Infusões de células T e células NK (Natural Killer) de sangue periférico estão sendo realizadas para tratamento de malignidades. Os linfócitos propagados ex vivo, em normóxia (20% O2), são intravenosamente infundidos e precisam sobreviver a hipóxia associada a circulação venosa, da medula óssea (5% O2) e do microambiente tumoral (1% O2). O objetivo principal deste estudo foi determinar a capacidade proliferativa das células humanas T e NK em normóxia (20% O2) versus hipóxia (1% O2), por 28 dias, utilizando uma célula apresentadora de antígeno artificial (aAPC) para propagação em grau clínico. As células T expostas a hipóxia cresceram 100 vezes menos que as células T cultivadas em normóxia, enquanto que houve uma diminuição de 1000 vezes na taxa proliferativa das células NK hipóxicas, que exibiram um aumento na apoptose bem como um prejuízo na citotoxicidade. Hipóxia também induziu uma diminuição na expressão dos receptores KIR, NCR e NKG2D das células NK. Nesta mesma condição, a produção de IL-2 e IFNγ nas células T estavam diminuídas, sendo que nas células NK esse efeito foi mais acentuado. Hipóxia aumentou a expressão de genes relacionados com apoptose, angiogênese e metabolismo glicolítico, os quais estavam moderadamente aumentados nas células T, mas profundamente super-regulados nas células NK. Os níveis de ATP nas células T foram muito similares em ambas as condições de oxigênio, mas intensamente diminuídos nas células NK cultivadas em hipóxia. Também se observou, que a expressão do miR-210 induzido por hipóxia, estava super regulada nas células NK hipóxicas correlacionando com a perda da expressão da molécula NCAM/CD56. Em conjunto, os resultados deste estudo demonstram um maior impacto da hipóxia sobre as atividades proliferativas e citotóxicas das células NK estimuladas por aAPCs. Estudos adicionais são necessários para o entendimento do impacto deste comportamento das células NK em condições hipóxicas sobre a imunoterapia celular adotiva. / Infusions of T cells and natural killer (NK) cells from peripheral blood (PB) are being undertaken for the treatment of malignancies. Lymphocytes are propagated ex vivo in normoxia (20% O2) and intravenously infused and must survive hypoxia associated with venous blood and bone marrow (5% O2), and the tumor environment (1% O2). The objective this study was to determine the ability of T and NK cells to proliferate under normoxia (20% O2) versus hypoxia (1% O2) over 28 days using an artificial antigen presenting cells (aAPC) to propagate clinical-grade lymphocytes. T cells continuously exposed to 4 weeks of hypoxia grew at a rate of 100-fold less than T cells cultured in normoxia while the proliferative rate of NK cells lagged by 1,000-fold, behind normoxic conditions. Hypoxic cultured NK cells exhibit an increase in apoptosis as well as a correspondent impairment in cytotoxicity. In low oxygen tension the expression of KIR, NCR, and NKG2D receptors were decreased in NK cells. In hypoxia, the production of IL-2 and IFNγ were decreased in T cell and more so in NK cell. Chronic hypoxia increased the expression of related apoptosis, glycolytic metabolism and angiogenesis genes which were moderately increased in T cells but profoundly upregulated in NK cells. ATP levels in T cell were very similar in both oxygen conditions, but profoundly diminished in NK cells under hypoxia. We also noted that hypoxia inducible miR-210 levels are up regulated in hypoxic NK cells correlating with loss of CD56 expression. Taken together, this data show that a greater impact of hypoxia on proliferative and cytotoxic activity of NK cells activated by artificial antigen-presenting cells. More studies are needed to understand the impact of this behavior on the cell adoptive immunotherapy.

Submitted by Fabio Sobreira Campos da Costa (fabio.sobreira@ufpe.br) on 2017-06-01T13:12:44Z No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TeseCompleta_AMADA.pdf: 1792118 bytes, checksum: f2bea5662ee9619c00105a395cd039ce (MD5) / Made available in DSpace on 2017-06-01T13:12:44Z (GMT). No. of bitstreams: 2 license_rdf: 811 bytes, checksum: e39d27027a6cc9cb039ad269a5db8e34 (MD5) TeseCompleta_AMADA.pdf: 1792118 bytes, checksum: f2bea5662ee9619c00105a395cd039ce (MD5) Previous issue date: 2016-04-27 / FACEPE / O objetivo deste estudo é identificar e analisar os conteúdos e a organização retórica mobilizados, em relatos da mídia e de militantes da causa da adoção, na construção discursiva da identidade dos filhos adotivos. Baseados nos teóricos da Psicologia Social Discursiva e em teóricos pós-estruturalistas que estudam a relação entre discurso e identidade, partimos do pressuposto de que as identidades são construídas por práticas sociais e discursivas e são objetos negociados e disputados por diferentes discursos. Para a realização deste estudo, entrevistamos militantes de dois grupos de apoio à adoção, coletamos o material discursivo disponibilizado no site da Associação Nacional de Grupos de Apoio à Adoção (ANGAAD) e matérias do Jornal Folha de S. Paulo veiculadas durante o período de 2009 a 2014. Para a análise desse material discursivo, utilizamos o referencial teórico-metodológico da Psicologia Social Discursiva, a qual dispensa uma especial atenção às ações realizadas com o uso da linguagem. Os resultados mostram que diferentes atributos são mobilizados para construir a identidade do filho adotivo. Um deles, mobilizado pela mídia, de maneira sutil, é a suposta periculosidade do filho adotivo. Esse atributo é combatido pelos militantes da causa da adoção. Denunciam a assimetria existente entre filhos adotivos e biológicos nesses relatos. Outro atributo é o abandono, apresentado pela mídia, e de maneira ambígua pelos militantes, como um atributo central dos filhos adotivos. A ideia de que os filhos adotivos têm uma predisposição para apresentarem distúrbios psicológicos e problemas de conduta também esteve presente, mas foi mais combatida do que endossada. Outra maneira de identificar os filhos adotivos consiste em afirmar que eles são filhos autênticos porque passaram pela via da adoção. Por fim, outro atributo presente diz respeito aos candidatos a futuros filhos adotivos. Eles são representados fundamentalmente a partir de características biológicas e sociais negativas. / The aim of this study is to identify and analyse the construction of identity discourses in media and adoption support groups reports regarding adoptive children. Taking in account the theories of Social Psychology and Post-structuralism, in which the relationship between discourse and identity is studied, it is argued that identities are constructed and negotiated by social practices and discourses. For this study we interviewed supporters of two adoption groups, also analysed discursive material available on the National Association of Adoption Support Groups (ANGAAD) site and finally news published by the newspaper Folha de S. Paulo from 2009 to 2014. An analytical framework was developed based on the theories of Discursive Psychology, taking in account the use of language in relation to social actions. The findings demonstrate that different attributes are negotiated to construct the adopted children identity. One of them, underlined by the media, subtly, is the supposed to the dangerousness of the adopted child. This discourse is contested by the supporters of the adoption groups, who underline the inequality between adoptive and biological children. Another attribute presented by the media and also by the adoption supporters, the latest in an unclear discourse, is related to rejection. The idea that the adoptive children have a predisposition to develop psychological disorders and behavioural problems was also present in the interviewees and media reports analysis. However, this perspective was more criticized than used to characterize the adoptive children. Another way to identify the adoptive children is to state that they are ‘true children’ because they have been through the adoption process. Finally, another attribute presented in the findings is related to the candidates to prospective adoptive children. These are mainly represented by using biological and social negative attributes.

Abstract Both genetic and environmental factors and gene-environment interaction have been found to contribute to the development of schizophrenia. Predisposition may manifest as prodromal vulnerability indicators before the onset of disease. The aim was to search for vulnerability signs of schizophrenia spectrum disorders, to establish the origin of these signs, and to predict the future mental disorders of adoptees with these signs. The study is a part of the Finnish Adoptive Family Study of Schizophrenia. Genetic vulnerabilty indicators were studied by comparing MMPI (Minnesota Multiphasic Personality Inventory) subscales of high-risk adoptees (HR, biological mother with a diagnosis of schizophrenia spectrum disorder) and low-risk adoptees (LR, biological mother with no diagnosed schizophrenia spectrum disorder) in the sample of all adoptees (n = 182) and in the sample of initially mentally healthy adoptees (n = 136). The later mental health status of the initially mentally healthy adoptees (assessed with DSM-III-R criteria) was predicted by MMPI subscales during the 11-year follow-up. The origins of the vulnerability indicators were investigated by assessing gene-environment interaction using parental Communication Deviance (CD) as a measure of environmental risk (n = 99). The MMPI subscales Hostility, Hypomania, and Social Maladjustment (these scales indicate emotional unresponsiveness, avolition, decreased energy, and introversion) were found to be vulnerability indicators of schizophrenia spectrum disorders. Social Maladjustment developed under gene-environment interaction when the environmental risk was assessed by CD. Psychopathic Deviate (asociality) was found to be a predictor of any later mental health disorder of the adoptees. Genetic vulnerability to schizophrenia spectrum disorders, gene-environment interaction and later onset of psychiatric disorders were found to manifest in the adoptees' MMPI. These results suggest a need to use a combination of multiple methodologies in the screening of at-risk individuals and are useful in the clinical practice of preventive mental health care. / Tiivistelmä Skitsofreniaan sairastumisessa keskeisiä ovat perintö- ja ympäristötekijät sekä näiden yhdysvaikutus. Skitsofrenia kehittyy siten, että jo ennen sairauden puhkeamista on olemassa alttiutta ilmentäviä, sairautta ennakoivia prodromaali piirteitä. Tämän tutkimuksen tarkoituksena oli etsiä skitsofreniaspektrin häiriöihin sairastumiseen liittyviä haavoittuvuutta ilmentäviä merkkejä, selvittää kuinka nämä kehittyvät ja ennustaa niillä adoptiolasten myöhempiä mielenterveydenhäiriöitä. Tutkimus on osa suomalaista adoptiolapsiperhetutkimusta. Perinnöllistä haavoittuvuuden ilmenemistä tutkittiin vertailemalla riskiadoptiolasten (biologisella äidillä oli skitsofreniaspektrin häiriö) ja heidän verrokkiensa (biologisella äidillä ei ollut skitsofreniaspektrin häiriötä) MMPI (Minnesota Multiphasic Personality Inventory) testin osa-asteikkoja kaikkien adoptiolasten ryhmässä (n = 182) ja tutkimuksen aloitusvaiheessa psyykkisesti terveiden adoptiolasten ryhmässä (n = 136). Tutkimuksen aloitusvaiheessa psyykkisesti terveiden adoptiolasten MMPI testin osa-asteikoilla ennustettiin 11 vuoden seurannassa heidän DSM-III-R kriteerein arvioitua mielenterveyttään. Perimän ja perheympäristön (adoptiovanhempien kommunikaatiohäiriöt) yhdysvaikutuksella pyrittiin selittämään haavoittuvuutta ilmentävien piirteiden syntyä (n = 99). MMPI testin osa-asteikot Hostility, Hypomania ja osittain myös Social Maladjustment (astekot ilmentävät emotionaalisen vastavuoroisuuden puutetta, tahdottomuutta, energian puutetta ja sosiaalista vetäytyneisyyttä) osoittivat perinnöllistä haavoittuvuutta skitsofreniaspektrin häiriöihin. Social Maladjustment kehittyi perinnöllisen riskin ja adoptiovanhempien poikkeavan kommunikaation yhdysvaikutuksen seurauksena. Psychopathic Deviate (asosiaalinen käyttäytyminen) ennusti adoptiolasten myöhempää sairastumista mihin tahansa mielenterveydenhäiriöön. Perinnöllinen alttius skitsofreniaspektrin häiriöihin, perintö- ja ympäristötekijöiden yhdysvaikutus sekä myöhempi sairastuminen mielenterveyden häiriöihin ilmenivät MMPI testin tuloksissa. Tuloksia voidaan käytää hyväksi mielenterveydenhäiriöiden ennaltaehkäisyssä.

PRIDE preservice training is a widely-used method of resource parent preparation, yet a program that has been the focus of very little research. This thesis project was carried out in two studies designed to examine the process of training, investigate selected outcomes of the training, and explore the transfer of training into practice. The first study involved 174 prospective resource parents. Investigation of the process of preservice training determined that participant engagement and participant-perceived fidelity, the combination of which was conceptualized as participant-perceived training quality, were high. In terms of outcomes, significant large gains from pre- to posttraining were observed in knowledge of the PRIDE competencies taught by the training. However, no differences were found in resource parent attitudes (erroneous beliefs or motivation to adopt) from pre- to posttraining. Higher training quality was a significant predictor of both greater knowledge gains and higher participant satisfaction. No differences between prospective foster parents and adoptive parents emerged in terms of participant dropout, knowledge gain, participant satisfaction, or attitudes about resource parenting. The second study was a follow-up with 11 foster, adoptive, and kinship parents from study one who had begun parenting a child in care. Interviews with these resource parents focused on the transfer of training of the PRIDE competencies and requested feedback about the training. Participants’ ratings of their transfer of training were high, while the researchers’ ratings fell in the mid-range. Overall, participants’ comments about PRIDE were positive. Participants highlighted how useful they found personal accounts of resource parents’ experiences during training and that child welfare workers played a key role in the implementation of training. The methodological contributions of this project include the development of three measures – a knowledge of PRIDE competencies questionnaire, a measure of participant-perceived quality, and a transfer of training rating scale – that can be used both in future research and in practice. In addition, this project supplied the first evidence of meaningful links between the process, outcomes, and transfer of PRIDE training, all of which were positive. The project provided essential foundational research which future studies of PRIDE should take into account.

Cancer immunotherapy has become a leading treatment modality in metastatic diseases. Although this novel therapy has changed the therapeutic algorithms and patients' outcomes in multiple malignancies, certain proportions of patients still fail to respond to these approaches. In our studies, we aimed to address the main mechanisms of tumor resistance to cancer immunotherapy. We have systematically defined the main challenges in adoptive cell transfer. We have focused on two key mechanisms of the tumor resistance to immunotherapy: poor trafficking of adoptively transferred immune cells into tumors, and the death receptor-induced apoptosis of the tumor-infiltrating immune cells. In our work, we have gone beyond the tumor tissue and searched for the immune cell populations and novel targets that would help to challenge the two mechanisms of resistance. Our data uncovered the therapeutic potential of the paratumoral tissue compartments and, thus, provided new avenues on how to challenge solid tumors by immunotherapy.

The purpose of this study was to critically examine differences in levels of anxiety, locus of control and stress between adoptive and biological parents of adolescents.

95% of adoption in the United States are open adoptions (Siegel & Smith, 2012). Past research has focused on the satisfaction of the adoptive parents, birth mother and adoptee in open adoption (Colaner & Scharp, 2016). However, there is a gap in research considering communication within the open adoption relationship (Grotevant, 2009). This qualitative phenomenological study sought to understand the experiences of birth mothers and adoptive parents in open adoption relationships as well as determine what is helpful and/or harmful within this relationship. The researchers conducted 20 semi-structured interviews with birth mothers and adoptive parents. Through open coding, key findings included a commonality of strong emotions and a consistent emphasis on the adoptee, as well as the benefit of healthy communication, boundaries and a relationship pre-placement. Based on the findings and limitations of this study recommendations were made for professionals, birth mothers, adoptive parents and future research.

The aim of this thesis is to try to understand the experiences of Swedish-born adoptees during the process of searching for and meeting their biological family. The subjects have been recruited from the Organisation of Adult Adoptees and Foster Children (AFO) and some other sources. The group consists of 20 adult Swedish-born adoptees, ten women and ten men.   Data have been collected through questionnaires with both open-ended and closed questions regarding their childhood and through interviews with structured questions and follow-up questions concerning the search process. The elaboration of data bas followed the search process and highlighted common features, which have brought about certain themes. The analysis of the descriptions has been made according to some existential key concepts in order to deepen the understanding of the search process. Thus, some broadly human existential dilemmas have emerged.  The results indicate a heterogeneous group of subjects. One salient feature is that the search process has been activated in critical situations when lack of knowledge about identity and heredity has been experienced. Another distinct result is the need to get physical likeness confirmed when meeting biological relatives. Such an experience has met a deficiency. Yet another distinct result is the need of contact, no matter the quality, with biological relatives so as to experience closeness built on biological bonds. There has been a will to establish lasting relationships in order to experience identity and continuity. Furthermore, many have experienced during the search process that getting a biological family has added a new dimension to their lives and contributed to personal healing. The adoptees' search for their origin can be seen as a process where broadly human existential dilemmas are particularly prominent.

Indiana University-Purdue University Indianapolis (IUPUI) / Text of thesis restricted indefinitely for privacy issues. Contact the Center for Digital Scholarship: digschol@iupui.edu.

Situated within the historiography of transnational child adoption, this dissertation explores the history of transnational child adoption from Vietnam by Americans in the Vietnam War. This story of Vietnamese adoption begins with comparing and contrasting representations of American and Vietnamese parenthood during the War. While American servicemen and women were highly praised for their humanitarianism in Vietnam and portrayed as good mothers and fathers to Vietnamese children, Vietnamese women were depicted as prostitutes, bar girls, and potential enemies in American public memory. This dissertation argues that the sexualized representation of Vietnamese women and the focus on American humanitarianism provided justifications for the transnational adoption of Vietnamese children but concealed the violence of the War that led to the displacement of Vietnamese children in the very beginning. It also shows how racial and religious relations in the U.S. complicated the picture of Vietnamese adoption. African American civil rights movement at home motivated black social workers to fight for the rights of black families to adopt black children domestically and transnationally. Meanwhile, American adoptive parents were subject to the scrutiny of Catholic orphanage directors in Vietnam and American social workers who tried to uphold religious matching in adoption. Finally, this dissertation ends with exploring controversies around Operation Babylift, a US government-sponsored evacuation of Vietnamese “orphans” to the US. Labeled as a humanitarian operation, the Babylift invoked criticism over its morality as more than 130 children were killed by an airplane crash and hundreds of children ended up being illegally brought to the US for adoption.