Generalized Dielectric Breakdown Model

We propose a generalized version of the Dielectric Breakdown Model (DBM) for generic breakdown processes. It interpolates between the standard DBM and its analog with quenched disorder, as a temperature like parameter is varied. The physics of other well known fractal growth phenomena as Invasion Percolation and the Eden model are also recovered for some particular parameter values. The competition between different growing mechanisms leads to new non-trivial effects and allows us to better describe real growth phenomena. Detailed numerical and theoretical analysis are performed to study the interplay between the elementary mechanisms. In particular, we observe a continuously changing fractal dimension as temperature is varied, and report an evidence of a novel phase transition at zero temperature in absence of an external driving field; the temperature acts as a relevant parameter for the ``self-organized'' invasion percolation fixed point. This permits us to obtain new insight into the connections between self-organization and standard phase transitions.Comment: Submitted to PR

Avalanche Dynamics in Evolution, Growth, and Depinning Models

The dynamics of complex systems in nature often occurs in terms of punctuations, or avalanches, rather than following a smooth, gradual path. A comprehensive theory of avalanche dynamics in models of growth, interface depinning, and evolution is presented. Specifically, we include the Bak-Sneppen evolution model, the Sneppen interface depinning model, the Zaitsev flux creep model, invasion percolation, and several other depinning models into a unified treatment encompassing a large class of far from equilibrium processes. The formation of fractal structures, the appearance of $1/f$ noise, diffusion with anomalous Hurst exponents, Levy flights, and punctuated equilibria can all be related to the same underlying avalanche dynamics. This dynamics can be represented as a fractal in $d$ spatial plus one temporal dimension. We develop a scaling theory that relates many of the critical exponents in this broad category of extremal models, representing different universality classes, to two basic exponents characterizing the fractal attractor. The exact equations and the derived set of scaling relations are consistent with numerical simulations of the above mentioned models.Comment: 27 pages in revtex, no figures included. Figures or hard copy of the manuscript supplied on reques

SARS-CoV-2-specific nasal IgA wanes 9 months after hospitalisation with COVID-19 and is not induced by subsequent vaccination

BACKGROUND: Most studies of immunity to SARS-CoV-2 focus on circulating antibody, giving limited insights into mucosal defences that prevent viral replication and onward transmission. We studied nasal and plasma antibody responses one year after hospitalisation for COVID-19, including a period when SARS-CoV-2 vaccination was introduced. METHODS: In this follow up study, plasma and nasosorption samples were prospectively collected from 446 adults hospitalised for COVID-19 between February 2020 and March 2021 via the ISARIC4C and PHOSP-COVID consortia. IgA and IgG responses to NP and S of ancestral SARS-CoV-2, Delta and Omicron (BA.1) variants were measured by electrochemiluminescence and compared with plasma neutralisation data. FINDINGS: Strong and consistent nasal anti-NP and anti-S IgA responses were demonstrated, which remained elevated for nine months (p < 0.0001). Nasal and plasma anti-S IgG remained elevated for at least 12 months (p < 0.0001) with plasma neutralising titres that were raised against all variants compared to controls (p < 0.0001). Of 323 with complete data, 307 were vaccinated between 6 and 12 months; coinciding with rises in nasal and plasma IgA and IgG anti-S titres for all SARS-CoV-2 variants, although the change in nasal IgA was minimal (1.46-fold change after 10 months, p = 0.011) and the median remained below the positive threshold determined by pre-pandemic controls. Samples 12 months after admission showed no association between nasal IgA and plasma IgG anti-S responses (R = 0.05, p = 0.18), indicating that nasal IgA responses are distinct from those in plasma and minimally boosted by vaccination. INTERPRETATION: The decline in nasal IgA responses 9 months after infection and minimal impact of subsequent vaccination may explain the lack of long-lasting nasal defence against reinfection and the limited effects of vaccination on transmission. These findings highlight the need to develop vaccines that enhance nasal immunity. FUNDING: This study has been supported by ISARIC4C and PHOSP-COVID consortia. ISARIC4C is supported by grants from the National Institute for Health and Care Research and the Medical Research Council. Liverpool Experimental Cancer Medicine Centre provided infrastructure support for this research. The PHOSP-COVD study is jointly funded by UK Research and Innovation and National Institute of Health and Care Research. The funders were not involved in the study design, interpretation of data or the writing of this manuscript

Large-scale phenotyping of patients with long COVID post-hospitalization reveals mechanistic subtypes of disease

One in ten severe acute respiratory syndrome coronavirus 2 infections result in prolonged symptoms termed long coronavirus disease (COVID), yet disease phenotypes and mechanisms are poorly understood1. Here we profiled 368 plasma proteins in 657 participants ≥3 months following hospitalization. Of these, 426 had at least one long COVID symptom and 233 had fully recovered. Elevated markers of myeloid inflammation and complement activation were associated with long COVID. IL-1R2, MATN2 and COLEC12 were associated with cardiorespiratory symptoms, fatigue and anxiety/depression; MATN2, CSF3 and C1QA were elevated in gastrointestinal symptoms and C1QA was elevated in cognitive impairment. Additional markers of alterations in nerve tissue repair (SPON-1 and NFASC) were elevated in those with cognitive impairment and SCG3, suggestive of brain–gut axis disturbance, was elevated in gastrointestinal symptoms. Severe acute respiratory syndrome coronavirus 2-specific immunoglobulin G (IgG) was persistently elevated in some individuals with long COVID, but virus was not detected in sputum. Analysis of inflammatory markers in nasal fluids showed no association with symptoms. Our study aimed to understand inflammatory processes that underlie long COVID and was not designed for biomarker discovery. Our findings suggest that specific inflammatory pathways related to tissue damage are implicated in subtypes of long COVID, which might be targeted in future therapeutic trials

Automated validation of conceptual schema constraints

For a database application, conceptual design methods such as fact-oriented modelling and entity-relationship modelling are commonly used to specify a conceptual schema, which may then be mapped to a structure in a chosen data model (e.g. a relational database schema). Since conceptual data models support a rich variety of constraints, and these constraints may impact on one another, the task of ensuring mat the constraints expressed in a conceptual schema are consistent is non-trivial. Moreover, because different constraint patterns may be equivalent, some optimization may be needed to select the best constraint pattern for explicit assertion. With reference to conceptual schemas expressed in FOrML (an enhanced version of NIAM) mis paper discusses metarules for strong satisfiability and constraint preference, and outlines an efficient algorithm for validating four main types of constraints. Complexity analyses and benchmarks of the implemented algorithm are included

Subtyping and polymorphism in object-role modelling

Although Entity-Relationship (ER) modelling techniques are commonly used for information modelling, Object-Role Modelling (ORM) techniques are becoming increasingly popular, partly because they include detailed design procedures providing guidelines for the modeller. As with the ER approach, a number of different ORM techniques exist. In this paper, we propose an integration of two theoretically well founded ORM techniques: FORM and PSM. Our main focus is on a common terminological framework, and on the notion of subtyping. Subtyping has long been an important feature of semantic approaches to conceptual schema design. It is also the concept in which FORM and PSM differ the most in their formalization. The subtyping issue is discussed from three different viewpoints covering syntactical, identification, and population issues. Finally, a wider comparison of approaches to subtyping is made, which encompasses other ER-based and ORM-based information modelling techniques, and highlights how formal subtype definitions facilitate a comprehensive specification of subtype constraints

Automated mapping of conceptual schemas to relational schemas

Many CASE tools for information systems engineering can input a conceptual data model of an application and map this to a logical data model for implementation. Typically this involves mapping an ER (Entity-Relationship) conceptual schema to a relational database schema. Since the graphic notation of ER, or the mapping algorithm itself, fails to capture many constraints and derivation rules, these additional features must be coded up manually. Object-Role Modelling (ORM) provides a simpler and richer notation, enabling most of these additional features to be catered for in the mapping. The most well known version of ORM is NIAM, and a number of CASE tools now support this method. Recently, an extended ORM language called FORML has been developed which is even more expressive, and a complete mapping algorithm has been developed and automated. This paper provides an overview of the mapping algorithm and the use of role-graphs for automation