Social workers' attitudes, beliefs and values have been shown to effect how they evalute and process gay adoptive parents paperwork.

Older adopted children and their families often express high need for support for attachment and trauma related concerns. Post-adoption mental health intervention focused on enhancing the parent-child relationship among adoptive parents and adoptees is essential for fostering placement permanency among these families. This single group pilot study explored the effect of Child-Parent Relationship Therapy (CPRT) for adoptive parents of preadolescents who reported attachment related concerns, stress in the parent-child relationship, and child behavior problems. Participants were 11 adoptive parents ages 25 to 64 (55% male; 91% couples; 100% married; 56% European American, 27% Asian, 9% Hispanic, and 9% Black American) with adoptees between the ages of 8 to 14 (56% male; 56% Hispanic, 33% European American, and 11% Black American). All child participants were adopted out of foster care. Data was collected at baseline, pretest, midtest, and posttest. Results from non-parametric Friedman test of differences across 4 points of measure indicated that CPRT demonstrated statistically significant improvement for the 3 outcome variables: parental empathy, child behavior, and parent child relationship stress. Specifically, results indicated that prior to receiving CPRT (baseline to pretest), parents demonstrated no change or worsening in functioning across all variables, whereas during the intervention phase findings showed a large treatment effect for parental empathy, a medium effect for parenting stress, and a small effect for child behavior problems. Findings from this pilot study support CPRT as a promising mental health intervention for adoptive parents and preadolescent children. Clinical implications and recommendations for working with adoptive parents of preadolescents are explored within the context of these findings.

Cancer is the second most common cause of death in the world, and the number of people with the disease increases each year. The therapy of the disease currently stands on four pillars; surgery, chemotherapy, radiotherapy, and immunotherapy. Through the past few years, immunotherapy has become the fastest developing treatment modality. However, despite its unprecedented efficacy in some patients, the majority of patients still does not respond to the therapy. Therefore, there is a need to investigate the mechanisms that make immunotherapy inefficient. Cell-based cancer immunotherapy is the treatment modality which uses live ex vivo-produced tumor-targeting immune cells to treat cancer. One of the mechanisms that may compromise its therapeutic efficacy is the expression of inhibitory molecules on the surface of the produced immune cells. Tim-3 is the inhibitory molecule which attracts attention in recent years. Tim-3 expression in the tumor cells and the tumor-infiltrating immune cells is often associated with worse prognosis and more aggressive forms of the disease. However, its role in the in vitro or ex vivo-produced immune cells is difficult to predict. In this work, an in vitro study model which is based on in vitro-produced antigen-specific CD8+ T cells with high expression of Tim-3 has been...

Indiana University-Purdue University Indianapolis (IUPUI) / Awaiting adoption is a social problem in America that affects thousands of children as well as families, agencies, communities, the mission of the child welfare system, and society at large. In 2014, over 101,000 children were awaiting adoption in the United States. On average, waiting children have been in out-of-home care for approximately three years. One phenomenon that plagues waiting children and their opportunity for adoption is the disruption of their pre-adoptive placements or the change in a waiting child's placement prior to a finalized adoption. Despite unique placement and permanency needs, waiting children and their foster parents are seldom recognized as unique cohorts. Thus, little is known about the experience of pre-adoptive placement disruption. The status of waiting children, foster care and adoption history and policy, and literature and theory relevant to pre-adoptive placement disruption are discussed. In-depth, semi-structured interviews and Interpretive Phenomenological Analysis were used to investigate the research question: What is the experience of pre-adoptive placement disruption for pre-adoptive foster parents? Eleven foster parents participated in nine interviews. Participants were licensed through public or private child welfare agencies. The majority of participants were married, Caucasian, and had adopted from foster care. Important findings emerged from the experiences participants shared. Pre-adoptive placement disruption is characterized by "compound loss" including both the loss of the child and the loss of purpose. Participants experienced the disruption like a broken social contract and attributed the disruption to the child welfare system or the children's perpetrators. Disruption experiences resulted in lasting effects including changes to the profiles of the children participants would foster or adopt in the future, pre-adoptive status, and advocacy efforts. Resolve emerged as a critical factor for participants to approach foster and pre-adoptive care in new ways. Vulnerability, isolation, and ambivalence emerged as essential elements of living through disruption. Findings suggest the importance of assessing pre-adoptive parents' motivations and expectations, validating their experiences, acknowledging their losses, and practicing with transparency and competency. Implications exist for child welfare and social work practice and education. Additional research is needed regarding barriers and supports of adoption from foster care.

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[pt] A presente pesquisa, apresentada no formato de dois artigos, tem como objetivo geral investigar a amplitude do direito de acesso às origens, assegurado por Lei aos adotados. O interesse pela temática surgiu a partir de um atendimento paradigmático em uma das Varas da Infância do Estado do Rio de Janeiro, no qual a genitora buscou o Judiciário a fim de estabelecer contato com a filha que fora entregue para adoção há mais de 30 anos. Para atingir o objetivo geral do trabalho, refletimos sobre a importância de serem incluídos no estudo de campo os representantes de cada um dos vértices da tríade adotiva –família biológica, filho e família adotiva – frente às particularidades de sua dinâmica de funcionamento para a análise do tema proposto. Assim, realizamos entrevistas semiestruturadas em separado com a genitora, demandante do contato, a filha e a mãe por adoção. As entrevistas foram analisadas segundo o método de análise de conteúdo e as categorias emergidas do material coletado foram articuladas à literatura sobre entrega voluntária, busca de contato entre as famílias biológica e adotiva e mediação do Judiciário. Percebemos que a experiência do encontro mediado pela Justiça teve avaliação positiva dos envolvidos, funcionando de forma integrativa para os componentes da tríade. Entretanto, a inexistência de um protocolo específico para atuar em situações dessa natureza quase inviabilizou a intervenção técnica, o que aponta para a necessidade de alguma sistematização pelo Judiciário no atendimento a esse tipo demanda. / [en] The present research, presented in the format of two articles, has the general objective of investigating the dimension of the right to access the origins, guaranteed by Law to adoptees. The interest in the theme emerged from a paradigmatic situation held in one of the Juvenile Courts of the State of Rio de Janeiro, in which the biological mother sought the Judiciary in order to establish contact with her daughter who had been voluntarily relinquished more than 30 years ago. To achieve the general objective of this work, we reflected on the importance of including in the field study the representatives of each of the vertices of the adoptive triad – biological family, adoptee and adoptive family - in view of the particularities of its dynamics for the analysis of the proposed theme. Thus, we conducted separate semi-structured interviews with the mother, the contact applicant, the daughter and the adoptive mother. The interviews were analyzed according to the content analysis method and the categories that emerged from the collected material were linked to the literature on voluntary relinquish, search and reunion and mediation by the Judiciary. We realized that the experience of the contact mediated by justice had a positive evaluation of those involved, working in an integrative way for the components of the triad. However, the lack of a specific protocol related to this kind of situation almost made the technical intervention in the case unfeasible, which points to the need for some systematization by the Judiciary on this type of demand.

<p>We showed previously that histone deacetylase (HDAC) inhibition with MS-275 in the context of boosting oncolytic immunotherapy can drive heightened antitumor responses, leading to increased survival in mouse intracranial melanoma models. However, it is currently unclear how the co-administration of MS-275 directly impacts tumor growth. Here, we investigated the role of MS-275 in preventing the outgrowth of antigen-deficient tumor variants as a result of suboptimal treatment protocols. By adoptively transferring tumor antigen-specific memory T cells (Tm) that were expanded <em>in vivo</em> with recombinant Vesicular Stomatitis Virus (VSV-gp33), we observed complete regression of 5-day old, intradermal B16-gp33 tumors (B16-F10 overexpressing the LCMV GP33-41 epitope); however, the tumors relapsed within a month of treatment. Relapsing tumor explants were able to grow in mice that were prophylactically immunized with recombinant Adenovirus (Ad-gp33), indicating that the tumor could no longer be recognized. Strikingly however, there was zero tumor recurrence if MS-275 was co-administered with Tm and VSV-gp33, suggesting that MS-275 may prevent the emergence and/or escape of antigen loss variants. Such a benefit is lost if the administration of the drug is delayed as little as five days post VSV treatment, suggesting that its synergistic effects coincide with early immune responses and oncolytic activity. Furthermore, transplantation studies of relapsing tumor explants showed that combination treatment was unable to provide tumor protection, confirming that the mechanisms by which MS-275 prevents tumor recurrence are unlikely through direct up-regulation of antigen presentation in low- or non-antigen-expressing variants <em>in vivo</em>. Indeed, CD4 depletion in the absence of MS-275 resulted in sustained tumor regression, implying that immunoregulatory cells such as CD4+ Treg play a prominent role in sustaining tumor regression. Moreover, MS-275 modulates the phenotypic status of tumor-infiltrating MDSCs toward the differentiation of inflammatory macrophages. Taken together, the data suggests that combination therapy with HDACi with oncolytic immunotherapy mediates a synergized immune attack against the tumor through subversion of immunomodulatory mechanisms.</p> / Master of Science in Medical Sciences (MSMS)

Durch den Transfer der Gene des heterodimeren T-Zellrezeptors (TZR) mithilfe viraler Vektoren können T-Zellen programmiert werden, ein ausgewähltes Antigen spezifisch zu erkennen. In klinischen Studien wurden solche T-Zellen bereits mit Erfolg zur Immuntherapie von Krebs und viralen Infektionen eingesetzt. Genmodifizierte T-Zellen unterscheiden sich jedoch von normalen T-Zellen, weil sie neben den beiden zelleigenen auch die zwei übertragenen TZR-Gene exprimieren. Diese Situation erlaubt die Bildung vier verschiedener TZR-Heterodimere: der zelleigene TZR, der übertragene TZR und zwei gemischte TZR, bestehend aus je einer übertragenen und einer zelleigenen TZR-Kette. Gemischte TZR bergen das Risiko von Nebenwirkungen, weil sie durch Zufall gesundes Körpergewebe erkennen und so Autoimmunität auslösen könnten. In dieser Arbeit wurden deshalb virale Vektoren entwickelt, die gleichzeitig mit der Übertragung von neuen TZR-Genen den zelleigenen TZR durch RNA Interferenz (RNAi) unterdrücken. Mikro-RNA (miRNA), die in den Vektor MP71 eingefügt wurden, reduzierten den zelleigenen TZR in Maus-T-Zellen um mehr als 85%. Dies hatte zur Folge, dass beide Ketten des übertragenen P14-TZR in gleicher Menge auf der Zelloberfläche exprimiert wurden und die Bildung von gemischten TZR reduziert wurde. In einem Mausmodell der adoptiven T-Zelltherapie verhinderte die Unterdrückung des zelleigenen TZR die Entstehung von Autoimmunität, die andernfalls durch gemischte TZR verursacht wurde. Im Gegensatz dazu führte die Anwendung von gentechnisch optimierten P14-TZR-Genen weder zur angeglichenen Oberflächenexpression der P14-TZR Ketten noch zu weniger Autoimmunität im Mausmodell. Ein anderes Tierexperiment zeigte, dass die miRNA die Funktion der genmodifizierten T-Zellen nicht beeinträchtigte. Schließlich wurde ein viraler Vektor entwickelt und getestet, der die Expression des zelleigenen TZR in menschlichen T-Zellen effektiv unterdrückte und die Bildung von gemischten TZR reduzieren konnte. / T cells can be genetically modified using viral vectors. The transfer of genes encoding both chains of the heterodimeric T cell receptor (TCR) programs T cells to specifically react towards an antigen of choice. Such TCR gene-modified T cells were already successfully applied in clinical studies to treat cancer and viral infections. However, in contrast to nonmanipulated T cells these cells express the transferred TCR in addition to the endogenous TCR and this situation allows the assembly of four different TCR heterodimers: the endogenous TCR, the transferred TCR, and two mixed TCR dimers, composed of one endogenous and one transferred TCR chain. The formation of mixed TCR dimers represents a safety issue because they may by chance recognize self-antigens and thereby cause autoimmune side effects. To overcome this problem, an RNAi-TCR replacement vector was developed that simultaneously silences the endogenous TCR and expresses an RNAi-resistant therapeutic TCR. The expression of miRNA encoded by a retroviral MP71 vector in transduced mouse T cells reduced the surface levels of the endogenous TCR by more than 85%. The knockdown of the endogenous TCR in turn resulted in equal surface expression levels of both transferred P14 TCR chains and prevented the formation of mixed TCR dimers. Accordingly, the development of lethal mixed TCR dimer-dependent autoimmunity (TI-GVHD) in a mouse model of adoptive T cell therapy was dramatically reduced by the knockdown of the endogenous TCR. In contrast, the usage of genetically optimized TCR genes neither resulted in equal surface levels of both P14 TCR chains nor in reduced autoimmunity. A second mouse model demonstrated that the in vivo functionality of the transduced T cells was not negatively influenced by the expression of the miRNA. Finally, an RNAi-TCR replacement vector for human T cells was developed that effectively reduced the expression of the endogenous TCR and prevented the formation of mixed TCR dimers.

The purpose of this study was to look at the factors that lead to disruption in the adoption of special needs children. Families that adopt special needs children may or may not be aware that they need post adoption services and may be reluctant to ask for them even when they are experiencing difficulty.

A questionaire was developed and given to post-adoptive parents with the results to be used as a guide to examine what services need to be provided in the pre-adoptive process for parents who are adopting children that are coming from foster homes. The results of the study could be utilized by adoption social workers as a means of targeting typical areas of need or resources for families during the adoption process.