Estimating traffic operations at multi-lane roundabouts: a case study

This paper addresses traffic modeling issues at urban multi-lane roundabouts where, despite circulating vehicles have priority, negotiation of the right-of-way can occur between antagonist traffic flows, as a result of minor drivers’ failing to obey the nominal operating rule (stop or yield control). Existing models for the estimation of operational performances have the shortcoming of not representing the interdependencies between entering and circulating vehicles at multi-lane roundabouts. An analytical capacity model derived from field observations was developed for this kind of intersections in a previous study. The complexity of the model lies in the difficulty of observing the behavioral parameters which are needed to implement the model. A procedure to get unknown behavioral parameters from traffic surveys is here proposed. This concerns saturation headways, often eluding direct observations due to rare occurrences of traffic conditions in which they can be observed. The unknown parameters were estimated through a regression model using on field data collected at a multi-lane roundabout. The presence of data correlation within a cluster of observations required the estimation of the regression parameters through a generalized estimating equation model. Results gave insight into the analysis of operations at multi-lane roundabouts, containing evidence to support assumptions made for the estimation of unobservable parameters

A Methodological Framework to Assess Road Infrastructure Safety and Performance Efficiency in the Transition toward Cooperative Driving

There is increasing interest in connected and automated vehicles (CAVs), since their implementation will transform the nature of transportation and promote social and economic change. Transition toward cooperative driving still requires the understanding of some key questions to assess the performances of CAVs and human-driven vehicles on roundabouts and to properly balance road safety and traffic efficiency requirements. In this view, this paper proposes a simulation-based methodological framework aiming to assess the presence of increasing proportions of CAVs on roundabouts operating at a high-capacity utilization level. A roundabout was identified in Palermo City, Italy, and built in Aimsun (version 20) to describe the stepwise methodology. The CAV-based curves of capacity by entry mechanism were developed and then used as target capacities. To calibrate the model parameters, the capacity curves were compared with the capacity data simulated by Aimsun. The impact on the safety and performance efficiency of a lane dedicated to CAVs was also examined using surrogate measures of safety. The paper ends with highlighting a general improvement with CAVs on roundabouts, and with providing some insights to assess the advantages of the automated and connected driving technologies in transitioning to smarter mobilit

Выбор оптимальных технических решений для улавливания углеводородных паров от резервуарных парков нефти

San Francisco, CA - US

Revisiting geochemical controls on patterns of carbonate deposition through the lens of multiple pathways to mineralization

The carbonate sedimentary record contains diverse compositions and textures that reflect the evolution of oceans and atmospheres through geological time. Efforts to reconstruct paleoenvironmental conditions from these deposits continue to be hindered by the need for process-based models that can explain observed shifts in carbonate chemistry and form. Traditional interpretations assume minerals precipitate and grow by classical ion-by-ion addition processes but are unable to reconcile a number of unusual features contained in Proterozoic carbonates. The realization that diverse organisms produce high Mg carbonate skeletal structures by non-classical pathways involving amorphous intermediates raises the question of whether similar processes are also active in sedimentary environments. This study examines the hypothesis that non-classical pathways to mineralization are the physical basis for some of the carbonate morphologies and compositions observed in natural and laboratory settings. We designed experiments with a series of different solution Mg : Ca ratios and saturation environments to investigate the effects on carbonate phase, Mg content, and morphology. Our observations of diverse carbonate mineral compositions and textures suggest geochemical conditions bias the mineralization pathway by a systematic relationship to Mg : Ca ratio and the abundance of carbonate ions. Environments with low Mg levels produce calcite crystallites with 0–12 mol% MgCO_3. In contrast, the combination of high initial Mg : Ca and rapidly increasing saturation opens a non-classical pathway that begins with extensive precipitation of an amorphous calcium carbonate (ACC). This phase slowly transforms to aggregates of very high Mg calcite nanoparticles whose structures and compositions are similar to natural disordered dolomites. The non-classical pathways are favored when the local environment contains sufficient Mg to inhibit calcite growth through increased solubility—a thermodynamic factor, and achieves saturation with respect to ACC on a timescale that is shorter than the rate of aragonite nucleation—a kinetic factor. Aragonite is produced when Mg levels are high but saturation is insufficient for ACC precipitation. The findings provide a physical basis for anecdotal claims that the interplay of kinetic and thermodynamic factors underlies patterns of carbonate precipitation and suggest the need to expand traditional interpretations of geological carbonate formation to include non-classical pathways to mineralization

A Clinically Relevant Variant of the Human Hydrogen Sulfide-Synthesizing Enzyme Cystathionine β -Synthase: Increased CO Reactivity as a Novel Molecular Mechanism of Pathogenicity?

The human disease classical homocystinuria results from mutations in the gene encoding the pyridoxal 5′-phosphate- (PLP-) dependent cystathionine β-synthase (CBS), a key enzyme in the transsulfuration pathway that controls homocysteine levels, and is a major source of the signaling molecule hydrogen sulfide (H2S). CBS activity, contributing to cellular redox homeostasis, is positively regulated by S-adenosyl-L-methionine (AdoMet) but fully inhibited upon CO or NO• binding to a noncatalytic heme moiety. Despite extensive studies, the molecular basis of several pathogenic CBS mutations is not yet fully understood. Here we found that the ferrous heme of the reportedly mild p.P49L CBS variant has altered spectral properties and markedly increased affinity for CO, making the protein much more prone than wild type (WT) CBS to inactivation at physiological CO levels. The higher CO affinity could result from the slightly higher flexibility in the heme surroundings revealed by solving at 2.80-Å resolution the crystallographic structure of a truncated p.P49L. Additionally, we report that p.P49L displays impaired H2S-generating activity, fully rescued by PLP supplementation along the purification, despite a minor responsiveness to AdoMet. Altogether, the results highlight how increased propensity to CO inactivation of an otherwise WT-like variant may represent a novel pathogenic mechanism in classical homocystinuria

Is the monoclonal spread of the ST258, KPC-3-producing clone being replaced in southern Italy by the dissemination of multiple clones of carbapenem nonsusceptible, KPC-3-producing Klebsiella pneumoniae?

Spread of carbapenemase-producing Klebsiella pneumoniae has been identified as an issue of serious worldwide concern from clinical and public health perspectives. Italy is an country endemic for and a reservoir of K. pneumoniae carbapenemases (KPC). Nineteen isolates of CR-Kp from 16 different patients admitted in two hospital of Palermo in the period April-May 2014 were studied. Seven of 16 isolates belonged to ST307, six to ST258 and three to ST273. All isolates were KPC-3 producers. Our data emphasize the increasing difficulties in controlling the spread of KPC-K

An update of the evolving epidemic of blaKPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: Emergence of multiple Non-ST258 Clones

Background: In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy. Methods and Results: Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates. Conclusions: Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic

Recommendations for neonatologists and pediatricians working in first level birthing centers on the first communication of genetic disease and malformation syndrome diagnosis: consensus issued by 6 Italian scientific societies and 4 parents’ associations

Background: Genetic diseases are chronic conditions with relevant impact on the lives of patients and their families. In USA and Europe it is estimated a prevalence of 60 million affected subjects, 75% of whom are in developmental age. A significant number of newborns are admitted in the Neonatal Intensive Care Units (NICU) for reasons different from prematurity, although the prevalence of those with genetic diseases is unknown. It is, then, common for the neonatologist to start a diagnostic process on suspicion of a genetic disease or malformation syndrome, or to make and communicate these diagnoses. Many surveys showed that the degree of parental satisfaction with the methods of communication of diagnosis is low. Poor communication may have short and long-term negative effects on health and psychological and social development of the child and his family. We draw up recommendations on this issue, shared by 6 Italian Scientific Societies and 4 Parents’ Associations, aimed at making the neonatologist’s task easier at the difficult time of communication to parents of a genetic disease/malformation syndrome diagnosis for their child. Methods: We used the method of the consensus paper. A multidisciplinary panel of experts was first established, based on the clinical and scientific sharing of the thematic area of present recommendations. They were suggested by the Boards of the six Scientific Societies that joined the initiative: Italian Societies of Pediatrics, Neonatology, Human Genetics, Perinatal Medicine, Obstetric and Gynecological Ultrasound and Biophysical Methodologies, and Pediatric Genetic Diseases and Congenital Disabilities. To obtain a deeper and global vision of the communication process, and to reach a better clinical management of patients and their families, representatives of four Parents’ Associations were also recruited: Italian Association of Down People, Cornelia de Lange National Volunteer Association, Italian Federation of Rare Diseases, and Williams Syndrome People Association. They worked from September 2019 to November 2020 to achieve a consensus on the recommendations for the communication of a new diagnosis of genetic disease. Results: The consensus of experts drafted a final document defining the recommendations, for the neonatologist and/or the pediatrician working in a fist level birthing center, on the first communication of genetic disease or malformation syndrome diagnosis. Although there is no universal communication technique to make the informative process effective, we tried to identify a few relevant strategic principles that the neonatologist/pediatrician may use in the relationship with the family. We also summarized basic principles and significant aspects relating to the modalities of interaction with families in a table, in order to create an easy tool for the neonatologist to be applied in the daily care practice. We finally obtained an intersociety document, now published on the websites of the Scientific Societies involved. Conclusions: The neonatologist/pediatrician is often the first to observe complex syndromic pictures, not always identified before birth, although today more frequently prenatally diagnosed. It is necessary for him to know the aspects of genetic diseases related to communication and bioethics, as well as the biological and clinical ones, which together outline the cornerstones of the multidisciplinary care of these patients. This consensus provide practical recommendations on how to make the first communication of a genetic disease /malformation syndrome diagnosis. The proposed goal is to make easier the informative process, and to implement the best practices in the relationship with the family. A better doctor-patient/family interaction may improve health outcomes of the child and his family, as well as reduce legal disputes with parents and the phenomenon of defensive medicine

An update of the evolving epidemic of blaKPC carrying Klebsiella pneumoniae in Sicily, Italy, 2014: Emergence of multiple Non-ST258 Clones

Background: In Italy, Klebsiella pneumoniae carbapenemase producing K. pneumoniae (KPC-Kp) strains are highly endemic and KPC producing CC258 is reported as the widely predominating clone. In Palermo, Italy, previous reports have confirmed this pattern. However, recent preliminary findings suggest that an epidemiological change is likely ongoing towards a polyclonal KPC-Kp spread. Here we present the results of molecular typing of 94 carbapenem non susceptible K. pneumoniae isolates detected during 2014 in the three different hospitals in Palermo, Italy. Methods and Results: Ninety-four consecutive, non replicate carbapenem non susceptible isolates were identified in the three largest acute general hospitals in Palermo, Italy, in the six-month period March-August 2014. They were characterized by PCR for β-lactam, aminoglycoside and plasmid mediated fluoroquinolone resistance genetic determinants. The mgrB gene of the colistin resistant isolates was amplified and sequenced. Clonality was assessed by pulsed field gel electrophoresis and multilocus sequence typing. Eight non-CC258 sequence types (STs) were identified accounting for 60% of isolates. In particular, ST307 and ST273 accounted for 29% and 18% of isolates. CC258 isolates were more frequently susceptible to gentamicin and non-CC258 isolates to amikacin. Colistin non susceptibility was found in 42% of isolates. Modifications of mgrB were found in 32 isolates. Conclusions: Concurrent clonal expansion of some STs and lateral transmission of genetic resistance determinants are likely producing a thorough change of the KPC-Kp epidemiology in Palermo, Italy. In our setting mgrB inactivation proved to substantially contribute to colistin resistance. Our findings suggest the need to continuously monitor the KPC-Kp epidemiology and to assess by a nationwide survey the possible shifting towards a polyclonal epidemic

Caspase-8 activation by cigarette smoke induces pro-inflammatory cell death of human macrophages exposed to lipopolysaccharide

Cigarette smoking impairs the lung innate immune response making smokers more susceptible to infections and severe symptoms. Dysregulation of cell death is emerging as a key player in chronic inflammatory conditions. We have recently reported that short exposure of human monocyte-derived macrophages (hMDMs) to cigarette smoke extract (CSE) altered the TLR4-dependent response to lipopolysaccharide (LPS). CSE caused inhibition of the MyD88-dependent inflammatory response and activation of TRIF/caspase-8/caspase-1 pathway leading to Gasdermin D (GSDMD) cleavage and increased cell permeability. Herein, we tested the hypothesis that activation of caspase-8 by CSE increased pro-inflammatory cell death of LPS-stimulated macrophages. To this purpose, we measured apoptotic and pyroptotic markers as well as the expression/release of pro-inflammatory mediators in hMDMs exposed to LPS and CSE, alone or in combination, for 6 and 24 h. We show that LPS/CSE-treated hMDMs, but not cells treated with CSE or LPS alone, underwent lytic cell death (LDH release) and displayed apoptotic features (activation of caspase-8 and -3/7, nuclear condensation, and mitochondrial membrane depolarization). Moreover, the negative regulator of caspase-8, coded by CFLAR gene, was downregulated by CSE. Activation of caspase-3 led to Gasdermin E (GSDME) cleavage. Notably, lytic cell death caused the release of the damage-associated molecular patterns (DAMPs) heat shock protein-60 (HSP60) and S100A8/A9. This was accompanied by an impaired inflammatory response resulting in inhibited and delayed release of IL6 and TNF. Of note, increased cleaved caspase-3, higher levels of GSDME and altered expression of cell death-associated genes were found in alveolar macrophages of smoker subjects compared to non-smoking controls. Overall, our findings show that CSE sensitizes human macrophages to cell death by promoting pyroptotic and apoptotic pathways upon encountering LPS. We propose that while the delayed inflammatory response may result in ineffective defenses against infections, the observed cell death associated with DAMP release may contribute to establish chronic inflammation. CS exposure sensitizes human macrophages to pro-inflammatory cell death. Upon exposure to LPS, CS inhibits the TLR4/MyD88 inflammatory response, downregulating the pro-inflammatory genes TNF and IL6 and the anti-apoptotic gene CFLAR, known to counteract caspase-8 activity. CS enhances caspase-8 activation through TLR4/TRIF, with a partial involvement of RIPK1, resulting on the activation of caspase-1/GSDMD axis leading to increased cell permeability and DAMP release through gasdermin pores [19]. At later timepoints caspase-3 becomes strongly activated by caspase-8 triggering apoptotic events which are associated with mitochondrial membrane depolarization, gasdermin E cleavage and secondary necrosis with consequent massive DAMP release