The role of complexity for digital twins of cities.

We argue that theories and methods drawn from complexity science are urgently needed to guide the development and use of digital twins for cities. The theoretical framework from complexity science takes into account both the short-term and the long-term dynamics of cities and their interactions. This is the foundation for a new approach that treats cities not as large machines or logistic systems but as mutually interwoven self-organizing phenomena, which evolve, to an extent, like living systems.

Radiotherapy plus temozolomide in elderly patients with glioblastoma: a "real-life" report.

BACKGROUND: The optimization of the management for elderly glioblastoma patients is crucial given the demographics of aging in many countries. We report the outcomes for a "real-life" patient cohort (i.e. unselected) comprising consecutive glioblastoma patients aged 70 years or more, treated with different radiotherapy +/- temozolomide regimens. METHODS: From 2003 to 2016, 104 patients ≥ 70 years of age, consecutively treated by radiotherapy for glioblastoma, were included in this study. All patients were diagnosed with IDH-wild type glioblastoma according to pathological criteria. RESULTS: Our patient cohort comprised 51 female patients (49%) and 53 male. The median cohort age was 75 years (70-88), and the median Karnofsky performance status (KPS) was 70 (30-100). Five (5%) patients underwent macroscopic complete resection, 9 (9%) had partial resection, and 90 (86%), a stereotactic biopsy. The MGMT promoter was methylated in 33/73 cases (45%). Fifty-two (50%), 38 (36%), and 14 (14%) patients were categorized with RPA scores of III, IV, and I-II. Thirty-three (32%) patients received normofractionated radiotherapy (60 Gy, 30 sessions) with temozolomide (Stupp), 37 (35%) received hypofractionated radiotherapy (median dose 40 Gy, 15 sessions) with temozolomide (HFRT + TMZ), and 34 (33%) HFRT alone. Patients receiving only HFRT were significantly older, with lower KPSs. The median overall survival (OS; all patients) was 5.2 months. OS rates at 12, 18, and 24 months, were 19%, 12%, and 5%, respectively, with no statistical differences between patients receiving Stupp or HFRT + TMZ (P = 0.22). In contrast, patients receiving HFRT alone manifested a significantly shorter survival time (3.9 months vs. 5.9 months, P = 0.018). In multivariate analyses, the prognostic factors for OS were: i) the type of surgery (HR: 0.47 [0.26-0.86], P = 0.014), ii) RPA class (HR: 2.15 [1.17-3.95], P = 0.014), and iii) temozolomide use irrespective of radiotherapy schedule (HR: 0.54 [0.33-0.88], P < 0.02). MGMT promoter methylation was neither a prognostic nor a predictive factor. CONCLUSIONS: These outcomes agree with the literature in terms of optimal surgery and the use of HFRT as a standard treatment for elderly GBM patients. Our study emphasizes the potential benefit of using temozolomide with radiotherapy in a real-life cohort of elderly GBM patients, irrespective of their MGMT status.

Substitution of insulin by exenatide in bad controlled type 2 diabetic patients: efficacy and predictive factors.

AIM: Exenatide therapy is indicated in type 2 diabetes after failure of oral antidiabetic agents (OAD). The aim of this observational prospective study was to assess efficacy of exenatide, in improving HbA1c of at least of 1% (responders) in type 2 diabetic patients treated previously with insulin. METHODS: Thirty-six patients (HbA1c >7.5%), with chronic bad glycemic control, were hospitalized to improve glycemia using transient continuous insulin infusion followed by administration of exenatide and OAD agents. In these patients, insulin had been introduced previously because of OAD failure without any sign of severe insulin deficiency. RESULTS: On the 27 patients analyzed at 3 months, 19 patients were responders (HbA1c: M0: 9.9±1.7%; M3: 7.6±1.2%). Among the 8 non-responders, only 4 deteriorated their HbA1c. After 9 months, 10 patients remained Responders (HbA1c: 7±0.9%). Predictive factors for an improvement of glycemic control were: diabetes duration shorter than 12 years, ratio fasting glycemia/C-peptide less than 1, fasting C-peptide higher than 2.0 µg/L and mean capillary blood glucose after 3 days of exenatide lower than 200 mg/dL. These criteria remained valid in case of a high HbA1c at baseline. CONCLUSION: In patients with no signs of insulin dependence and in case of insulin failure, exenatide associated to OAD may be tried in order to improve glycemic control, this objective was reached by 70% of our patients. Predictive factors for good response, easily available in clinical practice, may help therapeutic choices.

Nonlinear growth and condensation in multiplex networks.

Different types of interactions coexist and coevolve to shape the structure and function of a multiplex network. We propose here a general class of growth models in which the various layers of a multiplex network coevolve through a set of nonlinear preferential attachment rules. We show, both numerically and analytically, that by tuning the level of nonlinearity these models allow us to reproduce either homogeneous or heterogeneous degree distributions, together with positive or negative degree correlations across layers. In particular, we derive the condition for the appearance of a condensed state in which one node in each layer attracts an extensive fraction of all the edges.

Growing multiplex networks.

We propose a modeling framework for growing multiplexes where a node can belong to different networks. We define new measures for multiplexes and we identify a number of relevant ingredients for modeling their evolution such as the coupling between the different layers and the distribution of node arrival times. The topology of the multiplex changes significantly in the different cases under consideration, with effects of the arrival time of nodes on the degree distribution, average shortest path length, and interdependence.

Exciton diffusion in near-infrared absorbing solution-processed organic thin films.

We report on singlet-singlet annihilation and exciton diffusion in as-prepared p-type and annealed n-type thin films of the low-bandgap quinoidal quaterthiophene [QQT(CN)4] using ultrafast transient absorption measurements. The decay dynamics of exciton populations are well described by a one-dimensional diffusion-limited bimolecular recombination, indicating that the singlet excitons migrate preferentially along the stacking direction. Our results show that the exciton diffusion constants in QQT(CN)4 films do not vary significantly upon thermal annealing. Exciton diffusion lengths are measured to be as high as 4 and 5 nm in as-prepared and annealed QQT(CN)4 films, respectively. We also observe an influence of the excitation densities on the singlet exciton diffusion, which is attributed to phonon scattering. Because of the possibility of patterning p-n regions in QQT(CN)4 films by thermal nanolithography techniques, this study provides important insight not only into the photophysical properties of quinoidal oligothiophene derivatives but also for their future integration into high-performance p-n nanostructured near infrared light-sensing devices.

Transport on coupled spatial networks.

Transport processes on spatial networks are representative of a broad class of real world systems which, rather than being independent, are typically interdependent. We propose a measure of utility to capture key features that arise when such systems are coupled together. The coupling is defined in a way that is not solely topological, relying on both the distribution of sources and sinks, and the method of route assignment. Using a toy model, we explore relevant cases by simulation. For certain parameter values, a picture emerges of two regimes. The first occurs when the flows go from many sources to a small number of sinks. In this case, network utility is largest when the coupling is at its maximum and the average shortest path is minimized. The second regime arises when many sources correspond to many sinks. Here, the optimal coupling no longer corresponds to the minimum average shortest path, as the congestion of traffic must also be taken into account. More generally, results indicate that coupled spatial systems can give rise to behavior that relies subtly on the interplay between the coupling and randomness in the source-sink distribution.

Anti N1 cross-protecting antibodies against H5N1 detected in H1N1 infected people.

The A(H5N1) influenza virus pandemic may be the result of avian H5N1 adapting to humans, leading to massive human to human transmission in a context of a lack of pre-existing immunity. As A(H1N1) and A(H5N1) share the same neuraminidase subtype, anti-N1 antibodies subsequent to H1N1 infections or vaccinations may confer some protection against A(H5N1). We analysed, by microneutralization assay, the A/Vietnam/1194/04 (H5N1) anti-N1 cross-protection acquired either during A/New-Caledonia/20/99 (H1N1) infection or vaccination. In cases with documented H1N1 infection, H5N1 cross-protection could be observed only in patients born between 1930 and 1950. No such protection was detected in the sera of vaccinated individuals.

Cold oxygen plasma technology efficiency against different airborne respiratory viruses.

BACKGROUND: Respiratory infections caused by viruses are major causes of upper and lower respiratory tract infections. They account for an important mortality and morbidity worldwide. Amongst these viruses, influenza viruses and paramyxoviruses are major pathogens. Their transmission is mainly airborne, by direct transmission through droplets from infected cases. OBJECTIVES: In the context of an influenza pandemic, as well as for the reduction of nosocomial infections, systems that can reduce or control virus transmission will reduce the burden of this disease. It may also be part of the strategy for pandemic mitigation. STUDY DESIGN: A new system based on physical decontamination of surface and air has been developed. This process generates cold oxygen plasma (COP) by subjecting air to high-energy deep-UV light. To test its efficiency, we have developed an experimental device to assess for the decontamination of nebulized respiratory viruses. High titer suspensions of influenza virus type A, human parainfluenza virus type 3 and RSV have been tested. RESULTS: Different experimental conditions have been evaluated against these viruses. The use of COP with an internal device allowed the best results against all viruses tested. We recorded a reduction of 6.5, 3.8 and 4 log(10) TCID50/mL of the titre of the hPIV-3, RSV and influenza virus A (H5N2) suspensions. CONCLUSIONS: The COP technology is an efficient and innovative strategy to control airborne virus dissemination. It could successfully control nosocomial diffusion of respiratory viruses in hospital setting, and could be useful for the reduction of influenza transmission in the various consultation settings implemented for the management of cases during a pandemic.

sispread: A software to simulate infectious diseases spreading on contact networks.

OBJECTIVES: We present a simulation software which allows studying the dynamics of a hypothetic infectious disease within a network of connected people. The software is aimed to facilitate the discrimination of stochastic factors governing the evolution of an infection in a network. In order to do this it provides simple tools to create networks of individuals and to set the epidemiological parameters of the outbreaks. METHODS: Three popular models of infectious disease can be used (SI, SIS, SIR). The simulated networks are either the algorithm-based included ones (scale free, small-world, and random homogeneous networks), or provided by third party software. RESULTS: It allows the simulation of a single or many outbreaks over a network, or outbreaks over multiple networks (with identical properties). Standard outputs are the evolution of the prevalence of the disease, on a single outbreak basis or by averaging many outbreaks. The user can also obtain customized outputs which address in detail different possible epidemiological questions about the spread of an infectious agent in a community. CONCLUSIONS: The presented software introduces sources of stochasticity present in real epidemics by simulating outbreaks on contact networks of individuals. This approach may help to understand the paths followed by outbreaks in a given community and to design new strategies for preventing and controlling them.

The modeling of global epidemics: stochastic dynamics and predictability.

The global spread of emergent diseases is inevitably entangled with the structure of the population flows among different geographical regions. The airline transportation network in particular shrinks the geographical space by reducing travel time between the world's most populated areas and defines the main channels along which emergent diseases will spread. In this paper, we investigate the role of the large-scale properties of the airline transportation network in determining the global propagation pattern of emerging diseases. We put forward a stochastic computational framework for the modeling of the global spreading of infectious diseases that takes advantage of the complete International Air Transport Association 2002 database complemented with census population data. The model is analyzed by using for the first time an information theory approach that allows the quantitative characterization of the heterogeneity level and the predictability of the spreading pattern in presence of stochastic fluctuations. In particular we are able to assess the reliability of numerical forecast with respect to the intrinsic stochastic nature of the disease transmission and travel flows. The epidemic pattern predictability is quantitatively determined and traced back to the occurrence of epidemic pathways defining a backbone of dominant connections for the disease spreading. The presented results provide a general computational framework for the analysis of containment policies and risk forecast of global epidemic outbreaks.

The architecture of complex weighted networks.

Networked structures arise in a wide array of different contexts such as technological and transportation infrastructures, social phenomena, and biological systems. These highly interconnected systems have recently been the focus of a great deal of attention that has uncovered and characterized their topological complexity. Along with a complex topological structure, real networks display a large heterogeneity in the capacity and intensity of the connections. These features, however, have mainly not been considered in past studies where links are usually represented as binary states, i.e., either present or absent. Here, we study the scientific collaboration network and the world-wide air-transportation network, which are representative examples of social and large infrastructure systems, respectively. In both cases it is possible to assign to each edge of the graph a weight proportional to the intensity or capacity of the connections among the various elements of the network. We define appropriate metrics combining weighted and topological observables that enable us to characterize the complex statistical properties and heterogeneity of the actual strength of edges and vertices. This information allows us to investigate the correlations among weighted quantities and the underlying topological structure of the network. These results provide a better description of the hierarchies and organizational principles at the basis of the architecture of weighted networks.

Plasmodium chabaudi chabaudi chronic malaria and pathologies of the urogenital tract in male and female BALB/c mice.

BALB/c mice of both sexes were infected with a non-virulent strain of Plasmodium chabaudi chabaudi and any pathologies occurring in the urogenital tract and its accessory glands were investigated. Organs and tracts were removed from infected and control mice at 15, 40 and 100 days post-injection, weighed and processed for macroscopical and histological analyses. The relative weights of preputial, clitoral glands and testes were modified in infected mice during the 40 days following infection. The preputial glands show a marked hypotrophy at 15 days post-infection. The bladders of half of the infected female mice and a few infected male mice displayed a conspicuous haemoglobinuria and frequent interstitial cystitis that worsened throughout the experiment. Also, several chronic inflammatory reactions were detected in the prostates, preputial and clitoral glands up to 100 days post-infection. A probable cause of such a divergence in the characteristics of the infection and in the nature of the pathologies identified in infected male and female mice is the interaction between the infection and the immune and endocrine systems of the host. The cause of the pathologies and their consequences on the host condition are discussed.

Solution structure of microcin J25, the single macrocyclic antimicrobial peptide from Escherichia coli.

The three-dimensional solution structure of microcin J25, the single cyclic representative of the microcin antimicrobial peptide class produced by enteric bacteria, was determined using two-dimensional 1H NMR spectroscopy and molecular modeling. This hydrophobic 21-residue peptide exhibits potent activity directed to Gram-negative bacteria. Its primary structure, cyclo(-V1GIGTPISFY10GGGAGHVPEY20F-), has been determined previously [Blond, A., Péduzzi, J., Goulard, C., Chiuchiolo, M. J., Barthélémy, M., Prigent, Y., Salomón, R.A., Farías, R.N., Moreno, F. & Rebuffat, S. (1999) Eur. J. Biochem., 259, 747-755]. Conformational parameters (3JNHCalphaH coupling constants, quantitative nuclear Overhauser enhancement data, chemical shift deviations, temperature coefficients of amide protons, NH-ND exchange rates) were obtained in methanol solution. Structural restraints consisting of 190 interproton distances inferred from NOE data, 11 phi backbone dihedral angle and 9 chi1 angle restraints derived from the coupling constants and three hydrogen bonds in agreement with the amide exchange rates were used as input for simulated annealing calculations and energy minimization in the program XPLOR. Microcin J25 adopts a well-defined compact structure consisting of a distorted antiparallel beta sheet, which is twisted and folded back on itself, thus resulting in three loops. Residues 7-10 and 17-20 form the more regular part of the beta sheet. The region encompassing residues Gly11-His16 consists of a distorted beta hairpin, which divides into two small loops and is stabilized by an inverse gamma turn and a type I' beta turn. The reversal of the chain leading to the Phe21-Pro6 loop results from a mixed beta/gamma turn. A cavity, in which the hydrophilic Ser8 side-chain is confined, is delimited by two crab pincer-like regions that comprise residues 6-8 and 18-1.

Effect of water soluble extract of nacre (Pinctada maxima) on alkaline phosphatase activity and Bcl-2 expression in primary cultured osteoblasts from neonatal rat calvaria.

The nacre (mother of pearl) layer of the oyster Pinctada maxima shell can initiate bone formation by human osteoblasts in vivo and in vitro and is a new biomaterial that induces osteogenesis. This activity of nacre could be due to its water-soluble matrix. We examined the action of a water-soluble extract of nacre on the osteoblast phenotype of cells isolated from rat neonatal calvaria by measuring alkaline phosphatase (ALP) activity and by localization of the anti-apoptotic protein Bcl-2 by immunocytochemistry. ALP activity was increased 7% (p<0.001) by 100 microg proteins/ml extract and 20% (p<0.001) by 50 microg proteins/ml extract, but a low concentration of extract decreased the ALP activity by 8%. Cells treated with a high aspartic acid content fraction of the extract had increased ALP activity (23%, p<0.0001). Nacre extract and the fraction have no effect on the proliferation of mature osteoblasts. Immunoreactive Bcl-2 was overproduced in the cytoplasm and nuclei of osteoblasts at all stages of culture. Bcl-2 was found over the whole chromatin in quiescent and mitotic cells at the end of mitosis in the two nuclei in one cell, before cytodieresis. Bcl-2 was also found over chromosomes. Thus, nacre extract stimulates Bcl-2 production in osteoblasts, that is correlated with the cell cycle. Bcl-2 was also abundant in the nucleoli of extract-treated cells. Thus, the concentration and subcellular distribution of Bcl-2 in osteoblasts in primary cultures is influenced by nacre extract, and related to the cell cycle and the regulation of gene expression. Hence, knowledge of how water-soluble extracts of Pinctada maxima nacre act on osteoblasts in vitro may reveal the mechanisms involved in its action in vivo on bone cells and bone regeneration.

Self-consistent effective-medium approximations with path integrals

We study effective-medium approximations for linear composite media by means of a path integral formalism with replicas. We show how to recover the Bruggeman and Hori-Yonezawa effective-medium formulas. Using a replica-coupling ansatz, these formulas are extended into ones which have the same percolation thresholds as those of the Bethe lattice and Potts model of percolation, and critical exponents s=0 and t=2 in any space dimension d>/=2. Like the Bruggeman and Hori-Yonezawa formulas, the obtained formulas are exact to second order in the weak-contrast and dilute limits. The dimensional range of validity of the four effective-medium formulas is discussed, and it is argued that out formulas are of better relevance than the classical ones in dimensions d=3,4 for systems obeying the nodes-links-blobs picture, such as random-resistor networks.

Multifractal properties of the random resistor network

We study the multifractal spectrum of the current in the two-dimensional random resistor network at the percolation threshold. We consider two ways of applying the voltage difference: (i) two parallel bars, and (ii) two points. Our numerical results suggest that in the infinite system limit, the probability distribution behaves for small i as P(i) approximately 1/i, where i is the current. As a consequence, the moments of i of order q

Classes of small-world networks.

We study the statistical properties of a variety of diverse real-world networks. We present evidence of the occurrence of three classes of small-world networks: (a) scale-free networks, characterized by a vertex connectivity distribution that decays as a power law; (b) broad-scale networks, characterized by a connectivity distribution that has a power law regime followed by a sharp cutoff; and (c) single-scale networks, characterized by a connectivity distribution with a fast decaying tail. Moreover, we note for the classes of broad-scale and single-scale networks that there are constraints limiting the addition of new links. Our results suggest that the nature of such constraints may be the controlling factor for the emergence of different classes of networks.

Effect of water-soluble matrix fraction extracted from the nacre of Pinctada maxima on the alkaline phosphatase activity of cultured fibroblasts.

A new approach to the isolation of the water-soluble factors from nacre without any demineralization is described and examined their effect on fibroblast cells in culture. The soluble matrix in pure water from the nacre of Pinctada maxima was analysed by size-exclusion HPLC. Four fractions (SE1-SE4) of the water-soluble matrix (WSM) were further analysed by anion-exchange HPLC. The amino acid composition of the WSM showed that it is mainly composed of glycine and alanine. SE1 and SE4 had different amino acid compositions from the whole WSM. The WSM and SE4 tested on a culture of human foetus lung tissue fibroblasts increased the alkaline phosphatase (ALP) activity. SE1 caused a decrease in ALP activity. Our results support the hypothesis that WSM promotes the differentiation of cells in vitro.