Introduction: Amyotrophic lateral sclerosis (ALS) is a deadly, progressive neuromuscular disease that affects individuals all over the world. About 10% of the patients have a familial predisposition (FALS) while the remainder of cases are isolated or sporadic (SALS) and of unknown cause. To date, the principal recognized risk factors for ALS are higher age, male gender, slim figure (BMI<23) and a family history of ALS. In 1993, Rosen et al. observed that some FALS cases were associated with mutations in the gene encoding the CuZn superoxide dismutase enzyme (SOD1). Since then, several mutations in the SOD1 gene have been discovered, and mutations in more than 18 other genes have been associated with causing ALS. The aim of this thesis was to identify new mutations associated with ALS pathogenesis, and by comparing patients from different countries, were we also able to identify population-specific genetic variations. The studies are referred to as I–V. Methods: With written informed consent and adhering to the tenets of the Declaration of Helsinki, through a national network of ALS clinicians´, venous blood samples were collected from ALS patients and healthy subjects in Europe and the USA. The patients were diagnosed according to the El Escorial criteria, and as having FALS according to the criteria of Byrne et al. (2011). The DNA variations were amplified by various PCR techniques. (I, III and IV) The amplicons of ataxin 2 (ATXN2), profilin 1 (PFN1), and vesicle-associated membrane protein type B (VAPB) were characterised by direct sequencing. (II) After quantitative PCR, a genotype-phenotype correlation was performed to assess whether the survival motor neuron gene (SMN) modulates the phenotype of ALS. (V) The amplicons of the 50 base pair deletion in the SOD1 promotor (50 bp) were separated by electrophoresis on agarose. Results: (I) We observed a significant association between CAG expansions in the ATXN2 gene and ALS in a European cohort. (II) Abnormal copy number of the SMN1 gene was identified as a risk factor in France, but not in Sweden. Homozygosity of the SMN2 deletion prolonged survival among Swedish ALS patients, compared to French patients. (III) We identified two mutations in the PFN1 gene, the novel p.Thr109Met mutation and the p.Gln117Gly mutation, in two unrelated FALS patients. (IV) In our cohort, we identified five VAPB mutations p.Asp130Glu, p.Ser160del, p.Asp162Glu, p.Met170Ile, and p.Arg184Trp, two of which are novel. (V) The 50 bp deletion upstream of the SOD1 gene was found in equal frequencies in both the patient and control cohorts. The 50 bp deletion did not affect SOD1 enzymatic activity. Furthermore, we found no differences in age of onset or disease duration in relation to the 50 bp deletion genotype.VI Conclusions: (I) Our findings indicate that ATXN2 plays an important role in the pathogenesis of ALS, and that CAG expansions in ATXN2 are a significant risk factor for the disease. (II) We suggest that abnormal SMN1 gene copynumber cannot be considered a universal genetic susceptibility factor for ALS. We also propose that the effect of abnormal SMN2 gene copy number on ALS phenotype may differ between populations. (III) This work provides evidence that PFN1 mutations can cause ALS as a Mendelian dominant trait. The novel p.Thr109Met mutation also shows that disturbance of actin dynamics can cause motor neuron degeneration. (IV) We find it unlikely that the VAPB mutations cause ALS in our cohorts. (V) We find it unlikely that the 50 bp region contains important regulatory elements for SOD1 expression. This thesis supports the theory that ALS is a multigenetic disease, but there appears to be great genetic variation among apparently identical populations. These studies emphasise the importance of continuous genetic screening, to identify further mutations and genes involved in ALS disease, but it also highlights the importance of cooperation and comparison between countries. / On the aetiology of ALS: A comprehensive genetic study

BPH¡]Benign prostate hyperplasia¡^is one of the most common chronic diseases in aging male around the globe. TURP¡]Transurethral Resection of Prostate¡^remains the gold standard procedure of choice in BPH treatment. But limited literatures regarding the late complication of TURP was available. For understanding the long term follow up result after TURP, and predict the risk factors for re-intervention, we accessed the hospital claims for TURP from the National Health Insurance database, utilizing data from 2001 to 2007 , in 2001, 2002, 2003 TURP cases, we followed each cohort for 5 years to evaluate the late complications. We also examined the association between the characteristics of patient, hospital and the long term prognosis. In this study we found that from 2001to 2003, totally 1,225 patients under went TURP surgery, with the average age 71.52 ¡Ó 7.65 years (47-94 years). Among these cases, 140 patients (11.43%) experienced secondary surgery. Of the 140 secondary surgery patients, 71 received a secondary TURP, 35 received urethral stricture related surgery and 34 received bladder neck contracture related surgery. The study revealed both the characteristics of the patient and the hospital did not show significantly effect to the long term prognosis. In prediction the risk factors of the secondary surgery, the logistic regression analysis revealed those hospitals located at the central part of Taiwan compared to those at northern part of Taiwan showed a relative risk of 0.58, a significant trend of lower risk for secondary surgery. Otherwise, except this geographic location difference, other characteristics of the patient and the hospital show no significantly risk to the post-TURP second surgery. Conclusion of our study, the result of TURP surgery in Taiwan was fairly equal to that in advanced countries. Patient comorbidity, treated in different level, ownership hospitals resulted no significant difference in post-TURP prognosis.

Hintergrund. In klinischen und epidemiologischen Untersuchungen wurden retrospektiv Assoziationen zwischen Angst- und Alkoholstörungen bestätigt. Bei Personen, die von beiden Störungen betroffen waren, fand man restrospektiv meist einen früheren Beginn der Angststörungen im Vergleich zu den Alkoholstörungen, was kausal im Sinne der Selbstmedikationshypothese interpretiert wurde. Diese konnte bisher nicht eindeutig bestätigt werden. Zur Aufklärung notwendige prospektive Untersuchungen, die Angststörungen auf diagnostischer Ebene erfassen, zwischen verschiedenen Angststörungen unterscheiden und sich auf Jugendliche beziehen, fehlen bisher. Fragestellung. Die Bedeutung von Angststörungen für die Entwicklung von erhöhtem Alkoholkonsum und Alkoholstörungen bei Jugendlichen und jungen Erwachsenen. Methodik. Die Analysen basieren auf den Daten der prospektiv-longitudinalen EDSP-Studie (Follow-Up: insg. 4 Jahre) mit einer epidemiologischen, repräsentativen Stichprobe von 3021 Personen im Alter zwischen 14 und 24 Jahre zu T0 aus München und Umland. Zur Erhebung von DSM-IV-Diagnosen wurde das M-CIDI verwendet. Ergebnisse. Primäre Panikstörungen, Panikattacken und Soziale Phobie erwiesen sich prospektiv als spezifische Prädiktoren für Beginn und Aufrechterhaltung von Alkoholproblemen. Umgekehrt waren Alkoholprobleme mit einem erhöhten Risiko für den Beginn von Sozialer Phobie und GAS assoziiert. Bezüglich DSM-IV Diagnosekriterien fanden sich phobische Ängste sowie Episoden intensiver Angst als Risikofaktoren für den Beginn von Alkoholproblemen. Vermeidungsverhalten war mit einem verminderten Risiko für nachfolgende Alkoholprobleme verbunden. Schlussfolgerungen. Maßnahmen zur Prävention von Alkoholproblemen können sich zielgruppenorientiert an Jugendliche mit Sozialer Phobie und Paniksymptomatik richten. Bei Patienten, die sich wegen Alkoholproblemen in Behandlung begeben, ist eine umfassende Diagnostik zur Identifikation zusätzlicher Angststörungen ratsam. / Background. Many clinical and epidemiological studies have documented significant cross-sectional comorbidities between anxiety disorders and alcohol use disorders. Analysis of retrospective age-of-onset reports suggests that the anxiety disorders often start earlier than the alcohol disorders. These data have often been interpreted in terms of a self-medication-model implying a causal mechanism. Overall, in former studies this model couldn't definitely be proofed. Prospective studies that follow a sample of adolescents into adulthood assessing different anxiety disorders on an diagnostic level are needed to confirm these associations. Methods. Baseline and four-year-follow-up data from the EDSP-Study, a prospective community survey of 3021 (2548 at follow-up) adolescents and young adults aged 14 to 24 years at baseline carried out in Munich, were used. DSM-IV anxiety disorders, alcohol use and alcohol use disorders were assessed with the M-CIDI. Results. While in retrospective analyses strong associations between nearly all anxiety disorders and alcohol problems, especially harmful use and dependence, were found, prospective analyses showed that only primary panic disorder, panic attack and social phobia are specific predictors of subsequent onset and persistence of alcohol problems. Contrary, primary alcohol problems were related to subsequent onset of social phobia and GAD. Considering the different DSM-IV-criteria, phobic anxiety as well as episodes of intensive anxiety were found to be risk factors for the following onset of alcohol problems. Avoidance behavior was associated with a lower risk for subsequent alcohol problems. Conclusions. Alcohol prevention programs could be directed to target groups with social phobia and panic. Patients with alcohol problems should carefully be screened for comorbid anxiety disorders. In order to prevent relapses the treating of social phobia and panic should be part of the therapy with comorbid alcohol patients.

The purpose of this study was to determine how often smoking patients receive quit advice and if patient age, and number and type of clinical encounters are associated with odds of receipt. Behavioral Risk Factor Surveillance System (BRFSS) 2000 data were used to study 10,582 smokers (aged ³ 18) having ³ 1 of three types of clinical encounters in the past year: routine checkups, other physician encounters, or dental visits. Multivariate-adjusted odds ratios (ORs) for quit advice by patient age, encounter type, and number of doctor's visits were calculated. Almost 55% of patients were advised to quit smoking. There was a 4-23% chance of receiving quit advice at any given doctor's visit. Odds of receiving advice did not increase with increasing number of visits. With advancing age, men were more likely, women less likely, to receive quit advicebut only significantly for White men. Compared to those having dental visits, ORs for receiving quit advice for patients having checkups and other physician encounters were 3.35 (95% CI 2.ll, 5.31) and 3.03 (95%CI 1.32, 6.97) respectively. These cross-sectional data suggest that whereas a small majority of smoking patients are advised to quit at some clinical encounter, smoking patients are not advised to quit at the majority of encounters. Being young and male, or seeing dentists rather than doctors made patients less likely to receive quit adviceas did having lower education or BMI, no insurance or coverage other than military or private, not having asthma, or not having breast exams or follow-up Papanicolaou smears if female. Based on a previously-reported absolute quit difference of 1.9%, if smoking patients received quit advice just once at any of their encounters with physicians in a year, at least 800,000 more U.S. smokers would quit at an economic savings of $2.4 billion.

No description available.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

To identify the risk factors being associated with aetiology of amyotrophic lateral sclerosis (ALS), a series of systematic reviews based on existing observational epidemiological studies identified through searching of bibliographic databases were conducted. Associations between ALS and a number of genetic and environmental risk factors were examined using meta-analysis. Specifically we found that previous exposure to lead, pesticides, solvents, experience of trauma and electric shock were associated with relative increased risks of developing ALS of 86% [odds ratio (OR) =1.86, 95% CI: 1.39-2.48], 57% (OR=1.57,95% CI: 1.19-2.08), 47% (OR=1.47, 95%CI: 1.13-1.80), 64% (OR=1.64; 95%CI: 1.36-1.98), and 2.27% (OR=3.27, 95%CI:1.87-5.73) respectively, compared to their corresponding controls. The presence of intermediate CAG repeat expansion in the ATXN2 gene was associated with a 4.4 -fold increase in the risk of ALS (OR=4.44, 95%CI: 2.91-6.76). However, the attributable risk associated with each identified risk factor was estimated to be less than 5% of all ALS cases. These results confirm that ALS is a rare multifactorial degenerative condition of motor-neurons.

The rapid growth of biotechnology has promoted industries to harness the market in the field of human energy systems. A growing literature of research has linked human energy systems to weight loss, major diseases or illnesses. In our modern society, the general public is exposed to everyday stress, which often results in the development of chronic stress. Therefore, stress becomes an important area of medicine. It has been postulated that suppressing these physiological responses may help in disease prevention. Consequently, there is an urge for defining a model integrating stress with the human energy model. Over the past decades, a large amount of research has been put forward in defining the physiological responses or changes when an individual experiences psychological or environmental changes such as interpersonal dysfunction, traumatic experiences and diseases. Interestingly, it reveals that blood glucose fluctuation tends to be the end product of most psychological or physiological stressors. The blood glucose system is one of the major subsystems of the complete metabolic fuel system in humans. In this study, an empirical model and procedure for the derivation of the model due to various psychological influences on the human energy system are presented. This study can be divided into two main sections. An overview of a previously developed unit (ets: equivalent teaspoon sugar) for blood glucose quantification is given in the first section. Stress quantification methods are derived in the second section and a link between these methods and ets is drawn. A verification study of the derived model is also presented in the second section. Stress can be divided into physiological stress and psychological stress. Between the two types of stress, a generalised model based on studies of physiological stress has been drawn and accepted by the public. However, the generalised model does not account for psychological stress. Evidence shows that depending on the specific nature of a stressful circumstance, it can cause different activations of central circuits leading to the release of different neurotransmitters. However, these neurotransmitters have a common effect of increasing blood glucose concentrations. A substantial amount of literature shows that, when stress involves mental effort, epinephrine (EPI) is the main endocrine response. However, stress that does not require mental effort mainly induces cortisol release. The response models for different types of stress were derived using these relations. Furthermore, it is known that prolonged stress may lead to the development of disease. Several studies have used this observation and associated chronic stress with the relative risk factor of cardiovascular disease (CVD). Previously, different quartiles of risk factors for CVD have been related to blood glucose energy and ets expenditure. This link was further utilised to quantify chronic stress in this study. Increases in either of the two endocrine concentrations have been shown to raise the blood glucose level. In order to demonstrate the benefits of applying the ets concept, the cortisol and epinephrine responses were further quantified using the new glucose quantification method, the equivalent teaspoon sugar (ets) concept. The models derived in this study were verified against measured data. The models reveal a strong agreement with the measured data and therefore support the feasibility of these quantification methods. In conclusion, a link does exist between blood glucose energy and stress, and the highly accurate models derived for this association may serve as an adjunct tool for glycaemic control and stress management. / Thesis (Ph.D. (Electronical Engineering))--North-West University, Potchefstroom Campus, 2008.

The negative social and economic results of traffic accidents are the most serious problems within the concept of traffic safety. Every year, unfortunately, a huge number of traffic accidents result in destructive losses. Especially, when the holiness of human life is concerned, traffic safety has an invaluable role for the traffic improvement strategies. In this manner, Turkey places one of the highest ranks regarding the growing rate and severity of traffic accidents that should be immediately taken under control. In this study, an innovative model that constructs a hybrid between the spatial and statistical analyses is developed in order to examine the importance of enhancing statistical analysis with georeferenced data and so location-based studies in traffic accident analysis. Meanwhile, the effects of road characteristic and environment are considered for exploring the integral role of roadway factor to the occurrence of accidents, and consequently for emphasizing easily applicable and controllable engineering safety measures. Because of the rare and random distribution of traffic accident data, logistic regression is used for the statistical part of the study in order to find the pairwise risk factors among the roadway and environmental parameters. After unifying these relative risk factors with the logic of Analytic Hierarchy Process, the finalized accident risk factors are attached to the digitized road characteristics map through Geographic Information Systems (GIS). The abilities of GIS in mapping, displaying and overlaying different data sets ensure to visualize high risked accident areas with their corresponding potential causal factors. The integration of statistical and spatial analyses is essential for developing appropriate and effective precautions in addition to its easily understandable, applicable and modifiable structure. Finally, the model is proven to be appropriate for both interpreting the existing traffic accident problem or potential future accidents and also developing comprehensive and reliable location-based safety studies.

In the last decades our knowledge concerning cardiovascular risk factors has grown rapidly through results from longitudinal studies. However, despite new treatment, in Western countries coronary heart disease remains the leading cause of death and stroke is still the leading cause of severe disability. The studies reported in these papers examine the relationships between stroke/transient ischaemic attack (TIA) and a number of different factors measured on two different occasions in men born in Uppsala 1920-1924 and are epidemiological in their character. The findings indicate that in addition to already established risk factors, indices of an unhealthy dietary fat intake and high serum lipoprotein(a) are independent predictors of stroke/TIA. Among different glucometabolic variables a low insulin sensitivity index derived from the euglycaemic insulin clamp and proinsulin carries a high predictive value for later stroke, independently of diabetes. Moreover, cognitive test performance measured with Trail Making Test B at age 70 is a strong and independent predictor of brain infarction, indicating that the risk is already increased in the subclinical phase of milder cognitive dysfunction. Performance at a pre-stroke Trail Making Test is also of predictive value for mortality after first-ever stroke/TIA, but none of the studied pre-stroke variables or cognitive tests was found to be related to dependency after an event. In summary these studies provide further knowledge about predictors of stroke and of mortality after first-ever stroke. They also indicate the possible importance of new markers of risk, such as the level of lipoprotein(a), profile of fatty acids in the diet, low insulin sensitivity derived from clamp investigations, level of proinsulin, and cognitive performance measured with Trail Making Tests.