Correction: Cognitive Advantage in Children Enrolled in a Second-Language Immersion Elementary School Program for One Year.

[This corrects the article DOI: 10.5334/pb.469.].

Cognitive Advantage in Children Enrolled in a Second-Language Immersion Elementary School Program for One Year.

Early bilingualism has been shown to improve attentional and executive functioning. Nicolay and Poncelet (2013a, 2015) have shown that an early immersion program in school of 3 years improves the completion of tasks assessing these skills. This study aimed to determine whether similar benefits might be present after only 1 year of immersion education. The study also observed whether these potential advantages might also have a positive effect on the academic achievement. Participants included 59 immersed children and 57 monolingual controls. The two groups were compared using the same tasks as those employed by Nicolay and Poncelet (2015). The immersed children showed faster responses in comparison to monolinguals on the selective auditory task. No significant differences were observed on the other attentional, executive, or academic tasks. These outcomes suggest that a period of immersion education as short as 1 year can yield cognitive advantages associated with bilingualism.

Prospective Analysis of Adoptive TIL Therapy in Patients with Metastatic Melanoma: Response, Impact of Anti-CTLA4, and Biomarkers to Predict Clinical Outcome.

Purpose: Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) has consistently demonstrated clinical efficacy in metastatic melanoma. Recent widespread use of checkpoint blockade has shifted the treatment landscape, raising questions regarding impact of these therapies on response to TIL and appropriate immunotherapy sequence.Patients and Methods: Seventy-four metastatic melanoma patients were treated with autologous TIL and evaluated for clinical response according to irRC, overall survival, and progression-free survival. Immunologic factors associated with response were also evaluated.Results: Best overall response for the entire cohort was 42%; 47% in 43 checkpoint-naïve patients, 38% when patients were exposed to anti-CTLA4 alone (21 patients) and 33% if also exposed to anti-PD1 (9 patients) prior to TIL ACT. Median overall survival was 17.3 months; 24.6 months in CTLA4-naïve patients and 8.6 months in patients with prior CTLA4 blockade. The latter patients were infused with fewer TIL and experienced a shorter duration of response. Infusion of higher numbers of TIL with CD8 predominance and expression of BTLA correlated with improved response in anti-CTLA4 naïve patients, but not in anti-CTLA4 refractory patients. Baseline serum levels of IL9 predicted response to TIL ACT, while TIL persistence, tumor recognition, and mutation burden did not correlate with outcome.Conclusions: This study demonstrates the deleterious effects of prior exposure to anti-CTLA4 on TIL ACT response and shows that baseline IL9 levels can potentially serve as a predictive tool to select the appropriate sequence of immunotherapies. Clin Cancer Res; 24(18); 4416-28. ©2018 AACR.

Utilizing T-cell Activation Signals 1, 2, and 3 for Tumor-infiltrating Lymphocytes (TIL) Expansion: The Advantage Over the Sole Use of Interleukin-2 in Cutaneous and Uveal Melanoma.

In this study, we address one of the major critiques for tumor-infiltrating lymphocyte (TIL) therapy-the time needed for proper expansion of a suitable product. We postulated that T-cell receptor activation in the first phase of expansion combined with an agonistic stimulation of CD137/4-1BB and interleukin-2 would favor preferential expansion of CD8 TIL. Indeed, this novel 3-signal approach for optimal T-cell activation resulted in faster and more consistent expansion of CD8CD3 TIL. This new method allowed for successful expansion of TIL from cutaneous and uveal melanoma tumors in 100% of the cultures in <3 weeks. Finally, providing the 3 signals attributed to optimal T-cell activation led to expansion of TIL capable of recognizing their tumor counterpart in cutaneous and uveal melanoma. This new methodology for the initial phase of TIL expansion brings a new opportunity for translation of TIL therapy in challenging malignancies such as uveal melanoma.

A Novel Method to Generate and Expand Clinical-Grade, Genetically Modified, Tumor-Infiltrating Lymphocytes.

Following the clinical success achieved with the first generation of adoptive cell therapy (ACT) utilizing in vitro expanded tumor-infiltrating lymphocytes (TILs), the second and third generations of TIL ACT are evolving toward the use of genetically modified TIL. TIL therapy generally involves the transfer of a high number of TIL, ranging from 109 to 1011 cells. One of the technical difficulties in genetically modifying TIL, using a retroviral vector, is the ability to achieve large expansion of transduced TIL, while keeping the technique suitable to a Good Manufacturing Practices (GMP) environment. Consequently, we developed and optimized a novel method for the efficient production of large numbers of GMP-grade, gene-modified TIL for the treatment of patients with ACT. The chemokine receptor CXCR2 was used as the gene of interest for methodology development. The optimized procedure is currently used in the production of gene-modified TIL for two clinical trials for the treatment of metastatic melanoma at MD Anderson Cancer Center.

Funcionalidad familiar y embarazo, en adolescentes que asisten a controles prenatales en centros de ASSBASALUD ESE, Manizales (Colombia), 2012 / Family functionality and pregnancy, in adolescents attending to prenatal controls in ASSBASALUD ESE centers Manizales (Colombia) 2012

Objetivo: Analizar la funcionalidad familiar y factores relacionados en un grupo de adolescentes embarazadas que asisten a control prenatal en los centros de atenciónde ASSBASALUD ESE (Manizales, Colombia). Materiales y métodos: Estudio de corte transversal con una población de 190 adolescentes embarazadas entre los 12 y 21 años, el instrumento utilizado fue una encuesta escrita, anónima, que interrogaba sobre variables socio demográficas, relación con sus padres, niveles de comunicación con los padres, situaciones conflictivas en la familia y funcionalidad familiar medida por el APGAR familiar Resultados: Promedio de edad de 18 años, el 72,1% de la población presentó disfuncionalidad familiar de leve a severa, Entre ninguna y regular relación con el padre 46,9% y 25,3% con la madre, 38,9% presentaban antecedentes de violencia familiar, 25,8% depresión, 23,2% de consumo de alcohol, 36,3% pensaban que no iban a quedar embarazadas al tener relacione sexuales, 26,8% deseaban tener hijos. La buena funcionalidad familiar tuvo relación significativa con la no presencia de violencia intrafamiliar (p=0,000), la no presencia de embarazo en < de 17años (p=0,020), no empleo de métodos anticonceptivos (p=0,000), alto número de embarazos (p=0,025), no presencia de abortos inducidos (p=0,007), hablar sobre temas de embarazo y sexualidad con los padres (p=0,000). Conclusiones: La población de adolescentes gestantes estudiada tiene características similares a las poblaciones de otras ciudades de Colombia, y otros países. Se demuestra que, como prácticamente en todos los ámbitos del ser humano, en este también la familia es decisiva y determinante en la presencia de embarazo precoz en estas adolescentes.

Specific lymphocyte subsets predict response to adoptive cell therapy using expanded autologous tumor-infiltrating lymphocytes in metastatic melanoma patients.

PURPOSE: Adoptive cell therapy (ACT) using autologous tumor-infiltrating lymphocytes (TIL) is a promising treatment for metastatic melanoma unresponsive to conventional therapies. We report here on the results of an ongoing phase II clinical trial testing the efficacy of ACT using TIL in patients with metastatic melanoma and the association of specific patient clinical characteristics and the phenotypic attributes of the infused TIL with clinical response. EXPERIMENTAL DESIGN: Altogether, 31 transiently lymphodepleted patients were treated with their expanded TIL, followed by two cycles of high-dose interleukin (IL)-2 therapy. The effects of patient clinical features and the phenotypes of the T cells infused on the clinical response were determined. RESULTS: Overall, 15 of 31 (48.4%) patients had an objective clinical response using immune-related response criteria (irRC) with 2 patients (6.5%) having a complete response. Progression-free survival of more than 12 months was observed for 9 of 15 (60%) of the responding patients. Factors significantly associated with the objective tumor regression included a higher number of TIL infused, a higher proportion of CD8(+) T cells in the infusion product, a more differentiated effector phenotype of the CD8(+) population, and a higher frequency of CD8(+) T cells coexpressing the negative costimulation molecule "B- and T-lymphocyte attenuator" (BTLA). No significant difference in the telomere lengths of TIL between responders and nonresponders was identified. CONCLUSION: These results indicate that the immunotherapy with expanded autologous TIL is capable of achieving durable clinical responses in patients with metastatic melanoma and that CD8(+) T cells in the infused TIL, particularly differentiated effectors cells and cells expressing BTLA, are associated with tumor regression.