Browsing by Subject "optimization"
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Item Open Access Are we improving in the optimization of surgery for high-risk adult cervical spine deformity patients over time?(Journal of neurosurgery. Spine, 2023-07) Passias, Peter G; Tretiakov, Peter S; Smith, Justin S; Lafage, Renaud; Diebo, Bassel; Scheer, Justin K; Eastlack, Robert K; Daniels, Alan H; Klineberg, Eric O; Khabeish, Khaled M; Mundis, Gregory M; Turner, Jay D; Gupta, Munish C; Kim, Han Jo; Schwab, Frank; Bess, Shay; Lafage, Virginie; Ames, Christopher P; Shaffrey, Christopher IObjective
The aim of this study was to investigate whether surgery for high-risk patients is being optimized over time and if poor outcomes are being minimized.Methods
Patients who underwent surgery for cervical deformity (CD) and were ≥ 18 years with baseline and 2-year data were stratified by year of surgery from 2013 to 2018. The cohort was divided into two groups based on when the surgery was performed. Patients in the early cohort underwent surgery between 2013 and 2015 and those in the recent cohort underwent surgery between 2016 and 2018. High-risk patients met at least 2 of the following criteria: 1) baseline C2-7 Cobb angle > 15°, mismatch between T1 slope and cervical lordosis ≥ 35°, C2-7 sagittal vertical axis > 4 cm, or chin-brow vertical angle > 25°; 2) age ≥ 70 years; 3) severe baseline frailty (Miller index); 4) Charlson Comorbidity Index (CCI) ≥ 1 SD above the mean; 5) three-column osteotomy as treatment; and 6) fusion > 10 levels or > 7 levels for elderly patients. The mean comparison analysis assessed differences between groups. Stepwise multivariable linear regression described associations between increasing year of surgery and complications.Results
Eighty-two CD patients met high-risk criteria (mean age 62.11 ± 10.87 years, 63.7% female, mean BMI 29.70 ± 8.16 kg/m2, and mean CCI 1.07 ± 1.45). The proportion of high-risk patients increased with time, with 41.8% of patients in the early cohort classified as high risk compared with 47.6% of patients in the recent cohort (p > 0.05). Recent high-risk patients were more likely to be female (p = 0.008), have a lower BMI (p = 0.038), and have a higher baseline CCI (p = 0.013). Surgically, high-risk patients in the recent cohort were more likely to undergo low-grade osteotomy (p = 0.003). By postoperative complications, recent high-risk patients were less likely to experience any postoperative adverse events overall (p = 0.020) or complications such as dysphagia (p = 0.045) at 2 years. Regression analysis revealed increasing year of surgery to be correlated with decreasing minor complication rates (p = 0.030), as well as lowered rates of distal junctional kyphosis by 2 years (p = 0.048).Conclusions
Over time, high-risk CD patients have an increase in frequency and comorbidity rates but have demonstrated improved postoperative outcomes. These findings suggest that spine surgeons have improved over time in optimizing selection and reducing potential adverse events in high-risk patients.Item Open Access Cyclic Sulfones as Novel P3-Caps for Hepatitis C Virus NS3/4A (HCV NS3/4A) Protease Inhibitors: Synthesis and Evaluation of Inhibitors with Improved Potency and Pharmacokinetic Profiles(2010) Velázquez, Francisco; Sannigrahi, Mousumi; Bennett, Frank; Lovey, Raymond G; Arasappan, Ashok; Bogen, Stéphane; Nair, Latha; Venkatraman, Srikanth; Blackman, Melissa; Hendrata, Siska; Huang, Yuhua; Huelgas, Regina; Pinto, Patrick; Cheng, Kuo-Chi; Tong, Xiao; McPhail, Andrew T; Njoroge, F GeorgeHCV infection affects more than 170 million people worldwide and many of those patients will reach the end stage complications of the disease which include hepatocarcinoma and liver failure. The success rate for treatment of patients infected with genotype-1 is about 40%. Therefore, novel treatments are needed to combat the infection. The HCV NS3 protease inhibitor Boceprevir (1) was reported by our research group and efforts continue for the discovery of more potent compounds with improved pharmacokinetic profiles. A new series of HCV NS3 protease inhibitors having a cyclic sulfone P3-cap have been discovered. Compounds 43 and 44 showed K-i* values in the single-digit nM range and their cellular potency was improved by 10-fold compared to 1. The pharmacokinetic profiles of 43 and 44 in rats and monkeys were also improved to achieve higher plasma levels after oral administration.Item Open Access Goal-Driven Beam Setting Optimization for Whole-Breast Radiation Therapy.(Technology in cancer research & treatment, 2019-01) Wang, Wentao; Sheng, Yang; Yoo, Sua; Blitzblau, Rachel C; Yin, Fang-Fang; Wu, Q JackiePURPOSE:To develop an automated optimization program to generate optimal beam settings for whole-breast radiation therapy driven by clinically oriented goals. MATERIALS AND METHODS:Forty patients were retrospectively included in this study. Each patient's planning images, contoured structures of planning target volumes, organs-at-risk, and breast wires were used to optimize for patient-specific-beam settings. Two beam geometries were available tangential beams only and tangential plus supraclavicular beams. Beam parameters included isocenter position, gantry, collimator, couch angles, and multileaf collimator shape. A geometry-based goal function was defined to determine such beam parameters to minimize out-of-field target volume and in-field ipsilateral lung volume. For each geometry, the weighting in the goal function was trained with 10 plans and tested on 10 additional plans. For each query patient, the optimal beam setting was searched for different gantry-isocenter pairs. Optimal fluence maps were generated by an in-house automatic fluence optimization program for target coverage and homogeneous dose distribution, and dose calculation was performed in Eclipse. Automatically generated plans were compared with manually generated plans for target coverage and lung and heart sparing. RESULTS:The program successfully produced a set of beam parameters for every patient. Beam optimization time ranged from 10 to 120 s. The automatic plans had overall comparable plan quality to manually generated plans. For all testing cases, the mean target V95% was 91.0% for the automatic plans and 88.5% for manually generated plans. The mean ipsilateral lung V20Gy was lower for the automatic plans (15.2% vs 17.9%). The heart mean dose, maximum dose of the body, and conformity index were all comparable. CONCLUSION:We developed an automated goal-driven beam setting optimization program for whole-breast radiation therapy. It provides clinically relevant solutions based on previous clinical practice as well as patient specific anatomy on a substantially faster time frame.Item Open Access Test-Delivery Optimization in Manycore SOCs(2013-03-18) Agrawal, M; Richter, M; Chakrabarty, KWe present two test-data delivery optimization algorithms for system on-chip (SOC) designs with hundreds of cores, where a network-on-chip (NOC) is used as the interconnection fabric. We first present an e ective algorithm based on a subsetsum formulation to solve the test-delivery problem in NOCs with arbitrary topology that use dedicated routing. We further propose an algorithm for the important class of NOCs with grid topology and XY routing. The proposed algorithm is the first to co-optimize the number of access points, access-point locations, pin distribution to access points, and assignment of cores to access points for optimal test resource utilization of such NOCs. Testtime minimization is modeled as an NOC partitioning problem and solved with dynamic programming in polynomial time. Both the proposed methods yield high-quality results and are scalable to large SOCs with many cores. We present results on synthetic grid topology NOC-based SOCs constructed using cores from the ITC’02 benchmark, and demonstrate the scalability of our approach for two SOCs of the future, one with nearly 1,000 cores and the other with 1,600 cores. Test scheduling under power constraints is also incorporated in the optimization framework.