Macroscopic Dynamics of Multi-Lane Traffic

We present a macroscopic model of mixed multi-lane freeway traffic that can be easily calibrated to empirical traffic data, as is shown for Dutch highway data. The model is derived from a gas-kinetic level of description, including effects of vehicular space requirements and velocity correlations between successive vehicles. We also give a derivation of the lane-changing rates. The resulting dynamic velocity equations contain non-local and anisotropic interaction terms which allow a robust and efficient numerical simulation of multi-lane traffic. As demonstrated by various examples, this facilitates the investigation of synchronization patterns among lanes and effects of on-ramps, off-ramps, lane closures, or accidents.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

Development of a core descriptor set for Crohn's anal fistula

AIM: Crohn's anal fistula (CAF) is a complex condition, with no agreement on which patient characteristics should be routinely reported in studies. The aim of this study was to develop a core descriptor set of key patient characteristics for reporting in all CAF research. METHOD: Candidate descriptors were generated from published literature and stakeholder suggestions. Colorectal surgeons, gastroenterologists and specialist nurses in inflammatory bowel disease took part in three rounds of an international modified Delphi process using nine-point Likert scales to rank the importance of descriptors. Feedback was provided between rounds to allow refinement of the next ratings. Patterns in descriptor voting were assessed using principal component analysis (PCA). Resulting PCA groups were used to organize items in rounds two and three. Consensus descriptors were submitted to a patient panel for feedback. Items meeting predetermined thresholds were included in the final set and ratified at the consensus meeting. RESULTS: One hundred and thirty three respondents from 22 countries completed round one, of whom 67.0% completed round three. Ninety seven descriptors were rated across three rounds in 11 PCA-based groups. Forty descriptors were shortlisted. The consensus meeting ratified a core descriptor set of 37 descriptors within six domains: fistula anatomy, current disease activity and phenotype, risk factors, medical interventions for CAF, surgical interventions for CAF, and patient symptoms and impact on quality of life. CONCLUSION: The core descriptor set proposed for all future CAF research reflects characteristics important to gastroenterologists and surgeons. This might aid transparent reporting in future studies

Association of ITPA gene polymorphisms with adverse effects of AZA/6-MP administration: a systematic review and meta-analysis

Azathioprine (AZA) and its metabolite, mercaptopurine (6-MP), are widely used immunosuppressant drugs. Polymorphisms in genes implicated in AZA/6-MP metabolism, reportedly, could account in part for their potential toxicity. In the present study we performed a systematic review and a meta-analysis, comprising 30 studies and 3582 individuals, to investigate the putative genetic association of two inosine triphosphatase (ITPA) polymorphisms with adverse effects in patients treated with AZA/6-MP. We found that rs1127354 is associated with neutropenia in general populations and in children (OR: 2.39, 95%CI: 1.97–2.90, and OR: 2.43, 95%CI: 2.12–2.79, respectively), and with all adverse effects tested herein in adult populations (OR: 2.12, 95%CI: 1.22–3.69). We also found that rs7270101 is associated with neutropenia and leucopenia in all-ages populations (OR: 2.93, 95%CI: 2.36–3.63, and OR: 2.82, 95%CI: 1.76–4.50, respectively) and with all adverse effects tested herein in children (OR: 1.74, 95%CI: 1.06–2.87). Stratification according to background disease, in combination with multiple comparisons corrections, verified neutropenia to be associated with both polymorphisms, in acute lymphoblastic leukemia (ALL) patients. These findings suggest that ITPA polymorphisms could be used as predictive biomarkers for adverse effects of thiopurine drugs to eliminate intolerance in ALL patients and clarify dosing in patients with different ITPA variants. © 2021, The Author(s), under exclusive licence to Springer Nature Limited

Unraveling the mechanisms of extreme radioresistance in prokaryotes: Lessons from nature

The last 50 years, a variety of archaea and bacteria able to withstand extremely high doses of ionizing radiation, have been discovered. Several lines of evidence suggest a variety of mechanisms explaining the extreme radioresistance of microorganisms found usually in isolated environments on Earth. These findings are discussed thoroughly in this study. Although none of the strategies discussed here, appear to be universal against ionizing radiation, a general trend was found. There are two cellular mechanisms by which radioresistance is achieved: (a) protection of the proteome and DNA from damage induced by ionizing radiation and (b) recruitment of advanced and highly sophisticated DNA repair mechanisms, in order to reconstruct a fully functional genome. In this review, we critically discuss various protecting (antioxidant enzymes, presence or absence of certain elements, high metal ion or salt concentration etc.) and repair (Homologous Recombination, Single-Strand Annealing, Extended Synthesis-Dependent Strand Annealing) mechanisms that have been proposed to account for the extraordinary abilities of radioresistant organisms and the homologous radioresistance signature genes in these organisms. In addition, and based on structural comparative analysis of major radioresistant organisms, we suggest future directions and how humans could innately improve their resistance to radiation-induced toxicity, based on this knowledge. © 2015 Elsevier B.V