Optimal nonlinear information processing capacity in delay-based reservoir computers

Reservoir computing is a recently introduced brain-inspired machine learning paradigm capable of excellent performances in the processing of empirical data. We focus in a particular kind of time-delay based reservoir computers that have been physically implemented using optical and electronic systems and have shown unprecedented data processing rates. Reservoir computing is well-known for the ease of the associated training scheme but also for the problematic sensitivity of its performance to architecture parameters. This article addresses the reservoir design problem, which remains the biggest challenge in the applicability of this information processing scheme. More specifically, we use the information available regarding the optimal reservoir working regimes to construct a functional link between the reservoir parameters and its performance. This function is used to explore various properties of the device and to choose the optimal reservoir architecture, thus replacing the tedious and time consuming parameter scannings used so far in the literature.Comment: 37 pages, 8 figure

Comparison between 3D volumetric rendering and multiplanar slices on the reliability of linear measurements on CBCT images: an in vitro study

OBJECTIVE: The purpose of this study was to determine the accuracy and reliability of two methods of measurements of linear distances (multiplanar 2D and tridimensional reconstruction 3D) obtained from cone-beam computed tomography (CBCT) with different voxel sizes. MATERIAL AND METHODS: Ten dry human mandibles were scanned at voxel sizes of 0.2 and 0.4 mm. Craniometric anatomical landmarks were identified twice by two independent operators on the multiplanar reconstructed and on volume rendering images that were generated by the software Dolphin®. Subsequently, physical measurements were performed using a digital caliper. Analysis of variance (ANOVA), intraclass correlation coefficient (ICC) and Bland-Altman were used for evaluating accuracy and reliability (

Do Girls and Boys Perceive Themselves as Equally Engaged in School? The Results of an International Study from 12 Countries

This study examined gender differences in student engagement and academic performance in school. Participants included 3420 students (7th, 8th, and 9th graders) from Austria, Canada, China, Cyprus, Estonia, Greece, Malta, Portugal, Romania, South Korea, the United Kingdom, and the United States. The results indicated that, compared to boys, girls reported higher levels of engagement in school andwere rated higher by their teachers in academic performance. Student engagement accounted for gender differences in academic performance, but gender did not moderate the associations among student engagement, academic performance, or contextual supports. Analysis of multiple-group structural equation modeling revealed that perceptions of teacher support and parent support, but not peer support, were related indirectly to academic performance through student engagement. This partial mediation model was invariant across gender. The findings from this study enhance the understanding about the contextual and personal factors associated with girls' and boys' academic performance around the world

An international tool to measure perceived stressors in intensive care units: the PS-ICU scale.

Background The intensive care unit is increasingly recognized as a stressful environment for healthcare professionals. This context has an impact on the health of these professionals but also on the quality of their personal and professional life. However, there is currently no validated scale to measure specific stressors perceived by healthcare professionals in intensive care. The aim of this study was to construct and validate in three languages a perceived stressors scale more specific to intensive care units (ICU). Results We conducted a three-phase study between 2016 and 2019: (1) identification of stressors based on the verbatim of 165 nurses and physicians from 4 countries (Canada, France, Italy, and Spain). We identified 99 stressors, including those common to most healthcare professions (called generic), as well as stressors more specific to ICU professionals (called specific); (2) item elaboration and selection by a panel of interdisciplinary experts to build a provisional 99-item version of the scale. This version was pre-tested with 70 professionals in the 4 countries and enabled us to select 50 relevant items; (3) test of the validity of the scale in 497 ICU healthcare professionals. Factor analyses identified six dimensions: lack of fit with families and organizational functioning; patient- and family-related emotional load; complex/at risk situations and skill-related issues; workload and human resource management issues; difficulties related to team working; and suboptimal care situations. Correlations of the PS-ICU scale with a generic stressors measure (i.e., the Job Content Questionnaire) tested its convergent validity, while its correlations with the Maslach Burnout Inventory-HSS examined its concurrent validity. We also assessed the test–retest reliability of PS-ICU with intraclass correlation coefficients. Conclusions The perceived stressors in intensive care units (PS-ICU) scale have good psychometric properties in all countries. It includes six broad dimensions covering generic or specific stressors to ICU, and thus, enables the identification of work situations that are likely to generate high levels of stress at the individual and unit levels. For future studies, this tool will enable the implementation of targeted corrective actions on which intervention research can be based. It also enables national and international comparisons of stressors’ impact.post-print925 K

Association of Bevacizumab Plus Oxaliplatin-Based Chemotherapy With Disease-Free Survival and Overall Survival in Patients With Stage II Colon Cancer A Secondary Analysis of the AVANT Trial

IMPORTANCE: In the pivotal Bevacizumab-Avastin Adjuvant (AVANT) trial, patients with high-risk stage II colon cancer (CC) had 5-year and 10-year overall survival (OS) rates of 88% and 75%, respectively, with adjuvant fluorouracil and oxaliplatin-based chemotherapy; however, the trial did not demonstrate a disease-free survival (DFS) benefit of adding bevacizumab to oxaliplatin-based chemotherapy in stage III CC and suggested a detrimental effect on OS. The Long-term Survival AVANT (S-AVANT) study was designed to collect extended follow-up for patients in the AVANT trial. OBJECTIVE: To explore the efficacy of adjuvant bevacizumab combined with oxaliplatin-based chemotherapy in patients with high-risk, stage II CC. DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary end point analysis of the AVANT and S-AVANT studies included 573 patients with curatively resected high-risk stage II CC and at least 1 of the following criteria: stage T4, bowel obstruction or perforation, blood and/or lymphatic vascular invasion and/or perineural invasion, age younger than 50 years, or fewer than 12 nodes analyzed. The AVANT study was a multicenter randomized stage 3 clinical trial. Data were collected from December 2004 to February 2019, and data for this study were analyzed from March to September 2019. INTERVENTION: Patients were randomly assigned to receive 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX4), FOLFOX4 with bevacizumab, or capecitabine and oxaliplatin (XELOX) with bevacizumab. MAIN OUTCOMES AND MEASURES The primary end points of this secondary analysis were DFS and OS in patients with high-risk stage II CC. RESULTS The AVANT study included 3451 patients, of whom 573 (16.6%) had high-risk stage II CC (192 [33.5%] randomized to FOLFOX4 group; 194 [33.9%] randomized to FOLFOX4 with bevacizumab group; 187 [32.6%] randomized to XELOX with bevacizumab group). With a median (interquartile range) age of 57.0 (47.2-65.7) years, the study population comprised 325 men (56.7%) and 248 women (43.3%). After a median (interquartile range) follow-up of 6.9 (6.1-11.3) years, the 3-year DFS and 5-year OS rates were 88.2% (95% CI, 83.7%-93.0%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 group, 86.6% (95% CI, 81.8%-91.6%) and 89.7% (95% CI, 85.4%-94.2%) in the FOLFOX4 with bevacizumab group, and 86.7% (95% CI, 81.8%-91.8%) and 93.2% (95% CI, 89.6%-97.0%) in the XELOX with bevacizumab group, respectively. The DFS hazard ratio was 0.94 (95% CI, 0.59-1.48; P = .78) for FOLFOX4 with bevacizumab vs FOLFOX4 and 1.07 (95% CI, 0.69-1.67; P = .76) for XELOX with bevacizumab vs FOLFOX4. The OS hazard ratio was 0.92 (95% CI, 0.55-1.55; P = .76) for FOLFOX4 with bevacizumab vs FOLFOX4 and 0.85 (95% CI, 0.50-1.44; P = .55) for XELOX with bevacizumab vs FOLFOX4. CONCLUSIONS AND RELEVANCE: In this secondary analysis of data from the AVANT trial, adding bevacizumab to oxaliplatin-based chemotherapy was not associated with longer DFS or OS in patients with high-risk stage II CC. The findings suggest that the definition of high-risk stage II CC needs to be revisited

Comparison of Methods to Correct Survival Estimates and Survival Regression Analysis on a Large HIV African Cohort

The evaluation of HIV treatment programs is generally based on an estimation of survival among patients receiving antiretroviral treatment (ART). In large HIV programs, loss to follow-up (LFU) rates remain high despite active patient tracing, which is likely to bias survival estimates and survival regression analyses

Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles

BACKGROUND: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology. METHODS: Sporadic ALS patients were confirmed to be ALS according to El Escorial criteria and were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS-R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n = 27) or deltoids of aged-matched healthy subjects (n = 30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RT-qPCR, and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human-derived iPSC MNs and on healthy human myotubes, with untreated cells used as controls. RESULTS: An accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy-derived denervation-naïve differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome-like vesicles and disruption of RNA-processing. Compared with vesicles from healthy control myotubes, when administered to healthy MNs the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA-processing proteins. The RNA-processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient MNs was abolished by anti-CD63 immuno-blocking of vesicle uptake. CONCLUSIONS: ALS muscle vesicles are shown to be toxic to MNs, which establishes the skeletal muscle as a potential source of vesicle-mediated toxicity in ALS

Muscle cells of sporadic amyotrophic lateral sclerosis patients secrete neurotoxic vesicles

Background: The cause of the motor neuron (MN) death that drives terminal pathology in amyotrophic lateral sclerosis (ALS) remains unknown, and it is thought that the cellular environment of the MN may play a key role in MN survival. Several lines of evidence implicate vesicles in ALS, including that extracellular vesicles may carry toxic elements from astrocytes towards MNs, and that pathological proteins have been identified in circulating extracellular vesicles of sporadic ALS patients. Because MN degeneration at the neuromuscular junction is a feature of ALS, and muscle is a vesicle-secretory tissue, we hypothesized that muscle vesicles may be involved in ALS pathology. Methods: Sporadic ALS patients were confirmed to be ALS according to El Escorial criteria and were genotyped to test for classic gene mutations associated with ALS, and physical function was assessed using the ALSFRS-R score. Muscle biopsies of either mildly affected deltoids of ALS patients (n = 27) or deltoids of aged-matched healthy subjects (n = 30) were used for extraction of muscle stem cells, to perform immunohistology, or for electron microscopy. Muscle stem cells were characterized by immunostaining, RT-qPCR, and transcriptomic analysis. Secreted muscle vesicles were characterized by proteomic analysis, Western blot, NanoSight, and electron microscopy. The effects of muscle vesicles isolated from the culture medium of ALS and healthy myotubes were tested on healthy human-derived iPSC MNs and on healthy human myotubes, with untreated cells used as controls. Results: An accumulation of multivesicular bodies was observed in muscle biopsies of sporadic ALS patients by immunostaining and electron microscopy. Study of muscle biopsies and biopsy-derived denervation-naïve differentiated muscle stem cells (myotubes) revealed a consistent disease signature in ALS myotubes, including intracellular accumulation of exosome-like vesicles and disruption of RNA-processing. Compared with vesicles from healthy control myotubes, when administered to healthy MNs the vesicles of ALS myotubes induced shortened, less branched neurites, cell death, and disrupted localization of RNA and RNA-processing proteins. The RNA-processing protein FUS and a majority of its binding partners were present in ALS muscle vesicles, and toxicity was dependent on the expression level of FUS in recipient cells. Toxicity to recipient MNs was abolished by anti-CD63 immuno-blocking of vesicle uptake. Conclusions: ALS muscle vesicles are shown to be toxic to MNs, which establishes the skeletal muscle as a potential source of vesicle-mediated toxicity in ALS