members of the National Tractor Safety Coalition. Using the results from this survey, quantitative and qualitative evaluation tools were developed.

    Sub-study III utilized a repeat measure survey collected at four time points to capture changes in CFIR and Proctor constructs over time. Correlational analyses were conducted to compare each survey item to three outcome measures: state progress toward securing rebate funding for the Program, farmers intakes into the Program, and completed retrofits

    Thirteen individuals participated in qualitative research interviews for sub-study IV; nine of these individuals also participated in follow-up interviews. Interview guides were developed based on the survey results in sub-study III. Grounded Theory Situational Analysis was used to analyze each set of data. 

    Sub-study V was developed as a result of missing data from sub-studies III and IV. To conduct this analysis, media reports published about the ROPS Rebate Programs were collected. Discourse analysis for print media was used to assess the media reports in comparison to the ROPS Rebate Program trajectory in each state and nationally. 

    ResultsSub-study I led to the development of a modified T0-T4 research translation model, which takes into account the real-life challenges in moving proven innovations into widespread practice. The remaining sub-studies in this dissertation focused in the T3 phase of this model (widespread adoption). Sub-study II led to the identification of 21 CFIR and Proctor constructs that National Tractor Safety Coalition members believed would be important to the NRRP implementation. Sub-study III demonstrated that eight CFIR and Proctor constructs were highly correlated (rho ≥ 0.5) with at least one of the outcome measures (progress, intakes, or retrofits). Two primary themes were developed from the qualitative portion of the study (sub-study IV): 1) the implementation strategy evolved inconsistently across stakeholders, and 2) stakeholder engagement is a function of perceived feasibility and "small wins." Finally, sub-study V identified components of successful media strategies for implementation including diversity in actors and messages, timing, and frequency. In total, sub-studies III-V identified 27 CFIR and Proctor constructs that were relevant to the implementation of the NRRP, 10 of which were identified in more than one study. 

    ConclusionsThis dissertation has served to examine, specifically, the implementation of the NRRP, and more generally, the field of implementation science as it applies to occupational safety and health. The methods applied in this study as well as the findings have resulted in: application of implementation frameworks to the field of agricultural safety and health, assessment of the unique challenges associated with initiatives to scale up innovations, assessment of implementation from the perspective of the CFIR and Proctor Taxonomy, and assessment of the use of media advocacy as an implementation strategy. The knowledge gained through this research will be helpful in improving the implementation of the NRRP and in developing implementation science efforts within the specific public health field of occupational safety and health. 

  • Disputas: 2019-11-01 09:00 KBE301, Umeå
    Engvall, Sara
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för naturvetenskapernas och matematikens didaktik.
    Opening the black box of mathematics teachers’ professional growth: a study of the process of teacher learning2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    There is a lot of research done on professional development programs for teachers, especially with a focus on different characteristics of the program and whether it makes teachers change their teaching practice to such an extent that it enhances student achievement. However, there is not much research done on the learning process. As long as we do not open the black box of teacher learning it is difficult to say anything about what characteristics in a professional development program actually are important for teachers to learn, develop and grow as professionals.

    The aim of the thesis is to better understand the process of teacher learning while participating in aprofessional development program. The focus is on different aspects of the process of teacher professional growth, as well as on external factors that have an impact on the process of learning. The participants are secondary school teachers that participated in a professional development program in formative assessment. The data have been collected during and after the professional development program took place. Different types of data have been used in this thesis; teacher interviews, classroom observations and questionnaires, and have been collected over a time period of two and a half years. In two of the included papers the studies focus on four mathematics teachers, and the learning process is explored from two different perspectives: how the professional growth can develop, and how their testing of formative assessment activities relates to their understanding of formative assessment. In one of the papers all secondary school teachers are included and a comparison in expectancy of being able to use high quality formative assessment after the professional development program between the mathematics teachers and the other teachers were conducted. In the fourth paper focus is on all mathematics teachers in the study and their motivation are investigated over a time period of two years.

    The four papers take different perspectives to explore the professional growth for teachers while participating in a professional development program in formative assessment. The results show the complexity of teacher learning and indicate that large-scale implementations risk being inefficient and not reach the intended goals.

  • Disputas: 2019-11-07 09:00 KBF301-Stora Fokusrummet-KBC, Umeå
    Javadi, Ala
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten).
    Filament assembly and structural studies of intermediate filament like protein, FilP, in Streptomyces coelicolor2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    The cytoskeleton, known as intracellular connected filaments, has a prominent role in cellular behavior, motility, and stability. The following three major types of polymers have been characterized as cytoskeleton in eukaryotes: microtubules that are 25 nm in diameter, actin filaments that are 7 nm in diameter, and intermediate filaments (IF) that are 10 nm in diameter. IFs, unlike actin and microtubules, are not polarized and do not facilitate the directional movement of molecular motors. Further, IF assembly is different from that of actin and tubulin because they are independent of cofactors and they undergo instant self-assembly based on hydrophobic interactions.

    Cytoskeleton proteins were initially thought to be unique to eukaryotic cells, but we now know that all three cytoskeleton types have bacterial counterparts. Bacterial cytoskeleton is a novel field and it is less characterized than the eukaryotic cytoskeleton. The IF subfamily in bacteria are called IF-like proteins because of the lack of conserved sequences. FilP is a bacterial IF-like protein that is localized to the sub-apical area of Streptomyces coelicolor hyphae tips. Moreover, FilP forms two distinct structures in vitro, as follows: 1) filaments in branching bundles with a repetitive striation pattern of 60 nm intervals between the repeats; and 2) an interconnected hexagonal meshwork, which has a three-dimensional morphology with the same 60 nm unit. There have been several studies on different IF-like proteins from different bacterial species; however, there are no studies that have investigated their assembly mechanism or atomic resolution of their structures before this study.

    We present the first filament assembly model of an IF-like protein. The hierarchical stages of filament assembly were characterized and analyzed by utilizing physiological effects of different buffer systems. The basic building block was characterized by a single particle classification, revealing the length of primary coiled-coil unit. The following steps of protofilament assembly and filament bundling were revealed using negative-staining electron microscopy together with solubility assay and cryo-electron tomography. We demonstrated similarities and differences of FilP filamentation to eukaryotic IF lamin, because they both showed filaments with similar morphology in in vitro conditions. In a cytoplasm-mimicking buffer (Polymix), FilP proteins form hexagonal meshworks. By subjecting FilP to the ion components of the Polymix buffer, we found that K+ and Na+ triggered FilP meshwork formation and increased its solubility.

    Guided by the in vitro assembly studies of FilP we crystallized the FilP amino acid (aa) 184–288 fragment, which is a tailless construct containing the C-terminal coiled-coil domain of the FilP rod domain to 2.3 Å resolution. The crystal structure of the 184–288 fragment revealed that the C-terminus of FilP rod domain is composed of one single coiled-coil. Arrangement of the crystal indicated the formation of parallel homo-dimers and dissociation of the homo-dimers at the C-terminus, forming an open and fork-like structure. Further, the fork-like structure facilitates the end-to-end association of homodimers. These experiments were complimented by testing constructs containing different coiled-coil domains for in vitro filament assembly and their in vivo capability to restore the FilP phenotype ΔfilP S. coelicolor. Based on these findings, we showed a model for the in vitro FilP filament formation.

    We have shown that FilP, like its orthologous in other Streptomyces species, has cellulose affinity. Investigation of cellulose affinity of other IF-like proteins and eukaryotic IF protein such as lamin showed that cellulose binding of certain coiled-coil domains is an intrinsic property of all the tested IF and IF-like proteins and thereby adds IF coiled-coil domains to the list of carbohydrate binding motifs. Building upon this, coiled-coil domains of FilP can be utilized to purify recombinant fusion proteins from S. coelicolor and Escherichia coli lysates. We used truncated constructs of FilP to find the coiled-coil domains with the highest affinity for cellulose, which can be used as a cellulose affinity tag.

  • Disputas: 2019-11-08 09:00 Konferenscentrum, Aulan, Sunderby Sjukhus, Luleå
    Sawalha, Sami
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin.
    Chronic obstructive pulmonary disease: clinical phenotyping, mortality and causes of death2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]


    Chronic obstructive pulmonary disease (COPD) is common. The estimated prevalence is about 10% among adults, but varies largely dependent on the major risk factors age and smoking. Under-diagnosis of COPD is substantial and is related to disease severity. Thus, subjects with mild to moderate COPD are underrepresented in medical registers among health care providers as well as in national registers. Post- bronchodilator (BD) spirometry is mandatory for the diagnosis of COPD, but not sufficient to assess and manage COPD. Phenotyping based on spirometry and clinical manifestations can make it easier to apply individual assessment of subjects with COPD. COPD is a systemic disease with pulmonary and extra-pulmonary manifestations and comorbidities are common. Comorbidities most probably contribute to the observed increased mortality among subjects with COPD, however, the impact of comorbidities on mortality and causes of death among subjects with mild to moderate COPD is unclear. Furthermore, there seems to be sex-dependent differences with regard to susceptibility to risk factors, clinical manifestation and outcomes.


    The overall aim of this thesis was to identify and characterize clinical relevant COPD phenotypes in population-based studies, using spirometry together with clinical characteristics such as respiratory symptoms, exacerbations, and comorbidities, and their impact on mortality and further, also cause of death.


    This thesis is based on data from the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study. The study population was recruited in the years 2002-2004, when all 993 individuals with (FEV1/VC<0.70) were identified after examinations of population-based cohorts, together with age- and sex-matched non-obstructive referents (n=in total 1,986). In this thesis, cross-sectional data from recruitment were used together with mortality data from the Swedish Tax Agency from the date of recruitment in 2002-2004 and onwards. Data on cause of death was collected from the Swedish National Board for Health and Welfare register for all deaths until 31 December 2015. Spirometry was used to identify the following spirometric groups, in paper I: Non-COPD (FEV1/VC≥0.70); COPD (pre- BD FEV1/VC<0.70); in paper II: Non- obstructive (FEV1/VC≥0.70), Pre- not post-BD obstructive (pre- not post-BD FEV1/VC<0.70); COPD (post-BD FEV1/VC<0.70); In paper III: Normal Lung Function (NLF, FEV1/VC≥0.7 & FVC≥80% predicted), COPD (post BD FEV1/VC<0.70) and Lower Limit of Normal COPD (LLN-COPD, the LLN criterion applied among those with COPD); in paper IV: NLF and COPD defined as in paper III, and Restrictive Spirometric pattern (RSP, FEV1/VC≥0.70 & FVC<80% predicted). The OLIN-COPD study and collection of data on causes of death were approved by the regional ethical committee at Umeå University.


    Paper I: Subjects with COPD had more productive cough than non-COPD, and men more than women. Productive cough increased the risk for exacerbations in COPD and non-COPD and productive cough was associated with worse survival in both groups. In adjusted models (HR;95%CI) the increased risk for death associated with productive cough among those with COPD persisted (1.48;1.13-1.94) when compared with non-COPD without productive cough, significantly so also among men with COPD (1.63;1.17-2.26), but not among women (1.23;0.76-1.99).

    Paper-II: Pre-BD spirometry misclassified every fourth subject as having COPD. Subjects with pre- but not post-BD obstruction were similar to subjects with COPD regarding reported ‘any respiratory symptoms’, asthma before the age of 40, exacerbations, and comorbidities. The cumulative mortality among subjects with pre- not post-BD obstruction was similar to among subjects in the non-obstructive group, still, the survival was better than among those with COPD. The increased risk for death for COPD persisted also in an adjusted model (1.24; 1.04-1.49) when compared with the non-obstructive group, and the pattern was similar among men and women (1.27; 1.00-1.60 and1.24; 0.92-1.13).

    Paper III: Men with COPD had more CVD and DM compared to women, while anxiety/depression (A/D) was more common among women than men in all spirometric groups. Men had a higher cumulative mortality than women in all groups. However, CVD seemed to have a greater impact on mortality among women than men, while anxiety/depression increased the risk for death similarly in both sexes. The use of the LLN criterion did not change the observed pattern.

    Paper IV: CVD was the most common cause of death in all spirometric groups, NLF, RSP and COPD, followed by cancer. Those with COPD and RSP had a similar and higher cumulative mortality than those with NLF. RSP and COPD had an increased risk for CVD death and respiratory death, independent of age, sex, smoking habits and BMI-category, however, the increased risk for CVD death did not reach statistical significance in RSP. In all the groups, the risk for deaths due to cancer was similar, however, lung cancer was more common in COPD than in NLF and RSP. The pattern was fairly similar among men and women. 


    Simple diagnostic procedures like history of respiratory symptoms, exacerbations, and comorbidity can, together with spirometry, contribute with important clinical classification of prognostic importance. Productive cough increased the risk for exacerbations in both COPD and non-COPD. The highest risk for exacerbations and death was observed among subjects with COPD and productive cough. It was impossible to distinguish COPD from those with pre- not post-BD obstruction based on the history of respiratory symptoms, asthma, exacerbations and comorbidities. Still, COPD was associated with an increased risk for death while pre- not post-BD obstruction had better survival than COPD but similar as non-obstructive. There were sex-dependent differences regarding comorbidities and mortality. CVD was less common among women but had a greater impact on mortality compared to among men while A/D, less common among men, increased the risk for death similarly in both sexes. CVD and cancer were the most common causes of death in all spirometric groups. RSP had a similar and higher mortality as COPD when compared with NLF. The risk for cancer-related death was similar in all groups, while the results indicated that COPD and RSP had an increased risk for CVD and respiratory death.

  • Disputas: 2019-11-08 09:00 N410, Naturvetarhuset, Umeå
    Nyberg, Markus
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för fysik.
    My first-passage: target search in physics and biology2019Doktoravhandling, med artikler (Annet vitenskapelig)
    Abstract [en]

    Random walks and diffusing particles have been a corner stone in modelling the random motion of a varying quantity with applications spanning over many research fields. And in most of the applications one can ask a question related to when something happened for the first time. That is, a first-passage problem. Typical examples include chemical reactions which can not happen until the constituents meet for the first time, a neuron firing when a fluctuating voltage exceeds a threshold value and the triggering of buy/sell orders of a stock option. The applications are many, which is why first-passage problems have attracted researchers for a long time, and will keep doing so. In this thesis we analyse first-passage problems analytically.

    A stochastic system can always be simulated, so why bother with analytical solutions? Well, there are many system where the first passage is improbable in a reasonable time. Simulating those systems with high precision is hard to do efficiently. But evaluating an analytical expression happens in a heart beat. The only problem is that the first-passage problem is tricky to solve as soon as you take a small step away from the trivial ones. Consequently, many first-passage problems are still unsolved.

    In this thesis, we derive approximate solutions to first-passage related problems for a random walker and a diffusing particle bounded in a potential, which the current methods are unable to handle. We also study a continuous-time random walker on a network and solve the corresponding first-passage problem exactly in way that has not been done before. These results give access to a new set of analytical tools that can be used to solve a broad class of first-passage problems.