<p>Vid palliativ vård bör, enligt WHO, organiserat stöd erbjudas närstående såväl under patientens sjukdomstid som efter dödsfallet. Syftet med föreliggande arbete var att kvantitativt mäta effekterna av deltagande alternativt icke deltagande i efterlevandegrupp. Efterlevande (n=84) till patienter som vårdats hemma med hjälp av en palliativ enhet fick svara på enkätfrågor av likert-typ som mäter sorg, nedstämdhet och depression. Mätningarna skedde vid två tillfällen, före start av efterlevandegrupp och 10 veckor senare. Svar lämnades av 75 personer vid första mättillfället och 61 vid det andra. Av dessa svaranden deltog 17 i efterlevandegrupp. Svaren behandlades kvantitativt med icke parametriska metoder och deskriptiva data i frekvenstabeller. Materialet var inte tillräckligt stort för att kunna göra statistiska jämförelser mellan dem som deltog i och dem som inte deltog i efterlevandegrupper. Slutsatser: De flesta deltagare i studien uppvisade svår sorg vid båda mättillfällena. En fjärdedel visade på besvär med nedstämdhet och depression och av dessa deltog sex procent i efterlevandegrupp. Faktorer som kunde påverka deltagande i efterlevandegrupp var kön och geografiskt avstånd till sammankomsterna. Deltagande i efterlevandegrupp visade ingen mätbar effekt för sorgebearbetning.</p> / <p>In palliative care, organized support should be offered to family care givers during the disease and during bereavement according to the WHO. The aim of the study was to quantitatively measure the effects of participating in or not participating in bereavement-groups. The bereaved (n=84) to patients taken care of at home supported by a palliative unit were asked to answer questionnaires with likert-type, measuring mourning, anxiety and depression. The measures were done on two occasions, before the start of the bereavement-group and ten weeks later. On the first occasion 75 of the bereaved responded and 61 on the second occasion. In bereavement-groups participated 17 of the respondents. The data was analyzed with non-parametric tests and descriptive statistics. The analysis indicated that the material was not big enough to make statistic comparisons between participants and non participants in bereavement-groups.</p><p>Conclusions: Most of the participants in the study showed signs of severe grief on both occasions. One fourth showed signs of high levels of both anxiety and depression and six percent of these participated in bereavement-groups. Factors affecting those participating in bereavement-groups were their gender and geographical distance to the meetings. Participating in bereavement-groups had no measurable effects on bereavement.</p>

Vid palliativ vård bör, enligt WHO, organiserat stöd erbjudas närstående såväl under patientens sjukdomstid som efter dödsfallet. Syftet med föreliggande arbete var att kvantitativt mäta effekterna av deltagande alternativt icke deltagande i efterlevandegrupp. Efterlevande (n=84) till patienter som vårdats hemma med hjälp av en palliativ enhet fick svara på enkätfrågor av likert-typ som mäter sorg, nedstämdhet och depression. Mätningarna skedde vid två tillfällen, före start av efterlevandegrupp och 10 veckor senare. Svar lämnades av 75 personer vid första mättillfället och 61 vid det andra. Av dessa svaranden deltog 17 i efterlevandegrupp. Svaren behandlades kvantitativt med icke parametriska metoder och deskriptiva data i frekvenstabeller. Materialet var inte tillräckligt stort för att kunna göra statistiska jämförelser mellan dem som deltog i och dem som inte deltog i efterlevandegrupper. Slutsatser: De flesta deltagare i studien uppvisade svår sorg vid båda mättillfällena. En fjärdedel visade på besvär med nedstämdhet och depression och av dessa deltog sex procent i efterlevandegrupp. Faktorer som kunde påverka deltagande i efterlevandegrupp var kön och geografiskt avstånd till sammankomsterna. Deltagande i efterlevandegrupp visade ingen mätbar effekt för sorgebearbetning. / In palliative care, organized support should be offered to family care givers during the disease and during bereavement according to the WHO. The aim of the study was to quantitatively measure the effects of participating in or not participating in bereavement-groups. The bereaved (n=84) to patients taken care of at home supported by a palliative unit were asked to answer questionnaires with likert-type, measuring mourning, anxiety and depression. The measures were done on two occasions, before the start of the bereavement-group and ten weeks later. On the first occasion 75 of the bereaved responded and 61 on the second occasion. In bereavement-groups participated 17 of the respondents. The data was analyzed with non-parametric tests and descriptive statistics. The analysis indicated that the material was not big enough to make statistic comparisons between participants and non participants in bereavement-groups. Conclusions: Most of the participants in the study showed signs of severe grief on both occasions. One fourth showed signs of high levels of both anxiety and depression and six percent of these participated in bereavement-groups. Factors affecting those participating in bereavement-groups were their gender and geographical distance to the meetings. Participating in bereavement-groups had no measurable effects on bereavement.

An improved second generation approach to pestalotiopsin A and 6-epitaedolidol has been developed. A silicon group bonded directly to carbon has been used as a stereocontrol element in cyclisation substrates for a SmI2 – mediated 4-exo-trig radical cyclisation. The silicon groups acts as a steric block to set up three new stereocentres in high to complete diastereocontrol. Several approaches to the cyclisation substrates are outlined, including a silyl transfer/aldol cascade and a novel C2-symmetric N-heterocyclic carbene – copper catalyst to asymmetrically install a C-Si bond. The silicon group is a versatile handle for further manipulation and has been oxidised using Fleming oxidation conditions to install the hydroxyl functionality required in the target compounds. The silicon group also simplifies the alcohol protecting group strategy in the approach to pestalotiopsin A and 6‐epitaedolidol. The first application of N-heterocyclic carbene – copper catalysed silyl transfer in natural product synthesis and the first use of a SmI2 – mediated cyclisation directed by a C-Si stereocontrol element are described.

Le squelette indolo[2,3-b]quinoléique est une cible synthétique attrayante car il est présent notamment dans la néocryptolépine, alcaloïde aux propriétés cytotoxiques et antipaludéennes. Nous proposons ici une approche originale pour accéder à ce tétracycle, qui combine dans une réaction radicalaire en cascade une cyclisation à un réarrangement de Smiles. La mise au point des conditions expérimentales et l'étude mécanistique de cette voie ont constitué le premier objectif de ce travail. Outre les produits attendus, les études structurales approfondies ont mis en évidence la formation de composés inédits résultant d'étapes radicalaires supplémentaires. En parallèle, l'application de la méthode à un substrat judicieusement fonctionnalisé a conduit au 3-(2'-aryl-N-alkylacétamido)oxindole, un intermédiaire clé vers le système indolo[2,3-b]quinoléique 6 et 11 disubstitué ciblé. / The indolo[2,3-b]quinoline ring system is an attractive synthetic target present in neocryptolepine, an antiplasmodial and cytotoxic alkaloid. We proposed an original pathway toward this squeleton, combining as key step a 5-exo-trig cyclisation to a Smiles rearrangement in a domino radical process. We first focused on scope and limitations studies and mechanistic investigations. Apart from the cyclised-rearranged products we isolated new original structures resulting from supplementary radical reactions. The application of the developed method to a conveniently functionalised substrate led to 3-(2'-aryl-N-alkylacetamido)indolinone, a key intermediate which was further converted to the aimed 6,11-disubstituted indolo[2,3-b]quinoline tetracycle.

Biodiversitet innebär en hög artsammansättning och är viktigt för fungerande ekosystem. Almar (Ulmus-arter) är ett träd som hyser en mängd andra arter och som värderas högt i urbana miljöer. Almar drabbas tyvärr av svampsjukdomen almsjukan som leder till att trädet dör. Detta kan dock motverkas med hjälp av vaccinet Dutch Trig®. Det är känt att vaccinet motverkar almsjukan men kunskapen om vaccinet möjligen påverkar andra arter och organismer än almsjukan är låg. Denna studie utfördes i syfte att undersöka och jämföra om epifyters mångfald och allmäntillståndet mellan ovaccinerade och vaccinerade almar skiljde sig. Metoden för studien delades upp i två delar, en tillväxtmätning och visuell granskning samt en kartläggning av epifyter. Resultatet och analysen visade att skillnaden mellan grupperna hos en variabel var signifikant, hos resterande variabler kunde skillnaderna bero på slumpen. Trots detta kunde ändå vissa mönster utläsas och slutsatsen att det fanns en skillnad både i allmäntillstånd och biodiversitet kunde dras.

Lyconadin A (1) is a structurally unique Lycopodium alkaloid with antitumor properties, isolated from the club moss Lycopodium complanatum. We are developing a synthetic route to 1 based on a novel 7-exo-trig/6-exo-trig acyl radical cascade cyclization. The synthesis of model acyl radical cascade precursor 23 will be presented. Key features of this synthesis include the suppression of competing elimination during the alkylation of a hindered phenethyl bromide and the use of a lactone as a precursor to a compound bearing two differentially protected primary alcohols. An account of our studies on the model acyl radical cascade cyclization (23 to 24 above) will also be given, including a stereochemical analysis of the product. Our findings have been applied to develop a more detailed stereoselective synthetic plan for Lyconadin A (1).

No / The tetracyclic nucleus of puupehenone, 15-oxopuupehenol and other sesquiterpene¿phenol natural products can be assembled stereoselectively in three steps, the last of these being the 6-endo-trig cyclisation of an alpha-keto radical generated from a substituted 2-(2-cyclohexenyl)ethyl 3-bromo-4-chromanone under metal-free conditions. / EPSRC

De précédentes études dans notre groupe ont montré que l'α-1-C-nonyl-1,5-didésoxy-1,5-imino-D-xylitol était un inhibiteur puissant de la β-glucocérébrosidase, enzyme impliquée dans la maladie de Gaucher. Il a été supposé que la conformation chaise inversée de ce composé pouvait expliquer en partie sa forte affinité avec la glycosidase cible. L'objectif ce travail de thèse était la synthèse d'une nouvelle classe d’iminosucres, basée sur un squelette 1-azaspiro[3.3]heptane, possédant deux cycles à 4 membres, analogue conformationnellement contraint de notre "lead" en série iminoxylitol. La première stratégie de synthèse envisagée a permis de mettre en avant une nouvelle réaction tandem d'ouverture d'azétidines conduisant à des spirocyclopropyl γ-lactames. La seconde stratégie testée a conduit dans un premier temps à la formation hautement stéréosélective d'un cyclobutane tétrasubstitué par une réaction radicalaire induite par le SmI2 − permettant ainsi la synthèse des premiers exemples de carbasucres à 4 membres − puis à la formation du carbone azaspiranique de notre cible par une réaction de C-H amination catalysée par des complexes de rhodium. / Previous studies in our group has shown that α-1-C-nonyl-1,5-dideoxy-1,5-imino-D-xylitol was a strong inhibitor of β-glucocerebrosidase, the enzyme involved in Gaucher disease. It was supposed that the inverted chair conformation of this compound could partially explain its high affinity with the target glycosydase.The goal of this PhD work was the synthesis of a new class of iminosugars based on 1-azaspiro[3.3]heptane structures, as conformationally strained analogues of our lead in the iminoxylitol series. During the course of our synthetic study, new azetidine ring-opening tandem reaction leading to spirocyclopropyl γ-lactames has been discovered. The most promising strategy evaluated led to the highly stereoselective formation of a tetrasubstituted cyclobutane via a SmI2-mediated radical reaction − leading to the synthesis of the first exemples of 4-membered carbasugars − then to the formation of the azaspiranic carbon of our target by way of rhodium-catalyzed C-H amination reaction.

Plus de la moitié des médicaments mis sur le marché entre 1981 et 2014 sont des produits naturels ou des dérivés. Ainsi, les structures des produits naturels sont une excellente source d'inspiration pour la découverte de nouveaux médicaments. L'introduction de cette thèse met en lumière le rôle important joué par les produits naturels en chimie médicinale. De plus, la préparation de produits naturels peut déboucher sur le développement de nouvelles méthodes de synthèse. Ainsi, au cours de cette thèse une approche synthétique de plusieurs produits naturels a été réalisée. Ces composés présentent des motifs clés tels que des amino-alcools 1,3, des diamines 1,3 ou un tétrahydropyrane. Les études synthétiques réalisées comprennent le développement de nouvelles méthodes pour accéder à ces structures. D'autre part, une réaction de Heck permettant l'accès à des précurseurs de tri-aryl éthylènes a été mise au point. / It has been estimated that more than half of all approved drugs, from the period 1981 to 2014, are either natural products or their derivatives. This, thus, indicates that natural products (NP), together with natural product derived and natural product inspired structures are significant as sources for potential leads towards the discovery of new drugs. The introduction of this thesis thereby highlights the importance of natural products in the field of drug discovery. In addition, the introduction emphasizes on the importance of natural products as a field of research. This is as the synthesis of natural products can result in the development of new synthetic methods which can then be applied to a broader range of applications across the field of chemistry. This new information, thus, bridges a gap in the scientific knowledge and allows for progress in science. Therefore the content of this thesis describes the syntheses and development of new synthetic methods towards bioactive natural products containing 1,3-amino alcohol, 1.3-diamine, THP-ring as well as tri-aryl ethylene unit which represent the key themes of (+)-negamycin (Chapter 1), (-)-cernuine and (+)-cermizine D (Chapter 2), enigmazole A (Chapter 3) and tamoxifen (Chapter 4), respectively.

The present study had as main objective to analyze the potentialities of the Multiple Intelligences recognized by Gardner to help mobilize the learning of the notions of Trigonometry through a Didactic Sequence. Data collection focused on 14 (9th grade) students from a school in the city of Gararu / SE / Brazil. The theoretical arguments draw on Gardner's findings (1983, 1995, 1998, 2010), focusing his contributions to learning through the development of Multiple Intelligences Theory and Fonseca (2002, 2010, 2012, 2015) in his arguments that contribute to the Mathematics Education, in focus, the learning of Trigonometry. With the intention of answering the restlessness, that guides this study of - how to mobilize the learning of the notions of Trigonometry (trigonometric reasons in the triangle rectangle - sine, cosine and tangent) in the 9th year of Basic Education according to the Theory of Multiple Intelligences? - Artigue's Didactic Engineering (1988) was chosen as a research methodology based on a sequence of reflexive activities, based on the development stages of this methodology. At the end of this experiment, students' learning about the trigonometric ratios in the right triangle culminated significantly in the interrelationship with the Multiple Intelligences theory, and the results detected presuppose the permanence of expanding the search for understanding And approach of the contents directed to the learning of the notions of Trigonometry. / O presente estudo teve como objetivo principal analisar as potencialidades das Inteligências Múltiplas reconhecidas por Gardner, para auxiliar a mobilização da aprendizagem das noções de Trigonometria através de uma Sequência Didática. O levantamento de dados focalizou 14 alunos do (9º ano) de uma escola no município de Gararu/SE/ Brasil. Os argumentos teóricos discorreram dos achados de Gardner (1983, 1995, 1998, 2010), focando suas contribuições para a aprendizagem através do desenvolvimento da Teoria das Inteligências Múltiplas e Fonseca (2002, 2010, 2012, 2015) em seus argumentos que contribuem para a Educação Matemática, em foco, a aprendizagem da Trigonometria. Com o intento de responder a inquietação que norteia este estudo de - como mobilizar a aprendizagem das noções de Trigonometria (razões trigonométricas no triângulo retângulo – seno, cosseno e tangente) no 9º ano do Ensino Fundamental segundo a Teoria das Inteligências Múltiplas? – optou-se como metodologia de pesquisa a Engenharia Didática de Artigue (1988) fundamentada em uma sequência de atividades reflexivas, baseadas nas etapas de desenvolvimento desta metodologia. Ao final desta experiência, percebeu-se que a aprendizagem dos alunos no tocante, as razões trigonométricas no triângulo retângulo, culminou de maneira significativa ao interrelacionar com a Teoria das Inteligências Múltiplas, outrossim, os resultados detectados pressupõem a permanência de ampliar a busca pela compreensão e abordagem dos conteúdos direcionados a aprendizagem das noções de Trigonometria.