apeNEXT: A multi-TFlops Computer for Simulations in Lattice Gauge Theory

We present the APE (Array Processor Experiment) project for the development of dedicated parallel computers for numerical simulations in lattice gauge theories. While APEmille is a production machine in today's physics simulations at various sites in Europe, a new machine, apeNEXT, is currently being developed to provide multi-Tflops computing performance. Like previous APE machines, the new supercomputer is largely custom designed and specifically optimized for simulations of Lattice QCD.Comment: Poster at the XXIII Physics in Collisions Conference (PIC03), Zeuthen, Germany, June 2003, 3 pages, Latex. PSN FRAP15. Replaced for adding forgotten autho

Cool core remnants in galaxy clusters

X ray clusters are conventionally divided into two classes: "cool core" (CC) and "non cool core" (NCC) objects, on the basis of the observational properties of their central regions. Recent results have shown that the cluster population is bimodal (Cavagnolo et al. 2009). We want to understand whether the observed distribution of clusters is due to a primordial division into two distinct classes rather than to differences in how these systems evolve across cosmic time. We systematically search the ICM of NCC clusters in a subsample of the B55 flux limited sample of clusters for regions which have some characteristics typical of cool cores, namely low entropy gas and high metal abundance We find that most NCC clusters in our sample host regions reminiscent of CC, i. e. characterized by relative low entropy gas (albeit not as low as in CC systems) and a metal abundance excess. We have dubbed these structures "cool core remnants", since we interpret them as what remains of a cool core after a heating event (AGN giant outbursts in a few cases and more commonly mergers). We infer that most NCC clusters have undergone a cool core phase during their life. The fact that most cool core remnants are found in dynamically active objects provides strong support to scenarios where cluster core properties are not fixed "ab initio" but evolve across cosmic time.Comment: Accepted for publication in Astronomy & Astrophysics. Version with full resolution figures available at: http://www.iasf-milano.inaf.it/~rossetti/public/CCR/rossetti.pd

Impact of resistance mutations on virological efficacy of DTG-based maintenance two-drug regimens: an ARCA cohort study

Background: Two-drug regimens (2DR) are largely prescribed as maintenance therapy, nowadays mainly based on DTG. While many data have been reported about PI-based 2DR, the impact of resistance mutations and duration of virological suppression on DTG-based 2DR remains to be clarified. The aim of this study was to evaluate the impact of resistance mutations on virological outcome of DTG-based 2DR maintenance ART. Material and methods: Virologically suppressed patients (pts) switching to DTG+3TC or DTG+RPV with pre-baseline (time of switch=baseline, BL) resistance genotype (at least PR/RT) were selected from the ARCA database. Primary endpoint was virological failure (VF: an HIV-RNA, VL, >200 cps/mL or 2 consecutive >50 cps/mL). The probability of VF was estimated by Kaplan-Meier analysis. Resistance to 2DR was defined as occurrence of at least Stanford HIVdb (v.8.5) low-level resistance (LLR) to at least one drug included in the current 2DR, based on cumulative genotype. CD4 changes were assessed using Student’s t- test for paired samples. A secondary analysis comparing 2DR with DTG-based 3D regimens was also performed. Results: A total of 318 2DR pts were analysed: 260 (82%) switching to DTG+3TC, 58 (18%) to DTG+RPV; 68% were males, median age was 51 (44-56) years, 12 (6-23) years of HIV infection, 5 (3-8) years of virological suppression, nadir CD4 231 (121-329), 5 (3-9) previous ARV lines, 59% previously exposed to INSTI, 11% with resistance to current 2DR. The integrase sequence was available in 14% of patients, none harbouring resistance to DTG. 20 VF were observed, of whom 4 (3/17 VF in DTG+3TC, 1/3 in DTG+RPV) in patients with at least LLR at BL (M184V+K219Q; D67N+K70R+K219Q; D67N+K70R+T215Y+219Q; E138A), in a median FU of 1.3 years (IQR 0.6-2). The 2-year estimated probability of VF was 8.7% (95% CI 4.4;13); 8.6% (4.1;13.1) in those without resistance and 9.7% (-4.4;23.8) in those with resistance (Log rank: p=ns, figure 1). No factor was significantly associated with VF at multivariate analysis, but in pts with <6 years of virological suppression, BL resistance was associated with a higher probability of VF (p=0.003). After 48 weeks, a statistically significant increase in CD4+ was detected (+56 cells/mmc, p<0.001), independently from baseline resistance. The 2-year estimated probability of VF in the reference 3DR group (n=564) was not different from that for the 2DR group: 8.8% (5.9;11.7) in the whole case file and 9.7% (6.6;12.8) in the presence of baseline resistance. Longer time of virological suppression was the only factor associated with a lower risk of VF in the 3DR dataset. Conclusions: DTG-based 2DRs show high virological efficacy, even in the context of predicted incomplete activity, at least within a short-term follow-up. A longer duration of virological suppression seems to decrease the impact of resistance on virological outcome, however further studies are warranted to confirm this hypothesis and possibly define a clinically useful threshold

Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis

We reviewed literature and our data to find out mucinous breast cancer's overall survival (OS), disease free survival (DFS) and if there are differences between pure mucinous breast cancer and mixed mucinous breast cancer in terms of OS and DFS

Predicting 2-drug antiretroviral regimen efficacy by genotypic susceptibility score: results from a cohort study

Background: HIV drug resistance has a deleterious effect on the virological outcome of antiretroviral therapy (ART). The aim of the study was to evaluate the ability of genotypic susceptibility score (GSS) to predict virological outcome following an ART switch to a 2-drug regimen in virosuppressed HIV-1 infected patients. Material and methods: From the ARCA database we selected HIV-1 infected patients virologically suppressed switching to 2-drug ART (2006-2018, time of switch=baseline), with pre-baseline resistance genotype and at least one HIV-1 RNA determination during follow up. Primary endopoint was virological failure (VF: an HIV-RNA, VL, ≥ 200 cps/mL or 2 consecutive ≥ 50 cps/mL). Survival analysis was used to investigate predictors of VF. The GSS predicted by the latest and the cumulative genotype (CGSS) was calculated using the Stanford hivdb (v.8.5) with respect to the 2-drug regimen started. CD4 changes from baseline at weeks 24, 48 and 96 were assessed using Student’s t-test for paired samples. Results: We included 773 patients: 522 (68%) were males, 186 (24%) heterosexuals, with median age of 50 years (IQR, 43-56), 10 years of HIV (5-20), 7 years of ART (4-15) and 5 (3-8) previous antiretroviral (ARV) lines. At baseline patients had been virologically suppressed for 6.4 years (2.5-14), allowing isolated blips. The median zenith VL was 4.9 log10 (4.4-5.5), CD4 cells count at nadir 222 (108-324) and at baseline 640 (477-860). Median GSS was 2 (1.5-2), with GSS <2 in 213 (28%) pts, median CGSS was 2 (1-2), with CGSS <2 in 250 (33%). The previous ARV classes used were NRTI in 770 patients (99%), NNRTI in 416 (54%), boosted PI in 639 (83%) and INSTI in 218 (28%). Current ARV regimens included: PI+3TC in 455 pts (59%), of which 3TC+ ATV unboosted or ATV/r or ATV/c in 181 (23%) and DRV/r or DRV/c in 274 (36%), DTG+3TC in 260 (34%) and DTG+RPV in 58 (7%). During a median observation time of 75 wks (IQR 37-120) the estimated probability of VF at 48 weeks was 6% (95% CI 5-7) among patients with GSS=2, 4% (3-5) among patients with GSS 1-1.99 and 11% (4-18) among those with GSS <1 (Log Rank p=0.21). According to CGSS, the estimated probability of VF at 48 weeks was 5% (95% CI 1-6) among patients with CGSS =2, 6% (4-8) among patients with CGSS 1-1.99 and 8% (3-13) among those with CGSS <1 (Log Rank p=0.006) (Fig 1). Observed median changes of CD4+ counts from baseline were +24 cells/μL (IQR -67;+132) at 24 weeks, +49 cells/μL (IQR -31;+159) at 48 weeks and +74 cells/μL (IQR -30; +197) at 96 weeks (p<0.001 for all comparisons). At multivariate analysis, adjusting for years of ART, CD4 cell count at nadir and at baseline, CGSS strata, number of previous ARV lines, only longer time since last VL>50 cps/mL was associated with lower risk of VF (+ 1 year, aHR 0.89, 95% CI 0.82-0.98; p=0.01). Conclusions: Despite an effect of CGSS, the duration of virosuppression was the only independent predictor of virological efficacy of switching to 2-drug regimens

The apeNEXT project

Numerical simulations in theoretical high-energy physics (Lattice QCD) require huge computing resources. Several generations of massively parallel computers optimised for these applications have been developed within the APE (array processor experiment) project. Large prototype systems of the latest generation, apeNEXT, are currently being assembled and tested. This contribution explains how the apeNEXT architecture is optimised for Lattice QCD, provides an overview of the hardware and software of apeNEXT, and describes its new features, like the SPMD programming model and the C compiler

Evidence for alterations in fixational eye movements in glaucoma

BACKGROUND: Fixation changes in glaucoma are generally overlooked, as they are not strikingly evident as in macular diseases. Fundus perimetry might give additional insights into this aspect, along with traditional perimetric measures. In this work we propose a novel method to quantify glaucomatous changes in fixation features as detected by fundus perimetry and relate them to the extent of glaucomatous damage. METHODS: We retrospectively analysed fixation data from 320 people (200 normal subjects and 120 with glaucoma) from the Preferred Retinal Locus (PRL) detection of a Compass perimeter. Fixation stability was measured as Bivariate Contour Ellipse Area (BCEA), and using two novel metrics: (1) Mean Euclidean Distance (MED) from the Preferred Retinal Locus, and (2) Sequential Euclidean Distance (SED) of sequential fixation locations. These measures were designed to capture the spread of fixation points, and the frequency of position changes during fixation, respectively. RESULTS: In the age corrected analysis, SED was significantly greater in glaucomatous subjects than controls (P = 0.002), but there was no difference in BCEA (P = 0.15) or MED (P = 0.054). Similarly, SED showed a significant association with Mean Deviation (P  0.14 for both). CONCLUSION: Changes in the scanning pattern detected by SED are better than traditional measures of fixation spread (BCEA) for describing the changes in fixation stability observed in glaucoma

CHEX-MATE: A non-parametric deep learning technique to deproject and deconvolve galaxy cluster X-ray temperature profiles

Temperature profiles of the hot galaxy cluster intracluster medium (ICM) have a complex non-linear structure that traditional parametric modelling may fail to fully approximate. For this study, we made use of neural networks, for the first time, to construct a data-driven non-parametric model of ICM temperature profiles. A new deconvolution algorithm was then introduced to uncover the true (3D) temperature profiles from the observed projected (2D) temperature profiles. An auto-encoder-inspired neural network was first trained by learning a non-linear interpolatory scheme to build the underlying model of 3D temperature profiles in the radial range of [0.02-2] R$_{500}$, using a sparse set of hydrodynamical simulations from the THREE HUNDRED PROJECT. A deconvolution algorithm using a learning-based regularisation scheme was then developed. The model was tested using high and low resolution input temperature profiles, such as those expected from simulations and observations, respectively. We find that the proposed deconvolution and deprojection algorithm is robust with respect to the quality of the data, the morphology of the cluster, and the deprojection scheme used. The algorithm can recover unbiased 3D radial temperature profiles with a precision of around 5\% over most of the fitting range. We apply the method to the first sample of temperature profiles obtained with XMM{\it -Newton} for the CHEX-MATE project and compared it to parametric deprojection and deconvolution techniques. Our work sets the stage for future studies that focus on the deconvolution of the thermal profiles (temperature, density, pressure) of the ICM and the dark matter profiles in galaxy clusters, using deep learning techniques in conjunction with X-ray, Sunyaev Zel'Dovich (SZ) and optical datasets.Comment: 32 pages, 30 figures, 6 tables, Accepted in A&

Comparison of 5-year progression of retinitis pigmentosa involving the posterior pole among siblings by means of SD-OCT: a retrospective study

The blockchain technology promises to transform finance, money and evengovernments. However, analyses of blockchain applicability and robustness typicallyfocus on isolated systems whose actors contribute mainly by running the consensusalgorithm. Here, we highlight the importance of considering trustless platformswithin the broader ecosystem that includes social and communication networks. Asan example, we analyse the flash-crash observed on 21st June 2017 in the Ethereumplatform and show that a major phenomenon of social coordination led to acatastrophic cascade of events across several interconnected systems. We proposethe concept of “emergent centralisation” to describe situations where a single systembecomes critically important for the functioning of the whole ecosystem, and arguethat such situations are likely to become more and more frequent in interconnectedsocio-technical systems. We anticipate that the systemic approach we propose willhave implications for future assessments of trustless systems and call for the attentionof policy-makers on the fragility of our interconnected and rapidly changing world