Generating Fast Sparse Matrix Vector Multiplication From a High Level Generic Functional IR

Usage of high-level intermediate representations promises the generation of fast code from a high-level description, improving the productivity of developers while achieving the performance traditionally only reached with low-level programming approaches. High-level IRs come in two flavors: 1) domain-specific IRs designed only for a specific application area; or 2) generic high-level IRs that can be used to generate high-performance code across many domains. Developing generic IRs is more challenging but offers the advantage of reusing a common compiler infrastructure across various applications. In this paper, we extend a generic high-level IR to enable efficient computation with sparse data structures. Crucially, we encode sparse representation using reusable dense building blocks already present in the high-level IR. We use a form of dependent types to model sparse matrices in CSR format by expressing the relationship between multiple dense arrays explicitly separately storing the length of rows, the column indices, and the non-zero values of the matrix. We achieve high-performance compared to sparse low-level library code using our extended generic high-level code generator. On an Nvidia GPU, we outperform the highly tuned Nvidia cuSparse implementation of spmv multiplication across 28 sparse matrices of varying sparsity on average by 1.7×

Quality of life assessment in elderly patients with aggressive non-Hodgkin's Lymphoma treated with anthracycline-containing regimens. Report of a prospective study by the Intergruppo Italiano Linfomi

Background and Objectives. The aim of this study was to evaluate quality of life (QOL) in a group of elderly patients ( > 65 years) with aggressive non-Hodgkin's lymphoma (NHL) treated with chemotherapy regimens containing anthracyclines. Design and Methods. QOL was evaluated in a population of elderly patients with aggressive NHL enrolled in a phase III clinical trial run by the Intergruppo Italiano Linfomi (11L) from 1996 to 1999 to compare two different anthracycline-containing regimens (mini-CEOP vs P-VEBEC). The EORTC-QLQ-C30 questionnaire, which has already been validated in oncology, was used. The questionnaire was administered at the time of diagnosis, half way through the chemotherapy and at the time of restaging. Results. Ninety-one patients completed pre-therapy and post-therapy questionnaires and they are the subject of this report. Baseline QOL assessment showed a strong correlation of poor values of QOL with anemia and high risk according to the International Prognostic Index (IPI). At the end of treatment no functional scales showed worse values. A significant improvement was observed for pain (p = 0.003), appetite (p = 0.006), sleep (p = 0.015) and global health (p = 0.027). Considering only the 50 patients who achieved a complete remission (CR), an improvement was also recorded for emotional state (p = 0.10), role (P = 0.05), constipation (p = 0.04) and global QOL (p = 0.05). Interpretation and Conclusions. The EORTC-QLQ-C30 is feasible even in a population of elderly patients, in whom it had never been tested before. The improvement of QOL at the end of the treatment demonstrated that the symptoms of the disease have a greater negative influence on the patient's life than do the side effects of the therapy

The impact of the Hippo pathway and cell metabolism on pathological complete response in locally advanced Her2+ breast cancer: the TRISKELE multicenter prospective study

The Hippo pathway and its two key effectors, Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ), are consistently altered in breast cancer. Pivotal regulators of cell metabolism such as the AMP-activated protein kinase (AMPK), Stearoyl-CoA-desaturase 1 (SCD1), and HMG-CoA reductase (HMGCR) are relevant modulators of TAZ/YAP activity. In this prospective study, we measured the tumor expression of TAZ, YAP, AMPK, SCD1, and HMGCR by immunohistochemistry in 65 Her2+ breast cancer patients who underwent trastuzumab-based neoadjuvant treatment. The aim of the study was to assess the impact of the immunohistochemical expression of the Hippo pathway transducers and cell metabolism regulators on pathological complete response. Low expression of cytoplasmic TAZ, both alone and in the context of a composite signature identified by machine learning including also low nuclear levels of YAP and HMGCR and high cytoplasmic levels of SCD1, was a predictor of residual disease in the univariate logistic regression. This finding was not confirmed in the multivariate model including estrogen receptor > 70% and body mass index > 20. However, our findings were concordant with overall survival data from the TCGA cohort. Our results, possibly affected by the relatively small sample size of this study population, deserve further investigation in adequately sized, ad hoc prospective studies

Pathologic response and survival after neoadjuvant chemotherapy with or without pertuzumab in patients with HER2-positive breast cancer: the Neopearl nationwide collaborative study

PurposeClinical trials have shown a significant increase in pathologic complete response (pCR) with the addition of pertuzumab to neoadjuvant chemotherapy for patients with early-stage HER-2 positive breast cancer. To date, limited studies have examined comparative outcomes of neoadjuvant pertuzumab in real-world setting. The Neopearl study aimed to assess comparative real-life efficacy and safety of neoadjuvant pertuzumab for these patients.MethodsWe conducted a nationwide retrospective analysis involving 17 oncology facilities with a certified multidisciplinary breast cancer treatment committee. We identified patients with HER-2 positive stage II-III breast cancer treated with neoadjuvant chemotherapy based on trastuzumab and taxanes with or without pertuzumab. All patients underwent breast surgery and received a comprehensive cardiologic evaluation at baseline and after neoadjuvant treatment. Patients who received the combination of pertuzumab, trastuzumab, and chemotherapy constituted case cohort (PTCT), whereas those treated with trastuzumab and chemotherapy accounted for control cohort (TCT). The pCR rate and 5-year event free survival (EFS) were the primary outcomes. Secondary end-points were rates of conversion from planned modified radical mastectomy (MRM) to breast conservation surgery (BCS) and cardiotoxicities.ResultsFrom March 2014 to April 2021, we included 271 patients, 134 (49%) and 137 (51%) in TCT and PTCT cohort, respectively. Positive axillary lymph nodes and stage III were more frequent in PTCT cohort. The pCR rate was significantly increased in patients who received pertuzumab (49% vs 62%; OR 1.74, 95%CI 1.04-2.89) and with HER-2 enriched subtypes (16% vs 85%; OR 2.94, 95%CI 1.60-5.41). After a median follow-up of 5 years, the 5-year EFS was significantly prolonged only in patients treated with pertuzumab (81% vs 93%; HR 2.22, 95%CI 1.03-4.79). The same analysis performed on propensity score matched population showed concordant results. On univariate analysis, only patients with positive lymph nodes were found to benefit from pertuzumab for both pCR and 5-year EFS. The rates of conversion from MRM to BCS and cardiologic toxicities did not differ between the cohorts.ConclusionOur findings support previous data on improved outcomes with the addition of pertuzumab to trastuzumab-based neoadjuvant chemotherapy. This benefit seems to be more significant in patients with clinically positive lymph nodes

Sudden Unexpected Deaths and Vaccinations during the First Two Years of Life in Italy: A Case Series Study

Background The signal of an association between vaccination in the second year of life with a hexavalent vaccine and sudden unexpected deaths (SUD) in the two days following vaccination was reported in Germany in 2003. A study to establish whether the immunisation with hexavalent vaccines increased the short term risk of SUD in infants was conducted in Italy. Methodology/Principal Findings The reference population comprises around 3 million infants vaccinated in Italy in the study period 1999–2004 (1.5 million received hexavalent vaccines). Events of SUD in infants aged 1–23 months were identified through the death certificates. Vaccination history was retrieved from immunisation registries. Association between immunisation and death was assessed adopting a case series design focusing on the risk periods 0–1, 0–7, and 0–14 days after immunisation. Among the 604 infants who died of SUD, 244 (40%) had received at least one vaccination. Four deaths occurred within two days from vaccination with the hexavalent vaccines (RR = 1.5; 95% CI 0.6 to 4.2). The RRs for the risk periods 0–7 and 0–14 were 2.0 (95% CI 1.2 to 3.5) and 1.5 (95% CI 0.9 to 2.4). The increased risk was limited to the first dose (RR = 2.2; 95% CI 1.1 to 4.4), whereas no increase was observed for the second and third doses combined. Conclusions The RRs of SUD for any vaccines and any risk periods, even when greater than 1, were almost an order of magnitude lower than the estimates in Germany. The limited increase in RRs found in Italy appears confined to the first dose and may be partly explained by a residual uncontrolled confounding effect of age

A retrospective multicentric observational study of trastuzumab emtansine in HER2 positive metastatic breast cancer: A real-world experience

We addressed trastuzumab emtansine (T-DM1) efficacy in HER2+ metastatic breast cancer patients treated in real-world practice, and its activity in pertuzumab-pretreated patients. We conducted a retrospective, observational study involving 23 cancer centres, and 250 patients. Survival data were analyzed by Kaplan Meier curves and log rank test. Factors testing significant in univariate analysis were tested in multivariate models. Median follow-up was 15 months and median T-DM1 treatment-length 4 months. Response rate was 41.6%, clinical benefit 60.9%. Median progression-free and median overall survival were 6 and 20 months, respectively. Overall, no differences emerged by pertuzumab pretreatment, with median progression-free and median overall survival of 4 and 17 months in pertuzumab-pretreated (p=0.13), and 6 and 22 months in pertuzumab-na\uc3\uafve patients (p=0.27). Patients who received second-line T-DM1 had median progression-free and median overall survival of 3 and 12 months (p=0.0001) if pertuzumab-pretreated, and 8 and 26 months if pertuzumab-na\uc3\uafve (p=0.06). In contrast, in third-line and beyond, median progression-free and median overall survival were 16 and 18 months in pertuzumab-pretreated (p=0.05) and 6 and 17 months in pertuzumab-na\uc3\uafve patients (p=0.30). In multivariate analysis, lower ECOG performance status was associated with progression-free survival benefit (p < 0.0001), while overall survival was positively affected by lower ECOG PS (p < 0.0001), absence of brain metastases (p 0.05), and clinical benefit (p < 0.0001). Our results are comparable with those from randomized trials. Further studies are warranted to confirm and interpret our data on apparently lower T-DM1 efficacy when given as second-line treatment after pertuzumab, and on the optimal sequence order

Zero-cost abstractions for irregular data shapes in a high-performance parallel language

Modern parallel accelerators offer an unprecedented degree of performance, and are used pervasively in important application domains, such as High Performance Computing and Machine Learning. However, these accelerators are challenging to program. The primary option is using platform-specific low-level languages (eg. OpenCL, CUDA), but this requires a significant level of expertise to be used effectively. The other option is to rely on domain-specific libraries such as OpenBLAS and cuSparse. However, they cater to common use cases, and are sub-optimal for less popular architectures or applications. Data-Parallel Functional Languages such as Lift, Accelerate and Futhark facilitate the programming of parallel accelerators, offering a solution to these issues. They have extensive support for multi-dimensional array programming and excel in expressing parallel programs over regularly-shaped data structures. Raising the level of abstraction allows users to express the application more naturally, while the constrained nature of array operators enables the generation of high-performance code. However, many applications require irregularly shaped data, such as sparse or otherwise non-rectangular matrices. Expressing these structures in terms of dense multidimensional array is challenging. This thesis introduces the minimal number of constructs necessary to express such structures. Rather than add a completely new programming paradigm, it extends the array programming model, allowing for maximal composability and uniformity between the new and existing abstractions. The central language extension is the position-dependent arrays: heterogeneous multi-dimensional arrays whose element’s type is statically dependent on its position within the data structure. The construct is then progressively generalised, allowing the dependence to be not only static but also dynamic, enabling programs using sparse matrices. These abstractions are zero-cost, which is key to producing fast code. This is achieved by using dependent types to enforce complex invariants at compile time. As programs using sparse matrices often need a fast prefix-sum, the thesis also includes a novel implementation of work-efficient parallel scan for data-parallel languages. A comparison with state-of-the-art alternatives shows the effectiveness of these contributions. The compiler generates programs that are competitive or outright outperform those found in libraries such as OpenBlas, cuBlas and cuSparse. Examples include an average 1.2x speedup for sparse matrix-vector multiplication vs cuSparse’s implementation on a NVidia GTX 1070 GPU, and a 1.5x speedup for prefix sum vs a competitive handwritten implementation

L'Italie en vacance de l'Europe

Italy and Europe, by Federico Rampini Since the beginning of the Community, Italian leaders have relied on Europe as a way to impose a process of modernisation which otherwise would not have had sufficient national support. However for the first time, with the arrival of Silvio Berlusconi in 1994, the country has become divided over the European question. Supporters of Maastricht believe that Italy would pay dearly if excluded from the single currency. But an increasing number of people defend 'an alternative policy' and daim that by leaving EMS, Italy has been better able to defend its national interests. The vitality of the Italian economy contradicts the monetary dogmas of the Bundesbank; but the Germanisation of Europe has some drawbacks for those who stay outside. This is why it is necessary for Italy to participate fully in the European debate in order to try and influence the priorities of the EU toward growth and employment.Depuis la naissance de la Communauté, les dirigeants italiens ont choisi l'Europe pour imposer un processus de modernisation qui, autrement, n'aurait pas pu s'appuyer sur un consensus national suffisant. Or, pour la première fois, avec l'arrivée au pouvoir de Silvio Berlusconi en 1994, le pays s'est divisé sur la question européenne. Les partisans de Maastricht considèrent que l'Italie paierait très cher son exclusion de la monnaie unique. Mais les défenseurs d'une « autre politique », de plus en plus nombreux, peuvent affirmer qu'avec la sortie de la lire du SME, l'Italie a fini par mieux défendre ses intérêts nationaux. La vitalité de l'économie italienne contredit les dogmes monétaristes de la Bundesbank ; mais la germanisation de l'Europe présente des inconvénients pour ceux qui restent à l'écart. D'où la nécessité pour Rome de rentrer dans le jeu européen pour essayer d'infléchir les priorités de l'UE afin de privilégier la croissance et l'emploi.Rampini, Pizzuti Sylvie. L'Italie en vacance de l'Europe. In: Politique étrangère, n°1 - 1996 - 61ᵉannée. pp. 61-72