A type-safe arbitrary precision arithmetic portability layer for HLS tools

International audienceRecent studies have shown that High-Level Synthesis (HLS) is an efficient way to design operators for floating-point arithmetic, or for emerging alternative formats such as posits. However, HLS tools support different supersets of different subsets of the C language-for example, support for arbitrary-sized bit vectors may be provided through vendor-specific data-type libraries such as ac_int, ap_int, or int1 to int64, while others only support the standard C integer types. This is a problem when carefully tuning an operator's internal data-path, as there is no portable HLS standard for arbitrary width integers, and vendor libraries may introduce implicit casts and extensions that can hide subtle bugs. Each vendor also offers varying support for important operator-building primitives, such as platform-optimized leading-zero count. To address such problems, this work introduces Hint (hardware integer), a header-only compatibility layer offering a consistent and comprehensive interface to signed and unsigned arbitrary-sized integers. To avoid bugs Hint is strongly typed, requiring exact matching of expression widths and types-this type-checking is performed statically using the C++ template system, and adds no overhead at synthesis time. The current implementation wraps ac_int and ap_int with no performance or resource overhead when synthesized on Xilinx or Intel FPGAs. It also offers a Boost::multiprecision backend for fast simulation. Hint is open-source and extensible, and aims to provide an optimized superset of existing library primitives. This work is evaluated with arithmetic operators useful when implementing floating-point and posit operators (shifter, leading zero counter, fused shifter+sticky) deployed using two mainstream HLS tools (Xilinx VivadoHLS, and IntelHLS). A complete posit adder operator has also been written using Hint, showing no overhead when compared to the original operator written for Xilinx FPGAs

Pretransplant renal function according to CKD-EPI cystatin C equation is a prognostic factor of death after liver transplantation

International audienceBackground & aims - In patients with cirrhosis, cystatin C (CystC) based equations may be more accurate indicators of glomerular filtration rate (GFR) than creatinine (Pcr) based equations. Renal function before liver transplantation (LT) is thought to impact survival after LT. We aimed at assessing pretransplant creatinine and CystC based equations with respect to their predictive value on long-term survival after LT. Methods - From 2001 to 2011, CystC was determined at pre-LT evaluation in 682 patients together with GFR assessed using MDRD-4, MDRD-6, CKD-EPI-cystatin C, CKD-EPI-creatinine and CKD-EPI-creatinine-cystatin C equations. Patients were classified according to the Kidney Disease Outcomes Quality Initiative classification (KDOQI). Results - Median age at LT was 55 [49-60] years with a median MELD score of 13.5 [8.3-19.2] and a median post-transplant follow-up of 60 [26-89] months. Using CKD-EPI Cystatin C and the KDOQI classification, 21.1% of patients were stage 1, 43.1% stage 2, 29.1% stage 3 and 6.5% stage 4. Kaplan-Meier survival estimates were significantly different between KDOQI stages when determined using the CKD-EPI-CystatinC equation. This was not the case when using the other equations. At multivariate analysis, GFR and KDOQI estimated using the CKD-EPI-CystatinC equation were significantly associated with death (HR: 0.992; CI95%: 0.986-0.999 and 1.24; CI95%: 1.02-1.50 respectively). When assessed using the MDRD-4, MDRD-6, CKD-EPI-Creatinine-CystatinC and CKD-EPI-Creatinine equations GFR was not significantly associated with death. Conclusions - Estimated pre-LT renal function is predictive of post-LT survival only when assessed using the CKD-EPI cystatin C equation. This supports the use of Cystatine C and of its related equation for the assessment of renal function before liver transplantation

Influence of cirrhosis on outcomes of patients with advanced intrahepatic cholangiocarcinoma receiving chemotherapy

International audienceBackground: Cirrhosis is a risk factor for intrahepatic cholangiocarcinoma (iCC). However, its exact prevalence is uncertain and its impact on the management of advanced disease is not established.Methods: Retrospective analysis of patients treated with systemic chemotherapy for advanced iCC in the 1st-line setting at 2 tertiary cancer referral centres. Cirrhosis was diagnosed based on at least one element prior to any treatment: pathological diagnosis, baseline platelets <150 × 109/L, portal hypertension and/or dysmorphic liver on imaging.Results: In the cohort of patients (n = 287), 82 (28.6%) had cirrhosis (45 based on pathological diagnosis). Patients with cirrhosis experienced more grade 3/4 haematologic toxicity (44% vs 22%, respectively, P = 0.001), and more grade 3/4 non-haematologic toxicity (34% vs 14%, respectively, P = 0.001) than those without. The overall survival (OS) was significantly shorter in patients with cirrhosis: median 9.1 vs 13.1 months for those without (HR = 1.56 [95% CI: 1.19-2.05]); P = 0.002), confirmed on multivariable analysis (HR = 1.48 [95% CI: 1.04-2.60]; P = 0.028).Conclusion: Cirrhosis was relatively common in patients with advanced iCC and was associated with increased chemotherapy-induced toxicity and shorter OS. Formal assessment and consideration of cirrhosis in therapeutic management is recommended

Determination of the 3D failure envelope of a composite based on a modified Arcan test device

International audienceThis paper describes a 3D failure criterion identified through Arcan tests, to analyze the behavior of a laminate composite subjected to out-of-plane loadings. The proposed criterion is based on the Hashin’s hypothesis and the interactions between tensile and shear out-of-plane loadings are taken into account. The out-of-plane stresses generated in the composite subjected to an Arcan test are studied using 3D Finite Element calculations in order to determine the stack sequence influence. Using different angles of the loading and different stacking sequences allows the ply to be subjected to complex 3D stress state. Using the experimental results and an inverse identification procedure, it is possible to identify the out-of-plane failure envelope. It is shown that a quadratic failure envelope, which takes into account a decrease of the apparent shear strength in the presence of out-of-plane tensile stress, permits the model to describe in a correct manner the experimental results

Maturation by LctT Is Required for Biosynthesis of Full-Length Lantibiotic Lacticin 481

In lantibiotic lacticin 481 biosynthesis, LctT cleaves the precursor peptide and exports mature lantibiotic. Matrix-assisted laser desorption ionization-time of flight mass spectrometry revealed that a truncated form of lacticin 481 is produced in the absence of LctT or after cleavage site inactivation. Production of truncated lacticin 481 is 4-fold less efficient, and its specific activity is about 10-fold lower

Lymphocytes and Neutrophil-to-Lymphocyte Ratio Variations After Selective Internal Radiation Treatment for HCC: A Retrospective Cohort Study

International audiencePurpose Selective internal radiation therapy (SIRT) has been proposed for combination with immunotherapy to treat hepatocellular carcinoma (HCC). However, the toxicity of radiation toward lymphocytes is understudied after SIRT. The aim of this study was to describe variations of lymphocytes following SIRT and their potential prognostic impact.Materials and Methods This is a retrospective cohort study of 164 patients treated with SIRT for HCC. Lymphocyte count and neutrophil-to-lymphocyte (NLR) ratio were evaluated at baseline and at 3 months. Primary endpoint was overall survival (OS).Results Median baseline lymphocyte count was 1.32 Giga/Liter (G/L) (standard deviation (SD) 0.64) at baseline versus 0.68 G/L (SD 0.41) at 3 months. The mean decrease of lymphocyte count was - 44% (standard deviation 0.24). At 3 months, only 21% of patients had normal (1 G/L or more) lymphocyte count, and 23% had lymphocyte count < 0.5 G/L. NLR at 3 months was significantly and independently associated with OS in multivariate Cox model. Median OS was 9.9 months (95% confidence interval (CI) 6.2-13.5) for patients with NLR at 3 months higher than 7.2 compared to 19.9 months in patients with an NLR lower that the 7.2 threshold (95% CI 16.3-23.3) (p = 0.003).Conclusions The decrease in lymphocytes was frequent and deep after SIRT for HCC. NLR increase at 3 months was associated with poor survival

Yttrium-90 glass microspheres radioembolization (RE) for biliary tract cancer a large single-center experience

International audiencePurpose - Radioembolization (RE) is a promising treatment option for biliary tract cancers (BTC). We report here the largest series to date using this treatment modality. Methods - We retrospectively studied data from 64 patients treated outside prospective clinical trial at our institution. We studied baseline characteristics as potential prognostic factors. We studied dose delivered to the tumor as predictive factors of outcomes in patients not receiving concomitant chemotherapy. Results - The Progression-Free Survival and Overall Survival (OS) were 7.6 months [95% Confidence Interval (CI): 4.6-10.6] and 16.4 months [95% CI: 7.8-25.0] in the whole cohort. The factors independently associated with OS in multivariable analysis were the primary localization of ICC (HR = 0.27, 95% CI: 0.11-0.68, p = 0.005) and a PS > 0 (HR = 2.21, 95% CI: 1.11-4.38, p = 0.024). During follow-up, 12 patients (19%) underwent surgery following downstaging, with a median OS of 51.9 months. In patients not treated with concomitant chemotherapy (n = 31), OS was significantly higher in patients with a dose delivered to the tumor 260Gy or higher than in patients with a dose delivered to the tumor lower than 260Gy (median 28.2 vs 11.4 months, log-rank p = 0.019). Conclusion - Our results confirm that RE is a promising treatment modality in BTC. A high proportion of patients could be downstaged to surgery, with promising long-term survival. Dose delivered to the tumor correlated with clinical outcomes when chemotherapy was not used concomitantly