| 1. |
- Abraha Derbew, Atakelti, 1976-
(author)
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Bridging gaps in under-five child health : a comprehensive assessment of their social determinants and the health system performance in Tigray, Ethiopia
- 2024
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Doctoral thesis (other academic/artistic)abstract
- Background: Achieving the Sustainable Development targets related to child health necessitates a deep understanding of the multifaceted factors influencing their health.Aim: To comprehensively examine the social determinants of the access to, and quality of, child health services, and the performance of the health system in the region of Tigray.Methods: The study was conducted in six randomly selected rural districts of Tigray. The study employed focus group discussions and interviews (sub-study I), a retrospective case-control study (sub-study-II), a capture recapture method (sub-study III), and a two-stage mortality survey (sub-study IV).Results: Sub-study I: underscored a good knowledge on the causes and management of common childhood morbidity, and that the health posts were conveniently located and provided trusted services. However, several barriers to using health services were identified. These included cultural beliefs, seasonal mobility, economic constraints, limited decision-making power for women, and accessibility challenges.Sub-study II: Revealed that only 76% of eligible children born to HIV-positive mothers were tested, with 17% testing positive for HIV, and only 29% of them linked to anti-retroviral treatment.Sub-study III showed that the concordance correlation coefficient between the Family Folder data and the household survey for the total population, reproductive age women, and under-five year child population were all above 0.73, while they were close to zero for other child health parameters. Tracing and recording neonatal deaths, and the aggregation of data at various levels were the major operational challanges.Sub-study IV identified infectious diseases (52.9%), neonatal causes (35.6%), nutritional disorders (6.6%) and external causes (4.3%) as the major causes of child death. The cause for 76 (16.2%) children was indeterminate. Tracing neonatal deaths and logistical challenges, especially in remote areas were the major operational issues of conducting the mortality survey.Conclusion: In spite of the improvements in health literacy, access to cost-free reproductive, maternal, neonatal and child health services and improved utilization, various interrelated social determinants, including cultural beliefs, financial barriers and health system-related factors continue to hinder the optimal utilization of essential child health services. Moreover, the health system’s performance in the prevention of mother-to-child transmission of HIV and its effect in reducing mortality among exposed children is generally poor. Policymakers in the region should focus on tackling those social determinants, including the health system, to improve children´s health. The community health information system showed promising potential. However, the operational issue of capturing neonatal deaths adequately and the process by which community data can be aggregated upwards through the health system has to be improved. The study underscored the viability of implementing a cause-specific mortality survey using health extension workers, and the need to standardize data collection tools and logistics before implementation on a larger scale.
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| 2. |
- Achour, Cyrinne, 1991-
(author)
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Canonical and non-canonical functions of METTL3 in breast cancer
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Gene expression is spatially and temporally regulated at multiple levels. N6-methyladenosine (m6A) is the most prevalent internal modification in messenger RNA (mRNA) and long noncoding RNA (lncRNAs). m6A plays important roles in multiple cellular processes including stem cell pluripotency, adipogenesis, spermatogenesis, neurogenesis, circadian rhythm and development by modulating RNA splicing, export, stability, degradation and translation. Although aberrant m6A methylation has been reported in various types of cancer, the underlying molecular functions of METTL3, the solely catalytic subunit of the m6A-methylase complex, has yet to be defined.m6A has been recently identified in nascent pre-mRNA, and more specifically intronic m6A has been linked to exon skipping events. The occurrence of impaired alternative splicing (AS) is frequently found during the development of cancer. We performed transcriptome wide analysis in breast cancer cell lines and explored AS events. Our results define an AS signature for breast tumorigenesis. We found that METTL3 modulates AS directly through m6A deposition at the intron-exon junctions or indirectly by the m6A deposition in transcripts encoding for splicing factors and transcription factors. In particular, we show that MYC mRNA harbours the m6A mark, suggesting that METTL3 regulates AS indirectly via the regulation of MYC expression. Indeed, the targets of MYC overlapped with METTL3-associated AS events. Importantly, five of the AS events identified and validated in vitro, are linked to a worse prognosis in breast cancer patients. Additionally, we show that METTL3 enhances the breast cancer phenotype through a dual mechanism depending on its sub-cellular localization. We find that the canonical nuclear function of METTL3 decorates transcripts that are involved in cell proliferation and migration. We observe that METTL3 is highly expressed in the cytoplasmic compartment of breast cancer cells from patients. Remarkably, we uncover that the cytoplasmic METTL3 interacts with subunits of the exocyst, whose subunit EXOC7 has been linked to cell adhesion, migration and invasion. Notably, we show that breast cancer cell lines depleted of METTL3 display less gelatinase activity and invadopodia formation, supporting the role of METTL3 in cell invasion via exocytosis.m6A is a reversible modification, which can be demethylated by the erasers FTO and ALKBH5. Depletion of FTO has been shown to increase the level of m6A in mRNA, however recent studies have reported that FTO could demethylate N6,2´-O-dimethyladenosine (m6Am), adjacent to the 7-methylguanosine cap on mRNA. In the cellular model of colorectal cancer CRC1, depletion of FTO leads to a cancer stem cell phenotype and confers chemotherapy resistance. By performing m6A-RNA immunoprecipitation followed by sequencing (MeRIP), we show that knockdown of FTO in CRC1 cells does not affect the global level of m6A in mRNA but of m6Am level.
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| 3. |
- Aliashkevich, Alena, 1990-
(author)
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Molecular mechanisms and biological consequences of the production of non-canonical D-amino acids in bacteria
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Most bacteria possess a vital net-like macromolecule – peptidoglycan (PG). PG encases bacteria around the cytoplasmic membrane to withstand the high internal turgor pressure and thereby protect the cell from bursting. In addition, PG is a major morphological determinant of bacteria being both required and sufficient to maintain cell shape. During cell growth PG hydrolysis and synthesis are tightly controlled to keep proper cell shape and integrity at all times. Given the essentiality of PG for bacterial growth and survival, the synthesis of this polymer is a major target of many natural and synthetic antibiotics (e.g. penicillins, glycopeptides).For a long time, PG composition was considered to be conserved and static, however it’s now being recognized as a dynamic and plastic macromolecule. The structure and chemistry of PG is influenced by a myriad of environmental cues that include interkingdom/interspecies interactions. Recently, it was found that a wide set of non-canonical D-amino acids (D-amino acids different from D-Ala and D-Glu, NCDAAs) are produced and released to the extracellular milieu by diverse bacteria. In Vibrio cholerae these NCDAAs are produced by broad-spectrum racemase enzyme (BsrV) and negatively regulate PG synthesis through their incorporation into PG. We have shown that in addition to D-Met and D-Leu, which were reported previously, V. cholerae also releases high amounts of D-Arg, which inhibits a broader range of phylogenetically diverse bacteria. Thus, NCDAAs affect not only the producer, but might target other species within the same environmental niche. However, in contrast to D-Met, D-Arg targets cell wall independent pathways. We have shown that non-proteinogenic amino acids also can be racemized by Bsr. A plant amino acid L-canavanine (L-CAN) is converted into D-CAN by a broad-spectrum amino acid racemase (BSAR) of the soil bacterium Pseudomonas putida and subsequently released to the environment. D-CAN gets highly incorporated into the PG of Rhizobiales (such as Agrobacterium tumefaciens, Sinorhizobium meliloti) thereby affecting the overall PG structure, bacterial morphogenesis and growth fitness. We found that detrimental effect of D-CAN in A. tumefaciens can be suppressed by a single amino acid substitution in the cell division PG transpeptidase penicillin-binding protein 3a (PBP3a). Rhizobiales are a polar-growing species that encode multiple LD-transpeptidases (LDTs), enzymes that normally perform PG crosslinking, but that can also incorporate NCDAAs into termini of the PG peptides. As these species incorporate high amounts of D-CAN in their PG, we hypothesized that LDTs might represent the main path used by NCDAAs to edit A. tumefaciens’ PG and cause their detrimental effects. Therefore, we decided to further explore the significance of LDT proteins for growth and morphogenesis in A. tumefaciens. While in the Gram-negative model organism E. coli LDT proteins are non-essential under standard laboratory conditions, we found that A. tumefaciens needs at least one LDT for growth out of the 14 putative LDTs encoded in its genome. Moreover, clustering the LDT proteins based on their sequence similarity revealed that A. tumefaciens has 7 LDTs that are exclusively present among Rhizobiales. Interestingly, the loss of this group of LDTs (but not the rest) leads to reduced growth, lower PG crosslinkage and rounded cell phenotype, which suggests that this group of Rhizobiales- specific LDTs have a major role in maintaining LD-crosslinking homeostasis, which in turn is important for cell elongation and proper shape maintenance in A. tumefaciens.
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| 4. |
- Amani, Paul Joseph, 1975-
(author)
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Does health insurance contribute to improving responsiveness of the health system? : the case of elderly in rural Tanzania
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Financing healthcare in Tanzania has for years depended on out-of-pocket payments. This mechanism has been criticized as being inefficient, contributing to inequity and high cost as well as denying access to healthcare to those most in need, including the elderly in rural areas. Health insurance (HI) was recently introduced as an instrument to enable equitable access to healthcare and thus to improve the responsiveness of the health system. Even though health insurance is expected to bring benefits to those who are insured, there is a lack of specific studies in the country looking at the role of HI in facilitating the health system responsiveness among vulnerable populations of remote areas.Aim: The aim of this thesis is to understand if and how health insurance contributes to improving the responsiveness of the healthcare system among the elderly in rural Tanzania. Methods: Four interrelated sub-studies (2 quantitative and 2 qualitative) were conducted in Igunga and Nzega districts of Tabora region between July 2017 and December 2018. The first two sub-studies are based on a household survey using an adapted version of the World Health Organization’s Study on Global Ageing and Adult Health questionnaire. Elderly people aged 60 years and above who had used both outpatient and inpatient healthcare three and twelve months prior to the study, respectively, were interviewed. Whereas in sub-study 1 the focus was to investigate the role of health insurance status on facilitating access to healthcare, sub-study 2 assessed the relationship between health insurance and the health system responsiveness domains. In sub-study 3, interviews with healthcare providers were carried out to capture their perspective regarding the functioning of the health insurance. In the final sub-study 4, focus group discussions with elderly were conducted in order to explore their experience of healthcare, depending on their health insurance status. Crude and adjusted logistic and quantile regression models were applied to analyse the association between health insurance and access to healthcare (sub-study 1) and responsiveness (sub-study 2), respectively. For both sub-studies 3 and 4, qualitative content analysis was used to analyse the data.Results: Sub-studies 1 and 2 involved a total of 1899 insured and uninsured elderly, while sub-studies 3 and 4 included 8 health providers and 78 elderlies respectively. Sub-study 1 showed that about 45% of the elderly were insured and HI ownership improved access and utilization of healthcare, both outpatient and inpatient services. In sub-study two, however, health insurance was associated with a lower responsiveness of the healthcare system. In general, all six domains: cleanliness, access, confidentiality, autonomy, communication, and prompt attention were rated high, but three were of concern: waiting time; cleanliness; and communication. Sub-study 3 uncovered several challenges coexisting alongside the provision of insurance benefits and thus contributing to a lower responsiveness. These included shortage of human resources and medical supplies, as well as operational issues related to delays in funding reimbursement. In sub-study 4, the elderly revealed that HI did not meet their expectations, it failed to promote equitable access, provided limited-service benefits and restricted use of services within residential areas. Conclusion: While HI seems to increase the access to and use of healthcare services by the elderly in rural Tanzania, a lower responsiveness by the healthcare system among the insured elderly was reported. Long waiting times, limited-service benefits, restricted use of services within schemes, lack of health workforce in both numbers and skills as well as shortage of medical supplies were important explanations for the lower responsiveness. The results of this thesis, while supporting the national aim of expanding HI in rural areas, also exposed several weaknesses that require immediate attention. There is a need to, first, review the insurance policy to improve its implementation, expand the scope of services coverage, and where possible, to introduce cross-subsidization between the publicly owned schemes; additionally, improvements in the healthcare infrastructure, increasing the number of qualified health workforce and the availability of essential medicines and laboratory services, especially at the primary healthcare facilities, should be prioritized and further investments allocated.
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| 5. |
- Andersson-Evelönn, Emma, 1983-
(author)
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DNA methylation as a prognostic marker in clear cell Renal Cell Carcinoma
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Clear cell renal cell carcinoma (ccRCC) is the most common type of renal cell carcinoma worldwide. Metastatic ccRCC is correlated to poor prognosis whereas non-metastatic disease has a 5-year survival rate up to 90%. Due to increased accessibility to different types of diagnostic imaging the frequency of metastatic ccRCC at diagnosis has decreased since the beginning of the 21st century. This has led to an earlier detection of primary tumors before patients present symptoms. However, 20-30% of the non-metastatic patients at diagnosis will progress and metastasize within five years of primary nephrectomy. Identifying patients at high risk of tumor progression at an early stage after diagnosis is of importance to improve outcome and survival. Currently, in Sweden, the Mayo scoring system is used to divide tumors into low, intermediate or high risk for tumor progression.DNA methylation has been associated with tumor development and progression in different malignancies. In this thesis, Illumina Infinium HumanMeth27 BeadChip Arrays and Human Meth450K BeadChip Arrays have been used to evaluate the relationship between methylation and clinicopathological variables as well as ccRCC outcome in 45 and 115 patients.Our studies identified an association between higher level of promoter-associated DNA methylation and clinicopathological variables in ccRCC. There was a significant stepwise increase of average methylation from tumor-free tissue, via non-metastatic tumors to metastatic disease. Cluster analysis divided patients into two distinct groups that differed in average methylation levels, TNM stage, Fuhrman nuclear grade, tumor size, survival and tumor progression. We also presented two prognostic classifiers for non-metastatic tumors; the promoter methylation classifier (PMC) panel and the triple classifier. The PMC panel divided tumors depending on the methylation level, PMC low or PMC high, with significantly worse prognosis in the PMC high group. This data was verified in an independent, publically available cohort. The triple classifier was created using a combination of clinicopathological variables, previously identified CpGs biomarkers and a novel cluster analysis approach (Directed Cluster Analysis). The triple classifier had a higher specificity compared to the clinically used Mayo scoring system and predicted tumor progression with higher accuracy at a fixed sensitivity.The identification of two epigenetic classifiers that predicted outcome in non-metastatic ccRCC further establishes the role of DNA methylation as a prognostic marker. This knowledge can contribute to identification of patients with a high risk of tumor progression and can be of importance in the decision regarding adjuvant treatment post-nephrectomy.
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| 6. |
- Andersson, Johanna, 1990-
(author)
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Idiopathic normal pressure hydrocephalus : epidemiology and diagnostics
- 2021
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Doctoral thesis (other academic/artistic)abstract
- Idiopathic normal pressure hydrocephalus (iNPH) is a progressive neurological condition characterized by a deterioration of gait, cognition, and continence. The diagnosis is based on a combination of enlarged ventricles seen in neuroimaging, with typical clinical findings. iNPH often affects elderly individuals (i.e., over the age of 65). Shunt insertion is the only available treatment, with an improvement rate of up to 80%.The prevalence has previously been reported to be between 0.5 and 3% among individuals over age 65. However, most previous studies have been conducted on hospital-based materials, and there is a lack of epidemiological studies based on the general population. One of the challenges of diagnosing iNPH is that there are no common, widely accepted diagnostic criteria. There are currently two different diagnostic guidelines: the American-European guidelines and the Japanese ones, which makes it harder to compare different studies.The aim of this thesis was to determine the prevalence of iNPH in population-based materials and to evaluate the differences between the diagnostic guidelines. Furthermore, we wanted to assess the quality of life and depressive symptoms among individuals with iNPH compared to those without. In addition, we assessed longitudinal changes in the clinical and radiological findings of iNPH.We asked 1,000 individuals aged 65 and older to participate in the study by answering a questionnaire containing typical iNPH symptoms. We invited all participants who had marked at least two symptoms on the questionnaire for further investigation, in addition to a randomly selected group with fewer than two symptoms. A total of 168 participants underwent clinical examinations and computed tomography (CT) of the brain. We followed up with the same cohort two years later with repeated testing, with the addition of questionnaires on depressive symptoms and quality of life. A total of 122 individuals remained in the 2-year follow-up cohort. The clinical examinations included an iNPH-specific grading scale for symptoms and neurological examinations.The prevalence of iNPH for those 65 years and older was 3.7% according to the American-European guidelines and 1.5% according to the Japanese guidelines. The prevalence was higher for those over age 80, with no differences between the sexes. Furthermore, participants with iNPH had more depressive symptoms and lower quality of life than those without iNPH. Radiological findings and symptoms progressed slightly over two years, and those with symptom deterioration had an even higher degree of radiological progress compared to those with stationary or improved symptoms.This thesis shows that iNPH is fairly common in a normal population of elderly individuals. There is disagreement between the current diagnostic guidelines, which underscores the need for revisions, preferably into one common diagnostic system. In this thesis, individuals with iNPH had a lower functional status, more depressive symptoms, and lower quality of life than those without iNPH.Moreover, iNPH progresses slightly in both symptoms and radiological signs over two years, which underlines the value of clinical follow-up for asymptomatic individuals with radiological signs of iNPH. Finally, iNPH is probably underdiagnosed and an important diagnosis to consider in an elderly person with gait and balance impairments.
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| 7. |
- Andersson, Therese, 1983-
(author)
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Acute Pulmonary Embolism : not just an acute condition after all
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Acute pulmonary embolism (PE) is the third most common cardiovascular disease following myocardial infarction and stroke. Despite diagnostic improvements, the diagnosis of PE is still associated with many difficulties, as the symptoms of an acute PE are nonspecific. Even though an acute PE is associated with a high short-term mortality, less attention has been given to long-term mortality. In addition, the clinical course following an acute PE may be accompanied by substantial morbidity, and one feared complication is chronic thromboembolic pulmonary hypertension (CTEPH), a progressive pulmonary vasculopathy. In addition to CTEPH, increasing evidence suggests that a large proportion of patients report persistent functional impairment several years after an acute PE. Recently, the term chronic thromboembolic pulmonary disease (CTEPD) has been proposed for those with remaining symptoms and signs of residual thrombotic material in the pulmonary arteries. Methods and Results: A nation-wide Swedish cohort of all patients (n= 5793) diagnosed with an acute PE in 2005 was identified. The incidence of PE was 0.6/1000 person-years, and during a 4-year follow-up, the mortality was more than doubled compared with an age- and sex-matched control group. We found that the acute PE associated with multiple comorbidities, and with cardiovascular diseases in particular. All surviving patients in 2007 (n=3510) were invited to answer a questionnaire regarding dyspnea and related comorbidities. We demonstrated a substantially higher prevalence of both exertional dyspnea (53.0% vs. 17.3%) and wake-up dyspnea (12% vs. 1.7%) in patients compared to controls from the Northern Sweden MONICA study. Furthermore, PE associated independently with dyspnea in a multivariable analysis. Through a manual review of approximately 10 % of the patient’s medical records, a positive predictive value of 79% was found for the PE diagnosis. Post-PE patients with remaining dyspnea and/or previously known risk factors for CTEPH development were referred for blood sampling and levels of N-terminal (NT)-prohormone (pro) brain-type natriuretic peptide (BNP) were determined. Thereafter, they were referred to their local hospital for a pulmonary ventilation/perfusion (V/Q) scintigraphy and echocardiography. Approximately 45% of the V/Q-scans showed perfusion defects and 27 % of echocardiographies showed signs of pulmonary hypertension. In total, 24 cases of CTEPH were identified, resulting in a prevalence of 0.4 % (95 % confidence interval 0.2 %–0.6 %). Conclusion: An acute PE is a serious event, associated with decreased survival, multiple comorbidities, frequent dyspnea, and pathological investigational findings. The term CTEPD seems reasonable as it captures that this is a disease of the pulmonary vasculature, and that pharmacological and surgical interventions used for CTEPH may be useful. Regardless, proper follow-up after acute PE is essential for timely identification of patients in need of appropriate investigations and care.
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| 8. |
- Asklund, Ina, 1978-
(author)
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A mobile app for self-management of urinary incontinence : treatment effect and user experience
- 2020
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Doctoral thesis (other academic/artistic)abstract
- Background Urinary incontinence affects 25-45% of all women. The most common type is stress urinary incontinence, which is the leakage of urine on physical exertion. Pelvic floor muscle training is an effective first-line treatment for this condition but many women do not seek help from their ordinary health care service. There is a need to evaluate new methods to offer effective treatment, and internet-based treatment has previously been found to be effective for women with stress urinary incontinence.Aim To evaluate the mobile app Tät® which has a self-management program focused on pelvic floor muscle training for women with stress urinary incontinence, with respect to treatment effect, factors associated with successful treatment, user experience and use by pregnant and postnatal women.Methods Papers I, II and III are based on the same study population from a randomized controlled trial (RCT). We recruited adult women who had stress urinary incontinence at least weekly via our website. In total, 123 women were randomized to the app group (n=62) or the control group (n=61). The app included information about incontinence, the pelvic floor and lifestyle factors associated with incontinence, pelvic floor muscle training exercises and functions for reminders and training statistics. Treatment outcome after three months was evaluated using validated questionnaires assessing incontinence symptoms, quality of life, subjective improvement and a leakage diary. Outcomes were compared between the two groups. Factors associated with a successful outcome in the app group were further analysed using logistic regression. We strategically selected 15 women who had used the app and interviewed them about their experiences of using the app. The interviews were analysed according to Grounded Theory. After closing the RCT we made the app freely available and continued to follow its use on a larger scale by incorporating an anonymous questionnaire that appeared within the app upon download and after three months. The data from these questionnaires is used in paper IV. Results Participants in the RCT had a mean age of 44.7 years (range 27-72) and 120 of the 123 women had moderate/severe incontinence. The app group reported significant improvements in the primary outcomes, the incontinence symptom score (mean ICIQ-UI SF reduction 3.9, 95% CI 3.0-4.7) and the quality of life score (mean ICIQ LUTSqol reduction 4.8, 95% CI 3.4-6.2), and the difference between the groups was significant. The app group also reduced their number of leakages and use of incontinence aids compared to the control group. At follow-up 92% of women in the app group experienced subjective improvement and 56% had improved “much” or “very much” and were classified as having a successful treatment outcome.Factors associated with a successful outcome were higher expectations of treatment effect (OR 11.38, 95% CI 2.02-64.19), weight control (OR 0.44 per kg gained, 95% CI 0.24-0.79), and self-assessed improvement of pelvic floor muscle strength (OR 35.54, 95% CI 4.96-254.61).The main finding from the interviews was that women experienced that the app “enabled their independence”. They described that the app was “something new” that helped with “keeping motivation up” although they sometimes wondered whether their training efforts were “good enough”.The freely available app was downloaded by 10,456 pregnant and postnatal women during a period of ten months (41% of all users). At inclusion 51% experienced incontinence and their mean ICIQ-UI SF score was 6.7 (SD 3.45). After three months, 1,805 women answered the follow-up. The majority of women with incontinence at inclusion experienced improvement with greater improvement in the postnatal group than in the pregnant group.Conclusion The mobile app Tät® offers a new, easily accessible and effective self-management program for women with stress urinary incontinence. Women appreciated that the app enabled them to manage their pelvic floor muscle training independently. Once the app was freely released it reached a large population with many pregnant and postnatal women. We believe that the app could be useful for the prevention of urinary incontinence among pregnant women. We also believe that the app could be used both as a stand-alone treatment and as a complement to other treatments provided by the ordinary health care service.
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| 9. |
- Asplund, Sofia, 1982-
(author)
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Work-related stress among municipal employees in rural northern Sweden
- 2022
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Doctoral thesis (other academic/artistic)abstract
- Background: Many rural municipalities in Sweden are facing challenges like depopulation, decreased economy, and difficulties in recruiting staff. Living and working in rural areas may involve adverse working conditions and higher risks of ill-health. Work is generally good for employee health, but various physical and psychosocial aspects of work can also be hazards and cause work-related stress, health problems, reduced productivity, and long-term sick leave. Leadership by managers in the organisation is important for the work environment, work performance, and occupational health of employees. The Swedish municipal sector employs almost 20% of employees in the labour market, where school, preschool and care of older people are the dominating areas. Previous research has shown that there are adverse psychosocial working conditions in Swedish municipal organisations. The municipal sector has the highest rate of long-term sick leave compared to other sectors in the labour market, mainly due to stress-related disorders, such as exhaustion disorder (ED). Therefore, it is important to focus on organisational and psychosocial work environments, work-related stress, and health in the municipal sector of rural northern Sweden.Aim: The overall aim was to explore organisational and psychosocial work environments, work-related stress, and health among municipal employees in rural northern Sweden.Methods: Both quantitative and qualitative methods were used to collect data. Study I and II had a quantitative approach, a cross-sectional design, and used a questionnaire for collecting data. Participants were employees (n =1093) in the municipal sector in two municipalities in rural northern Sweden. The questionnaire was constructed to contain instruments measuring the organisational and psychosocial work environments, perceived stress, self-rated exhaustion disorder (s-ED), and physical activity. Quantitative data were analysed using logistic regression in Study I, and partial least squares regression in Study II. Studies III and IV had a qualitative approach. In Study III, semi-structured individual interviews were conducted with 15 municipal employees with high self-reported stress. In Study IV, semi-structured individual interviews were conducted with 15 managers at different levels in the municipal sector. All qualitative data were analysed using inductive qualitative content analysis.Results: In Study I, results showed that 21.5 % of the municipal employees reported s-ED.Cognitive problems, sleep problems,depressiveivsymptoms, high stress, poor self-rated health, and stomach problems were the health-related factors most strongly associated with s-ED. In Study II, results showed that there were significant differences between the s-ED and the non–s-ED group in all but one of the 32 organisational and psychosocial environmental work factors. Various demands—i.e., quantitative, emotional, intellectual—and work conflicts were important factors associated with s-ED. Social support, resources, and time for work and reflection were important factors associated with non–s-ED. Findings from Study III showed that the employees with high self-reported stress experienced feelings of suffering through endless chaos when they worked in an organisation with high demands and low resources, control, and support. They also experienced feelings of insufficiency, and negative effects on health and family life. Findings from Study IV showed that managers in the municipal sector experienced feelings of striving for stability on shaky ground. They struggled inside slimmed-down organisations with a substitute shortage and reduced means, were burdened by conflicting demands, and experienced health and family life impairments. Managers expressed the importance of motivation, social support, and coping strategies.Conclusion: This thesis illuminates adverse psychosocial working conditions among municipal employees in two municipalities in the rural context of northern Sweden, where a stressful work environment, s-ED and health impairments are relatively common.It also provides important insights of municipal employee’s experiences of work-related stress, the importance of acknowledging suffering, and managers’ experiences of working in municipal organisations with shrinking resources, as in addition to a work–family imbalance. It seems important that organisations in the municipal sector have supportive and effective leadership, and allow employees control over their work. Furthermore, it seems important that various demands are balanced by sufficient resources; such as staff, social support, and economic resources in order to prevent work-related stress. Findings from this thesis can contribute to future interventions, aiming to prevent work-related stress and improve occupational well-being and work performance. They also have value for development work in municipal organisations.
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| 10. |
- Awad, Amar, 1988-
(author)
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Functional brain imaging of sensorimotor dysfunction and restoration : investigations of discomplete spinal cord injury and deep brain stimulation for essential tremor
- 2022
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Doctoral thesis (other academic/artistic)abstract
- The nervous system exists to generate adaptive behaviour by processing sensory input from the body and the environment in order to produce appropriate motor output, and vice versa. Consequently, sensorimotor dysfunction is the basis of disability in most neurological pathologies. In the current thesis, I explore two conditions with different types and degrees of sensorimotor dysfunction by means of functional magnetic resonance imaging (fMRI). In part 1, I assess residual sensory connections to the brain in clinically complete spinal cord injury (SCI) with seemingly complete loss of sensorimotor function below the injury level. In part 2, fMRI is combined with deep brain stimulation (DBS) to investigate interventional mechanisms of restoring dysfunctional sensorimotor control in essential tremor (ET).Part 1: SCI disrupts the communication between the brain and below-injury body parts, but rarely results in complete anatomical transection of the spinal cord. In studies I and II, we demonstrate somatosensory cortex activation due to somatosensory (tactile and nociceptive) stimulation on below-level insensate body parts in clinically complete SCI. The results from studies I and II indicate preserved somatosensory conduction across the spinal lesion in some cases of clinically complete SCI, as classified according to international standards. This subgroup is referred to as sensory discomplete SCI, which represents a distinct injury phenotype with an intermediate degree of injury severity between clinically complete and incomplete SCI.Part 2: ET is effectively treated with DBS in the caudal zona incerta, but the neural mechanisms underlying the treatment effect are poorly understood. By exploring DBS mechanisms with fMRI, DBS was shown to cause modulation in the activity of the sensorimotor cerebello-cerebral regions during motor tasks (study III), but did not modulate the functional connectivity during resting-state (study IV).fMRI is a valuable tool to investigate sensorimotor dysfunction and restoration in SCI and DBS-treated ET. There is evidence for sensory discomplete SCI in about half of the patients with clinically complete SCI. DBS modulates DBS modulation of the activity in the sensorimotor cerebello-cerebral circuit during motor tasks, but not during resting-state, is action-dependent.
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