Summary. The lasso penalizes a least squares regression by the sum of the absolute values (L 1 -norm) of the coefficients. The form of this penalty encourages sparse solutions (with many coefficients equal to 0). We propose the 'fused lasso', a generalization that is designed for problems with features that can be ordered in some meaningful way. The fused lasso penalizes the L 1 -norm of both the coefficients and their successive differences. Thus it encourages sparsity of the coefficients and also sparsity of their differences-i.e. local constancy of the coefficient profile. The fused lasso is especially useful when the number of features p is much greater than N, the sample size. The technique is also extended to the 'hinge' loss function that underlies the support vector classifier.We illustrate the methods on examples from protein mass spectroscopy and gene expression data.

Traditional reporting of toxicity data (CTCAE) has under-reported ototoxicity and minimized the significance of hearing loss in children. As pediatric patients experience improved survival, the effects and implications of high-frequency hearing loss with regard to academic achievement and speech and language development are important considerations, especially in patients younger than 5 years.

A B S T R A C T PurposeThe platinum chemotherapy agents cisplatin and carboplatin are widely used in the treatment of adult and pediatric cancers. Cisplatin causes hearing loss in at least 60% of pediatric patients. Reducing cisplatin and high-dose carboplatin ototoxicity without reducing efficacy is important. Patients and MethodsThis review summarizes recommendations made at the 42nd Congress of the International Society of Pediatric Oncology (SIOP) in Boston, October 21-24, 2010, reflecting input from international basic scientists, pediatric oncologists, otolaryngologists, oncology nurses, audiologists, and neurosurgeons to develop and advance research and clinical trials for otoprotection. ResultsPlatinum initially impairs hearing in the high frequencies and progresses to lower frequencies with increasing cumulative dose. Genes involved in drug transport, metabolism, and DNA repair regulate platinum toxicities. Otoprotection can be achieved by acting on several these pathways and generally involves antioxidant thiol agents. Otoprotection is a strategy being explored to decrease hearing loss while maintaining dose intensity or allowing dose escalation, but it has the potential to interfere with tumoricidal effects. Route of administration and optimal timing relative to platinum therapy are critical issues. In addition, international standards for grading and comparing ototoxicity are essential to the success of prospective pediatric trials aimed at reducing platinum-induced hearing loss. ConclusionCollaborative prospective basic and clinical trial research is needed to reduce the incidence of irreversible platinum-induced hearing loss, and optimize cancer control. Wide use of the new internationally agreed-on SIOP Boston ototoxicity scale in current and future otoprotection trials should help facilitate this goal.

EHF audiometry and DPOAEs have the potential to reveal earlier changes in auditory function than conventional frequency audiometry during platinum chemotherapy in children.