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Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.

In Experiment I, four children with asthma were taught to use the intermittent positive-pressure breathing (IPPB) apparatus, a device that delivers bronchodilator medication to the lungs under positive pressure. Because these youngsters had not learned to use the device with repeated instructions, script with back-up reinforcement was introduced to train sequentially three responses - eye fixation, facial posturing, and diaphragmatic breathing - according to a multiple-baseline design. The procedures were effective in teaching appropriate use of the IPPB apparatus. Further, the children's use of the apparatus after training resulted in significantly more effective relief of asthma symptoms. In a second experiment, nurses were instructed in the application of the operant techniques used in the first study, and then served as experimenters in a partial replication of Experiment I. The data once again reflected a strong impact of the intervention program on IPPB responses.