Developmental and evolutionary assumptions in a study about the impact of premature birth and low income on mother–infant interaction

In order to study the impact of premature birth and low income on mother–infant interaction, four Portuguese samples were gathered: full-term, middle-class (n=99); premature, middle-class (n=63); full-term, low income (n=22); and premature, low income (n=21). Infants were filmed in a free play situation with their mothers, and the results were scored using the CARE Index. By means of multinomial regression analysis, social economic status (SES) was found to be the best predictor of maternal sensitivity and infant cooperative behavior within a set of medical and social factors. Contrary to the expectations of the cumulative risk perspective, two factors of risk (premature birth together with low SES) were as negative for mother–infant interaction as low SES solely. In this study, as previous studies have shown, maternal sensitivity and infant cooperative behavior were highly correlated, as was maternal control with infant compliance. Our results further indicate that, when maternal lack of responsiveness is high, the infant displays passive behavior, whereas when the maternal lack of responsiveness is medium, the infant displays difficult behavior. Indeed, our findings suggest that, in these cases, the link between types of maternal and infant interactive behavior is more dependent on the degree of maternal lack of responsiveness than it is on birth status or SES. The results will be discussed under a developmental and evolutionary reasonin

Clinical Development of Novel Drug-Radiotherapy Combinations.

Radiotherapy is a fundamental component of treatment for the majority of patients with cancer. In recent decades, technological advances have enabled patients to receive more targeted doses of radiation to the tumor, with sparing of adjacent normal tissues. There had been hope that the era of precision medicine would enhance the combination of radiotherapy with targeted anticancer drugs; however, this ambition remains to be realized. In view of this lack of progress, the FDA-AACR-ASTRO Clinical Development of Drug-Radiotherapy Combinations Workshop was held in February 2018 to bring together stakeholders and opinion leaders from academia, clinical radiation oncology, industry, patient advocacy groups, and the FDA to discuss challenges to introducing new drug-radiotherapy combinations to the clinic. This Perspectives in Regulatory Science and Policy article summarizes the themes and action points that were discussed. Intelligent trial design is required to increase the number of studies that efficiently meet their primary outcomes; endpoints to be considered include local control, organ preservation, and patient-reported outcomes. Novel approaches including immune-oncology or DNA-repair inhibitor agents combined with radiotherapy should be prioritized. In this article, we focus on how the regulatory challenges associated with defining a new drug-radiotherapy combination can be overcome to improve clinical outcomes for patients with cancer

Cytoneme-Mediated Delivery of Hedgehog Regulates the Expression of Bone Morphogenetic Proteins to Maintain Germline Stem Cells in Drosophila

Genetic manipulation of the germline stem cell niche in Drosophila ovaries reveals that support cells ensure the maintenance of stem cells by modulating the spread of Hedgehog within the niche

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Moldear la arcilla. El proceso de construcción del self y su relación con la psicoterapia.

Cognitive psychotherapists are concerned with the implication of the self and the process of construction of self for psychotherapy. This paper considers what attachment theory, with its emphasis on developmental processes and the protective function of attachment figures, toghether with current information from the cognitive neurosciences, can contribute to an understanding of psychological disorders of the self (Guidano, 1995a)Los psicoterapeutas cognitivos se interesan por las implicaciones del self y el proceso de construcción del self durante la psicoterapia. Este artículo considera qué tipo de teorías de apego, con su énfasis en los procesos de desarrollo y en la función protectora de las figuras de apego, junto con la información actual de las neurociencias cognitivas, pueda contribuir a una comprensión de los desórdenes psicológicos del self (Guidano, 1995a)

Comparing models of borderline personality disorder: mothers' experience, self-protective strategies, and dispositional representations

This study compared aspects of the functioning of mothers with borderline personality disorder (BPD) to those of mothers without psychiatric disorder using two different conceptualizations of attachment theory. The Adult Attachment Interviews (AAIs) of 32 mothers were classified using both the Main and Goldwyn method (M&G) and the Dynamic-Maturational Model method (DMM). We found that mothers with BPD recalled more danger, reported more negative effects of danger, and gave evidence of more unresolved psychological trauma tied to danger than other mothers. We also found that the DMM classifications discriminated between the two groups of mothers better than the M&G classifications. Using the DMM method, the AAIs of BPD mothers were more complex, extreme, and had more indicators of rapid shifts in arousal than those of other mothers. Representations drawn from the AAI, using either classificatory method, did not match the representations of the mother’s child drawn from the Working Model of the Child Interview; mothers with very anxious DMM classifications were paired with secure-balanced child representations. We propose that the DMM offers greater clinical utility, conceptual coherence, empirical validity, and coder reliability than the M&G

Transformaciones en las relaciones de apego en la adolescencia: adaptación frente a necesidad de psicoterapia

Adolescence is a period of dramatic change in attachment relationships. Furthermore, adolescence culminates a developmental process in which interaction with parents has shaped children’s minds and behavior in ways that may or may not prepare them for life outside their families. On the other hand, the neurological maturation occurring in adolescence creates the first opportunity for individuals to consider and change, independently from their parents, the heritage they take from their childhood families. This article first places attachment in a developmental framework and then focuses on the process of change for those adolescents who require professional intervention to make the transition from a distorted childhood to an adaptive adulthood.La adolescencia es un periodo de cambios significativos en las relaciones de apego. Además, la adolescencia culmina un proceso de desarrollo en el cual la interacción con los padres ha modelado la mente y el comportamiento de los hijos de manera que estarán o no preparados para la vida fuera de sus familias de origen. Por otro lado, la maduración neurológica que ocurre durante la adolescencia crea la primera oportunidad para los individuos de considerar y cambiar, independientemente de sus padres, la herencia familiar. Este artículo sitúa en primer lugar el apego en un marco de desarrollo y luego se centra en el proceso de cambio para aquellos adolescentes que necesitan una intervención profesional para realizar la transición desde una infancia distorsionada a una edad adulta con capacidad de adaptación