Title: Prolonged apnea: monitoring brain activity in freedivers Objectives: The aim of this study is to monitor the brain electrical activity during the prolonged apnea in freedivers. Prolonged apnea in the water and prolonged dry apnea were compared to each other and also to a resting state before the apnea, all states with the eyes closed. Brain activity was obtained from the scalp EEG and evaluated using the sLORETA program. Methods: The research was conducted in 11 healthy men at the age of 23 - 51. The data was obtained from the scalp EEG. The record was first taken at a resting state before the apneas with eyes closed, then at maximum prolonged dry apnea with eyes closed and finally at maximum prolonged apnea in the water with eyes closed. The lenghts of the prolonged apneas ranged from 2:15 minutes to 5:30 minutes in idividual probands. There were pauses of at least three minutes between each apnea as by the proband's needs. The compared pair groups were following: prolonged apnea in the water against prolonged dry apnea, prolonged apnea in the water against resting state before the apnea and finally prolonged dry apnea against resting state before the apnea, all with the eyes closed. Selected sections of EEG record without artefacts were processed by sLORETA program. In the statistical...

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Background: Prolonged Grief Disorder (PGD) is now included in Section II of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition, Text Revision (DSM- 5-TR). To understand the health burden and then allocate economic and professional resources, it is necessary to provide epidemiological data for this new disorder. This is especially relevant since the new diagnostic criteria differ from its predecessors, which may affect the generalizability of previous findings. More information on the characteristics of people suffering from PGD is also beneficial to better identify individuals at risk. This study, therefore, aimed to estimate the prevalence of the new PGD criteria in a representative population-based sample, evaluate the factor structure, sociodemographic, and loss-related correlates of PGD caseness and explore possible predictors. Methods: Out of a representative sample of the German general population (N = 2,531), n = 1,371 (54.2%) reported to have experienced a significant loss throughout lifetime. Participants provided sociodemographic data and loss-related characteristics. PGD symptoms were measured using items from the German versions of the Prolonged Grief Scale (PG-13) and the Inventory of Complicated Grief (ICG), which could be matched to the DSM-5-TR criteria for PGD. Results: The conditional prevalence of PGD was 3.4% (n = 47). The most frequently reported symptoms were intense emotional pain and intense yearning or longing for the deceased. The confirmatory factor analysis confirmed a unidimensional model of PGD. Regression analysis demonstrated that time since the death, the relationship to the deceased, and unpreparedness for the death were significant predictors of PGD. Conclusion: Although the prevalence of 3.4% using the new diagnostic criteria is lower than the prevalence previously suggested by a meta-analysis, PGD remains a substantial disorder in the general population. In particular, the loss of a partner or child increases the risk for PGD, as does unpreparedness for the death of a loved one. Clinicians should pay particular attention to these high-risk groups. Further clinical implications are discussed.

(1) Background: The aim of the present study was to examine symptom classes of major depressive disorder (MDD), prolonged grief disorder (PGD), and posttraumatic stress disorder (PTSD) in a sample of suicide-bereaved individuals, while accounting for loss-related characteristics. (2) Methods: A latent class analysis was conducted to identify classes of the suicide bereaved, sharing symptom profiles, in a German suicide-bereaved sample (N = 159). (3) Results: Our analyses revealed three main classes: a resilient class (16%), a class with high endorsement probability for PGD symptoms (50%), and a class with high endorsement probability for combined PGD/PTSD symptoms (34%). Prolonged grief and intrusive symptoms emerged across all classes, while MDD showed low endorsement probability. Our results indicate an association between class membership and time passed since the loss; however, this applies only to the comparison between the PGD and the resilient class, and not for the PGD/PTSD class. (4) Conclusions: Our results may provide information about the predictability of symptom clusters following suicide bereavement. The findings also represent a significant step towards tailoring treatments based on the needs of relevant suicide-bereaved subgroups through a symptom-level approach. Time passed since loss might explain differences between symptom clusters.

Refugees from war zones often have missing significant others. A loss without confirmation is described as an ambiguous loss. This physical absence with simultaneous mental persistence can be accompanied by economic, social or legal problems, boundary ambiguity (i.e., uncertainty about who belongs to the family system), and can have a negative impact on mental health. The aim of this study was to identify sociodemographic and loss-related predictors for prolonged grief, anxiety, depression, post-traumatic stress disorder (PTSD) and somatization in treatment-seeking Syrian refugees with post-traumatic stress symptoms in Germany experiencing ambiguous loss. For the present study, data were based on the treatment-seeking baseline sample of the “Sanadak” randomized-controlled trial, analyzing a subsample of 47 Syrian refugees with post-traumatic stress symptoms in Germany experiencing ambiguous loss. Sociodemographic and loss-related questions were applied, along with standardized instruments for symptoms of prolonged grief (ICG), anxiety (GAD-7), depression (PHQ-9), PTSD (PDS-5) and somatization (PHQ-15). Linear regression models were used to predict mental health outcomes. Having lost a close family member and higher boundary ambiguity showed a statistically significant association with higher severity in prolonged grief. The overall model for somatization reached statistical significance, while no predictor independently did. Boundary ambiguity showed a statistically significant positive association with depression, while the overall model showed no statistically significant associations. Boundary ambiguity and missing family members seemed to be important predictors for prolonged grief. These findings support the importance of reunification programs and suggest an inclusion of the topic into psychosocial support structures, e.g., including psychoeducational elements on boundary ambiguity in support groups for traumatized individuals and families experiencing ambiguous loss. Further research is needed for a more detailed understanding of the impact of ambiguous loss on refugee populations.

L’une des principales problématiques du développement de produits biologiques, comme les probiotiques, réside dans l’impact du processus de fabrication sur la souche d’intérêt. Le maintien de l’activité thérapeutique est d’un intérêt capital pour obtenir l’effet bénéfique et, des travaux ont également optimisé les propriétés de la souche Lcr35® au travers du procédé de fabrication. Ainsi, toutes les étapes de fabrication du produit sont autant d’étapes qui peuvent modifier les caractéristiques de la souche bactérienne. La compression a été reconnue comme étant une étape qui permet d’éliminer les contaminations bactériennes et a également été décrite comme néfaste pour la viabilité d’une souche probiotique. Ces données constituent donc un a priori négatif au développement de probiotiques comprimés.Inversement, cette forme galénique est reconnue pour améliorer la demi-Vie des produits et améliorer la stabilité des bactéries dans un milieu gastrique. Cependant, aucune étude complète des propriétés d’une souche probiotique, après compression, n’a été effectuée. Or, afin d’établir un dossier d’AMM, toutes ces propriétés se doivent d’être vérifiées sur le produit final.Les travaux présentés se sont donc attachés à étudier les principales propriétés de la souche Lcr35® après compression. Tout d’abord, la perte de viabilité initiale en fonction de la pression de compression a été évaluée expérimentalement et une loi de décroissance d’ordre 1 est proposée. Un tel modèle permet ainsi d’anticiper la perte de viabilité selon la formulation et les conditions de compression. D’autre part, le profil génétique ainsi que le profil d’expression des gènes de la souche Lcr35® ont été étudiés après compression. Ni l’un ni l’autre n’a été modifié par le stress mécanique généré par la compression. De même, les propriétés d’inhibition du pathogène vaginal C. albicans ainsi que la résistance à pH acide de la souche sont maintenues. La résistance au pH gastrique est même améliorée par une protection mécanique vis-À-Vis du milieu.Selon les données de stabilité (ICH Q1A), la viabilité de la souche Lcr35® n’est pas non plus affectée par la compression. Les données de stabilité ont fait l’objet d’une modélisation par l’équation d’Arrhenius permettant d’obtenir un modèle fiable de prédiction de la stabilité, à partir des données en conditions accélérées (40°C).Dans une approche QbD de développement des produits pharmaceutiques, ces données serviront de base de comparaison pour la caractérisation de formulations en développement où des éléments tels que le milieu de culture, la souche ou la forme galénique peuvent être modifiés.Cette caractérisation globale de la souche Lcr35®, après compression, a permis d’infirmer l’a priori négatif sur la compression des bactéries. Ces travaux ont permis de comprendre, de caractériser et de modéliser les aspects liés à la compression des probiotiques. Ils constituent un prérequis primordial au développement d’un nouveau produit sous la forme d’un comprimé. Suite à une étape de développement complémentaire, ils ont d’ailleurs permis d’aboutir au premier produit commercialisé sous la forme d’un comprimé à libération prolongée, par la société Probionov : Gynophilus® LP.Ces données sur la compression élargissent la connaissance fondamentale de l’effet des procédés pharmaceutiques sur les propriétés des probiotiques et ouvrent de manière considérable leur champ de développement. Cette forme est un atout considérable en termes de stabilité mais surtout, elle fait intervenir de nombreuses perspectives de développement : gastro-Résistants, effervescents, multicouches, etc. Par l’intermédiaire de cette technologie, une administration plus ciblée de la souche par exemple dans les parties distales de l’intestin pourra être envisagée pour optimiser le bénéfice thérapeutique des souches probiotiques. Le but final étant de pouvoir diminuer la posologie des traitements tout en améliorant l’observance et le confort des patients. / One of the main issues in the development of biological products, such as probiotics, is the impact of the manufacturing process on the strain of interest. Maintaining therapeutic activity is of great interest for the expected beneficial effect and work has even optimized the properties of the Lcr35® strain through the manufacturing process. Therefore, all process stages leading to the final product are steps that can alter the characteristics of the bacterial strain.Compression is recognized in some publications as being a step which eliminates bacterial contaminations present for example in the excipients. For the development of new probiotic products, compression has also been described as negative for bacterial viability. These data are therefore a negative a priori on development of probiotic products in the tablet form. Conversely, this dosage form is known to improve the half-Life of products and improve the stability of bacteria in gastric environment. However, no comprehensive study of the properties of a probiotic strain after compression was done. Nevertheless, to establish a marketing authorization, all the properties of the strain must be checked on the final product.This work has proposed a review of the main properties of the Lcr35® strain after compression. First of all, the initial loss of viability as a function of compression pressure was studied experimentally and was modeled by a first order law. It allows us to anticipate the loss of viability of a strain depending on the formulation and compression conditions. Furthermore, the genetic profile and the profile of gene expression have not been changed due to the compression step. We also noticed that the inhibition properties of the pathogen C. albicans growth and acid resistance of the strain are maintained. Resistance to gastric pH is also enhanced by a phenomenon of mechanical protection against the environment.According to the data of stability under ICH conditions, the viability of the compressed Lcr35® strain is not affected by the compression. Stability data have therefore been modeled by the Arrhenius equation to obtain a reliable model for predicting the stability data from accelerated conditions (40°C). In a QbD approach to pharmaceutical development, these data serve as a basis of comparison for the characterization of developing formulations where parameters such as the culture environment, the drying method, the strain or the galenic form can be changed. This global characterization of Lcr35® strain after compression has set aside the negative a priori against the compression of bacteria. This work helped to understand, characterize and model aspects linked to probiotics compression. They are an essential prerequisite for the development of a new probiotic product in the form of a tablet. Following a further development step, they also helped to lead to the first product in the tablet form, marketed by the company Probionov : Gynophilus® LP (vaginal administration). These compression data considerably broaden the field of development of probiotics. Indeed, this form is a considerable advantage in terms of stability but more importantly, the tablet form involves many development opportunities: gastro-Resistant, effervescent, multi-Layered tablets, etc. Through this technology, a more targeted administration of the strain such as up to the colon may be considered to maximize the therapeutic benefit of the probiotic strains. The ultimate goal is to be able to decrease the dosage of treatment while improving observance of the treatment and the patient comfort.

Introduction : L’hémophilie B (HB) est une maladie hémorragique héréditaire caractérisée par un déficit en facteur IX (FIX) de la coagulation. La thérapie génique de l’HB par injection de virus adéno-associés (AAV) montre des résultats prometteurs, mais entraine une toxicité hépatique à forte dose. La création de nouveau transgène de FIX permettant d’injecter de moindres doses d’AAV est un réel enjeu. Matériel et Méthodes : Des transgènes thérapeutiques exprimant une protéine humaine de FIX à demi-vie prolongée par fusion à l’albumine (hFIX-Alb) ou exprimant un FIX une activité spécifique augmentée, le hFIX-E410H, ont été créés et injectés à des modèles murins. Une nouvelle molécule recombinante de hFIX à demi-vie prolongée par fusion à la sous-unité B du FXIII via un linker clivable par le facteur X activé (hFIX-LXa-FXIIIB) a été crée, produite et caractérisée. Résultats : Le transgène hFIX-Alb n’accumulait pas le niveau plasmatique du FIX par rapport au FIX sauvage. Des expériences ont été entreprises pour comprendre les mécanismes responsables du défaut d’expression. Le transgène hFIX-E410H, montrant une activité spécifique augmentée in vitro et in vivo chez les souris HB, permettait de diminuer les doses d’AAV d’environ 2,5 fois. La molécule hFIX-LXa-FXIIIB était fonctionnelle, corrigeait la génération de thrombine chez les souris HB, et présentait une demi-vie augmentée 3,9 fois chez la souris et 2,3 fois chez le rat. Conclusion : Nous avons développé et caractérisé de nouveaux transgènes de FIX modifiés et une nouvelle molécule de FIX à demi-vie prolongée, qui pourraient constituer de nouvelles perspectives thérapeutiques de l’HB / Introduction: Haemophilia B (HB) is an inherited bleeding disorder due to coagulation factor IX (FIX) deficiency. Adeno-associated virus (AAV)-based gene therapy for HB has shown promising results but can cause liver toxicity after administration of high dose of AAV vectors.The design of new transgene expressing modified FIX that would allow injecting fewer doses of AAV is a real challenge. Materials & Methods: Therapeutic transgene expressing human FIX with prolonged half-life due to fusion to mature albumin (hFIX-Alb) or expressing FIX with improved specific activity, hFIX-E410H, were designed and injected to murine animal model. A novel recombinant FIX molecule exhibiting enhanced half-life through fusion to the FXIIIB subunit via activated factor X-cleavable linker was design, produced and characterised. Results: The hFIX-Alb transgene did not increase the plasma FIX clotting activity compared to the transgene expressing wild-type hFIX. Experiments were undertaken to understand the mecanisms responsible for lower expression. The hFIX-E410H transgene, which showed improved specific activity in vitro and in vivo in HB mice, allowed injecting a 2.5-fold lower dose of AAV. The hFIX-LXa-FXIIIB molecule was functional, corrected the generation capacity in HB mice, and exhibited a 3.9-fold and 2.2-fold enhanced half-life in mice and in rats, respectively, compared to wild-type FIX. Conclusion: We have developed and characterised new transgenes expressing modified FIX, and a novel FIX molecule with prolonged half-life, which could become interesting perspectives for the treatment of HB

Made available in DSpace on 2016-12-23T14:21:17Z (GMT). No. of bitstreams: 1 Alexandre Severino Pereira.pdf: 1741258 bytes, checksum: d4dcaac23d5b65c5cc2152c367bc056f (MD5) Previous issue date: 2013-11-11 / A retenção no ensino superior foi definida como a condição em que o estudante demanda um tempo maior do que o previsto na matriz curricular para conclusão do curso. Esse fenômeno atua contrariamente à finalidade da instituição comprometendo a taxa de sucesso, gerando ociosidade de recursos humanos e materiais e pode provocar a evasão. Os principais objetivos desta pesquisa foram identificar os fatores associados à retenção dos estudantes dos cursos de graduação presenciais da Universidade Federal do Espírito Santo e propor ações institucionais visando à redução desses índices. Para tanto foi realizada uma pesquisa aplicada, de abordagem quantitativa, utilizando dados secundários. Informações obtidas da revisão da literatura articuladas com recursos de estatística descritiva, tabelas de contingência, testes Qui-quadrado de Pearson e Regressão Logística foram utilizados para análise dos dados. A área de Linguística, Letras e Artes apresentou o maior percentual de retenção discente, enquanto o menor nível foi observado na área de Ciências da Saúde. Os principais fatores intervenientes no processo de retenção foram coeficiente de rendimento acumulado, número de reprovações, relação candidato/vaga do vestibular, área do conhecimento, desempenho na segunda etapa do vestibular e trancamento de curso. Assim foi confirmado que o desempenho acadêmico é o componente vital para o sucesso do estudante. O indicador Nível de retenção baseado no ritmo do aluno se mostrou como boa alternativa para monitoramento da retenção. As ações institucionais propostas foram a realização de pesquisas sobre desempenho acadêmico e trancamentos de curso, a estruturação de programas de apoio acadêmico, a aproximação entre a Universidade e escolas de nível médio, a utilização do indicador testado e a criação de um banco de dados acadêmico unificado / Retention in higher education was defined as the condition in which the student requires a period longer than the fixed in the curriculum for course completion. This phenomenon acts against the purpose of the institution affecting the success rate, generating idleness human and material resources and can lead to dropout. The main objectives of this research was to identify factors associated with to retention of undergraduate students in classroom course of the Federal University of Espírito Santo and propose institutional actions focused on reducing these rates. Thus an applied research of a quantitative approach was conducted using secondary data. The information obtained from the reviewed literature articulated with resources of descriptive statistics, contingency tables, chi-square test and logistic regression were used for data analysis. The area of Linguistics, Letters and Arts had the highest percentage of student retention, while the lowest level was observed in the area of Health Sciences. The main factors involved in the process of retention were accumulated coefficient, number of failures, the ratio of applicants per vacancy in vestibular, area of knowledge, performance in the second part of entrance exam and the locking of the course. Thus it was confirmed that academic performance is the vital component for student success. The indicator Level of retention based on rhythm of the student proved to be a good alternative for monitoring the retention. The institutional actions proposed were the conduction of researches on academic performance and the locking of the course, the structuring of academic support programs, the union of the University and High Schools, the utilization of the indicator tested and the creation of an unified academic database

Aim: The overall aim of this thesis was to illuminate, describe, and promote understanding of women’s experiences of prolonged labour. The thesis compromises four studies. Methods: Paper I describes a case-referent study that recruited women (n = 255) giving singleton live birth to their first child by spontaneous labour after more than 37 completed weeks’ pregnancy. Participants completed a questionnaire that investigated childbirth experiences, previous family relationships, and childhood experiences. Paper II presented a cross-sectional study of 644 women who had been expecting their first child. Participants were asked to complete a questionnaire measuring psychosocial resources (social network and support), work-related psychosocial factors, control of daily life, and health characteristics. Papers III and IV presented interviews performed with 10 women, who, following prolonged labour, had given singleton live birth to their first children. Results: The risk of a negative birth experience was increased for women following prolonged labour. Both women experiencing prolonged and normal labours perceived the support given by their partners and midwives during labour to be very important, and felt pain relief to be a key issue. The suffering experienced during labour was more likely to mark the women for life if the labour was prolonged than if the experience of giving birth was positive and labour was normal. Both women, including those who had and those who had not experienced prolonged labour reported a high level of psychosocial resources, support, and sense of wellbeing in early pregnancy. The difficulties of prolonged labour were interpreted as an experience of being caught up in pain and fear: the women described how they had felt exhausted, powerless, and out of control. They described their dependency on others, and said that the caregiver’s decision to assist with the delivery was experienced as being relieved from pain. Prolonged labour could be understood as an experience of suddenly falling ill or of finding oneself in a life-threatening condition associated with an overwhelming fear of losing oneself and the child. The difficulties and suffering involved in becoming a mother after a prolonged labour were interpreted to be like “fumbling in the dark”. Women had experienced bodily fatigue accompanied by feelings of illness and detachment from the child. Meeting the child when in this condition entailed a struggle to become a mother. The negativity connected with prolonged labour and a struggle for motherhood may be comparable to the experience of illness and recovery. In spite of these experiences, reassurance of these women regarding their capacity for motherhood was crucial: it was central to their happiness as mothers, encouraged their interaction and relationship with the child, and contributed to their adaptation to motherhood. Conclusion: Women experiencing prolonged labour require advanced medical and obstetric care, which may limit their ability to participate in making decisions about their care. They have a special need for extra support and encouragement, as well as increased nursing and midwifery care during delivery.

Syftet med studien har varit att undersöka varför, hur och med vilket resultat en del sörjande söker professionellt samtalsstöd efter en närståendes död. Som forskningsdesign valdes en kvalitativ deskriptiv studie omfattande halvstrukturerade intervjuer med fem sörjande. Datamaterialet analyserades enligt Tema Analys. Studiens resultat pekar på att deltagarna har upplevt att deras sorg och behov av en längre sjukskrivning i sorgearbetet inte tagits på allvar av varken läkare, försäkringskassan eller arbetsgivare, vilket har orsakat dem onödig stress som försämrat sorgearbetet. Samtalsstödet inom den offentliga vården hos sjukhus, akutmottagning och vårdcentral har upplevts som icke tillfredställande p.g.a. personalens bristande förmåga att bemöta, informera och stödja sörjande.  Man har också upplevt att behandlingsmetoderna inte anpassas efter patienters specifika behov av hjälp utan utifrån politiska krav på lönsamhet och effektivitet. Den KBT-behandling som erbjuds upplevs inte vara lämplig för att kunna bearbeta en komplicerad sorg. Sörjande efterfrågar i stället psykodynamisk kris-/sorgterapi individuellt och/eller i grupp, som de upplevt positivt från privata vårdgivare, men som anses för dyrt. Svenska kyrkans kostnadsfria sorggrupper har också upplevts positivt, men icke troende och de som har en annan tro tvekar inför att söka sig dit. Det finns ett starkt behov av förbättringar inom professionellt samtalsstöd som idag erbjuds sörjande i Sverige. Det vore önskvärt att fler läkare utbildas till psykoterapeuter så att sörjande skulle kunna få både medicinsk och psykoterapeutisk behandling av en och samma person. Detta skulle bidra till ökad trygghet som är positivt i sorgearbete. Införande av den diskuterade diagnosen förlängt sorgesyndrom i det kommande DSM-V och ICD11, skulle förmodligen underlätta för sörjande att få rätt till sjukskrivning och ge enklare tillgång till lämplig och subventionerad samtalsbehandling. Detta skulle kunna bidra till bättre hälsa och snabbare återgång till arbetslivet, vilket är positivt både ur mänskligt såväl som samhällsmässigt perspektiv.