FuturICT: Participatory computing to understand and manage our complex world in a more sustainable and resilient way

We have built particle accelerators to understand the forces that make up our physical world. Yet, we do not understand the princi-ples underlying our strongly connected, techno-socio-economic systems. We have enabled ubiquitous Internet connectivity and instant, global information access. Yet we do not understand how it impacts our be-havior and the evolution of society. To fill the knowledge gaps and keep up with the fast pace at which our world is changing, a Knowledge Accelerator must urgently be cre-ated. The financial crisis, international wars, global terror, the spread-ing of diseases and cyber-crime as well as demographic, technological and environmental change demonstrate that humanity is facing seri-ous challenges. These problems cannot be solved within the traditional paradigms. Moving our attention from a component-oriented view of the world to an interaction-oriented view will allow us to understand the com-plex systems we have created and the emergent collective phenomena characterising them. This paradigm shift will enable new solutions to long-standing problems, very much as the shift from a geocentric to a heliocentric worldview has facilitated modern physics and the ability to launch satellites. The FuturICT flagship project will develop new science and technology to manage our future in a complex, strongly connected world. For this, it will combine the power of information and communication technol-ogy (ICT) with knowledge from the social and complexity sciences. ICT will provide the data to boost the social sciences into a new era. Complexity science will shed new light on the emergent phenomena in socially interactive systems, and the social sciences will provide a better understanding of the opportunities and risks of strongly net-worked systems, in particular future ICT systems. Hence, the envisaged FuturICT flagship will create new methods and instruments to tackle the challenges of the 21 st century. FuturICT could indeed become one of the most important scientific endeavours ever, by revealing the principles that make socially inter-active systems work well, by inspiring the creation of new platforms to explore our possible futures, and by initiating an era of social and socio-inspired innovations

Chondrogenic Potency Analyses of Donor-Matched Chondrocytes and Mesenchymal Stem Cells Derived from Bone Marrow, Infrapatellar Fat Pad, and Subcutaneous Fat.

Autologous chondrocyte implantation (ACI) is a cell-based therapy that has been used clinically for over 20 years to treat cartilage injuries more efficiently in order to negate or delay the need for joint replacement surgery. In this time, very little has changed in the ACI procedure, but now many centres are considering or using alternative cell sources for cartilage repair, in particular mesenchymal stem cells (MSCs). In this study, we have tested the chondrogenic potential of donor-matched MSCs derived from bone marrow (BM), infrapatellar fat pad (FP), and subcutaneous fat (SCF), compared to chondrocytes. We have confirmed that there is a chondrogenic potency hierarchy ranging across these cell types, with the most potent being chondrocytes, followed by FP-MSCs, BM-MSCs, and lastly SCF-MSCs. We have also examined gene expression and surface marker profiles in a predictive model to identify cells with enhanced chondrogenic potential. In doing so, we have shown that Sox-9, Alk-1, and Coll X expressions, as well as immunopositivity for CD49c and CD39, have predictive value for all of the cell types tested in indicating chondrogenic potency. The findings from this study have significant clinical implications for the refinement and development of novel cell-based cartilage repair strategies

Magnetic Resonance Imaging Parameters at 1 Year Correlate With Clinical Outcomes Up to 17 Years After Autologous Chondrocyte Implantation

Background: The ability to predict the long-term success of surgical treatment in orthopaedics is invaluable, particularly in clinical trials. The quality of repair tissue formed 1 year after autologous chondrocyte implantation (ACI) in the knee was analyzed and compared with clinical outcomes over time. Hypothesis: Better quality repair tissue and a better appearance on magnetic resonance imaging (MRI) 1 year after ACI lead to improved longer-term clinical outcomes. Study Design: Cohort study; Level of evidence, 3. Methods: Repair tissue quality was assessed using either MRI (11.5 ± 1.4 [n = 91] or 39.2 ± 18.5 [n = 76] months after ACI) or histology (16.3 ± 11.0 months [n = 102] after ACI). MRI scans were scored using the whole-organ magnetic resonance imaging score (WORMS) and the magnetic resonance observation of cartilage repair tissue (MOCART) score, with additional assessments of subchondral bone marrow and cysts. Histology of repair tissue was performed using the Oswestry cartilage score (OsScore) and the International Cartilage Repair Society (ICRS) II score. Clinical outcomes were assessed using the modified Lysholm score preoperatively, at the time of MRI or biopsy, and at a mean 8.4 ± 3.7 years (maximum, 17.8 years) after ACI. Results: At 12 months, the total MOCART score and some of its individual parameters correlated significantly with clinical outcomes. The degree of defect fill, overall signal intensity, and surface of repair tissue at 12 months also significantly correlated with longer-term outcomes. The presence of cysts or effusion (WORMS) significantly correlated with clinical outcomes at 12 months, while the presence of synovial cysts/bursae preoperatively or the absence of loose bodies at 12 months correlated significantly with long-term clinical outcomes. Thirty percent of repair tissue biopsies contained hyaline cartilage, 65% contained fibrocartilage, and 5% contained fibrous tissue. Despite no correlation between the histological scores and clinical outcomes at the time of biopsy, a lack of hyaline cartilage or poor basal integration was associated with increased pain; adhesions visible on MRI also correlated with significantly better histological scores. Conclusion: These results demonstrate that MRI at 12 months can predict longer-term clinical outcomes after ACI. Further investigation regarding the presence of cysts, effusion, and adhesions and their relationship with histological and clinical outcomes may yield new insights into the mechanisms of cartilage repair and potential sources of pain

Human Articular Chondrocytes Retain Their Phenotype in Sustained Hypoxia While Normoxia Promotes Their Immunomodulatory Potential.

Objective To assess the phenotype of human articular chondrocytes cultured in normoxia (21% O2) or continuous hypoxia (2% O2). Design Chondrocytes were extracted from patients undergoing total knee replacement ( n = 5) and cultured in ~21% (normoxic chondrocytes, NC) and 2% (hypoxic chondrocytes, HC) oxygen in both monolayer and 3-dimensional (3D) pellet culture and compared with freshly isolated chondrocytes (FC). Cells were assessed by flow cytometry for markers indicative of mesenchymal stromal cells (MSCs), chondrogenic-potency and dedifferentiation. Chondrogenic potency and immunomodulatory gene expression was assessed in NC and HC by reverse transcription quantitative polymerase chain reaction. Immunohistochemistry was used to assess collagen II production following 3D pellet culture. Results NC were positive (>97%, n = 5) for MSC markers, CD73, CD90, and CD105, while HC demonstrated 60%) compared with HC and FC in which production was <2%. Hypoxic conditions upregulated expression of SOX9, frizzled-related protein ( FRZB), fibroblast growth factor receptor 3 ( FGFR3), and collagen type II ( COL2A1) and downregulated activin receptor-like kinase 1 ( ALK1) in 3 out of 4 patients compared with normoxic conditions for monolayer cells. Conclusions Hypoxic conditions encourage retention of a chondrogenic phenotype with some immunomodulatory potential, whereas normoxia promotes dedifferentiation of chondrocytes toward an MSC phenotype with loss of chondrogenic potency but enhanced immunomodulatory capacity

A Holder Continuous Nowhere Improvable Function with Derivative Singular Distribution

We present a class of functions $\mathcal{K}$ in $C^0(\R)$ which is variant of the Knopp class of nowhere differentiable functions. We derive estimates which establish \mathcal{K} \sub C^{0,\al}(\R) for 0<\al<1 but no $K \in \mathcal{K}$ is pointwise anywhere improvable to C^{0,\be} for any \be>\al. In particular, all $K$'s are nowhere differentiable with derivatives singular distributions. $\mathcal{K}$ furnishes explicit realizations of the functional analytic result of Berezhnoi. Recently, the author and simulteously others laid the foundations of Vector-Valued Calculus of Variations in $L^\infty$ (Katzourakis), of $L^\infty$-Extremal Quasiconformal maps (Capogna and Raich, Katzourakis) and of Optimal Lipschitz Extensions of maps (Sheffield and Smart). The "Euler-Lagrange PDE" of Calculus of Variations in $L^\infty$ is the nonlinear nondivergence form Aronsson PDE with as special case the $\infty$-Laplacian. Using $\mathcal{K}$, we construct singular solutions for these PDEs. In the scalar case, we partially answered the open $C^1$ regularity problem of Viscosity Solutions to Aronsson's PDE (Katzourakis). In the vector case, the solutions can not be rigorously interpreted by existing PDE theories and justify our new theory of Contact solutions for fully nonlinear systems (Katzourakis). Validity of arguments of our new theory and failure of classical approaches both rely on the properties of $\mathcal{K}$.Comment: 5 figures, accepted to SeMA Journal (2012), to appea

Synaesthesia: a distinct entity that is an emergent feature of adaptive neurocognitive differences

In this article, I argue that synaesthesia is not on a continuum with neurotypical cognition. Synaesthesia is special: its phenomenology is different; it has distinct causal mechanisms; and is likely to be associated with a distinct neurocognitive profile. However, not all synaesthetes are the same, and there are quantifiable differences between them. In particular, the number of types of synaesthesia that a person possesses is a hitherto underappreciated variable that predicts cognitive differences along a number of dimensions (mental imagery, sensory sensitivity, attention to detail). Together with enhanced memory, this may constitute a common core of abilities that may go some way to explaining why synaesthesia might have evolved. I argue that the direct benefits of synaesthesia are generally limited (i.e. the synaesthetic associations do not convey novel information about the world) but, nevertheless, synaesthesia may develop due to other adaptive functions (e.g. perceptual ability, memory) that necessitate changes to design features of the brain. The article concludes by suggesting that synaesthesia forces us to reconsider what we mean by a ‘normal’ mind/brain. There may be multiple ‘normal’ neurodevelopmental trajectories that can sculpt very different ways of experiencing the world, of which synaesthesia is but one. This article is part of a discussion meeting issue ‘Bridging senses: novel insights from synaesthesia’

Combination schemes for turning point prediction

We propose new forecast combination schemes for predicting turning points of business cycles. The combination schemes deal with the forecasting performance of a given set of models and possibly providing better turning point predictions. We consider turning point predictions generated by autoregressive (AR) and Markov-Switching AR models, which are commonly used for business cycle analysis. In order to account for parameter uncertainty we consider a Bayesian approach to both estimation and prediction and compare, in terms of statistical accuracy, the individual models and the combined turning point predictions for the United States and Euro area business cycles

Garden and landscape-scale correlates of moths of differing conservation status: significant effects of urbanization and habitat diversity

Moths are abundant and ubiquitous in vegetated terrestrial environments and are pollinators, important herbivores of wild plants, and food for birds, bats and rodents. In recent years, many once abundant and widespread species have shown sharp declines that have been cited by some as indicative of a widespread insect biodiversity crisis. Likely causes of these declines include agricultural intensification, light pollution, climate change, and urbanization; however, the real underlying cause(s) is still open to conjecture. We used data collected from the citizen science Garden Moth Scheme (GMS) to explore the spatial association between the abundance of 195 widespread British species of moth, and garden habitat and landscape features, to see if spatial habitat and landscape associations varied for species of differing conservation status. We found that associations with habitat and landscape composition were species-specific, but that there were consistent trends in species richness and total moth abundance. Gardens with more diverse and extensive microhabitats were associated with higher species richness and moth abundance; gardens near to the coast were associated with higher richness and moth abundance; and gardens in more urbanized locations were associated with lower species richness and moth abundance. The same trends were also found for species classified as increasing, declining and vulnerable under IUCN (World Conservation Union) criteria

Discourse or dialogue? Habermas, the Bakhtin Circle, and the question of concrete utterances

This is the author's accepted manuscript. The final publication is available at Springer via the link below.This article argues that the Bakhtin Circle presents a more realistic theory of concrete dialogue than the theory of discourse elaborated by Habermas. The Bakhtin Circle places speech within the “concrete whole utterance” and by this phrase they mean that the study of everyday language should be analyzed through the mediations of historical social systems such as capitalism. These mediations are also characterized by a determinate set of contradictions—the capital-labor contradiction in capitalism, for example—that are reproduced in unique ways in more concrete forms of life (the state, education, religion, culture, and so on). Utterances always dialectically refract these processes and as such are internal concrete moments, or concrete social forms, of them. Moreover, new and unrepeatable dialogic events arise in these concrete social forms in order to overcome and understand the constant dialectical flux of social life. But this theory of dialogue is different from that expounded by Habermas, who tends to explore speech acts by reproducing a dualism between repeatable and universal “abstract” discursive processes (commonly known as the ideal speech situation) and empirical uses of discourse. These critical points against Habermas are developed by focusing on six main areas: sentences and utterances; the lifeworld and background language; active versus passive understandings of language; validity claims; obligation and relevance in language; and dialectical universalism