The increased performance requirements of applications running on safety-critical systems have led to the use of complex platforms with several CPUs, GPUs, and AI accelerators. However, higher platform and system complexity challenge performance verification and validation since timing interference across tasks occurs in unobvious ways, hence defeating attempts to optimize application consolidation informedly during design phases and validating that mutual interference across tasks is within bounds during test phases.In that respect, the SafeSU has been proposed to extend inter-task interference monitoring capabilities in simple systems. However, modern mixed-criticality systems are complex, with multilayered interconnects, shared caches, and hardware accelerators. To that end, this paper proposes a non-intrusive add-on approach for monitoring interference across tasks in multilayer heterogeneous systems implemented by leveraging existing security frameworks and the SafeSU infrastructure.The feasibility of the proposed approach has been validated in an RTL RISC-V-based multicore SoC with support for AI hardware acceleration. Our results show that our approach can safely track contention and properly break down contention cycles across the different sources of interference, hence guiding optimization and validation processes.

Increasing the performance of safety-critical systems via introducing multicore processors is becoming the norm. However, when multiple cores access a shared cache, inter-core evictions become a relevant source of interference that must be appropriately controlled. To solve this issue, one can statically partition caches and remove the interference. Unfortunately, this comes at the expense of less flexibility and, in some cases, worse performance. In this context, enabling more flexible cache allocation policies requires additional monitoring support. This paper proposes HashTAG, a novel approach to accurately upperbound inter-core eviction interference. HashTAG enables a low-overhead implementation of an Auxiliary Tag Directory to determine inter-core evictions. Our results show that no inter-task interference underprediction is possible with HashTAG while providing a 44% reduction in ATD area with only 1.14% median overprediction

With the continued success of the open RISC-V architecture, practical deployment of RISC-V processors necessitates an in-depth consideration of their testability, safety and security aspects. This survey provides an overview of recent developments in this quickly-evolving field. We start with discussing the application of state-of-the-art functional and system-level test solutions to RISC-V processors. Then, we discuss the use of RISC-V processors for safety-related applications; to this end, we outline the essential techniques necessary to obtain safety both in the functional and in the timing domain and review recent processor designs with safety features. Finally, we survey the different aspects of security with respect to RISC-V implementations and discuss the relationship between cryptographic protocols and primitives on the one hand and the RISC-V processor architecture and hardware implementation on the other. We also comment on the role of a RISC-V processor for system security and its resilience against side-channel attacks.

Background Radiological complete response (CR-MRI) to neoadjuvant chemotherapy (NAC) by MRI predicts pathologic complete response (pCR) rates in pts with TNBC treated preoperatively with A/TX-based regimens and in some studies, it correlates with disease-free survival (DFS). The main aim of this study was to assess the relevance of the MRI response to primary chemotherapy associated with clinical stage and HER2 expression (Zero vs Low), in a cohort of 143 TNBC pts treated with A and TX +/- carboplatin (CP) in the NAC setting. Methods Retrospective study of pts treated with NAC for TNBC between January 2002 and June 2021, who underwent MRI to assess tumour response before NAC, after 4 cycles of anthracycline and cyclophosphamide (AC) and after TX. Survival analysis was based on the Kaplan-Meier and survival curves were compared using the log-rank test. A p value of less than 0.05 was considered as statistically significant. Results A total of 143 TNBC pts with a median age of 52 years; 7, 63 and 73 pts had stage I, II and III disease, respectively. The NAC regimen consisted in 117 pts 4 cycles of AC followed by TX and in 24 pts the same adding CP (in 21 pts with non-CR-MRI, 2 with CR-MRI and 1 without MRI after AC). PCR was observed in 41%. Of 30 pts with CR-MRI after AC, 83% obtain a pCR (p< 0.001), and of 52 pts with CR-MRI at the end of NAC, 70.7% obtain a pCR (p< 0,001) of which 90% had a CR-MRI after AC. Adding CP increased pCR by 6% (p=0.564). According HER2-zero vs low expression, the pCR was 38% and 47% respectively, with no significant differences. With a median follow-up of 60 months, 34% recurred and 16% died of TNBC. In pts with pCR, the DFS at 5 years (y) was 96% and 47% for pts without pCR (p< 0.001), with a DFS of 91% if CR-MRI at the end of NAC and 48% if non-CR-MRI (p< 0.001). In HER2-Zero tumours the DFS at 5 y was 64% vs 66% in HER-2 low. Interestingly, overall survival (OS) at 5 y was 72% in HER2-Zero and 84% in HER2-low (p=0.080). Conclusions Performing serial MRI in the course of NAC in TNBC may be a reliable indicator of pCR, adding platinum to TX in pts with CR-MRI may increase pCR rate. HER2-Zero expression in TNBC, seems to confer worse OS rates. Citation Format: Marina Sierra Boada, Luis Antonio Fernandez, Elsa Dalmau, Gemma Llort, Maria Marin, Pablo Andreu, Natalia Lopez, Carla Climent, Marta Rodriguez, Sandra Soriano, Miquel Angel Segui. Magnetic resonance imaging (MRI) and clinicopathological analysis of triple-negative breast cancer (TNBC) patients (pts) treated with primary anthracyclines(A)/taxanes(TX)-based chemotherapy. [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P4-07-40.

The category of non-clear cell renal cell carcinoma (nccRCC) includes several clinically, histologically, and molecularly diverse entities. Traditionally, they comprise type 1 and type 2 papillary, chromophobe, unclassified, and other histologies (medullary, collecting duct carcinoma, and translocation-associated). Molecular knowledge has allowed the identification of some other specific subtypes, such as fumarate hydratase-deficient renal cell carcinoma (RCC) or succinate dehydrogenase-associated RCC. In addition, it has recognized some alterations with a possible predictive role, e.g., MET proto-oncogene receptor tyrosine kinase (MET) alterations in papillary tumors. Standard therapies for the management of advanced clear cell RCC (ccRCC), i.e., vascular endothelial growth factor receptor (VEGFR) pathway inhibitors and mammalian target of rapamycin inhibitors, have shown poorer results in nccRCC patients. Therefore, there is a need to improve the efficacy of the treatment for advanced nccRCC. Immunotherapy, especially immune checkpoint inhibitors (ICIs) targeting programmed death 1/programmed death ligand 1 and cytotoxic T-lymphocyte associated protein 4 (CTLA-4), has demonstrated a significant survival benefit in several malignant neoplasias, including ccRCC, with a proportion of patients achieving long survival. The combinations of ICI or ICI + VEGFR tyrosine kinase inhibitors (TKIs) are the standard of care in advanced ccRCC. Unfortunately, major pivotal trials did not include specific nccRCC populations. In recent years, several studies have retrospectively or prospectively evaluated ICIs alone or in combination with another ICI or with TKIs in nccRCC patients. In this article, we review data from available trials in order to elucidate clinical and molecular profiles that could benefit from immunotherapy approaches.

This paper presents the end-to-end QoS approach to provide performance guarantees followed in the SELENE platform, a high-performance RISC-V based heterogeneous SoC for safety-related real-time systems. Our QoS approach includes smart interconnect solutions for buses and NoCs, along with multicore interference-aware statistics units to, cooperatively, achieve end-to-end QoS.

The goal of the H2020 SELENE project is the development of a flexible computing platform for autonomous applications that includes built-in hardware support for safety. The SELENE computing platform is an open-source RISC-V heterogeneous multicore system-on-chip (SoC) that includes 6 NOEL-V RISC-V cores and artificial intelligence accelerators. In this paper, we describe the approach followed in the SELENE project to accelerate neural network inference processes. Our intermediate results show that both the FPGA and ASIC accelerators provide real-time inference performance for the analyzed network models at a reasonable implementation cost.

e24020 Background: Elderly patients (pts) diagnosed with cancer may present frailty conditions at baseline that could have a direct impact on tolerance and toxicity of oncological treatments (ttm). Comprehensive geriatric assessment (CGA) is considered a useful tool in the approach of these pts. CGA allows assessing functional reserve and potentially treatable comorbidities, leading to pt classification into 3 categories (fit, medium fit, unfit) before ttm decision. We evaluated the implantation of a CGA program in our center and its impact on ttm-decision and ttm-related toxicities. Furthermore, we evaluated survival outcomes. Methods: Retrospective, observational, single-institution analysis between 2017-2020. Pts ≥70 years with a cancer diagnosis and suspected frailty were evaluated by Oncogeriatry division before ttm decision. Pt characteristics at baseline (functional status [st], cognitive st, nutritional st, and comorbidity) were recorded. IBM SPSS Statistics software was used for statistical analysis. Variance analysis was calculated with Kolmogorov-Smirnov. Survival was calculated with Kaplan-Meier. Results: 147 pts were included (median [m] age 83 years). Referred pts presented good functional st (mBarthel Index 95), cognitive st (mMMSE 28, mMiniCog 3), and nutritional st (m abbreviated MNA13), and low comorbidity (mCharlson Index 1). After CGA, 49% pts were classified as fit, 28.6% as medium fit, and 22.4% as unfit. 71.4% pts received cancer-specific ttm (fit 91.6%, medium-fit 78.5%, unfit 18%). The correlation index between the initial ttm proposal and final ttm performed after CGA was 56.4% (76% in fit, 57.1% in medium-fit, and 12% in unfit). 18.4% of pts had ttm-related complications. 74 pts died during follow-up (34.7% fit, 59.5% medium fit, 72.7% unfit). 35.4% of deaths were related to cancer and 10.9% to comorbidity. Only 4 deaths were related to ttm. The median survival was 29 months (mo) in fit, 12.8 mo in medium-fit, and 8.5 mo in unfit pts. Conclusions: The majority of pts had preserved cognitive functions and low comorbidity, and were independent for daily-life activities. After CGA, almost 50% pts had modifications in their initial treatment strategy (higher rates in medium fit and unfit). Most fit pts received standard oncospecific ttm and had higher survival rates compared to unfit pts. These results show the relevance of geriatric approach in elderly cancer pts, which allows a personalized ttm.

Staggered Redundant execution (SRE) is a fault-tolerance mechanism that has been widely deployed in the context of safety-critical applications. SRE not only protects the system in the presence of faults but also helps relaxing safety requirements of individual elements. However, in this paper, we show that SRE does not effectively protect the system against a wide range of faults and thus, new mechanisms to increase the diversity of homogeneous cores are needed. In this paper, we propose Register File Randomization (RFR), a low-cost diversity mechanism that significantly increases the robustness of homogeneous multicores in front of common-cause faults (CCFs) and register file wearout. Our results show that RFR completely removes the failure rate for register file CCFs for certain workloads and reduces by a factor of 5X the impact of stress related register file aging for the workloads analysed. Our implementation requires less than 50 RTL lines of code and the area (FPGA logic) overhead of RFR is less than 0.2% of a 64-bit RISC-V core FPGA implementation.