目的：針對心血管初級預防，世界各國均推薦某一年齡段人群全部測量膽固醇以估算心血管病發病風險。此舉耗費高且非必須，本研究旨在建立並驗證一個新型的选择性膽固醇篩查模型，用以篩查需藥物治療之高危人群，并在成本效益方面與其它篩查模型相比較。 / 方法：本模型具體采用兩步法：首先利用一個足夠高的假設膽固醇值代入心血管病風險預測方程，用以系統性的高估絶大多數人的心血管病風險；其次只有假設心血管病風險高於推薦治療閾值時，該個體才需要測量膽固醇，並進行實際心血管病風險分析。 / 英国健康调查和中国营养与健康调查是本次研究的合适数据。我們首先探索最優的假設膽固醇值，尋找到最後膽固醇值之後，我們將繼續測試我們的新型膽固醇篩查模型，在不同的治療閾值下，表現是否穩定。我們以靈敏度，特異度和徐篩查人群為指標，比較我們模型與全民篩查模型和英國NICE 選擇篩查模型相比較。之後我們估算在中英人群中應用該篩查模型，所需耗費的成本和可預防心血管事件數。 / 结果：與全名篩查模型相比，我們的模型靈敏度相若但可以節省80%左右的篩查費用。模型的靈敏度主要取決於所採用的假設膽固醇值，與所用風險預測方程，治療閾值和人群心血管風險分佈無關。當以均數加2 倍標準差作為假設膽固醇值時，靈敏度可達到97.5%左右，特異度可以達到90%左右，符合預期。模型應用於中國人群得到的結果類似。值得註意的是，在中國人群中，即使不測量膽固醇，模型靈敏度亦接近95%。此外，將膽固醇篩查項目限制于男性50-84歲，女性60-84 歲年齡段可以進一步減少篩檢費用。在人群影響方面，我們模型可預防心血管事件數比全名篩查模型略少，但成本大大降低。英國NICE 模型適用於某些特定情況，但並非全部。 / 結論：我們的新型篩查模型靈敏度與全民篩查模型相若，但可以節省大量篩查費用。在资源匮乏地区，可考虑在某一特定年龄段运用我们的模型已达到进一步减少费用的效果。如果本研究结果得到进一步数据证实，對於中國人群而言，膽固醇測量可能並非心血管風險評估所必須。 / Objectives / Since the mid 1990s, most guidelines on primary prevention of cardiovascular disease (CVD) have recommended regular cholesterol measurement for all adults or those above a certain age (which is known as mass screening). Cholesterol measurement comprises a large cost of CVD prevention and is not necessarily required in those who do not need drug intervention. In order to reduce this cost, we have developed a new selective cholesterol screening model in order to determine whose cholesterol should be measured for drug prevention. The model was evaluated and compared with other widely adopted models in basic model performance as well as cost effectiveness. / Methods / The new model has two steps. In the first step, we purposely over-estimated the majority of respondents’ CVD risk by substituting a sufficiently high hypothetical cholesterol value in the risk estimation. We then recommend cholesterol measurement only to those with the estimated CVD risk above a predetermined risk threshold for drug treatment. In the second step, the CVD risk is re-estimated based on the individual’s real cholesterol consentration. Those with a risk above the treatment threshold are recommended for drug treatment. / We evaluated the performance of our two-step model with data from the Health Survey for England and re-evaluated it with data from the China Nutrition and Health Survey 2002. By varying the hypothetical cholesterol values and treatment thresholds in CVD risk, we assessed the sensitivity, specificity and proportion of the population who need to measure cholesterol and compared it with the US mass screening model and the UK NICE selective screening model. We further compared the costs and CVD events avoided in the compared screening programmes. We also examined how the age restriction should be set in cholesterol screening programmes. / Results / As compared to mass screening, our new model can achieve a high sensitivity and save some 80% the cost of cholesterol measurements. The sensitivity depends mainly on the hypothetical cholesterol level used and seems independent of population’s CVD risk, treatment cut-off values and risk prediction model. The model performed well in almost all the conditions tested. When the hypothetical cholesterol was set at MEAN+2SD, the resulting sensitivity of our selective screening model was almost always above 95% and close to the expected 97.5%. The sensitivity was only compromised slightly if cholesterol is not measured at all for the Chinese population. Furthermore, in order to save more costs, cholesterol measurement could be better restricted to men aged 50-84 and women 60-84 years regardless of the screening model used. In CVD events prevented, mass screening is always the best but our model can prevent almost as many. In costs, mass screening is always the most expensive but our model can save all or most of the cost. The NICE selective model can perform as well as our model only when it is used in an appropriate manner and in certain circumstances. / Conclusion / Our new cholesterol screening model has a high sensitivity which is comparable to that of universal screening programs but can save most of the cost on cholesterol measurements. In where resources are particular sparse, our model can also perform well by applying it only to certain age groups, which will further save cholesterol measurement costs. Cholesterol measurement could even be completely avoided for the Chinese population if our findings can be re-confirmed correct with more updated data. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Hu, Xuefeng. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 114-121). / Abstract also in Chinese. / Abstract (in English) --- p.i / Abstract (in Chinese) --- p.iv / Acknowledgements --- p.vi / Abbreviations used in the thesis --- p.viii / List of Tables --- p.xvi / List of Figures --- p.xviii / List of Boxes --- p.xix / Chapter 1. --- Introduction --- p.1 / Chapter 1.1 --- The burden of cardiovascular disease --- p.1 / Chapter 1.2 --- Primary prevention of CVD --- p.2 / Chapter 1.3 --- The high-risk individual strategy for CVD primary prevention --- p.3 / Chapter 1.3.1 --- The high risk individual strategy is effective --- p.4 / Chapter 1.3.2 --- The high risk individual strategy is cost-effective --- p.4 / Chapter 1.4 --- Who should be treated with drugs? --- p.5 / Chapter 1.4.1 --- The single risk factor strategy --- p.5 / Chapter 1.4.2 --- The overall CVD risk strategy --- p.7 / Chapter 1.4.3 --- Scope of CVD primary prevention --- p.8 / Chapter 1.5 --- Methods for assessing the CVD risk --- p.9 / Chapter 1.6 --- Current strategies for cholesterol measurements --- p.10 / Chapter 1.6.1 --- United States National Cholesterol Education Program --- p.13 / Chapter 1.6.2 --- American Heart Association CVD and Stroke prevention guideline --- p.14 / Chapter 1.6.3 --- The U.S. Preventive Services Task Force guideline --- p.15 / Chapter 1.6.4 --- New Zealand guideline 2003 --- p.16 / Chapter 1.6.5 --- Australian guideline 2009 --- p.17 / Chapter 1.6.6 --- The Joint British Society guideline-2 --- p.17 / Chapter 1.6.7 --- UK Department of Health guideline on vascular check --- p.18 / Chapter 1.6.8 --- China Blood Lipid Modification Guideline 2007 --- p.18 / Chapter 1.6.9 --- Summary of the reviewed guidelines --- p.19 / Chapter 1.7 --- Rationale for a selective screening model --- p.20 / Chapter 1.8 --- The UK NICE model --- p.22 / Chapter 1.9 --- Objectives of this study --- p.24 / Chapter 2 --- Methods --- p.25 / Chapter 2.1 --- The new cholesterol screening model --- p.25 / Chapter 2.2 --- Framework for evaluating the new screening model --- p.27 / Chapter 2.3 --- Indexes for evaluating the basic performance of screening models --- p.28 / Chapter 2.3.1 --- Sensitivity, specificity and % need cholesterol measurement --- p.28 / Chapter 2.3.2 --- Sensitivity analysis for model performance --- p.29 / Chapter 2.3.2.1 --- Using different hypothetical cholesterol values --- p.29 / Chapter 2.3.2.2 --- Using different treatment cut-off thresholds --- p.30 / Chapter 2.3.2.3 --- Using different populations --- p.30 / Chapter 2.3.2.4 --- Using different risk equations --- p.31 / Chapter 2.4 --- Data --- p.31 / Chapter 2.4.1 --- The Health Survey for England --- p.31 / Chapter 2.4.1.1 --- Background and aim of the survey --- p.31 / Chapter 2.4.1.2 --- Survey design --- p.32 / Chapter 2.4.1.2.1 --- Sampling Frame --- p.32 / Chapter 2.4.1.2.2 --- Weighting variables --- p.33 / Chapter 2.4.1.3 --- Data collection --- p.33 / Chapter 2.4.1.3.1 --- Blood cholesterol --- p.34 / Chapter 2.4.1.3.2 --- Blood pressure --- p.34 / Chapter 2.4.1.3.3 --- Smoking --- p.34 / Chapter 2.4.1.3.4 --- History of CVD and diabetes --- p.34 / Chapter 2.4.1.3.5 --- Treatment history --- p.35 / Chapter 2.4.2 --- The 2002 China National Nutrition and Health Survey --- p.35 / Chapter 2.4.2.1 --- Survey design --- p.36 / Chapter 2.4.2.2 --- Data collection --- p.36 / Chapter 2.4.2.2.1 --- Blood pressure --- p.36 / Chapter 2.4.2.2.2 --- Blood cholesterol --- p.38 / Chapter 2.4.2.2.3 --- Smoking --- p.38 / Chapter 2.4.2.2.4 --- History of CVD, diabetes and drug treatment --- p.38 / Chapter 2.4.3 --- Subjects eligible for analysis in this study --- p.38 / Chapter 2.5 --- CVD risk prediction --- p.43 / Chapter 2.5.1 --- The Framingham risk equation for the UK population --- p.43 / Chapter 2.5.2 --- The Asian equation for the Chinese population --- p.44 / Chapter 2.5.3 --- Adjusting for cholesterol and blood pressure --- p.45 / Chapter 2.5.4 --- Deriving the hypothetical cholesterol --- p.46 / Chapter 2.6 --- Identifying the appropriate age ranges for cholesterol measurement --- p.47 / Chapter 2.7 --- Comparing various screening models and options --- p.47 / Chapter 2.7.1 --- Compared screening models and options --- p.47 / Chapter 2.7.1 --- Indices for the performance of the screening options --- p.49 / Chapter 2.7.2 --- Costs of different screening options --- p.50 / Chapter 2.7.2.1 --- Components of screening cost from societal perspective --- p.50 / Chapter 2.7.2.1.1 --- Cost for inviting people for data collection --- p.50 / Chapter 2.7.2.1.2 --- Cost for the full risk assessment --- p.51 / Chapter 2.7.2.1.3 --- Treatment cost --- p.51 / Chapter 2.7.2.1.4 --- Cost saved for avoided CVD events --- p.52 / Chapter 2.7.2.2 --- Components of screening cost from health system’s perspective --- p.52 / Chapter 2.7.3 --- Number of CVD events avoidable --- p.53 / Chapter 2.8 --- Statistical analysis --- p.54 / Chapter 2.8.1 --- Descriptive analysis --- p.54 / Chapter 2.8.2 --- Cross-tabulation analysis --- p.54 / Chapter 2.8.3 --- Survey data analysis --- p.54 / Chapter 3 --- Results --- p.57 / Chapter 3.1 --- Description of data --- p.57 / Chapter 3.1.1 --- The UK population --- p.57 / Chapter 3.1.1.1 --- Sumamry of CVD risk and risk factors --- p.57 / Chapter 3.1.1.2 --- Distribution of age --- p.57 / Chapter 3.1.1.3 --- Distribution of blood pressure and blood cholesterol --- p.58 / Chapter 3.1.1.4 --- Distribution of the predicted 10-year CVD risk --- p.62 / Chapter 3.1.1.5 --- Relation between the risk threshold and age --- p.63 / Chapter 3.1.2 --- The Chinese population --- p.65 / Chapter 3.1.2.1 --- Summary of CVD risk and risk factors --- p.65 / Chapter 3.1.2.2 --- Distribution of age --- p.65 / Chapter 3.1.2.3 --- Distribution of blood pressure and blood cholesterol --- p.66 / Chapter 3.1.2.4 --- Distribution of the predicted 10-year CVD risk --- p.69 / Chapter 3.1.2.5 --- Relation between the risk threshold and age --- p.70 / Chapter 3.2 --- Performance of our new screening model --- p.72 / Chapter 3.2.1 --- Performance according to cholesterol values in the UK population --- p.72 / Chapter 3.2.2 --- Performance according to treatment cut-offs in the UK population --- p.73 / Chapter 3.2.3 --- Performance according to cholesterol values in the Chinese population --- p.73 / Chapter 3.2.4 --- Performance according to the risk cut-offs in the Chinese population --- p.74 / Chapter 3.2.4 --- Performance using different risk equations --- p.76 / Chapter 3.3 --- Comparison with other existing screening models --- p.77 / Chapter 3.3.1 --- Performance of the 3 models within an age-restricted UK population --- p.79 / Chapter 3.3.2 --- Performance of the 3 models within an age-restricted Chinese population --- p.81 / Chapter 3.3.3 --- Performance of the 3 models in the entire UK population --- p.83 / Chapter 3.3.4 --- Performance of the 3 models in the entire Chinese population --- p.84 / Chapter 3.3.5 --- Costs of various screening options --- p.87 / Chapter 3.3.6 --- Number of CVD events avoidable of the screening programmes --- p.92 / Chapter 4 --- Discussion --- p.96 / Chapter 4.1.1 --- Performance at different hypothetical cholesterol values --- p.96 / Chapter 4.1.2 --- Performance at various treatment cut-off thresholds --- p.97 / Chapter 4.1.3 --- Performance with different risk equations --- p.98 / Chapter 4.1.4 --- Performance in different populations --- p.99 / Chapter 4.1.5 --- Performance with different survival functions --- p.99 / Chapter 4.2 --- Further modifications of the model --- p.100 / Chapter 4.2.1 --- A model without any cholesterol measurement --- p.100 / Chapter 4.2.2 --- Age restriction for selective models --- p.102 / Chapter 4.2.3 --- Our model with potential personalized treatment cut-off --- p.103 / Chapter 4.2.4 --- Three key things to ensure model performance in other population --- p.104 / Chapter 4.3 --- CVD events preventable --- p.105 / Chapter 4.3.1 --- Importance of age restriction --- p.105 / Chapter 4.3.2 --- Limitations of the NICE model --- p.106 / Chapter 4.4 --- Costs of different screening models --- p.107 / Chapter 4.4.1 --- Cost from different perspectives --- p.107 / Chapter 4.4.2 --- Cholesterol measurement cost and routine data collection --- p.108 / Chapter 4.4.3 --- Cost components --- p.109 / Chapter 4.4.4 --- Ways to reduce cholesterol measurement costs --- p.109 / Chapter 4.4.5 --- Costs and gain of the missing 2.5% high risk individuals --- p.109 / Chapter 4.5 --- Strengths and limitations of this study --- p.110 / Chapter 4.6 --- Recommendations --- p.113 / References --- p.114

Background: The role of cytokines in the pathogenesis of periodontal disease and the effect of smoking on these mediators has been reported. However, findings have been variable and simultaneous measurement of multiple cytokines has been limited. This study utilized a quantitative multiplex assay to measure a comprehensive panel of Th1, Th2, and pro-inflammatory cytokines and chemokines (including several novel cytokines) in gingival crevicular fluid (GCF) in chronic periodontitis subjects. The impact of cigarette smoking on these GCF mediators was also assessed. Methods: Forty subjects (age 40-75 years) with generalized severe chronic periodontitis (20 smokers and 20 non-smokers) and 12 periodontally healthy controls participated in the study. GCF was collected from four sites in the diseased groups: 2 diseased sites [(probing depth (PD) and clinical attachment level (CAL) ≥5mm with bleeding on probing (BOP)] and 2 healthy sites (PD and CAL ≤3mm, no BOP); 2 healthy sites were sampled in the healthy controls. The volumes of the GCF samples were measured and the GCF mediators assessed in duplicate utilizing a multiplex immunoassay (Luminex). Intragroup, intergroup and pooled comparisons were performed using non-parametric tests including the Mann-Whitney and the Wilcoxon matched-pairs signed-rank test. Results: GCF in diseased sites (vs. controls) contained significantly (p<0.05) higher amounts of IL-2, IFN-γ, IL-3, IL-4 (Th1/Th2 cytokines); IL-1α, IL-1β, IL-6, IL-12 (p40) (pro-inflammatory cytokines); IL-8, MIP-1, RANTES (chemokines); and IL-15 (regulator of T-cells and NK cells). IP-10 was the only mediator exhibiting lower levels (p<0.0005) in diseased sites compared to controls. Smoking had an inhibitory effect (p<0.05) on pro-inflammatory cytokines (IL-1α, IL-6, IL-12 (p40)); chemokines (IL-8, IP-10, MCP-1, MIP-1, RANTES) and regulators of T-cells and NK cells (IL-7, IL-15) in comparison to sites within non-smokers. Interestingly, smokers had elevated GCF levels (p<0.05) of IL-1α, IL-1β and IL-3 relative to sites in healthy controls. Conclusions: Similar to previous reports, periodontitis subjects had significantly elevated cytokines and chemokines compared to healthy controls. Smokers exhibited a decrease in several pro-inflammatory cytokines, chemokines and regulators of T-cells and NK-cells as compared to nonsmokers however; little influence was observed on Th1/Th2 cytokines. Interestingly, smokers exhibited decreased amounts of GCF IL-7, IL-12(p40), IL-15, IP-10, MCP-1, MIP-1 and RANTES, which calls for future investigation. The multiplex comprehensive assay used in this study to assess cytokines in a single GCF sample is a significant advancement. This technology can be used to compare serum and GCF cytokine profiles in periodontitis and correlate systemic and localized immune responses. This should provide insight into the impact of smoking, as well as other host modifiers, on important systemic and periodontal interactions.

Introduction: Oropharyngeal tumours belong to the most common malignancies situated in the head and neck area. In the past, their incidence has been associated with classical risk factors (smoking and alcohol use). In the recent years, the increase of oropharyngeal carcinomas resulting from HPV (human papilloma virus) infection incidence has been observed. The change of their aetiology also implies a number of clinical differences, the most important being a significantly better survival prognosis in patients with HPV+ carcinomas. Aims: The main goal of this thesis was to characterize correctly patients with oropharyngeal carcinomas and to identify different specifics of nursing intensive care for these patients. Methods: The quantitative prospective study involved 30 patients following their surgical treatment of oropharyngeal carcinoma, hospitalised in an intensive care unit. The patients were divided into 3 groups: HPV+ non-smokers, HPV+ smokers, HPV- smokers. Results: The study confirmed the demographic differences between individual patient groups. The HPV+ non-smokers group is characterized by a lower age in average, which is significantly reflected in a reduced duration of hospital stay. In addition, opioid administration rate, infection rates and postoperative complications incidences are...

The major goal of this study was to achieve sustained cultivation of virulent T. pallidum in vitro. The putatuive binding of host proteins to the outer membrane (OM) of intact, virulent T. pallidum subsp. pallidum has been investigated. A major breakthrough was the development of a filtration assay, usinglow protein-binding membrane filters, for the measurement of substances bound to or incorporated into th eOM of T. pallidum. This avoided the conventional manipulations which can damage the fragile OM of T. pallidum. Using this filtration assay, studies on the binding of host serum proteins demonstrated that intact treponemes did not bind host proteins as previously reported. It also indicated that previous studies were probably performed with damaged by this research. The studies on the binding of polyclonal and monoclonal antibodies to intact and detergent treated treponemes provided evidence of the low level binding of antibody to intact treponemes which was greatly enhanced but the removal of the outer membrane with 0.1% Triton X. This research research corroborated that of others which suggests that the outer membrane of T. pallidum contains very little protein or surface exposed antigen.

Bibliography: leaves 171-211 / 211 leaves : / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (M.D.)--University of Adelaide, 1988

Includes bibliographical references. / 1 v. (various foliations) : ill. (some col) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Community Medicine, 1994

"December 2004" / Includes bibliographical references (leaves 342-379) / xiii, 379 leaves : ill. (col.) ; 30 cm. / Title page, contents and abstract only. The complete thesis in print form is available from the University Library. / Thesis (Ph.D.)--University of Adelaide, Dept. of Medicine, 2005

<p>This thesis evaluates surgical correction in patients with paralytic scoliosis with emphasis on function and activity. The thesis includes four studies of 100 consecutive patients preoperatively evaluated and surgically corrected between 1992 and 1996 at Linköping University Hospital. Eighteen different diagnoses were represented. The postoperative follow-ups were at one year and in average seven years. Six patients dropped out during the first year and twelve during the long-term follow-up period. The assessments included general information, lung function, and measurements of radiographs, function and activity - seating posture, ADL, pain, care and need for rest. The patients or relatives view on the effects of surgery were evaluated in follow-up questionnaires.</p><p>The preoperative results of the 100 patients described a heterogeneous group in terms of function and activity. Even when the patients were grouped into subgroups according to the Scoliosis Research Society classification, they remained heterogeneous. In patients who could understand verbal instructions assessments that needed co-operation could be used and in those who could not understand verbal instructions, assessments relied more heavily on measures of function and level of dependence. Preoperative results of weight distribution on the seating surface were explained by thoracolumbar/lumbar spinal imbalance and pelvic obliquity R²=0.45 (n=45).</p><p>The one-year follow-up of 94 patients showed improvements in angle of scoliosis, sitting balance, weight distribution to the seating surface, seating supports in the wheelchair, time needed for rest. The results in subgroups were almost the same as in the whole group. The subjective results for patients or relatives in the follow-up questionnaire showed a positive outcome of surgery. In the comparison between the one-year follow-up and the long-term follow-up there were further improvements in sitting balance, ADL, and care given, but the angle of scoliosis was increased. These results were in line with patients’ and relatives’ assessments in the follow-up questionnaire and in the open-ended questions.</p><p>Due to the heterogeneity of patients with paralytic scoliosis, irrespective of disorder, it is important to focus on different subgroups with regards to the patients’ total situation. The surgically corrected and stabilised spine resulted in the strength to keep the body upright with improvements in function, activity and possibilities to belong in social activities. Further improvements were shown between the one-year follow-up and the long-term follow-up. It is recommended that patients who have been surgically corrected for paralytic scoliosis are followed for more than one year.</p>

Amyotrophic lateral sclerosis (ALS) is a devastating disease characterized by the progressive degeneration of motor neurons. Dominantly-inherited mutations to the antioxidant enzyme Cu,Zn superoxide dismutase (SOD1) cause 3-6% of all ALS cases. The complete mechanism behind the toxicity of mutant SOD1 remains unclear, although significant evidence points to aberrant or incomplete metal-binding having a role in a toxic gain-of-function. However, the relevance of the metal-binding of SOD1 to mutant-SOD1-linked ALS remains controversial. Direct assessments of protein metal-binding from transgenic, SOD1-overexpressing rodent models of the disease are difficult to acquire due to the non-covalent nature of the interaction. The relatively small amount of disease-afflicted spinal cord tissue in which the motor neurons reside compounds the difficulty of measuring the protein metal binding of SOD1 from transgenic mice. This dissertation addresses the metals bound to SOD1 throughout the disease course in transgenic mice using a novel mass spectrometry assay. The methodology developed here offers the first detailed examination of partially unfolded intermediates of SOD1 present in the spinal cord of pre-symptomatic, symptomatic, and end-stage transgenic mice overexpressing the ALS-associated SOD1 mutation G93A (glycine mutated to alanine at position 93). These results were compared to age-matched transgenic mice expressing wild-type SOD1 that do not develop ALS symptoms. To extract SOD1 from relevant spinal cord tissue, a 300 ��m necropsy punch was used to remove a small piece of tissue from the ventral or dorsal gray matter of a 1 mm-thick slice of spinal cord. Physiological salts that interfere with electrospray mass spectrometry were removed by binding the proteins to a C4 Ziptip��, a pipette tip containing hydrophobic, reversed-phase packing material. Washing the Ziptip-bound proteins with water eliminated interfering salts. Bound proteins could then be eluted into a mass spectrometer with low concentrations of acetonitrile plus formic acid. Electrospray ionization conditions were determined that could keep both copper and zinc bound to SOD1. Using a high-resolution Fourier transform-ion cyclotron resonance mass spectrometer, we used the assay to collect isotopically-resolved protein mass data. Theoretical protein isotope distributions were calculated from the empirical formulas of SOD1 and matched to the experimental data with a least squares fitting algorithm to determine the multiple intermediates of SOD1 present. Spinal cord tissue, wild-type in particular, was notable for containing significantly more one-metal SOD1 than any other tissue, despite having 3-fold less SOD1 than liver. We quantitatively compared the levels of soluble, partially unfolded intermediates of SOD1 from wild-type and G93A SOD1 spinal cords. Wild-type mouse spinal cord contained significantly more of all of the partially unfolded intermediates copper-deficient SOD1, disulfide reduced SOD1, and apo SOD1. The amount of zinc-containing SOD1 was exceptionally high in wild-type mice, comprising 60% of the total SOD1 in wild-type spinal cord. The larger amounts of these SOD1 intermediates in wild-type transgenic mice indicate that they are not directly responsible for toxicity in vivo. However, copper-containing, zinc-deficient SOD1 was the one species found in higher concentrations in G93A SOD1 spinal cord. The concentration was on average 0.6-0.8 ��M in G93A spinal cord, compared to 0.1-0.3 ��M zinc-deficient SOD1 found in the wild-type mouse spinal cord. A concentration above 0.5 ��M zinc-deficient SOD1 was sufficient to induce motor neuron death in vitro. These results suggest that copper-containing, zinc-deficient SOD1 could be the toxic species responsible for motor neuron death in ALS. / Graduation date: 2013

Displaced femoral neck fractures comprise more than a third of all hip fractures. There is controversy as to the optimal treatment. Despite attempts to improve the methods for internal fixation, complication rates have been almost unchanged: 20-40% non-union and late segmental collapse in another 10-20%. Internal fixation has been the preferred treatment in Scandinavia, whereas primary hemi- or total arthroplasty have been more prevalent in the rest of Europe and North America. In this study, patients 75 years or older, including those with mental impairment, were randomized to either internal fixation or cemented primary total hip arthroplasty (THA). A total of 146 hips in 143 patients were followed for two years. After one year 23% had died, and after two years 29%. Mortality was about the same in both groups. The accumulated mortality was pronounced among the mentally impaired patients. In the internal fixation group, 44% underwent further surgery. In the THA group, 18% dislocated. The dislocation rate was higher for the mentally impaired patients. The Harris hip scores were higher in the THA group, whereas pain was more common in the internal fixation group. The first 50 patients in each treatment group were studied concerning heterotopic ossification (HO), a well-known complication after THA. The incidence of HO in the THA group was similar to what is found after THA due to osteoarthritis. However, only 1/39 developed severe symptoms. A subgroup of 100 patients was included in a study concerning nutritional status and functional capacity using the Modified Norton scale, Katz index of ADL and a questionnaire measuring instrumental activities of daily living. The THA group fared better concerning weight change over time, locomotion and pain. The nutritional intervention did not show any measurable effects. All patients were followed until two years postoperatively and all fracturerelated hospital costs, including reoperations, were calculated. We found no difference in total costs between the treatment groups. Costs to the municipality were calculated comparing the baseline cost before surgery with the average cost per month during the first postoperative year. No difference was found between the treatment groups. On the basis of our results, we recommend arthroplasty for patients in this age group with normal mental function and high functional demands.