27 research outputs found

    Random parking, Euclidean functionals, and rubber elasticity

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    We study subadditive functions of the random parking model previously analyzed by the second author. In particular, we consider local functions SS of subsets of Rd\mathbb{R}^d and of point sets that are (almost) subadditive in their first variable. Denoting by ξ\xi the random parking measure in Rd\mathbb{R}^d, and by ξR\xi^R the random parking measure in the cube QR=(R,R)dQ_R=(-R,R)^d, we show, under some natural assumptions on SS, that there exists a constant SˉR\bar{S}\in \mathbb{R} such that % limR+S(QR,ξ)QR=limR+S(QR,ξR)QR=Sˉ \lim_{R\to +\infty} \frac{S(Q_R,\xi)}{|Q_R|}\,=\,\lim_{R\to +\infty}\frac{S(Q_R,\xi^R)}{|Q_R|}\,=\,\bar{S} % almost surely. If ζS(QR,ζ)\zeta \mapsto S(Q_R,\zeta) is the counting measure of ζ\zeta in QRQ_R, then we retrieve the result by the second author on the existence of the jamming limit. The present work generalizes this result to a wide class of (almost) subadditive functions. In particular, classical Euclidean optimization problems as well as the discrete model for rubber previously studied by Alicandro, Cicalese, and the first author enter this class of functions. In the case of rubber elasticity, this yields an approximation result for the continuous energy density associated with the discrete model at the thermodynamic limit, as well as a generalization to stochastic networks generated on bounded sets.Comment: 28 page

    A variational approach to the local character of G-closure: the convex case

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    This article is devoted to characterize all possible effective behaviors of composite materials by means of periodic homogenization. This is known as a GG-closure problem. Under convexity and pp-growth conditions (p>1p>1), it is proved that all such possible effective energy densities obtained by a Γ\Gamma-convergence analysis, can be locally recovered by the pointwise limit of a sequence of periodic homogenized energy densities with prescribed volume fractions. A weaker locality result is also provided without any kind of convexity assumption and the zero level set of effective energy densities is characterized in terms of Young measures. A similar result is given for cell integrands which enables to propose new counter-examples to the validity of the cell formula in the nonconvex case and to the continuity of the determinant with respect to the two-scale convergence.Comment: 24 pages, 1 figur

    Interactions between the RepB initiator protein of plasmid pMV158 and two distant DNA regions within the origin of replication

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    Plasmids replicating by the rolling circle mode usually possess a single site for binding of the initiator protein at the origin of replication. The origin of pMV158 is different in that it possesses two distant binding regions for the initiator RepB. One region was located close to the site where RepB introduces the replication-initiating nick, within the nic locus; the other, the bind locus, is 84 bp downstream from the nick site. Binding of RepB to the bind locus was of higher affinity and stability than to the nic locus. Contacts of RepB with the bind and nic loci were determined through high-resolution footprinting. Upon binding of RepB, the DNA of the bind locus follows a winding path in its contact with the protein, resulting in local distortion and bending of the double-helix. On supercoiled DNA, simultaneous interaction of RepB with both loci favoured extrusion of the hairpin structure harbouring the nick site while causing a strong DNA distortion around the bind locus. This suggests interplay between the two RepB binding sites, which could facilitate loading of the initiator protein to the nic locus and the acquisition of the appropriate configuration of the supercoiled DNA substrate

    Disease-specific and general health-related quality of life in newly diagnosed prostate cancer patients: The Pros-IT CNR study

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    Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

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    BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

    Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

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    Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

    Prenatal detection of the cystic form of meconium peritonitis: No issues for delayed postnatal surgery

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    Prenatal ultrasound (US) diagnosis and postnatal outcome are reviewed in three babies with the complex form of meconium peritonitis (MP), the cystic type. Perinatal management is discussed. Large intra-abdominal cysts with signs of calcifications were detected during the second mid-trimester. Meconium ascites and polyhydramnios appeared between 32 and 35 weeks of gestation. Signs of anaemia were assessed on median cerebral artery peak systolic velocity. Sudden appearance of hydrops and anaemia required preterm delivery, neonatal resuscitation and urgent abdominal drainage. Postnatal US imaging confirmed prenatal sonographic evidence. Abdominal X-ray showed calcifications and no free abdominal air. Intestinal diversion was performed in two patients on their first day of life and evolution was uneventful. Hospital death occurred in one baby, who was submitted to delayed surgery due to unstable hemodynamic conditions. Distal ileal perforation walled off by pseudocysts was detected in all cases. One baby was found to be affected by cystic fibrosis. Ileal intussusception was described in the non-surviving infant. The cystic type of MP may have a potentially rapid lethal course and the onset of foetal anaemia and polyhydramnios is a bad prognostic factor. Severe evolution in hydrops and foetal distress may occur at any moment suggesting the persistence of a leakage or re-rupture of the cysts with new meconium spillage into the abdomen. Prenatal detection of ascites, polyhydramnios and pseudocysts requires a strict follow-up, and timing of delivery has to be planned in a tertiary centre. Postnatal radiological imaging does not offer further information over prenatal imaging and surgical decision should not be influenced by the absence of abdominal free air. Urgent abdominal drainage at birth, followed by intestinal diversion of persistent intestinal perforation on the first day of life, may prevent bacterial colonisation and improve prognosis
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