Primary gliosarcoma: key clinical and pathologic distinctions from glioblastoma with implications as a unique oncologic entity

This report presents the historical experience, clinical presentation, treatment, prognosis, and pathogenesis of gliosarcoma described to date in the English literature. PubMed query of term “gliosarcoma” was performed, followed by a rigorous review of cited literature. Articles selected for analysis included: (1) case reports of gliosarcoma, (2) review articles of gliosarcoma, and (3) studies of the pathogenesis or genetics of gliosarcoma in humans. Our review identified 219 cases of gliosarcoma in 34 reports and eight articles addressing the pathogenesis. Survival in larger series ranged 4–11.5 months. Features unique to gliosarcoma compared to glioblastoma (GBM) include their temporal lobe predilection, potential to appear similar to a meningioma at surgery, repeated reports of extracranial metastases, and infrequency of EGFR mutations. Published experience is limited to small case series, and the pathogenesis remains unclear. Clinical and pathologic characteristics distinct from GBM suggest that they may warrant specific treatment, separate from conventional GBM therapy

Plio-Pleistocene exhumation of the eastern Himalayan syntaxis and its domal ‘pop-up’

The eastern termination of the Himalayan orogen forms a structural syntaxis that is characterised by young (from 10 to < 1 Ma) mineral growth and cooling ages that document Late Miocene to Pleistocene structural, metamorphic, igneous and exhumation events. This region is a steep antiformal and in part domal structure that folds the suture zone between the Indian and Asian plates. It is dissected by the Yarlung Tsangpo, one of the major rivers of the eastern Himalayan–Tibet region, which becomes the Brahmaputra River in the Indian foreland basin before emptying into the Bay of Bengal. Exceptionally high relief and one of the deepest gorges on Earth have developed where the river's tortuous route crosses the Namche Barwa–Gyala Peri massif (> 7 km in elevation) in the core of the syntaxis. Very high erosion rates documented in sediment downstream of the gorge at the foot of the Himalaya contribute ~ 50% of total detritus to the sediment load of the Brahmaputra. The initiation of very high rates of exhumation has been attributed either to the extreme erosive power of a river flowing across a deforming indentor corner and the associated positive feedback, or to the geometry of the Indian plate indentor, with the corner being thrust beneath the Asian plate resulting in buckling which accommodates shortening; both processes may be important. The northern third of the syntaxis corresponds to a steep domal ‘pop-up’ structure bounded by the India–Asia suture on three sides and a thrust zone to the south. Within the dome, Greater Himalaya rocks equilibrated at ~ 800 °C and 25–30 km depth during the Miocene, with these conditions potentially persisting into the latest Miocene and possibly the Pliocene, with modest decompression prior to ~ 4 Ma. This domal ‘pop-up’ corresponds to the area of youngest bedrock ages on a wide variety of thermochronometers and geochronometers. In this paper we review the extensive scientific literature that has focused on the eastern syntaxis and provide new chronological data on its bedrock and erosion products to constrain the age of inception of the very rapid uplift and erosion. We then discuss its cause, with the ultimate aim to reconstruct the exhumation history of the syntaxis and discuss the tectonic context for its genesis. We use zircon and rutile U–Pb, white mica Ar–Ar and zircon fission track dating methods to extract age data from bedrock, Brahmaputra modern sediments (including an extensive compilation of modern detrital chronometry from the eastern Himalaya) and Neogene palaeo-Brahmaputra deposits of the Surma Basin (Bangladesh). Numerical modelling of heat flow and erosion is also used to model the path of rocks from peak metamorphic conditions of ~ 800 °C to < 250 °C. Our new data include U–Pb bedrock rutile ages as young as 1.4 Ma from the Namche Barwa massif and 0.4 Ma from the river downstream of the syntaxis. Combined with existing data, our new data and heat flow modelling show that: i) the detrital age signature of the modern syntaxis is unique within the eastern Himalayan region; ii) the rocks within the domal pop-up were > 575 ± 75 °C only 1–2 Myr ago; iii) the Neogene Surma Basin does not record evidence of the rise and erosion of the domal pop-up until latest Pliocene–Pleistocene time; iv) Pleistocene exhumation of the north-easternmost part of the syntaxis took place at rates of at least 4 km/Myr, with bedrock erosion of 12–21 km during the last 3 Ma; v) the inception of rapid syntaxial exhumation may have started as early as 7 Ma or as late as 3 Ma; and vi) the Yarlung Tsangpo is antecedent and subsequently distorted by the developing antiform. Together our data and modelling demonstrate that the domal pop-up with its exceptional erosion and topographic relief is likely a Pleistocene feature that overprinted earlier structural and metamorphic events typical of Himalayan evolution. Keywords: Eastern Himalayan syntaxis; Namche Barwa; Surma Basin; Yarlung Tsangpo–Brahmaputra; U–Pb rutile dating; Thermal modellin

Urban Dynamics and Simulation Models

International audienceThe new generation of Simpop models presented in this book, as well as the approach followed all along their construction and evaluation, has specifically targeted and tackled the equifinality challenge of (urban) modelling. It is presented as a progression from solving elementary generative problems to adapting models for encompassing a variety of urban situations by sharing open tools.The first chapter presents our empirical knowledge of systems of cities, and ways of summarizing their regular properties. It builds the ‘system of reference’ upon which model-building can take place. Indeed, by generalizing processes and structural properties of empirical case studies in different spatio-temporal contexts, it specifies the elements that can be forecasted (the total urban growth, the degree of differentiation of city sizes, the spatial balance of growth, etc.) and ways to do it (theories of innovation diffusion, of agglomeration economies, of spatial distribution, etc.). By asking ‘is urban future predictable’, we question the logics of urban evolution as well as the different levels of uncertainty attached to different aspects of urban growth and interactions. Identifying the possibility of prediction makes the task of modelling interesting. Identifying key features of systems of cities provides a stylized empirical ground to evaluate simulations and study alternative trajectories. Finally, identifying areas of uncertainty as leading to the processes responsible for the urban evolution calls for a multi-modelling approach that tackles equifinality in the virtual laboratory.The second chapter addresses the first step of the modelling of system of cities. It presents a parsimonious model of the emergence of cities from a homogenous settlement system. It aims to answer a very basic question: are we able to identify a simple set of meaningful mechanisms that reproduces the observed emergence of cities at the scale of thousands of years? The SimpopLocal model is an answer to this question and it raises the challenge of calibration, in order to prove that there exists a set of parameters that are sufficient to model this emergence. It also raises the challenge of formalizing what a good simulation is in terms of long-term urban evolution, in order to automate the search for this parameter set (for which there exists no empirical ways of determination).The third chapter goes beyond the possibility of finding one way of simulating the emergence of cities. It presents a new method for assessing parameter sensitivity, by looking at the necessity of each mechanism within a given model structure. Indeed, despite the diversity of solutions to the calibration challenge, are some parameters isolated, not interacting with other parameters in the simulated output? Are they all necessary, besides being sufficient? A new method called ‘calibration profiling’ was developed to validate not only sufficiency of modelled mechanisms but also the necessity of theoretical hypotheses that are behind the construction of the model. It is a progress of social sciences towards the scientific methods (all things being equal), and it allows to increase the parsimony of urban models.The fourth chapter builds on this quest for parsimony, as it presents an incremental model-building approach to simulate empirical systems of cities. Given the specificity of the system we aim to model, we expect the mechanisms needed to reproduce the observed trajectory to be multiple and interacting in a complex way. Therefore, we have built a framework of hypothesis-testing and implemented modules of mechanisms that we combine and simulate. The combination follows a path of complexification as well as particularisation from any system of cities to a specific case study. The quality of each simulation is evaluated with respect to the populations observed in the corresponding empirical cities. This approach was developed to model the evolution of Soviet and post-Soviet cities from the 1960s on. Its strength is to be transferable at a very low cost to any other national system. A tentative check was performed on Indian cities. We finally show in this chapter that a theoretical-based modular model allows to evaluate and compare the power of different hypotheses to explain urban growth at different periods of time and in different geographical contexts, and therefore suggests a way to account for equifinality in urban models.The fifth chapter corresponds to an innovative way of exploring simulation models, and especially urban models. It considers a parsimonious structure of mechanisms and looks for the diversity of possible outcomes that the model can reach within a reasonable range of parameters. This means that it explores what the trajectory of a system of cities could have been, if we simulate past trends, or what it could be in the future, in terms of two or three properties of the system (like its total population, or the degree of inequality of city sizes). We present the algorithm developed to maximize the diversity of a model’s output, as well as the kind of knowledge it leads to in an empirical context. For instance, we analyze the alternative pasts of the Soviet system of cities (as modelled within different model structures) and the corresponding parameters and their meaning. In particular, we highlight configurations that result in population growth and configurations that result in population shrinkage, configurations that result in hierarchization or in the equalization of city sizes for each of the demographic regimes at two periods of time (Soviet and post-Soviet eras).In the last chapter, we present the platform that brings together and enables all the cutting-edge exploration methods in urban simulation. This integrated, innovative and open toolbox for urban modelling is called OpenMOLE.As an epilogue, we present what could be a world atlas of urban models for global prospective on urban future. We also stress the challenges that hamper its construction so far, especially because of the data challenge that is comparing cities over time and over space. Indeed, each country having (or having not) developed its own way of defining cities and quantifying urban features, there remains a monumental amount of work to collect and harmonize urban data over large period of time, as well as to identify what in each national evolution relates to generic and specific processes. Cumulative modelling could help perform this task, or at least to highlight areas of uncertainties. Our guess is that it will only be achieved by a large collective and interdisciplinary collaboration (between urban and regional specialists, modellers, computer scientists, empirical and theoretical experts, data providers and data analysts) based on open practices (as to data, methods and models)

Learning Multiple Conflicting Tasks with Artificial Evolution

The paper explores the issue of learning multiple competing tasks in the domain of artificial evolution. In particular, a robot is trained so as to be able to perform two different tasks at the same time, namely a gradient following and rough terrain avoidance behaviours. It is shown that, if the controller is trained to learn two tasks of different difficulty, then the robot performance is higher if the most difficult task is learnt first, before the combined learning of both tasks. An explanation to this superiority is also discussed, in comparison with previous results

A hybrid model of integer programming and variable neighbourhood search for highly-constrained nurse rostering problems

This paper presents a hybrid multi-objective model that combines integer programming (IP) and variable neighbourhood search (VNS) to deal with highly-constrained nurse rostering problems in modern hospital environments. An IP is first used to solve the subproblem which includes the full set of hard constraints and a subset of soft constrains. A basic VNS then follows as a postprocessing procedure to further improve the IP's resulting solutions. The satisfaction of the excluded constraints from the preceding IP model is the major focus of the VNS. Very promising results are reported compared with a commercial genetic algorithm and a hybrid VNS approach on real instances arising in a Dutch hospital. The comparison results demonstrate that our hybrid approach combines the advantages of both the IP and the VNS to beat other approaches in solving this type of problems. We also believe that the proposed methodology can be applied to other resource allocation problems with a large number of constraints