373 resultados para aristolan-10-ol-9-one


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The purpose of this study is to examine how transformation is defining feminist bioethics and to determine the nature of this transformation. Behind the quest for transformation is core feminism and its political implications, namely, that women and other marginalized groups have been given unequal consideration in society and the sciences and that this situation is unacceptable and should be remedied. The goal of the dissertation is to determine how feminist bioethicists integrate the transformation into their respective fields and how they apply the potential of feminism to bioethical theories and practice. On a theoretical level, feminist bioethicists wish to reveal how current ways of knowing are based on inequality. Feminists pay special attention especially to communal and political contexts and to the power relations endorsed by each community. In addition, feminist bioethicists endorse relational ethics, a relational account of the self in which the interconnectedness of persons is important. On the conceptual level, feminist bioethicists work with beliefs, concepts, and practices that give us our world. As an example, I examine how feminist bioethicists have criticized and redefined the concept of autonomy. Feminist bioethicists emphasize relational autonomy, which is based on the conviction that social relationships shape moral identities and values. On the practical level, I discuss stem cell research as a test case for feminist bioethics and its ability to employ its methodologies. Analyzing these perspectives allowed me first, to compare non-feminist and feminist accounts of stem cell ethics and, second, to analyze feminist perspectives on the novel biotechnology. Along with offering a critical evaluation of the stem cell debate, the study shows that sustainable stem cell policies should be grounded on empirical knowledge about how donors perceive stem cell research and the donation process. The study indicates that feminist bioethics should develop the use of empirical bioethics, which takes the nature of ethics seriously: ethical decisions are provisional and open for further consideration. In addition, the study shows that there is another area of development in feminist bioethics: the understanding of (moral) agency. I argue that agency should be understood to mean that actions create desires.

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Somatic embryogenesis (SE) is an asexual form of plant propagation that occurs in nature and mimics many of the events of sexual reproduction. Pinus sylvestris (L.) is an important source of timber in Northern Eurasia but it is recalcitrant to somatic embryogenesis. Several factors important for the success of the P. sylvestris embryogenic cultures have not been thoroughly investigated. In this study, we examined the effects of parental genotypes on the SE in P. sylvestris, the involvement of the gaseous plant growth regulator, ethylene in SE, and also biotic effects on somatic embryos as well as on seedlings. We tested parental effects on immature embryo initiation for different media, storage periods, and on the maturation process. Maternal effects were found to be crucial for SE in the absence of paternal effects. No maternal-paternal interaction was observed at any stage of somatic embryo production. Additionally the role of ethylene at different developmental stages of SE was investigated. Two ACC synthase genes, PsACS1 and PsACS2, were isolated and characterized. PsACS1 was expressed during the proliferation stage in all tested genotypes, whereas PsACS2 was only expressed in somatic embryos of each genotype. Ethylene production in embryos at stage 3 was significantly higher than the other stages. In a parallel study, the response of somatic embryos to fungal elicitors was investigated. Three fungi, a mutualistic ectomycorrhizal (ECM) fungus (Suillus bovinus), a weak Scots pine pathogen (Heterobasidion parviporum) and a strong pathogen (H. annosum) were used. The gene expression patterns for embryos exposed to the H. parviporum elicitor were found to be similar to that documented for S. bovinus among the tested genes. By contrast somatic embryos exposed to the H. annosum elicitor had a different pattern of regulation which was marked by a delayed response, and in some cases death of the embryos. Furthermore, interaction without direct contact between P. sylvestris seedlings and microbes (mutualistic and pathogenic fungus, cyanobacterium) were investigated. Several novel genes expressed in seedlings treated with ECM fungus were isolated which suggested that physical contact is not necessary for elicitation of host responses. The results suggest that somatic embryos and seedlings of P. sylvestris are genetically well equipped to respond to fungal elicitor/exudates and could serve as a suitable model for reproducible molecular studies in conifer tree patho- and symbiotic systems.

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Health-related quality of life (HRQoL) measurement has become an important outcome in treatment trials and in health policy decisions. HRQoL can be measured by using generic or disease-specific tools. Generic instruments can be used for comparing health status among patients in different health states and conditions but they do not focus specifically on the issues relevant in a particular disease. Disease-specific tools may be more responsive to changes within a specific condition. In earlier studies, impairment of HRQoL has been evident in patients with inflammatory bowel disease (IBD), especially when the disease is active. Data about the impact of comorbidity or demographic characteristics of the patients on HRQoL are partly controversial. This study, which comprised 2913 adult IBD patients, examined HRQoL using the disease-specific IBDQ and the general 15D instruments. The 15D scores of IBD patients were compared with scores of a gender and age matched general population sample. Frequency of IBD symptoms and arrangement of therapy were studied and compared with those of IBD patients in an earlier European study. Furthermore, data of other chronic diseases of the patients were obtained from the Social Insurance Institution s reimbursement register and comorbidity of IBD patients was compared with that of age and gender matched controls. --- Of the respondents, 37% reported that they suffered from disturbing IBD symptoms weekly. In 17% of the patients, the symptoms greatly affected the ability to enjoy leisure activities, and 14% stated that these symptoms greatly affected their capacity to work. Despite that, the great majority (93%) of patients expressed satisfaction with their current treatment, which exceeded the rate observed in the other European patients. The mean IBDQ score was 163, as the possible range is 32-224, and disease activity was strongly correlated with HRQoL. Older age, comorbid diseases, and female gender were also related to impairment of HRQoL. Lower HRQoL scores were seen also in newly-diagnosed patients and in those with a history of surgery, especially after stoma or ileal pouch-anal anastomosis (IPAA) operation. The range of 15D scores was 0.30-1.00, with mean of 0.87. As with the IBDQ, disease activity, older age and history of surgery were correlated with the score. Both the newly-diagnosed patients and patients with a long-lasting disease had lower scores than average even after adjusting for age. The 15D scores of IBD patients were significantly lower than those of the control group. A strong correlation was seen between the 15D and the IBDQ scores. Comorbidity with other chronic diseases was observed in 29% of IBD patients. Connective tissue diseases, chronic obstructive pulmonary diseases, pernicious anaemia, and coronary heart disease (CHD) were significantly increased in patients with IBD. Especially female IBD patients appeared to be at increased risk for CHD, and patients who reported weekly IBD symptoms had a higher risk for having other chronic diseases in addition to IBD. Comorbidity impaired HRQoL, as measured with both generic and disease-specific tools. In conclusion, HRQoL is impaired in IBD patients. An understanding of predictors of HRQoL will help to recognise patients who will need special support.

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The aim of this study has been to challenge or expand the present views on special education. In a series of six articles this thesis will directly or indirectly debate questions relating to inclusive and exclusive mechanisms in society. It is claimed that the tension between traditionalism and inclusionism within special education may harm the legitimation of special education as a profession of the welfare state. The articles address the relationship between these two approaches. The traditionalism-inclusionism controversy is partly rooted in different ways of understanding the role of special education with respect to democracy. It seems, however, that the traditionalism-inclusionism controversy tends to lead researchers to debate paradigmatic positions with each other than to develop alternative strategies for dealing with the delicate challenge of the differences within education. ---- There are three major areas of this discussion. The first part presents the theory of research programmes as a way of describing the content, the possibilities, and the problems of the different approaches. The main argument is that the concept of research programmes more clearly emphasizes the ethical responsibilities involved in research within the field of special education than does the paradigmatic approach. The second part considers the social aspects of the debate between traditionalism and inclusionism from different perspectives. A central claim made is that the work seen within special education must be understood as a reaction to the social and political world that the profession is part of, and that this also is part of a specific historical development. Even though it is possible to claim that the main aim for special education is to help people that are looked at as disabled or feel disabled, it is also necessary to understand that the profession is highly constrained by the grand narrative of the welfare state and the historical discourse that this profession is part of. The third part focuses on a central aspect of special education: the humanistic solutions towards people who are left behind by ordinary education. The humanistic obligation for special education is part of the general aim of the welfare state to provide an education for a democratic and an inclusive society. This humanistic aim and the goal to offer an education for democracy seem therefore, to dominate the understanding of how special education works.

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Soon after the Bolshevik Revolution of 1917, a three-year civil war broke out in Russia. As in many other civil wars, foreign powers intervened in the conflict. Britain played a leading role in this intervention and had a significant effect on the course of the war. Without this intervention on the White side, the superiority of numbers in manpower and weaponry of the Bolsheviks would have quickly overwhelmed their opponents. The aim of this dissertation is to explain the nature and role of the British intervention on the southern, and most decisive, front of the Civil War. The political decision making in London is studied as a background, but the focus of the dissertation is on the actual implementation of the British policy in Russia. The British military mission arrived in South Russia in late 1918, and started to provide General Denikin s White army with ample supplies. General Denikin would have not been able to build his army of more than 200,000 men or to make his operation against Moscow without the British matériel. The British mission also organized the training and equipping of the Russian troops with British weapons. This made the material aid much more effective. Many of the British instructors took part in fighting the Bolsheviks despite the orders of their government. The study is based on primary sources produced by British departments of state and members of the British mission and military units in South Russia. Primary sources from the Whites, including the personal collections of several key figures of the White movement and official records of the Armed Forces of South Russia are also used to give a balanced picture of the course of events. It is possible to draw some general conclusions from the White movement and reasons for their defeat from the study of the British intervention. In purely material terms the British aid placed Denikin s army in a far more favourable position than the Bolsheviks in 1919, but other military defects in the White army were numerous. The White commanders were unimaginative, their military thinking was obsolete, and they were incapable of organizing the logistics of their army. There were also fundamental defects in the morale of the White troops. In addition to all political mistakes of Denikin s movement and a general inability to adjust to the complex situation in Revolutionary Russia, the Whites suffered a clear military defeat. In South Russia the Whites were defeated not because of the lack of British aid, but rather in spite of it.

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Molecular machinery on the micro-scale, believed to be the fundamental building blocks of life, involve forces of 1-100 pN and movements of nanometers to micrometers. Micromechanical single-molecule experiments seek to understand the physics of nucleic acids, molecular motors, and other biological systems through direct measurement of forces and displacements. Optical tweezers are a popular choice among several complementary techniques for sensitive force-spectroscopy in the field of single molecule biology. The main objective of this thesis was to design and construct an optical tweezers instrument capable of investigating the physics of molecular motors and mechanisms of protein/nucleic-acid interactions on the single-molecule level. A double-trap optical tweezers instrument incorporating acousto-optic trap-steering, two independent detection channels, and a real-time digital controller was built. A numerical simulation and a theoretical study was performed to assess the signal-to-noise ratio in a constant-force molecular motor stepping experiment. Real-time feedback control of optical tweezers was explored in three studies. Position-clamping was implemented and compared to theoretical models using both proportional and predictive control. A force-clamp was implemented and tested with a DNA-tether in presence of the enzyme lambda exonuclease. The results of the study indicate that the presented models describing signal-to-noise ratio in constant-force experiments and feedback control experiments in optical tweezers agree well with experimental data. The effective trap stiffness can be increased by an order of magnitude using the presented position-clamping method. The force-clamp can be used for constant-force experiments, and the results from a proof-of-principle experiment, in which the enzyme lambda exonuclease converts double-stranded DNA to single-stranded DNA, agree with previous research. The main objective of the thesis was thus achieved. The developed instrument and presented results on feedback control serve as a stepping stone for future contributions to the growing field of single molecule biology.

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This dissertation is an onomastic study of variation in women s name phrases in official documents in Finland during the period 1780−1930. The aim is to discuss from a socio-onomastic perspective both the changeover from patronymics to inherited family names and the use of surnames after marriage (i.e. whether women adopted their husbands family names or retained their maiden names), before new laws in this area entered into force in Finland in the early 20th century. In 1920, a law on family names that required fixed names put an end to the use of the patronymic as a person s only surname. After 1929, it was no longer possible for a married woman to retain her maiden name. Methodologically, to explain this development from a socio-onomastic perspective, I have based my study on a syntactic-semantic analysis of the actual name phrases. To be able to demonstrate the extensive material, I have elaborated a scheme to divide the 115 different types of name phrases into 13 main categories. The analysis of the material for Helsinki is based on frequency calculations of the different types of name phrases every thirtieth year, as well as on describing variation in the structure and semantic content of the name phrases, e.g. social variation in the use of titles and epithets. In addition to this, by applying a biographic-genealogical method, I have conducted two case studies of the usage of women s name phrases in the two chosen families. The study is based on parish registers from the period 1780−1929, estate inventory documents from the period 1780−1928, registration forms for liberty of trade from the period 1880−1908, family announcements on newspapers from the period 1829−1888, gravestones from the period 1796−1929 and diaries from the periods 1799−1801 and 1818−1820 providing a corpus of 5 950 name phrases. The syntactic-semantic analysis has revealed the overall picture of various ways of denoting women in official documents. In Helsinki, towards the end of the 19th century, the use of inherited family names seems to be almost fully developed in official contexts. At the late 19th century, a patronymic still appears as the only surname of some working-class women whereas in the early 20th century patronymics were only entered in the parish register as a kind of middle name. In the beginning of the 19th century, most married women were still registered under their maiden names, with a few exceptions among the bourgeoisie and upper class. The comparative analysis of name phrases in diaries, however, indicates that the use of the husband s family name by married women was a much earlier phenomenon in private contexts than in official documents. Keywords: socio-onomastics, syntactic-semantic analysis, name phrase, patronymic, maiden name, husband s family name

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Lung cancer accounts for more cancer-related deaths than any other cancer. In Finland, five-year survival ranges from 8% to 13%. The main risk factor for lung cancer is long-term cigarette smoking, but its carcinogenesis requires several other factors. The aim of the present study was to 1) evaluate post-operative quality of life, 2) compare clinical outcomes between minimally invasive and conventional open surgery, 3) evaluate the role of oxidative stress in the carcinogenesis of non-small lung cancer (NSCLC), and 4) to identify and characterise targeted agents for therapeutic and diagnostic use in surgery. For study I, pneumonectomy patients replied to 15D quality of life and baseline dyspnea questionnaires. Study III involved a prospective quality of life assessment using the 15D questionnaire after lobectomy or bi-lobectomy. Study IV was a retrospective comparison of clinical outcomes between 212 patients treated with open thoracotomy and 116 patients who underwent a minimally invasive technique. Study II measured parameters of oxidative metabolism (myeloperoxidase activity, glutathione content and NADPH oxidase activity) and DNA adducts. Study V employed the phage display method and identified a core motif for homing peptides. This method served in cell-binding, cell-localisation, and biodistribution studies. Following both pneumonectomy and lobectomy, NSCLC patients showed significantly decreased long-term quality of life. No significant correlation was noted between post-operative quality of life and pre-operative pulmonary function tests. Women suffered more from increased dyspnea after pneumonectomy which was absent after lobectomy or bi-lobectomy. Patients treated with video-assisted thoracoscopy showed significantly decreased morbidity and shorter periods of hospitalization than did open surgery patients. This improvement was achieved even though the VATS patients were older and suffered more comorbid conditions and poorer pulmonary function. No significant differences in survival were noted between these two groups. An increase in NADPH oxidase activity was noted in tumour samples of both adenocarcinoma and squamous cell carcinoma. This increase was independent from myeloperoxidase activity. Elevated glutathione content was noted in tumour tissue, especially in adenocarcinoma. After panning the clinical tumour samples with the phage display method, an amino acid sequence of ARRPKLD, the Thx, was chosen for further analysis. This method proved selective of tumour tissue in both in vitro and in vivo cell-binding assay, and biodistribution showed tumour accumulation. Because of the significantly reduced quality of life following pneumonectomy, other operative strategies should be implemented as an alternative (e.g. sleeve-lobectomy). To treat this disease, implementation of a minimally invasive surgical technique is safe, and the results showed decreased morbidity and a shorter period of hospitalisation than with thoracotomy. This technique may facilitate operative treatment of elderly patients with comorbid conditions who might otherwise be considered inoperable. Simultaneous exposure to oxidative stress and altered redox states indicates the important role of oxidative stress in the pathogenesis and malignant transformation of NSCLC. The studies showed with great specificity and with favourable biodistribution that Thx peptide is specific to NSCLC tumours. Thx thus shows promise in imaging, targeted therapy, and monitoring of treatment response.

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For the past decades reflection has been the buzzword of adult and higher education. Reflection is facilitated in many practices and there is abundant research on the issue. Despite the popularity of the concept, the reasons why bringing about reflection in educational practices is difficult remain unclear. The prevailing theories inform of the process in its ideal form. However, to a great extent, they fail to offer conceptual tools for understanding and working with the actualities of reflection. The aim of the doctoral thesis was to explore the challenges and prerequisites of reflection in order to theorize the nature of reflection. By the term reflection it is here referred to becoming aware of and questioning the assumptions that orient our thinking, feelings and actions. The doctoral thesis consists of five studies that approach these questions from different viewpoints and within different contexts. The methods involve both a philosophical and an empirical approach. This multifaceted approach embodies the aim of both gaining a more thorough grasp of the phenomenon and to develop the methodology of researching reflection. The theory building is based on conceptual analysis and rational reconstruction (see Davia 1998; Habermas 1979; Rorty1984) of Mezirow s (1981; 1991; 2000; 2009) theory of transformative learning. In order to explore the aspects which, based on the analysis, appeared insufficiently considered within Mezirow s theory, Damasio s (1994; 1999; 2003; 2010) theory on emotions and consciousness as well as Clausewitz s (1985) view on friction are used as complementary theories. Empirical analyses are used in dialogue with the theoretical, in order to challenge and refine the emerging theorization. Reflection is examined in three different contexts; regarding university teachers pedagogical growth, involuntarily childless women recovering from a life-event crisis, and soldiers preparing to act in chaotic situations of the battlefield as well as recovering from it. The choice of these contexts is based on Mezirow s notion of disorienting dilemma as a trigger for reflection. This notion indicates that reflection may more naturally emerge in association to life-event crises or other cumulative sets of instances, which bring our worldview and beliefs under question. Nevertheless, reflection is often being promoted in educational contexts in which the trigger conditions may not readily prevail. These contextual issues as well as the differences between the facilitated and non-facilitated contexts have not, however, been considered in detail within the research on reflection (or transformative learning). The doctoral thesis offers a new perspective into reflection which, as a further development on Mezirow s transformative learning theory, theorizes the nature of reflection. The developed theory explicates the prerequisites and challenges to reflection. The theory suggests that the challenges of reflection are fundamentally connected to the way the biological life-support system affects our thinking through emotions. While depicting the mechanisms that function as a counterforce to reflection, the developed theory also opens a perspective for considering possibilities for carrying out reflection, and suggests ways to locate and deal with the assumptions to be reflected on. The basic dynamic of the challenges to reflection was explicated by conceptually bridging the gap between Mezirow s and Damasio s theories, through exploring the connections between the meaning perspective and the biological functions of emotions. The concepts of comfort zone and edge-emotions were formed so as to depict the emotional orientation of our thinking, as part of the explanation of the nature of reflection.

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Background Acute bacterial meningitis (BM) continues to be an important cause of childhood mortality and morbidity, especially in developing countries. Prognostic scales and the identification of risk factors for adverse outcome both aid in assessing disease severity. New antimicrobial agents or adjunctive treatments - except for oral glycerol - have essentially failed to improve BM prognosis. A retrospective observational analysis found paracetamol beneficial in adult bacteraemic patients, and some experts recommend slow β-lactam infusion. We examined these treatments in a prospective, double-blind, placebo-controlled clinical trial. Patients and methods A retrospective analysis included 555 children treated for BM in 2004 in the infectious disease ward of the Paediatric Hospital of Luanda, Angola. Our prospective study randomised 723 children into four groups, to receive a combination of cefotaxime infusion or boluses every 6 hours for the first 24 hours and oral paracetamol or placebo for 48 hours. The primary endpoints were 1) death or severe neurological sequelae (SeNeSe), and 2) deafness. Results In the retrospective study, the mortality of children with blood transfusion was 23% (30 of 128) vs. without blood transfusion 39% (109 of 282; p=0.004). In the prospective study, 272 (38%) of the children died. Of those 451 surviving, 68 (15%) showed SeNeSe, and 12% (45 of 374) were deaf. Whereas no difference between treatment groups was observable in primary endpoints, the early mortality in the infusion-paracetamol group was lower, with the difference (Fisher s exact test) from the other groups at 24, 48, and 72 hours being significant (p=0.041, 0.0005, and 0.005, respectively). Prognostic factors for adverse outcomes were impaired consciousness, dyspnoea, seizures, delayed presentation, and absence of electricity at home (Simple Luanda Scale, SLS); the Bayesian Luanda Scale (BLS) also included abnormally low or high blood glucose. Conclusions New studies concerning the possible beneficial effect of blood transfusion, and concerning longer treatment with cefotaxime infusion and oral paracetamol, and a study to validate our simple prognostic scales are warranted.

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Forest certification has been put forward as a means to improve the sustainability of forest management in the tropical countries, where traditional environmental regulation has been inefficient in controlling forest degradation and deforestation. In these countries, the role of communities as managers of the forest resources is rapidly increasing. However, only a fraction of tropical community forests have been certified and little is known about the impacts of certification in these systems. Two areas in Honduras where community-managed forest operations had received FSC certifications were studied. Río Cangrejal represents an area with a longer history of use, whereas Copén is a more recent forest operation. Ecological sustainability was assessed through comparing timber tree regeneration and floristic composition between certified, conventionally managed and natural forests. Data on woody vegetation and environmental conditions was collected within logging gaps and natural treefall gaps. The regeneration success of shade-tolerant timber tree species was lower in certified than in conventionally managed forests in Río Cangrejal. Furthermore, the floristic composition was more natural-like in the conventionally managed than the certified forests. However, the environmental conditions indicated reduced logging disturbance in the certified forests. Data from Copén demonstrated that the regeneration success of light-demanding timber species was higher in the certified than the unlogged forests. In spite of this, the most valuable timber species Swietenia macrophylla was not regenerating successfully in the certified forests, due to rapid gap closure. The results indicate that pre-certification loggings and forest fragmentation may have a stronger impact on forest regeneration than current, certified management practices. The focus in community forests under low-intensive logging should be directed toward landscape connectivity and the restoration of degraded timber species, instead of reducing mechanical logging damage. Such actions are dependent on better recognition of resource rights, and improving the status of small Southern producers in the markets of certified wood products.

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Cognitive health is of central importance for independent and balanced old age, while memory disorders represent the leading cause of intensive and long-term care among the Finnish elderly. The aims of this study were to analyse the effect of height, body mass index, weight change, metabolic conditions and coffee drinking in midlife on cognitive performance in old age among a sample of 2606 Finnish twins aged 65 years or older who had participated in a telephone interview to assess their cognitive status. Since coffee drinking associates with several metabolic conditions and Finns are known to be the greatest consumers of coffee in the world, the heritability and stability of coffee drinking was analysed in the whole Older Finnish Twin Cohort (n=10716). In order to investigate the association between height and cognitive performance in a population with more supportive childhood living conditions, a total of 2161 Danish twins were included in this study. A greater height was found to clearly associate with better cognitive performance in Finnish subjects, but less so among the Danish sample, which may reflect the childhood environmental differences between these cohorts. In the Finnish subjects, there was greater variance in cognitive performance among shorter subjects, and environmental factors were found to play a greater role in their cognitive performance, whereas the cognitive performance of taller participants was mainly explained by genetic factors. Midlife metabolic variables that were found to be significantly associated with a poorer cognitive performance in old age included a higher body mass index and three metabolic conditions: cardiovascular disease, hypertension and, most significantly of all, diabetes. Moreover, both weight gain and loss, even to a lesser degree than suggested previously, were found to be associated with poorer cognition. Furthermore, evidence of a causal relationship between midlife cardiovascular disease and cognitive performance in old age was demonstrated among discordant twin pairs. Conversely, no effect of coffee drinking in midlife on cognitive performance in old age was observed, although coffee drinking was demonstrated to be stable in the study population. The heritability of coffee drinking was found to differ across sexes and age groups, being 51% in men and 52% in women in the whole study population. This study supports the contention that cognitive performance in old age reflects the effects of multiple genetic and environmental exposures, including their complex interactions during the life-span. The demonstrated associations and evidence of a causal pathway between potentially preventable exposures and poorer cognitive performance highlight the importance of preventive medicine.

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Inelastic x-ray scattering spectroscopy is a versatile experimental technique for probing the electronic structure of materials. It provides a wealth of information on the sample's atomic-scale structure, but extracting this information from the experimental data can be challenging because there is no direct relation between the structure and the measured spectrum. Theoretical calculations can bridge this gap by explaining the structural origins of the spectral features. Reliable methods for modeling inelastic x-ray scattering require accurate electronic structure calculations. This work presents the development and implementation of new schemes for modeling the inelastic scattering of x-rays from non-periodic systems. The methods are based on density functional theory and are applicable for a wide variety of molecular materials. Applications are presented in this work for amorphous silicon monoxide and several gas phase systems. Valuable new information on their structure and properties could be extracted with the combination of experimental and computational methods.

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