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  • Disputation: 2018-10-19 09:00 Lilla hörsalen KBE301, Umeå
    Ghorbani, Ramin
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Real-time breath gas analysis of carbon monoxide: laser-based detection and pulmonary gas exchange modeling2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [sv]

    Detektion av spårgaser i utandningsluften har stor potential för icke-invasiv medicinsk diagnostik och fysiologisk övervakning. Realtid andningsgasanalys av enskilda andningscykler underlättar datatolkningen och kan förbättra det diagnostiska värdet av andningstester, eftersom utandningsprofiler bär spatiotemporal information om biomarkörens ursprung och gasutbyte i andningssystemet. Denna avhandling presenterar och granskar en ny analysmetod, där utandningsprofiler simuleras med hjälp av en matematisk modell för gasutbytet, och anpassas till uppmätta expirogram för att bestämma luftvägs- och alveolära bidrag och diffusionsförmågor. Metoden demonstreras på utandad kolmonoxid (eCO), en potentiell biomarkör för oxidativ stress och respiratoriska sjukdomar. Avhandlingen omfattar huvudsakligen (1) konstruktionen av en kompakt optisk sensor baserat på mid-infraröd diodlaserabsorptionsspektroskopi (TDLAS) vid 4.7 μm för selektiv och precis realtidsmätning av CO i utandnings- och omgivningsluften (detektionsgräns 9 ± 5 ppb vid 0.1 s), (2) design av ett avancerat system för online provtagning, (3) adaption av en matematisk lungmodell med axiell diffusion (TMAD) för simulation av CO gasutbytet, och (4) tillämpningen av utökad eCO analys i kliniska studier för att fastställa baslinjen för eCO parametrarna i friska icke-rökare, och för att studera effekten av exponering för CO och trärök. Det visas att modellen väl beskriver gasutbytet under systemiskt CO utsläpp för olika andningsmönster, och att det inte finns någon skillnad mellan eCO parametrarna från utandning via mun och näsa. Utandningsprofilerna och eCO parametrarna ändras beroende på utandningsflödet, men för ett visst andningsmönstret ligger parametrarna i ett smalt område. Koncentrationen av CO i luftvägarna ligger nära och korrelerar med CO i omgivningsluften, vilket indikerar att CO produktionen i luftvägarna är försumbart hos den friska befolkningen. Den alveolär diffusionsförmågan är oberoende av endogen CO, även efter exponering för förhöjd exogen CO, och kan möjligtvis användas för att diagnosticera en nedsatt diffusionsförmåga. Jämfört med exponering för CO observeras ingen tydlig ytterligare effekt av exponering för trärökpartiklar. Att åtskilja endogena och exogena eCO källor förbli en utmaning.

  • Disputation: 2018-10-19 09:00 Major groove, Umeå
    Dzhygyr, Ievgen
    Umeå universitet, Medicinska fakulteten, Institutionen för molekylärbiologi (Medicinska fakulteten). Umeå universitet, Medicinska fakulteten, Molekylär Infektionsmedicin, Sverige (MIMS).
    Functional studies of Escherichia coli stringent response factor RelA2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    RelA is a ribosome associated multi-domain enzyme, which plays a crucial role in adaptation ofEscherichia coli to nutritional stress as such as amino acid deficiency. It detects the deficiency of aminoacids in the cell by monitoring whether a tRNA at the acceptor site (A-site) of the ribosome is chargedwith amino acid or not. When RelA detects uncharged, i.e. deacylated tRNA, it starts to producealarmone guanosine penta- or tetraphosphate, collectively referred to as (p)ppGpp. (p)ppGpp is aglobal metabolism regulator in bacteria. Increase in (p)ppGpp concentration alters crucial metabolicprocesses, such as DNA replication, gene expression, cell wall synthesis and translation. Thesechanges also include activation of different virulence factors and are proposed to drive formation of abacterial sub-population that is highly resilient to antibiotic treatment, the so-called persisters.

    For a long time the molecular mechanism of RelA’s activation by and interaction with the ribosomedeacylatedtRNA complex was unknown. Only recently several cryo-EM structures of RelA-ribosomecomplex have shed light on how C-terminal domains of RelA interact with ribosome-deacylated tRNAcomplex. Guided by these structures we investigated the role of RelA’s domains in this interaction byconstructing a set of RelA C-terminal truncates and subjecting these to biochemical and microbiologicalexperimentation. These experiments were complemented with mutations in ribosomal RNA atpositions that interact with RelA, namely A-site finger and sarcin-ricin loop.

    We have shown that only the full-length wild type RelA can be activated by ribosome-tRNA complex,whereas, the set of truncated proteins missing either one, two or three C-terminal domains do notrespond to the presence of uncharged tRNA in the A-site of the ribosome. However, these truncatedversions can still be activated by vacant 70S ribosome as well as pppGpp, suggesting that N-terminaldomain of RelA has an allosteric regulation site for (p)ppGpp and is able to interact with the ribosome.The mechanism of this interaction is yet to be elucidated.

    We have shown that A-site finger of the ribosome is required for RelA activation and recruitment tothe ribosome. Using EMSA assays, we have shown that RelA and deacylated tRNA do not form a stablecomplex off the ribosome. His432 located in TGS domain of RelA is crucial for recognition of deacylatedtRNA and a mutation of this histidine to glycine abolishes RelA activation by deacylated tRNA.Since (p)ppGpp plays an important role in bacterial survival and pathogenicity we have also testedseveral strategies for RelA inhibition by antibiotics, which target ribosomes and the interactionbetween RelA and ribosome-deacylated tRNA complex. We have shown that antibiotic thiostreptoninhibits (p)ppGpp synthesis by preventing RelA-tRNA interaction on the ribosome. (p)ppGppproduction is also inhibited by chloramphenicol and tetracycline.

  • Disputation: 2018-10-22 13:00 N300, Naturvetarhuset, Umeå, Sweden
    Brembilla, Christian
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Efficiency factors for space heating system in buildings2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    The thesis focuses on the efficiency of the space heating system. In particular, the efficiency factors measure the efficiency of thermal zone. The efficiency factors measures how the energy is used in a space heating. Efficiency factors relatively close to one mean that the energy is used "efficiently'', by contrast, efficiency factors close to the zero mean that the majority of the energy is lost to the outdoor environment. This method for the appraisal of space heating performance reads as if it is apparently simple and intuitive. In reality, the efficiency factor method has several pitfalls.

    The thesis provides tools, insights and remarks on how to apply the efficiency factor method to space heating systems equipped with hydronic panel radiator and floor heating respectively. Models of the latter heaters together with the multilayer wall were developed and validated to understand the reliability of their predictions. The hypothesis is that the heat stored in the building thermal mass and heaters plays a role in defining the building thermal performance and as a result in the appraisal of the efficiency factors. The validation is based on the sensitivity bands of the models' predictions. The heaters were tested in in a thermostatic booth simulator. Benefits and drawbacks of each model were highlighted to increase awareness of their use in the engineering fields. The results showed how the models accounting for the heat stored performed the charging phase. In addition, results of how the multilayer wall delayed and damped down the heat wave coming from the outdoor environment were presented with the appraisal of the decrement factor and time delay of the indoor temperature. The results of the efficiency factors analysis reveal how the weather affects the efficiency of each locality situated in cold climates. Lastly how different control strategies impact on the efficiency factors of space heating and its distribution system. To conclude, this study highlights the paradoxes around the efficiency factor method. The thesis proposes how such factors have to be interpreted by researchers and scientists tackling the lack of information around this topic.

  • Disputation: 2018-10-26 09:00 Hörsal D, Unod T9, Umeå
    Pujilestari, Cahya Utamie
    Umeå universitet, Medicinska fakulteten, Institutionen för folkhälsa och klinisk medicin, Epidemiologi och global hälsa.
    Abdominal obesity among older population in Indonesia: socioeconomic and gender inequality, pattern and impacts on disability and death2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Population ageing has contributed to the rise of chronic non-communicable diseases (NCDs). Concurrently, obesity prevalence is increasing in all age groups and has become a serious public health problem. Obesity is the main risk factors of the major chronic NCDs such as type 2 diabetes and has been linked to disability and mortality. Studies of socioeconomic inequalities in obesity among older people in Indonesia are scarce. Understanding socioeconomic inequalities are essential to develop appropriate health programme to improve the population health. This thesis describes the pattern of socioeconomic and gender inequality in abdominal obesity and analyses its impact on disability and all-cause mortality among older people in Indonesia.

    Methods: This thesis is based on four studies conducted in Purworejo Health and Demographic Surveillance System (HDSS) site in Purworejo district, Central Java, Indonesia. This thesis uses both quantitative and qualitative methods. The qualitative study (sub-study 1) was based on 12 Focus Group Discussions (FGDs) with 68 participants from different age groups, sex, and living area. Content analysis was used to describe the community perceptions on diabetes and its risk factors. The quantitative studies (sub-study 2 to 4) utilized longitudinal panel data from the 1st (n = 11,753 individuals) and 2nd wave (n = 14,235 individuals) of the WHO-INDEPTH Study on global AGEing and adult health (SAGE) conducted among all individuals aged 50 years and older in 2007 and 2010. Sub-study 2 used concentration index and decomposition analysis to analyse the pattern of socioeconomic and gender inequality in abdominal obesity. Sub-study 3 used linear regression to examine the association between abdominal obesity and disability. Sub-study 4 used Cox regression analysis with restricted cubic splines to examine the impact of abdominal obesity on all-cause mortality.

    Results: The FGDs reveals that the community holds unrealistic optimism in perceiving diabetes its risk factors. The community stated that chronic NCD such as diabetes is caused by modern lifestyles and mostly attacks those who are considered as the wealthy (sub-study 1). Socioeconomic inequality in abdominal obesity exists in Purworejo HDSS. Abdominal obesity was more prevalent among the affluent men and women, with a lesser inequality gaps between rich and poor among women. The main contributing factors to inequalities in abdominal obesity were occupation, wealth index, and education (sub-study 2). In three-year period, the mean waist circumference decreased significantly among the poor. An increase in waist circumference was significantly associated with disability, and the poor people were more disabled compared to the rich (sub-study 3). A U-shaped association was observed between waist circumference and all-cause mortality, particularly among women. This indicated an increased risk of mortality in the lower and upper end of the waist circumference distribution. The poor with low waist circumference had a higher risk of mortality than the rich (sub-study 4).

    Conclusion: Abdominal obesity was disproportionately more prevalent among older Indonesian women. Though the wealthy people have higher burden of abdominal obesity, the poor people experiences more disability and higher risk of death. Misperception on chronic NCDs and its risk factors exist among the Indonesian population. Abdominal obesity prevention strategies are needed to prevent chronic NCDs, disabilities, and mortality among Indonesian older population. The prevention strategies should be culturally sensitive and address all socioeconomic levels. Special attention should be given to disadvantaged women as the most vulnerable group.

  • Disputation: 2018-10-26 10:00 N430, Umeå
    Holmgren, Per
    Umeå universitet, Teknisk-naturvetenskapliga fakulteten, Institutionen för tillämpad fysik och elektronik.
    Entrained flow studies on biomass fuel powder conversion and ash formation2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Reducing the global dependence on fossil fuels is of paramount importance in tackling the environmental challenges we face, not only tomorrow, but already today. Biomass offers a renewable supply of CO2-neutral raw material that can be converted into many different forms of fuels and valuable chemicals, making it a prime candidate for the technologies of tomorrow. However, the heterogeneous nature and distinctly different elemental composition of biomass compared to traditional fossil sources present new challenges to be solved. When it comes to thermochemical technologies, key issues concern fuel conversion efficiency, ash formation, ash/fuel interactions and ash/reactor material interactions.

    The objective of the present thesis was to provide new knowledge and insights into thermochemical fuel conversion, in particular its application in entrained flow technologies. A laboratory-scale reactor was constructed, evaluated and was used to study several aspects of high-temperature entrained flow biomass fuel conversion. Pulverized fuel particles from different biomass sources were used, and their physical and chemical interactions with the surrounding atmosphere, the concurrent ash element release, ash formation, and phase interactions were also studied in detail. In addition to the entrained flow reactor designed and constructed for this purpose, the main method for data collection was in situ optical studies of converting particles, either while entrained in the flow or when impacting upon surfaces. Elemental composition analysis of collected samples and gas analysis were also performed, allowing for a deeper understanding of ash element fractionation and interactions and thus explaining the observed properties of the resulting deposits or slag.

    The degree of conversion of fuels with very low ash content, such as stem wood, was well described and modeled by a novel method using optical data, offering a non-intrusive and non-destructive alternative to traditional techniques. Coupling computational fluid dynamics with optical data allowed for improved experimental data interpretation and provided improved accuracy for fuel particle residence time estimations, which is an important parameter when studying fast chemical reactions such as those taking place in reactors for entrained flow conditions. The results from studies on ash formation gave new insights into the feasibility of using dry-mixed K-rich additives for improving slag properties during gasification of Ca-rich and Si-rich fuels. Interpretations of the experimental results were supported by thermodynamic equilibrium calculations, and the conclusions highlight both possibilities and challenges in gasification with high fuel flexibility while at the same time producing a flowing slag. Applications and future implications are discussed, and new topics of interest are presented.

  • Disputation: 2018-11-02 09:00 Bergasalen, Umeå
    Semasaka Sengoma, Jean Paul
    Umeå universitet, Medicinska fakulteten, Institutionen för klinisk vetenskap, Obstetrik och gynekologi. University of Rwanda.
    Pregnancy and delivery-related complications in Rwanda: prevalence, associated risk factors, health economic impact, and maternal experiences2018Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
    Abstract [en]

    Background: Every year more than 1.5 million women suffer from pregnancy and delivery-related complications (PDCs) during pregnancy and childbirth worldwide, and these women are a vulnerable population for lifelong consequences, somatically, psychologically and financially. Following the establishment of Millennium Development Goal no 5, which targeted a reduction of 75% of the maternal mortality ratio from 1990 to 2015, many efforts were made to reduce maternal mortality worldwide. In low-income countries saving a pregnant woman’s life requires a focused medical intervention so that near-miss cases of death are considered as obstetric success and thus postpartum follow-up may be neglected. In Rwanda, maternal mortality is estimated to 210 per 100,000 live births and main obstetric complications are hypertensive disorders during pregnancy, obstructive/prolonged labour, post-partum haemorrhage (PPH) and sepsis/infections. However, the specific prevalence of PDCs as well as their consequences to the woman and her family is currently relatively unknown.

    Aims: The overall aim of this thesis was to determine the prevalence of PDCs and their associated risk factors and to investigate delivered women’s experiences of PDCs, the consequences of these complications on postpartum health and family situation, and to estimate the societal economic costs of pregnancy, delivery and postpartum-related problems.

    Subjects and methods: A population-based cross-sectional study including 921 women who gave birth within the past 13 months prior to time of data collection (Paper I) and a health facility-based study including 817 women that were at discharge time (Paper II) were conducted in the Northern Province of Rwanda and Kigali City. Fifteen women who experienced PDCs were interviewed through individual in-depth qualitative interviews (Paper III). A micro costing approach to collect health facility data and household costs including opportunity cost, transport and food cost was conducted to estimate the societal economic cost of PDCs (Paper I-V). Descriptive statistics, Chi-Square, bi- and multivariable logistic regression, Cox regression, and health economic analysis were applied for quantitative data analyses (Papers I, II and IV). Qualitative manifest and latent content analysis was used for qualitative data analyses (Paper III).

    Results: Prevalence of anaemia, hypertension, diabetes mellitus during pregnancy, and severe bleeding during pregnancy and labour were estimated to 15.0%, 4.9%, 2.4%, and 3.7%, respectively (Paper I). In total, 56.4% of the participants were transferred and the majority were transferred from health centres to district hospitals, with caesarean section (CS) as the main reason for transfer. Almost three-quarters of the women started labour spontaneously; 5% had induced labour and 28.4% of all pregnant women were delivered by CS (Paper II). Pre-eclampsia/eclampsia, PPH, and caesarean section (CS) due to prolonged labour/dystocia represented 1%, 2.7% and 5.4% of all participants, respectively (Paper II). Risk factors for CS due to prolonged labour or dystocia were poverty, nulliparity, and residence far from health facility (Paper II). The prevalence of poor-self rated health (poor-SRH) for participants who gave birth within the past 14 months prior to time of data collection was 32.2% at one day postpartum, 7.8% at one month, and 11.7% at time of the interview (Paper I). Most participants who had experienced PDCs reported that they were previously unaware of the complications they had developed, and they claimed that at discharge they should have been better informed about the potential consequences of these complications (Paper III). Most participants blamed the health care system as the cause of their problems due to the provision of inadequate care. Participants elaborated different strategies for coping with persistent health problems (Paper III). PDCs negatively affected participants’ economic situation due to increased health care expenses and lowered income because of impaired working capacity (Paper III). The estimated total societal cost of a normal uncomplicated vaginal delivery was 107 United States dollars (USD). The incremental cost of a vaginal delivery followed by PPH was 55 USD. The incremental cost of prolonged, dystocic or obstructed labour resulting in a CS was 146 USD. The incremental cost of pre-eclampsia with vaginal delivery and pre-eclampsia with CS were 289 and 339 USD, respectively. The major cost categories of the estimated costs for each mode of delivery were staff, the hospitalisation rooms, and household expenditures (Paper IV).

    Conclusions: A high prevalence of poor self-rated health status was reported in the early postpartum period. Identified factors associated with poor-SRH were severe bleeding, hypertension, infection, and anaemia during pregnancy and postpartum haemorrhage. The estimated prevalences of specific pregnancy and delivery-related complications were relatively low, probably in part due to underestimation. Rwandan women experiencing PDCs are facing many challenges and problems during pregnancy, delivery and postpartum period. The costs of PDCs were calculated to be very high in comparison to the net median monthly wage in Rwanda. In addition, the Rwandan health system presents weaknesses in relation to the prevention of PDCs. Above all, there is an insufficient postpartum health care provision and community support to women experiencing PDCs. The results from this thesis call for interventions, to improve the postpartum health care services and call for the community sensitisation for the increased support to women who face difficult living circumstances because they have experienced severe pregnancy and delivery-related complications.