Bike Lane Design: the Context Sensitive Approach

In these days of increasing congestion on roads, bicycles continue to provide a valuable contribution to mobility in Europe. Their relatively small size and low cost enable them to blend efficiently into in the traffic flow while needing less space compared to other vehicles. However, cyclists form one of the most vulnerable groups of road users. So the design of safe infrastructures for all travellers categories, included the cyclists, becomes a primary requirement. To obtain these results, a Context Sensitive Design approach is a very useful tool. In this way, in fact, it is possible to examine a project or existing road, reporting its crash potential and safety performances and detecting its deficiencies, taking into consideration communities and lands which it passes through. In this paper the authors, starting from results collected on a bike lane placed in Rimini, provide useful results for designers, construction and maintenance contractors, in order to obtain safe bike lanes

Comparative analysis of different approaches for dealing with candidate regions in the context of a genome-wide association study

Genome-wide association studies (GWAS) test hundreds of thousands of single-nucleotide polymorphisms (SNPs) for association to a trait, treating each marker equally and ignoring prior evidence of association to specific regions. Typically, promising regions are selected for further investigation based on p-values obtained from simple tests of association. However, loci that exert only a weak, low-penetrant role on the trait, producing modest evidence of association, are not detectable in the context of a GWAS. Implementing prior knowledge of association in GWAS could increase power, help distinguish between false and true positives, and identify better sets of SNPs for follow-up studies

How to Assess the Carbon Footprint of a Large University? The Case Study of University of Bologna’s Multicampus Organization

University campuses represent a heterogeneous ecosystem as to social, economic, energetic, and personal travel planning with a huge impact on hosting cities and territories. Sustainable policies are thus fundamental to reduce this impact and to adopt ecological behaviors. The measures for any University Sustainability Plan should be evaluated in terms of GHG emissions, as well as the overall impact of the university itself. Carbon footprint (CF) calculation is a relevant Decision Support tool that allows university organizations to measure and communicate the environmental effects of their activities. The aim of this paper is to present a carbon footprint methodology specifically designed to calculate the carbon footprint of large universities. The methodology was applied to calculate the CF of the University of Bologna by following international standards—i.e., the GHG protocol, the ISO 14064, and the ISO/TR 14069 guide—to understand the environmental impact caused by greenhouse gas emissions from direct and indirect university activities. The study was conducted upon the data available in 2020 and then was compared to the 2018 data, with the aim to recognize if the effect of the pandemic could have altered the results. In 2020, the University of Bologna emitted 16,467 tCO2e which became 15,753 tCO2e considering the offset and avoided emission provided by the internal production of energy from renewable sources. Comparison between 2020 and 2018 shows how, in 2018, most of the emissions came from transportation, representing 74% of the total emissions, while in 2020 almost 50% of total emissions derived by IT procurements. The case application demonstrates the way with which the methodology may be applied to assess environmental impact for complex university campuses

Copy number variations in candidate genomic regions confirm genetic heterogeneity and parental bias in Hirschsprung disease

Background: Hirschsprung Disease (HSCR) is a congenital defect of the intestinal innervations characterized by complex inheritance. Many susceptibility genes including RET, the major HSCR gene, and several linked regions and associated loci have been shown to contribute to disease pathogenesis. Nonetheless, a proportion of patients still remains unexplained. Copy Number Variations (CNVs) have already been involved in HSCR, and for this reason we performed Comparative Genomic Hybridization (CGH), using a custom array with high density probes. Results: A total of 20 HSCR candidate regions/genes was tested in 55 sporadic patients and four patients with already known chromosomal aberrations. Among 83 calls, 12 variants were experimentally validated, three of which involving the HSCR crucial genes SEMA3A/3D, NRG1, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs while, interestingly, several gains and losses did co-occur with another RET defect, thus confirming that more than one predisposing event is necessary for HSCR to develop. New loci were also shown to be involved, such as ALDH1A2, already found to play a major role in the enteric nervous system. Finally, all the inherited CNVs were of maternal origin. Conclusions: Our results confirm a wide genetic heterogeneity in HSCR occurrence and support a role of candidate genes in expression regulation and cell signaling, thus contributing to depict further the molecular complexity of the genomic regions involved in the Enteric Nervous System development. The observed maternal transmission bias for HSCR associated CNVs supports the hypothesis that in females these variants might be more tolerated, requiring additional alterations to develop HSCR disease

Optimization of Ex Vivo Machine Perfusion and Transplantation of Vascularized Composite Allografts

Background: Machine perfusion is gaining interest as an efficient method of tissue preservation of Vascularized Composite Allografts (VCA). The aim of this study was to develop a protocol for ex vivo subnormothermic oxygenated machine perfusion (SNMP) on rodent hindlimbs and to validate our protocol in a heterotopic hindlimb transplant model. Methods: In this optimization study we compared three different solutions during 6 h of SNMP ( n = 4 per group). Ten control limbs were stored in a preservation solution on Static Cold Storage [SCS]). During SNMP we monitored arterial flowrate, lactate levels, and edema. After SNMP, muscle biopsies were taken for histology examination, and energy charge analysis. We validated the best perfusion protocol in a heterotopic limb transplantation model with 30-d follow up ( n = 13). As controls, we transplanted untreated limbs ( n = 5) and hindlimbs preserved with either 6 or 24 h of SCS ( n = 4 and n = 5). Results: During SNMP, arterial outflow increased, and lactate clearance decreased in all groups. Total edema was significantly lower in the HBOC-201 group compared to the BSA group ( P = 0.005), 4.9 (4.3-6.1) versus 48.8 (39.1-53.2) percentage, but not to the BSA + PEG group ( P = 0.19). Energy charge levels of SCS controls decreased 4-fold compared to limbs perfused with acellular oxygen carrier HBOC-201, 0.10 (0.07-0.17) versus 0.46 (0.42-0.49) respectively ( P = 0.002). Conclusions: Six hours ex vivo SNMP of rodent hindlimbs using an acellular oxygen carrier HBOC-201 results in superior tissue preservation compared to conventional SCS. (c) 2021 Elsevier Inc. All rights reserved

Exceeding the Limits of Static Cold Storage in Limb Transplantation Using Subnormothermic Machine Perfusion

Background For 50 years, static cold storage (SCS) has been the gold standard for solid organ preservation in transplantation. Although logistically convenient, this preservation method presents important constraints in terms of duration and cold ischemia-induced lesions. We aimed to develop a machine perfusion (MP) protocol for recovery of vascularized composite allografts (VCA) after static cold preservation and determine its effects in a rat limb transplantation model. Methods Partial hindlimbs were procured from Lewis rats and subjected to SCS in Histidine-Tryptophan-Ketoglutarate solution for 0, 12, 18, 24, and 48 hours. They were then either transplanted (Txp), subjected to subnormothermic machine perfusion (SNMP) for 3 hours with a modified Steen solution, or to SNMP + Txp. Perfusion parameters were assessed for blood gas and electrolytes measurement, and flow rate and arterial pressures were monitored continuously. Histology was assessed at the end of perfusion. For select SCS durations, graft survival and clinical outcomes after transplantation were compared between groups at 21 days. Results Transplantation of limbs preserved for 0, 12, 18, and 24-hour SCS resulted in similar survival rates at postoperative day 21. Grafts cold-stored for 48 hours presented delayed graft failure (p = 0.0032). SNMP of limbs after 12-hour SCS recovered the vascular resistance, potassium, and lactate levels to values similar to limbs that were not subjected to SCS. However, 18-hour SCS grafts developed significant edema during SNMP recovery. Transplantation of grafts that had undergone a mixed preservation method (12-hour SCS + SNMP + Txp) resulted in better clinical outcomes based on skin clinical scores at day 21 post-transplantation when compared to the SCS + Txp group (p = 0.01613). Conclusion To date, VCA MP is still limited to animal models and no protocols are yet developed for graft recovery. Our study suggests that ex vivo SNMP could help increase the preservation duration and limit cold ischemia-induced injury in VCA transplantation.</p

Free energy and molecular dynamics calculations for the cubic-tetragonal phase transition in zirconia

The high-temperature cubic-tetragonal phase transition of pure stoichiometric zirconia is studied by molecular dynamics (MD) simulations and within the framework of the Landau theory of phase transformations. The interatomic forces are calculated using an empirical, self-consistent, orthogonal tight-binding (SC-TB) model, which includes atomic polarizabilities up to the quadrupolar level. A first set of standard MD calculations shows that, on increasing temperature, one particular vibrational frequency softens. The temperature evolution of the free energy surfaces around the phase transition is then studied with a second set of calculations. These combine the thermodynamic integration technique with constrained MD simulations. The results seem to support the thesis of a second-order phase transition but with unusual, very anharmonic behaviour above the transition temperature

Hirschsprung disease, associated syndromes and genetics: A review

Hirschsprung disease (HSCR, aganglionic megacolon) represents the main genetic cause of functional intestinal obstruction with an incidence of 1/5000 live births. This developmental disorder is a neurocristopathy and is characterised by the absence of the enteric ganglia along a variable length of the intestine. In the last decades, the development of surgical approaches has importantly decreased mortality and morbidity which allowed the emergence of familial cases. Isolated HSCR appears to be a non-Mendelian malformation with low, sex-dependent penetrance, and variable expression according to the length of the aganglionic segment. While all Mendelian modes of inheritance have been described in syndromic HSCR, isolated HSCR stands as a model for genetic disorders with complex patterns of inheritance. The tyrosine kinase receptor RET is the major gene with both rare coding sequence mutations and/or a frequent variant located in an enhancer element predisposing to the disease. Hitherto, 10 genes and five loci have been found to be involved in HSCR development.published_or_final_versio

A metagenomics study on Hirschsprung&apos;s disease associated enterocolitis: Biodiversity and gut microbial homeostasis depend on resection length and patient&apos;s clinical history

Objectives: Since 2010, several researches demonstrated that microbiota dynamics correlate and can even predispose to Hirschsprung (HSCR) associated enterocolitis (HAEC). This study aims at assessing the structure of the microbiota of HSCR patients in relation to extent of aganglionosis and HAEC status. Methods: All consecutive HSCR patients admitted to Gaslini Institute (Genova, Italy) between May 2012 and November 2014 were enrolled. Institutional review board (IRB) approval was obtained. Stools were sampled and 16S rDNA V3-V4 regions were sequenced using the Illumina-MiSeq. Taxonomy assignments were performed using QIIME RDP. Alpha diversity indexes were analyzed by Shannon and Simpson Indexes, and Phylogenetic Diversity. Results: We enrolled 20 patients. Male to female ratio was 4:1. Six patients suffered from Total Colonic Aganglionosis (TCSA). Considering sample site (i.e., extent of aganglionosis), we confirmed the known relationship between sample site and both biodiversity and composition of intestinal microbiota. Patients with TCSA showed lower biodiversity and increased Proteobacteria/Bacteroidetes relative abundance ratio. When addressing biodiversity, composition and dynamics of TCSA patients we could not find any significant relationship with regard to HAEC occurrences. Conclusions: The composition of HAEC predisposing microbiota is specific to each patient. We could confirm that total colon resections can change the composition of intestinal microbiota and to dramatically reduce microbial diversity. The subsequent reduction of system robustness could expose TCSA patients to environmental microbes that might not be part of the normal microbiota. Future long-term studies should investigate both patients and their family environment, as well as their disease history