Flexible Timing Simulation of Multiple-Cache Configurations

Abstract As the gap between processor and memory speeds increases, cache performance becomes more critical to overall system performance. Behavioral cache simulation is typically used early in the design cycle of new processor/cache configurations to determine the performance of proposed cache configurations on target workloads. However, behavioral cache simulation does not account for the latency seen by each memory access. The Latency-Effects (LE) cache model presented in this paper accounts this nominal latency as well as the additional latencies due to trailing-edge effects, bus width considerations, port conflicts, and the number of outstanding accesses that a cache allows before it blocks. We also extend the LE cache model to handle the latency effects of moving data among multiple caches. mlcache, a new, easily configurable and extensible tool, has been built based on the extended LE model. We show the use of mlcache in estimating the performance of traditional and novel cache configurations, including odd/even, 2-level, Assist, Victim, and NTS caches. We also show how the LE cache timing model provides more useful, realistic performance estimates than other possible behavioral-level cache timing models. Keywords: cache timing simulation model evaluation Introduction Cache performance becomes ever more critical to overall system performance as the gap between processor and memory speed increases. The performance of a particular cache configuration depends not only on the miss ratio incurred during the execution of a particular workload but also on where in the program's execution the misses occur and the latency of each miss. However, useful timing simulation of caches is typically unavailable until late in the design stage. Using today's behavioral simulators, simple, traditional caches are evaluated early in the design cycle; however, novel cache designs are often not considered since they are difficult to model. The issue of providing more useful cache timing simulation analysis early in the design cycle has been addressed by the Latency-Effects (LE) cache model [Tam96], which incorporates latency-adding effects into a behavioral-level simulation, particularly trailing-edge effects, bus width considerations, the effects of port conflicts, and the number of outstanding accesses that a cache can handle before blocking. Existing methods of modifying behavioral cache simulators to incorporate timing effects include adjusting the total cycle count reported by a perfect cache simulation by adding an estimated number of cycles due to cache misses (the adjusted model) or assigning a nominal leading-edge penalty to each miss as it occurs (a model we will refer to as LEnominal). To illustrate the advantages of the LE cache model, we will compare the LE cache model's results to the results of using these other models. 1. This research was funded in part by a gift from IBM

The Role of Palliative Surgery for Malignant Bowel Obstruction and Perforation in Advanced Microsatellite Instability-High Colorectal Carcinoma in the Era of Immunotherapy: Case Report.

The role of palliative surgery in the management of acute complications in patients with disseminated malignancy remains controversial given the complexity of assessing acute surgical risk and long-term oncologic outcome. With the emergence of checkpoint blockade immunotherapy, there appears to be an increasing role for historically palliative procedures as a bridge to systemic immunotherapy. This is especially evident in advanced microsatellite instability-high (MSI-H) colorectal cancer where malignant obstruction and fistula formation are more common and where immunotherapy with checkpoint blockade (anti-PD-1/PD-L1, anti-CTLA-4) has a high response rate with potential for favorable oncologic outcomes. We present a series of three patients with MSI-H metastatic colorectal cancer complicated by malignant bowel obstruction and fistula formation, who having progressed on standard chemotherapy, underwent palliative intervention as a bridge to immune checkpoint blockade with durable and clinically meaningful anti-cancer responses. These cases highlight the need to re-evaluate the role of historically palliative operations in the setting of disease progression for immunotherapy-responsive tumors

Directly observed antiretroviral therapy: a systematic review and meta-analysis of randomised clinical trials.

BACKGROUND: Directly observed therapy has been recommended to improve adherence for patients with HIV infection who are on highly active antiretroviral therapy, but the benefit and cost-effectiveness of this approach has not been established conclusively. We did a systematic review and meta-analysis of randomised trials of directly observed versus self-administered antiretroviral treatment. METHODS: We did duplicate searches of databases (from inception to July 27, 2009), searchable websites of major HIV conferences (up to July, 2009), and lay publications and websites (March-July, 2009) to identify randomised trials assessing directly observed therapy to promote adherence to antiretroviral therapy in adults. Our primary outcome was virological suppression at study completion. We calculated relative risks (95% CIs), and pooled estimates using a random-effects method. FINDINGS: 12 studies met our inclusion criteria; four of these were done in groups that were judged to be at high risk of poor adherence (drug users and homeless people). Ten studies reported on the primary outcome (n=1862 participants); we calculated a pooled relative risk of 1.04 (95% CI 0.91-1.20, p=0.55), and noted moderate heterogeneity between the studies (I(2)= 53.8%, 95% CI 0-75.7, p=0.0247) for directly observed versus self-administered treatment. INTERPRETATION: Directly observed antiretroviral therapy seems to offer no benefit over self-administered treatment, which calls into question the use of such an approach to support adherence in the general patient population. FUNDING: None

Association Between Raised Blood Pressure and Dysglycemia in Hong Kong Chinese

OBJECTIVE—To investigate the association between raised blood pressure and dysglycemia

The relationship of self-efficacy to catastrophizing and depressive symptoms in community-dwelling older adults with chronic pain: A moderated mediation model

Self-efficacy has been consistently found to be a protective factor against psychological distress and disorders in the literature. However, little research is done on the moderating effect of self-efficacy on depressive symptoms in the context of chronic pain. This cross-sectional study aimed to examine if pain self-efficacy attenuated the direct relationship between pain intensity and depressive symptoms, as well as their indirect relationship through reducing the extent of catastrophizing when feeling pain (moderated mediation). 664 community-dwelling Chinese older adults aged 60–95 years who reported chronic pain for at least three months were recruited from social centers. They completed a battery of questionnaires on chronic pain, pain self-efficacy, catastrophizing, and depressive symptoms in individual face-to-face interviews. Controlling for age, gender, education, self-rated health, number of chronic diseases, pain disability, and pain self-efficacy, pain catastrophizing was found to partially mediate the connection between pain intensity and depressive symptoms. Furthermore, the relationship between pain intensity and depressive symptoms was moderated by pain self-efficacy. Self-efficacy was also found to moderate the relationship between pain intensity and catastrophizing and the moderated mediation effect was confirmed using bootstrap analysis. The results suggested that with increasing levels of self-efficacy, pain intensity’s direct effect on depressive symptoms and its indirect effect on depressive symptoms via catastrophizing were both reduced in a dose-dependent manner. Our findings suggest that pain self-efficacy is a significant protective factor that contributes to psychological resilience in chronic pain patients by attenuating the relationship of pain intensity to both catastrophizing and depressive symptoms

Structure of CD20 in complex with the therapeutic monoclonal antibody rituximab.

Cluster of differentiation 20 (CD20) is a B cell membrane protein that is targeted by monoclonal antibodies for the treatment of malignancies and autoimmune disorders but whose structure and function are unknown. Rituximab (RTX) has been in clinical use for two decades, but how it activates complement to kill B cells remains poorly understood. We obtained a structure of CD20 in complex with RTX, revealing CD20 as a compact double-barrel dimer bound by two RTX antigen-binding fragments (Fabs), each of which engages a composite epitope and an extensive homotypic Fab:Fab interface. Our data suggest that RTX cross-links CD20 into circular assemblies and lead to a structural model for complement recruitment. Our results further highlight the potential relevance of homotypic Fab:Fab interactions in targeting oligomeric cell-surface markers