Editorial: The functional anatomy of the reticular formation

Editorial on the research topic of a special issue on the functional anatomy of the reticular formatio

Search-Based Predictive Modelling for Software Engineering: How Far Have We Gone?

In this keynote I introduce the use of Predictive Analytics for Software Engineering (SE) and then focus on the use of search-based heuristics to tackle long-standing SE prediction problems including (but not limited to) software development effort estimation and software defect prediction. I review recent research in Search-Based Predictive Modelling for SE in order to assess the maturity of the field and point out promising research directions. I conclude my keynote by discussing best practices for a rigorous and realistic empirical evaluation of search-based predictive models, a condicio sine qua non to facilitate the adoption of prediction models in software industry practices.Predictive analytics Predictive modelling Search-based software engineering Machine learning Software analytic

Epigenetics and immune cells in medulloblastoma

: Medulloblastoma (MB) is a highly malignant childhood tumor of the cerebellum. Transcriptional and epigenetic signatures have classified MB into four molecular subgroups, further stratified into biologically different subtypes with distinct somatic copy-number aberrations, driver genes, epigenetic alterations, activated pathways, and clinical outcomes. The brain tumor microenvironment (BTME) is of importance to regulate a complex network of cells, including immune cells, involved in cancer progression in brain malignancies. MB was considered with a "cold" immunophenotype due to the low influx of immune cells across the blood brain barrier (BBB). Recently, this assumption has been reconsidered because of the identification of infiltrating immune cells showing immunosuppressive phenotypes in the BTME of MB tumors. Here, we are providing a comprehensive overview of the current status of epigenetics alterations occurring during cancer progression with a description of the genomic landscape of MB by focusing on immune cells within the BTME. We further describe how new immunotherapeutic approaches could influence concurring epigenetic mechanisms of the immunosuppressive cells in BTME. In conclusion, the modulation of these molecular genetic complexes in BTME during cancer progression might enhance the therapeutic benefit, thus firing new weapons to fight MB

Durability of Benefits From Supervised Treadmill Exercise in People With Peripheral Artery Disease.

Background It is currently unknown whether 6 months of supervised treadmill exercise has a durable benefit on 6-minute walk performance, even after exercise is completed, in people with peripheral artery disease. Methods and Results A total of 156 participants with peripheral artery disease were randomized to 1 of 3 groups: supervised treadmill exercise, supervised resistance training, or attention control. Participants received supervised sessions during months 1 to 6 and telephone contact during months 6 to 12. Primary outcomes were change in 6-minute walk distance and short physical performance battery at 6-month follow-up and have been reported previously. Secondary outcomes were change in 6-minute walk and short physical performance battery at 12-month follow-up and are reported here. A group of 134 participants (86%) completed the 12-month follow-up. At 6-month follow-up, compared with control, 6-minute walk distance improved in the treadmill exercise group (+36.1 m, 95% CI =13.9-58.3, P=0.001). Between 6- and 12-month follow-up, 6-minute walk distance significantly declined (-28.6 m, 95% CI=-52.6 to -4.5, P=0.020) and physical activity declined -272 activity units (95% CI =-546 to +2, P=0.052) in the treadmill exercise group compared with controls. At 12-month follow-up, 6 months after completing supervised treadmill exercise, change in 6-minute walk distance was not different between the treadmill exercise and control groups (+7.5, 95% CI =-17.5 to +32.6, P=0.56). There were no differences in short physical performance battery change between either exercise group and control at 6-month or 12-month follow-up. Conclusions A 6-month supervised treadmill exercise intervention that improved 6-minute walk distance at 6-month follow-up did not have persistent benefit at 12-month follow-up. These results do not support a durable benefit of supervised treadmill exercise in peripheral artery disease. Clinical Trial Registration URL : https://www.clinicaltrials.gov . Identifier: NCT 00106327

Associations of Weight Change With Changes in Calf Muscle Characteristics and Functional Decline in Peripheral Artery Disease.

Background Among people with lower extremity peripheral artery disease, obesity is associated with faster functional decline than normal weight. The association of weight loss with functional decline in peripheral artery disease is unknown. Methods and Results Adults with an ankle-brachial index <0.90 were identified from Chicago-area hospitals in 2002-2004. Weight and 6-minute walk distance were measured annually. Weight change categories were weight loss or gain (≥5 pounds/year at ≥1 visit) or stable (weight change <5 pounds at each visit). Participants reported whether weight loss was "intentional" or "unintentional." Calf muscle area was measured with computed tomography every 2 years. Associations of weight change with changes in calf muscle area and 6-minute walk distance were analyzed using mixed-effects models and adjusted for age, body mass index, ankle-brachial index, physical activity, and other confounders. Among 389 participants, mean ankle-brachial index was 0.63±0.16, mean age was 74.5±7.8, and mean body mass index was 28.1±5.1 kg/m2. Over 3.23±1.37 years, muscle area declined more in adults with intentional weight loss versus stable or gain (pair-wise comparisons, P<0.001). Intentional weight loss was associated with less annual decline in 6-minute walk distance than weight gain (intentional loss, 3.7 m; stable, -14.0 m; gain, -28.5 m; unintentional loss, -20.8 m; pair-wise comparison intentional loss versus gain, P=0.003). Conclusions Despite a greater loss of calf muscle area, adults with peripheral artery disease who intentionally lost ≥5 pounds experienced less functional decline than those who gained weight. A randomized trial is needed to establish whether benefits of weight loss in peripheral artery disease outweigh potential adverse effects

Estimation of ash injection in the atmosphere by basaltic volcanic plumes: the case of the Eyjafjallajökull 2010 eruption

During explosive eruptions, volcanic plumes inject ash into the atmosphere and may severely affect air traffic, as illustrated by the 2010 Eyjafjallajökull eruption. Quantitative estimates of ash injection can be deduced from the height reached by the volcanic plume on the basis of scaling laws inferred from models of powerful Plinian plumes. In less explosive basaltic eruptions, there is a partitioning of the magma influx between the atmospheric plume and an effusive lava flow on the ground. We link the height reached by the volcanic plume with the rate of ash injection in the atmosphere via a refined plume model that (1) includes a recently developed variable entrainment law and (2) accounts for mass partitioning between ground flow and plume. We compute the time evolution of the rate of injection of ash into the atmosphere for the Eyjafjallajökull eruption on the basis of satellite thermal images and plume heights and use the dispersion model of the Volcanic Ash Advisory Center of Toulouse to translate these numbers into hazard maps. The classical Plinian model would have overestimated ash injection by about 20% relative to the refined estimate, which does not jeopardize risk assessment. This small error was linked to effective fragmentation by intense interactions of magma with water derived from melting of ice and hence strong mass partitioning into the plume. For a less well fragmented basaltic dry eruption, the error may reach 1 order of magnitude and hence undermine the prediction of ash dispersion, which demonstrates the need to monitor both plume heights and ground flows during an explosive eruption

Racial Differences in the Effect of Granulocyte Macrophage Colony-Stimulating Factor on Improved Walking Distance in Peripheral Artery Disease: The PROPEL Randomized Clinical Trial.

Background The effects of race on response to medical therapy in people with peripheral artery disease ( PAD ) are unknown. Methods and Results In the PROPEL (Progenitor Cell Release Plus Exercise to Improve Functional Performance in PAD) Trial, PAD participants were randomized to 1 of 4 groups for 6 months: supervised treadmill exercise+granulocyte-macrophage colony-stimulating factor ( GM - CSF ) (Group 1), exercise+placebo (Group 2), attention control+ GM - CSF (Group 3), or attention control+placebo (Group 4). Change in 6-minute walk distance was measured at 12- and 26-week follow-up. In these exploratory analyses, groups receiving GM - CSF (Groups 1 and 3), placebo (Groups 2 and 4), exercise (Groups 1 and 2), and attention control (Groups 2 and 4) were combined, maximizing statistical power for studying the effects of race on response to interventions. Of 210 PAD participants, 141 (67%) were black and 64 (30%) were white. Among whites, GM - CSF improved 6-minute walk distance by +22.0 m (95% CI : -4.5, +48.5, P=0.103) at 12 weeks and +44.4 m (95% CI : +6.9, +82.0, P=0.020) at 26 weeks, compared with placebo. Among black participants, there was no effect of GM - CSF on 6-minute walk distance at 12-week ( P=0.26) or 26-week (-5.0 m [-27.5, +17.5, P=0.66]) follow-up, compared with placebo. There was an interaction of race on the effect of GM - CSF on 6-minute walk change at 26-week follow-up ( P=0.018). Exercise improved 6-minute walk distance in black ( P=0.006) and white ( P=0.034) participants without interaction. Conclusions GM - CSF improved 6-minute walk distance in whites with PAD but had no effect in black participants. Further study is needed to confirm racial differences in GM - CSF efficacy in PAD . Clinical Trial Registration URL : http://www.clinicaltrials.gov . Unique identifier: NCT 01408901

Ambiguous Effects of Autophagy Activation Following Hypoperfusion/Ischemia

Autophagy primarily works to counteract nutrient deprivation that is strongly engaged during starvation and hypoxia, which happens in hypoperfusion. Nonetheless, autophagy is slightly active even in baseline conditions, when it is useful to remove aged proteins and organelles. This is critical when the mitochondria and/or proteins are damaged by toxic stimuli. In the present review, we discuss to that extent the recruitment of autophagy is beneficial in counteracting brain hypoperfusion or, vice-versa, its overactivity may per se be detrimental for cell survival. While analyzing these opposite effects, it turns out that the autophagy activity is likely not to be simply good or bad for cell survival, but its role varies depending on the timing and amount of autophagy activation. This calls for the need for an appropriate autophagy tuning to guarantee a beneficial effect on cell survival. Therefore, the present article draws a theoretical pattern of autophagy activation, which is hypothesized to define the appropriate timing and intensity, which should mirrors the duration and severity of brain hypoperfusion. The need for a fine tuning of the autophagy activation may explain why confounding outcomes occur when autophagy is studied using a rather simplistic approach

Real-life appraisal on blood pressure targets achievement in adult outpatients at high cardiovascular risk

Background and aim: Although hypertension guidelines highlight the benefits of achieving the recommended blood pressure (BP) targets, hypertension control rate is still insufficient, mostly in high or very high cardiovascular (CV) risk patients. Thus, we aimed to estimate BP control in a cohort of patients at high CV risk in both primary and secondary prevention. Methods and results: A single-center, cross-sectional study was conducted by extracting data from a medical database of adult outpatients aged 40–75 years, who were referred to our Hypertension Unit, Rome (IT), for hypertension assessment. Office BP treatment targets were defined according to 2018 ESC/ESH guidelines as: a)<130/80 mmHg in individuals aged 40–65 years; b)<140/80 mmHg in subjects aged >65 years. Primary prevention patients with SCORE <5% were considered to be at low-intermediate risk, whilst individuals with SCORE ≥5% or patients with comorbidities were defined to be at very high risk. Among 6354 patients (47.2% female, age 58.4 ± 9.6 years), 4164 (65.5%) were in primary prevention with low-intermediate CV risk, 1831 (28.8%) in primary prevention with high-very high CV risk and 359 (5.6%) in secondary prevention. In treated hypertensive outpatients, uncontrolled hypertension rate was significantly higher in high risk primary prevention than in low risk primary prevention and secondary prevention patients (18.4% vs 24.4% vs. 12.5%, respectively; P < 0.001). In high risk primary prevention diabetic patients only 10% achieved the recommended BP targets. Conclusions: Our data confirmed unsatisfactory BP control among high-risk patients, both in primary and secondary prevention, and suggest the need for a more stringent BP control policies in these patients