This paper presents an ultra-low power circuit design methodology which combines the Multi-Threshold CMOS (MTCMOS) technique with quasi delay-insensitive (QDI) asynchronous logic, in order to solve the three major problems of synchronous MTCMOS circuits: (1) Sleep signal generation, (2) storage element data loss during sleep mode, and (3) sleep transistor sizing. In contrast to most power reduction methods that result in area overhead, the QDI asynchronous MTCMOS circuits are usually smaller than their original versions. Moreover, QDI circuits utilize handshaking protocols instead of clocks for circuit control, resulting in flexible timing requirements, which yields increased circuit robustness and allows for extreme supply voltage scaling to subthreshold region for further power reduction, without requiring any circuit modifications. This QDI asynchronous MTC-MOS methodology is used to design a 4-stage pipelined 8-bit × 8-bit unsigned multiplier, which is then compared against the original QDI design (i.e., without incorporating MTCMOS) and its synchronous version. All designs use the IBM 8RF-DM 0.13 m process. Results show 150× and 1.8× leakage power and active energy reductions on average in the QDI asynchronous MTCMOS design compared to the original QDI version, respectively.
e15021 Background: Regorafenib is a multi-kinase inhibitor that was FDA approved for the treatment of refractory advanced colorectal cancer. It has been found in the clinical trials to have modest benefit and relatively high toxicity, but the outcome of its routine use in the clinic practice is lacking. Our aim is to assess the outcome in our local clinic practice. Methods: Records of all colorectal cases who were treated with regorafenib were reviewed. Structured CRF was developed. Clinical, pathological and molecular data were collected. Efficacy and toxicity details were analyzed. Results: Thirty-two cases of metastatic colorectal cancer were treated with regorafenib from February 2014 to February 2016. All patients received prior oxaliplatin, irinotecan and bevacizumab based regimens, and cetuximab if wild type. Median age: 53.5 years. Male: 15 (46.9%). Primary tumor was right sided in 10 patients (31.3%), and left sided (including rectum) in 22 (68.7%). Pan RAS mutant: 21 (65.6%). Fifteen patients (46.9 %) had ECOG Performance Status of one, whereas 16 patients (50%) have ECOG 2. Starting dose was reduced to 120mg in 11 (34.4%). Only 5 (15.6%) continued beyond 3 cycles. 18 patients (56.3%) required dose reduction. Overall response: PR/CR: zero; Stable disease: 4 (12.5%); Progressive disease: 25 (78.1%); Clinical progression in 1 (3.1%), and 2 cases were not evaluated. After median follow up of 7 months, 22 patients (68.8%) have died, 5 (15.6%) are still alive and 5 (15.6%) are lost to follow up. Median survival: 9.3 months, and median PFS: 2.5 months. Conclusions: Regorafenib has poor tumor response in the routine clinic practice when given to patients with ECOG PS > 1. The median survival in this series is probably overestimated because of the relatively high rate of loss to follow up. Selection of patients is required in the routine clinic practice. Predictive markers are more important for such treatment with modest benefit, and significant toxicity and cost.
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