Les Méthionine sulfoxyde réductases (Msr) catalysent la réduction spécifique des méthionine sulfoxydes (Met-O) en méthionines (Met). Elles sont impliquées dans la résistance des cellules à un stress oxydant et dans la virulence des bactéries pathogènes du genre Neisseria. Cette famille d'enzyme se compose de trois classes, les MsrA et B, structuralement distinctes, et présentant une stéréosléctivité respectivement pour l'isomère S et R de la fonction sulfoxyde du substrat. Une troisième classe, découverte récemment, et appelée fRMsr, catalyse la réduction spécifique de la forme libre de l'isomère R de la fonction sulfoxyde. La fRMsr appartient à la famille des domaines GAF, généralement impliqués dans la signalisation cellulaire, et les fRMsr représentent le premier domaine GAF présentant une activité enzymatique. Les études réalisées au cours de ma thèse sur la fRMsr de Neisseria meningitidis ont permis de montrer que : 1) fRMsr de N. meningitidis présente un mécanisme catalytique identique à MsrA/B avec la formation d'au moins un pont disulfure intramoléculaire Cys84-Cys118 réduit par la thiorédoxine (Trx) ; 2) La Cys118 est le résidu catalytique sur lequel l'intermédiaire acide sulfénique doit se former ; 3) L'étape réductase est l'étape cinétiquement déterminante du mécanisme à deux étapes conduisant à la formation du pont disulfure Cys84-Cys118. La combinaison de l'analyse des résultats cinétiques, et de la structure tridimensionnelle de la fRMsr de N. meningitidis en complexe avec le substrat ont permis de montrer : 1) L'existence d'un site de reconnaissance oxyanion impliqué dans la stabilisation de la fonction carboxylate ; 2) Un rôle de la fonction carboxylate du résidu Asp143 dans la catalyse de l'étape réductase ; 3) Le résidu Glu125 est impliqué dans la reconnaissance et/ou le positionnement du substrat Met-O probablement via la stabilisation du groupement NH3+ ; 4) Un rôle du résidu Asp141 dans le positionnement des résidus Asp143 et Glu125 ; 5) le noyau indole du Trp62 est impliqué dans la stabilisation du groupe méthyle-[epsilon] / Methionine sulfoxide reductases (Msr) catalyze the specific reduction of methionine sulfoxides (Met-O) into methionine (Met). They are involved in cell defences against oxidative stress and virulence of pathogenic bacteria of Neisseria genius. This family of enzymes consists of three classes, MsrA and MsrB, structurally-unrelated, Specific for the S and the R epimer of the sulfoxide function of the substrate, respectively. A third class, recently discovered and called fRMsr, selectively reduce the free form of the R epimer of the sulfoxide function. The fRMsr belongs to the family of GAF domains, they are usually involved in cell signaling, and fRMsr represent the first GAF domain to show enzymatic activity. The studies of the Neisseria meningitidis fRMsr have shown that: 1) The Neisseria meningitidis fRMsr have a identical catalytic mechanism to MsrA and MsrB with the formation of at least one intramolecular disulfide bond, Cys84-Cys118 reduced by thioredoxin (Trx) ; 2) The Cys118 is demonstrated to be the catalytic Cys on which a sulfenic acid is formed ; 3) The Reductase step is the rate determining step of the mechanism leading to the formation of the disulfide bond Cys84-Cys118. The combination of the biochemical and kinetics data, and the examination of the 3D structure of the N. meningitidis fRMsr in complex with its substrate shown: 1) an oxyanion hole involved in the accommodation of the carboxylate group ; 2) the carboxylate group of the Asp143 residue involved in the catalysis of step reductase, and 3) The Glu125 residue involved in the recognition and/or positioning of the Met-O probably by the stabilization of the NH3+; 4) the Asp141 residue involved in the positioning of Asp143 and Glu125 residues ; 5) the indole ring of the Trp62 residue involved in stabilizing of the epsilon-methyl group

The application of diagnostic thresholds plays an important role in the classification of mental disorders. Despite their importance, many diagnostic thresholds are set arbitrarily, without much empirical support. This paper seeks to introduce and analyze a new empirically based way of setting diagnostic thresholds for a category of mental disorders that has historically had arbitrary thresholds, the personality disorders (PDs). I analyzed data from over 2,000 participants that were part of the Methods to Improve Diagnostic Assessment and Services (MIDAS) database. Results revealed that functional outcome scores, as measured by Global Assessment of Functioning (GAF) scores, could be used to identify diagnostic thresholds and that the optimal thresholds varied somewhat by personality disorder (PD) along the spectrum of latent severity. Using the Item response theory (IRT)-based approach, the optimal threshold along the spectrum of latent severity for the different PDs ranged from θ = 1.50 to 2.25. Effect sizes using the IRT-based approach ranged from .34 to 1.55. These findings suggest that linking diagnostic thresholds to functional outcomes and thereby making them less arbitrary is an achievable goal. This study has introduced a new and uncomplicated way to empirically set diagnostic thresholds while also taking into consideration that items within diagnostic sets may function differently. Although purely an initial demonstration meant only to serve as an example, by using this approach, there exists the potential that diagnostic thresholds for all disorders could one day be set on an empirical basis.

Patients suffering from transsexualism (TS) who apply for sex reassignment surgery (SRS) go through a complex evaluation process before being accepted for treatment. In general, the results from SRS are satisfying. However, further knowledge is needed to clearly delineate transsexualism from other related gender identity disorders (GID) and to improve the selection of candidates for SRS. Personality has for a long time been considered as the key concept for that purpose but systematic studies using reliable instruments are lacking. The present study aims at improving the assessment procedure, validating the concept of transsexualism and studying the outcome of SRS and important prognostic factors. Two methodological studies deal with the development and validation of two self-report instruments based on DSM-III-R: SCID screen covering Axis II personality disorders/traits and Global Assessment of Functioning (GAF-scale, Axis V). SCID screen diagnoses of personality disorders (PD) were compared with diagnoses from independent structured interviews by means of the SCID-II. The overall kappa in identifying a PD was 0.78 varying from 0.34 to 0.81 for the specific PDs when cut-off was adjusted. When applied to a group of GID-patients SCID screen diagnoses agreed well with clinical diagnoses (kappa 0.77). Self-report of the GAF also proved to be a reliable (overall Pearson r=0.62) and useful method and the study lends further support to the validity of Axis V. In three papers a group of 19 transsexuals was studied by means of a) SCID screen to examine their personality in a dimensional and traditional categorical way, b) the GAF-scale to study psychosocial functioning, c) Structural Analysis of Social Behavior (SASB) to examine self-image and d) Defense Mechanism Test (DMT) to analyze psychological defense structures from a psychodynamic perspective. Patients with atypical gender identity disorders (GIDAANT) and patients with borderline personality disorders as well as healthy subjects were used as contrast groups. Among the transsexuals 10 out of 19 had an additional axis I disorder and 37% had at least one PD, predominantly within cluster B. When analyzed dimensionally according to SCID screen, frequent subthreshold personality pathology was found and biological women fulfilled more axis II criteria than men. TS had less axis I and II pathology compared with GIDAANT and psychiatric patients. According to SASB, TS had a positive self-image with both self-control and spontaneous self and predominating self-love. They appeared significantly more healthy on self-image measures than GIDAANT patients. The DMT revealed a different pattern; TS patients were more disturbed in several areas than patients with borderline personality disorder. TS showed no ”emotional investment” and poorer reality orientation in contrast to both healthy controls and the borderline group but shared a similar pregenital pathology with the borderline patients. Finally, five-year outcome was studied among the transsexuals from a multidimensional approach (e.g. work, interpersonal relations, partnership, subjective opinion) and related to index- measurements on DSM-III-R, SCID screen, GAF, SASB and DMT. Based on combined outcome variables, 68% of the subjects were judged to have improved and 16% had an unsatisfactory outcome. One single case regretted the sex change. SCID screen pathology and SASB disturbances emerged as significant predictors for negative outcome, as well as male biological sex and lack of partnership. It was concluded, that although outcome is in general very favorable, the instruments under investigation, in particular SCID screen and SASB, revealed valuable prognostic information and they are suggested to become part of the future routine assessment of candidates for SRS. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1995, härtill 6 uppsatser.</p> / digitalisering@umu

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No description available.

<p>The general aim of the studies presented in this thesis is to investigate the possibility of using clinical data to measure outcomes in psychiatric outpatient services. The specific aims are to investigate whether routine clinical assessments and ratings are reliable and have adequate validity, and then to use these data to calculate treatment outcomes and explore factors that affect these outcomes.</p><p>The main result shows that ratings of global mental health made by clinicians in routine clinical work can be used to evaluate treatment outcomes in outpatient settings. The clinicians responsible for diagnosing and assessing patients used the GAF scale with satisfactory reliability (ICC1,1 = 0.81) and fair interrater reliability (overall kappa = 0.53) when categorizing main diagnostic groups of the DSM-IV axis I. The GAF scale can thus be used to assess global mental health and to monitor outcomes in clinical settings. However, a GAF culture bias was observed. This bias can probably be corrected with feedback and training.</p><p>Psychiatric treatment in outpatient settings had a generally positive effect on patients’ global mental heath (ES = 0.65). The overall result when clinical significance methodology was used showed that 28.1% of the patients had recovered and a further 6.6% showed reliable improvement. Patients being treated with psychotherapeutically influenced methods showed a considerably better effect (ES = 1.00). There is a dose of sessions effect that is particularly marked for short treatment episodes. Thirteen sessions are required for 50% of the patients to show reliable improvement. The strongest influence on treatment outcome was whether the termination of a patient’s treatment was planned or unplanned.</p><p>In conclusion: Clinical databases can be used to study the outcome of psychiatric services provided they a) include a large number of subjects representing an intention-to-treat perspective; b) the instruments used are clinically relevant and reliable; c) the raters contributing to the data base are motivated to decrease attrition; d) the database includes extensive data to allow for control of confounding factors; and e) data are collected at critical occasions in treatment, such as at the start of treatment and at discharge from treatment, making it possible to focus on effects. Psychiatric outpatient treatment has a positive effect, but considerable improvements may be possible with more stringent use of psychotherapeutic methods, sufficient doses of sessions, and planned terminations. However, the progress of treatment is also affected by such factors as pre-treatment severity and diagnoses.</p>

The general aim of the studies presented in this thesis is to investigate the possibility of using clinical data to measure outcomes in psychiatric outpatient services. The specific aims are to investigate whether routine clinical assessments and ratings are reliable and have adequate validity, and then to use these data to calculate treatment outcomes and explore factors that affect these outcomes. The main result shows that ratings of global mental health made by clinicians in routine clinical work can be used to evaluate treatment outcomes in outpatient settings. The clinicians responsible for diagnosing and assessing patients used the GAF scale with satisfactory reliability (ICC1,1 = 0.81) and fair interrater reliability (overall kappa = 0.53) when categorizing main diagnostic groups of the DSM-IV axis I. The GAF scale can thus be used to assess global mental health and to monitor outcomes in clinical settings. However, a GAF culture bias was observed. This bias can probably be corrected with feedback and training. Psychiatric treatment in outpatient settings had a generally positive effect on patients’ global mental heath (ES = 0.65). The overall result when clinical significance methodology was used showed that 28.1% of the patients had recovered and a further 6.6% showed reliable improvement. Patients being treated with psychotherapeutically influenced methods showed a considerably better effect (ES = 1.00). There is a dose of sessions effect that is particularly marked for short treatment episodes. Thirteen sessions are required for 50% of the patients to show reliable improvement. The strongest influence on treatment outcome was whether the termination of a patient’s treatment was planned or unplanned. In conclusion: Clinical databases can be used to study the outcome of psychiatric services provided they a) include a large number of subjects representing an intention-to-treat perspective; b) the instruments used are clinically relevant and reliable; c) the raters contributing to the data base are motivated to decrease attrition; d) the database includes extensive data to allow for control of confounding factors; and e) data are collected at critical occasions in treatment, such as at the start of treatment and at discharge from treatment, making it possible to focus on effects. Psychiatric outpatient treatment has a positive effect, but considerable improvements may be possible with more stringent use of psychotherapeutic methods, sufficient doses of sessions, and planned terminations. However, the progress of treatment is also affected by such factors as pre-treatment severity and diagnoses.

Electronic energy transfer has been investigated in pure donor systems by means of computer simulations. Calculated properties were the probability that the initially excited donor is excited at a time t after the excitation, Gs(t), the mean square displacement of the excitation and different fluorescence observables. For three dimensional systems the results obtained by Monte Carlo simulations were compared to the so-called GAF-theory {Gouchanour,C. R., Andersen, H. C. and Fayer, M. D., J. Chem. Phys. 81, 4380 (1984)}, and the agreement was found to be good. Anisotropic systems, i.e. mono-, bi- and multilayer systems, were compared to the two-particle model {Baumann,J. and Fayer, M. D., J. Chem. Phys. 85, 4087 (1986)}. The agreement between the Gs(t) calculated from the tp- model and the Monte Carlo simulations were good for all systems investigated. However, the agreement between the fluorescence observables obtained by MC and the tp-model were in general poor. A much better agreement was found when a phenomenological approach was used for calculating the fluorescence depolarization ratios. Three dimensional systems where the donors are rotating on the same time scale as the energy transfer takes place have also been studied and compared to analytical theories. The Molecular Dynamics simulations of decapeptide H142 shows that simulations in a continuum with a relative permeability do not provide a reliable alternative to simulations with explicit solvent molecules. / <p>Diss. (sammanfattning) Umeå : Umeå universitet, 1991, härtill 5 uppsatser</p> / digitalisering@umu

This study is about the gender dimensions of land reform in South Africa. The case study is that of a housing and resettlement project in Daggakraal, Mpumalanga Province. The aim of the study was to describe and analyse empirical realities for rural women, in relation to land, in Daggakraal. The focus was on the research questions for the study namely the nature of land reform practice; whether gender issues were central in land reform at all stages of the project; whether or not participation of women was truly genuine; and the constraints that were faced in the process of land reform delivery. The study was conducted in Daggakraal, a rural town in Mpumalanga province, South Africa. Research methods employed were both quantitative and qualitative with more emphasis on the latter. A total of 100 respondents participated in the study. This number included 10 key informants 3 of whom were trained as research assistants. The findings indicate that there was very little gender analysis carried out prior to land reform. For this reason land reform has not benefitted the women and men of Daggakraal. Land reform policies and other legislation put in place were not followed to the letter in Daggakraal and in other areas of the country where land reform was implemented; the first land reform (SLAG) has not benefitted the poor, especially women; the rural terrain is an area of contestation and competing interests between women and men. There is also a lack of institutional arrangements to implement a gendered approach to land reform. This study demonstrates the need to tackle and transform the existing power relations at the household level, if government is serious about the gender dimension of land reform in South Africa. In a small way it is hoped that this study will contribute to the limited writing on land reform and gender and also provide a gendered critique of the land reform programme in South Africa. The Gender Analysis Framework (GAF) and the feminist and gender perspectives have helped the researcher to understand and explain the gender dynamics in Daggakraal. / Development Studies / D. Litt. et Phil. (Development Studies)

This study is about the gender dimensions of land reform in South Africa. The case study is that of a housing and resettlement project in Daggakraal, Mpumalanga Province. The aim of the study was to describe and analyse empirical realities for rural women, in relation to land, in Daggakraal. The focus was on the research questions for the study namely the nature of land reform practice; whether gender issues were central in land reform at all stages of the project; whether or not participation of women was truly genuine; and the constraints that were faced in the process of land reform delivery. The study was conducted in Daggakraal, a rural town in Mpumalanga province, South Africa. Research methods employed were both quantitative and qualitative with more emphasis on the latter. A total of 100 respondents participated in the study. This number included 10 key informants 3 of whom were trained as research assistants. The findings indicate that there was very little gender analysis carried out prior to land reform. For this reason land reform has not benefitted the women and men of Daggakraal. Land reform policies and other legislation put in place were not followed to the letter in Daggakraal and in other areas of the country where land reform was implemented; the first land reform (SLAG) has not benefitted the poor, especially women; the rural terrain is an area of contestation and competing interests between women and men. There is also a lack of institutional arrangements to implement a gendered approach to land reform. This study demonstrates the need to tackle and transform the existing power relations at the household level, if government is serious about the gender dimension of land reform in South Africa. In a small way it is hoped that this study will contribute to the limited writing on land reform and gender and also provide a gendered critique of the land reform programme in South Africa. The Gender Analysis Framework (GAF) and the feminist and gender perspectives have helped the researcher to understand and explain the gender dynamics in Daggakraal. / Development Studies / D. Litt. et Phil. (Development Studies)