A Study of the Behavioural and Affective Profile of Inpatient Adolescent Girls Presenting a Restrictive Anorexia Nervosa

Essai doctoral d'intégration présenté à la Faculté des Études Supérieures et Postdoctorales en vue de l'obtention du grade de Docteur en psychologie (D.Psy.), en psychologie clinique

The administration route is decisive for the ability of the vaccine adjuvant CAF09 to induce antigen-specific CD8+ T-cell responses:the immunological consequences of the biodistribution profile

A prerequisite for vaccine-mediated induction of CD8+ T-cell responses is the targeting of dendritic cell (DC) subsets specifically capable of cross-presenting antigen epitopes to CD8+ T cells. Administration of a number of cationic adjuvants via the intraperitoneal (i.p.) route has been shown to result in strong CD8+ T-cell responses, whereas immunization via e.g. the intramuscular (i.m.) or subcutaneous (s.c.) routes often stimulate weak CD8+ T-cell responses. The hypothesis for this is that self-drainage of the adjuvant/antigen to the lymphoid organs, which takes place upon i.p. immunization, is required for the subsequent activation of cross-presenting lymphoid organ-resident CD8α+ DCs. In contrast, s.c. or i.m. immunization usually results in the formation of a depot at the site of injection (SOI), which hinders the self-drainage and targeting of the vaccine to cross-presenting CD8α+ DCs. We investigated this hypothesis by correlating the biodistribution pattern and the adjuvanticity of the strong CD8+ T-cell inducing liposomal cationic adjuvant formulation 09 (CAF09), which is composed of dimethyldioctadecylammonium bromide/monomycoloyl glycerol liposomes with polyinosinic:polycytidylic acid electrostatically adsorbed to the surface. Biodistribution studies with radiolabeled CAF09 and a surface-adsorbed model antigen [ovalbumin (OVA)] showed that a significantly larger fraction of the vaccine dose localized in the draining lymph nodes (dLNs) and the spleen 6 h after i.p. immunization, as compared to after i.m. immunization. Studies with fluorescently labelled OVA + CAF09 demonstrated a preferential association of OVA + CAF09 to DCs/monocytes, as compared to macrophages and B cells, following i.p. immunization. Administration of OVA + CAF09 via the i.p. route did also result in DC activation, whereas no DC activation could be measured within the same period with unadjuvanted OVA and OVA + CAF09 administered via the s.c. or i.m. routes. In the dLNs, the highest level of activated, cross-presenting CD8α+ DCs was detected at 24 h post immunization, whereas an influx of activated, migrating and cross-presenting CD103+ DCs to the dLNs could be measured after 48 h. This suggests that the CD8α+ DCs are activated by self-draining OVA + CAF09 in the lymphoid organs, whereas the CD103+ DCs are stimulated by the OVA + CAF09 at the SOI. These results support the hypothesis that the self-drainage of OVA + CAF09 to the draining LNs is required for the activation of CD8α+ DCs, while the migratory CD103+ DCs may play a role in sustaining the subsequent induction of strong CD8+ T-cell responses.

A Study of the Behavioural and Affective Profile of Inpatient Adolescent Girls Presenting a Restrictive Anorexia Nervosa

Essai doctoral d'intégration présenté à la Faculté des Études Supérieures et Postdoctorales en vue de l'obtention du grade de Docteur en psychologie (D.Psy.), en psychologie clinique

Toxicity profile of bevacizumab in the UK Neurofibromatosis Type 2 cohort

Bevacizumab is considered an established part of the treatment strategies available for schwannomas in patients with Neurofibromatosis Type 2(NF2). In the UK, it is available through NHS National Specialized Commissioning to NF2 patients with a rapidly growing target schwannoma. Regrowth of the tumour on suspension of treatment is often observed resulting in prolonged periods of exposure to bevacizumab to control the disease. Hypertension and proteinuria are common events with bevacizumab use and there are concerns with regards to the long-term risks of prolonged treatment. Dosing, demographic and adverse event(CTCAE 4.03) data from the UK NF2 bevacizumab cohort are reviewed with particular consideration of renal and cardiovascular complications. Eighty patients (48 male:32female), median age 24.5 years (range 11-66years), were followed for a median of 32.7 months (range 12.0–60.2months). The most common adverse events were fatigue, hypertension and infection. A total of 19/80 patients (24%) had either a grade 2 or grade 3 hypertension event and 14/80 patients (17.5%) had proteinuria. Of 36 patients followed for 36 months, 78% were free from hypertension and 86% were free of proteinuria. Logistic regression modeling identified age and induction dosing regime to be predictors of development of hypertension with dose of 7.5mg/kg three weekly and age >30years having higher rates of hypertension. Proteinuria persisted in one of three patients after cessation of bevacizumab. One patient developed congestive heart failure and the details of this case are described. Further work is needed to determine optimal dosing regimes to limit toxicity without impacting on efficacy.

Between "uxor", "mater" and "concubina". Profile and identity of the Emperor Constantine in Late Roman legislation

We aspire to shape the Constantine’s personality in particular by analyzing his loving relationship, first with Minervina and then with Fausta, and not forgetting the bond with his mother Helena, hence the reference to uxor, mater and concubina in our title. We will analyze if these women exercised any influence on the composition of his production rules and, if so, to what extent they were able to determine the historical development of the following decades. From this point of view we must consider in general the emperor had to combine their political claims and government with these relationships, showing great skill in handling times and ways, always putting the first to the second.

Erection induced by Tx2-6 toxin of Phoneutria nigriventer spider: expression profile of genes in the nitric oxide pathway of penile tissue of mice

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Energy Intake, Profile, and Dietary Sources in the Spanish Population: Findings of the ANIBES Study

[EN]Energy intake, and the foods and beverages contributing to that, are considered key to understanding the high obesity prevalence worldwide. The relative contributions of energy intake and expenditure to the obesity epidemic, however, remain poorly defined in Spain. The purpose of this study was to contribute to updating data of dietary energy intake and its main sources from food and beverages, according to gender and age. These data were derived from the ANIBES A three-day dietary record, collected by means of a tablet device, was used to obtain information about food and beverage consumption and leftovers.

The evolving profile, role and relevance of the medical director in a pharmaceutical company

Over the last years, operations in Pharmaceutical Companies have become more complex, trying to adapt to new demands of the market environment. Overall, the observed change of paradigm requires adapting, mainly by the setting of new priorities, diversification of investments, cost containment strategies, exploring new markets and developping new sets of skills. In this context, new functions have been created, the relevance of some has diminished, and the importance of others has arisen. Amongst these, the medical structure within a Pharmaceutical Company, increased to meet demands, with companies adopting different models to respond to these needs, and becoming a pillar to the business. Assuming the leading role within a medical department, the medical director function often lies in the shadow. It is a key function within Pharma Industry, either on a country or on a Global basis. It has evolved and changed in the past years to meet the constant demands of a changing environment. The Medical Director is a highly skilled and differeniated professional who provides medical and scientific governance within a Pharmaceutical company, since early stages of drug development and up to loss of exclusivity, not only but also by leading a team of other physicians, pharmacists or life scientists whose functions comprise specificities that the medical director needs to understand, provide input to, oversee and lead. As the organization of Pharmaceutical Companies tends to be different, in accordance to values, culture, markets and strategies, the scope of activities of a Medical Director can be broader or may be limited, depending on size of the organization and governance model, but they must fulfil a large set of requirements in order to leverage impact on internal and internal customers. Key technical competencies for medical directors such as an MD degree, a strong clinical foundation, knowledge of drug development, project and team management experience and written and verbal skills are relatively easy to define, but underlying behavioural competencies are more difficult to ascertain, and these are more often the true predictors of success in the role. Beyond seamless proficiency in technical skills, at this level interpersonal skills become far more important, as they are the driver and the distinctive factor between a good and an excelent medical director. And this has impact in the business and in the people doing it.

An Exploration of Clinical Psychologist and Educational Psychologist Constructs of Mental Health in the Context of Secondary School Aged Children

Over the past decade, Mental Health (MH) has increasingly appeared on the ‘school agenda’, both in terms of rising levels of MH difficulties in the student population, and also the expectation that schools have a role to play in supporting good MH. MH is a term fraught with ambiguities leading to uncertainty around the most appropriate ways to provide support. A review of current literature reveals a wide range of definitions and interpretations, sometimes within the same team of supporting professionals. The current study seeks to explore the perspectives held by two professional groups seemingly well placed to support young persons’ (YPs’) MH. Six Clinical Psychologists (CPs) and six Educational Psychologists (EPs) are interviewed, exploring their constructs of MH, and their perceptions of their own role and the roles of others in supporting secondary school aged YPs’ MH. The data are analysed through Thematic Analysis. Findings suggest that there are variations between the two professions’ constructs of MH, and EPs in particular have no unified concept of MH. This is likely due to less experience or training in this area. CPs and EPs hold similar perceptions of the school’s role for promoting good MH, and flagging up concerns to more specialist professionals when necessary. However, there are discrepancies in the EP and CP perceptions of each other’s roles. The conflicting views appear to emerge through incomplete information about the other, and professional defensiveness in a context where resources and funding are scarce. The current study suggests that these challenges can be addressed through: greater reflectivity on professional biases, exploration of MH constructs within other epistemological positions, and greater communication regarding professional roles, leading to clearer collaboration in supporting the MH of YP.

Effects of the frequency and satisfaction with leisure profile ondementia caregivers distress

El modelo PEAR (“Actividades Agradables Restricción Conductual”) ha sido propuesto como una manera de entender los efectos del ocio sobre el malestar de cuidadores de personas con demencia. En base al modelo PEAR y al de estrés y afrontamiento, el objetivo de este estudio fue analizar de forma conjunta el papel de la frecuencia y la satisfacción con la activación conductual en la explicación del malestar del cuidador (depresión, ansiedad, salud percibida), el riesgo de institucionalización de la persona cuidada, los estresores y recursos del cuidador (rumiación y reevaluación cognitiva) en una muestra de 275 cuidadores. Se dividió a la muestra en cuatro grupos en función de sus niveles en la frecuencia y la satisfacción con la activación conductual: BFBS = Baja frecuencia + baja satisfacción; BFAS = Baja frecuencia + alta satisfacción; AFBS = Alta frecuencia + baja satisfacción; y AFAS = Alta frecuencia + alta satisfacción. Mientras que los cuidadores del grupo AFAS mostraron un perfil más positivo en variables relacionadas con los recursos y de salud, y menores puntuaciones en riesgo de institucionalización en comparación con el resto de los grupos, los cuidadores del grupo BFBS utilizaron en mayor medida estrategias de regulación emocional desadaptativas y mostraron peores consecuencias sobre variables de resultado de salud. Los resultados sugieren la importancia de considerar el perfil de frecuencia y satisfacción con el ocio a la hora de entender el malestar del cuidador.

Analysis of the entrepreneurial profile of students attending higher education in Portugal: the Carland Entrepreneurship Index application

Background The societal changes have created new necessities in terms of health care and of professionals with diverse skills. The institutions of higher education should promote the development of an entrepreneurial profile in students which may boost the exploration of new opportunities. Objectives: To identify the entrepreneurial profile in the students in higher education and its relationship to some personal characteristics and training. Methods Correlational quantitative study, accomplished with 1,604 students from 18 institutions of polytechnic Institutes of Portugal. The collection of data occurred between July and November/2015. The Carland Entrepreneurship Index (CEI) entrepreneurial skills questionnaire was applied, along with the acquisition of socio-demographic variables of the students. Data was analysed with the SPSS 23.0. The study followed the ethical requirements. Results The (CEI) application, allowed us to note that 75.7 % of the students presented an entrepreneurial profile, 20.8 % a Micro entrepreneurial profile and 3.4 % a Macro entrepreneurial. Additionally, we verified that older students (r = 0.193, p < = 0.000), of the male gender (Female = 0.55; Male, M= 0.580 p < 0.000), that had already worked or would like to work for others, showed the greatest entrepreneurial potential (Yes M= 0.60; No 0.54; p < 0.000), along with those who participated in entrepreneurial contents during their training (Did not participate M= 0.53; Participated 0.58; p < 0.000). Conclusions The entrepreneurial profile is related with some social demographic characteristics of the students; however, the educational institutions may have a preponderant role in the development of that profile, which may contribute to a greater contribution in the wellbeing of the populations.

Chromatographic techniques to obtain the biomolecules profile of wild Suillus granulates

In recent years the interest in naturally occurring compounds has been increasing worldwide. Indeed, many of the bioactive compounds currently used as medicines have been synthesized based on the structure of natural compounds [1]. In order to obtain bioactive fractions and subsequently isolated compounds derived from natural matrices, several procedures have been carried out. One of these is to separate and assess the concentration of the active compound(s) present in the samples, a step in which the chromatographic techniques stand out [2]. In the present work the mushroom Sui/Ius granulatus (L.) Roussel was chemically characterized by chromatographic techniques coupled to different detectors, in order to evaluate the presence of nutritional and/or bioactive molecules. Some hydrophilic compounds, namely free sugars, were identified by high performance liquid chromatography coupled to a refraction index detector (HPLC-RI), and organic and phenolic acids were assessed by HPLC coupled to a photodiode array detector (HPLC-PDA). Regarding lipophilic compounds, fatty acids weredetermined by gas chromatography with a flame ionization detector (GC-FID) and tocopherols by HPLC-fluorescence detection. Mannitol and trehalose were the main free sugars detected. Different organic acids were also identified (i.e. oxalic, quinic and fumaric acids), as well as phenolic acids (i.e. gallic and p-hydroxybenzoic acids) and the related compound cinnamic acid. Mono- and polyunsaturated fatty acids were the prevailing fatty acids and a-, ~- and ~-tocopherol were the isoforms of vitamin E detected in the samples. Since this species proved to be a source of biologically active compounds, the antioxidant and antimicrobial properties were evaluated. The antioxidant activity was measured through the reducing power, free radical's scavenging activity and lipid peroxidation inhibition of its methanolic extract, and the antimicrobial activity was also tested in Gram positive and Gram negative bacteria and iri different fungi. S. granulatus presented antioxidant properties in all the performed assays, and proved to inhibit the growth of different bacterial and fungal strains. This study is a first step for classifying S. granulatus as a functional food, highlighting the potential of mushrooms as a source of nutraceutical and biologically active compounds.