| 1. |
- Boivie, Patrik, 1976-
(författare)
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Cerebrovascular accidents associated with aortic manipulation during cardiac surgery
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: Despite the successful development in cardiac surgery, cerebrovascular accidents (CVA) remain a devastating complication. Aortic atherosclerosis has been identified as a major risk factor for CVA. The present thesis addresses this question in relation to aortic manipulation during cardiac surgery, being divided into a clinical (I-II) and an experimental part (III-V). Material and methods: Consecutive cardiac surgery cases (n=2641) were analyzed. Patients with CVA were extracted from a database designed to monitor clinical symptoms. Patient records were used to confirm clinical data and diagnosis. Subdivision was made into three groups: control subjects, immediate, and delayed CVA, being analyzed for neurological symptoms (I). Patients with CVA who also had been investigated with computer tomography (CT) (n=77) were further evaluated in terms of hemispheric and vascular distribution of lesions. The CT-findings were compared with CVA symptoms (II). An aortic perfusion model was developed using cadaver aorta onto which multiple cross-clamp manipulations were applied (III). Washout samples of perfusate were analyzed by computerized image processing and with subdivision into different particle spectra. The model was further developed with the introduction of intraluminal manipulation from cannula and intra-aortic filter (IV). A technique for macro-anatomic mapping of plaque distribution of cadaver thoracic aorta was developed (V). Variation in plaque density was analyzed in different anatomical segments, monitored by digital image analysis. Hazards associated with surgical manipulation were studied by superimposing cannulation and cross-clamp sites onto the aortic maps in a blinded fashion. Results: The incidence of immediate and delayed CVA was 3.0% and 0.9%, respectively. Aortic quality was a strongly associated with immediate but not delayed CVA. Left-sided symptoms of immediate CVA were significantly more frequent than of the contra-lateral side. Positive signs on CT were seen in 66% of the CVA patients. Right-hemispheric lesions were more frequent compared with the contra-lateral side and the middle-cerebral artery territory dominated. Aortic cross-clamping produced a substantial output of particulate matter. Manipulation by intra-aortic filter produced a significant washout of embolic particles that escaped the filter, although some particles were captured. Cannulation was an additional source of embolic material. In terms of plaque distribution was the anterior wall of the ascending part and arch of the aorta more affected than its posterior side. However, observing a plaque in the anterior wall of this aortic segment predicted to 83% a concomitant plaque in the posterior wall. Increased age correlated positively with plaque density. The theoretical chance of interfering with a plaque during cannulation and/or clamp positioning was 45.8%. Conclusions: Both CT scans and clinical symptoms confirmed that CVA after cardiac surgery had a right-hemispheric predominance. The perfusion model resulted in a profound output of material during cross-clamp maneuvers. The intra-aortic filter successfully collected particles but also generated embolic debris on its own. Aortic cannulation was an additional source of embolic debris. Plaques were frequently found in the cadaveric aorta, and there was a high risk of plaque interference during surgical manipulation. As expected, plaque density was age-dependent.
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| 2. |
- Chilkova, Olga, 1976-
(författare)
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Functional and structural properties of eukaryotic DNA polymerase epsilon
- 2006
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- In eukaryotes there are three DNA polymerases which are essential for the replication of chromosomal DNA: DNA polymerase alpha (Pol alpha), DNA polymerase delta (Pol delta) and DNA polymerase epsilon (Pol epsilon). In vitro studies of viral DNA replication showed that Pol alpha and Pol delta are sufficient for DNA replication on both leading and lagging DNA strands, thus leaving the function of Pol epsilon unknown. The low abundance and the reported protease sensitivity of Pol epsilon were holding back biochemical studies of the enzyme. The aim of this study was to characterize the structural and functional properties of eukaryotic Pol epsilon. We first developed a protocol for over-expression and purification of Pol epsilon from the yeast Saccharomyces cerevisiae. Pol epsilon consists of four subunits: Pol2 (catalytic subunit), Dpb2, Dpb3 and Dpb4. This four-subunit complex was purified to homogeneity by conventional chromatography and the subunit stoichiometry of purified Pol epsilon was estimated from colloidal coomassie-stained gels to be 1:1:1:1. The quaternary structure was determined by sedimentation velocity and gel filtration experiments. Molecular mass (371 kDa) was calculated from the experimentally determined Stokes radius (74.5 Å) and sedimentation coefficient (11.9 S) and was in good agreement with a theoretical molecular mass calculated for a heterotetramer (379 kDa). Analytical sedimentation equilibrium ultracentrifugation experiments supported the proposed heterotetrameric structure of Pol epsilon. By cryo-electron microscopy and single-particle image analysis we determined the structure of Saccharomyces cerevisiae Pol epsilon to 20-Å resolution. The four-subunit complex was found to consist of a globular domain, comprising the Pol2 subunit, flexibly connected to an elongated domain, including Dpb2, Dpb3 and Dpb4 subunits. We found that Pol epsilon requires a minimal length of 40 base pairs of primer-template duplex to be processive. This length corresponds to the dimensions of the elongated domain. To characterize the fidelity by which Pol epsilon synthesizes DNA, we purified wild type and exonuclease-deficient Pol epsilon. Wild type Pol epsilon synthesizes DNA with a very high accuracy. Analysis of the exonuclease-deficient Pol epsilon showed that Pol epsilon proofreads more than 90% of the errors made by its polymerase activity. Exonuclease-deficient Pol epsilon was shown to have a specific spectrum of errors not seen in other DNA polymerases: a high proportion of transversions resulting from T-dTTP, T-dCTP and C-dTTP mispairs. This unique error specificity and amino acid sequence alignment suggest that the structure of the polymerase active site of Pol epsilon differs from those of other members of B family DNA polymerases. With recombinant proteins and circular single-stranded DNA templates, we partially reconstituted DNA replication in vitro, in which we challenged Pol epsilon and Pol delta in side-by-side comparisons regarding functional assays for polymerase activity and processivity, as well as physical interactions with nucleic acids and PCNA. We found that Pol epsilon activity and “on-DNA” PCNA interactions are dependent on RPA-coated template DNA. By the surface plasmon resonance technique, we showed that Pol epsilon has a high affinity for DNA and low affinity for immobilized PCNA. By contrast, Pol delta was found to have low affinity for DNA and high affinity for PCNA. We suggest that a possible function of RPA is to regulate down the DNA synthesis through Pol epsilon, and that the mechanism by which Pol epsilon and Pol delta load onto the template is different due to different properties of the interaction with DNA and PCNA.
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| 3. |
- Jonsson, Bertil, 1956-
(författare)
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Interaction between humans and car seats : studies of occupant seat adjustment, posture, position, and real world neck injuries in rear-end impacts
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The latest generation of rear-end whiplash protection systems, as found in the WHIPS Volvo and SAHR Saab, have reduced injury rates by almost 50% in comparison with the previous generation of seat/head restraint systems. Occupant behaviour, such as seated posture and seat adjustment settings, may affect the injury risk. Method: Five studies were conducted. Studie I was an injury outcome study based on insurance data. Studies II-IV investigated seat adjustment, occupant backset, and cervical retraction for drivers and occupants in different postures and positions in the car, during stationary and driving conditions. Study V compared the occupant data from studies II and III with a vehicle testing tool, the BioRID dummy, using the protocols of the ISO, RCAR, and the RCAR-IIWPG. Results: Female drivers and passengers had a threefold increased risk for medically-impairing neck injury in rear-end impacts, compared to males. Driver position had a double risk compared with front passenger seat position. Female drivers adjusted the driver seat differently to male drivers; they sat higher and closer to the steering wheel and with more upright back support. The volunteers also adjusted their seat differently to the ISO, RCAR, and RCAR-IIWPG protocol settings; both sexes sat further away from the steering wheel, and seat back angle was more upright then in the protocols. In stationary cars, backset was highest in the rear seat position and lowest in the front passenger seat position. Males had a larger backset than females. Cervical retraction decreased and backset increased for both sexes when posture changed from self-selected posture to a slouched posture. The BioRID II dummy was found to represent 96th percentile female in stature, and a 69th percentile female in weight in the volunteer group. Conclusions: Risks in car rear-end impacts differ by sex and seated position. This thesis indicates the need for a 50th percentile female BioRID dummy and re-evaluation of the ISO, RCAR, and RCAR-IIWPG protocols, and further development of new safety systems to protect occupants in rear-end impacts.
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| 4. |
- Li, ShuShun, 1963-
(författare)
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Thrombospondin 1, an autocrine regulator in T cell adhesion and migration
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Lymphocytes, the principal cells of the immune system, perform the immune function throughout the body by their unique capacity to circulate in blood stream and lymphatic vessels and migrate in lymphoid and non-lymphoid tissues. The mechanisms regulating lymphocyte adhesion and migration, interactions with cells and components within the extracellular matrix are not fully understood. The aim of this work has been to elucidate molecular mechanisms governing T lymphocyte adhesion and migration by endogenous molecules. The studies presented in this thesis have shown that thrombospondin-1 (TSP-1) is expressed in T lymphocytes with a high turnover, manifested by variable cell surface expression, and is regulated by SDF-1a, adhesion to fibronectin and collagen type IV. The TSP-1 binding site of calreticulin (CRT), spanning amino acid 19-32, was shown to be a major triggering factor for T cell migration within a three-dimensional collagen type 1 matrix. The chemokine SDF-1a stimulated migration via a calreticulin-TSP-1 pathway. Endogenous calreticulin binding to the N-terminal domain of endogenous TSP-1 elicited a motogenic signal to the T cells through the C-terminal domain of TSP-1 and its cell surface receptor integrin-associated protein (IAP, CD47). Inhibition experiments of ligand binding of CD91 by receptor associated protein (RAP) and small interfering RNA technology indicated that CD91 is an important factor in TSP-1-mediated T cell adhesion and migration. These results unveil an autocrine mechanism of CRT-TSP-1-CD47-CD91 interaction for the control of T cell motility and migration within 3D extracellular matrix substrata. The data demonstrated that T cell adhesion and migration are sequential events governed by a series of interacting cell surface molecules comprising a CRT-TSP-1-CD47-CD91 pathway where endogenous TSP-1 functions as the hub. Ligation of the CD3/T cell antigen receptor complex determines T cell adhesion through this mechanism. CRT interaction with the N-terminal domain of TSP-1 elicits cytoplasmic spreading, and augments adhesion, while a counter-adhesive motogenic pathway, triggering interaction of the C-terminal domain of TSP-1, induces migration. CD91-dependent internalization of TSP-1 is a crucial event of this motogenic pathway. In conclusion, the studies provide a novel mechanism governing T cell adhesion and migration within extracellular matrix substrata.
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| 5. |
- Aasa, Ulrika
(författare)
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Ambulance Work : Relationships between occupational demands, individual characteristics and health-related outcomes
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Although musculoskeletal disorders (MSDs) and other health complaints are an occupational problem for ambulance personnel, there is a lack of knowledge regarding work-related factors associated with MSDs and other health complaints. The overall aim of this thesis was to investigate the relationships between occupational demands, individual characteristics and health-related outcomes among ambulance personnel. A random sample of 234 female and 953 male ambulance personnel participated in a national questionnaire survey on work-related factors, and musculoskeletal and other health complaints. Physical demands was associated with activity limitation due to neck-shoulder and low-back complaints among the female personnel. Among the male personnel, physical demands was associated with low-back complaints and activity limitation due to low-back complaints. Psychological demands was significantly associated with neck-shoulder complaints, sleeping problems, headache and stomach symptoms among both female and male ambulance personnel. Worry about work conditions was associated with musculoskeletal disorders and sleeping problems, headache and stomach symptoms. A local sample of 26 ambulance personnel was followed during a 24-hour work shift and for the next two work-free days. Subjective stress- and energy levels, and cortisol levels were measured at regular intervals, and heart rate was registered continuously by electrocardiogram (ECG). Autonomic reactivity to standardized tests before (pre-work) and at the end of the work shift (post-work) was also investigated. For the whole group, baseline values of heart rate were higher pre-work than post-work, but autonomic reactivity did not differ. Increased reactivity to the mental test, modest deviation in heart rate variability (HRV) pattern during the late night hours at work and higher morning cortisol values during work than during leisure time were observed in personnel with many health complaints, but not among their co-workers without or with few complaints. Ambulance personnel with many health complaints also reported higher psychological demands and tended to be more worried about work conditions. Heart rate (HR), lactate level (LL) and perceived exertion (RPE) were investigated in 17 female and 48 male ambulance personnel during a simulated standardized work task “carry a loaded stretcher”. The ambulance personnel had to carry the loaded stretcher (920 N) up and down three flights of stairs twice. The high physiological strain (HR, LL, RPE) for the male, and near or at maximal strain for the female ambulance personnel, implied the importance to identify what kind of physical capacity is most important for ambulance personnel. Therefore, the explained variance of developed fatigue by tests of cardiorespiratory capacity, muscular strength and endurance, and coordination was investigated. The results showed that VO2max and isometric back endurance were important predictors for development of fatigue when carrying a loaded stretcher. The influence of body size on the relationships between maximal strength and functional performance was investigated in a methodological study. The results confirm that the assessment of physical performance could be confounded by the body weight. Therefore, the models for explaining development of fatigue when carrying the loaded stretcher were adjusted for height and weight. Including height in the models significantly increased the explained variance of accumulated lactate among female, but not among male personnel. Lactate levels were higher among short compared to tall female personnel. Weight had no effect on any of the models. In conclusion, the national survey showed that self-reported physical demands was a risk factor of having MSDs, and that self-reported psychological demands and worry about work were important risk factors of having MSDs and other health complaints. Stress monitoring of ambulance personnel during work and leisure time showed that physiological and subjective stress markers did not show any differences between the 24-hour ambulance work shift and leisure time afterwards. However, ambulance personnel with many health complaints had certain physiological changes during the work shift in comparison with the next two work-free days. The physiological and subjective responses during carrying a loaded stretcher, especially among the female ambulance personnel, showed that female and male ambulance personnel could be exposed to internal exposures at different levels when performing the same work task. A better understanding of the relationships between occupational demands and health-related outcomes require further studies on age- and gender matched groups in long-term perspective studies.
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| 6. |
- af Bjerkén, Sara, 1979-
(författare)
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On dopamine neurons : nerve fiber outgrowth and L-DOPA effects
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Parkinson’s disease is a disorder mainly characterized by progressive degeneration of dopamine producing neurons in the substantia nigra of the midbrain. The most commonly used treatment strategy is to pharmacologically restore the lost function by the administration of the dopaminergic precursor L-DOPA. Another treatment strategy is to replace the degenerated neurons with immature fetal ventral mesencephalic tissue, or ultimately stem cell-derived tissue. Grafting trials have, however, revealed poor reinnervation capacity of the grafts, leaving much of the striata dopamine-denervated. An additional drawback is the upcoming of dyskinesia (involuntary movements), a phenomenon also observed during L-DOPA treatment of Parkinson’s disease patients. Attempts to characterize nerve fiber formation from dopamine neurons have demonstrated that the nerve fibers are formed in two morphologically diverse outgrowth patterns, one early outgrowth seen in the absence of astrocytes and one later appearing outgrowth seen in co-existence with astrocytes. The overall objective of this thesis has been to study the dopaminergic outgrowth including guidance of nerve fiber formation, and to look into the mechanisms of L-DOPA-induced dyskinesia. The first paper in this thesis characterizes the different outgrowth patterns described above and their relation to different glial cells. The study demonstrated the two different outgrowth patterns to be a general phenomenon, applying not only to dopamine neurons. Attempts of characterization revealed no difference of origin in terms of dopaminergic subpopulations, i.e. A9 or A10, between the outgrowth patterns. Furthermore, the “roller-drum” technique was found optimal for studying the dual outgrowth sequences. The second and the third paper also utilized the “roller-drum” technique in order to promote both patterns of neuronal fiber formation. The effects of glial cell line-derived neurotrophic factor (GDNF) on the formation of dopamine nerve fibers, was investigated. Cultures prepared from gdnf knockout mice revealed that dopaminergic neurons survive and form nerve fiber outgrowth in the absence of GDNF. The dopaminergic nerve fibers exhibited an outgrowth pattern consistent with that previous observed in rat. GDNF was found to exert effect on the glial-associated outgrowth whereas the non-glial-associated was not affected. Astrocytic proliferation was inhibited using cytosine β-D-arabinofuranoside, resulting in reduced glial-associated outgrowth. The non-glial-associated dopaminergic outgrowth was on the other hand promoted, and was retained over longer time in culture. Furthermore, the non-glial-associated nerve fibers were found to target the fetal frontal cortex. Different developmental stages were shown to promote and affect the outgrowths differently. Taken together, these data indicate and state the importance of astrocytes and growth factors for neuronal nerve fiber formation and guidance. It also stresses the importance of fetal donor age at the time for transplantation. The fourth and fifth studies focus on L-DOPA dynamics and utilize in vivo chronoamperometry. In study four, 6-OHDA dopamine-depleted rats were exposed to chronic L-DOPA treatment and then rated as dyskinetic or non-dyskinetic. The electrochemical recordings demonstrated reduced KCl-evoked release in the intact striatum after chronic L-DOPA treatment. Time for maximal dopamine concentration after L-DOPA administration was found to be shorter in dyskinetic animals than in non-dyskinetic animals. The serotonergic nerve fiber content in the striatum was evaluated and brains from dyskinetic animals were found to exhibit significantly higher nerve fiber density compared to non-dyskinetic animals. Furthermore, the mechanisms behind the conversion of L-DOPA to dopamine in 6-OHDA dopamine-depleted rats were studied. Local administration of L-DOPA in the striatum increased the KCl-evoked dopamine release in the intact striatum. Acute application of L-DOPA resulted sometimes in a rapid conversion to dopamine, probably without vesicle packaging. This type of direct conversion is presumably occurring in non-neuronal tissue. Furthermore, KCl-evoked dopamine releases were present upon local application of L-DOPA in the dopamine-depleted striatum, suggesting that the conversion to dopamine took place elsewhere, than in dopaminergic nerve fibers. In conclusion, these studies state the importance of astrocytes for neuronal nerve fiber formation and elucidate the complexity of L-DOPA conversion in the brain.
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| 7. |
- Alanentalo, Tomas, 1978-
(författare)
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Optical projection tomography based 3D-spatial and quantitative assessments of the diabetic pancreas
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The gastrointestinal tract comprises a number of digestive organs including the stomach and pancreas. The stomach is involved in the digestion and short term storage of food while the pancreas is a mixed endocrine and exocrine gland which provides the body with hormones and enzymes essential for nutritional utilisation. The pancreas consists of three different cell lineages, acinar, ductal and endocrine cells. The endocrine cells, organised in the islets of Langerhans, are scattered throughout the exocrine parenchyma and regulate blood glucose levels by production of hormones such as glucagon and insulin. The Nkx family of homeodomain proteins controls numerous processes during development. Previous studies have identified two members belonging to the Nkx6 subfamily of Nkx proteins, Nkx6.1 and Nkx6.2. We have described the cloning and embryonic expression pattern of Nkx6.3. All three members of the Nkx6 gene family were shown to be expressed in partially overlapping domains during the development of the gastrointestinal tract and the central nervous system. Nkx6.2 was also identified as a transient marker for pancreatic exocrine cells. Analysing gene expression patterns and morphological features in tissues and organs is often performed by stereologic sampling which is a labour-intensive two dimensional approach that rely on certain assumptions when calculating e.g. β-cell mass and islet number in the pancreas. By combined improvements in immunohistochemical protocols, computational processing and tomographic scanning, we have developed a methodology based on optical projection tomography (OPT) allowing for 3D visualisation and quantification of specifically labelled objects within intact adult mouse organs. In the pancreas, this technique allows for spatial and quantitative measurements of total islet number and β-cell mass. We have further developed a protocol allowing for high resolution regional analyses based on global OPT assessments of the pancreatic constitution. This methodology is likely to facilitate detailed cellular and molecular analysis of user defined regions of interest in the pancreas, at the same time providing information on the overall disease state of the gland. Type 1 diabetes mellitus (T1D) can occur at any age and is characterized by the marked inability of the pancreas to secrete insulin due to an autoimmune destruction of the insulin producing β-cells. Information on the key cellular and molecular events underlying the recruitment of lymphocytes, their infiltration of the islets of Langerhans and consequent β-cell destruction is essential for understanding the pathogenesis of T1D. Using the developed methodology we have recorded the spatial and quantitative distribution of islet β-cells and infiltrating lymphocytes in the non obese diabetic (NOD) mouse model for T1D. This study shows that the smaller islets, which are predominantly organised in the periphery of the organ, are the first to disappear during the progression of T1D. The larger islets appear more resistant and our data suggest that a compensatory proliferative process is going on side by side with the autoimmune-induced β-cell destruction. Further, the formation of structures resembling tertiary lymphoid organs (TLOs) in areas apparently unaffected by insulitis suggests that local factors may provide cues for the homing of these lymphocytes back to the pancreas.
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| 8. |
- Albertsson, Pontus, 1958-
(författare)
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Occupant casualties in bus and coach traffic : injury and crash mechanisms
- 2005
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Background: The relevance of conducting this thesis is evident by the fact that bus and coach casualties have been “stubbornly stable” in Europe recent years and a need for investigating if a similar trend could be found in Sweden is therefore obvious. It was also important to add new knowledge to the bus and coach research in Sweden, since many areas were scarcely addressed. Aims: To describe bus and coach occupants’ injuries, crash and injury mechanisms generated in a traffic environment based on data from the medical sector. Additional aims were to investigate the injury reducing effect of a 3-point belt, the effect of cross-winds, and crucial factors in the emergency- and rescue response. Material and methods: Injury data analyses were based on a complete ten-year medical data set from a catchment-area with about 130,000 inhabitants. A number of crash studies with the scope in different crash phases were conducted by applying and elaborating the Haddon matrix as a framework. An additional framework, Protocol for Major Incidents was used in order to investi-gate the emergency- and rescue response to a severe coach crash. Results: Between the first and second five-year period, the incidence of injured in non-crash in-cidents was increased by 24%. In non-crash incidents, 54% were injured; 2/3 while alighting from a bus or coach. The pre-crash factor cross-wind, in addition to vehicle design, vehicle speed and road friction, was investigated in ten crashes. It was confirmed that cross-wind, in relation to vehicle speed and slippery road conditions, needs more attention. The importance of goods load-ing and passengers’ position in the bus, was indicated by the fact that a displacement of the cen-tre of mass rearwards with 10% increased the necessary coefficient of friction with, on average 45%, which in many cases corresponded to dry road conditions. Three Swedish rollover crashes were analysed with regard to the injury outcome, mechanisms and the possible injury reduction for occupants using a safety belt. A considerable increase in safety for occupants belted with 3-point belts was shown through limiting interior contacts, occupant interaction and the possibility of ejection. Crucial post-crash factors in the emergency- and rescue response showed that ordi-nary ways of working and equipment are not always useful and proper equipment for lifting a coach body is essential in the case of a rollover. Finally, the communication between the hospitals is important, and the telephone systems may be overloaded by calls from worried relatives and media. Conclusions: In non-crash events: Non-crash events constitute a majority of all bus and coach casualties with a high proportion of elderly female occupants among the MAIS 2+ injury cases. Boarding and, especially alighting causes many injuries to the lower extremities. In the pre-crash phase: Cross-winds do affect the safety of buses and coaches and requires more at-tention. Seat belt usage among bus and coach occupants has to be increased. In the crash phase: Rollover and ejection are the major causes behind serious and fatal injuries to bus and coach occupants, consequently, retentive glazing, pillars or rails need more attention. An upgrade from 2-point seat belts to 3-point seat belts yields an increase in the estimated injury re-duction from approximately 50% up to 80% for the MAIS 2+ casualties in a rollover crash. In the post-crash phase: In order to be able to lift a coach body proper equipment originated from experience and development is essential in a rescue operation of a crashed bus or coach. Fur-thermore, to improve the emergency response inside crashed coaches proper methods originated from experience need to be developed. Euro NBAP: Based on the results and conclusions generated in this thesis, a European New Bus and Coach Assessment Programme is suggested, which would provide bus and coach occupants with a assessment programme similar to the Euro NCAP.
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| 9. |
- Aléx, Lena
(författare)
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Äldre människors berättelser om att bli och vara gammal tolkade utifrån genus- och etnicitetsperspektiv
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The overall aim of the five studies that make up this thesis is to elucidate constructions of being old from the perspectives of gender and ethnicity. One of the studies uses quantitative data and four use qualitative data.The sample in study I consisted of 125 participants from the Umeå 85+ study, aged 85 to 103 years old, who were able to use Likert scales in responding to questions. Studies II and III involved content analysis of interviews with old persons scoring on the extremes of the resilience scale. In study IV, interviews with nine Sami women were analysed using grounded theory. In study V, four interview situations were subjected to discourse analysis.Study I showed statistically significant correlations between the scales measuring resilience, sense of coherence, purpose in life and self-transcendence. These scales were supposed to measuring a common dimension, which is here interpreted as “inner strength”. There was a significant correlation between women’s “inner strength” and perceived mental health.The femininities found were associated with “being connected”, “being an actor”, “living in the shadow of others” and “being alienated”. The masculinities found were associated with “being in the male centre”, “striving to maintain the male facade” and “being related”. The femininity associated with “being an actor” and the masculinity associated with “being in the male centre” were pronounced in those participants assessed as having high resilience.Old Sami woman were found to be balancing within various discourses, including being a reindeer owner versus not owning reindeer, being Sami versus being Swedish, speaking in Sami versus speaking in Swedish, dreaming about the past versus looking to the future, being equal to men versus living in the shadow of the male herders, and changing for survival versus striving to retain uniqueness as a Sami.Study V revealed that shifts in power between the interviewer and the interviewed can be related to the discourses of age, gender, education, body, ethnicity and ideology.This thesis presents a complex picture of what it means to be among the oldest old. The ageing, gendered and ethicised selves cannot be seen as socially and culturally fixed. For the women, the femininity expressed in “being connected” involved being satisfied, content and having positive relationships. “Being an actor” involved a stress on the person’s own strength and own choices. The femininities experienced as “living in the shadow of others” and “being alienated” generated narratives about dissociation and loneliness. For the men, it seemed important to relate to themselves and to other men. However, the masculinity expressed in “being related” involved an alternative form of masculinity, focusing on the importance of daily work, new relationships, and reflecting on the meaning of life. The Sami women showed strength in being able to position themselves between various discourses, but their narratives also showed tender sadness when they spoke of their longing for the past and for their mother tongue. The reflection on how narratives are constructed by both the interviewed and the interviewer in relation to their access to various discourses of age, gender, education, ethnicity and ideology in different interview situations can be important for increasing awareness of the role of these discourses. Various ways of constructing femininities and masculinities must be studied if we are to avoid ageism developing in society. Analyzing and reflecting on the importance of age, gender and ethnicity from a constructivist perspective may reduce stereotypical descriptions of the oldest old.
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| 10. |
- Andersson, Britta, 1979-
(författare)
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Manipulation of potassium ion fluxes to induce apoptosis in lung cancer cells
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Apoptosis is a special form of cell death that if non-functional may lead to diseases such as cancer. A reduction of the intracellular potassium ion (K+) content is necessary for activating enzymes important for the execution of apoptosis. Pharmacological modulation of K+ fluxes to reduce intracellular K+ in cancer cells might therefore force the cells into apoptosis and decrease tumour cell mass. Human malignant pleural mesothelioma (MPM) is a form of cancer often caused by asbestos exposure. Although asbestos has been banned in the Western World, the incidence of MPM is expected to increase. Cisplatin is the first-line chemotherapy for MPM, but acquired resistance to the drug is a clinical problem. This thesis is mainly based on work with the human malignant pleural mesothelioma cell line (P31 wt) and a cisplatin-resistant sub-line (P31 res). The aim was to first characterize K+ fluxes in P31 wt and P31 res cells, and then manipulate them in order to reduce intracellular K+ and induce apoptosis with K+ manipulation alone or in combination with cisplatin. Characterization of K+ fluxes in P31 wt cells showed that: 1) ouabain, a digitalis-like drug, and specific blocker of the Na+, K+, ATPase pump, effectively inhibited K+ uptake, 2) bumetanide, a diuretic, and an inhibitor of the Na+, K+, 2Cl-¬-cotransporter, had a transient effect on K+ uptake, and 3) the antifungal drug amphotericin B stimulated K+ efflux. In order to determine intracellular K+ content, the potassium-binding fluorescent probe PBFI-AM was used in a 96-well plate assay. After a 3-h incubation with ouabain, with or without bumetanide, combined with amphotericin B, the intracellular K+ content was reduced in P31 wt cells but not in P31 res cells. Ouabain induced apoptosis in both P31 wt and P31 res cells. P31 res cells were sensitized to cisplatin by ouabain, since 10 mg/L cisplatin in combination with ouabain induced about the same percentage of apoptotic cells as 40 mg/L cisplatin. Apoptosis was executed via caspase-3 activation in both P31 wt and P31 res cells. Amphotericin B enhanced ouabain-induced apoptosis in P31 wt cells via caspase-9 activation, with increased caspase-3 activation and DNA fragmentation as consequences. Ouabain-induced apoptosis in P31 res cells was executed via increased expression of pro-apoptotic Bak. The combination of cisplatin with ouabain and amphotericin B was stressful to both P31 wt and P31 res cells, since SAPK/JNK a known factor in stress-induced apoptosis was activated. In conclusion, K+ flux manipulation with clinical used drugs can induce apoptosis per se and also enhance cisplatin-induced apoptosis in P31 wt and P31 res cells.
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