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An enhanced transmission line model has been recently proposed by the authors to perform the frequency-domain full-wave analysis of high-speed interconnects operating in non-TEM condition. Here this model is used to investigate the effects of such operating conditions on the time-domain signal waveforms. The interconnects are described by a reduced-order model, obtained by using the vector fitting method to identify its Z-parameters. The time-domain analysis of the performance of some case-studies highlights degradation of the signal, due to the effects of radiation loss and finite-length dispersion. The solution of the ETL model provides useful indications to control such degradation.