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Multiple myeloma (MM) is the second most common blood cancer following non-Hodgkin's lymphoma. While the treatments for MM have improved over the past decade, for the most part, it remains an incurable disease. For this reason newer therapeutic agents are needed to combat this malignancy. Panobinostat is a pan-deacetylase inhibitor that impedes protein destruction by disturbing the enzymatic activity of deacetylases. It was US FDA approved in February 2015 for the management of relapsed/refractory MM in combination with bortezomib and dexamethasone. Several trials are ongoing, exploring the utility of panobinostat in various other settings for the management of MM. This review will detail the biology, clinical efficacy and potential future applications of panobinostat in the treatment of MM.

An 8.2 Gb/s-to-10.3 Gb/s full-rate referenceless CDR in 0.18 m CMOS is presented. By realizing an asymmetric phase detector transfer curve, the linear CDR's "single-sided" capture range increases, which allows the Hogge phase detector itself to function as a frequency detector, thus eliminating the need for the reference clock and the separate frequency detector in conventional dual-loop CDRs. Robust frequency and phase acquisition is demonstrated. Furthermore, a new phase adjustment mode is added to further improve the jitter tolerance performance. The measurement results show that with a 10.3 Gb/s 2 -1 PRBS input, the random jitter at the output data is 0.336 ps , and the out-ofband jitter tolerance is 0.34 UI -.Index Terms-Analog, clock-and-data recovery (CDR), CMOS, jitter tolerance, linear phase detector, receiver, referenceless, wideband data communication. 0018-9200

Comprehensive recommendations for maintenance therapy after autologous stem cell transplantation (ASCT) for patients with multiple myeloma (MM) have yet to be defined. Bortezomib has been utilized as maintenance therapy after ASCT, but data attesting to the safety and efficacy of this agent compared with lenalidomide in the post-ASCT setting are limited. Therefore, we retrospectively analyzed the outcomes of 102 patients with MM who received maintenance therapy with bortezomib after ASCT at Duke University's adult bone marrow transplant clinic between 2005 and 2015. Maintenance with bortezomib was initiated between 60 and 90 days after ASCT as a single agent 1.3 mg/m once every 2 weeks (n = 92) or in combination with lenalidomide (10 mg/day) (n = 10). The median age at ASCT was 64 (range, 31 to 78). Of the 99 patients with molecular data available, 42% had high-risk cytogenetics (including d17p, t(4;14), +1q, and t(14;16) by fluorescein in situ hybridization). Overall, 46% of patients experienced side effects from maintenance therapy, with 31% of all patients experiencing peripheral neuropathy. In total, 2% of patients required discontinuation of bortezomib maintenance because of adverse events. No secondary malignancies were reported from the therapy. The median progression-free survival (PFS) for patients receiving maintenance therapy with bortezomib after ASCT was 36.5 months (95% confidence interval [CI], 21.3 to not available) and median overall survival was 72.7 months (95% CI, 63.9 to not available). The PFS of patients with high-risk cytogenetics was not statistically significantly different from those with standard-risk cytogenetics, suggesting that maintenance with bortezomib may help overcome the impact of high-risk cytogenetics on early progression. These results indicate that maintenance therapy with bortezomib represents a safe, well-tolerated, and efficacious option for patients with high-risk cytogenetics, renal insufficiency, an inability to tolerate lenalidomide, or a previous history of another cancer.

An oscillator scheme based on the degenerate band edge (DBE) in a periodic, double-ladder resonant circuit made of lumped elements is proposed for the first time. The circuit exhibits a DBE in the dispersion diagram of its phase-frequency eigenstates and possesses unique resonance features associated with a high loaded Q-factor resonance, compared to a singleladder circuit. This oscillator is shown to have an oscillation threshold that is half that of a single LC ladder circuit having the same total quality factor, and thus is more robust than an LC oscillator in the presence of losses. Moreover, the double-ladder oscillators have a unique mode selection scheme that leads to stable single-frequency oscillations even when the load is varied. It is also shown that the output amplitude of the double-ladder oscillator is much less sensitive to the output loading compared to single-ladder oscillators. The authors show the analysis and design of such oscillators that potentially lead to enhancing the efficiency of RF components and sources.

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