Treatment of solid organ transplant recipients with autologous Epstein Barr virus-specific cytotoxic T lymphocytes (CTLs).

We have investigated the in vivo safety, efficacy, and persistence of autologous Epstein Barr virus (EBV)-specific cytotoxic T lymphocytes (CTLs) for the treatment of solid organ transplant (SOT) recipients at high risk for EBV-associated posttransplantation lymphoproliferative disease (PTLD). EBV-CTLs generated from 35 patients expanded with normal kinetics contained both CD8 and CD4 lymphocytes and produced significant specific killing of autologous EBV-transformed B lymphoblastoid cell lines (LCLs). Twelve SOT recipients at high risk for PTLD, or with active disease, received autologous CTL infusions without toxicity. Real-time polymerase chain reaction (PCR) monitoring of EBV-DNA showed a transient increase in plasma EBV-DNA suggestive of lysis of EBV-infected cells, although there was no consistent decrease in virus load in peripheral-blood mononuclear cells. Interferon-gamma enzyme-linked immunospot (ELISPOT) assay and tetramer analysis showed an increase in the frequency of EBV-responsive T cells, which returned to preinfusion levels after 2 to 6 months. None of the treated patients developed PTLD. One patient with liver PTLD showed a complete response, and one with ocular disease has had a partial response stable for over one year. These data are consistent with an expansion and persistence of adoptively transferred EBV-CTLs that is limited in the presence of continued immunosuppression but that nonetheless produces clinically useful antiviral activity.

Teacher support and encouragement in the classroom and its impact on childhood obesity

Objectives. Obesity is a growing problem in the United States among children. Great efforts are being made to target this problem, both at home and at school. While parents and peers have proven an effective means of distributing information, the well of the influence of teacher encouragement of health behaviors remains untapped. The purpose of this study is to assess the association of teacher encouragement with diet and physical activity behaviors and obesity in a sample of eighth grade students in central Texas. ^ Methods. In the spring of 2011, the Coordinated Approach to Child Health (CATCH) study distributed teacher surveys to each of the teachers in the schools on the grant. In addition to questions concerning the implementation of CATCH, this survey employed social support questions to gauge the prevalence of teacher encouragement of health behaviors in the classroom. During the same time frame, eighth graders in these same schools completed student surveys which assessed dietary and physical activity knowledge and behaviors and demographics and participated in objective measures of student height and weight. A cross-sectional secondary data analysis was conducted in order to compare self-reported teacher encouragement to student behaviors and several student obesity measures on a by school basis. ^ Results. 1150 teachers and 2582 students from 29 of the 30 measurement schools returned completed surveys. No statistically significant relationship was found between the six teacher encouragement measures and their corresponding student reported health behaviors, nor was one found the mean support per school and child percent overweight. A menial positive relationship was found between the mean support per school and child BMI z-scores, BMI, and percent obese (p = 0.035, 0.003 and 0.003, respectively); however, these relationships were not in the predicted direction. ^ Conclusion. While the findings of this investigation show primarily null results, motivating questions as to the impact to teacher encouragement on middle school student's health remain. It is possible that in order to draw more effective conclusions, more comprehensive studies are warranted which specifically target these relationships.^

DEVELOPMENT OF NOVEL METHODS TO MINIMIZE THE IMPACT OF SEQUENCING ERRORS IN THE NEXT-GENERATION SEQUENCING DATA ANALYSIS

Next-generation sequencing (NGS) technology has become a prominent tool in biological and biomedical research. However, NGS data analysis, such as de novo assembly, mapping and variants detection is far from maturity, and the high sequencing error-rate is one of the major problems. . To minimize the impact of sequencing errors, we developed a highly robust and efficient method, MTM, to correct the errors in NGS reads. We demonstrated the effectiveness of MTM on both single-cell data with highly non-uniform coverage and normal data with uniformly high coverage, reflecting that MTM’s performance does not rely on the coverage of the sequencing reads. MTM was also compared with Hammer and Quake, the best methods for correcting non-uniform and uniform data respectively. For non-uniform data, MTM outperformed both Hammer and Quake. For uniform data, MTM showed better performance than Quake and comparable results to Hammer. By making better error correction with MTM, the quality of downstream analysis, such as mapping and SNP detection, was improved. SNP calling is a major application of NGS technologies. However, the existence of sequencing errors complicates this process, especially for the low coverage (